bluuebunny/crossref_metadata_2025_split huggingface dataset:
The correlation analysis of 21-gene assay use in uninsured and underrepresented minorities with estrogen receptor (ER) positive HER2 negative breast cancer.
Authors: Jeon Hyein , Kim Eileen , Subramanian Megana , Suarez-Ligon Adriana , Jaloudi Mohammed 
Published: June 2022

e12531 Background: 21-gene breast cancer recurrence-score assay (Oncotype DX) have been used to predict recurrence risks and guide adjuvant chemotherapy. However, access to such tests is limited, especially in a population concentrated with uninsured and underserved patient populations. Previously equations such as the Magee equation has been proposed to predict correlation of the recurrence score and the estimated recurrence score with high concordance rate. This study examines the concordance of such an assay to predicted scores in uninsured and underrepresented minority heavy public hospital. Methods: We performed a retrospective chart review of 68 women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer seen at University Hospital (public safety net hospital in Newark, New Jersey with greater majority of the patient population consists of underrepresented minorities such as Black/African Americans and Latino/Hispanics). 6 patients did not have pathology records, 9 patients did not have the Oncotype information available, and 4 patients were waiting on the results. Of the pre-menopausal eligible patients, two did not have any treatment or follow up information available and were included as part of the correlation assay, however, no. Results: Of the 47 eligible patients with follow-up information, 13 had a low recurrence score of up to 10 if post-menopausal and up to 15 if pre-menopausal, 22 had an intermediate recurrence score of 11 to 25 if post-menopausal and 16 to 25 if pre-menopausal, and 12 had a high recurrence score of greater than 26 according to the national comprehensive cancer network guidelines. The Pearson correlation between the Magee predicted score and Oncotype recurrence score was 0.73 (p < 0.001). All patients received hormone therapy and 5 patients total had recurred. 2 were pre-menopausal and had received adjuvant chemotherapy. 3 were post-menopausal in low and intermediate categories who had not received adjuvant chemotherapy. Conclusions: This study shows a high correlation between the predicted Magee score and Oncotype recurrence score. This reflects a possible use in the prediction scoring system as another resource for prognostication and guidance in treatment especially in the underinsured population.
Using a multimodal approach to elucidate racial disparities in breast cancer biology by integrating tumor imaging and -omics data.
Authors: Liadis Nicole , Earnest Tyler M , Braun Eduardo , Antony Anu K. , Hallock Micahel J , Team The SimBioSys , Cook Daniel 
Published: June 2022

e12541 Background: Race-related differences in breast cancer incidence and clinical outcome have been well documented, with many studies focusing on socioeconomic determinants contributing to African American (AA) breast cancer patients having higher mortality rates. Far less is understood about the underlying biological differences in tumors between AA and Caucasian patients. In recent years, there have been more and more individual accounts identifying specific somatic mutations or observed breast tumor behaviors associated with racial disparities in breast cancer. Understanding how these specific observations coincide to give rise to alternative tumor biology in AA women, remains a challenge. Given the multifactorial nature of cancer, we have developed a platform that integrates the combinatorial phenotypic, molecular, and biological hallmarks of cancer. Our technology combines imaging and multi-omics data, providing a systematic approach for understanding race-specific biological differences and how they contribute to patient survival. Methods: Imaging and transcriptomic data from 1108 patients were integrated within the SimBioSys TumoScope biophysical modeling software to understand racial differences in tumor biology, coordinated tumor behavior, and corresponding patient outcome. Results: AA patients have tumors that display higher growth rates, characteristically have higher adipose tissue around the tumor, higher spatial variation in drug/ nutrient delivery, and increased tumor stiffness. We also identified biological features, including tumor/gland density and intertumoral heterogeneity that are prognostic for overall survival even when accounting for race and cancer subtype. Conclusions: Our results outline characteristic biological features that along with race and FDA breast cancer subtype may promote the disproportionately poor survival rates observed in AA breast cancer patients. This is the first study demonstrating a systematic approach being used to elucidate race-specific biological difference that may coordinate to impact patient survival. Our findings emphasize the importance of accounting for racial disparities and patient-specific biology to develop tailored intervention strategies and personalize race-specific clinical management of breast cancer.
Brain 18-FDG-PET patterns in early breast cancer subtypes: Relationship with headache.
Authors: De Sanctis Rita , Antunovic Lidija , Benvenuti Chiara , Jacobs Flavia , Gaudio Mariangela , Ilieva Mariya , Viganò Alessandro , Chiti Arturo , Santoro Armando 
Published: June 2022

e12560 Background: Brain metabolic response on 18F-fuorodeoxiglucose(FDG)-PET in breast cancer (BC) patients is not routinely investigated, although several bidirectional relationships have been described between BC (and BC therapies) and brain functions. For example, common forms of headaches, as migraine (Mi) and tension-type headache (TTH), seem to be oddly distributed among BC subtypes and possibly influence the outcome. Methods: We recruited patients with early BC referring to IRCCS Humanitas Research Hospital who received neoadjuvant chemotherapy. Demographic data, BC characteristics and headache diagnosis were recorded, through detailed interview and instrumental investigation. Ki67 was considered high if above 20%. All patients underwent dedicated 18F-FDG PET scan for the evaluation of brain metabolism. Semiquantitative image analysis was performed using Cortex ID software (GE), comparing patient’s scan with a control group by the means of Z-score. The difference between patients’ subgroups were assessed using One-way ANOVA model. Results: Twenty-three patients were recruited. The median age was 52.5±10.8 years; 65.2% were postmenopausal, 30% premenopausal, and one patient perimenopausal. Ten patients were diagnosed as triple-negative BC, 6 as HER2-positive and 7 as Luminal B/HER2+. Nearly 70% (16/23) of patients had high Ki67 values. All patients had ECOG PS 0. Ten patients were diagnosed with TTH, 9 with migraine of whom two with aura, and four patients had no headache. Eleven patients had active headache at the moment of the study. At the whole brain level, we found a significant increase of brain metabolism in the left hemisphere of BC patients with high Ki-67 (p=0.007). Moreover, the same result was found in parietal cortex and in general associative areas bilaterally. Instead, HER-2 positive BC patient showed a reduced metabolism in right temporal cortex compared to HER-2 negative (p=0.04). Grading and other tumor characteristics did not influence FDG-PET uptake. BC patients with TTH had a reduced activity in right medial frontal lobe compared with migraine patients (p=0.01). Those with an active headache had increased activity in posterior cingulate and reduced activity in visual networks (p=0.03). Conclusions: Although exploratory, this study suggests that BC subtypes could present different metabolic pattern of cerebral activity, particularly in dominant hemisphere and associative areas. The high prevalence of headache in our sample does not affect the above pattern, but it is associated with an altered activation in other networks, mainly cingulate and visual cortex, which are well-known areas involved in primary headache.
Differences in tumor microenvironment between HER2-positive and HER2-negative breast cancer.
Authors: Gong Chang , Lin Qun , Cen Yinghuan , Fang Xiaolin , Shi Yu , Chen Letian , Luo Qing , Duan Zhuxi 
Published: June 2022

e12562 Background: The tumor microenvironment of breast cancer is extremely complex, which containing different types of lymphocytes, macrophages, NK cells and other immune cell subtypes. At present, the relationship between immune cell subtypes and molecular subtypes of breast cancer is still unclear. Methods: Tumor tissue samples of 20 breast cancer patients were collected from January 2020. Then the density (number of positive cells/mm2) and ratio of immune cells in intratumoral area and stromal area were detected by multiple fluorescence immunohistochemistry (mIHC), the detection range was included CD3+T cells, CD4+T cells,CD8+T cells,PD-1+CD8+T cells,Tregs,M1/M2 tumor associated macrophages (TAM), PD-L1+CD68+TAM,B cells,CD56bright NK cells and CD56dim NK cells and so on. The immune cell subtypes of all area were included both intratumoral area and stromal area. Graphpad prism (version 7.01) was used for t test and the statistical significance was set at p=0.05. Results: These 20 patients were divided into two groups, HER2 positive (n=8) and HER2 negative group (n=12). The density of CD3+T cells in all area (including intratumoral area and stromal area) of tumor tissue in HER2 positive breast cancer patients were significantly higher than that of HER2 negative breast cancer patients (median density, HER2 positive group vs. HER2 negative group=2998 vs. 1520/mm², p=0.031) as well as the CD8+T cells (median density, HER2 positive group vs. HER2 negative group=536 vs. 175/mm², p=0.015). Meanwhile, the density of Tregs in all area of tumor tissue in HER2 positive breast cancer patients was also significantly higher (median density, HER2 positive group vs. HER2 negative group=119 vs. 27/mm², p=0.022).However, there was no significant difference in the other subtypes of immune cells infiltrated in tumor tissue between HER2 positive and HER2 negative samples, such as CD4+T cells, M1/M2 macrophages, B cells and so on (p＞0.05). Conclusions: Our research indicates that the patterns of immune cell subtypes in different types of early breast cancer are different. Further exploration of the immune microenvironment in different molecular types of breast cancer may provide additional targets for immunotherapy.
Novel imaging marker for low- and mid-recurrence score patients at risk for recurrence.
Authors: Peterson Joseph R , Antony Anu K. , Team The SimBioSys , Cole John A. 
Published: June 2022

e12565 Background: The 21-gene (Oncotype DX) recurrence score (RS) has been utilized as a prognostic assay in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. The results stratify patients into low-, mid- and high-risk of disease recurrence. Patients with a low recurrence score tend to have lower recurrence rates and are less responsive to chemotherapy. On the other hand, patients with high-recurrence scores are more likely to respond to chemotherapy. While for patients at the high end of the RS spectrum it is apparent that chemotherapy carries benefit, distinguishing chemotherapy benefit for low- and mid-recurrence score (RS-low/-mid) patients is less clear. Methods: To address this, we used a novel 2-paramenter pharmacokinetic modeling framework that allows biosignatures to be extracted from dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI) studies that contain 3-6 timepoints spaced 60-90 seconds apart. These parameters, referred to as P1 and P2, represent leakiness from vessels to the extravascular space and vice versa. Results: Using this model, we performed a study in a cohort of 111 breast cancer patients with 21-gene assay RS and DCE-MRIs available. P1 and P2 were extracted from patient standard clinical DCE-MRIs. We performed univariate (Kaplan-Meier) survival analyses to test the prognostic value of the parameters covariate in predicting recurrence free survival (RFS). A pre-specified value of the median P1 and P2 across the patient population was used for stratifying patients into “low” and “high” groups, representing patients with “low” or “high” vessel leakiness. We analyzed patients according to RS. Low P1 showed better outcomes in RS-low and RS-mid patients (n=88, p≤0.028; log-rank test). Patients with a high P1 had a 20.2% chance recurrence at six years. The same trend was observed when considering just RS-mid patients only (n=23, p≤0.058). No recurrences were observed in patients with low P1 in either the RS-low or RS-mid categories. Additionally, there were no recurrences in the high P1, RS-low/-mid category that received chemotherapy, suggesting that chemotherapy could be beneficial in this category of patients, although the trend was not statistically significant (n=10, p=0.46). Similar results were seen for P2. Conclusions: Overall, we demonstrate how our prognostic imaging marker can identify a subset of patients with low-/mid-recurrence scores that could benefit from chemotherapy. This new prognostic approach has the potential to optimize treatment and improve personalized care by providing clarity on the use of chemotherapy in low-/mid-recurrence score patients.[Table: see text]
Tumor copy number alterations were associated with primary endocrine resistance in ER+ breast cancer.
Authors: Lu Qianyi , Xu Fei , Wang Shusen , Wang Na , Shao Yang , Ouyang Yuming 
Published: June 2022

e12567 Background: Several studies has showed alterations in genes were associated with endocrine resistance in breast cancer. Nevertheless, genomic landscape in primary endocrine-resistant breast cancer has not been thoroughly reported. Whether the genomic landscape of primary endocrine-resistant breast cancer is different from that of secondary endocrine-resistant breast cancer is unknown. Methods: We analyzed the genomic landscape of primary tumor of consecutive patients with estrogen-receptor positive (ER+) breast cancer in real-world clinical practice in our center between September, 2019 to December, 2020. According to the duration of endocrine treatment, we classified them into primary endocrine resistance group and secondary endocrine resistance group. Results: A total of 41 tumor samples of which 25 cases in primary endocrine resistance and 16 cases in secondary endocrine resistance were included for analysis. TP53 (65.9%, 27/41), PIK3CA (46.3%, 19/41), MYC (36.6%, 15/41), MCL1 (31.7%, 13/41), CCND1 (31.7%, 13/41) were the most frequently altered genes in all 41 BCs. Copy number amplification of MYC was common in primary endocrine resistant group (48.0%, 12/25), while lower in secondary endocrine resistant group (18.8%, 3/16, P = NS). Copy number alteration (CNA) of CCND1, MCL1, FGF19, ZNF217, ZNF703 and FGFR1 were commonly observed in primary endocrine resistance group. Percentage of CNA in all mutation types was significant increased in primary endocrine resistance group than in secondary resistance group (33.0% vs. 21.0%, P = 0.03). Then we further analyzed and found CNA burden, which was defined as number rather the percentage of the CNA event, was associated with the prognosis in ER+ breast cancer. When defining 6 as the cut-off value of CNA-High, DFS, PFS and OS were practically poorer in patients with CNA-High than those with CNA-Low. Conclusions: Copy number alterations were more commonly seen in primary endocrine-resistant breast cancer and associated with prognosis in ER+ breast cancer. This founding urged to further investigate the prognostic value of CNA burden in predicting the effectiveness of endocrine therapy.
Investigate the accuracy and economic value of the upstaging prediction model for ductal carcinoma in situ.
Authors: Chiu Ching-Wen , Tam Ka-Wai , Shih Shen Liang Jerry 
Published: June 2022

e12577 Background: The current study aims to define the “high-risk upstaging model” in ductal carcinoma in situ (DCIS) and investigate its accuracy in order to suggest the most precise application of sentinel lymph node biopsy (SLNB). Methods: PubMed, EMBASE, and Cochrane library databases were searched. Prospective and retrospective cohort studies that evaluated the pathological outcomes of SLNB and the upstaging rate in women with DCIS were included. We analyzed factors that potentially indicate nodal involvement risk and combine the significant ones into “high-risk upstaging model”. Consecutively, we conducted a retrospective study by applying our model and NCCN guideline model into DCIS patients extracted from hospital database. Both the excess treatment rate and incomplete treatment rate of SLNB were analyzed. The diagnostic performance of the model in predicting upstaging risk was evaluated with receiver operating characteristic (ROC) curve. Results: We retrieved 43 prospective and 69 retrospective studies including 44,001 DCIS patients. The upstaging rate was significantly higher in patients with estrogen receptor-negative status, palpable mass, tumor size > 2 cm on imaging, and high-nuclear grade and those who received a preoperative diagnosis through core needle biopsy. We then collected 168 DCIS patients who entered in Shuang-Ho hospital from February 2017 to August 2021. Ninety-six patients who didn’t upstage in final pathology have received extra SLNB and two patients who upstaged in final pathology did not receive SLNB in primary surgery. The areas under the ROC curve of the model developed by multivariable logistic regression for predicting upstaging risk in the NCCN guideline group and “high-risk upstaging model” group were 0.642 and 0.706, the sensitivity at 66.0% and 83.0%, and the specificities at 62.5% and 49.2%, respectively. Conclusions: “High-risk upstaging model” shows higher areas under the ROC curve and sensitivity as well compared with current NCCN guideline. Our prediction model can provide surgeons with a more accurate and specific indications of SLNB in DCIS.
Lymphocyte populations in wound fluid in breast cancer patients after mammoplasty with textured implants.
Authors: Przhedetskiy Yuriy V. , Sagakyants Aleksandr B. , Przhedetskaya Viktoria Yu , Zlatnik Elena Yu , Bondarenko Elena S. , Shulgina Oksana G. , Zolotareva Ekaterina I. , Ulianova Elena P. , Pozdnyakova Viktoria V. , Ulianova Yulia V. , Volkova Viktoriya L. , Bauzhadze Mamuka V. , Pustovaya Irina V. , Chertova Natalia A. , Goncharova Elena G. , Maldonado Mary L. 
Published: June 2022

e12588 Background: Breast reconstruction after skin-sparing mastectomy for breast cancer (BC) is an important rehabilitation stage. Its results depend on many factors, with the immune system status playing the main role. The purpose of this study was to identify characteristics of the local lymphocyte populations in patients with breast cancer in the early postoperative period after reconstructive surgery with textured implants (TI). Methods: The study included 30 patients aged 32-68 years, mean age 42.9±1.98 years, with stage I-IIb BC (monocentric nodular BC, T1N0M0 - T2N1M0). All patients underwent skin-sparing mastectomy with level II axillary lymph node dissection and immediate implant reconstruction in 2017-2019. Populations and subpopulations of lymphocytes were determined in wound fluid from the cavity with TI on days 1, 3-4 and 7 after the surgery using the FacsCanto II flow cytometer (Becton Dickinson, USA) with markers: CD3 FITC /CD15+56 PE /CD45 PerCP /CD4 PE-Cy7/CD19 APC/ CD8 APC-Cy7; CD45RA FITC /CD45RO PE /CD3 PerCP /CD8 APC; CD45RA FITC /CD62L PE /CD3 PerCP /CD4 APC; CD4 FITC /CD127 PE /CD3 PerCP / CD25 APC-Cy7; CD4 FITC /CD38PE /CD3 PerCP / HLADR APC. At least 50,000 cells were accumulated in each sample for the analysis. Results: The relative number of total lymphocytes exceeded the initial values by 3.3 (p=0.025) and 10.9 (p=0.012) times, respectively, on days 3-4 and 7 after surgery. Levels of CD3+CD4+ cells increased gradually and were 29% (p=0.042) higher by day 7, while levels of CD3+CD8+ decreased during the whole observation period. Levels of Tregs did not change, while B lymphocytes decreased by 36% (p=0.035) and 67% (p=0.026), respectively, on days 3-4 and 7. The levels of activated T lymphocytes increased by 33% (p=0.038) on days 3-4, compared with the initial values, probably due to the elevation of CD3+CD8+ levels (by 32%, p=0.037). The number of activated T lymphocytes with the CD3+CD4+ phenotype increased by 44% (p=0.024) on days 6-7. While the content of CD3+CD4+ cells with early activation markers (CD38+) significantly decreased (by 40%, p=0.031) and remained the same on days 3-4 and 7, the number of CD3+CD8+ with similar markers (CD38+) significantly increased by 28% (p=0.044) and 43%. Conclusions: TI implantation was accompanied by the activation of the cytotoxic T unit during the observation period, together with a decrease in immunosuppressive populations of lymphocytes, which may indicate a favorable development of the patient's body reaction.
Phase 2 study of anlotinib combined with taxanes and lobaplatin in the neoadjuvant treatment of triple-negative breast cancer: Efficacy, safety and biomarker analysis.
Authors: Tian Hao , Zhang Guozhi , Liang Yan , Liu Jing , Fan Linjun , Zhu Kai , Zhang Yi , Qi Xiaowei 
Published: June 2022

e12605 Background: Pathological complete response (pCR) is associated with improved prognosis in triple-negative breast cancer (TNBC). Anlotinib, a novel multi-target tyrosine kinase inhibitor that effectively inhibits VEGFR, FGFR, c-KIT, c-MET, and RET, monotherapy has been proven effective in HER-2 negative metastatic breast cancer, but its efficacy in early-stage TNBC is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients (pts) with primary TNBC. Methods: Pts with clinical stage II/III TNBC were to be treated with 5 cycles of anlotinib (12mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m2 or nab-paclitaxel 260 mg/m2, d1, q3w) and lobaplatin (30 mg/m2, d1, q3w), followed by surgery. The primary endpoint was the total pCR (tpCR; ypT0/is ypN0). A Simon’s two-stage optimum design was used, and ＞5 of 11 pts were required to achieve tpCR in the first stage, with a pre-specified tpCR rate of 54.5% before proceeding to the second stage. A total of 31 participants was required for the study. Results: Six out of 11 pts achieved tpCR in the first stage, reaching the threshold for the second stage. From Jan 2021 to Jan 2022, a total of 22 pts were enrolled and 12 received surgery after the completion of neoadjuvant therapy, but a total of 2 pts withdrew from the study due to the COVID-19 pandemic or serious adverse events. Of the 22 eligible pts, the median age was 49 years (range, 29-64), 64% were postmenopausal, and 73% were nodal involved. At the time of surgery, 58.3% (7/12) achieved tpCR. Of the 9 pts with the node-positive disease at diagnosis, 88.9% (8/9) became ypN0. The results of FUSCC TNBC classification (IHC-based) revealed the tpCR rates were 57.1% (4/7), 100% (3/3), and 0% (0/2) for BLIS subtype, IM subtype and LAR/unknown subtypes, respectively. Biomarker analysis showed the tpCR rates were 100% (3/3) and 100% (4/4) in patients with gBRCA1 mutation and MYC amplification, respectively. The most common grade 3 or 4 treatment-related adverse events were leucopenia (6/22, 27%), neutropenia (6/22, 27%), anemia (5/22, 23%), decreased appetite (5/22, 23%), hypertension (2/22, 9%), ALT increased (1/22, 5%) and oral mucositis (1/22, 5%). No treatment-related deaths occurred. The trial is ongoing. Conclusions: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for patients with early-stage TNBC. Clinical trial information: ChiCTR2100043027.