bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune phenotype and response to neoadjuvant systemic therapy (NAST) in triple negative breast cancer (TNBC).
Authors: Yam Clinton , Alatrash Gheath , Yen Er-Yen , Garber Haven , Philips Anne V. , Huo Lei , Yang Fei , Bassett Roland L. , Sun Xiangjie , Parra Cuentas Edwin Roger , Symmans William Fraser , Seth Sahil , White Jason B , Rauch Gaiane M , Damodaran Senthil , Litton Jennifer Keating , Wargo Jennifer Ann , Hortobagyi Gabriel N. , Moulder Stacy L. , Mittendorf Elizabeth A. 
Published: May 2020

509 Background: In TNBC patients (pts) receiving NAST, increasing tumor infiltrating lymphocytes (TILs) is associated with higher pathologic complete response (pCR) rates. However, since the presence of TIL do not consistently predict pCR, the current study was undertaken to more fully characterize the immune cell response and its association with pCR. Methods: T cell receptor (TCR) sequencing, PD-L1 immunohistochemistry and multiplex immunofluorescence were performed on prospectively collected pre-NAST tumor samples from 98 pts with stage I-III TNBC enrolled in ARTEMIS (NCT: 02276443). TCR clonality was calculated using Shannon’s entropy. PD-L1+ was defined as ≥1% immune cell staining. Response to NAST was defined using the residual cancer burden (RCB) index. Associations between TCR clonality, immune phenotype, and response were examined with the Wilcoxon rank sum test, Spearman’s rank correlation and multivariable logistic regression using stepwise elimination (threshold p > 0.2), as appropriate. Results: The pCR rate was 39% (38/98). pCR was associated with higher TCR clonality (median = 0.2 [in pts with pCR] vs 0.1 [in pts with residual disease], p = 0.05). Notably, the association between pCR and higher TCR clonality was observed in pts with ≥5% TIL (n = 61; p = 0.05) but not in pts with < 5% TIL (n = 37; p = 0.87). Among pts with ≥5% TIL, TCR clonality emerged as the only independent predictor of response in a multivariable model of tumor immune characteristics (odds ratio/0.1 increase in TCR clonality: 3.0, p = 0.021). PD-L1+ status was associated with higher TCR clonality (median = 0.2 [in PD-L1+] vs 0.1 [in PD-L1-], p = 0.004). Higher TCR clonality was associated with higher CD3+ (rho = 0.32, p = 0.0018) and CD3+CD8+ (rho = 0.33, p = 0.0013) infiltration but lower expression of PD-1 on CD3+ (rho = -0.24, p = 0.021) and CD3+CD8+ cells (rho = -0.21, p = 0.037). Conclusions: In TNBC, a more clonal T cell population is associated with an immunologically active microenvironment (higher CD3+ and CD3/8+ T cell; lower PD-1+CD3+ and PD-1+CD3/8+ T cell; PD-L1+) and favorable response to NAST, especially in pts with ≥5% TIL, suggesting a role for deep immune phenotyping in further refining the predictive value of TILs.
De-escalated chemotherapy versus endocrine therapy plus pertuzumab+ trastuzumab for HR+/HER2+ early breast cancer (BC): First efficacy results from the neoadjuvant WSG-TP-II study.
Authors: Gluz Oleg , Nitz Ulrike , Christgen Matthias , Kuemmel Sherko , Holtschmidt Johannes , Priel Jan , Hartkopf Andreas , Potenberg Jochem , Luedtke-Heckenkamp Kerstin , Just Marianne , Wuelfing Pia , von Schumann Raquel , Graeser Monika , Wuerstlein Rachel , Kates Ronald E. , Kreipe Hans Heinrich , Harbeck Nadia 
Published: May 2020

515 Background: HR+/HER2+ breast cancer (BC) is a distinct entity associated with better prognosis compared to HR-/HER2+ BC. However, combination of chemotherapy (CT) with (dual) anti-HER2 blockade is standard in HER2+ early BC (EBC), irrespective of HR-status. Despite of some promising data on combination of endocrine therapy (ET) with dual anti-HER2 blockade in EBC and metastatic HR+/HER2+ BC, no prospective comparison of neoadjuvant CT vs. ET + dual HER2-blockade has yet been performed. Methods: In the prospective WSG TP-II phase II-trial (NCT03272477; Sponsor: Palleos GmbH, Wiesbaden, Germany), 207 patients (pts) (257 screened; 40 centers) with centrally confirmed HR+/HER2+ EBC were randomized to 12 weeks of standard ET (n=100) vs. paclitaxel 80 mg/m2 weekly (n=107) +trastuzumab+pertuzumab q3w for all pts. Primary endpoint was pCR (ypT0/is/ypN0). Secondary endpoints include safety, disease-free and overall survival, translational research, and quality of life (QoL). Omission of further CT was allowed in all pts with pCR; dual HER2-blockade was administered in the adjuvant setting in all pts. Results: Baseline characteristics were well balanced between the arms. Median age was 53 years; 58% had cT2-4, 28% had cN+; 43% had G3 tumors. pCR data were available in 198 pts (ET: n=96; Pac: n=102). pCR was observed in 24% (95% CI: 16-34%) with ET+T+P vs. 57% (95% CI:47-67%) with Pac+T+P (OR 0.24, 95% CI: 0-0.46, p<0.001). In multivariable logistic regression analysis and corresponding sensitivity analysis (bootstrap/subsample inclusion frequencies and lasso regression) including study arm, BMI, menopausal, cT, and cN status, histological grade, HER2-status, Ki67, ER, PR as continuous variables, only study arm and HER2 3+ status were significantly associated with pCR. Neoadjuvant treatment was well tolerated in both study arms and completed per protocol in 93/92 (ET+P+T/Pac+P+T) patients. Only 9/13 SAEs (ET+P+T/Pac+P+T) were reported during neoadjuvant therapy. PAM50 and QoL analysis are ongoing. Conclusions: WSG TP-II is the first randomized prospective trial comparing two neoadjuvant de-escalation treatments in HR+/HER2+ EBC. The excellent pCR rate of 57% after only 12 weeks of Pac+P+T was clearly superior to the still promising 24% pCR rate in pts treated by ET+P+T. In both arms, treatment efficacy was most pronounced in HER2 3+ tumors. Survival results need to be awaited before definite recommendations for a de-escalated regimen in HR+/HER2+ EBC can be made. Clinical trial information: 2016-005157-21 .
Towards data-driven decision-making for breast cancer patients undergoing mastectomy and reconstruction: Prediction of individual patient-reported outcomes at two-year follow-up using machine learning.
Authors: Pfob André , Mehrara Babak , Nelson Jonas , Wilkins Edwin G. , Pusic Andrea , Sidey-Gibbons Chris 
Published: May 2020

520 Background: Post-surgical satisfaction with breasts is a key outcome for women undergoing cancer-related mastectomy and reconstruction. Current decision making relies on group-level evidence, which may not offer optimal choice of treatment for individuals. We developed and validated machine learning algorithms to predict individual post-surgical breast-satisfaction. We aim to facilitate individualized data-driven decision making in breast cancer. Methods: We collected clinical, perioperative, and patient-reported data from 3058 women who underwent breast reconstruction due to breast cancer across 11 sites in North America. We trained and evaluated four algorithms (regularized regression, Support Vector Machine, Neural Network, Regression Tree) to predict significant changes in satisfaction with breasts at 2-year follow up using the validated BREAST-Q measure. Accuracy and area under the receiver operating characteristics curve (AUC) were used to determine algorithm performance in the test sample. Results: Machine learning algorithms were able to accurately predict changes in women’s satisfaction with breasts (see table). Baseline satisfaction with breasts was the most informative predictor of outcome, followed by radiation during or after reconstruction, nipple-sparing and mixed mastectomy, implant-based reconstruction, chemotherapy, unilateral mastectomy, lower psychological well-being, and obesity. Conclusions: We reveal the crucial role of patient-reported outcomes in determining post-operative outcomes and that Machine Learning algorithms are suitable to identify individuals who might benefit from alternative treatment decisions than suggested by group-level evidence. We provide a web-based tool for individuals considering mastectomy and reconstruction. importdemo.com . Clinical trial information: NCT01723423 . [Table: see text]
Early-stage breast cancer (BC) patients: Factors associated with aromatase inhibitor-induced musculoskeletal symptoms.
Authors: Elder Simran Arora , Sun Yamin , Jung Seungyoun , Mainor Candace Bavette , Murali Shruti , Rosenblatt Paula , Tkaczuk Katherine H. R. 
Published: May 2020

525 Background: Hormone receptor positive (HR+) breast cancer comprises the largest subgroup of breast cancer. Aromatase Inhibitors (AI) are a key treatment for HR+ BC patients (pts) and reduce mortality. Aromatase Inhibitor-Associated Musculoskeletal Symptoms (AIMSS), defined as myalgias, arthralgias, or joint stiffness, occur in up to 50% of pts leading to low adherence to and often discontinuation of therapy. Little is known of the mechanism of AIMSS or its predisposing risk factors. This study aims to identify risk factors associated with AIMSS development in BC patients on AI therapy. Methods: We conducted a medical record review of pts with non-metastatic HR+ BC on adjuvant AI therapy between January 2009 and June 2017 at the University of Maryland Comprehensive Cancer Center. This study included 194 ptswho were free of arthralgia prior to AI therapy. We analyzed pts’ demographics, lifestyle factors, reproductive history, tumor characteristics, medications, cancer treatment, co-morbidities, AI type, onset and severity of AIMSS. Severe AIMSS was defined as requiring change in AI therapy or discontinuation. Multivariable-adjusted logistic regression was used to identify risk factors for severe AIMSS. Results: The mean age of participants was 61. The mean BMI at diagnosis was 30 kg/m2. 41% of pts were White, 40% were Black, 7% other and 12% unknown. Most (79%) did not have a history of tamoxifen and 16% were on GnRH agonists. Most (71%) used letrozole as initial AI therapy; 18% anastrozole; and 11% exemestane. 56% experienced AIMSS while on AI therapy and 20% required change or hold of AI therapy. 4% permanently discontinued AI due to AIMSS severity. BMI at diagnosis was significantly positively associated with risk of AIMSS. Multivariate odds ratio (95% confidence intervals) comparing the highest to lowest tertile of body mass index (BMI) at diagnosis was 4.01 (1.07-10.90; Ptrend: 0.05). There were no significant associations with race, smoking, reproductive factors, type of AI therapy, tamoxifen use prior to AI therapy, medication use, experience of other cancer treatments, and tumor characteristics. Conclusions: 56% of BC pts on adjuvant AI therapy experienced AIMSS. 24% of these changed, held or discontinued AI regimen due to severe AIMSS. Higher BMI at diagnosis was associated with a higher risk of AIMSS. Our results confirm clinical significance of AIMSS among BC pts on AI therapy and suggest BMI as a modifiable factor for AIMSS. A larger study is warranted to replicate our findings and seek other possible risk factors for AIMSS.
Safety and efficacy of single-agent adjuvant trastuzumab in older women with early-stage breast cancer.
Authors: Owusu Cynthia , Margevicius Seunghee P , Klepin Heidi D. , Vogel Charles L. , Alahmadi Asrar , Vuyyala Sowjanya , Brufsky Adam 
Published: May 2020

528 Background: Older adults with multiple comorbidities and poor functional status may not be appropriate candidates for chemotherapy. We conducted a phase II trial to examine the safety and efficacy of single-agent Trastuzumab for older women with early stage Human Epidermal Growth Factor Receptor Type 2 (Her2)-positive breast cancer. Methods: This was a single-arm open label multi-institutional clinical trial of adjuvant single-agent Trastuzumab in women aged ≥ 60 years with stage I-III Her2-positive breast cancer who had either declined chemotherapy or were not chemotherapy candidates. Patients received Trastuzumab monotherapy, (8 mg/kg) for cycle 1 followed by (6 mg/kg) every 3 weeks for 12 months. The primary end point was one-year cumulative incidence of symptomatic congestive heart failure with reduced ejection fraction (HFrEF). Secondary endpoints were disease free survival (DFS) and overall survival (OS) at 5 years. Results: Fifty-six patients were enrolled across four centers with a median follow-up period of 5.0 years, (range 0-6.5). The median age was 72.5 years (range 60-90), 64% had stage I disease, 77% had estrogen-receptor positive disease and 82% had node-negative breast cancer. Only two patients had symptomatic congestive HFrEF with a one-year cumulative incidence of 3.6%; (95% confidence interval [CI], 0.09 to 13.8). Five patients had asymptomatic declines in ejection fraction with a one-year cumulative incidence of 9.1%; (95% CI, 3.9 to 20.1). The 5-year DFS was 86.4%; (95% CI, 73.6 to 93.3). Among seven relapses seen, two were due to distant metastatic breast cancer. The 5-year rate of overall survival was 90.2%; (95% CI, 78.1 to 95.8). Among five deaths, one was due to distant metastatic breast cancer. Conclusions: Among older women with stage I-III HER2-positive breast cancer who decline chemotherapy or are not chemotherapy candidates, treatment with her2 targeted therapy only without chemotherapy may offer a reasonable treatment option without an inordinate rate of cardiac toxicity. Clinical trial information: NCT00796978 .
Estimation of absolute benefit of S-1 postoperative therapy for ER-positive, HER2-negative breast cancer: Exploratory analysis of the phase III potent trial.
Authors: Takada Masahiro , Imoto Shigeru , Ishida Takanori , Ito Yoshinori , Iwata Hiroji , Masuda Norikazu , Mukai Hirofumi , Saji Shigehira , Ikeda Takafumi , Haga Hironori , Saeki Toshiaki , Aogi Kenjiro , Sugie Tomoharu , Ueno Takayuki , Ohno Shinji , Ishiguro Hiroshi , Kanbayashi Chizuko , Miyamoto Takeshi , Ohashi Yasuo , Toi Masakazu 
Published: May 2020

532 Background: Estimation of risk of recurrence is critical for adjuvant therapy decision making in patients with primary breast cancer. The POTENT trial examined outcomes associated with standard postoperative endocrine therapy with/without S-1 in patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer (Toi et al, San Antonio Breast Cancer Symposium 2019). The aim of this study was to investigate absolute treatment effect across recurrence risk score to individualize indication for the concurrent administration of standard postoperative endocrine therapy with S-1. Methods: The POTENT trial included 1930 patients with ER-positive and HER2-negative breast cancer. The primary end point was invasive disease-free survival (iDFS). A continuous, composite measure of recurrence risk for each patient was determined from a Cox model incorporating age, tumor size, nodal status, grade, estrogen receptor, and Ki-67 expression levels. Absolute treatment effect of S-1 was estimated in each risk group defined by the composite risk score. Results: Of 1930 patients, we included the data from 1897 patients without unavailable data. Tumor grade, ER expression, and Ki-67 expression were available from central assessment. A Cox proportional hazards model for iDFS was estimated in standard endocrine therapy only group (N = 954). Age was excluded from the model because it did not add prognostic information. 5-year iDFS estimates were 91.6%, 82.0%, and 67.2% for low, intermediate, and high composite risk group, respectively. Absolute improvement in 5-year iDFS by the addition of S-1 to standard endocrine therapy were 0.9%, 6.7%, and 8.1% for low, intermediate, and high composite risk group, respectively. Hazard ratio for S-1 in each risk group were 0.86 (95%CI: 0.45-1.63, P = 0.642), 0.51 (95%CI: 0.34-0.78, P = 0.001), and 0.71 (95%CI: 0.49-1.02, P = 0.064), respectively. Continuous value of composite risk was also prognostic in a Cox proportional hazards model stratified by S-1 and neoadjuvant/adjuvant chemotherapy use (HR 2.58, 95%CI: 2.13-3.11, P < 0.0001). Conclusions: Patients with ER-positive and HER2-negative disease, and intermediate to high risk, defined by clinicopathological factors, experienced absolute improvement of about 7-8% in 5-year iDFS with addition of S-1 to standard endocrine therapy, while improvement was minimal in those at low risk. Clinical trial information: 000003969 .
Impact of delays in initiation of adjuvant endocrine therapy and survival among patients with breast cancer.
Authors: Lee Kimberley , Jacobs Lisa K. , Segal Jodi 
Published: May 2020

537 Background: Time to adjuvant endocrine therapy concerns patients and clinicians, but its impact on overall survival is not clear. There are no population level studies that address this question. Our primary objective is to describe the relationship between time from diagnosis of breast cancer to start of adjuvant endocrine therapy and overall survival. Methods: This is a population-based cohort study using prospectively collected population level data from the National Cancer Database (NCDB). The NCDB prospectively collects data on incident cancer cases from over 1500 Commission on Cancer-accredited facilities nationally. NCDB captures approximately 70% of incident cases of cancer in the United States. The participants are women with Stage II and III estrogen or progesterone receptor positive, human epidermal receptor 2 negative, invasive breast cancer who underwent definitive surgical treatment. Results: Of the 391,594 women in this study, 12,162 (3.1%) began treatment with adjuvant endocrine therapy more than 12 months after initial diagnosis of hormone receptor positive, invasive breast cancer. Mean age at diagnosis was 59.7 years (SD 13.4). Predictors of delayed initiation of adjuvant endocrine therapy include Black race or Hispanic ethnicity (adjusted odds ratio [aOR] of Black vs White, 1.57; 95% CI, 1.48-1.66; P < .001, Hispanic vs White, aOR 1.22, 95% CI 1.13-1.32; P < .001), Insurance other than private insurance (Medicare vs Private, aOR 1.09, 95% CI 1.01-1.17; P = .007, Medicaid vs Private, aOR 1.36, 95% CI 1.28-1.45; P < .001), higher stage of disease at diagnosis (Stage III vs II, aOR 1.24, 95% CI 1.19-1.30; P < .001), and delayed surgery or chemotherapy (Delayed surgery vs On-time lumpectomy, aOR 2.76, 95% CI 2.60-2.93; P < .001 and Delayed chemotherapy vs no chemotherapy, aOR 11.5, 95%CI 10.6-12.5). With median follow-up of 63.2 months, 67,335 (17.2%) patients died by the end of follow-up. Delayed initiation of AET resulted in no change in the hazard of death (HR, 1.00; 95% CI, 0.95-1.05; P = .97) compared to initiation within 12 months of diagnosis after adjusting for age, race and ethnicity, insurance type, urban vs rural residence, neighborhood income and education, comorbidity, cancer grade, stage, and receipt of timely or delayed surgery, chemotherapy, and/or radiation therapy. Conclusions: These results suggest that there may be no detriment to survival if initiation of adjuvant endocrine therapy occurs 12 to 24 months after initial diagnosis compared to within 12 months of diagnosis, as currently recommended.
Is hypofractionated radiation associated with improved timely completion of adjuvant radiation in breast conserving therapy? A National Cancer Database study.
Authors: Woodward Steven Gerard , George Brandon , Varshney Karan , Willis Alliric Isaac 
Published: May 2020

539 Background: Timely completion (TC) of adjuvant radiation therapy following breast conservation therapy (BCT) has been associated with improved mortality and disease-free survival (DFS). Little data exists comparing TC of hypofractionated radiation (HR) and traditional radiation (TR). Methods: We performed a retrospective review of the National Cancer Data Base (2012-2016) on patients undergoing BCT. A multivariable logistic regression model was used to compare TC of HR (within 5 weeks of initiation) and TR (within 7 weeks of initiation) with interaction terms to look at within treatment effects of patient, tumor, and facility characteristics. Results: A total of 360,834 patients who underwent BCT were identified with 65% (n=235,783) undergoing TR and 35% (n=125,051) undergoing HR. TC of HR was achieved in 93.5% of patients and 74.2% of TR patients (p<0.0001). Across categories of year of diagnosis, age, race, median income, facility type, distance to treatment, T-stage, chemotherapy use, and lymph node status it was found that rate of TC was greater in HR compared to TR. The effect on TC by these factors was different in HR patients compared to TR in all categories except median income, distance to treatment, and T-stage (table). Conclusions: The decision between use of HR or TR in BCT is an essential component in treatment of breast cancer patients. Providers may improve mortality and DFS by identifying patients who are more likely to finish HR or TR on time based on patient, facility, and tumor factors. [Table: see text]
CanAssist breast: An affordable breast cancer prognostic test validated on Asian patients.
Authors: Patil Poonam , Bakre Manjiri Manohar , Basavaraj Chetana , Malpani Sukriti , Gunda Aparna , Prakash Chandra , Somashekhar S.P. 
Published: May 2020

541 Background: Treatment decisions for early stage HR+/HER2neu- breast cancer patients in the West routinely depend on prognostic tests that predict risk of recurrence. However, such tests are rarely used in Asia due to prohibitive costs and lack of validation data on Asian patients. Chemotherapy is thus often a default treatment leading to physiological and financial toxicity. To address these, we have developed CanAssist Breast (CAB) as an affordable IHC-based prognostic test, retrospectively validated on ~1400 patients, 63% South Asians and rest Caucasians. To date CAB has been prescribed by 180+ doctors across 30 cities in India for ~600 patients in clinics, enabling personalized treatment decisions. Methods: Primary surgical FFPE blocks and clinical follow-up data were obtained from hospitals. GraphPad Prism and MedCalc were respectively used for Kaplan-Meier survival analyses and Cox logistic regression to calculate hazard ratios. Results: The median age of diagnosis in the validation cohort was 56 years, 63% patients with stage II disease and 60% node negative tumors. Distant Metastasis Free Survival (DMFS) in the low-risk category of the validation cohort was 95%, and 84% in high-risk (P < 0.0001). Similar results were obtained with the Caucasian subgroup, as also with the chemotherapy-naive subgroup (30% of the cohort), demonstrating that risk stratification by CAB is unaffected by race or chemotherapy. Next, the performance of CAB was compared with Oncotype DX (ODX). 83% patients stratified as low risk by ODX (RS 0-25) in a sub-cohort of 109 were also stratified as low-risk by CAB. To assess the impact of CAB in treatment decision making, we assessed the data of 589 patients who have undergone CAB testing so far, 288 were identified as low-risk. 93% of these CAB low-risk patients were not given chemotherapy, demonstrating the clinical impact of CAB. Conclusions: CAB is the first test of its kind to be retrospectively validated in Asia. It shows high concordance with ODX in risk stratification of patients. CAB has been in clinical practice in India and near-India markets for 2 years and is helping clinicians and patients in making affordable treatment decisions.