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Evaluating the effect of nurses supportive and educational care on GATA2 gene expression and quality of life in patients with endometriosis.

Endometriosis is one of the womens aggressive but benign diseases, formed by the presence of endometrial glands and stroma outside the uterine cavity. Various genes, including the GATA2 gene, are involved in the pathogenesis of endometriosis. Since this disease affects patients quality of life, this study was conducted to investigate the effect of nurses supportive and educational care on the quality of life of endometriosis patients and its role in GATA2 gene expression. For this purpose, 45 patients with endometriosis participated in this research, a semi-experimental before-and-after study. The instrument used was demographic information and quality of life questionnaires affiliated with Beckman Institute, which were completed in two stages before and after implementing patient training and support sessions. The real-time PCR technique was also used to evaluate the expression level of the GATA2 gene after obtaining endometrial tissue from patients before and after the intervention. Finally, the received information was analyzed using SPSS software and statistical tests. Based on the obtained results, the average quality of life score before the intervention was 51.73±13.91, and after the intervention was 60.46±13.80 (P<0.001). Also, in all four dimensions of quality of life, patients average scores increased after the intervention compared to before the intervention. Still, this difference was significant only in the two dimensions of physical and mental health (P<0.001). GATA2 gene expression before intervention was 0.35 ± 0.13 among endometriosis patients. After the intervention, its amount reached about three times, i.e., 0.96 ± 0.32, which showed a significant difference between the two groups at the 5% probability level. In general, the results of this research confirmed the positive effect of educational and support programs in improving the quality of life of breast cancer patients. Therefore, it is suggested to design and implement such programs in a broader manner and based on patients educational and support needs.

18F-FDG PET-CT in Cutaneous Metastases in Breast Carcinoma An unusual presentation.

Cutaneous and subcutaneous metastases are an exceedingly rare presentation in various malignancies. These represent poor prognosis and disease progression. Early detection of such findings helps in changing the management plan. 18F-FDG PET-CT has played a key role in deciding treatment plan for patients with breast cancer, by detecting metastatic sites, with a high sensitivity in detecting cutaneous metastases as seen in the following case.

Efficacy of pre - operative axillary ultrasonography in excluding nodal disease Can it replace sentinel lymph node biopsy in early stage breast cancer

To determine false negative rate, negative predictive value and the factors predicting false negativity of pre-treatment axillary ultrasound. The retrospective study was conducted at Shaukat Khanum Memorial Cancer Hospital, Lahore, Pakistan, and comprised data from January 2019 to December 2020 of patients with normal lymph nodes on ultrasound, tumour stages T1, T2 or T3 having invasive cancer who underwent sentinel lymph node biopsy. Ultrasound findings were compared with the biopsy results, dividing the sample into false negative group A and true negative group B. Clinical, radiological, histopathological parameters and therapeutic strategies were compared between the two groups. Data was analysed using SPSS 20. Of the 781 patients with mean age 49.39±11.51 years, 154(19.7%) were in group A and 627(80.2%) were in group B, with negative predictive value of 80.2%. Initial tumour size, histopathology, tumour grade, receptors, timing of chemotherapy, and type of surgery has significant difference between the groups (p<0.05). Multivariate analysis showed larger, high-grade, progesterone receptor negative and human epidermal growth factor receptor 2 positive tumours were significantly associated with lower false negative rate on axillary ultrasound (p<0.05). Axillary ultrasound was found to be effective in ruling out axillary nodal disease, especially in patients with high-burden axillary disease, aggressive tumour biology, larger tumour size and higher timour grade.

Is complete pathological response truly a complete response in breast cancer

To check if complete pathological response in breast cancer is a good prognostic factor. The retrospective study was conducted at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised data from January 2012 to December 2015 of all patients who received neo-adjuvant chemotherapy and had no distant metastasis at diagnosis. Mastectomy patients were excluded. Complete pathological response was defined as no detectable tumour cell in breast and axilla on pathological examination of the resected specimen. Tumour characteristics and 5-year disease free survival and overall survival were recorded. Data was analysed using SPSS 20. Of the 353 patients whose data was evaluated, 91(25.8%) had complete pathological response. Mean age at diagnosis was 43±10 years. Among them, 62(68%) patients had grade III tumour, 39(42.9%) were negative for oestrogen receptor, 58(63.7%) were negative for progesterone receptor, 25(27.5%) were positive for human epidermal growth factor receptor 2, and 26(28.6%) patients were triple negative. Overall, 28((30.7%) patients had recurrence 20(71.4%) had distant metastasis, 6(21.4%) had local recurrence, and 2(7.14%) had contralateral cancer. The 5-year disease-free survival and overall survival rates (Kaplan-Meier Survial curve) were 70% (28 patients-recurrence) and 87% (15 patients-deaths), respectively. Despite complete disappearance of tumour, a significant number of patients developed recurrences.

Experiences of a Multiethnic Cohort of Patients Enrolled in a Financial Reimbursement Program for Cancer Clinical Trials.

Financial reimbursement programs (FRPs) offset out-of-pocket (OOP) expenses from therapeutic clinical trial (TCT) participation. The study explores patients experience in TCTs after enrollment in a FRP at two academic medical centers, including barriers and opportunities to improve trial participation. From May 2019 to January 2020, adults diagnosed with cancer and eligible for TCTs and FRP were recruited from the Improving Patient Access to Cancer Clinical Trials randomized trial at the University of California San Francisco and University of Southern California. Patients with income ≤ 700% of national poverty guidelines were eligible. Semistructured interviews were conducted in patients preferred language. Qualitative analysis was performed by site and preferred language by two independent coders. Of 65 trial patients, 53 participated (38%, University of California San Francisco 62%, USC). The median age was 59 (IQR, 46-65) years, and 58% were female. Nearly half (49%) identified as LatinxHispanic compared with 32% non-Hispanic White, 10% Asian, 4% Black, 1% Native American, and 4% Others. A third were non-English speakers, 42% had college education or more, and 55% were retiredunemployed. Most common malignancies were gastrointestinal (42%), breast (19%), and genitourinary (13%), and 66% had metastatic disease. Patients experienced long travel time (1-4.5 hours) among 57% and financial toxicity from OOP costs (68%). High acceptability of the FRP was reported (81%). Although 30% of patients reported willingness to discuss finances of cancer treatmenttrial with physicians, majority (87%) preferred discussion with social workers or TCT staff. Proposed modifications to TCTs included decentralization, recruitment strategies, voucher structure, and established rates for OOP expenses. Patients experience with TCTs reveal financial and logistical stressors that may be lessened by the Improving Patient Access to Cancer Clinical Trial reimbursement program. FRPs may address inequities in clinical trial access among low-income and diverse populations.

Breast cancer knowledge in Lebanese females with positive family history.

Breast cancer is the most commonly diagnosed cancer in women and the second leading cause of cancer-related death worldwide. Positive family history increases the likelihood of developing this disease. As late-stage presentation and poor survival rates are associated with a lack of knowledge about breast cancer and its screening methods, this study aimed to evaluate the knowledge of Lebanese women with first-degree relatives who were diagnosed with breast cancer. In this cross-sectional study, 200 women with a positive family history accompanying their relatives to oncology clinics or the infusion center at the American University of Beirut Medical Center, completed an online survey after institutional review board approval was granted. Demographic information and answers to questions related to breast cancer risk factors, warning signs, and screening techniques were collected and analyzed using descriptive statistics and chi-square tests. Eighty-one percent of the study participants agreed that a history of breast cancer is associated with a higher disease risk. The smaller portions were aware of other potential risk factors, such as hormone replacement therapy, alcohol consumption, late menopause, early menarche, and overweight and sedentary lifestyles. Also, 93% to 96.5% of the participants recognized breast self-examination and mammography as useful tools for early detection. Furthermore, younger participants who reached university level and were employed had more insights into breast cancer. Breast cancer knowledge and early diagnosis are key elements in preventing late presentations and reducing the associated morbidity and mortality. Further educational and awareness campaigns should be conducted in Lebanon to improve women knowledge of breast cancer.

Screening and identification of hub-gene associated with brain metastasis in breast cancer.

The presence of breast cancer in the brain, also known as brain metastasis (BMS), is the primary reason for a bad prognosis in cases of breast cancer. Breast cancer is the most prevalent malignant tumor seen in women in developing nations. At present, there is no effective method to inhibit brain metastasis of breast cancer. Therefore, it is necessary to conduct a systematic study on BMS of breast cancer, which will not provide ideas and sites for follow-up studies on the treatment and inhibition of BMS. In this study, data set GSE43837 was screened from gene expression omnibus database, and then R language tool was used for differential analysis of its expression spectrum, The gene ontology functional enrichment and Kyoto encyclopedia of genes and genomes signal pathway enrichment analyses, as well as the interactive gene retrieval tool for hub-gene analysis, were performed. According to the findings, the primary genes linked to breast cancer brain metastases are those that involve interactions between cytokines and their respective receptors and between neuroactive ligands and their respective receptors. The majority of the gene ontology enrichment took place in the extracellular structural tissues, the extracellular matrix tissues, and the second message-mediated signaling. We were able to identify 8 genes that are linked to breast cancer spreading to the brain. The gene score for matrix metallopeptidase1 (MMP-1) was the highest among them, and the genes MMP10, tumor necrosis factor alpha-inducible protein 8, collagen type I alpha 2 chain, vascular cell adhesion molecule 1, and TNF superfamily member 11 were all connected to 1 another in an interaction way. There is a possibility that the 8 key genes that were identified in this research are connected to the progression of BMS in breast cancer. Among them, MMP1 is 1 that has the potential to have a role in the diagnosis and treatment of BMS in breast cancer.

RacialEthnic Disparity in the Relationship of Mental and Physical Health With Colorectal Cancer Screening Utilization Among Breast and Prostate Cancer Survivors.

We examined colorectal cancer (CRC) screening utilization among non-Hispanic White, non-Hispanic Black (NHB), non-Hispanic other (NHO)Hispanic cancer survivors. We also determined whether experiencing poor physical andor mental health affects CRC screening utilization in breast and prostate cancers across different racialethnic groups. Data from years 2016, 2018, and 2020 of the Behavioral Risk Factor Surveillance System on 3,023 eligible treatment-utilizing cancer survivors with complete treatment were used. We performed descriptive statistics and multivariable logistic regression to examine the mentioned association. Among 3,023 eligible survivors, 67.7% of NHOHispanic survivors demonstrated lower CRC screening use compared with non-Hispanic White (82%) and NHB (89%) survivors ( NHOHispanic survivors demonstrated lower CRC screening use. Frequent poor mental andor physical health was strongly associated with lower CRC screening use among NHB and NHOHispanic survivors. Our study suggests that cancer survivorship care considering mental and physical health status may improve adherence to CRC screening recommendation (for secondary cancer prevention) for NHB, NHO, and Hispanic survivors.

Perceptions of Transgender and Nonbinary Persons Toward Breast and Cervical Cancer Development, Screening, and Potential Impact on Gender-Affirming Hormone Therapy.

Approximately 1.6% of adult Americans identify as transgender (TG) or nonbinary (NB) and many take gender-affirming hormone therapy (GAHT). Little data exist to inform breast and cervical cancer risks, gender-specific screening guidelines, and inclusive cancer treatment algorithms that consider GAHT. We aimed to assess TGNB persons perceptions on breast and cervical cancer development, screening knowledge and practices, and attitude toward GAHT in the setting of a hormone receptor-positive breast cancer diagnosis. This single-institution survey study was conducted through an LGBTQ focused clinic from 2021 to 2022. Noncisgender patients age ≥ 18 years who were English speaking were eligible to participate. A 5-point Likert scale was used to assess concern of developing breast (all participants) and cervical cancer (those assigned female sex at birth). Demographic and quantitative variables were examined in comparison with responses via chi-squared tests. Eighty-six participants completed the survey 43% TG men, 24% TG women, and 20% NB persons. Most (84.9%) were age < 40 years, and 86% were non-Hispanic White. The majority were unaware of breast (77%) or cervical (60%) cancer screening recommendations for their sex assigned at birth or their gender. Approximately 35% reported concern regarding breast cancer development and of those age > 40 years only 50% had undergone screening mammography. Of those assigned female sex at birth with an intact cervix, 47% were concerned about cervical cancer development and 46.6% had a Papanicolaou smear within the past 5 years. Nearly all (87.2%) were on GAHT, and 35.1% reported they would not consider stopping GAHT if diagnosed with a hormone receptor-positive breast cancer. The findings support the need for patient and provider education on screening options and large prospective cohort data to elucidate optimal gender-specific screening guidelines and treatment algorithms.

Incremental Health Care Costs of Anxiety and Depression Among Medicare Beneficiaries With Cancer.

Mental health comorbidities are commonplace among patients with cancer and have been associated with adverse health outcomes and elevated health care costs. Given the rapidly evolving cancer care landscape, an updated understanding of the prevalence and costs of mental health conditions among patients with cancer is needed. This study assessed the incremental costs of anxiety and depression among Medicare beneficiaries with cancer. This retrospective cohort study used the SEER-Medicare database. Patients diagnosed with melanoma, breast, lung, prostate, or colorectal cancer between July 2013 and December 2017 were followed for at least 12 months and up to 36 months after cancer diagnosis. Patients were categorized on the basis of anxietydepression (AD) diagnosis (1) predating cancer, (2) onset after cancer, or (3) no AD. Multivariable regression was used to estimate differences in all-cause incremental costs (before Of 230,626 patients, 10% had AD before their cancer diagnosis and 22% were diagnosed after cancer. In the first year after cancer diagnosis, average monthly health care costs were $5,750 in US dollars (USD) for patients with newly onset, $5,208 (USD) for patients with preexisting, and $3,919 (USD) for patients without a diagnosis of AD. The incremental cost of cancer was the greatest among patients with newly onset AD-$1,458 (USD) per month greater than those with no AD. Similar patterns were observed across cancer types and stages. One in three Medicare beneficiaries with cancer in this study had a diagnosis of anxiety or depression. Newly onset AD is associated with an increase in health care costs of $17,496 (USD) per year. Screening and management of mental health conditions for patients with cancer should be part of coordinated oncology care.

Applications of Artificial Intelligence in Breast Pathology.

Increasing implementation of whole slide imaging together with digital workflow and advances in computing capacity enable the use of artificial intelligence (AI) in pathology, including breast pathology. Breast pathologists often face a significant workload, with diagnosis complexity, tedious repetitive tasks, and semiquantitative evaluation of biomarkers. Recent advances in developing AI algorithms have provided promising approaches to meet the demand in breast pathology. To provide an updated review of AI in breast pathology. We examined the success and challenges of current and potential AI applications in diagnosing and grading breast carcinomas and other pathologic changes, detecting lymph node metastasis, quantifying breast cancer biomarkers, predicting prognosis and therapy response, and predicting potential molecular changes. We obtained data and information by searching and reviewing literature on AI in breast pathology from PubMed and based our own experience. With the increasing application in breast pathology, AI not only assists in pathology diagnosis to improve accuracy and reduce pathologists workload, but also provides new information in predicting prognosis and therapy response.

SGN-CD228A is an investigational CD228-directed antibody-drug conjugate with potent antitumor activity across a wide spectrum of preclinical solid tumor models.

SGN-CD228A is an investigational antibody-drug conjugate (ADC) directed to melanotransferrin (CD228, MELTF, MFI2, p97), a cell-surface protein first identified in melanoma. SGN-CD228A consists of a humanized antibody, hL49, with high specificity and affinity for CD228 that is stably conjugated to 8 molecules of the clinically validated microtubule-disrupting agent monomethyl auristatin E (MMAE) via a novel glucuronide linker. We performed comprehensive immunohistochemical studies, which corroborated published RNA-seq data and confirmed low CD228 expression in normal tissues and high expression in several cancers, including melanoma, squamous non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), colorectal cancer, and pancreatic cancer. SGN-CD228A was efficiently internalized in various tumor cell types, and its cytotoxic activity was dependent on CD228 expression and internalization and intrinsic sensitivity to the MMAE payload. Compared to the valine-citrulline dipeptide linker, the novel glucuronide linker increased the cellular retention of MMAE in vitro and conferred improved antitumor activity against melanoma cell lines in vitro and in vivo. Additionally, SGN-CD228A was active across melanoma, TNBC, and NSCLC cell line- and patient-derived xenograft models with heterogeneous antigen expression. In vivo, CD228 expression was important for response to SGN-CD228A but was not well-correlated across all tumor types, suggesting that other factors associated with ADC activity are important. Overall, SGN-CD228A is a CD228-directed, investigational ADC that employs innovative technology and has compelling preclinical antitumor activity. SGN-CD228A is being investigated in an ongoing Phase I clinical trial (NCT04042480) in patients with advanced solid tumors.

Immunosuppressive reprogramming of neutrophils by lung mesenchymal cells promotes breast cancer metastasis.

Neutrophils, the most abundant innate immune cells, function as crucial regulators of the adaptive immune system in diverse pathological conditions, including metastatic cancer. However, it remains largely unknown whether their immunomodulatory functions are intrinsic or acquired within the pathological tissue environment. Here, using mouse models of metastatic breast cancer in the lungs, we show that, although neutrophils isolated from bone marrow (BM) or blood are minimally immunosuppressive, lung-infiltrating neutrophils are robustly suppressive of both T cells and natural killer (NK) cells. We found that this tissue-specific immunosuppressive capacity of neutrophils exists in the steady state and is reinforced by tumor-associated inflammation. Acquisition of potent immunosuppression activity by lung-infiltrating neutrophils was endowed by the lung-resident stroma, specifically CD140a

Rapid generation of homogenous tumor spheroid microtissues in a scaffold-free platform for high-throughput screening of a novel combination nanomedicine.

Combination nanomedicine is a potent strategy for cancer treatment. Exploiting different mechanisms of action, a novel triple drug delivery system of 5-fluorouracil, curcumin, and piperine co-loaded human serum albumin nanoparticles (5FU-CUR-PIP-HSA-NPs) was developed via the self-assembly method for suppressing breast tumor. Both hydrophobic and hydrophilic drugs were successfully encapsulated in the HSA NPs with a high drug loading efficiency (DLE) of 10%. Successful clinical translation of nanomedicines, however, is a challenging process requiring considerable preclinical in vitro and in vivo animal tests. The aim of this study was to develop a homemade preclinical 3D culture model in the standard 96-well plates in a cost and time-effective novel approach for the rapid generation of homogenous compact tumor spheroids for disease modeling, and anticancer therapeuticnanomedicine screening. The knowledge of drug screening can be enhanced by employing such a model in a high-throughput manner. Accordingly, to validate the formulated drug delivery system and investigate the cellular uptake and cytotoxicity effect of the nanoformulation, 3D tumor spheroids were employed. The practicality of the nanomedicine system was substantiated in different tests. The in vitro uptake of the NPs into the tight 3D tumor spheroids was facilitated by the semi-spherical shape of the NPs with a proper size and surface charge. 5FU-CUR-PIP-HSA-NPs demonstrated high potency of migration inhibition as a part of successful anti-metastatic therapy as well. The remarkable differences in 2D and 3D cytotoxicities emphasize the importance of employing 3D tumor models as an intermediate step prior to in vivo animal experiments for drugnanomedicine screening.

Breast Cancer and Physiologic Avidity From Breast Feeding on FDG PETCT.

A 35-year-old woman presented with breast cancer diagnosed during pregnancy. Eleven days after delivery, the patient underwent FDG PETCT for systemic staging. Avidity was seen diffusely in both breasts, with a more avid focus at the site of a biopsy clip in the right breast. There were no lymph nodes or distant metastases. The patient was actively breast feeding, explaining the diffuse breast avidity. This case demonstrates both malignant and benign FDG avidity in the breasts at the same time, with a focal FDG-avid right breast malignancy identified among bilateral breast parenchyma with elevated physiologic FDG-avid secondary to breast feeding.

Increased 18F-Fluoroestradiol Uptake of Radiation Pneumonitis in a Patient With Metastatic Breast Cancer.

A 42-year-old woman diagnosed with de-novo stage IV breast cancer underwent 18F-fluoroestradiol (FES) PETCT to evaluate the estrogen receptor status of metastatic lesions. The largest pulmonary nodule showed obvious FES uptake, consistent with pulmonary metastases from breast cancer. Interestingly, the images revealed a striking accumulation of FES in ground-glass attenuation in the left lobe of lung, suggestive of radiation pneumonitis.

A Transcriptomic and Reverse-Engineering Strategy Reveals Molecular Signatures of Arachidonic Acid Metabolism in 12 Cancers.

Cancer and arachidonic acid (AA) have important linkages. For example, AA metabolites regulate several critical biological functions associated with carcinogenesis angiogenesis, apoptosis, and cancer invasion. However, little is known about the comparative changes in metabolite expression of the arachidonic acid pathway (AAP) in carcinogenesis. In this study, we examined transcriptome data from 12 cancers, such as breast invasive carcinoma, colon adenocarcinoma, lung adenocarcinoma, and prostate adenocarcinoma. We also report here a reverse-engineering strategy wherein we estimated metabolic signatures associated with AAP by (1) making deductive inferences through transcriptome-level data extraction, (2) remodeling AA metabolism, and (3) performing a comparative analysis of cancer types to determine the similarities and differences between different cancer types with respect to AA metabolic alterations. We identified 77 AAP gene signatures differentially expressed in cancers and 37 AAP metabolites associated with them. Importantly, the metabolite 15(S)-HETE was identified in almost all cancers, while arachidonate, 5-HETE, PGF2α, 14,15-EET, 8,9-EET, 5,6-EET, and 20-HETE were discovered as other most regulated metabolites. This study shows that the 12 cancers studied herein, although in different branches of the AAP, have altered expression of AAP gene signatures. Going forward, AA related-cancer research generally, and the molecular signatures and their estimated metabolites reported herein specifically, hold broad promise for precisionpersonalized medicine in oncology as potential therapeutic and diagnostic targets.

Changes in mammographic density and risk of breast cancer among a diverse cohort of women undergoing mammography screening.

Mammographic density (MD) is a strong breast cancer risk factor. MD may change over time, with potential implications for breast cancer risk. Few studies have assessed associations between MD change and breast cancer in racially diverse populations. We investigated the relationships between MD and MD change over time and breast cancer risk in a large, diverse screening cohort. We retrospectively analyzed data from 8462 women who underwent ≥ 2 screening mammograms from Sept. 2010 to Jan. 2015 (N 20,766 exams) 185 breast cancers were diagnosed 1-7 years after screening. Breast percent density (PD) and dense area (DA) were estimated from raw digital mammograms (Hologic Inc.) using LIBRA (v1.0.4). For each MD measure, we modeled breast density change between two sequential visits as a function of demographic and risk covariates. We used Cox regression to examine whether varying degrees of breast density change were associated with breast cancer risk, accounting for multiple exams per woman. PD at any screen was significantly associated with breast cancer risk (hazard ratio (HR) for PD 1.03 (95% CI 1.01, 1.05, p < 0.0005), but neither change in breast density nor more extreme than expected changes in breast density were associated with breast cancer risk. We found no evidence of differences in density change or breast cancer risk due to density change by race. Results using DA were essentially identical. Using a large racially diverse cohort, we found no evidence of association between short-term change in MD and risk of breast cancer, suggesting that short-term MD change is not a strong predictor for risk.

Screening behaviours, demographics, and stage at diagnosis in the publicly funded Ontario Breast Screening Program.

The Ontario Breast Screening Program (OBSP) offers free screening mammograms every 2 years, to women aged 50-74. Study objectives were to determine demographic characteristics associated with the adherence to OBSP and if women screened in the OBSP have a lower stage at diagnosis than non-screened eligible women. We used the Ontario cancer registry (OCR) to identify 48,927 women, aged 51-74 years, diagnosed with breast cancer between 2010 and 2017. These women were assigned as having undergone adherent screening (N 26,108), non-adherent screening (N 6546) or not-screened (N 16,273) in the OBSP. We used multinomial logistic regression to investigate the demographic characteristics associated with screening behaviour, as well as the association between screening status and stage at diagnosis. Among women with breast cancer, those living in rural areas (versus the largest urban areas) had a lower odds of not being screened (odds ratio OR 0.73, 95% confidence interval CI 0.68, 0.78). Women in low-income (versus high-income) communities were more likely not to be screened (OR 1.42, 95% CI 1.33, 1.51). When stratified, the association between income and screening status only held in urban areas. Non-screened women were more likely to be diagnosed with stage II (OR 1.91, 95% CI 1.82, 2.01), III (OR 2.96, 95% CI 2.76, 3.17), or IV (OR 8.96, 95% CI 7.94, 10.12) disease compared to stage I and were less likely to be diagnosed with ductal carcinoma in situ (DCIS) (OR 0.91, 95% CI 0.84-0.98). This study suggests that targeting OBSP recruitment efforts to lower income urban communities could increase screening rates. OBSP adherent women were more likely to be diagnosed with earlier stage disease, supporting the value of this initiative and those like it.

Justifying Ribociclib Dose in Patients with Advanced Breast Cancer with Renal Impairment Based on PK, Safety, and Efficacy Data An Innovative Approach Integrating Data from a Dedicated Renal Impairment Study and Oncology Clinical Trials.

Renal impairment is common in patients with cancer and can alter the PK and thus the safety and efficacy of drugs. We assessed the impact of renal impairment during treatment with ribociclib, a cyclin-dependent kinase 46 inhibitor, and determined dose recommendations for patients with advanced breast cancer with renal impairment. A comprehensive assessment integrating pharmacokinetic, safety, and efficacy data from a phase I dedicated renal impairment study in non-cancer subjects and six phase I-III trials in patients with cancer was performed. Ribociclib showed higher pharmacokinetic exposure in subjects with renal impairment than those with normal renal function following a single 400-mg dose in the dedicated renal impairment study. However, in patient trials, both single-dose and steady‑state ribociclib exposure was comparable between patients with cancer with mildmoderate renal impairment and those with normal renal function following the recommended starting dose of 600 mg. Model-predicted steady‑state exposure in patients with advanced breast cancer was also similar across the renal function groups. Progression-free survival was similar and safety profiles were generally consistent across the renal cohorts (normalmildmoderate) in patients with advanced breast cancer, with low-grade and manageable adverse events, demonstrating a positive benefit-risk profile. From the collective evidence and considering a real-world clinical setting, no dose adjustment is recommended for patients with mildmoderate renal impairment, whereas a reduced dose is recommended for patients with severe renal impairment. This report presented a holistic and innovative strategy to determine dose in patients with renal impairment and demonstrated the effectiveness of integrating the data of both a clinical pharmacology study and patient trials to justify doses in patients with renal impairment. Clinicaltrials.gov identifiers NCT02431481, NCT01958021, NCT02422615, NCT02278120, NCT01237236, NCT01898845, NCT01872260.

Breast Cancer Screening Should Embrace Precision Medicine Evidence by Reviewing Economic Evaluations in China.

The cost-effectiveness of conventional population-based breast cancer screening strategies (e.g. mammography) has been found controversial, while evidence shows that genetic testing for early detection of pathogenic variants is cost-effective. We aimed to review the economic evaluations of breast cancer screening in China to provide an information summary for future research on this topic. We searched the literature to identify the economic evaluations that examined breast cancer screening and testing in China, supplemented by hand-searching the reference lists of the included studies. We finally included five studies satisfying our inclusion criteria. Four articles examined mammography while the rest investigated multigene testing. The existing breast cancer screening programmes were found to be cost-effective among urban Chinese women, but one study concluded that they might cause harm to women in rural areas. Contextual factors, such as data absence, urban-rural disparity, willingness-to-pay threshold, and model design, imposed barriers to cost-effectiveness analysis. Multigene testing was found to be cost-effective and has a promising population impact among all women with breast cancer in China. Future research should investigate the cost-effectiveness of screening and identifying breast cancer through precision medicine technologies, including genetic testing, genome sequencing, cascade testing, and the return of secondary findings.

Protein kinase D1 overexpression potentiates epidermal growth factor signaling pathway in MCF-7 cells.

Protein kinase D1, PKD1, is a serine-threonine kinase implicated in cell proliferation, migration, invasion, andor apoptosis and its activation by several growth factors sets this enzyme as a key regulator of tumorigenesis and tumor progression. Despite many studies, its role in the regulation of intracellular signaling pathways remains widely disparate and needs to be clarified. By using human breast cancer cells MCF-7, overexpressing or not PKD1, we demonstrated that PKD1 expression level modulated the tumor growth-promoting epidermal growth factor (EGF) signaling pathway. We also showed that EGF acutely stimulated PKD1 phosphorylation with similar time courses both in control and PKD1-overexpressing cells. However, PKD1 overexpression specifically and markedly increased EGF-induced phosphorylation of Akt (onto T308 and S473 residues) and extracellular-regulated protein kinase (ERK12). Finally, pharmacological inhibition of PKD1 activity or lowering its expression level using specific siRNAs drastically reduced EGF-stimulated Akt and ERK phosphorylation in PKD1overexpressing cells, but not in control cells. Overall, these results identified the level of PKD1 expression as a key determinant in the regulation of the EGF signaling pathway highlighting its crucial role in a tumorigenic setting.

Dysregulation of mitochondrial translation caused by CBFB deficiency cooperates with mutant PIK3CA and is a vulnerability in breast cancer.

Understanding functional interactions between cancer mutations is an attractive strategy for discovering unappreciated cancer pathways and developing new combination therapies to improve personalized treatment. However, distinguishing driver gene pairs from passenger pairs remains challenging. Here, we designed an integrated omics approach to identify driver gene pairs by leveraging genetic interaction analyses of top mutated breast cancer genes and the proteomics interactome data of their encoded proteins. This approach identified that PIK3CA oncogenic gain-of-function (GOF) and CBFB loss-of-function (LOF) mutations cooperate to promote breast tumor progression in both mice and humans. The transcription factor CBFB localized to mitochondria and moonlighted in translating the mitochondrial genome. Mechanistically, CBFB enhanced the binding of mitochondrial mRNAs to TUFM, a mitochondrial translation elongation factor. Independent of mutant PI3K, mitochondrial translation defects caused by CBFB LOF led to multiple metabolic reprogramming events, including defective oxidative phosphorylation (OXPHOS), the Warburg effect, and autophagymitophagy addiction. Furthermore, autophagy and PI3K inhibitors synergistically killed breast cancer cells and impaired the growth of breast tumors, including patient-derived xenografts (PDXs) carrying CBFB LOF and PIK3CA GOF mutations. Thus, our study offers mechanistic insights into the functional interaction between mutant PI3K and mitochondrial translation dysregulation in breast cancer progression and provides a strong preclinical rationale for combining autophagy and PI3K inhibitors in precision medicine for breast cancer.

High Dynamic Range Dual-Modal White Light Imaging Improves the Accuracy of Tumor Bed Sampling After Neoadjuvant Therapy for Breast Cancer.

Accurate evaluation of residual cancer burden remains challenging because of the lack of appropriate techniques for tumor bed sampling. This study evaluated the application of a white light imaging system to help pathologists differentiate the components and location of tumor bed in specimens. The high dynamic range dual-mode white light imaging (HDR-DWI) system was developed to capture antiglare reflection and multiexposure HDR transmission images. It was tested in 60 specimens of modified radical mastectomy after neoadjuvant therapy. We observed the differential transmittance among tumor tissue, fibrosis tissue, and adipose tissue. The sensitivity and specificity of HDR-DWI were compared with x-ray or visual examination to determine whether HDR-DWI was superior in identifying tumor beds. We found that tumor tissue had lower transmittance (0.12 ± 0.03) than fibers (0.15 ± 0.04) and fats (0.27 ± 0.07) (P < .01). HDR-DWI was more sensitive in identifying fiber and tumor tissues than cabinet x-ray and visual observation (P < .01). In addition, HDR-DWI could identify more fibrosis areas than the currently used whole slide imaging did in 12 samples (1260). We have determined that HDR-DWI can provide more in-depth tumor bed information than x-ray and visual examination do, which will help prevent diagnostic errors in tumor bed sampling.

Overview of Adductomics in Toxicology.

Adductomics is epidemiology at the molecular level. Untargeted adductomics compares levels of chemical adducts on albumin, hemoglobin, and DNA between healthy and exposed individuals. The goal is to determine a cause-and-effect relationship between chemical exposure and illness. Chemical exposures are not necessarily due to synthetic chemicals but are often due to oxidation products of naturally occurring lipids, for example, 4-hydroxynonenal and acrolein produced by lipid peroxidation of arachidonic and linoleic acids. The preferred method used in adductomics is ultra-high pressure liquid chromatography coupled to with nanoelectrospray tandem mass spectrometry. The mass of the adduct indicates its structure and identifies the chemical. The advantages of molecular epidemiology include information about the many toxicants to which a person is exposed over a period of weeks or months and the relative exposure levels. The disadvantage is the absence of information about the mechanism of toxicity. Untargeted adductomics examines albumin and hemoglobin adducts, which serve as biomarkers of exposure but do not identify the proteins and genes responsible for the toxicity. Targeted adductomics is used when the origin of the toxicity is known. This can be either an adducted protein, such as the butyrylcholinesterase protein modified by nerve agents, or a toxicant, such as acetaminophen. Untargeted adductomics methods have identified potential protein adduct biomarkers of breast cancer, colorectal cancer, childhood leukemia, and lung cancer. Adductomics is a new research area that offers structural insights into chemical exposures and a platform for the discovery of disease biomarkers. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Novel synthetic derivatives of cinnamic and

Changes in Stage at Presentation among Lung and Breast Cancer Patients During the COVID-19 Pandemic.

The COVID-19 pandemic altered access to healthcare by decreasing number of patients able to receive preventative care and cancer screening. We hypothesized that given these changes in access to care, radiologic screening for breast and lung cancer would be decreased, and patients with these cancers would consequently present at later stages of their disease. Retrospective cross-sectional study of 2017-September 2021 UMass Memorial Tumor Registry for adult breast and lung cancer patients. Changes in stage at presentation of breast and lung cancer during the COVID-19 pandemic were measured, defined as prior to and during COVID-19. There were no statistically significant changes in the overall stage of presentation before or during the COVID-19 pandemic for either breast or lung cancer patients. Analysis of case presentation and stage during periods of COVID-19 surges that occurred over the time of this study compared to pre-pandemic data demonstrated a statistically significant decrease in overall presentation of breast cancer patients in the first surge, with no other statistically significant changes in breast cancer presentation. A non-statistically significant decrease in lung cancer presentations was seen during the initial surge of COVID-19. There was also a statistically significant increase in early-stage presentation of lung cancer during the second and third COVID-19 surges. In the two years after the COVID-19 pandemic we were not able to demonstrate stage migration at presentation of breast and lung cancer patients to later stages despite decreases in overall presentation during the initial two years of the COVID pandemic. An increase in early-stage lung cancer during the second and third surges is interesting and could be related to increased chest imaging for COVID pneumonia.

Enhanced characterization of breast cancer phenotypes using Raman micro-spectroscopy on stainless steel substrate.

Biochemical insights into varying breast cancer (BC) phenotypes can provide a fundamental understanding of BC pathogenesis, while identifying novel therapeutic targets. Raman spectroscopy (RS) can gauge these biochemical differences with high specificity. For routine RS, cells are traditionally seeded onto calcium fluoride (CaF

Broad reactivity and enhanced potency of recombinant anti-EGFR × anti-CD3 bispecific antibody-armed activated T cells against solid tumours.

Dairy animals and breast cancer reflections on a long-term study from the 1970s that was never done.

In this short commentary I recall a long-term experiment that was sketched out to determine if the low incidence of mammary cancer in dairy animals reflects a low incidence in these species generally or is the result of a protective effect of early pregnancy and long lactations. Although that experiment was never done, I discuss these questions in the light of developing knowledge on the incidence of cancer in ruminants generally and in the mammary gland in particular.

Effect of DPP4CD26 expression on SARS‑CoV‑2 susceptibility, immune response, adenosine (derivatives m

The worldwide COVID‑19 pandemic was brought on by a new coronavirus (SARS Cov‑2). A markerreceptor called Dipeptidyl peptidase 4CD26(DPP4CD26) may be crucial in determining susceptibility to tumors and coronaviruses. However, the regulation of DPP4 in COVID‑invaded cancer patients and its role on small molecule compounds remain unclear. The present study used the Human Protein Atlas, Monaco, and Schmiedel databases to analyze the expression of DPP4 in human tissues and immune cells. The association between DPP4 expression and survival in various tumor tissues was compared using GEPIA 2. The DNMIVD database was used to analyze the correlation between DPP4 expression and promoter methylation in various tumors. On the cBioPortal network, the frequency of

LAPTM5 regulated by FOXP3 promotes the malignant phenotypes of breast cancer through activating the Wntβ‑catenin pathway.

Breast cancer remains the most common malignancy and the leading cause of cancer‑associated mortality in women worldwide. Lysosomal protein transmembrane 5 (LAPTM5), a lysosomal membrane protein, plays an important role in several human malignancies. However, the biological functions and mechanism of LAPTM5 in breast cancer remain unclear. In the present study, the potential tumor‑promoting effect of LAPTM5 was predicted by bioinformatics analysis. LAPTM5 was highly expressed in breast cancer clinical specimens. Moreover,

Lactate secreted via MCT4 from bone‑colonizing breast cancer excites sensory neurons via GPR81.

Breast cancer (BC) bone metastasis causes bone pain (BP), which detrimentally damages the quality of life and outcome of patients with BC. However, the mechanism of BC‑BP is poorly understood, and effective treatments are limited. The present study demonstrated a novel mechanism of BC‑BP using a mouse model of bone pain, in which mouse (EO771) and human (MDA‑MB‑231) BC cells were injected in the bone marrow cavity of tibiae. Western blot analysis using sensory nerves,

THE EFFECT OF ADJUVANT RADIOTHERAPY ON SKIN BIOPHYSICAL PROPERTIES IN PATIENTS WITH BREAST CANCER AT RISK FOR BREAST LYMPHEDEMA A PROSPECTIVE STUDY.

Breast cancer (BC) is the most common type of cancer among women. Radiotherapy (RT) is one of the main and primary treatment options for BC, especially in breast-conserving surgery (BCS). BC patients who underwent RT experience a wide range of symptoms, in which breast edema and irritation of the skin take the lions share. Breast edemalymphedema, which is also a prominent side effect after RT should be well determined in earlier settings due to the chronicity of lymphedema. Therefore, this study aimed to analyze the biophysical parameters of skin on the ipsilateral (IL) and contralateral (CL) sites via Tissue dielectric constant (TDC) and Trans epidermal water loss (TEWL) methods in terms of edema and skin barrier function (SBF). The following reference points before and after the RT were measured (R1 Pectoralis muscle, R2 Upper breast, R3 Lower breast, R4 Lateral site of the thorax). A total of 24 BC patients (mean age and BMI 52.78±9.85 years and 28.42±5.64 kgm

A dose planning study for cardiac and lung dose sparing techniques in left breast cancer radiotherapy Can free breathing helical tomotherapy be considered as an alternative for deep inspiration breath hold

To investigate the possibility to be able to offer left sided breast cancer patients, not suitable for DIBH, an organ at risk saving treatment. Twenty patients receiving radiotherapy for left breast cancer in DIBH were enrolled in the study. Planning CT scans were acquired in the same supine treatment position in FB and DIBH. 3DCRTDIBH plans were designed and optimized using two parallel opposed tangent beams (with some additional segments) for the breast and chest wall and anterior-posterior fields for regional lymph nodes irradiation. Additionally, FB helical tomotherapy plans were optimized to minimize heart and lung dose. All forty plans were optimized with at least 95% of the total CTV covered by the 95% of prescribed dose of 50 Gy in 25 fractions. HTFB plans showed significantly better dose homogeneity and conformity compared to the 3DCRTDIBH specially for regional nodal irradiation. The heart mean dose was almost comparable in 3DCRTDIBH and HTFB while the volume (%) of the heart receiving 25 Gy had a statistically significant reduction from 7.90 ± 3.33 in 3DCRTDIBH to 0.88 ± 0.66 in HTFB. HTFB was also more effective in left descending artery (LAD) mean dose reduction about 100% from 30.83 ± 9.2 Gy to 9.7 ± 3.1. The ipsilateral lung volume receiving 20 Gy has a further reduction of 43 % in HTFB compared with 3DCRTDIBH. For low dose comparison, 3DCRTDIBH was superior for contralateral organ sparing compared to the HTFB due to the limited angle for dose delivery. For patients who cannot be a candidate for DIBH for any reason, HT in free breathing may be a good alternative and provides heart and ipsilateral lung dose sparing, however with the cost of increased dose to contralateral breast and lung.

The optimal regional irradiation volume for breast cancer patients A comprehensive systematic review and network meta-analysis of published studies.

Currently, the optimal adjuvant regional nodal irradiation (RNI) volume for breast cancer (BC) remained controversial. We aimed to define the optimal RNI treatment volume for BC by using a comprehensive network meta-analysis (NMA) of published studies. PubMed, Embase, Medline, and Cochrane Central Register of Controlled Trials were searched from database inception to 30 May 2022. Studies assessing different adjuvant RNI volumes for BC were eligible for inclusion. The primary outcome was overall survival (OS), and secondary outcome was disease-free survival (DFS) and distant-metastasis-free survival (DMFS). A total of 29,640 BC patients from twenty studies were included. The pooled hazard ratio demonstrated that internal mammary node irradiation (IMNI) in BC patients significantly improved OS giving HR (hazard ratio) of 0.87 (95%CI 0.83-0.91, Our pooled results demonstrated that RNI with IMNI yielded a significant survival advantage for BC patients. NMA showed that CWWBRNI with IMNI was the optimal radiation volume for BC patients.

Dual Sensitization Anti-Resistant Nanoparticles for Treating Refractory Breast Cancers via Apoptosis-Inducing.

Current chemotherapy fails to offer a desirable efficacy in clinical treatment against breast cancer due to the extensive multi-drug resistance. In this study, we developed dual sensitization anti-resistant nanoparticles to treat refractory breast cancer, aiming to benefit from photodynamic therapy and chemotherapy. Hyaluronic acid (HA) derivative and photosensitizer chlorin e6 (Ce6) derivative were synthesized and confirmed by mass spectrometry. These derivatives and the chemotherapy agent paclitaxel were incorporated into nanoparticles by an emulsion-solvent evaporation method. The prepared nanoparticles were characterized by dynamic laser scattering, atomic force microscopy, and high performance liquid chromatography (HPLC). The efficacy and mechanisms of the nanoparticles, both in vitro and in vivo, were investigated by flow cytometry, confocalfluorescence microscopy, and a high-content screening system. The prepared dual sensitization anti-resistant nanoparticles were round with a diameter of 100 nm, exhibiting high encapsulation efficiency for the anticancer agent paclitaxel. The nanoparticles demonstrated a robust inhibitory effect against drug-resistant breast cancer cells by enhanced uptake, synergistic effect of photodynamic therapy and chemotherapy, and apoptosis-inducing via multiple pathways. In vivo efficacy, biocompatibility and safety were further confirmed acceptable in tumor-bearing mice. The prepared dual sensitization anti-resistant nanoparticles were promising to treat refractory breast cancer with a controllable treatment site and minimal side effects.

Prognostic Significance of the CXCLs and Its Impact on the Immune Microenvironment in Ovarian Cancer.

The chemokine (C-X-C motif) ligand (CXCL) family in tumor tissue is closely related to tumor growth, metastasis, and survival. However, the differential expression profile and prognostic value of the CXCLs in ovarian cancer (OC) have not been elucidated. Therefore, we studied the expression levels and mutations of CXCLs in OC patient in TCGA and various public databases. The expression differences of CXCLs in OC cancer tissues and normal tissues were compared through the Gene Expression Profiling Interactive Analysis (GEPIA) database. The effect of CXCLs on OC prognosis was analyzed using the Kaplan-Meier curves in GEPIA database. The impact of CXCLs on immune infiltration and clinicopathological outcomes in OC was assessed using the TIMER algorithm. Compared with normal tissues, we found that eight CXCLs were significantly differentially expressed in OC. The expression levels of CXCL9 (

Myocardial Infarction-Induced INSL6 Decrease Contributes to Breast Cancer Progression.

Myocardial infarction (MI) induces early-stage breast cancer progression and increases breast cancer patients mortality and morbidity. Insulin-like peptide 6 (INSL6) overexpression can impede cardiotoxin-induced injury through myofiber regeneration, playing a significant role in MI progression. To investigate the diverse significance of INSL6 in a variety of malignant tumors, we explored INSL6 through MI GEO dataset and multiple omics data integrative analysis, such as gene expression level, enriched pathway analysis, protein-protein interaction (PPI) analysis, and immune subtypes as well as diagnostic value and prognostic value in pancancer. INSL6 expression was downregulated in the MI group, and overall survival analysis demonstrated that INSL6 could be the prognostic biomarkers in the overall survival of breast cancer (BRCA). INSL6 expression differs significantly not only in most cancers but also in different molecular and immune subtypes of cancers. INSL6 might be a potential diagnostic and prognostic biomarker of cancers due to the high accuracy in diagnostic and prognostic value. Furthermore, we focused on BRCA and further investigated INSL6 from the perspective of the correlations with clinical characteristics, prognosis in different clinical subgroups, coexpression genes, and differentially expressed genes (DEGs) and PPI analysis. Overall survival and disease-specific survival analysis of subgroups in BRCA demonstrated that lower INSL6 expression had a worse prognosis. Therefore, INSL6 aberrant expression is associated with the progression and immune cell infiltration of the tumor, especially in KIRP and BRCA. Therefore, INSL6 may serve as a potential prognostic biomarker and the crosstalk between MI and tumor progression.

Flexible human serum albumin nanocapsules to enhance drug delivery and cellular uptake for photodynamicchemo cancer therapy.

As a non-invasive cancer treatment, photodynamic therapy (PDT) has great applications in superficial tumors because of its high selectivity and low cumulative toxicity. However, the poor tumor-targeting ability and short blood circulation time of conventional photosensitizers (PSs) limit the efficacy of PDT to some extent. In this study, we synthesized flexible hollow human serum albumin (HHSA) and loaded photosensitizer Chlorin e6 (Ce6) and the chemotherapeutic drug Doxorubicin (DOX) for synergistic cancer therapy. HHSA can enhance drug delivery and cellular uptake through targeting gp60 and SPARC receptors and unique flexible hollow structures. The TEM images show that HHSA possesses distinct flexible hollow structures, as well as good monodispersity and deformability. After loading Ce6 and DOX, HHSACe6-DOX displays better therapeutic effects than HHSADOX on the growth of 4T1 breast cancers without irradiation. Remarkably, it has a significantly higher therapeutic effect (relative cell activity 45%

End-of-neoadjuvant treatment circulating microRNAs and HER2-positive breast cancer patient prognosis An exploratory analysis from NeoALTTO.

The absence of breast cancer cells in surgical specimens, Patients treated within the trastuzumab arm ( Starting from 23 circulating miRNAs associated with EFS in the training set, we generated a 3-circulating miRNA prognostic signature consisting of miR-185-5p, miR-146a-5p, miR-22-3p, which was confirmed in the testing set. The 3-circulating miRNA signature showed a C-statistic of 0.62 (95% confidence interval 95%CI 0.53-0.71) in the entire study cohort. By resorting to a multivariate Cox regression model we found a statistical significant interaction between the expression values of miR-194-5p and pCR status (p.interaction 0.005) with an estimate Hazard Ratio (HR) of 1.83 (95%CI 1.14- 2.95) in patients with pCR, and 0.87 (95%CI 0.69-1.10) in those without pCR. Notably, the model including this interaction along with the abovementioned 3-circulating miRNA signature provided the highest discriminatory capability with a C-statistic of 0.67 (95%CI 0.58-0.76). Circulating miRNAs are informative to identify patients with different prognosis among those with heterogeneous response after trastuzumab-based neoadjuvant treatment, and may be an exploitable tool to select candidates for salvage adjuvant therapy.

Intermammary breast cancer A rare case of cancer with origin of breast cells in an unusual location.

The most common type of cancer among the female population is breast cancer. The most common site for the occurrence of breast cancer is the upper outer quadrant the upper inner quadrant is the second site, and both the lower outer and the lower inner quadrants are in the third place. This problem is rarely seen in the central portion. Intermammary metastasis due to breast cancer is an infrequent finding. This article presents a 62-year-old lady who presented to the surgical ward with intermammary swelling that appeared suddenly 3 months ago. Ultrasound examination showed a hypoechoic micro-lobulated mass with internal vascularity on the chest wall. Although core needle biopsy suspected invasive ductal carcinoma, both right and left axillary lymph nodes were normal and free. The patient was consulted by an oncologist who recommended radiotherapy before surgery and chemotherapy before and after surgery. This study aims to report and discuss a rare case of intermammary cancer with the origin of breast cells without breast and axillary lymph node involvement. Although the intermammary region is an extremely rare location where breast cancer could occur, its management strategy is the same as other breast cancers.

Corrigendum Systemic treatment of breast cancer. 1st Central-Eastern European professional Consensus Statement on breast cancer.

This corrects the article DOI 10.3389pore.2022.1610383..

National Patterns of Early Adoption of Magnetic Resonance Imaging-Guided Linear Accelerators in 2018 to 2019.

Adaptive magnetic resonance imaging-guided linear accelerators (aMRI-LINACs) are an emerging technology with the potential to improve radiation treatment for cancer through improved visualization and adaptive treatment. Given the competing forces of the increased cost, knowledge, and staff required for aMRI-LINAC therapy, it is unpredictable how rapidly and for whom aMRI-LINAC therapy is being adopted. Therefore, given that aMRI-LINAC therapy was granted approval from the Food and Drug Administration in late 2017, we evaluated the National Cancer Database (NCDB) to obtain a nationwide view of early aMRI-LINAC adoption in 2018 to 2019. Forty-three disease sites were aggregated. A sample of patients who underwent intensity modulated radiation therapy (IMRT) from 2018 to 2019 were matched 11 by stage for the top 4 cancer sites. We then compared 9 characteristics of interest (age, % White vs non-White, % residing in metro areas, % living in the greatest income quartile, % insured by Medicare, % uninsured or unknown insurance status, % treated at a comprehensive cancer center or academic center, % with no recorded Charlson-Deyo comorbidities, and % residing in an area with highest educational) between the 2 samples (aMRI-LINAC and matched IMRT). Only 171 patients were recorded as having been treated with aMRI-LINACs in the NCDB in 2018 to 2019. Fifty-six percent were male, 89% White, and 54% enrolled in Medicare. The most common sites of disease treated were lung (33 patients), pancreas (30 patients), prostate (29 patients), and breast (23 patients). There were no significant differences between aMRI-LINAC- and IMRT-matched patients except that patients with lung or breast cancer treated with aMRI-LINAC were significantly more likely to be treated at a comprehensive cancer center or academic center. aMRI-LINAC adoption recorded in the NCDB after Food and Drug Administration approval was potentially underreported, slow, and attributed to academic sites of practice. Further longitudinal study will be needed to assess how practice patterns evolve with greater adoption.

Estimating Carbon Dioxide Emissions and Direct Power Consumption of Linear Accelerator-Based External Beam Radiation Therapy.

Climate change is one of the direst health threats that humanity faces. We aim to estimate the carbon dioxide (CO We identified patients with the 4 most common cancer types treated with curative-intent EBRT. Beam-on time for each fraction was extracted from the treatment planning system and averaged over each site and treatment modality. The power was multiplied by the beam-on time in hours to yield kilowatt hours (kWh). Using the US Environmental Protection Agency Greenhouse Gas Equivalencies calculator, we converted the kWh into estimates of CO A total of 10 patients were included for each of the following modalities conventionally fractionated for prostate cancer (28 fractions fx), prostate stereotactic body radiation therapy (SBRT) (5 fx), 15- and 5-fx regimens for early-stage breast cancer, 3- and 5-fx SBRT regimens for early-stage lung cancer, conventional EBRT (30 fx) for locally advanced lung cancer, and short- (5 fx) and long-course (25-28 fx) for rectal cancer. The modality with the lowest and highest carbon emissions per course, on average, was prostate SBRT (2.18 kg CO We have estimated CO

Smart Chondroitin Sulfate Micelles for Effective Targeted Delivery of Doxorubicin Against Breast Cancer Metastasis.

Metastasis is a major challenge in breast cancer therapy. The successful chemotherapy of breast cancer largely depends on the ability to block the metastatic process. Herein, we designed a dual-targeting and stimuli-responsive drug delivery system for targeted drug delivery against breast cancer metastasis. AS1411 aptamer-modified chondroitin sulfate A-ss-deoxycholic acid (ACSSD) was synthesized, and the unmodified CSSD was used as the control. Chemotherapeutic drug doxorubicin (DOX)-containing ACSSD (D-ACSSD) micelles were prepared by a dialysis method. The ACSSD conjugate was confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and transmission electron microscopy (TEM). In vitro cellular uptake and cytotoxicity of D-ACSSD micelles were studied by confocal laser scanning microscopy (CLSM) and MTT assay in breast tumor cells. The inhibition capability of D-ACSSD micelles in cell migration and invasion was carried out in 4T1 cells. In vivo antitumor activity of DOX-containing micelles was investigated in metastatic 4T1-bearing Balbc mice. D-ACSSD and DOX-loaded CSSD (D-CSSD) micelles exhibited high drug encapsulation content and reduction-responsive characteristics. D-ACSSD micelles were spherical in shape. Compared with D-CSSD, D-ACSSD showed higher cellular uptake and more potent killing activity in 4T1 and MDA-MB-231 cells. Additionally, D-ACSSD exhibited stronger inhibitory effects on the invasion and migration of highly metastatic 4T1 cells than unmodified D-CSSD. Among the DOX-containing formulations, D-ACSSD micelles presented the most effective inhibition of tumor growth and lung metastasis in orthotopic 4T1-bearing mice in vivo. It also revealed that ACSSD micelles did not exhibit obvious systemic toxicity. The smart D-ACSSD micelles could be a promising delivery system for the therapy of metastatic breast cancer.

Role of miR‑200 family in brain metastases A systematic review.

Brain metastasis (BM) represents the single most severe neurological complication of systemic cancer. The prognosis of patients with BM is poor, irrespective of the implemented treatment. The present study performed a systematic review of the literature using three online databases (PubMed, Scopus and Web of Science). Recently, a number of small RNA molecules, the microRNAs (miRNAsmiRs), have attracted increasing scientific attention. Members of the miR-200 family, which includes five miRNAs (miR-141, miR-200a, miR-200b, miR-200c and miR-429) appear to play pivotal roles in cancer initiation and metastasis. Indeed, a systematic review of the pertinent literature revealed that miR-200 family members regulate the brain metastatic cascade, particularly by modulating epithelial-to-mesenchymal transition. That holds true for the major representatives of BM, including lung and breast cancer, as well as for other less frequent secondary lesions originating from melanoma and the gastrointestinal tract. Therefore, the miRNAs may serve as potential diagnostic andor prognostic markers, and under specific circumstances, as invaluable therapeutic targets. However, the available clinical evidence is relatively limited. A number of studies have suggested that the miR-200 family members are accurate prognostic markers of survival and resistance to chemotherapy in patients with breast cancer. Similarly, they may prove helpful in differentiating a metastatic lesion from a malignant glioma, or a hemangioblastoma from a renal cell carcinoma in patients with von Hippel Lindau syndrome, based on a cerebrospinal fluid sample. However, currently, there is no known therapeutic role for miR-200 family members in the setting of BM.

Translation and linguistic validation of the Pittsburgh Fatigability Scale for Korean breast cancer survivors A cognitive interviewing study.

Fatigability-the perception of fatigue contextualized to activities of fixed intensity and duration-has received growing attention in oncology research. This study aimed to translate and linguistically validate a Korean-language version of the Pittsburgh Fatigability Scale. Following the Linguistic Validation Manual for Health Outcome Assessment, we applied a multi-stage cognitive interviewing (CI) method to ensure accurate translation and interpretation of the Pittsburgh Fatigability Scale. After forward- and backward-translation were completed, three rounds of CI regarding the translated instrument were performed with 18 participants having or not having breast cancer. The first round of CI showed that seven items of the 10-item Korean-language instrument required revision to reflect the physical abilities of breast cancer patients with similar levels of physical activity. After the second round, two additional items were revised to reflect the cultural context and gender roles. During the third round, all participants exhibited full understanding of the Korean-language instrument. The translated instrument, its quality enriched by cross-cultural linguistic validation in combination with CI, can be effectively used to assess perceived physical and mental fatigability. Use of the Pittsburgh Fatigability Scale can facilitate oncology nurses assessment of perceived fatigue levels in cancer patients and can expand understanding of how patients fatigue perceptions are related to their exercise capacity. This study is valuable as an example of how a multi-stage CI process can be effectively applied in cross-cultural oncology research.

Environmentally Induced Sperm RNAs Transmit Cancer Susceptibility to Offspring in a Mouse Model.

DNA sequence accounts for the majority of disease heritability, including cancer. Yet, not all familial cancer cases can be explained by genetic factors. It is becoming clear that environmentally induced epigenetic inheritance occurs and that the progenys traits can be shaped by parental environmental experiences. In humans, epidemiological studies have implicated environmental toxicants, such as the pesticide DDT, in intergenerational cancer development, including breast and childhood tumors. Here, we show that the female progeny of males exposed to DDT in the pre-conception period have higher susceptibility to developing aggressive tumors in mouse models of breast cancer. Sperm of DDT-exposed males exhibited distinct patterns of small non-coding RNAs, with an increase in miRNAs and a specific surge in miRNA-10b levels. Remarkably, embryonic injection of the entire sperm RNA load of DDT-exposed males, or synthetic miRNA-10b, recapitulated the tumor phenotypes observed in DDT offspring. Mechanistically, miR-10b injection altered the transcriptional profile in early embryos with enrichment of genes associated with cell differentiation, tissue and immune system development. In adult DDT-derived progeny, transcriptional and protein analysis of mammary tumors revealed alterations in stromal and in immune system compartments. Our findings reveal a causal role for sperm RNAs in environmentally induced inheritance of cancer predisposition and, if confirmed in humans, this could help partially explain some of the missing heritability of breast, and other, malignancies.

Chemoproteomic Profiling Reveals that Anti-Cancer Natural Product Dankastatin B Covalently Targets Mitochondrial VDAC3.

Chlorinated gymnastatin and dankastatin alkaloids derived from the fungal strain

Paracrine enhancement of tumor cell proliferation provides indirect stroma-mediated chemoresistance via acceleration of tumor recovery between chemotherapy cycles.

The ability of tumors to survive therapy is mediated not only by cell-intrinsic but also cell-extrinsic, microenvironmental mechanisms. Across many cancers, including triple-negative breast cancer (TNBC), a high stromatumor ratio correlates with poor survival. In many contexts, this correlation can be explained by the direct reduction of therapy sensitivity by stroma-produced paracrine factors through activating pro-survival signaling and stemness. We sought to explore whether this direct effect contributes to the link between stroma and poor responses to chemotherapies in TNBC. Our

LINKIN-associated proteins necessary for tissue integrity during collective cell migration.

Cell adhesion plays essential roles in almost every aspect of metazoan biology. Previously, using the developmental migration of the nematode male gonad as a platform, LINKIN (Human ITFG1,

Breast adipose tissue-derived extracellular vesicles from women with obesity stimulate mitochondrial-induced dysregulated tumor cell metabolism.

Breast adipose tissue is an important contributor to the obesity-breast cancer link. Dysregulated cell metabolism is now an accepted hallmark of cancer. Extracellular vesicles (EVs) are nanosized particles containing selective cargo, such as miRNAs, that act locally or circulate to distant sites to modulate target cell functions. Here, we found that long-term education of breast cancer cells (MCF7, T47D) with EVs from breast adipose tissue of women who are overweight or obese (O-EVs) leads to sustained increased proliferative potential. RNA-Seq of O-EV-educated cells demonstrates increased expression of genes, such as ATP synthase and NADH ubiquinone oxidoreductase, involved in oxidative phosphorylation. O-EVs increase respiratory complex protein expression, mitochondrial density, and mitochondrial respiration in tumor cells. Mitochondrial complex I inhibitor, metformin, reverses O-EV-induced cell proliferation. Several miRNAs, miR-155-5p, miR-10a-3p, and miR-30a-3p, which promote mitochondrial respiration and proliferation, are enriched in O-EVs relative to EVs from lean women. O-EV-induced proliferation and mitochondrial activity are associated with stimulation of the AktmTORP70S6K pathway, and are reversed upon silencing of P70S6K. This study reveals a new facet of the obesity-breast cancer link with human breast adipose tissue-derived EVs causing the metabolic reprogramming of ER breast cancer cells.

Evaluating ChatGPT as an Adjunct for Radiologic Decision-Making.

ChatGPT, a popular new large language model (LLM) built by OpenAI, has shown impressive performance in a number of specialized applications. Despite the rising popularity and performance of AI, studies evaluating the use of LLMs for clinical decision support are lacking. To evaluate ChatGPTs capacity for clinical decision support in radiology via the identification of appropriate imaging services for two important clinical presentations breast cancer screening and breast pain. We compared ChatGPTs responses to the American College of Radiology (ACR) Appropriateness Criteria for breast pain and breast cancer screening. Our prompt formats included an open-ended (OE) format, where ChatGPT was asked to provide the single most appropriate imaging procedure, and a select all that apply (SATA) format, where ChatGPT was given a list of imaging modalities to assess. Scoring criteria evaluated whether proposed imaging modalities were in accordance with ACR guidelines. ChatGPT achieved an average OE score of 1.83 (out of 2) and a SATA average percentage correct of 88.9% for breast cancer screening prompts, and an average OE score of 1.125 (out of 2) and a SATA average percentage correct of 58.3% for breast pain prompts. Our results demonstrate the feasibility of using ChatGPT for radiologic decision making, with the potential to improve clinical workflow and responsible use of radiology services.

Diffsig Associating Risk Factors With Mutational Signatures.

Somatic mutational signatures elucidate molecular vulnerabilities to therapy and therefore detecting signatures and classifying tumors with respect to signatures has clinical value. However, identifying the etiology of the mutational signatures remains a statistical challenge, with both small sample sizes and high variability in classification algorithms posing barriers. As a result, few signatures have been strongly linked to particular risk factors. Here we present

LRRC3B and its promoter hypomethylation status predicts response to anti-PD-1 based immunotherapy.

The leucine rich repeat containing 3B (LRRC3B) gene is a tumor suppressor gene involved in the anti-tumor immune microenvironment. Expression of LRRC3B and DNA methylation at the LRRC3B promoter region may serve as a useful marker to predict response to anti-PD-1 therapy. However, no studies have yet systematically explored the protective role of LRRC3B methylation in tumor progression and immunity. Expression of LRRC3B of 33 cancer types in The Cancer Genome Atlas (TCGA) was downloaded from UCSC Xena (httpxena.ucsc.edu). And, we evaluated the differential expression of LRRC3B according to tumor stage, overall survival, and characteristics of the tumor microenvironment. The immunotherapeutic cohorts included IMvigor21, GSE119144, and GSE72308 which were obtained from the Gene Expression Omnibus database. We conducted pearson correlation analysis of LRRC3B and tumor microenvironment (TME) in pan-cancer. Also, six immune cell types (B cells, CD8 T cells, CD4 T cells, macrophages, neutrophils, and dendritic cells) and tumor purity were analyzed using the Tumor IMmune Estimation Resource (TIMER1.0) (Tumor IMmune Estimation Resource (TIMER2.0). And, a silencing score model base on LRRC3B promoter methylation to predict overall survival (OS) by multivariate Cox regression analysis was constructed. Finally, the model was applied to predict anti-PD-1 therapy in non-small cell lung cancer (NSCLC) and breast cancer (BRCA). LRRC3B expression associated with less tumor invasion, less severe tumor stage, and decreased metastasis. The inactivation of LRRC3B promoted the enrichment of immuneosuppressive cells, including myeloid-derived suppressor cells (MDSCs), cancer-associated fibroblasts (CAFs), M2 subtype of tumor-associated macrophages (M2-TAMs), M1 subtype of tumor-associated macrophages (M1-TAMs), and regulatory T (Treg) cells. A high silencing score was significantly associated with immune inhibition, low expression of LRRC3B, poor patient survival, and activation of cancer-related pathways. Our comprehensive analysis demonstrated the potential role of LRRC3B in the anti-tumor microenvironment, clinicopathological features of cancer, and disease prognosis. It suggested that LRRC3B methylation could be used as a powerful biomarker to predict immunotherapy responses in NSCLC and BRCA.

Translating an Economic Analysis into a Tool for Public Health Resource Allocation in Cancer Survivorship.

Model complexity and unclear purpose are 2 barriers that prevent lay users from integrating decision science tools into their workflow.Modelers could integrate the user-centered design framework when developing a model for lay users to reduce complexity and ensure the model meets the needs of the users.

Small-cell lung cancer metastasis to a meningioma Case report and review of the literature.

Tumor-to-tumor metastasis is a rare event with meningioma as the recipient tumor accounting for 20% of the reported cases. The most common primary cancers showing this phenomenon are lung and breast cancer. Most lung cancers metastasizing to a meningioma are due to lung adenocarcinoma with the literature containing only 3 prior reports of small-cell lung cancer showing this pattern of spread. Herein, we present the case of a 67-year-old-patient with small-cell lung cancer that developed a metastasis to a meningioma.

Positive Nipple Margins and Oncologic Outcomes of Nipple-Sparing Mastectomy in a Large Community-Based Hospital System.

The American Society of Breast Surgeons recommends sending separate nipple margins (NMs) when performing nipple-sparing mastectomies (NSMs). However, the definition of a positive NM is vague. We evaluated NM management and outcomes in breast cancer patients undergoing NSM from 2010 to 2021 at our community-based hospital system through a retrospective review and descriptive analysis. A total of 619 patients (1086 NSM) were included. Median invasive tumor size was 1.5cm and median follow-up 30 months. Fourteen therapeutic NSMs had tumor within the NMs. Nine were positive using the definition any tumor within the separate NM, and nipple-areolar complex (NAC) excised. Two were negative when positive was defined as any tumor on ink, and were observed without recurrence. Our results suggest positive NMs warranting NAC excision could be interpreted as any tumor on ink and NSMs can be safely performed with low rates of positive NMs and recurrences in high-volume hospitals.

Factors associated with anxiety and depression in cancer patients Demographic factors and the role of demoralization and satisfaction with care.

Anxiety and depression are common in cancer patients and seem to affect quality of life, treatment compliance and even survival. Defining factors related to anxiety and depression and exploring the role of demoralization and satisfaction with care, could contribute to the improvement of patients quality of life and quality of health services as well. A convenience sample of 150 cancer inpatients and outpatients from two oncology centers, with various types of solid tumors, participated in a prospective cross-sectional observational study. The psychometric tools used were the Greek versions of the Hospital Anxiety and Depression Scale (HADS), FAMCARE-Patient Scale and Oncology Palliative Care (FAMCARESCALE) and Demoralization Scale (DEMORALIZATION SCALE II, DS-II). Patients mean age was 62 years (20-85 years) and 89 patients (59.3%) were women. Among patients, 33% had breast, 24% gastrointestinal and 15% lung cancer. Eighty-two patients (54.7%) had metastatic disease. Women showed higher rates of anxiety (p 0.054). Anxiety was inversely related to age (p 0.043) and positively correlated with time since diagnosis (p 0.076). Unmarried patients presented with higher rates of depression (p0.026). Multiple linear regression showed a statistically significant impact of Demoralization factor Meaning and Purpose on anxiety (p <0.001, R2 36.3%) and depression (p <0.001, R2 49%). Moreover, higher educational level (p 0.038, R2 3.1%) is related to higher levels of anxiety and higher scores of FAMCARESCALE factor-Informationinteraction with the health care professionals, is related to lower levels of depression (p0.008, R22.7%). The results highlight the significant impact of demoralization on anxiety and depression in cancer patients. Early recognition of demoralization and early referral to mental health professionals will hopefully alleviate the mental burden of cancer patients. This article is protected by copyright. All rights reserved.

Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-𝜅B-IL-6 axis of tumor-associated macrophages.

Circular RNAs (circRNAs) have important regulatory functions in cancer, but the role of circRNAs in the tumor microenvironment (TME) remains unclear. Moreover, we also explore the effects of si-circRNAs loaded in nanoparticles as therapeutic agent for anti-tumor in vivo. We conducted bioinformatics analysis, qRT-PCR, EdU assays, Transwell assays, co-culture system and multiple orthotopic xenograft models to investigate the expression and function of circRNAs. Additionally, PLGA-based nanoparticles loaded with si-circRNAs were used to evaluate the potential of nanotherapeutic strategy in anti-tumor response. We identified oncogene SERPINE2 derived circRNA, named as cSERPINE2, which was notably elevated in breast cancer and was closely related to poor clinical outcome. Functionally, tumor exosomal cSERPINE2 was shuttled to tumor associated macrophages (TAMs) and enhanced the secretion of Interleukin-6 (IL-6), leading to increased proliferation and invasion of breast cancer cells. Furthermore, IL-6 in turn increased the EIF4A3 and CCL2 levels within tumor cells in a positive feedback mechanism, further enhancing tumor cSERPINE2 biogenesis and promoting the recruitment of TAMs. More importantly, we developed a PLGA-based nanoparticle loaded with si-cSERPINE2, which effectively attenuated breast cancer progression in vivo. Our study illustrates a novel mechanism that tumor exosomal cSERPINE2 mediates a positive feedback loop between tumor cells and TAMs to promote cancer progression, which may serve as a promising nanotherapeutic strategy for the treatment of breast cancer.

Participation in screening for breast and cervical cancer among women with current or previous drug use a survey study.

Women with current or previous drug use (WCPDU) have an increased risk of poor breast and cervical cancer outcomes. Screening is known to decrease the mortality of these common cancer forms, but screening participation has been sparsely investigated among women with drug dependency. The aim of this study was to assess participation in screening for breast and cervical cancer among WCPDU. We recruited WCPDU to a survey study, from six opioid substitution treatment (OST) clinics and one needle exchange program (NEP) in Malmö, Sweden, and through the Drug Users Union in Stockholm, Sweden. The survey was constructed according to results from focus group discussions about cancer screening in a sample of women in OST. Survey data were analyzed using descriptive statistics. We analyzed associations between non-compliance to screening and healthcare contact (OST, NEP or none) by logistic regression analysis unadjusted and adjusted for age, native language, housing situation, educational attainment and main source of income. A total of 298 women (median age 43 years) responded to the survey. The self-reported compliance with cancer screening recommendations was 29% for breast cancer screening and 41% for cervical cancer screening. Non-compliance with cervical cancer screening was associated with NEP participation in univariate but not multivariate analysis. We did not find an association between non-compliance with breast cancer screening and healthcare contact. Non-compliance with screening for cervical cancer was also associated with unstable housing in univariate and multivariate analyses, and inversely associated with increasing age in a univariate analysis. Non-compliance with breast cancer was associated with unstable housing in a univariate analysis, and inversely associated with not having Swedish as a native language in a multivariate analysis. The self-reported compliance with the national cancer screening programs for breast cancer and cervical cancer of WCPDU is notably lower than in the Swedish general population. Women with unstable housing seem to be particularly vulnerable to non-compliance with cancer screening. Interventions to minimize barriers to cancer screening are crucial to decrease the increased cancer morbidity and mortality among WCPDU.

Recent advances of small extracellular vesicle biomarkers in breast cancer diagnosis and prognosis.

Current clinical tools for breast cancer (BC) diagnosis are insufficient but liquid biopsy of different bodily fluids has recently emerged as a minimally invasive strategy that provides a real-time snapshot of tumour biomarkers for early diagnosis, active surveillance of progression, and post-treatment recurrence. Extracellular vesicles (EVs) are nano-sized membranous structures 50-1000 nm in diameter that are released by cells into biological fluids. EVs contain proteins, nucleic acids, and lipids which play pivotal roles in tumourigenesis and metastasis through cell-to-cell communication. Proteins and miRNAs from small EVs (sEV), which range in size from 50-150 nm, are being investigated as a potential source for novel BC biomarkers using mass spectrometry-based proteomics and next-generation sequencing. This review covers recent developments in sEV isolation and single sEV analysis technologies and summarises the sEV protein and miRNA biomarkers identified for BC diagnosis, prognosis, and chemoresistance. The limitations of current sEV biomarker research are discussed along with future perspective applications.

Expression of substance P, neurokinin 1 receptor, Ki-67 and pyruvate kinase M2 in hormone receptor negative breast cancer and evaluation of impact on overall survival.

Chronic inflammation is a hallmark of cancer, and it can be stimulated by many factors. Substance P (SP), through binding to neurokinin 1 receptor (NK1R), and pyruvate kinase M2 (PKM2) play critical roles in cancer development and progression via modulating the tumor microenvironment. This study aimed to investigate the prognostic significance of SP and PKM2 in combination with NK1R and Ki-67 in hormone receptor negative (HR-ve) breast cancer. Immunohistochemical expression levels of SP, NK1R, PKM2, and Ki-67 were measured in 144 paraffin-embedded breast cancer tissues (77 h -ve and 67 h ve). SP, NK1R, and PKM2 were scored semiquantitatively, while Ki-67 was obtained by the percentage of total number of tumor cells with nuclear staining. The optimal cutoff value for SP, NK1R, PKM2, and Ki-67 were assessed by Cutoff Finder. High SP expression in HR -ve breast cancer was associated with TNM stage (p 0.020), pT stage (p 0.035), pN stage (p 0.002), axillary lymph node metastasis (p 0.003), and NK1R expression level (p 0.010). In HR ve breast cancer, SP expression was associated with HER2 status (p 0.001) and PKM2 expression level (p 0.012). Regarding PKM2 expression level, it significantly associated with HER2 status (p 0.001) and history of DCIS (p 0.046) in HR-ve tumors, and with HER2 status (p < 0.001) and SP expression level (p 0.012) in HR ve tumors. Survival analysis revealed that high SP level negatively impacted overall survival in HR-ve tumors that had low NK1R level (p 0.021). Moreover, high SP negatively impacted overall survival in HR-ve tumors that had low Ki-67 level (p 0.005). High PKM2 negatively impacted overall survival in HR-ve cases with low SP (p 0.047). Combined expression levels of SP with NK1R or Ki-67, and PKM2 with SP could be used to predict survival in breast cancer patients with HR-ve tumors. Our findings suggest a role of SPNK1R pathway and PKM2 in HR-ve breast cancer pathogenesis which should be further investigated to unveil the underlying molecular mechanisms.

Cost-effectiveness of ribociclib versus palbociclib in combination with an aromatase inhibitor as first-line treatment of postmenopausal women with HRHER2- advanced breast cancer analysis based on final OS results of MONALEESA-2 and PALOMA-2.

Background and AimsCombination of a cyclin-dependent kinase 4 and 6 (CDK46) inhibitor and an aromatase inhibitor is the standard of care first-line (1L) treatment of hormone receptor-positive (HR), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Updated clinical data have become available from the MONALEESA-2 and PALOMA-2 trials for ribociclib and palbociclib, respectively. This analysis with updated data assessed the cost-effectiveness of ribociclib versus palbociclib, both in combination with letrozole, in the setting of 1L therapy of postmenopausal women with HRHER2- ABC, from a United Kingdom (UK) National Health Service perspective.MethodsA three state (progression-free, progressed disease, and death) partitioned survival model with a 1-month cycle was developed. Clinical data were derived from MONALEESA-2 (NCT01958021) and PALOMA-2 (NCT01740427). Treatment effect was modelled using hazard ratios (HRs) for progression-free survival and overall survival derived through a matched-adjusted indirect comparison. Trial data and published literature were used to derive utility values. Cost inputs included drug acquisition, disease monitoring, subsequent therapies, and adverse events. Costs and outcomes were discounted by 3.5%, over a 40-year lifetime horizon. One-way and probabilistic sensitivity analyses were performed.ResultsRibociclib dominated palbociclib, and was both overall cost saving (-£3,273) and more effective (1.251 quality-adjusted life years QALYs). Ribociclib total drug costs were £17,156 lower than palbociclib. At a £30,000 per QALY willingness-to-pay threshold, the probability of ribociclib being cost-effective was almost 100%. Ribociclib remained cost-effective when varying HRs, utilities, drug cost, and health state costs.ConclusionsRibociclib is both cost-saving and cost-effective compared with palbociclib for the 1L treatment of postmenopausal women with HRHER2- ABC in the UK.

Using Machine Learning Methods to Assess Lymphovascular Invasion and Survival in Breast Cancer Performance of Combining Preoperative Clinical and MRI Characteristics.

Preoperative assessment of lymphovascular invasion (LVI) in invasive breast cancer (IBC) is of high clinical relevance for treatment decision-making and prognosis. To investigate the associations of preoperative clinical and magnetic resonance imaging (MRI) characteristics with LVI and disease-free survival (DFS) by using machine learning methods in patients with IBC. Retrospective. Five hundred and seventy-five women (range 24-79 years) with IBC who underwent preoperative MRI examinations at two hospitals, divided into the training (N 386) and validation datasets (N 189). Axial fat-suppressed T2-weighted turbo spin-echo sequence and dynamic contrast-enhanced with fat-suppressed T1-weighted three-dimensional gradient echo imaging. MRI characteristics (clinical T stage, breast edema score, MRI axillary lymph node status, multicentricity or multifocality, enhancement pattern, adjacent vessel sign, and increased ipsilateral vascularity) were reviewed independently by three radiologists. Logistic regression (LR), eXtreme Gradient Boosting (XGBoost), k-Nearest Neighbor (KNN), and Support Vector Machine (SVM) algorithms were used to establish the models by combing preoperative clinical and MRI characteristics for assessing LVI status in the training dataset, and the methods were further applied in the validation dataset. The LVI score was calculated using the best-performing of the four models to analyze the association with DFS. Chi-squared tests, variance inflation factors, receiver operating characteristics (ROC), Kaplan-Meier curve, log-rank, Cox regression, and intraclass correlation coefficient were performed. The area under the ROC curve (AUC) and hazard ratios (HR) were calculated. A P-value <0.05 was considered statistically significant. The model established by the XGBoost algorithm had better performance than LR, SVM, and KNN models, achieving an AUC of 0.832 (95% confidence interval CI 0.789, 0.876) in the training dataset and 0.838 (95% CI 0.775, 0.901) in the validation dataset. The LVI score established by the XGBoost model was an independent indicator of DFS (adjusted HR 2.66, 95% CI 1.22-5.80). The XGBoost model based on preoperative clinical and MRI characteristics may help to investigate the LVI status and survival in patients with IBC. 3 TECHNICAL EFFICACY Stage 2.

Peritumoural Oedema as a Predictor of Overall Survival for Patients with Posterior Fossa Metastases.

To analyse the relationship between peritumoural oedema volume and tumour volume in relation to the impact of metastatic posterior fossa tumour survival rates. An observational study. Umraniye Training and Research Hospital, İstanbul, Turkey, from 2011-2021. Fifty-six cancer patients who had been operated upon for cerebellar metastases were analysed retrospectively. To investigate the effect of oedema on survival, patients with a single cerebellar metastasis were evaluated retrospectively. Those patients had a single metastasis located in the cerebellum and did not receive radiotherapy or corticosteroids before surgery. OsiriX MD DICOM viewer was used to calculate the volumes of the tumour and the oedema using fluid-attenuated inversion recovery (FLAIR) and contrast-enhanced magnetic resonance imaging (MRI). The patients were separated into two groups, and the cut-off limit for the oedema to-tumour ratio was set to two. Survival analysis was performed on the two groups. When the primary sites of the tumours were evaluated, 60.7% were located in the lungs (n 34), 10.7% were located in the breasts (n 6), 10.7% were located in the gastrointestinal tract (n 6), 7.1% were located in the renal region (n 4), 5.4% were located in the gynaecologic tract (n 3), and 5.4% were located in other parts of the body (n 3). A univariate analysis showed that overall survival duration was significantly longer in the subgroup with breast cancer (83.3%) and in those patients with a peritumoural oedema volume to tumour volume ratio of less than two (27.6%, p <0.05). Negative prognostic factors were lung cancer and high peritumoural oedema volume. Significant peritumoural oedema was linked to a poor prognosis for cancer patients with a single cerebellar metastasis, especially with lung cancer as the primary source. Cerebellar metastases, Cerebellum, OsiriX MD, Tumour volume.

Effect of hybrid compounds of stilbene and pentadienone on inhibition of tubulin polymerization.

Tubulin polymerization inhibitors induce cancer cell death therefore, they can be developed as chemotherapeutic agents. We hypothesized that hybrid compounds, including the trans-stilbene moiety contained in resveratrol and penta-1,4-dien-3-one contained in curcumin, could inhibit tubulin polymerization. Twenty-six hybrid stilbene and pentadienone compounds were designed and synthesized. The cytotoxicity of the hybrid compounds against MDA-MB-231 human breast cancer cells was determined using a clonogenic long-term survival assay. The relationship between cytotoxicity and structural properties was evaluated. Biological activities, including inhibition of tubulin polymerization and cell cycle progression, were investigated to select compounds with excellent anticancer properties. The molecular binding mode between the selected compound and the α,β-tubulin dimers was investigated. Twenty-six hybrid stilbene and pentadienone compounds were designed and synthesized. Among them, compound 13 exhibited the highest inhibitory effect on the clonogenicity of MDA-MB-231 cells. Compound 13 induced the destabilization of tubulins and inhibited cell cycle progression at the G2M phase. Through in silico molecular docking analysis, compound 13 was predicted to bind to the colchicine binding site of α, β-tubulin. The stilbene and pentadienone hybrid compound 13 has a binding mode similar to that of colchicine. Compound 13 inhibited the clonogenicity of MDA-MB-231 cells through a mechanism that destabilizes tubulin polymerization, leading to cell cycle arrest at the G2M phase.

The role of theragnostics in breast cancer a systematic review of the last 12 years.

Breast cancer is the most common malignancy in women, with high morbidity and mortality. Molecular alterations in breast cancer involve the expression or upregulation of various molecular targets that can be used for diagnostic nuclear medicine imaging and radiopharmaceutical treatment. Theragnostics is based on the binding of radionuclides to molecular targets. These radionuclides can induce a cytotoxic effect on the specific tumor cell (target) or its vicinity, thus allowing a personalized approach to patients with effective treatment and comparably small side effects. This review aims to describe the most promising molecular targets currently under investigation for theragnostics and precision oncology in breast cancer. A comprehensive literature search of studies on theragnostics in breast cancer was performed in the PubMed, PMC, Scopus, Google Scholar, Embase, Web of Science, and Cochrane library databases, between 2010 and 2022, using the following terms breast neoplasm, breast, breast cancer, theragnostic, theranostic, radioligand therap, RLT, MET, FLT, FMISO, FES, estradiol, trastuzumab, PD-L1, PSMA, FAPI, FACBC, fluciclovine, FAZA, GRPR, DOTATOC, DOTATATE, CXC4, endoglin, gastrin, mucin1, and syndecan1. Fifty-three studies were included in the systematic review and summarized in six clinical sections 1) human epidermal growth factor receptor 2 (HER2) 2) somatostatin receptors (SSTRS) 3) prostate-specific membrane antigen radiotracers (PSMA) 4) fibroblast activation protein-α targeted radiotracers 5) gastrin-releasing peptide receptor-targeted radiotracers 6) other radiotracers for theragnostics. The theragnostic approach will progressively allow better patient selection, and improve the prediction of response and toxicity, avoiding unnecessary and costly treatment.

Reciprocal interactions between innate immune cells and astrocytes facilitate neuroinflammation and brain metastasis via lipocalin-2.

Brain metastasis still encompass very grim prognosis and therefore understanding the underlying mechanisms is an urgent need toward developing better therapeutic strategies. We uncover the intricate interactions between recruited innate immune cells and resident astrocytes in the brain metastatic niche that facilitate metastasis of melanoma and breast cancer. We show that granulocyte-derived lipocalin-2 (LCN2) induces inflammatory activation of astrocytes, leading to myeloid cell recruitment to the brain. LCN2 is central to inducing neuroinflammation as its genetic targeting or bone-marrow transplantation from LCN2

Defining the heterogeneity of unbalanced structural variation underlying breast cancer susceptibility by nanopore genome sequencing.

Germline structural variants (SVs) are challenging to resolve by conventional genetic testing assays. Long-read sequencing has improved the global characterization of SVs, but its sensitivity at cancer susceptibility loci has not been reported. Nanopore long-read genome sequencing was performed for nineteen individuals with pathogenic copy number alterations in BRCA1, BRCA2, CHEK2 and PALB2 identified by prior clinical testing. Fourteen variants, which spanned single exons to whole genes and included a tandem duplication, were accurately represented. Defining the precise breakpoints of SVs in BRCA1 and CHEK2 revealed unforeseen allelic heterogeneity and informed the mechanisms underlying the formation of recurrent deletions. Integrating read-based and statistical phasing further helped define extended haplotypes associated with founder alleles. Long-read sequencing is a sensitive method for characterizing private, recurrent and founder SVs underlying breast cancer susceptibility. Our findings demonstrate the potential for nanopore sequencing as a powerful genetic testing assay in the hereditary cancer setting.

Overexpression of POU3F2 promotes radioresistance in triple-negative breast cancer via Akt pathway activation.

POU3F2 is associated with malignant behaviors and poor prognosis in cancer. However, the function and mechanism of POU3F2 in breast cancer remain to be elucidated. Our study aimed to explore the role of POU3F2 in triple-negative breast cancer and radiotherapy. POU3F2 expression was examined by RT-PCR and Western blot. The proliferation of cancer cells was measured by MTT assay. Migration of cancer cells was determined by Transwell assay and wound healing assay. To determine which protein interacts with POU3F2, Co-IP was performed. Survival analysis was performed based on the online database GEPIA. DNA damage after radiation was examined by Comet Assay. Radiosensitivity was evaluated with clonogenic survival assays. A tumor xenograft model was established with MDA-MB-231 breast cancer cells in BALBc nude mice to explore the effect of POU3F2 in vivo. We found that the expression of POU3F2 was significantly elevated in breast cancer cells, especially in TNBC, and higher POU3F2 expression was related to poor prognosis of patients with breast cancer. Functional assays revealed that POU3F2 promoted proliferation, migration, and invasion of triple-negative breast cancer (TNBC) cells in vitro and in vivo. In addition, the knockdown of POU3F2 decreased the radioresistance of TNBC cells in vitro. Furthermore, POU3F2 could enhance the activation of the Akt pathway by interacting with ARNT2, thereby promoting proliferation and radioresistance in TNBC cells. Our results provide evidence that high expression of POU3F2 promotes radioresistance in triple-negative breast cancer via Akt pathway activation by interacting with ARNT2.

Translating transcriptomic findings from cancer model systems to humans through joint dimension reduction.

Model systems are an essential resource in cancer research. They simulate effects that we can infer into humans, but come at a risk of inaccurately representing human biology. This inaccuracy can lead to inconclusive experiments or misleading results, urging the need for an improved process for translating model system findings into human-relevant data. We present a process for applying joint dimension reduction (jDR) to horizontally integrate gene expression data across model systems and human tumor cohorts. We then use this approach to combine human TCGA gene expression data with data from human cancer cell lines and mouse model tumors. By identifying the aspects of genomic variation joint-acting across cohorts, we demonstrate how predictive modeling and clinical biomarkers from model systems can be improved.

Clinical outcome and prognostic factors for Asian patients in Phase I clinical trials.

Patient selection is key in Phase I studies, and prognosis can be difficult to estimate in heavily pre-treated patients. Previous prognostic models like the Royal Marsden Hospital (RMH) score or using the neutrophil-lymphocyte ratio (NLR) have not been validated in current novel therapies nor in the Asian Phase I population. We conducted a retrospective review of 414 patients with solid tumours participating in Phase I studies at our centre between October 2013 and December 2020. The RMH model showed poorer prognosis with increasing scores RMH score 1, HR 1.28 (95% CI 0.96-1.70) RMH score 2, HR 2.27 (95% CI 1.62-3.17) RMH score 3, HR 4.14 (95% CI 2.62-6.53). NLR did not improve the AUC of the model. Poorer ECOG status (ECOG 1 vs. 0 HR 1.59 (95% CI 1.24-2.04), P < 0.001) and primary tumour site (GI vs. breast cancer HR 3.06, 95% CI 2.16-4.35, P < 0.001) were prognostic. We developed a NCIS prognostic score with excellent prognostic ability for both short-term and longer-term survival (iAUC 0.71 95% CI 0.65-0.76), and validated the RMH model in the largest Asian study to date.

AKTmTOR signaling modulates resistance to endocrine therapy and CDK46 inhibition in metastatic breast cancers.

Endocrine therapy (ET) in combination with CDK46 inhibition is routinely used as first-line treatment for HRHER2- metastatic breast cancer (MBC) patients. However, 30-40% of patients quickly develop disease progression. In this open-label multicenter clinical trial, we utilized a hypothesis-driven proteinphosphoprotein-based approach to identify predictive markers of response to ET plus CDK46 inhibition in pre-treatment tissue biopsies. Pathway-centered signaling profiles were generated from microdissected tumor epithelia and surrounding stromaimmune cells using the reverse phase protein microarray. Phosphorylation levels of the CDK46 downstream substrates Rb (S780) and FoxM1 (T600) were higher in patients with progressive disease (PD) compared to responders (p 0.02). Systemic PI3KAKTmTOR activation in tumor epithelia and stromaimmune cells was detected in patients with PD. This activation was not explained by underpinning genomic alterations alone. As the number of FDA-approved targeted compounds increases, functional protein-based signaling analyses may become a critical component of response prediction and treatment selection for MBC patients.

Regulation of the tumor immune microenvironment by cancer-derived circular RNAs.

Circular RNA (circRNAs) is a covalently closed circular non-coding RNA formed by reverse back-splicing from precursor messenger RNA. It is found widely in eukaryotic cells and can be released to the surrounding environment and captured by other cell types. This, circRNAs serve as connections between different cell types for the mediation of multiple signaling pathways. CircRNAs reshape the tumor microenvironment (TME), a key factor involved in all stages of cancer development, by regulating epithelial-stromal transformation, tumor vascularization, immune cell function, and inflammatory responses. Immune cells are the most abundant cellular TME components, and they have profound toxicity to cancer cells. This review summarizes circRNA regulation of immune cells, including T cells, natural killer cells, and macrophages highlights the impact of circRNAs on tumor progression, treatment, and prognosis and indicates new targets for tumor immunotherapy.

Polo-like kinase 4 (Plk4) potentiates anoikis-resistance of p53KO mammary epithelial cells by inducing a hybrid EMT phenotype.

Polo-like kinase 4 (Plk4), the major regulator of centriole biogenesis, has emerged as a putative therapeutic target in cancer due to its abnormal expression in human carcinomas, leading to centrosome number deregulation, mitotic defects and chromosomal instability. Moreover, Plk4 deregulation promotes tumor growth and metastasis in mouse models and is significantly associated with poor patient prognosis. Here, we further investigate the role of Plk4 in carcinogenesis and show that its overexpression significantly potentiates resistance to cell death by anoikis of nontumorigenic p53 knock-out (p53KO) mammary epithelial cells. Importantly, this effect is independent of Plk4s role in centrosome biogenesis, suggesting that this kinase has additional cellular functions. Interestingly, the Plk4-induced anoikis resistance is associated with the induction of a stable hybrid epithelial-mesenchymal phenotype and is partially dependent on P-cadherin upregulation. Furthermore, we found that the conditioned media of Plk4-induced p53KO mammary epithelial cells also induces anoikis resistance of breast cancer cells in a paracrine way, being also partially dependent on soluble P-cadherin secretion. Our work shows, for the first time, that high expression levels of Plk4 induce anoikis resistance of both mammary epithelial cells with p53KO background, as well as of breast cancer cells exposed to their secretome, which is partially mediated through P-cadherin upregulation. These results reinforce the idea that Plk4, independently of its role in centrosome biogenesis, functions as an oncogene, by impacting the tumor microenvironment to promote malignancy.

Iodine-125 seed versus hook-wire guided breast conserving surgery do post operative complication rates differ

Radio-guided occult lesion localisation using iodine 125 seeds (ROLLIS) is used to localize impalpable breast cancers for breast conserving surgery (BCS). Previous studies have suggested improved efficiency and patient outcomes with ROLLIS compared with hook-wire localisation (HWL). The aim of this report is to compare the post-operative complication rates and safety profiles of ROLLIS versus hook-wire guided surgery. Between September 2013 and March 2018, 690 women with non-palpable breast cancer eligible for breast-conserving surgery were randomly assigned to either pre-operative localisation with 125 I seed or hook-wire as part of the ROLLIS clinical trial. Medical record review of 170 women (30% of the total participants) from three tertiary hospitals in Western Australia was performed. Post-operative complications were classified using the Common Terminology Criteria for Adverse Events(CTCAE) grade I to V. Total of 170 surgeries were performed 82 by ROLLIS and 88 by hook-wire. The overall complication rate in the ROLLIS group was 19.5%, with 15.9% being grade II and 3.66% grade III. In the HWL group, the complication rate was 22.7% with 20.5% being grade II and 2.27% grade III. There was no statistically significant difference in complication grades between the 2 groups. No grade IV or grade V complications were reported. Complications observed included drainable seroma, drainable haematoma and surgical site infection. ROLLIS is a safe method of localisation for surgical resection with similar complication rates as hookwires. We encourage its use as an alternative localisation technique as it has demonstrable superiority and efficacy.

Psychosocial needs of older patients with metastatic breast cancer treated at community centers.

Psychosocial status contributes to overall quality of life (QOL) for patients with cancer as psychosocial distress is commonly seen in this population. We sought to describe the psychosocial needs of older adults with metastatic breast cancer (MBC) treated in the community. We evaluated the correlation between the patients psychosocial status and the presence of other geriatric abnormalities in this patient population. This is a secondary analysis of a completed study evaluating older adults (≥65 years) with MBC treated at community practices who received a geriatric assessment (GA). This analysis evaluated psychosocial factors collected during GA, including depression assessed by Geriatric Depression Scale (GDS), perceived social support (SS) assessed by Medical Outcomes Study Social Support Survey (MOS), and objective social supportassessed by demographic variables (living situation and marital status). Perceived SS was further subdivided into tangible social support (TSS) and emotional social support (ESS). Kruskal-Wallis tests, Wilcoxon tests, and Spearmans correlations were used to assess the relationship between psychosocial factors, patient characteristics, and geriatric abnormalities. One hundred older patients with MBC were enrolled and completed GA with a median age of 73 years (65-90). Almost half of the participants (47%) were either single, divorced, or widowed and 38% lived alone, demonstrating a significant number of patients with objective social support deficits. Patients with HER2 or triple negative MBC had lower overall SS scores compared to patients with ERPR or HER2- MBC (p 0.033). Patients on fourth line of therapy were more likely to screen positive for depression compared to patients on earlier lines of therapy (p 0.047). About half (51%) of the patients indicated at least one SS deficit on the MOS. A higher GDS and lower MOS score correlated with greater total GA abnormalities (p 0.016). Evidence of depression correlated with poor functional status, decreased cognition, and a high number of co-morbidities (p < 0.005). Abnormalities in functional status, cognition, and high GDS are associated with lower ESS (p 0.025,0.031,0.006 respectively). Psychosocial deficits are common among older adults with MBC treated in the community and are associated with the presence of other geriatric abnormalities. These deficits require a thorough evaluation and management to optimize treatment outcomes.

Lessons from other fields of medicine, Part 1 Breast cancer.

Through the understanding of multiple etiologies, pathologies, and disease progression trajectories, breast cancer shifted historically from a singular malignancy of the breast to a complex of molecularbiological entities, translating into individualized disease-modifying treatments. As a result, this led to various de-escalations of treatment compared with the gold standard in the era preceding systems biology radical mastectomy. Targeted therapies have minimized morbidity from the treatments and mortality from the disease. Biomarkers further individualized tumor genetics and molecular biology to optimize treatments targeting specific cancer cells. Landmark discoveries in breast cancer management have evolved through histology, hormone receptors, human epidermal growth factor, single-gene prognostic markers, and multigene prognostic markers. Relevant to the reliance on histopathology in neurodegenerative disorders, histopathology evaluation in breast cancer can serve as a marker of overall prognosis rather than predict response to therapies. This chapter reviews the successes and failures of breast cancer research through history, with focus on the transition from a universal approach for all patients to divergent biomarker development and individualized targeted therapies, discussing future areas of growth in the field that may apply to neurodegenerative disorders.

Renaissance of prepectoral implant-based breast reconstruction theoretical basis and research status.

To overview the theoretical basis and research status of prepectoral implant-based breast reconstruction. The domestic and foreign researches on the application of prepectoral implant-based breast reconstruction in breast reconstruction were retrospectively analyzed. The theoretical basis, clinical advantages, and limitations of this technique were summarized and the future development trend in this field was discussed. The recent advances in breast cancer oncology, the development of materials and the concept of oncology reconstruction have provided a theoretical basis for prepectoral implant-based breast reconstruction. The selection of patients and the experience of surgeons are crucial for postoperative outcomes. Ideal thickness and blood flow of flaps are the most important considerations for the selection of prepectoral implant-based breast reconstruction. However, its long-term reconstruction outcomes and clinical benefits and risks in Asian populations still need to be confirmed by more studies. Prepectoral implant-based breast reconstruction has a broad application prospect in breast reconstruction following mastectomy. However, the evidence is limited at present. Randomized study with long-term follow-up is urgently in need to provide sufficient evidence to evaluate the safety and reliability of prepectoral implant-based breast reconstruction. 对近期乳房假体重建的热门术式——乳房胸肌前假体重建的理论依据及研究现状进行综述。. 查阅近年国内外关于胸肌前平面假体植入在乳房重建中应用的相关研究，分析乳房胸肌前假体重建复兴的理论依据、临床应用现状及局限性，探讨该领域发展趋势。. 乳腺肿瘤生物学研究进展、材料学及肿瘤整形理念的发展是乳房胸肌前假体重建复兴的重要理论基础。患者选择及术者经验是胸肌前假体重建复兴获得良好疗效的重要前提，理想的皮瓣厚度和血运是选择该术式最重要考量因素。然而，该术式长期重建效果及在亚洲人群的临床获益、风险仍需更多研究明确。. 乳房胸肌前假体重建具有广阔应用前景，但目前证据有限，缺乏随机、大样本长期随访的研究，以获取足够证据评估乳房胸肌前假体重建的安全性及可靠性。.

Propranolol reduces IFN-γ driven PD-L1 immunosuppression and improves anti-tumour immunity in ovarian cancer.

The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a cold tumour, a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and in vivo EOC models. Noradrenaline (NA), an adrenergic agonist, did not directly regulate PD-L1 expression but PD-L1 was significantly upregulated by IFN-γ in EOC cell lines. IFN-γ also increased PD-L1 on extracellular vesicles (EVs) released by ID8 cells. PRO significantly decreased IFN-γ levels in primary immune cells activated ex vivo and showed increased viability of the CD8

PLA2G2A

Our previous research defined a novel metabolic cancer associated fibroblasts subset (meCAFs) enriched in loose-type pancreatic ductal adenocarcinoma (PDAC) and related toCD8

Putative interactions between transthyretin and endosulfan II and its relevance in breast cancer.

The unregulated use of organochlorine pesticides has been linked to spread of breast cancer (BC), but the underlying biomolecular interactions are unknown. Using a case-control study, we compared OCP blood levels and protein signatures among BC patients. Five pesticides were found in significantly higher concentrations in breast cancer patients than in healthy controls p,p dichloro diphenyl trichloroethane (DDT), pp dichloro diphenyl dichloroethane (DDD), endosulfan II, delta-hexachlorocyclohexane (dHCH), and heptachlor epoxide A (HTEA). According to the odds ratio analysis, these OCPs, which have been banned for decades, continue to raise the risk of cancer in Indian women. Proteomic analysis and enzyme-linked immunosorbent assays (ELISA) of plasma from estrogen receptor-positive breast cancer patients revealed 17 dysregulated proteins, but transthyretin (TTR) was three times higher than in healthy controls. Molecular docking and molecular dynamics studies revealed a competitive affinity between endosulfan II and the thyroxine-binding site of TTR, pointing towards the significance of the competition between thyroxin and endosulfan, resulting in endocrine disruption leading to breast cancer. Our study sheds light on the putative role of TTR in OCP-mediated BC, but more research is needed to decipher the underlying mechanisms that can be used to prevent the carcinogenic effects of these pesticides on womens health.

A local strategy towards concurrent chemoradiotherapy based on fibrin gel for post-surgical cancer treatment.

Postoperative cancer recurrence and metastasis have always been a huge challenge in cancer therapy. Concurrent cisplatin (CDDP)-based chemoradiotherapy regimen is a standard therapeutic strategy in some cancer treatment after surgical resection. However, severe side-effects and unsatisfactory local tumor concentrations of CDDP have hampered the application of this concurrent chemoradiotherapy. Therefore, a superior option that can enhance CDDP-based chemoradiotherapy efficacy with milder concurrent therapy-related toxicity is highly desirable. We developed a platform based on fibrin gel (Fgel) loaded with CDDP (CDDPFgel) to be implanted into the tumor bed after surgery combined with concurrent radiotherapy (RT) for the prevention of postoperative local cancer recurrence and distant metastasis. The postoperative subcutaneous tumor mouse models established by incomplete resect of primary tumors were utilized to evaluate the therapeutic advantages of this chemoradiotherapy regimen for post-surgical treatment. The local and sustained release of CDDP from Fgel could enhance the antitumor efficacy of RT in the residual tumor with lower systemic toxicity. The therapeutic benefits of this approach are demonstrated in breast cancer, anaplastic thyroid carcinoma, and osteosarcoma mouse models. In conclusion, our work offers a general platform for concurrent chemoradiotherapy to prevent post-operative cancer recurrence and metastasis.

Phase II Study of Preoperative Stereotactic Ablative Body Radiotherapy for Early-Stage Breast Cancer Introduction of a Novel Form of Accelerated Partial Breast Radiotherapy.

Pre-operative delivery of partial breast irradiation (PBI) facilitates smaller target volumes and reduced dose to normal tissues. We hypothesized that pre-operative stereotactic ablative radiotherapy (SABR) delivered to intact breast tumor would achieve pathological complete response (pCR) in 25% of patients while preserving low rates of toxicity and good cosmesis. Eligible patients had hormone receptor-positive, clinically node-negative breast cancer measuring ≤2cm on magnetic resonance imaging (MRI). Patients received SABR to 28.5 Gy in three fractions of 9.5 Gy to the tumor defined on MRI and computed tomography in the prone position. Lumpectomy was performed 6-8 weeks later. Tumor pathologic response was assessed and adverse events (AEs) were rated on the Common Terminology Criteria for AEs version 4.0 scale. Physician-rated cosmesis are also reported. Twenty patients were enrolled and completed treatment the study was terminated prior to full accrual due to pre-specified stopping rules. Median follow-up was 14 months. Median patient age was 65 years (range 54-78) and median tumor size on MRI was 10.5mm (range 5-22). All patients had negative surgical margins. Four patients (20%) required post-operative whole breast and axillary radiation due to positive sentinel lymph nodes. No pCR were observed, although the median percent residual tumor cellularity was 30% (range 10-80) and 90% had ≤50% residual cellularity. Three patients had late grade 3 AEs, including 2 of the 4 patients who received post-operative RT. Cosmesis was good in 85% of cases, fair in 10%, and poor in 5%. We observed a 0% incidence of pCR with pre-operative SABR for early-stage BrCa as evaluated 6-8 weeks following treatment. Evolution of pCR may require longer than 6-8 weeks. Patients requiring post-operative whole breast radiotherapy after pre-operative SABR may be at increased risk for high-grade soft tissue toxicity. Further studies are needed to determine optimal patient selection, treatment methodology and timing of pathologic response evaluation.

Clinical impact of fine needle aspiration cytology on sentinel node biopsy after preoperative chemotherapy for core needle biopsy-proven metastatic lymph nodes.

Sentinel node biopsy (SNB) has been increasingly performed for patients with lymph node (LN)-positive (cN1) breast cancer that converted to LN-negative (ycN0) status after neoadjuvant chemotherapy (NAC). This study aimed to clarify the SNB avoidance rates using fine needle aspiration cytology (FNAC) for mLNs after NAC. This study included 68 patients with cN1 breast cancer undergoing NAC from April 2019 to August 2021. Patients with biopsy-proven metastatic clip-marked LNs (clipped LNs) underwent eight cycles of NAC. Ultrasonography (US) was performed to evaluate the effect of the treatment on the clipped LNs, and FNAC was performed after NAC. Patients with ycN0 status determined using FNAC underwent SNB. Those with positive results for FNAC or SNB underwent axillary LNs dissection. Histopathology results and FNA were compared for clipped LNs after NAC. Of the 68 cases, 53 were ycN0 and 15 were clinically positive LNs after NAC( ycN1) on US. Further, 13% (753) of all ycN0 and 60% (915) of all ycN1 cases showed residual metastasis in the LNs on FNAC. FNAC was diagnostically useful for patients with ycN0 status on US imaging. Using FNAC for LNs after NAC helped to avoid unnecessary SNB in 13% of the cases.

The Negative Impact of the New Coronavirus Pandemic on the Trend of Breast Biopsies and Their Direct Costs Interrupted Time Series Analysis.

The overload of health services because of the COVID-19 pandemic has reduced the populations access to treatment and prevention of other diseases. This study aimed to identify whether there was a change in the trend of breast biopsies and their direct costs during the COVID-19 pandemic in a developing countrys public and universal healthcare system. This was an ecological time series study of mammograms and breast biopsies in women aged 30 years or older from an open-access data set of the Public Health System of Brazil from 2017 to July 2021. In 2020, there was a reduction of -40.9% in mammograms and -7.9% in breast biopsies compared with the prepandemic period. From 2017 to 2020, there was an increase in the breast biopsies ratio per mammogram (1.37%-2.55%), the percentage of Breast Imaging-Reporting and Data System (BI-RADS) IV and V mammograms (0.79%-1.14%), and the annual direct cost of breast biopsies (Brazilian Real 3 477 410.00 to Brazilian Real 7 334 910.00). In the time series, the negative impact of the pandemic was lower on BI-RADS IV to V mammograms than on BI-RADS 0 to III. There was an association between the trend of breast biopsies and BI-RADS IV to V mammography. The COVID-19 pandemic harmed the increasing trend of breast biopsies, their total direct costs, BI-RADS 0 to III and IV to V mammograms, observed in the prepandemic period. Furthermore, there was a tendency to screen women at a higher risk for breast cancer during the pandemic.

Reverse Abdominoplasty for Mastectomy Defect Closure in Advanced Breast Cancer.

Breast cancer patients with locally advanced breast cancer who require radical mastectomy are left with large chest wall defects. This poses a significant reconstructive challenge as many high-risk patients require timely postmastectomy adjuvant therapy. While the reverse abdominoplasty technique is commonly used for aesthetic improvement of the anterior trunk, it can be also be effectively used for closure of extensive mastectomy defects in this patient population. We conducted a retrospective cohort study of all consecutive patients who underwent an extensive radical mastectomy followed by immediate closure with the reverse abdominoplasty technique at a single tertiary cancer center from June 2017 to July 2022. Patients who had concurrent skin grafting or breast mound flap reconstruction were excluded. Demographic, medical, oncologic, and reconstructive data were collected. Six patients were treated with reverse abdominoplasty for 9 chest wall defects after surgical excision of locally advanced breast cancer. The median tumor size was 10.7 cm (range, 6.7-10 cm) and the median mastectomy weight was 865.7 g (range, 356.4-1247.7 g). On average, the operation length was 191 minutes (range, 86-257 minutes) and the postoperative length of stay was 2.2 days (range, 1-5 days). All patients underwent systemic adjuvant therapy and the median time from surgery to initiation of therapy was 44.5 days (range, 32-75 days). Reverse abdominoplasty is a simple and safe technique to reliably close large defects after locally advanced breast cancer excision. It has a short operative time, hospital stay, and turnaround time to initiation of adjuvant therapy.

Access to Radiation Therapy and Related Clinical Outcomes in Patients With Cervical and Breast Cancer Across Sub-Saharan Africa A Systematic Review.

To better understand the barriers to accessing standard-of-care radiation therapy (RT) for breast and cervical cancer in sub-Saharan Africa and their impact on outcomes. A comprehensive literature search was completed with a medical librarian. Articles were screened by title, abstract, and full text. Included publications were analyzed for data describing barriers to RT access, available technology, and disease-related outcomes, and further grouped into subcategories and graded according to predefined criteria. A total of 96 articles were included 37 discussed breast cancer, 51 discussed cervical cancer, and eight discussed both. Financial access was affected by health care system payment models and combined burdens of treatment-related costs and lost wages. Staffing and technology shortages limit the ability to expand service locations andor increase capacity within existing centers. Patient factors including use of traditional healers, fear of stigma, and low health literacy decrease the likelihood of early presentation and completion of therapies. Survival outcomes are worse than most high- and middle-income countries and are affected by many factors. Side effects are similar to other regions, but these findings are limited by poor documentation capabilities. Access to palliative RT is more expeditious than definitive management. RT was noted to lead to feelings of burden, lower self-esteem, and worsened quality of life. Sub-Saharan Africa represents a diverse region with barriers to RT that differ on the basis of funding, available technology and staff, and community populations. Although long-term solutions must focus on building capacity by increasing the number of treatment machines and providers, short-term improvements should be implemented, such as interim housing for traveling patients, increased community education to reduce late-stage diagnoses, and use of virtual visits to avoid travel.

Cancer-Related Stigma in Malawi Narratives of Cancer Survivors.

Stigma is an impediment across the cancer care continuum, leading to delayed presentation to care, elevated morbidity and mortality, and reduced quality of life. The goal of this study was to qualitatively examine the drivers, manifestations, and impacts of cancer-related stigma among individuals who received cancer treatment in Malawi, and to identify opportunities to address stigma. Individuals who had completed treatment for lymphoma (n 20) or breast cancer (n 9) were recruited from observational cancer cohorts in Lilongwe, Malawi. Interviews explored the individuals cancer journey, from first symptoms through diagnosis, treatment, and recovery. Interviews were audio-recorded and translated from Chichewa to English. Data were coded for content related to stigma, and thematically analyzed to describe the drivers, manifestations, and impacts of stigma along the cancer journey. Drivers of cancer stigma included beliefs of cancer origin (cancer as infectious cancer as a marker of HIV cancer due to bewitchment), perceived changes in the individual with cancer (loss of socialeconomic role physical changes), and expectations about the individuals future (cancer as death sentence). Cancer stigma manifested through gossip, isolation, and courtesy stigma toward family members. The impacts of cancer stigma included mental health distress, impediments to care engagement, lack of cancer disclosure, and self-isolation. Participants suggested the following programmatic needs community education about cancer counseling in health facilities and peer support from cancer survivors. The results highlight multifactorial drivers, manifestations, and impacts of cancer-related stigma in Malawi, which may affect success of cancer screening and treatment programs. There is a clear need for multilevel interventions to improve community attitudes toward people with cancer, and to support individuals along the continuum of cancer care.

Duplex Phenotype Detection and Targeting of Breast Cancer Cells Using Nanotube Nanoprobes and Raman Imaging.

We designed, synthesized, and characterized a Raman nanoprobe made of dye-sensitized single-walled carbon nanotubes (SWCNTs) that can selectively target biomarkers of breast cancer cells. The nanoprobe is composed of Raman-active dyes encapsulated inside a SWCNT, whose surface is covalently grafted with poly(ethylene glycol) (PEG) at a density of ∼0.7% per carbon. Using α-sexithiophene- and β-carotene-derived nanoprobes covalently bound to an antibody, either anti-E-cadherin (E-cad) or anti-keratin-19 (KRT19), we prepared two distinct nanoprobes that specifically recognize biomarkers on breast cancer cells. Immunogold experiments and transmission electron microscopy (TEM) images are first used to guide the synthesis protocol for higher PEG-antibody attachment and biomolecule loading capacity. The duplex of nanoprobes was then applied to target E-cad and KRT19 biomarkers in T47D and MDA-MB-231 breast cancer cell lines. Hyperspectral imaging of specific Raman bands allows for simultaneous detection of this nanoprobe duplex on target cells without the need for additional filters or subsequent incubation steps. Our results confirm the high reproducibility of the nanoprobe design for duplex detection and highlight the potential of Raman imaging for advanced biomedical applications in oncology.

Perceived Participation in Decision-Making on Primary Surgery and Associated Factors Among Early Breast Cancer Patients A Cross-sectional Study.

Breast cancer patients wish to participate in the treatment decision-making, but the perceived participation was inconsistent with the willingness, leading to poor patient outcomes. The aims of this study were to explore the perceived participation in the primary surgery decision-making among Chinese patients with early-stage breast cancer (BCa) and to analyze the relationships of demographic and clinical factors, participation competence, self-efficacy, social support, and doctors promotion of participation with the guidance of the capability, opportunity, motivation-behavior system (the COM-B system). Paper surveys were used to collect data from 218 participants. The participation competence, self-efficacy, social support, and the doctor facilitation of involvement were evaluated to measure factors related to perceived participation among early-stage BCa. Perceived participation was low, and participants with a high level of participation competence, self-efficacy, and social support and who were employed and had a higher education level and higher family income perceived higher participation in primary surgery decision-making. Perceived participation was low and may be facilitated by patients internal and external factors during the decision-making process. Health professionals should be aware that patient participation in decision-making is a type of self-care health behavior, and targeted decision support interventions should be provided to facilitate participation. Patient-perceived participation may be evaluated from the perspective of self-care management behaviors among BCa patients. Nurse practitioners should emphasize their important roles in providing information, patient education, and psychological support to better contribute to the course of the treatment decision-making process for BCa patients who faced primary surgery.

lncRNA

Notch has been implicated in human cancers and is a putative therapeutic target. However, the regulation of Notch activation in the nucleus remains largely uncharacterized. Therefore, characterizing the detailed mechanisms governing Notch degradation will identify attractive strategies for treating Notch-activated cancers. Here, we report that the long noncoding RNA (lncRNA)

Drivers of disparities in stage at diagnosis among women with breast cancer South African breast cancers and HIV outcomes cohort.

In low- and middle-income countries (LMICs), advanced-stage diagnosis of breast cancer (BC) is common, and this contributes to poor survival. Understanding the determinants of the stage at diagnosis will aid in designing interventions to downstage disease and improve survival from BC in LMICs. Within the South African Breast Cancers and HIV Outcomes (SABCHO) cohort, we examined factors affecting the stage at diagnosis of histologically confirmed invasive breast cancer at five tertiary hospitals in South Africa (SA). The stage was assessed clinically. To examine the associations of the modifiable health system, socio-economichousehold and non-modifiable individual factors, hierarchical multivariable logistic regression with odds of late-stage at diagnosis (stage III-IV), was used. The majority (59%) of the included 3497 women were diagnosed with late-stage BC disease. The effect of health system-level factors on late-stage BC diagnosis was consistent and significant even when adjusted for both socio-economic- and individual-level factors. Women diagnosed in a tertiary hospital that predominantly serves a rural population were 3 times (OR 2.89 (95% CI 1.40-5.97) as likely to be associated with late-stage BC diagnosis when compared to those diagnosed at a hospital that predominantly serves an urban population. Taking more than 3 months from identifying the BC problem to the first health system entry (OR 1.66 (95% CI 1.38-2.00)), and having luminal B (OR 1.49 (95% CI 1.19-1.87)) or HER2-enriched (OR 1.64 (95% CI 1.16-2.32)) molecular subtype as compared to luminal A, were associated with a late-stage diagnosis. Whilst having a higher socio-economic level (a wealth index of 5) reduced the probability of late-stage BC at diagnosis, (OR 0.64 (95% CI 0.47-0.85)). Advanced-stage diagnosis of BC among women in SA who access health services through the public health system was associated with both modifiable health system-level factors and non-modifiable individual-level factors. These may be considered as elements in interventions to reduce the time to diagnosis of breast cancer in women.

Cancer detection for small-size and ambiguous tumors based on semantic FPN and transformer.

Early detection of tumors has great significance for formative detection and determination of treatment plans. However, cancer detection remains a challenging task due to the interference of diseased tissue, the diversity of mass scales, and the ambiguity of tumor boundaries. It is difficult to extract the features of small-sized tumors and tumor boundaries, so semantic information of high-level feature maps is needed to enrich the regional features and local attention features of tumors. To solve the problems of small tumor objects and lack of contextual features, this paper proposes a novel Semantic Pyramid Network with a Transformer Self-attention, named SPN-TS, for tumor detection. Specifically, the paper first designs a new Feature Pyramid Network in the feature extraction stage. It changes the traditional cross-layer connection scheme and focuses on enriching the features of small-sized tumor regions. Then, we introduce the transformer attention mechanism into the framework to learn the local feature of tumor boundaries. Extensive experimental evaluations were performed on the publicly available CBIS-DDSM dataset, which is a Curated Breast Imaging Subset of the Digital Database for Screening Mammography. The proposed method achieved better performance in these models, achieving 93.26% sensitivity, 95.26% specificity, 96.78% accuracy, and 87.27% Matthews Correlation Coefficient (MCC) value, respectively. The method can achieve the best detection performance by effectively solving the difficulties of small objects and boundaries ambiguity. The algorithm can further promote the detection of other diseases in the future, and also provide algorithmic references for the general object detection field.

Breast Cancer Tumor Board A Radiologists Guide to Postmastectomy Radiation Therapy.

Radiation therapy represents a pillar in the current management of breast cancer. Historically, postmastectomy radiation therapy (PMRT) has been administered only in patients with locally advanced disease and a poor prognosis. These included patients with large primary tumors at diagnosis andor more than three metastatic axillary lymph nodes. However, during the past few decades, several factors have prompted a shift in perspective, and recommendations for PMRT have become more fluid. Guidelines for PMRT in the United States are outlined by the National Comprehensive Cancer Network and the American Society for Radiation Oncology. Because evidence to support performing PMRT is frequently discordant, the decision to offer radiation therapy often requires team discussion. These discussions are usually held in multidisciplinary tumor board meetings in which radiologists play a pivotal role by providing critical information such as the location and extent of disease. Breast reconstruction after mastectomy is optional and is safe in cases in which the patients clinical status allows it. The preferred method in the setting of PMRT is autologous reconstruction. If this is not possible, then a two-step implant-based reconstruction is recommended. Radiation therapy does involve a risk of toxicity. Complications can be seen in acute and chronic settings and range from fluid collections and fractures to radiation-induced sarcomas. Radiologists have a key role in detecting these and other clinically relevant findings and should be prepared to recognize, interpret, and address them.

Coordinated activation of c-Src and FOXM1 drives tumor cell proliferation and breast cancer progression.

Activation of the tyrosine kinase c-Src promotes breast cancer progression and poor outcomes, yet the underlying mechanisms are incompletely understood. Here, we show that deleting c-Src abrogates the activity of Forkhead Box M1 (FOXM1), a master transcriptional regulator of the cell cycle, in a genetically engineered model mimicking the Luminal B molecular subtype of breast cancer. By phosphorylating it on two tyrosine residues, c-Src stimulates the nuclear localization of FOXM1 and the expression of its target genes, including key regulators of G2-M cell cycle progression as well as c-Src itself. This positive feedback loop drives proliferation in genetically engineered and patient-derived models of Luminal B-like breast cancer. Targeting this mechanism, including through novel compounds that destabilize the FOXM1 protein, induces G2-M cell cycle arrest and apoptosis, blocking tumor progression and impairing metastasis. We identify a positive correlation between FOXM1 and c-Src expression in human breast cancer and show that the expression of FOXM1 target genes predicts poor outcomes and associates with the Luminal B subtype, which responds poorly to approved therapies. These findings indicate that a regulatory network centered on c-Src and FOXM1 is a targetable vulnerability in aggressive luminal breast cancers.

Regulatory Approval, Reimbursement, and Clinical Use of Cyclin-Dependent Kinase 46 Inhibitors in Metastatic Breast Cancer in the Netherlands.

The number of new cancer medicines that are being approved by regulatory agents is increasing exponentially. Yet little is known about the pace at which these medicines reach eligible patients in daily clinical practice during different phases of the postapproval access pathway. To describe the entire postapproval access pathway of cyclin-dependent kinase 46 (CDK46) inhibitors in the Netherlands, from regulatory approval to reimbursement and to investigate the adoption of these medicines in clinical practice among patients with metastatic breast cancer. This cohort study reviewed approval and reimbursement decisions of the CDK46 inhibitors palbociclib, ribociclib, and abemaciclib and estimated the number of patients with metastatic breast cancer who were eligible for these medicines compared with the actual use in clinical practice. The study used nationwide claims data that were obtained from the Dutch Hospital Data. Claims and early access data for patients with hormone receptor-positive and ERBB2 (formerly HER2)-negative metastatic breast cancer who were treated with CDK46 inhibitors from November 1, 2016, to December 31, 2021, were included. Description of the postapproval access pathway, monthly number of patients who were treated with CDK46 inhibitors in clinical practice, and estimated number of patients who were eligible for treatment. Aggregated claims data were used, and patient characteristics and outcomes data were not collected. Three CDK46 inhibitors have received European Union-wide regulatory approval for the treatment of HR-positive and ERBB2-negative metastatic breast cancer since November 2016. In the Netherlands, the number of patients who have been treated with these medicines increased to approximately 1847 (based on 1 624 665 claims over the entire study period) from approval to the end of 2021. Reimbursement for these medicines was granted between 9 and 11 months after approval. While awaiting reimbursement decisions, 492 patients received palbociclib, the first approved medicine of this class, via an expanded access program. By the end of the study period, 1616 patients (87%) were treated with palbociclib, whereas 157 patients (7%) received ribociclib, and 74 patients (4%) received abemaciclib. The CKD46 inhibitor was combined with an aromatase inhibitor in 708 patients (38%) and with fulvestrant in 1139 patients (62%). The pattern of use over time appeared to be somewhat lower compared with the estimated number of eligible patients (1847 vs 1915 in December 2021), especially in the first 2.5 years after approval. This study found that CDK46 inhibitors rapidly reached many eligible patients with metastatic breast cancer and were adopted gradually over time in the Netherlands. Adoption of innovative medicines may be further optimized, and better transparency of the availability of new medicines during different phases of the postapproval access pathway is needed.

Association of Social Determinants and Tumor Biology With Racial Disparity in Survival From Early-Stage, Hormone-Dependent Breast Cancer.

Black women with hormone receptor-positive breast cancer experience the greatest racial disparity in survival of all breast cancer subtypes. The relative contributions of social determinants of health and tumor biology to this disparity are uncertain. To determine the proportion of the Black-White disparity in breast cancer survival from estrogen receptor (ER)-positive, axillary node-negative breast cancer that is associated with adverse social determinants and high-risk tumor biology. A retrospective mediation analysis of factors associated with the racial disparity in breast cancer death for cases diagnosed between 2004 and 2015 with follow-up through 2016 was carried out using the Surveillance, Epidemiology, and End Results (SEER) Oncotype registry. The study included women in the SEER-18 registry who were aged 18 years or older at diagnosis of a first primary invasive breast cancer tumor that was axillary node-negative and ER-positive, who were Black (Black), non-Hispanic White (White), and for whom the 21-gene breast recurrence score was available. Data analysis took place between March 4, 2021, and November 15, 2022. Census tract socioeconomic disadvantage, insurance status, tumor characteristics including the recurrence score, and treatment variables. Death due to breast cancer. The analysis with 60 137 women (mean IQR age 58.1 50-66 years) included 5648 (9.4%) Black women and 54 489 (90.6%) White women. With a median (IQR) follow-up time of 56 (32-86) months, the age-adjusted hazard ratio (HR) for breast cancer death among Black compared with White women was 1.82 (95% CI, 1.51-2.20). Neighborhood disadvantage and insurance status together mediated 19% of the disparity (mediated HR, 1.62 95% CI, 1.31-2.00 P < .001) and tumor biological characteristics mediated 20% (mediated HR, 1.56 95% CI, 1.28-1.90 P < .001). A fully adjusted model that included all covariates accounted for 44% of the racial disparity (mediated HR, 1.38 95% CI, 1.11-1.71 P < .001). Neighborhood disadvantage mediated 8% of the racial difference in the probability of a high-risk recurrence score (P .02). In this study, racial differences in social determinants of health and indicators of aggressive tumor biology including a genomic biomarker were equally associated with the survival disparity in early-stage, ER-positive breast cancer among US women. Future research should examine more comprehensive measures of socioecological disadvantage, molecular mechanisms underlying aggressive tumor biology among Black women, and the role of ancestry-related genetic variants.