bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal circulating tumor DNA monitoring for detection of molecular residual disease in patients with surgically resected stage II/III melanoma.
Authors: Kollipara Revathi , Budde Griffin , Aushev Vasily N. , Brunsgaard Elise Kornreich , Kuzel Timothy , O'Donoghue Cristina , Riddell Timothy , Palsuledesai Charuta C. , Krainock Michael , Liu Minetta C. , Tan Alan
Published: June 2023

9582

Background: Over the past decade, advances in immunotherapy (IO) have dramatically improved overall survival (OS) for patients with metastatic melanoma. Immune checkpoint inhibitors and BRAF/MEK inhibitors also became standard of care for surgically resected stage III melanoma, and most recently pembrolizumab was approved for stage IIB/C patients. Although the phase III trials that led to their respective approvals met their primary endpoints for relapse-free survival, no benefit in OS has been observed. Given that a large proportion of early-stage melanoma patients are cured with surgery alone, the decision to proceed with adjuvant therapy should be weighed against the risk of potential life-altering toxicity. There is a high unmet need to develop biomarkers to accurately select patients who are most likely to benefit from adjuvant IO while sparing a group of low risk patients from unnecessary treatment. In this study, we evaluated the prognostic value of personalized, tumor-informed circulating tumor DNA (ctDNA) testing in patients with resectable stage II/III melanoma. Methods: In this real-world study, longitudinal plasma samples (n = 159) were analyzed in real-time from 45 stage IIA-IIID cutaneous melanoma patients treated at Rush University between 03/30/2021 and 01/12/2023. A personalized, tumor-informed ctDNA assay (Signatera bespoke, mPCR-NGS assay) was used for detection and quantification of ctDNA in plasma samples. Results: Personalized, tumor-informed ctDNA assays were successfully designed for 93% (42/45) of patients using tissue samples from either surgical resection (14/42, 33%) or biopsy (26/42, 67%; 16 shave, 10 excisional, 1 punch, 1 core). ctDNA was detectable at one or more time points in 36% (15/42) of patients. We observed a higher ctDNA-positivity rate in stage III patients (11/20, 55%) compared to stage II patients (4/22, 18%). Twelve of the 15 ctDNA-positive patients received adjuvant IO/treatment escalation after a positive ctDNA result; 6 patients had sustained ctDNA clearance, 2 had transient clearance, and 4 continue to receive adjuvant IO and follow-up ctDNA testing. Radiographic recurrence was observed in 7/42 patients, 6 of whom were ctDNA-positive. Ninety-six percent (26/27) of patients with persistent ctDNA-negativity remain clinically and radiographically progression-free. Conclusions: Our data suggest that molecular residual disease detection using a personalized, tumor-informed ctDNA assay is highly prognostic in melanoma patients undergoing curative resection. Sustained clearance of ctDNA was achieved with adjuvant therapy in a subset of this cohort. Prospective studies evaluating the utility of ctDNA to aid clinical decision-making regarding adjuvant treatment intensification or de-escalation are warranted.
Correlation of breast arterial calcification with overall survival in patients with breast cancer.
Authors: Dusi Vidya Sagar , Attili Suresh VS , Vutukuru Anuradha , Peri Soumya V , Sharma Rakesh
Published: June 2023

e12501

Background: Calcifications in breast tissue are common and indicate an array of conditions. Based on pattern of calcifications it indicate cancerous/ precancerous changes. Similarly vascular calcifications indicate a systemic vasculopathy. Aim of this study is to correlate Breast Arterial Calcification (BAC) with overall survival/all cause mortality in patients with breast cancer. Methods: It is a retrospective analysis of all breast cancer patients diagnosed across 3 specialty hospitals In the period of 2013-2017 with at least 5 years of follow up. All cause mortality, breast cancer specific mortality were measured. The comparison was made between the patients with no calcifications (Gr I), vascular calcifications (GrII) ductal calcifications (Gr III), and any breast calcification (Gr IV). Results: The baseline characters of all these groups and the treatment received were balanced. The median survival of the Groups were 43.6+22.6 mo vs 28.6+14.2 mo vs38.5+20.2 mo vs41.6+22.3 months (p=<0.02). Presence of vascular calcifications confers shorter overall survival and the main reason being death due to cardiovascular events. The risk is more in presence of co-morbid conditions (>2 have increased risk of 2.8 fold compared to less than 2), which were defined as diabetes, hypertension, dyslipidemia, history of cardiac illness in family, obesity. Those who received Adriamycin based therapy have 1.16 times higher risk than those who did not. Those who smoke are 3.2 times at higher risk than non smokers to have cardiovascular event in presence of breast arterial calcification. Alcohol did not have any impact. Conclusions: BAC is an important marker to predict underlying vasculopathy and risk of coronary cardiac diseases. It confers poor prognosis and reduced overall survival compared to those who do not have it. The challenges to assess CAD risk through CT/angio on community basis is high. Mammograms are being done annually across nations as a routine basis. Risk factors of breast cancer and CAD are common. The cancer detection rates of mammo as <0.2% compared to arterial calcifications, which is almost 12.8%. A simple extra attention towards BAC could help in preventing cardiac related mortality in women both with and without cancer. [Table: see text] [Table: see text]
Possible advantage of granulocyte colony-stimulating factor in breast cancer chemotherapy during COVID-19 pandemic: A single center experience in Japan.
Authors: Yokoyama Kioto
Published: June 2023

e12505

Background: The COVID-19 pandemic seems to be ongoing in many countries, including Japan. ASCO and ESMO guidelines recommend treatment with during chemotherapy, and their use also reduces the risk of febrile neutropenia. On the other hand, there is a report that use of granulocyte colony-stimulating factor (G-CSF) increases the risk of admission and mortality due to COVID-19, so appropriate G-CSF use is still under discussion. Methods: Breast cancer patients treated with chemotherapy at our hospital from October 2020 to December 2022 were included in this study. We retrospectively collected patient data, including chemotherapy regimens, G-CSF use, COVID-19 infection, and COVID-19 severity, from electronic medical records. Results: Twenty-four patients (two bilateral breast cancers) received chemotherapy during this period. Twenty-three patients were female (95.8%) and one was male (4.2%), the mean age was 58.7 (34–79) years; 11 (45.8%) had early-stage breast cancer and 14 (58.3%) had advanced or recurrent breast cancer (one patient with early-stage breast cancer developed recurrent breast cancer during the study period). Seventeen cases (65.4%) were ER positive and nine cases (34.6%) were negative, 15 cases (57.7%) were PgR positive and 11 cases (42.3%) were negative, and six cases (23.1%) were HER2 positive and 20 cases (76.9%) were negative. The major chemotherapy regimens were ddAC in three patients (12.5%), AC in eight patients (33.3%), wPTX in 11 patients (45.8%), DTX in four patients (16.7%), TC in one patient (4.2%) and S-1 in eight patients (33.3%). Some patients also received treatment with anti-HER2 or anti-VEGF drugs or an immune check-point inhibitor but we did not consider these. Of the 13 patients who received AC, DTX and TC, 11 patients received PEG-GCSF in all their cycles. Among all patients receiving, COVID-19 symptoms were suspected on four occasions, and the COVID-19 antigen test was conducted, but all were negative, so no cases of COVID-19 were observed. Of the 46 cycles of AC, DTX, and TC, the proportion of patients with suspected COVID-19 symptoms who underwent antigen testing tended to be lower in the PEG-GCSF group (37 cycles) than in the no PEG-GCSF group (nine cycles) (2.7% vs. 22.2%; p = 0.0933, Fisher’s exact test). Conclusions: In this study, we did not find any cases of COVID-19 infection during chemotherapy, and so were unable to analyze the association between G-CSF use and COVID-19 infection severity. However, we did observe a trend toward a lower rate of potential COVID-19 with administration of PEG-GCSF. This might reflect a better quality of life for breast cancer chemotherapy patients.
Systematic review of breast implant associated squamous cell carcinoma.
Authors: Niraula Sujan , Katel Anjan , Barua Amit , Weiss Anna , Strawderman Myla S. , Zhang Huina , Manrique Oscar , O'Connell Avice , Pandey Sirish Raj , Dhakal Ajay
Published: June 2023

e12508

Background: Breast augmentation is a cosmetic procedure with low rates of complication like bleeding, infection, implant rupture, and capsular contracture. However, rare cases of breast implant-associated (BIA) malignancies, including anaplastic large cell lymphoma (ALCL) and squamous cell carcinoma (SCC), have been reported. BIA-SCC is rarer than ALCL and current literature is limited to case reports. In 2022, the American Society of Plastic Surgeons (ASPS) issued a BIA-SCC summary statement based on 16 reported cases in response to an FDA safety communication. The aim of this study is to review published cases of BIA-SCC and present clinical and outcome data systematically. Methods: We conducted a literature search in English to identify studies reporting BIA-SCC from inception to October 2022. Patient characteristics and relevant outcomes were gathered from the studies. The mortality rates at 6 and 12 months were calculated as the inverse of the Kaplan-Meier survival estimate and presented with a 95% confidence interval (CI). Results: 14 articles and 18 cases of BIA-SCC were identified through a literature search. A rising trend in case reporting was observed, with 4 cases in the 1990s and 14 cases since 2010. The mean patient age was 56 years (range 40-81), and the mean time from breast augmentation to symptom appearance was 21 years (range 10-35). Most patients (13/18, 72%) underwent the procedure for cosmetic reasons. Out of 17 cases with available implant information, 11 cases had silicone based implants and 6 cases saline implants. Implant surface information was available in 5 cases, 4 smooth and 1 textured. 16 patients had swelling of the breast and 15 patients had breast pain at presentation of BIA-SCC. All patients had their implants removed and 10 underwent mastectomy after a diagnosis of SCC. Of the 12 cases with available treatment information, 7 received adjuvant chemotherapy and/or radiotherapy, 2 received neoadjuvant chemotherapy, and 3 did not receive perioperative chemotherapy or radiotherapy. Follow-up data was available for 10 cases. The 6-month and 12-month mortality rates were 11.1% (95% CI: 0.5% to 40.6%) and 23.8% (95% CI: 2.8% to 56.1%). Conclusions: The estimated 6-month mortality rate of 11% (95% CI: 0.5%-40.6%) should be interpreted cautiously due to the small sample size. It is lower than the rate reported by ASPS (44%), but the reason for this difference cannot be accurately explained as the methodology for determining then mortality rate is not provided in the ASPS statement. This study provides a valuable systematic review of a rare and poorly understood condition with a poor prognosis. Monitoring and sharing information is crucial to improve detection and management of BIA-SCC. [Table: see text]
Accelerated partial breast irradiation (APBI) for ductal carcinoma in situ.
Authors: Roth O'Brien Diana A , Boe Lillian A , Mueller Boris , Cuaron John J , Xu Amy , Bernstein Michael B. , McCormick Beryl , Powell Simon N. , Khan Atif J. , Braunstein Lior Zvi
Published: June 2023

e12516

Background: Landmark studies of accelerated partial breast irradiation (APBI) included patients with DCIS, but with limited guidance regarding subgroups of in situ disease. Suitability criteria defined by national guidelines for APBI are narrowly constrained among those with DCIS, and controversy persists regarding optimal patient selection. Here, we report disease outcomes for a heterogeneous cohort of patients with DCIS who received APBI. Methods: Using a prospectively maintained institutional database, we identified patients with DCIS who underwent lumpectomy and adjuvant APBI from 2000 to 2022. Clinicopathologic characteristics were collected, and patients were classified as suitable, cautionary, or unsuitable for APBI by the latest American Society for Radiation Oncology (ASTRO) criteria. Outcomes of interest included local recurrence (LR), overall survival (OS), and follow up time. Cumulative incidence functions were calculated to estimate the incidence of LR over time. All statistical analyses were performed in R version 4.2.2. Results: The cohort comprised 176 patients, median age 60 years (IQR 52, 66). Median DCIS size was 9 mm (IQR 4, 15 mm), and approximately 20% had multifocal disease. Most patients had negative final surgical margins (160, 91%), with 10 patients having ≤2 mm margins and 6 having ≤1 mm margins for DCIS. 18 (10%) patients had nuclear grade I disease, 111 (63%) had grade II disease, and 33 (19%) had grade III disease, with a small subset classified as grade I-II or II-III. Most patients (161, 91%) had ER+ DCIS, and 72 (41%) received endocrine therapy. By ASTRO criteria, 118 (67%) patients were suitable for APBI, 57 (32%) cautionary, and 1 (0.6%) was unsuitable. At a median 24 months of follow up (range 2 to 127 months) we observed only one LR, yielding a 2-year LR rate of 0.6%. The LR occurred in the cautionary group, yielding a 2-year LR rate of 1.8% for the cautionary subset. The patient with LR was 56 years old, with 24 mm of high grade DCIS, ER+, with lumpectomy to negative margins, and did not receive endocrine therapy. No breast cancer mortality events were observed. Conclusions: Our early-term results exhibit excellent local control for patients with DCIS who received lumpectomy and APBI, even among those classified as “cautionary” by national guidelines. Although our findings are limited by short follow up, these results suggest that broadening the application of APBI for patients with DCIS may warrant further investigation.
Nomograms for predicting survival in patients with HER2 negative breast cancer.
Authors: Xu Yiyue , Zou Bing , Fan Bingjie , Li Butuo , Wang Linlin
Published: June 2023

e12528

Background: It is increasingly recognized that there is considerable heterogeneity in HER2-negative breast cancer. The clinicopathological characteristics differed between HER2-low and HER2-0 breast cancer evaluated by immunohistochemistry (IHC) or in situ hybridization (ISH). HER2-low breast cancer may benefit from novel antibody-drug conjugates. However, the immunohistochemical agreement of HER2-low is poor. We aimed to construct nomograms to predict the survival of HER2-negative breast cancer and to evaluate the effects of HER2 on survival at the RNA transcript level. Methods: A retrospective analysis was performed on breast cancer patients who were evaluated HER2-negative by IHC or ISH in the TCGA database. Univariate and multivariate cox regression analysis was used to evaluate whether the HER2 RNA transcript level and clinical parameters were independent predictors for overall survival (OS), progression-free survival (PFS), and Disease-Specific Survival (DSS), and nomograms were generated for the prediction of 1-, 2-, 3-, 5-year OS, PFS, and DSS based on significant parameters. Survival curves were drawn using the Kaplan-Meier methods to compare mortality outcomes according to HER2 RNA transcript level (75% vs. 25%). Results: A total of 769 HER2-negative patients were included in the analysis. The median age of patients was 56 years (range 26-30), and the majority were White (80.3%). Univariate and multivariate cox regression analysis showed that age, pN_stage, and pM_stage were independent predictors for OS, but HER2 was not. The C-index of a nomogram based on these three parameters was 0.723 (95%CI, 0.6555-1). HER2, pT_stage, pN_stage, and pM_stage were analyzed as independent predictors of PFS. HER2, pN_stage, and pM_stage were independent predictors of DSS. The C-indexes of established nomograms were 0.734 (95%CI, 0.672-1) and 0.775 (95%CI, 0.686-1) respectively. PFS and DSS were significantly better for patients with high HER2 RNA transcript levels (PFS, log-rank p = 0.00446, HR = 0.352; DSS, log-rank p = 0.0119, HR = 0.247). Conclusions: In the TCGA database, the HER2 RNA transcript level was an independent predictor for PFS and DSS in HER2-negative breast cancer. Stratification of patients at the RNA level can help clinicians optimize treatment for HER2-negative breast cancer.
Real world treatment patterns and survival by germline BRCA (gBRCA) mutation status in patients with HER2-negative early breast cancer (eBC) in the US community oncology setting: A retrospective observational study.
Authors: Andersen Jay C. , Earla Jagadeswara Rao , Fulcher Nicole , Ndukum Juliet , Robert Nicholas J. , Robson Mark E. , Li Weiyan , Mejia Jamie
Published: June 2023

e12535

Background: Germline BRCA mutations (gBRCAm) are associated with a higher risk of breast cancer at a younger age. Generally, gBRCA gene testing is performed in patients perceived as high risk for gBRCAm. Olaparib, a targeted poly (ADP-ribose) polymerase inhibitor (PARPi), has significantly improved overall survival (OS) in the randomized, double-blind OlympiA trial of patients with HER2-negative gBRCAm and was subsequently approved for the adjuvant treatment of patients with gBRCAm HER2-negative high-risk early breast cancer (eBC) treated with neoadjuvant or adjuvant chemotherapy. This study examines the real-world patient characteristics, treatment patterns and OS by gBRCA status among patients with HER2-negative eBC in a US community oncology setting prior to olaparib US approval for treatment of eBC. Methods: This retrospective observational study used structured data from The US Oncology Network's iKnowMed database. Adult patients were included if diagnosed with HER2-negative eBC (stage I-III) and if they initiated systemic neoadjuvant or adjuvant therapy between January 1, 2012-December 31, 2018 (followed through December 31, 2021). Patients were excluded if they progressed to stage IV within 6 months after neoadjuvant treatment or were diagnosed with another primary cancer. Descriptive analyses assessed patient characteristics, early-stage systemic treatments and OS among patients by gBRCA status. Results: Among 19,258 patients with BC meeting initial criteria, 1436 (7.5%) had a documented gBRCA test result. Among them, 10% had gBRCAm (n = 141, 43% hormone receptor positive [HR+], 57% triple-negative BC [TNBC]), 90% BRCAwt (n = 1294, 70% HR+, 30% TNBC), and 1 had a variant of uncertain significance. Median age at surgery was numerically lower in gBRCAm (43 years) than gBRCAwt (48 years) patients. Treatments included neoadjuvant-only therapy (gBRCAm 58%; gBRCAwt 34%), adjuvant-only therapy (gBRCAm 42%; gBRCAwt 66%) and both neoadjuvant and adjuvant therapy (gBRCAwt 0.1%). Median OS in both study cohorts was not reached. Median follow-up from surgery was less than 4 years (gBRCAm 47 months; gBRCAwt 46 months). At 48 months, estimated survival was 95% in gBRCAm and 94% in gBRCAwt patients. Conclusions: In this cohort of patients with HER2-negative eBC, among the 7.5% with a documented gBRCA result, 10% were identified with gBRCAm, reinforcing the need for gBRCA testing. Using structured real-world data through 2021 (prior to PARPi approval for eBC) with limited follow-up of < 4 years, our study found that OS by gBRCA status was similar among patients with HER2-negative eBC. Our further research with chart review data containing granular clinical information looking at intermediate endpoints such as recurrence in eBC is under way.
Symptom burden of patients with breast cancer on adjuvant hormone therapy: A preliminary report.
Authors: Gomaa Sameh , Lopez Ana Maria , Smith Rita , Slamon Rachel , Wen Kuang-Yi
Published: June 2023

e12536

Background: Breast cancer (BCa) is the most common cancer in women. Adjuvant hormone therapy (AHT) showed consistent improvements in recurrence and survival rates. AHT use is associated with multiple side effects that cause a lack of adherence. This report aims to describe the symptom burden of BCA patients at treatment initiation from our ongoing RCT, which is directed at improving adherence through the innovative use of smart pill bottles. Methods: Descriptive statistics included socio-demographic information and medication use. Symptom burden and distress are assessed using the breast cancer prevention trial (BCPT) symptom scales. Self-efficacy is assessed using a modified version of Lorig’s Chronic Disease Self-Efficacy Scale for managing symptoms. Results are summarized as means (M), standard deviation (SD), ranges (R), and percentages. The relationship between patients’ symptoms and self-efficacy was analyzed using a multivariable linear regression model controlling for age and race. Results: Of the 119 patients included, the majority were White 80.7 %, with ages ranging from 31-81 with a mean age of 59.74 (SD=11.057). The majority had a college education or higher (61.3 %), married (66.4%), full-time workers (42.9 %) and had incomes of 75,000 USD or higher (59.0 %). The patients were on either Tamoxifen (17.7%), Anastrozole (55.4%), Letrozole (12.3%) or Exemestane (4.6 %). The (BCPT) subscales were; vasomotor symptoms (R=0-12.5, M= 5.8, SD= 3.14), Gastrointestinal symptoms (R=0-7.5, M= 2.97, SD= 1.14), bladder control (R=0-10, M= 3.09, SD= 1.87), Dyspareunia subscale (R=0-10, M= 3.53, SD= 2.27), Musculoskeletal pain (R=0-15, M= 7.5, SD= 3.53), Weight concerns (R=0-10, M= 4.22, SD= 2.16), Cognitive symptoms (R=0-15, M= 6.02, SD= 2.81). For the LORIG scales (R=1- 8.83, M= 6.04, SD=1.61). Patient symptoms were inversely correlated with higher LORIG scores for vasomotor symptoms (β = -.18, t(3) = -2.00, p= .048), Gastrointestinal symptoms (β = -.27, t(3) = -2.92, p= 0.004), Musculoskeletal pain (β = -.378, t(3) = -4.31, p= .000), Weight concerns (β = -.286, t(3) = -3.26, p= .0002), Cognitive symptoms (β = -.34, t(3) = -3.841, p= .000). Conclusions: Our results explore symptom burden and distress for breast cancer patients on AET. Based on the BCPT instrument subscales, musculoskeletal symptoms tend to be the most intrusive, with the highest mean score. Symptom burden was inversely related to higher self-efficacy represented by LORIG scores. This needs to be validated with further analysis in comparison to a control group across time points in the study to determine what would be a minimally important difference or change in score. This will help understand the interrelationships between physical symptoms and adherence to AHT. Clinical trial information: NCT04086875 .
Factors associated with oncotype and recurrence among a diverse breast cancer population seeking care at an urban safety-net hospital.
Authors: Wang Judy Jiaqi , Beaulieu-Jones Brendin , Acevedo Jose , Oshry Lauren , Merrill Andrea , Hirsch Ariel , Cassidy Michael Ryan , Ko Naomi Yu
Published: June 2023

e12537

Background: The landmark trials, TAILORx and RxPONDER have established Oncotype DX (ODX) as a prognostic and predictive tool in the management of estrogen receptor positive (ER+), early-stage breast cancer. However, recent studies have revealed existing racial disparities in the ODX test. These findings call into question whether ODX is generalizable to diverse populations. We evaluated the prognostic value of ODX RS at an urban, academic safety net hospital. Methods: We conducted a single-institution retrospective study of patients diagnosed with invasive breast cancer and had an ODX test performed between January 1, 2010 to December 31, 2021. Demographic, tumor and treatment characteristics were obtained. Chi-square and ANOVA were used to examine associated factors among recurrences and non-recurrences. Results: We identified 315 patients diagnosed with ER+ breast cancer with an ODX test obtained. Racial breakdown was 47% White, 35% Black and 18% Other. 69% of the patients had public or no insurance. 20% of the patients had a low RS (0-10), 62% had intermediate (11-25) and 18% were high (26-100). 264 patients had no evidence of recurrence, 15 patients had a local or distant recurrence and 36 were unknown. Recurrence was significantly associated with younger age (p = 0.04), higher histologic grade (P < 0.001, < 0.001), intermediate oncotype score (p = 0.002) and no receipt of chemotherapy (p = 0.014). Focused analysis of the recurrence cohort demonstrates a significant proportion with an Intermediate ODX RS classification (93.3%, P = 0.001). 53% had distant recurrence, 20% had received adjuvant chemotherapy and 93.3% were adherent to hormonal therapy. Conclusions: In a diverse patient population, recurrences were significantly more likely among younger patients with high grade tumors, intermediate RS and those who did not receive chemotherapy. Further investigation and understanding whether Oncotype DX is generalizable to diverse breast cancer patient populations is needed.
BMI and mortality in hormone-negative breast cancer: A PLCO trial subgroup analysis.
Authors: Chamseddine Reem , Major Stella , Rafii Arash , Elmalik Hind Doha
Published: June 2023

e12544

Background: Body Mass Index (BMI) is a significant prognostic factor in the survival of patients with hormone receptor-positive breast cancer (BC).[1-2] However, the relationship between BMI and survival is not well-established in hormone receptor-negative (HR-) breast tumors. [3] Emerging data is mixed: some studies show that BMI does not impact outcomes in HR- tumors [4], while others reveal worse survival in patients with elevated BMI.[5] In this study, our objective was to corroborate recent evidence about the relationship between BMI and mortality in hormone-negative breast cancer. Methods: We used the PLCO cancer screening trial, a publicly available database containing information about 155,000 participants enrolled in the United States between 1993 and 2001. Data were collected on cancer mortality through 2018 (median follow-up of 19.2 years post enrollment). The methodology of the PLCO trial has been described previously.[6] All female patients with a diagnosis of HR- BC diagnoses were selected for data retrieval, including HR-/HER2+ and HR-/HER2- tumors. Patients with equivocal receptor status were excluded. We used multivariate Cox regression to analyze mortality by BMI category, after adjusting for all significant variables at the bivariate level ( p <0.25). Results: 348 women with confirmed HR- BC at the time of study participation were included. Mean age was 69 years old, and 62 patients (17.8%) passed away due to breast cancer during study enrollment or follow-up. Patients who were of normal weight (BMI 25-<30) at age of trial enrollment were not significantly more likely to survive compared to overweight or obese patients (Hazard Ratio 1.274, p= 0.623). Conclusions: Our results show no significant relationship between BMI and mortality in patients with HR- BC tumors. This finding adds to the growing literature about weight status in hormone receptor-negative tumors. Our data suggests that the mechanism of tumor progression in HR- breast tumors is unlikely to involve signaling mechanisms in adipocytes. Clinical trial information: NCT00002540 , NCT01696968 , NCT01696981 , NCT01696994 . [Table: see text]
Genomic and transcriptomic profiling of inflammatory breast cancers and non-inflammatory breast cancers in Asian women.
Authors: Zhou Kaiwen , Lin Ying , Zhang Mengmeng , Shao Nan , Shan Zhen
Published: June 2023

e12546

Background: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Despite its rare incidence, it accounts for 10% of breast cancer-caused mortality. Previous studies based on NGS have focused on western populations and found no common genomic and transcriptomic difference that could distinguish IBC from non-IBC. Methods: We performed WES on 15 IBC samples and their paired normal blood to identify somatic genomic alterations, copy number variants and large structural variants. RNA-seq was performed on 16 IBC samples to examine the RNA expression, pathway enrichment and gene fusions. WES and RNA-seq data were further investigated to discover genes that were dysregulated in both genomics and transcriptomics. For comparison, we performed WES and RNA-seq on 5 non-IBC samples and acquired additional 33 non-IBC samples of Asian women from the Cancer Genome Atlas Program (TCGA). Results: Apart from results similar to the previous reports in western IBC, ZNF74 and DYNC2H1 were identified as Asian-IBC-specific somatic mutations in our cohort. Elevated HRD mutational signature and scarHRD score indicated increased HRD events in Asian IBC patients. Structural variation analysis showed that deletions were found more frequent in IBC. RNA-seq indicated increased immune activation in IBC samples, but the immune cell infiltration within the tumor microenvironment were similar between IBC and non-IBC. Multiple gene fusions were more frequently found in IBC, including CTC-786C10.1—RP11-680G10.1, TULP4—RP11-732M18.3, RN7SL4P—RN7SL173P. Combined analysis of WES and RNA-seq showed more frequent mutation and increased pathway enrichment of RAS pathway in IBC, which may explain the aggressive biological behavior of IBC, inhibitors such as sorafenib, tipifarnib and trametinib targeting RAS signaling and its downstream pathways were predicted to possess promising effects in IBC treatment. Conclusions: Our study is the first to provide a complete genomic and transcriptomic landscape of IBC based on combined analysis of WES and RNA-seq and the first to focus on Asian women. We discovered intriguing differences unique in Asian women that could potentially explain IBC etiology and presented RAS signaling pathway as a potential therapeutic target in IBC treatment.
The race, staging and clinical correlations with genetic mutations detected in breast cancer patients.
Authors: Kyaw Nay Yee Wint , Durana Theresa , Natarajan Vijaya , Xu Yiqing
Published: June 2023

e12547

Background: Genetic testing has been applied widely in oncology and guidelines and criteria have been established for selection of testing. We aimed to study the variants of genetic mutations detected in a cohort of breast cancer patients of multiple ethnicity background, and its pathoclinical correlations. Methods: Breast cancer patients who have had a genetic test performed between 1/1/2010 until 1/31/2022 were eligible. Results: Among 767 patients tested, 77 patients were found to have germline mutations, including BRCA 1 (n = 20), BRCA 2 (n = 19), PALB2 (n = 12), CHEK 2 (n = 6), ATM (n = 4), RAD50 (n = 4), and others (n = 12). The race and ethnic groups were White/Caucasian (n = 23), African American (AA) (n = 25), Asian (n = 13), Jewish (n = 12) and Hispanic (n = 4). Genetic testing were performed when the tumors were diagnosed of stage 1-2 in 77.8% in white + jewish, 100% in Asian, 75% in Hispanic patients, but only 64% in AA patients. Non metastatic tumors with BRCA 1/2 mutation had a distribution in stage 1, 2, and 3 to be 30%, 37.5%, 27.5% respectively, while that for PALB2 was 0%, 83.3%, 8.3% respectively. BRCA 1 cancers showed 61.9% triple negative, 23.8% ER+/Her-2 neg, 14.3% ER-/Her-2 + distribution, and BRCA 2 cancers showed 31.6% triple negative, 63.2% ER+/Her-2 neg, and 5.3% ER+/Her-2 + distribution. PALB2 cancers showed 16.7% triple negative, 58.3% ER+/Her-2 neg, and 25% ER+/Her-2 + distribution. 4 (5.2%) patients were male, who had BRCA 2 (n = 2), RAD 50 (n = 1), and APC (n = 1), 3 were ER+/Her-2 neg, and 1 was ER+/Her-2 +. If NCCN criteria is used for selection for genetic testing, 8 (10.4%) patients will not meet the test criteria. Conclusions: Performance of genetic testing was done in more than 77% of the patient in early stage 1-2 breast cancer, which is significantly lower in AA subgroup (64%). BRCA 1/2 cancers presented in all early stages, while PALB2 cancers were predominantly stage 2 at diagnosis. Triple negative cancers were most common in BRCA 1, but can present in BRCA 2 and PALB2 mutations . RAD 50 and APC mutations can cause male breast cancer. Applying NCCN guideline, 10% patients will be missed for testing.
Characterizing the mental health of South African women living with comorbid HIV and breast cancer.
Authors: O'Neil Daniel , Blanchard Charmaine , Joffe Maureen , Ream Molly , Tshabalala Gugulethu , Diaz Alain , Chen Wenlong Carl , Mkwanazi Nontlantla , Blomberg Bonnie , Antoni Michael
Published: June 2023

e12549

Background: In South Africa’s public hospitals, 20% of new breast cancer (BC) diagnoses are in women living with HIV (WLWH). These women experience 49% higher mortality than BC patients without HIV. Mental health disorders are prevalent in both WLWH and women with BC. Symptoms of depression, anxiety, and acute stress are linked to increased circulating serum inflammatory markers, which may provide a pathophysiologic explanation for poorer outcomes. We aimed to explore whether South African BC patients living with HIV report more mental health symptoms than women with HIV alone, BC alone, or neither and to determine if comorbid HIV and BC is associated with greater systemic inflammation. Methods: We conducted a cross-sectional study of black South African women ≥18 years old. We enrolled four arms: newly diagnosed BC patients with HIV, newly diagnosed BC patients without HIV, WLWH without BC, and women with benign breast diagnoses. Participants were recruited from the breast clinic or HIV clinic at Chris Hani Baragwanath Academic Hospital. Consenting women completed the Center for Epidemiologic Studies Depression Scale (CES-D), the Generalized Anxiety Disorder 7-item Scale (GAD-7), and the Perceived Stress Scale (PSS). Blood samples were tested for serum concentrations of inflammatory markers (c-reactive protein (CRP) and S100A8/A9), pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-α), and anti-inflammatory cytokines (IL-4, IL-5, and IL-10) via ELISA assays performed at the University of Miami. Results: The first three arms enrolled 25 women each and the benign arm enrolled 22 women. Participant scores on the CES-D, GAD-7, and PSS were higher than expected in all groups and seemed to be worse in participants with HIV alone. Scores consistent with clinical depression, moderate to severe anxiety, and moderate to severe stress were reported by 68-88%, 28-76%, and 72-94% of participants, respectively. We found trends towards higher concentrations of CRP, TNF-α, IL-6, and IL-8 in participants with co-morbid BC and HIV versus benign breast disease but no pattern of increased inflammatory marker concentrations in participants with dual diagnoses versus either diagnosis alone. Conclusions: Our pilot study did not find evidence of increased mental health symptom burden or systemic inflammation in South African women with comorbid breast cancer and HIV, versus either diagnosis alone. Increased mental health symptoms in women with HIV alone may reflect reduced access to supportive service available at the HIV clinic compared to the breast clinic. [Table: see text]
Fatty acid desaturase activity and single nucleotide polymorphism of fatty acid desaturase gene and breast cancer risk in estrogen receptor subtype.
Authors: Sonkusare Shipra
Published: June 2023

e12551

Background: Breast cancer (BC) is the most common cancer in women. Various mechanisms are known to promote tumourogenesis. Arachidonic acid and its metabolites are one such pathway which promote tumorigenesis by inflammation and angiogenesis. It can be hypothesized that fatty acid metabolism is dysregulated in women with BC. We compared the fatty acid desaturases activity in women with BC and the control women. Breast cancer, which is a diet-related inflammatory disease, is also associated with the plasma concentration of omega fatty acids (n-3 and n-6), and can have an impact of its genetic variants. We studied the association between genetic variant rs174537 of fatty acid desaturase gene 1(FADS 1) and the estrogen receptor positive BC. Methods: Sixty women diagnosed with BC and 40 control women without BC between the age group of 25-60years of age were recruited for comparing the fatty acid desaturases activity. The tumors were classified by Estrogen Receptor (ER) status. Fatty acid Desaturases activities (D5, D6 and D9) were estimated as the ratio of product to precursor of individual fatty acids in plasma lipids. To study the association between genetic variant rs174537 of fatty acid desaturase gene 1(FADS 1) and the estrogen receptor positive BC, we recruited 102 (ER +ve, n = 53; ER -ve,n = 49) women with proven BC, prior to therapy. SNP rs 174537(G > T) showed maximum variability and the strongest genetic determinant in the Genome-wide association study were genotyped using Sanger sequencing. Results: Decreased levels of delta 5 and delta 9 desaturases activity and increased delta 6 desaturase activity were associated with the adverse profile of BC than the control group. Estrogen Receptor status also showed variation in desaturase activity. The highest tertile of Alphalinolenic acid (ALA) showed a significantly reduced association with BC compared to the lowest tertile (OR = 0.2, 95 %CL = 0.1–1.14, P = 0.03). Median values of ALA were higher in GT/TT genotype in ER +ve molecular subtype (P = 0.03) and Docosapentaenoic acid (DPA) was higher in GG genotype of ER -ve molecular subtype (P = 0.037). When both the groups were put together the highest tertile of GG tertile showed significantly reduced association with BC compared with the other lowest tertiles of GG and GT/TT genotypes (OR, 95% CL = 0.45(0.2–0.9). Conclusions: We conclude that unbalanced polyunsaturated fatty acids and impaired fatty acid desaturation plays a role in the pathogenesis of BC. The high levels of arachidonic acid and low levels of n-3 fatty acids result in a pro-inflammatory milieu which might contribute to the pathogenesis of BC. We also conclude that the individuals with genetically determined lower activity of FADS1 (minor allele T) will derive greater advantage from n-3 fatty acids than those with higher FADS1 activity (G allele).
Incidental discovery of second primary malignancies in patients diagnosed with breast cancer: An institutional case series.
Authors: Iancu Alexandra , Manohar Poorni , Vinayak Shaveta , Gwin William R. , Linden Hannah M. , Specht Jennifer M. , Symonds Lynn Katherine , Davidson Nancy E. , Hunter Natasha
Published: June 2023

e12552

Background: National guidelines recommend tissue biopsy of suspected recurrent breast cancer, to confirm diagnosis and to characterize disease phenotype, receptor status, and molecular markers. Despite this, clinicians frequently rely on imaging alone to diagnose recurrent breast cancer; indeed, our group recently published data revealing that only half of patients in Washington state diagnosed with metastatic breast cancer between 2008 and 2017 underwent confirmatory biopsies for suspected metastatic disease on imaging. Here we present evidence of how this failure to fully evaluate suspected breast cancer recurrence could potentially lead to misdiagnosis. Methods: We surveyed our breast medical oncology faculty to identify patients treated at Fred Hutchinson Cancer Center (FHCC) from 2018 to 2022 in which a second primary carcinoma (not including non-melanoma skin cancers) was discovered as part of breast cancer workup and treatment. Results: We identified 10 cases of second primary diagnoses. Of these, the majority (7/10) were lung cancer; other diagnoses included neuroendocrine tumors (1), chronic lymphocytic leukemia (1), and thyroid cancer (1). In the case of lung cancers, patients were typically diagnosed during staging or CT evaluation for radiation or reconstruction, in which a pulmonary nodule raised suspicion for malignancy. In five cases, patients were treated with curative intent for both of their early-stage primary malignancies, and remain disease-free on endocrine therapy alone. In two cases, patients with biopsy-proven metastatic breast cancer were found to have new suspicious lung lesions, which on biopsy were found to represent lung adenocarcinoma; these patients were treated surgically for their lung cancer and continued long-term therapy for metastatic breast cancer. Conclusions: While imaging can raise strong suspicion for metastatic recurrence of breast cancer, the assumption that an apparently metastatic lesion 1) indeed represents metastasis and 2) represents metastatic spread of the known primary rather than another malignancy, risks treating both the primary tumor and the newly detected condition inappropriately. Biopsy is critical for confirmation of metastatic disease vs second primary or other etiology. As patients with metastatic breast cancer are surviving longer as our cancer-directed therapies improve, appropriate diagnostic measures for a suspicious non-breast malignancy are recommended for optimal care. Novel imaging modalities such as 18F-fluoroestradiol (FES) PET and others could be explored in discriminating between metastatic lesions and unrelated conditions.
In search for new targets: Differences of HER2 receptor expression between CNB and synchronous axillary lymph node metastases in 205 patients.
Authors: Weydandt Laura , Dogan Senol , Nel Ivonne , Horn Lars-Christian , Aktas Bahriye
Published: June 2023

e12559

Background: Lately large clinical trials have provided new treatment options for patients with metastatic HER2-low breast cancer. Studies have shown that there may be change in the expression of HER2 during disease progression. Yet, it is rarely considered that there can be already differences between primary tumor and synchronous lymph node metastases (LMN) in the primary setting. The aim of the present study was to analyze different HER2 expression profiles between primary tumor and synchronous LNM. Methods: We included 205 patients with primary breast cancer and LNM who underwent oncologic surgery between 2008 and 2021. Formalin-fixed and paraffin-embedded (FFPE) material were routinely examined immunohistochemically according to the ASCO guidelines. Membranous HER2-staining was scored as follows: zero = 0, low = 1+, equivocal = 2+ and positive = 3+. Results: 205 patients were either HER2 low or HER2 zero in CNB. When comparing CNB and LNM 5 (2,4%) patients were HER2 zero in CNB and HER2 low in LNM. 161 (78.5%) patients were HER2 zero in both CNB and LNM. 21 (10.2%) patients had a shift from HER2 low to HER2 zero in LNM. 18 (8,8%) patients had a HER2 low expression in CNB and HER2 zero expression in LNM. Conclusions: There seems to be a high frequency of HER2 heterogeneity between primary tumor and LNM in the primary setting. Different HER2 expression profiles should be considered for an optimal and individual treatment.
Prevalence and patterns of breast white adipose tissue inflammation among American Black women and indigenous Nigerian women with early-stage breast cancer.
Authors: Liu Bethina , Shen Sherry , Omoyiola Oluwatosin Zainab , Odujoko Oluwole O. , Sharma Avinash , Ogunleye Gbenga Samson , Owoade Israel Adeyemi , Olasehinde Olalekan , Wuraola Funmilola Olanike , Ntiamoah Peter , Flynn Jessica , Chen Yuan , Giri Dilip D. , Carpio Andrea , Kahn Rivka , Chang Cassandra , Morrow Monica , Alatise Olusegun Isaac , Kingham T. Peter , Iyengar Neil M.
Published: June 2023

e12560

Background: Racial disparities in breast cancer outcomes pose a major public health challenge. Complex interactions between social determinants of health and tumor biology, mediated by obesity and adiposity, may play an important role in these disparities. White adipose tissue inflammation (WATi) of the breast, which is histologically defined by the presence of crown-like structures (CLS-B), occurs in the setting of excess adiposity and promotes tumor growth via elevated levels of aromatase, proinflammatory growth factors, and metabolic dysregulation. Here we examined relationships between race, body mass index (BMI), and WATi in two cohorts of patients with early-stage breast cancer: 1) American Black women and 2) indigenous Nigerian women. Methods: Non-tumor breast WAT specimens were collected from patients undergoing mastectomy for treatment or prevention of breast cancer at Memorial Sloan Kettering Cancer Center (MSK) in the US and Obafemi Awolowo University Teaching Hospital (OAUTH) in Nigeria. WATi was defined by the presence of CLS-B as detected by CD68 immunostaining. All tissue analyses were performed at MSK. Associations among BMI and WATi were tested within each cohort using Kendall’s tau rank correlation and compared between cohorts using Pearson's Chi-squared test. Results: A total of 224 American women were enrolled at MSK between 2011-2018, of whom 39 self-reported Black race. At OAUTH, 97 Nigerian women were enrolled between 2018-2022. Invasive carcinoma was present in 32 American Blacks and 97 Nigerians. Of those with invasive carcinoma, the prevalence of WATi among American Black women was 72% vs. 37% in the Nigerian cohort ( p<0.001). In the US cohort, there was no significant difference between the prevalence of WATi among Black vs. non-Black patients (72% vs. 62%; p=0.3). 44% of American Blacks were obese and 34% overweight compared with 27% and 39% of Nigerians, respectively (p=0.07). The prevalence of WATi varied by BMI category within each cohort, as shown. Overweight/obesity was associated with WATi in the Nigerian (p=0.009) and American cohorts (p<0.001); a trend was observed in the American Black subgroup (p=0.13). Conclusions: Breast WATi and obesity were more prevalent among American Black women with breast cancer compared with Nigerian women. These findings highlight the need for further investigation of environment, lifestyle patterns, and body composition differences between indigenous and diaspora populations. [Table: see text]
Clinical subtypes and survival outcomes in invasive breast cancer with Paget’s disease: A SEER population-based study.
Authors: Bae Soo Youn , Lee Ji Eun , Park Woo-Chan , Yoon Chang Ik , Kim Dooreh , Shin Kabsoo , Lee Youngjoo
Published: June 2023

e12564

Background: The objective of this study was to investigate the clinicopathological characteristics, especially subtypes and survival outcomes of Invasive breast cancer with Paget's disease. Methods: 4930 patients were identified using the histopathology codes from the International Classification of Disease for Oncology third edition (ICD-O-3), from 2000 to 2019 in the Surveillance, Epidemiology, and End Results (SEER) database. Excluding 787 patients whose ICD-O-3 and TNM stages did not match, there were 663 patients with '8540/3, Paget disease, mammary', 976 patients with ‘8543/3, Paget disease and intraductal carcinoma(DCIS)’ and 2540 patients with ‘8541/3, and ‘8541/3, Paget disease and infiltrating ductal carcinoma (IDC) of breast’. ER and PR status have been available since 1990, and HER2 status since 2010. Results: Among patients with IDC and Paget's disease, 24.6% were under the age of 50 and 2.7% were male, which was higher than the other two groups. Expressions of ER and PR were higher than both groups, and HER2 expression was lower. The ratio of HR-/HER2+ subtype was also lower than the other two groups at 29.6%. ER+, Paget 43.7%, DCIS with Paget 36.4%, IDC with Paget 53.6%. PR+ Paget 21.6%, DCIS with Paget 21.7%, IDC with Paget 40.1%. HER2+ Paget 69.2%, DCIS with Paget 83.1 %, IDC with Paget 58.3%. HR-/HER2+subtype, Paget 40.7%, DCIS with Paget 49.2%, IDC with Paget 29.6%. As a result of survival analysis in patients with IDC and Paget's disease, the HR-/HER2+ subtype had shown the best prognosis in Overall Survival (OS) analysis (5year OS, HR+/HER2- 70.8%, HR+/HER2+ 74.9%, HR-/HER2- 63.7%, HR-/HER2+ 80.7% P=0.010) In the BCSS analysis, the 5-year BCSS was the best at 87.0% in the HR-HER2+ subtype, but there was no statistically significant difference. Conclusions: In IDC with Paget's disease, the distribution of subtypes is different from that of DCIS with Paget's, and HER2 expression can be considered as a favor prognostic factor. It is considered necessary to study the relationship between the loss of HER2 overexpression and invasion/progression in invasive breast cancer with Paget's disease.