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Breast Neoplasms: HELP
Articles from Allegheny General Hospital
Based on 48 articles published since 2010
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These are the 48 published articles about Breast Neoplasms that originated from Allegheny General Hospital during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Editorial Ductal carcinoma in situ: a rose by any other name. 2013

Wickerham, D Lawrence / Julian, Thomas B. ·Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA (DLW, TBJ) · Allegheny Cancer Center, Allegheny General Hospital, Pittsburgh, PA (DLW, TBJ). ·J Natl Cancer Inst · Pubmed #24068770.

ABSTRACT: -- No abstract --

2 Review Landmark clinical trials influencing surgical management of non-invasive and invasive breast cancer. 2015

Julian, Thomas B / Venditti, Charis A / Duggal, Shivani. ·National Surgical Adjuvant Breast and Bowel Project Operations Center (The NSABP is now part of NRG Oncology), Pittsburgh, Pennsylvania; Allegheny Cancer Center, Allegheny General Hospital, Pittsburgh, Pennsylvania. ·Breast J · Pubmed #25521007.

ABSTRACT: The surgical management of breast cancer has changed considerably since the use of the Halstedian radical mastectomy early in the 20th century. Over the last 50 years, several landmark clinical trials from the USA and Europe have resulted in a paradigm shift in the management of breast cancer toward less radical forms of surgery with the combined use of multi-modality treatments including systemic chemotherapy, endocrine therapy, and radiotherapy. Advances in such research have established a new worldwide standard of care for breast cancer surgical management and treatment, which has become more patient centric and which places a higher emphasis on cosmesis and improved patient quality of life. In this chapter, we review the landmark clinical trials that have influenced surgical management for non-invasive and invasive breast cancer and that serve to guide current clinical practices to date.

3 Review Ductal Carcinoma In Situ of the Breast: Evaluating the Role of Radiation Therapy in the Management and Attempts to Identify Low-risk Patients. 2015

Shah, Chirag / Vicini, Frank A / Berry, Sameer / Julian, Thomas B / Wilkinson, John Ben / Shaitelman, Simona F / Khan, Atif / Finkelstein, Steven E / Goldstein, Neal. ·*Department of Radiation Oncology, Summa Health System, Akron, OH †Michigan Healthcare Professionals/21st Century Oncology, Farmington Hills, MI ‡Department of Surgery, Division of Breast Surgical Oncology, Allegheny General Hospital, Pittsburgh, PA §Department of Radiation Oncology, Willis Knighton Health System, Shreveport, LA ∥University of Texas M.D. Anderson Cancer Center, Houston, TX ¶Department of Radiation Oncology, The Cancer Institute of New Jersey, Robert Wood Johnson University Hospital, New Brunswick, NJ #21st Century Oncology Translational Research Consortium, Scottsdale, AZ **Clarient Laboratory, Aliso Viejo, CA. ·Am J Clin Oncol · Pubmed #25036472.

ABSTRACT: Ductal carcinoma in situ of the breast has rapidly increased in incidence over the past several decades secondary to an increased use of screening mammography. Local treatment options for women diagnosed with ductal carcinoma in situ include mastectomy or breast-conserving therapy. Although several randomized trials have confirmed a >50% reduction in the risk of local recurrence with the administration of radiation therapy (RT) compared with breast-conserving surgery alone, controversy persists regarding whether or not RT is needed in selected "low-risk" patients. Over the past two decades, two prospective single-arm studies and one randomized trial have been performed and confirm that the omission of RT after surgery is associated with higher rates of local recurrence even after selecting patients with optimal clinical and pathologic features. Importantly, these trials have failed to consistently and reproducibly identify a low-risk cohort of patients (based on clinical and pathologic features) that does not benefit from RT. As a result, adjuvant RT is still advocated in the majority of patients, even in low-risk cases. Future research is moving beyond traditional clinical and pathologic risk factors and instead focusing on approaches such as multigene assays and biomarkers with the hopes of identifying truly low-risk patients who may not require RT. However, recent studies confirm that even low-risk patients identified from multigene assays have higher rates of local recurrence with local excision alone than would be expected with the addition of RT.

4 Review HER2 in breast cancer: a review and update. 2014

Krishnamurti, Uma / Silverman, Jan F. ·Department of Pathology and Laboratory Medicine, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA. ·Adv Anat Pathol · Pubmed #24508693.

ABSTRACT: HER2 (human epidermal growth factor receptor 2) receptor is a membrane tyrosine kinase and when activated affects cell proliferation and survival. The HER2 oncogene is located on chromosome 17q12. HER2 amplification is the primary pathway of HER2 receptor overexpression and is a major driver of tumor development and progression in a subset of breast cancers. HER2 is amplified in about 15% to 20% of breast cancers. The overexpressed HER2 receptor is a valuable therapeutic target. The 2007 ASCO guidelines mandate that HER2 should be evaluated in every invasive breast cancer, either at the time of diagnosis or recurrence to guide therapy. Currently HER2 testing is carried out by several methods. It is crucial to standardize testing techniques to accurately assess HER2 status. The aim of this review on HER2 in breast cancer is to discuss the important aspects of HER2 biology, its significance in breast cancer, and the current standards for its detection.

5 Clinical Trial Quality of Life Following Stereotactic Body Radiotherapy 2018

Sprave, Tanja / Verma, Vivek / Förster, Robert / Schlampp, Ingmar / Bruckner, Thomas / Bostel, Tilman / El Shafie, Rami Ateayh / Nicolay, Nils Henrik / Debus, Jürgen / Rief, Harald. ·Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany tanja.sprave@med.uni-heidelberg.de. · Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany. · Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA, U.S.A. · Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany. · Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland. · Department of Medical Biometry, University Hospital of Heidelberg, Heidelberg, Germany. · Department of Radiation Oncology, University Hospital of Freiburg, Freiburg, Germany. ·Anticancer Res · Pubmed #30061276.

ABSTRACT: BACKGROUND/AIM: This was a prespecified secondary analysis of a randomized trial, which analyzed quality of life (QOL), fatigue, and emotional distress following stereotactic body radiotherapy (SBRT) versus conventional three-dimensional conformal radiotherapy (3DCRT) as part of palliative management of painful spinal metastases. MATERIALS AND METHODS: Fifty-five patients were enrolled in this single-institutional randomized exploratory phase II trial (NCT02358720). Participants were randomly assigned to receive SBRT (single-fraction 24 Gy) or 3DCRT (30 Gy/10 fractions). QOL (EORTC QLQ-BM22), fatigue (EORTC QLQ FA13), and emotional distress (QSC-R10) at the end of radiotherapy, along with 3- and 6-month follow-up were assessed. RESULTS: At all recorded time points, there were no significant QOL differences between cohorts, including painful sites, pain characteristics, functional impairment, or psychosocial aspects (p>0.05 for all). There were also no differences in all dimensions of fatigue between groups at each recorded time point (p>0.05 for all). Emotional distress was also similar at three (p=0.248) and six months (p=0.603). CONCLUSION: Although these results demonstrate that SBRT does not cause worse QOL deteriorations compared to 3DCRT, larger randomized investigations are recommended to corroborate these findings.

6 Clinical Trial Anthracyclines in Early Breast Cancer: The ABC Trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). 2017

Blum, Joanne L / Flynn, Patrick J / Yothers, Greg / Asmar, Lina / Geyer, Charles E / Jacobs, Samuel A / Robert, Nicholas J / Hopkins, Judith O / O'Shaughnessy, Joyce A / Dang, Chau T / Gómez, Henry Leonidas / Fehrenbacher, Louis / Vukelja, Svetislava J / Lyss, Alan P / Paul, Devchand / Brufsky, Adam M / Jeong, Jong-Hyeon / Colangelo, Linda H / Swain, Sandra M / Mamounas, Eleftherios P / Jones, Stephen E / Wolmark, Norman. ·Joanne L. Blum, Lina Asmar, Nicholas J. Robert, Joyce A. O'Shaughnessy, Svetislava J. Vukelja, Devchand Paul, and Stephen E. Jones, US Oncology Research · Lina Asmar, McKesson Specialty Health, The Woodlands · Joanne L. Blum and Joyce A. O'Shaughnessy, Texas Oncology-Baylor Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas · Svetislava J. Vukelja, Texas Oncology-Tyler, Tyler, TX · Patrick J. Flynn, Charles E. Geyer Jr, Samuel A. Jacobs, Judith O. Hopkins, Louis Fehrenbacher, Alan P. Lyss, Adam M. Brufsky, Sandra M. Swain, Eleftherios P. Mamounas, and Norman Wolmark, National Surgical Adjuvant Breast and Bowel Project/NRG Oncology · Greg Yothers, Jong-Hyeon Jeong, and Linda H. Colangelo, NRG Oncology · Greg Yothers, John-Hyeon Jeong, and Linda H. Colangelo, The University of Pittsburgh · Samuel A. Jacobs, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine · Adam M. Brufsky, Magee-Womens Hospital at University of Pittsburgh Medical Center · Norman Wolmark, Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh · Henry Leonidas Gómez, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network, Philadelphia, PA · Patrick J. Flynn, Metro-Minnesota Community Oncology Research Consortium, Minneapolis, MN · Charles E. Geyer Jr, Massey Cancer Center, Virginia Commonwealth University, Richmond · Nicholas J. Robert, Virginia Cancer Specialists, Fairfax, VA · Judith O. Hopkins, The Southeastern Medical Oncology Center, Goldsboro, NC · Chau T. Dang, The Alliance, Boston, MA · Chau T. Dang, Memorial Sloan Kettering Cancer Center, New York, NY · Henry Leonidas Gómez, Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru · Louis Fehrenbacher, Kaiser Permanente Oncology Clinical Trials Northern California, Vallejo, CA · Alan P. Liss, Heartland Cancer Research National Cancer Institute Community Oncology Research Program at Missouri Baptist Cancer Center, St Louis, MO · Devchand Paul, Rocky Mountain Cancer Centers, Denver, CO · Sandra M. Swain, MedStar Washington Hospital Center Washington Cancer Institute, and Georgetown University Medical Center, Washington, DC · and Eleftherios P. Mamounas, UF Cancer Center at Orlando Health, Orlando, FL. ·J Clin Oncol · Pubmed #28398846.

ABSTRACT: Purpose Docetaxel and cyclophosphamide (TC) was superior to doxorubicin and cyclophosphamide (AC) in a trial in early breast cancer. However, activity of TC relative to AC regimens with a taxane (TaxAC) is unknown. Methods In a series of three adjuvant trials, women were randomly assigned to TC for six cycles (TC6) or to a standard TaxAC regimen. US Oncology Research (USOR) 06-090 compared TC6 with docetaxel, doxorubicin, and cyclophosphamide (TAC6). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-46-I/USOR 07132 compared TC6, TAC6, or TC6 plus bevacizumab. NSABP B-49 compared TC6 with several standard AC and taxane combination regimens. Before any analysis of individual trials, a joint efficacy analysis of TC versus the TaxAC regimens was planned, with invasive disease-free survival (IDFS) as the primary end point. Patients who received TC6 plus bevacizumab on NSABP B-46-I/USOR 07132 were not included. A hazard ratio (HR) from a stratified Cox model that exceeded 1.18 for TC6 versus TaxAC was predefined as inferiority for TC6. The prespecified interim monitoring plan was to report for futility if the HR was > 1.18 when 334 IDFS events were observed (50% of 668 events required for definitive analysis). Results A total of 2,125 patients were randomly assigned to receive TC6 regimens and 2,117 patients were randomly assigned to receive TaxAC regimens. The median follow-up time was 3.3 years. There were 334 IDFS events, and the HR for TC6 versus TaxAC was 1.202 (95% CI, 0.97 to 1.49), which triggered early reporting for futility. The 4-year IDFS was 88.2% for TC6 and was 90.7% for TaxAC ( P = .04). Tests for treatment interaction by protocol, hormone receptor status, and nodal status were negative. Conclusion The TaxAC regimens improved IDFS in patients with high-risk human epidermal growth factor receptor 2-negative breast cancer compared with the TC6 regimen.

7 Clinical Trial Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5. 2017

Smith, John W / Buyse, Marc E / Rastogi, Priya / Geyer, Charles E / Jacobs, Samuel A / Patocskai, Erica J / Robidoux, André / Conlin, Alison K / Ansari, Bilal / Keogh, George P / Stella, Philip J / Gross, Howard M / Lord, Raymond S / Polikoff, Jonathan A / Mauquoi, Celine / Mamounas, Eleftherios P / Swain, Sandra M / Wolmark, Norman. ·National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Columbia River Oncology Program, Portland, OR. · International Drug Development Institute, Louvain-la-Neuve, Belgium. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Department of Medicine, Oncology, University of Pittsburgh Cancer Institute, and Magee-Womens Hospital Womens Cancer Clinic, Pittsburgh, PA. Electronic address: rastogip@upmc.edu. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Virginia Commonwealth University Massey Cancer Center, Richmond, VA. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Department of Medicine, Oncology, University of Pittsburgh Cancer Institute, and Magee-Womens Hospital Womens Cancer Clinic, Pittsburgh, PA. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Centre hospitalier de l'Université de Montreal (CHUM), Montréal, Québec, Canada. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Western Oncology Research Consortium, Portland, OR. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Community Clinical Oncology Program (CCOP) Northern Indiana Cancer Research Consortium, Mishawaka, IN. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Southeast Clinical Oncology Research Consortium, Roper St Francis Cancer Care, Charleston, SC. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Community Clinical Oncology Program (CCOP) Michigan Cancer Research Consortium Community, Ann Arbor, MI. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Community Clinical Oncology Program (CCOP) Dayton, Dayton, OH. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Community Clinical Oncology Program (CCOP) Kalamazoo, and the West Michigan Cancer Center, Kalamazoo, MI. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Kaiser Permanente, San Diego, CA. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Department of Oncology, UF Cancer Center at Orlando Health, Orlando, FL. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Washington Cancer Institute, MedStar Washington Hospital Center, Washington, DC; Georgetown University Medical Center, Washington, DC. · National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, Pittsburgh, PA; Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA. ·Clin Breast Cancer · Pubmed #27693116.

ABSTRACT: BACKGROUND: The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC). PATIENTS AND METHODS: Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m RESULTS: A total of 105 patients were accrued, 76 with LABC treated with neoadjuvant therapy and 29 with PS3BC treated with adjuvant therapy. Median follow-up was 59.2 months. Among 99 evaluable patients for cardiac safety, 4 (4%; 95% confidence interval [CI], 1.1%-10.0%) met CE criteria. The pCR percentage in LABC patients was 46% (95% CI, 34%-59%). Five-year recurrence-free survival (RFS) and overall survival (OS) for all patients was 79.9% and 90.8%, respectively. CONCLUSION: The regimen met predefined criteria for activity of interest with an acceptable rate of CEs. Although the pCR percentage was comparable with chemotherapy regimens with trastuzumab alone the high RFS and OS are of interest in these high-risk populations.

8 Clinical Trial Patient-reported outcomes with anastrozole versus tamoxifen for postmenopausal patients with ductal carcinoma in situ treated with lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. 2016

Ganz, Patricia A / Cecchini, Reena S / Julian, Thomas B / Margolese, Richard G / Costantino, Joseph P / Vallow, Laura A / Albain, Kathy S / Whitworth, Patrick W / Cianfrocca, Mary E / Brufsky, Adam M / Gross, Howard M / Soori, Gamini S / Hopkins, Judith O / Fehrenbacher, Louis / Sturtz, Keren / Wozniak, Timothy F / Seay, Thomas E / Mamounas, Eleftherios P / Wolmark, Norman. ·NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; University of California, Los Angeles, CA, USA. Electronic address: pganz@mednet.ucla.edu. · NRG Oncology, Pittsburgh, PA, USA; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Department of Surgical Oncology, Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; The Jewish General Hospital, McGill University, Montréal, QC, Canada. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Southwest Oncology Group, San Antonio, TX, USA; Department of Medicine, Loyola University Chicago Stritch School of Medicine, Chicago, IL, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Alliance for Clinical Trials in Oncology/American College of Surgeons Oncology Group, Chicago, IL, USA; Nashville Breast Center, Nashville, TN, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Southwest Oncology Group, San Antonio, TX, USA; Eastern Cooperative Oncology Group/American College of Radiology Imaging Network, Philadelphia, PA, USA; Department of Hematology/Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Department of Hematology/Oncology, Magee Womens Hospital/University of Pittsburgh, Pittsburgh, PA, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Dayton Physicians, Dayton, OH, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Missouri Valley Cancer Consortium, Omaha, NE, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Southeast Clinical Oncology Research Consortium National Cancer Institute Community Oncology Research Program, Winston Salem, NC, USA; Department of Hematology/Oncology, Forsyth Regional Cancer Center, Winston Salem, NC, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Department of Medical Oncology, Kaiser Permanente, Northern California Vallejo, CA, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Department of Medical Oncology Colorado Cancer Research Program, Denver, CO, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Community Clinical Oncology Program, Christiana Care Health Systems, Wilmington, DE, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; Atlanta Regional Community Clinical Oncology Program, Atlanta, GA, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA, USA; UF Health Cancer Center at Orlando Health, Orlando, FL, USA. ·Lancet · Pubmed #26686960.

ABSTRACT: BACKGROUND: The NSABP B-35 trial compared 5 years of treatment with anastrozole versus tamoxifen for reducing subsequent occurrence of breast cancer in postmenopausal patients with ductal carcinoma in situ. This report assesses the effect of these drugs on quality of life and symptoms. METHODS: The study was done at 333 hospitals in North America. Postmenopausal women with hormone-positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole breast irradiation were randomly assigned to receive either tamoxifen (20 mg/day) or anastrazole (1 mg/day) for 5 years, stratified by age (<60 years vs ≥60 years). Patients and investigators were masked to treatment allocation. Patients completed questionnaires at baseline and every 6 months thereafter for 6 years. The primary outcomes were SF-12 physical and mental health component scale scores, and vasomotor symptoms (as per the BCPT symptom scale). Secondary outcomes were vaginal symptoms and sexual functioning. Exploratory outcomes were musculoskeletal pain, bladder symptoms, gynaecological symptoms, cognitive symptoms, weight problems, vitality, and depression. We did the analyses by intention to treat, including patients who completed questionnaires at baseline and at least once during follow-up. This study is registered with ClinicalTrials.gov, NCT00053898. FINDINGS: Between Jan 6, 2003, and June 15, 2006, 3104 patients were enrolled in the study, of whom 1193 were included in the quality-of-life substudy: 601 assigned to tamoxifen and 592 assigned to anastrozole. We detected no significant difference between treatment groups for: physical health scores (mean severity score 46·72 for tamoxifen vs 45·85 for anastrozole; p=0·20), mental health scores (52·38 vs 51·48; p=0·38), energy and fatigue (58·34 vs 57·54; p=0·86), or symptoms of depression (6·19 vs 6·39; p=0·46) over 5 years. Vasomotor symptoms (1·33 vs 1·17; p=0·011), difficulty with bladder control (0·96 vs 0·80; p=0·0002), and gynaecological symptoms (0·29 vs 0·18; p<0·0001) were significantly more severe in the tamoxifen group than in the anastrozole group. Musculoskeletal pain (1·50 vs 1·72; p=0·0006) and vaginal symptoms (0·76 vs 0·86; p=0·035) were significantly worse in the anastrozole group than in the tamoxifen group. Sexual functioning did not differ significantly between the two treatments (43·65 vs 45·29; p=0·56). Younger age was significantly associated with more severe vasomotor symptoms (mean severity score 1·45 for age <60 years vs 0·65 for age ≥60 years; p=0·0006), vaginal symptoms (0·98 vs 0·65; p<0·0001), weight problems (1·32 vs 1·02; p<0·0001), and gynaecological symptoms (0·26 vs 0·22; p=0·014). INTERPRETATION: Given the similar efficacy of tamoxifen and anastrozole for women older than age 60 years, decisions about treatment should be informed by the risk for serious adverse health effects and the symptoms associated with each drug. For women younger than 60 years old, treatment decisions might be driven by efficacy (favouring anastrozole); however, if the side-effects of anastrozole are intolerable, then switching to tamoxifen is a good alternative. FUNDING: US National Cancer Institute, AstraZeneca Pharmaceuticals.

9 Clinical Trial Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy (NSABP B-35): a randomised, double-blind, phase 3 clinical trial. 2016

Margolese, Richard G / Cecchini, Reena S / Julian, Thomas B / Ganz, Patricia A / Costantino, Joseph P / Vallow, Laura A / Albain, Kathy S / Whitworth, Patrick W / Cianfrocca, Mary E / Brufsky, Adam M / Gross, Howard M / Soori, Gamini S / Hopkins, Judith O / Fehrenbacher, Louis / Sturtz, Keren / Wozniak, Timothy F / Seay, Thomas E / Mamounas, Eleftherios P / Wolmark, Norman. ·NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; Jewish General Hospital, McGill University, Montreal, QC, Canada. Electronic address: richard.margolese@mcgill.ca. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; Department of Surgical Oncology, Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; University of California, Los Angeles, CA, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; SWOG, San Antonio, TX, USA; Department of Medicine, Loyola University Chicago Stritch School of Medicine, Chicago, IL, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; ALLIANCE/ACOSOG, Chicago, IL, USA; Nashville Breast Center, Nashville, TN, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; SWOG, San Antonio, TX, USA; ECOG/ACRIN, Philadelphia, PA, USA; Department of Hematology/Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; Department of Hematology/Oncology, Magee Womens Hospital/University of Pittsburgh Department of Hematology/Oncology, Pittsburgh, PA, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; Dayton Physicians LLC, Dayton, OH, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; Missouri Valley Cancer Consortium, Omaha, NE, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; SCOR NCORP, Winston Salem, NC, USA; Department of Hematology/Oncology, Forsyth Regional Cancer Center, Winston Salem, NC, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; Department of Medical Oncology, Kaiser Permanente Northern California Vallejo, CA, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; Department of Medical Oncology Colorado Cancer Research Program, Denver, CO, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; CCOP, Christiana Care Health Systems, Newark, DE, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; Atlanta Regional Community Clinical Oncology Program, Atlanta, GA, USA. · NRG Oncology/National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA, USA; UF Health Cancer Center at Orlando Health, Orlando, FL, USA. ·Lancet · Pubmed #26686957.

ABSTRACT: BACKGROUND: Ductal carcinoma in situ is currently managed with excision, radiotherapy, and adjuvant hormone therapy, usually tamoxifen. We postulated that an aromatase inhibitor would be safer and more effective. We therefore undertook this trial to compare anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy. METHODS: The double-blind, randomised, phase 3 National Surgical Adjuvant Breast and Bowel Project (NSABP) B-35 trial was done in 333 participating NSABP centres in the USA and Canada. Postmenopausal women with hormone-positive ductal carcinoma in situ treated by lumpectomy with clear resection margins and whole-breast irradiation were enrolled and randomly assigned (1:1) to receive either oral tamoxifen 20 mg per day (with matching placebo in place of anastrozole) or oral anastrozole 1 mg per day (with matching placebo in place of tamoxifen) for 5 years. Randomisation was stratified by age (<60 vs ≥60 years) and patients and investigators were masked to treatment allocation. The primary outcome was breast cancer-free interval, defined as time from randomisation to any breast cancer event (local, regional, or distant recurrence, or contralateral breast cancer, invasive disease, or ductal carcinoma in situ), analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00053898, and is complete. FINDINGS: Between Jan 1, 2003, and June 15, 2006, 3104 eligible patients were enrolled and randomly assigned to the two treatment groups (1552 to tamoxifen and 1552 to anastrozole). As of Feb 28, 2015, follow-up information was available for 3083 patients for overall survival and 3077 for all other disease-free endpoints, with median follow-up of 9·0 years (IQR 8·2-10·0). In total, 212 breast cancer-free interval events occurred: 122 in the tamoxifen group and 90 in the anastrozole group (HR 0·73 [95% CI 0·56-0·96], p=0·0234). A significant time-by-treatment interaction (p=0·0410) became evident later in the study. There was also a significant interaction between treatment and age group (p=0·0379), showing that anastrozole is superior only in women younger than 60 years of age. Adverse events did not differ between the groups, except for thrombosis or embolism--a known side-effect of tamoxifen-for which there were 17 grade 4 or worse events in the tamoxifen group versus four in the anastrozole group. INTERPRETATION: Compared with tamoxifen, anastrozole treatment provided a significant improvement in breast cancer-free interval, mainly in women younger than 60 years of age. This finding means that women will benefit from having a choice of effective agents for ductal carcinoma in situ. FUNDING: US National Cancer Institute and AstraZeneca Pharmaceuticals LP.

10 Clinical Trial Symptoms and QOL as Predictors of Chemoprevention Adherence in NRG Oncology/NSABP Trial P-1. 2016

Land, Stephanie R / Walcott, Farzana L / Liu, Qing / Wickerham, D Lawrence / Costantino, Joseph P / Ganz, Patricia A. ·National Surgical Adjuvant Breast and Bowel Project (now a part of NRG Oncology), Pittsburgh, PA (SRL, DLW, PAG) · Division of Cancer Control and Population Sciences (SRL) and Division of Cancer Prevention (FLW), National Cancer Institute, Rockville, MD · NRG Oncology, Pittsburgh, PA and Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (QL, JPC) · Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA (DLW) · UCLA Schools of Medicine and Public Health, and Jonsson Comprehensive Cancer Center, Division of Cancer Prevention & Control Research, Department of Health Services, Los Angeles, CA (PAG). ·J Natl Cancer Inst · Pubmed #26615179.

ABSTRACT: BACKGROUND: Tamoxifen provides a 50% reduction in the incidence of breast cancer (BC) among high-risk women, yet many do not adhere to the five-year course of therapy. Using the prospective double-blind National Surgical Adjuvant Breast and Bowel Project P-1 study, we evaluated whether participant-reported outcomes were associated with drug adherence and whether baseline behavioral risk factors modified those associations. METHODS: P-1 participants were randomly assigned to placebo vs tamoxifen (20mg/day). Mixed effects logistic regression was used to evaluate whether baseline or three-month SF-36 quality of life (QOL) mental and physical component summaries (MCS, PCS), and participant-reported symptoms (gynecologic, vasomotor, sexual, and other) predicted 12-month drug adherence (76-100% of assigned medication). The evaluation accounted for age, treatment, estimated breast cancer risk, education, baseline smoking, alcohol consumption, and obesity. All statistical tests were two-sided. RESULTS: Participants enrolled at least three years before trial unblinding and without medically indicated discontinuation before 12 months were eligible for the present analyses (n = 10 576). At 12 months, 84.3% were adherent. Statistically significant predictors of adherence were: three-month MCS (odds ratio [OR] = 1.15 per 10 points, 95% confidence interval [CI] = 1.06 to 1.25); three-month gynecologic symptoms among moderate alcohol drinkers (OR = .79, 95% CI = 0.72 to 0.88); baseline vasomotor symptoms among participants assigned tamoxifen (OR = .88, 95% CI = 0.80 to 0.97); and three-month sexual symptoms among younger participants (OR = .89 at age 41 years, 95% CI = 0.80 to 0.99). The strongest association was with three-month other symptoms (OR = .77, 95% CI = 0.63 to 0.93). PCS was not associated with adherence. Symptom and QOL associations were not modified by smoking or obesity. CONCLUSIONS: Promoting QOL and managing symptoms early in therapy may be important strategies to improve adherence.

11 Clinical Trial Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial. 2015

Bear, Harry D / Tang, Gong / Rastogi, Priya / Geyer, Charles E / Liu, Qing / Robidoux, André / Baez-Diaz, Luis / Brufsky, Adam M / Mehta, Rita S / Fehrenbacher, Louis / Young, James A / Senecal, Francis M / Gaur, Rakesh / Margolese, Richard G / Adams, Paul T / Gross, Howard M / Costantino, Joseph P / Paik, Soonmyung / Swain, Sandra M / Mamounas, Eleftherios P / Wolmark, Norman. ·National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, VA, USA. Electronic address: hdbear@vcu.edu. · NRG Oncology and the University of Pittsburgh, Pittsburgh, PA, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Virginia Commonwealth University School of Medicine and the Massey Cancer Center, Richmond, VA, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Centre Hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Minority-Based CCOP, San Juan, Puerto Rico. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; University of Pittsburgh Cancer Institute, Magee Womens Hospital, Pittsburgh, PA, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; University of California at Irvine, Division of Hematology/Oncology, Chao Family Comprehensive Cancer Center, Orange, CA, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Kaiser Permanente Oncology Clinical Trials, Northern California, Vallejo, CA, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Colorado Cancer Research Program, Colorado Springs, CO, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Northwest Medical Specialties, Tacoma, WA, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; CCOP, Kansas City, MO, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Jewish General Hospital, McGill University, Montréal, QC, Canada. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Genesys Regional Medical Center, Grand Blanc, MI, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; CCOP, Dayton, Dayton, OH, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Washington Cancer Institute, MedStar Washington Hospital Center, Washington, DC, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; UF Health Cancer Center at Orlando Health, Orlando, FL, USA. · National Surgical Adjuvant Breast and Bowel Project (NSABP/NRG Oncology), Pittsburgh, PA, USA; Allegheny Cancer Center at Allegheny General Hospital, Pittsburgh, PA, USA. ·Lancet Oncol · Pubmed #26272770.

ABSTRACT: BACKGROUND: NSABP B-40 was a 3 × 2 factorial trial testing whether adding capecitabine or gemcitabine to docetaxel followed by doxorubicin plus cyclophosphamide neoadjuvant chemotherapy would improve outcomes in women with operable, HER2-negative breast cancer and whether adding neoadjuvant plus adjuvant bevacizumab to neoadjuvant chemotherapy regimens would also improve outcomes. As reported previously, addition of neoadjuvant bevacizumab increased the proportion of patients achieving a pathological complete response, which was the primary endpoint. We present secondary patient outcomes, including disease-free survival, a specified endpoint by protocol, and data for distant recurrence-free interval, and overall survival, which were not prespecified endpoints but were collected prospectively. METHODS: In this randomised controlled trial (NSABP B-40), we enrolled women aged 18 years or older, with operable, HER2-non-amplified invasive adenocarcinoma of the breast, 2 cm or greater in diameter by palpation, clinical stage T1c-3, cN0, cN1, or cN2a, without metastatic disease and diagnosed by core needle biopsy. Patients received one of three docetaxel-based neoadjuvant regimens for four cycles: docetaxel alone (100 mg/m(2)) with addition of capecitabine (825 mg/m(2) oral twice daily days 1-14, 75 mg/m(2) docetaxel) or with addition of gemcitabine (1000 mg/m(2) days 1 and 8 intravenously, 75 mg/m(2) docetaxel), all followed by neoadjuvant doxorubicin and cyclophosphamide (60 mg/m(2) and 600 mg/m(2) intravenously) every 3 weeks for four cycles. Those randomly assigned to bevacizumab groups were to receive bevacizumab (15 mg/kg, every 3 weeks for six cycles) with neoadjuvant chemotherapy and postoperatively for ten doses. Randomisation was done (1:1:1:1:1:1) via a biased-coin minimisation procedure to balance the characteristics with respect to clinical nodal status, clinical tumour size, hormone receptor status, and age. Intent-to-treat analyses were done for disease-free survival and overall survival. This study is registered with ClinicalTrials.gov, number NCT00408408. FINDINGS: Between Jan 5, 2007, and June 30, 2010, 1206 patients were enrolled in the study. Follow-up data were collected from Oct 31, 2007 to March 27, 2014, and were available for overall survival in 1186 patients, disease-free survival in 1184, and distant recurrence-free interval in 1181. Neither capecitabine nor gemcitabine increased disease-free survival or overall survival. Median follow-up was 4·7 years (IQR 4·0-5·2). The addition of bevacizumab significantly increased overall survival (hazard ratio 0·65 [95% CI 0·49-0·88]; p=0·004) but did not significantly increase disease-free survival (0·80 [0·63-1·01]; p=0·06). Four deaths occurred on treatment due to vascular disorder (docetaxel plus capecitabine followed by doxorubicin plus cyclophosphamide group), sudden death (docetaxel plus capecitabine followed by doxorubicin plus cyclophosphamide group), infective endocarditis (docetaxel plus bevacizumab followed by doxorubicin plus cyclophosphamide and bevacizumab group), and visceral arterial ischaemia (docetaxel followed by doxorubicin plus cyclophosphamide group). The most common grade 3-4 adverse events in the bevacizumab group were neutropenia (grade 3, 99 [17%]; grade 4, 37 [6%]), hand-foot syndrome (grade 3, 63 [11%]), and hypertension (grade 3, 60 [10%]; grade 4, two [<1%]) and in the non-bevacizumab group were neutropenia (grade 3, 98 [16%]; grade 4, 36 [6%]), fatigue (grade 3, 53 [9%]), and hand-foot syndrome (grade 3, 43 [7%]). INTERPRETATION: The addition of gemcitabine or capecitabine to neoadjuvant docetaxel plus doxorubicin plus cyclophosphamide does not seem to provide any benefit to patients with operable breast cancer, and should not change clinical practice in the short term. The improved overall survival with bevacizumab contradicts the findings of other studies of bevacizumab in breast cancer and may indicate the need for additional investigation of this agent. FUNDING: National Institutes of Health, Genentech, Roche Laboratories, Lilly Research Laboratories, and Precision Therapeutics.

12 Article Comparison of outcomes between metaplastic and triple-negative breast cancer patients. 2019

Polamraju, Praveen / Haque, Waqar / Cao, Kevin / Verma, Vivek / Schwartz, Mary / Klimberg, V Suzanne / Hatch, Sandra / Niravath, Polly / Butler, E Brian / Teh, Bin S. ·Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX, USA. · Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. Electronic address: waqarh786@gmail.com. · Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA, USA. · Department of Pathology, Houston Methodist Hospital, Houston, TX, USA. · Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA. · Department of Medical Oncology, Houston Methodist Hospital, Houston, TX, USA. · Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. ·Breast · Pubmed #31675684.

ABSTRACT: PURPOSE: Metaplastic breast cancer (MBC) is a rare, aggressive variant of breast cancer that has been associated with poor clinical outcomes, as has triple-negative breast (TNBC) cancer. Limited studies compare the clinical characteristics and prognosis of MBC to TNBC. This study uses a large, contemporary US cancer database to compare clinical characteristics and survival outcomes for patients with MBC to those with TNBC. METHODS: The National Cancer Database was queried for women with cT1-4N1-3M0 MBC or TNBC diagnosed between 2004 and 2013 and treated with definitive surgery. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier curves compared overall survival (OS), and Cox regression determined patient factors associated with OS. RESULTS: Altogether, 55,847 patients met the inclusion criteria; 50,705 (90.8%) had TNBC and 5,142 (9.2%) had MBC. Most patients had no comorbid conditions (82%), N0 disease (71%), poorly differentiated histology (77%), received chemotherapy (87%), and received radiation therapy (60%). Amongst all patients, patients with TNBC disease were observed to have greater OS than those with MBC (5-year OS 72.0% vs 55.8%, p < 0.001). The greater observed OS for patients with TNBC persisted when controlling for stage and when comparing propensity score matched cohorts. On Cox regression, lower age, T1 status, N0 status, chemotherapy, TNBC disease, and radiation therapy (RT) were associated with improved OS. CONCLUSIONS: MBC had an association with poorer OS compared to TNBC, while RT and chemotherapy receipt were associated with improved OS for patients regardless of stage. Further studies are needed to corroborate the conclusions herein.

13 Article Early assessment with magnetic resonance imaging for prediction of pathologic response to neoadjuvant chemotherapy in triple-negative breast cancer: Results from the phase III BrighTNess trial. 2019

Golshan, Mehra / Wong, Stephanie M / Loibl, Sibylle / Huober, Jens Bodo / O'Shaughnessy, Joyce / Rugo, Hope S / Wolmark, Norman / Ansell, Peter / Maag, David / Sullivan, Danielle M / Metzger-Filho, Otto / Von Minckwitz, Gunter / Geyer, Charles E / Sikov, William M / Untch, Michael. ·Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA; Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA. Electronic address: mgolshan@bwh.harvard.edu. · McGill University Health Centre, Montreal, QC, Canada. · German Breast Group, Neu-Isenburg, Germany. · University of Ulm, Ulm, Germany. · Texas Oncology-Baylor Sammons Cancer Center/U.S. Oncology, Dallas, TX, USA. · University of California San Francisco, San Francisco, CA, USA. · NSABP Foundation and Allegheny General Hospital, Pittsburgh, PA, USA. · AbbVie, North Chicago, IL, USA. · Breast Oncology Program, Dana-Farber/Brigham and Women's Cancer Center, Boston, MA, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. · NSABP Foundation and Virginia Commonwealth University Massey Cancer Center, Richmond, VA, USA. · Women and Infants Hospital of Rhode Island, Providence, RI, USA. · Helios Klinikum Berlin-Buch, Berlin, Germany. ·Eur J Surg Oncol · Pubmed #31606288.

ABSTRACT: INTRODUCTION: The ability of breast magnetic resonance imaging (MRI) to predict pathologic complete response (pCR) to neoadjuvant systemic therapy (NST) varies across biological subtypes. We sought to determine how well breast MRI findings following initial treatment on the phase III BrighTNess trial correlated with pCR in patients with triple negative breast cancer (TNBC). METHODS: Baseline and mid-treatment imaging and pathologic response data were available in 519 patients with stage II-III TNBC who underwent NST as per protocol. MRI complete response (mCR) was defined as disappearance of all target lesion(s) and MRI partial response (mPR) as a ≥50% reduction in the largest tumor diameter. RESULTS: Overall, mCR was demonstrated in 116 patients (22%), whereas 166 (32%) had mPR and 237 (46%) had stable/progressive disease (SD/PD). The positive predictive value (PPV), negative predictive value, and overall accuracy of the mid-treatment MRI for pCR were 78%, 56%, and 61%, respectively; accuracy did not differ significantly between gBRCA mutation carriers and non-carriers (52% vs. 63%, p = 0.10). When compared to patients with SD/PD, those with mPR or mCR were 3.35-fold (95% CI 2.07-5.41) more likely to have pCR at surgery. MRI response during NST was significantly associated with eligibility for breast-conserving surgery following completion of treatment (93.1% for mCR vs. 81.6% for SD/PD, p < 0.001). CONCLUSIONS: Complete response on mid-treatment MRI in the BrighTNess trial had a PPV of 78% for demonstration of pCR after completion of NST in TNBC. However, a substantial proportion of patients with mPR or SD/PD also achieved a pCR. CLINICAL TRIAL REGISTRATION: NCT02032277.

14 Article Clinical presentation, national practice patterns, and outcomes of breast adenomyoepithelioma. 2019

Haque, Waqar / Verma, Vivek / Suzanne Klimberg, Vickie / Nangia, Julie / Schwartz, Mary / Brian Butler, Edward / Teh, Bin S. ·Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. · Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA, USA. · Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA. · Department of Medical Oncology, Baylor College of Medicine, Houston, TX, USA. · Department of Pathology, Houston Methodist Hospital, Houston, TX, USA. ·Breast J · Pubmed #31578797.

ABSTRACT: Breast adenomyoepithelioma (AME) is a rare tumor with the published literature mainly in the form of case reports. Thus, there is currently only limited published data to guide evidence-based management. We sought to use a large, contemporary US database to evaluate how these patients are managed and describe expected outcomes. The National Cancer Database was queried (2004-2013) for women with AME. Statistics included multivariable logistic regression, Kaplan-Meier analysis to evaluate overall survival (OS) and Cox proportional hazards modeling. Overall, 110 patients were analyzed. At diagnosis, the median age was 67 years and the median tumor size was 2.0 cm. All but four patients had node-negative disease. A majority (55%) of tumors were estrogen receptor negative, and only one was positive for HER2/neu. The most common surgical procedure was lumpectomy (60%); a minority (10.9%) of subjects underwent complete axillary nodal dissection, with one-quarter not undergoing pathologic nodal sampling. Chemotherapy, hormonal therapy, and radiotherapy were utilized in a minority of patients (26%, 8%, and 36%, respectively), and none were associated with OS. At median follow-up of 52 months, the 5-year OS for the entire population was 74.4%. Disease-related characteristics and practice patterns are described for AME, the largest study of this rare tumor to date. Resection is the most important aspect of management, and based on this dataset the low rate of nodal involvement suggests that in some cases nodal sampling could be safely omitted. Adjuvant therapy may be considered on a case-by-case basis. Taken together, these data provide valuable insight into a rare neoplasm that may better inform management of these patients.

15 Article The ongoing evaluation and evolution of breast cancer surgical care. 2019

Ferstenberg, Marielle / Julian, Thomas B. ·Department of Surgery, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, Pennsylvania. ·Breast J · Pubmed #31493300.

ABSTRACT: Surgery has always been the backbone of breast cancer management. Throughout the past century, there have been great advances in chemotherapy regimens, especially in the neo-adjuvant setting. As a result of this progress, a patient's disease can be potentially down-staged and thus surgical intervention can therefore be de-escalated for the breast as well as the axilla. Current clinical trials are evaluating the role of imaging and core needle biopsy as predictive tools for the efficacy of neo-adjuvant chemotherapy. Results from these trials may help to clarify how the intricate relationship among imaging, pathology, radiotherapy, and surgery will affect the future management of patients undergoing neo-adjuvant chemotherapy for invasive breast cancer.

16 Article Omission of radiation therapy following breast conservation in older (≥70 years) women with T1-2N0 triple-negative breast cancer. 2019

Haque, Waqar / Verma, Vivek / Hsiao, Kuan-Yin / Hatch, Sandra / Arentz, Candy / Szeja, Sean / Schwartz, Mary / Niravath, Polly / Bonefas, Elizabeth / Miltenburg, Darlene / Brian Butler, Edward / Teh, Bin S. ·Department of Radiation Oncology, Houston Methodist Hospital, Houston, Texas, USA. · Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA. · Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. · Department of Surgery, Houston Methodist Hospital, Houston, Texas, USA. · Department of Radiation Oncology, City of Hope, Duarte, California, USA. · Department of Pathology, Houston Methodist Hospital, Houston, Texas, USA. · Department of Medical Oncology, Houston Methodist Hospital, Houston, Texas, USA. ·Breast J · Pubmed #31273872.

ABSTRACT: BACKGROUND: Although randomized data support omitting adjuvant radiotherapy (RT) following breast conservation for T1-2N0 estrogen receptor positive breast cancer in ≥70-year-old women, there remains a knowledge gap regarding its omission for triple-negative BC (TNBC). METHODS AND MATERIALS: The National Cancer Database (NCDB) was queried for ≥70-year-old females with newly diagnosed T1-2N0M0 TNBC treated with breast conservation. Multivariable logistic regression ascertained factors associated with adjuvant RT administration. Overall survival (OS) between patients treated with or without adjuvant RT was estimated using the Kaplan-Meier method. Cox proportional hazards modeling determined variables associated with OS. RESULTS: Of 8526 patients, 6283 (74%) patients received adjuvant RT, and 2243 (26%) did not. RT was more frequently withheld in older patients, those with higher comorbidities, lower income, pT2 disease, following margin-positive resection, receipt of chemotherapy, and at academic centers (P < 0.05 for all). Median follow-up was 38.0 months. Five-year OS was greater in the adjuvant RT group (77.2% vs 55.3%, P < 0.001); these differences persisted when stratifying for age, T stage, and chemotherapy utilization (P < 0.001 for all). Omission of RT was also independently associated with poorer OS on multivariate analysis (P < 0.001). CONCLUSIONS: This investigation, the largest known such study to date, observed that omission of adjuvant RT for elderly women with T1-2N0 TNBC was associated with poorer OS; this was observed across a range of age groups, as well as following stratification by T stage and chemotherapy usage. Although these results do not imply causation, caution must be exercised when considering omission of adjuvant RT in node-negative TNBC patients.

17 Article Dynamic Modulated Brachytherapy (DMBT) Balloon Applicator for Accelerated Partial Breast Irradiation. 2019

Guy, Christopher L / Oh, Seungjong / Han, Dae Yup / Kim, Siyong / Arthur, Douglas / Song, William Y. ·Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia. · Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania. · Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut. · Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia. Electronic address: william.song@vcuhealth.org. ·Int J Radiat Oncol Biol Phys · Pubmed #30910767.

ABSTRACT: PURPOSE: To propose a novel high-dose-rate brachytherapy applicator for balloon-based dynamic modulated brachytherapy (DMBT) for accelerated partial breast irradiation (APBI) and to demonstrate its dosimetric advantage compared to the widely used Contura applicator. METHODS AND MATERIALS: The DMBT balloon device consists of a fixed central channel enabling real-time, in vivo dosimetry and an outer motion-dynamic, adjustable-radius channel capable of moving to any angular position within the balloon. This design allows placement of dwell positions anywhere within the balloon volume, guaranteeing optimal placement and generation of the applicator and treatment plan, respectively. Thirteen clinical treatment plans for patients with early-stage breast cancer receiving APBI after lumpectomy using Contura were retrospectively obtained under institutional review board approval. New treatment plans were created by replacing the Contura with the DMBT device. DMBT plans were limited to 4 angular positions and an outer channel radius of 1.5 cm. The new plans were optimized to limit dose to ribs and skin while maintaining target coverage similar to that of the clinical plan. RESULTS: Similar target coverage was obtained for the DMBT plans compared with clinical Contura plans. Across all patients the mean (standard deviation) reductions in D0.1 cc to the ribs and skin were 6.70% (6.28%) and 5.13% (6.54%), respectively. A threshold separation distance between the balloon surface and the organ at risk (OAR), below which dosimetric changes of greater than 5% were obtained, was observed to be 12 mm for ribs and skin. When both OARs were far from the balloon, DMBT plans were of similar quality to Contura plans, as expected. CONCLUSIONS: This study demonstrates the superior ability of the APBI DMBT applicator to spare OARs while achieving target coverage comparable to current treatment plans, especially when in close proximity. The DMBT balloon may enable new modes of dynamic high-dose-rate treatment delivery and allow for ultrahypofractionated dose regimens to be safely used.

18 Article Postmastectomy radiation therapy for triple negative, node-negative breast cancer. 2019

Haque, Waqar / Verma, Vivek / Farach, Andrew / Brian Butler, E / Teh, Bin S. ·Department of Radiation Oncology, Houston Methodist Hospital, USA. Electronic address: waqarh786@gmail.com. · Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, USA. · Department of Radiation Oncology, Houston Methodist Hospital, USA. ·Radiother Oncol · Pubmed #30825969.

ABSTRACT: PURPOSE: The use of post-mastectomy radiation therapy (PMRT) for patients with node-negative, triple negative breast cancer (TNBC) is controversial. This study of a large, contemporary US database described national practice patterns and addressed the impact of PMRT on survival for patients with node-negative TNBC. METHODS: The National Cancer Data Base was queried (2004-2014) for women with non-metastatic TNBC with pT1-4N0M0 disease undergoing mastectomy. Use of PMRT was assessed. Multivariable logistic regression ascertained factors associated with PMRT use. The Kaplan-Meier analysis evaluated overall survival (OS) between patients managed with either PMRT or observation following mastectomy when stratifying by pT stage. Cox proportional hazards modeling determined variables associated with OS. RESULTS: A total of 14,464 patients met the selection criteria; of these, 1,569 (10.8%) received PMRT, whereas 12,895 (89.2%) did not receive PMRT. Use of PMRT varied significantly with pT stage, with only 5.7% of T1 patients undergoing PMRT, while 51.6% of patients with T3 disease underwent PMRT. Use of PMRT was associated with superior OS for patients with pT3 disease but not for patients with other T stages. Greater age was associated with decreased likelihood of PMRT use, while increased T stage and positive surgical margins were associated with use of PMRT. On multivariate analysis, increased age, T stage, and positive surgical margins were associated with worse OS. CONCLUSIONS: In the largest study to date evaluating the use of PMRT in patients with node-negative TNBC, the use of PMRT was low in patients with T1 and T2 disease. Additionally, while an OS benefit was observed with the use of PMRT in patients with T3 disease, there was no benefit with the use of PMRT in other T stage groups. Further prospective studies are recommended to further elucidate the benefit on PMRT in patients with node-negative TNBC.

19 Article Outcomes of pleomorphic lobular carcinoma versus invasive lobular carcinoma. 2019

Haque, Waqar / Arms, Ashley / Verma, Vivek / Hatch, Sandra / Brian Butler, E / Teh, Bin S. ·Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. Electronic address: waqarh786@gmail.com. · Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX, USA. · Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA, USA. · Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. · Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. Electronic address: bteh@houstonmethodist.org. ·Breast · Pubmed #30496936.

ABSTRACT: PURPOSE: Pleomorphic lobular carcinoma (PLC) is a rare histologic variant of invasive lobular carcinoma (ILC) that has been associated with worse clinical outcomes than classic ILC. Owing to its rarity, high-volume studies of its clinical characteristics and prognosis are lacking. The purpose of this study was to use a large, contemporary cancer database to investigate the clinical characteristics and survival outcomes for patients with PLC. METHODS: The National Cancer Database (NCDB) was queried for women with cT1-4N1-3M0 breast cancer with either ILC or PLC histology having received definitive surgical therapy. Chi-squared analysis was performed to determine differences between the cohorts. Kaplan-Meier analysis evaluated overall survival (OS) between all patients and between patients when stratifying by age and subtype. Cox proportional hazards modeling determined variables associated with OS. RESULTS: A total of 115,260 patients met the study criteria; of these, 114,859 (99.6%) had ILC, while 401 (0.4%) had PLC. A greater proportion of patients with PLC had T3-4 and node-positive disease, and were more likely to have ER- and HER2+ disease. PLC histology was associated with worse OS on both univariate and multivariate analysis (p < 0.001). PLC was associated with poorer OS in subgroups that were T3-4/N+ (but not T1-2N0) disease and ER+ (but not ER-) cancers, but not by HER2 status. CONCLUSIONS: Patients with PLC, who were more likely to have ER- and HER2+ disease, experienced worse OS than patients with ILC, which may be limited to patients with more advanced clinical stage and ER + disease. Further work is needed to determine the optimal treatment for this more aggressive form of breast cancer.

20 Article Inhibition of histone lysine-specific demethylase 1 elicits breast tumor immunity and enhances antitumor efficacy of immune checkpoint blockade. 2019

Qin, Ye / Vasilatos, Shauna N / Chen, Lin / Wu, Hao / Cao, Zhishen / Fu, Yumei / Huang, Min / Vlad, Anda M / Lu, Binfeng / Oesterreich, Steffi / Davidson, Nancy E / Huang, Yi. ·Women's Cancer Research Center, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. · Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA, USA. · Allegheny General Hospital Pathology, Pittsburgh, PA, USA. · Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, and University of Washington, Seattle, WA, USA. · Women's Cancer Research Center, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. yih26@pitt.edu. · Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. yih26@pitt.edu. ·Oncogene · Pubmed #30111819.

ABSTRACT: Immunotherapy strategies have been emerging as powerful weapons against cancer. Early clinical trials reveal that overall response to immunotherapy is low in breast cancer patients, suggesting that effective strategies to overcome resistance to immunotherapy are urgently needed. In this study, we investigated whether epigenetic reprograming by modulating histone methylation could enhance effector T lymphocyte trafficking and improve therapeutic efficacy of immune checkpoint blockade in breast cancer with focus on triple-negative breast cancer (TNBC) subtype. In silico analysis of The Cancer Genome Atlas (TCGA) data shows that expression of histone lysine-specific demethylase 1 (LSD1) is inversely associated with the levels of cytotoxic T cell-attracting chemokines (C-C motif chemokine ligand 5 (CCL5), C-X-C motif chemokine ligand 9 and 10 (CXCL9, CXCL10)) and programmed death-ligand 1 (PD-L1) in clinical TNBC specimens. Tiling chromatin immunoprecipitation study showed that re-expression of chemokines by LSD1 inhibition is associated with increased H3K4me2 levels at proximal promoter regions. Rescue experiments using concurrent treatment with small interfering RNA or inhibitor of chemokine receptors blocked LSD1 inhibitor-enhanced CD8+ T cell migration, indicating a critical role of key T cell chemokines in LSD1-mediated CD8+ lymphocyte trafficking to the tumor microenvironment. In mice bearing TNBC xenograft tumors, anti-PD-1 antibody alone failed to elicit obvious therapeutic effect. However, combining LSD1 inhibitors with PD-1 antibody significantly suppressed tumor growth and pulmonary metastasis, which was associated with reduced Ki-67 level and augmented CD8+ T cell infiltration in xenograft tumors. Overall, these results suggest that LSD1 inhibition may be an effective adjuvant treatment with immunotherapy as a novel management strategy for poorly immunogenic breast tumors.

21 Article Effects of Radiotherapy in Early-Stage, Low-Recurrence Risk, Hormone-Sensitive Breast Cancer. 2018

Jayasekera, Jinani / Schechter, Clyde B / Sparano, Joseph A / Jagsi, Reshma / White, Julia / Chapman, Judith-Anne W / Whelan, Timothy / Anderson, Stewart J / Fyles, Anthony W / Sauerbrei, Willi / Zellars, Richard C / Li, Yisheng / Song, Juhee / Huang, Xuelin / Julian, Thomas B / Luta, George / Berry, Donald A / Feuer, Eric J / Mandelblatt, Jeanne / Anonymous6260962. ·Department of Oncology, Georgetown University Medical Center and Cancer Prevention and Control Program, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC. · Departments of Family and Social Medicine and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY. · NRG Oncology, and the Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA. · Department of Radiation Oncology, University of Michigan, Ann Arbor, MI. · The James Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH. · Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada. · Research Department of Oncology, Division of Radiation Oncology, McMaster University, Hamilton, ON, Canada. · Radiation Medicine Program, Princess Margaret Cancer Centre, Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada. · Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY. · Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center - University of Freiburg, Freiburg, Germany. · Department of Radiation Oncology, Indiana University, Bloomington, IN. · Department of Biostatistics, Division of Quantitative Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX. · NRG Oncology, and The Division of Breast Surgical Oncology, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA. · Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC. · Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD. ·J Natl Cancer Inst · Pubmed #30239794.

ABSTRACT: Background: Radiotherapy after breast conservation has become the standard of care. Prior meta-analyses on effects of radiotherapy predated availability of gene expression profiling (GEP) to assess recurrence risk and/or did not include all relevant outcomes. This analysis used GEP information with pooled individual-level data to evaluate the impact of omitting radiotherapy on recurrence and mortality. Methods: We considered trials that evaluated or administered radiotherapy after lumpectomy in women with low-risk breast cancer. Women included had undergone lumpectomy and were treated with hormonal therapy for stage I, ER+ and/or PR+, HER2- breast cancer with Oncotype scores no greater than 18. Recurrence-free interval (RFI), type of RFI (locoregional or distant), and breast cancer-specific and overall survival were compared between no radiotherapy and radiotherapy using adjusted Cox models. All statistical tests were two-sided. Results: The final sample included 1778 women from seven trials. Omission of radiotherapy was associated with an overall adjusted hazard ratio of 2.59 (95% confidence interval [CI] = 1.38 to 4.89, P = .003) for RFI. There was a statistically significant increase in any first locoregional recurrence (P = .001), but not distant recurrence events (P = .90), or breast cancer-specific (P = .85) or overall survival (P = .61). Five-year RFI rate was high (93.5% for no radiotherapy vs 97.9% for radiotherapy; absolute reduction = 4.4%, 95% CI = 0.7% to 8.1%, P = .03). The effects of radiotherapy varied across subgroups, with lower RFI rates for those with Oncotype scores of less than 11 (vs 11-18), older (vs younger), and ER+/PR+ status (vs other). Conclusions: Omission of radiotherapy in hormone-sensitive patients with low recurrence risk may lead to a modest increase in locoregional recurrence event rates, but does not appear to increase the rate of distant recurrence or death.

22 Article A Prospective Study of L-Dex Values in Breast Cancer Patients Pretreatment and Through 12 Months Postoperatively. 2018

Ridner, Sheila H / Dietrich, Mary S / Spotanski, Kandace / Doersam, Jennifer K / Cowher, Michael S / Taback, Bret / McLaughlin, Sarah / Ajkay, Nicolas / Boyages, John / Koelmeyer, Louise / DeSnyder, Sarah / Shah, Chirag / Vicini, Frank. ·1 School of Nursing, Vanderbilt University , Nashville, Tennessee. · 2 Department of Biostatistics, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, Tennessee. · 3 Department of Surgery, Allegheny General Hospital , Pittsburgh, Pennsylvania. · 4 Division of Breast Surgery, Department of Surgery, Columbia University Medical Center , New York, New York. · 5 Section of Surgical Oncology, Mayo Clinic , Jacksonville, Florida. · 6 Department of Surgical Oncology, University of Louisville , Louisville, Kentucky. · 7 Faculty of Medicine and Health Sciences, Macquarie University , New South Wales, Australia . · 8 Division of Surgery, Department of Breast Surgical Oncology, MD Anderson Cancer Center , Houston, Texas. · 9 Department of Radiation Oncology, Taussig Cancer Institute , Cleveland Clinic, Cleveland, Ohio. · 10 Michigan Healthcare Professionals, 21st Century Oncology , Farmington Hills, Michigan. ·Lymphat Res Biol · Pubmed #30130147.

ABSTRACT: BACKGROUND: Data regarding pretreatment, bioimpedance spectroscopy (BIS) L-Dex METHODS AND RESULTS: Patients were enrolled in a parent, clinical trial that compares the effectiveness of BIS for early detection of breast cancer-related lymphedema to tape measurement. A total of 280 women with a pretreatment and at least one postoperative L-Dex measurement (within 12 months of surgery) were included. Pretreatment L-Dex readings were compared with population norms and maximum L-Dex changes within 12 months were examined. An L-Dex U400 device was used to obtain BIS measurements. The documented normative mean value using this device is 0.00, which is at the 49th percentile for this sample. Approximately 6% of patients had a pretreatment L-Dex value of ≥7.0; 1.8% had an L-Dex value ≥10.0. For 12 months, 17.1% (n = 48) of patients had a maximum change in L-Dex value from pretreatment of ≥7.0 L-Dex units, suggestive of clinical lymphedema. CONCLUSIONS: At the time of breast cancer diagnosis, L-Dex values are similar to normative values. Identified maximum changes in L-Dex values 12 months postoperatively suggest that frequent L-Dex measurements during that time frame are of potential clinical benefit. Our findings are consistent with research supporting an L-Dex value of ≥7 as indicative of clinical lymphedema with subclinical lymphedema logically occurring at somewhat lower likely, near ≥6.5.

23 Article Omission of chemotherapy for low-grade, luminal A N1 breast cancer: Patterns of care and clinical outcomes. 2018

Haque, Waqar / Verma, Vivek / Hatch, Sandra / Klimberg, V Suzanne / Butler, E Brian / Teh, Bin S. ·Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. Electronic address: waqarh786@gmail.com. · Department of Radiation Oncology, Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA, USA. · Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX, USA. · Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA. · Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. ·Breast · Pubmed #30007270.

ABSTRACT: PURPOSE: Multiple ongoing randomized studies are assessing the impact of omission of chemotherapy (CT) in low-risk node-positive Luminal A breast. The goal of this investigation was to evaluate trends and practice patterns of adjuvant CT use in Luminal A pT1-3N1 breast cancer, along with determining the clinical benefit from adjuvant CT in this patient population. METHODS: The National Cancer Data Base was queried (2004-2014) for women with pT1-3N1 luminal A invasive ductal carcinoma receiving adjuvant hormonal therapy (HT). Multivariable logistic regression ascertained factors associated with adjuvant CT administration. Kaplan-Meier analysis evaluated overall survival (OS) between patients treated with CT/HT vs. HT alone, while sub-stratifying patients by age. RESULTS: Of 8548 total patients, 5182 (61%) received CT/HT, while 3366 (39%) received HT alone. A steady rise in omission of adjuvant CT was observed, from 14% (2004-2005) to 41% (2012-2014). A decision not to use CT was more likely in more recent time periods, in older patients, at academic centers, following lumpectomy, and with lower T classification (p < 0.05 for all). CT was associated with higher OS in all patients (p < 0.001) and women ≤50 years old (p = 0.030), but not for ages 51-60 (p = 0.116), 61-70 (p = 0.222), or >70 (p = 0.239). CONCLUSIONS: Using CT for Luminal A N1 breast cancer is decreasing over time, primarily in older patients and at academic centers. Although CT is still associated with an OS advantage in all patients, subgroup analysis demonstrated no OS benefit in women >50 years of age. These results have implications on the ongoing randomized trials.

24 Article Simulation Modeling of Cancer Clinical Trials: Application to Omitting Radiotherapy in Low-risk Breast Cancer. 2018

Jayasekera, Jinani / Li, Yisheng / Schechter, Clyde B / Jagsi, Reshma / Song, Juhee / White, Julia / Luta, George / Chapman, Judith-Anne W / Feuer, Eric J / Zellars, Richard C / Stout, Natasha / Julian, Thomas B / Whelan, Timothy / Huang, Xuelin / Shelley Hwang, E / Hopkins, Judith O / Sparano, Joseph A / Anderson, Stewart J / Fyles, Anthony W / Gray, Robert / Sauerbrei, Willi / Mandelblatt, Jeanne / Berry, Donald A / Anonymous4010945. ·Department of Oncology, Georgetown University Medical Center and Cancer Prevention and Control Program, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC. · Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX. · Departments of Family and Social Medicine and Epidemiology and Population Health and Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY. · Department of Radiation Oncology, University of Michigan, Ann Arbor, MI. · Department of Radiation Oncology, The James, The Ohio State University Comprehensive Cancer Center, Columbus, OH. · Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown University Medical Center, Washington, DC. · Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada. · Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD. · Department of Radiation Oncology, Indiana University, Indianapolis, IN. · Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA. · NRG Oncology, and the Division of Breast Surgical Oncology, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA. · McMaster University and Hamilton Heath Sciences, Hamilton, ON, Canada. · Department of Surgery, Duke Cancer Institute, Duke University Medical School, Chapel Hill, NC. · Novant Health Oncology Specialists, Winston-Salem, NC. · NRG Oncology, and the Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA. · Cancer Clinical Research Unit, University of Toronto Princess Margaret Cancer Centre, Toronto, ON, Canada. · Department of Biostatistics at Harvard University and Department of Biostatistics and Computational Biology at the Dana-Farber Cancer Institute, Boston, MA. · Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany. ·J Natl Cancer Inst · Pubmed #29718314.

ABSTRACT: Background: We used two models to simulate a proposed noninferiority trial of radiotherapy (RT) omission in low-risk invasive breast cancer to illustrate how modeling could be used to predict the trial's outcomes, inform trial design, and contribute to practice debates. Methods: The proposed trial was a prospective randomized trial of no-RT vs RT in women age 40 to 74 years undergoing lumpectomy and endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, stage I breast cancer with an Oncotype DX score of 18 or lower. The primary endpoint was recurrence-free interval (RFI), including locoregional recurrence, distant recurrence, and breast cancer death. Noninferiority required the two-sided 90% confidence interval of the RFI hazard ratio (HR) for no-RT vs RT to be entirely below 1.7. Model inputs included published data. The trial was simulated 1000 times, and results were summarized as percent concluding noninferiority and mean (standard deviation) of hazard ratios for Model GE and Model M, respectively. Results: Noninferiority was demonstrated in 18.0% and 3.7% for the two models. The respective means (SD) of the RFI hazard ratios were 1.8 (0.7) and 2.4 (0.9); most were locoregional recurrences. The mean five-year RFI rates for no-RT vs RT (SD) were 92.7% (2.9%) vs 95.5% (2.2%) and 88.4% (2.0%) vs 94.5% (1.6%). Both models showed little or no difference in breast cancer-specific or overall survival. Alternative definitions of low risk based on combinations of age and grade produced similar results. Conclusions: The proposed trial was unlikely to show noninferiority of omitting radiotherapy even using alternative definitions of low-risk, as the endpoint included local recurrence. Future trials regarding radiotherapy should address absolute reduction in recurrence and impact of type of recurrence on the patient.

25 Article Response rates and pathologic complete response by breast cancer molecular subtype following neoadjuvant chemotherapy. 2018

Haque, Waqar / Verma, Vivek / Hatch, Sandra / Suzanne Klimberg, V / Brian Butler, E / Teh, Bin S. ·Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. waqarh786@gmail.com. · Department of Radiation Oncology, Houston Methodist Hospital, Cancer Center, and Research Institute, Weil Cornell Medical College, Houston, TX, 77030, USA. waqarh786@gmail.com. · Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA, USA. · Department of Radiation Oncology, University of Texas Medical Branch, Galveston, TX, USA. · Department of Surgery, University of Texas Medical Branch, Galveston, TX, USA. · Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA. ·Breast Cancer Res Treat · Pubmed #29693228.

ABSTRACT: PURPOSE: This is the largest study to date evaluating response rates and pathologic complete response (pCR) and predictors thereof, based on molecular subtype, in women with breast cancer having undergone neoadjuvant chemotherapy (NC). METHODS: The National Cancer Database was queried for women with cT1-4N1-3M0 breast cancer having received NC. Patients were divided into four subtypes: luminal A, luminal B, Her2, or triple negative (TN). Multivariable logistic regression ascertained factors associated with developing pCR. Kaplan-Meier analysis evaluated overall survival (OS) between patients by degree of response to NC when stratifying patients by subtype. RESULTS: Of a total of 13,939 women, 322 (2%) were luminal A, 5941 (43%) luminal B, 2274 (16%) Her2, and 5402 (39%) TN. Overall, 19% of all patients achieved pCR, the lowest in luminal A (0.3%) and the highest in Her2 (38.7%). Molecular subtype was an independent predictor of both pCR and OS in this population. Clinical downstaging was associated with improved survival, mostly in women with luminal B, Her2, and TN subtypes. Subgroup analysis of the pCR population demonstrated 5-year OS in the luminal B, Her2, and TN cohorts of 93.0, 94.2, and 90.6%, respectively (Her2 vs. TN, p = 0.016). CONCLUSIONS: Assessing nearly 14,000 women from a contemporary United States database, this is the largest known study examining the relationship between response to NC and molecular subtype. Women with luminal A disease are the least likely to undergo pCR, with the highest rates in Her2 disease. Degree of response is associated with OS, especially in luminal B, Her2, and TN patients. Despite the comparatively higher likelihood of achieving pCR in TN cases, this subgroup may still experience a survival detriment, which has implications for an ongoing national randomized trial.

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