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Purpose: Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT)., Methods and Materials: The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change)., Results: Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale., Conclusions: For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The optimal adjuvant therapy (antiestrogen therapy [ET] + radiation therapy or ET alone, or in some reports radiation therapy alone) in older women with early-stage breast cancer has been highly debated. However, granular details on the role of insurance in the out-of-pocket cost for patients receiving ET with or without radiation therapy are lacking. This project disaggregates out-of-pocket costs by insurance plans to increase treatment cost transparency., Methods and Materials: Several radiation therapy schedules are accepted standards as per the National Comprehensive Cancer Network guidelines. For our financial estimate model, we used the 5-fraction and 15-fraction radiation therapy and ET prescribed over a 5-year duration. The total aggregate out-of-pocket costs were determined from the sum of treatment costs, deductibles, and copays/coinsurance based on Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D Rx plans. The model assumes a Medicare- and/or Medicaid-eligible patient ≥70 years of age with node-negative, early-stage estrogen-receptor-positive breast cancer. Patient out-of-pocket costs were estimated from publicly available insurance data from plan-specific benefit coverage materials using a 5-year time horizon., Results: Original Medicare beneficiaries face a total out-of-pocket treatment charge of $2738.52 for ET alone, $2221.26 for 5-fraction radiation therapy alone, $2573.92 for 15-fraction radiation therapy alone, $3361.26 for combined ET+ 5-fraction radiation therapy, and $3713.92 for combined ET + 15-fraction radiation therapy. Medigap Plan G beneficiaries have an out-of-pocket charge of $1130.00 with radiation therapy alone and face an out-of-pocket of $2270.00 for ET alone and combined ET+ radiation therapy. For Medicaid beneficiaries, all treatments approved by Medicaid are covered without limit, resulting in no out-of-pocket expense for either adjuvant treatment option., Conclusions: This model (based on actual cost estimates per insurance plan rather than claims data), by estimating expenses within Medicare and Medicaid plans, provides a level of transparency to patient cost. With knowledge of the costs borne by patients themselves, treatment decisions informed by patients' individual priorities and preferences may be further enhanced., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The efficacy and long-term safety of hypofractionated whole breast irradiation (HF-WBI) have been established through multiple randomized trials, yet data about acute toxicities remain more limited. Since 2013, our group has prospectively collected acute toxicity data from weekly treatment evaluations and additional assessment after completion. In 2016, we intentionally shifted the posttreatment assessment follow-up visit from 1 month to 2 weeks to evaluate for missed acute toxicity occurring in that immediate posttreatment window. Here, we report whether 2-week follow-up has resulted in increased detection of acute toxicities compared with 4-week follow-up., Methods and Materials: We prospectively compared acute toxicity for patients treated with HF-WBI between January 1, 2013, and August 31, 2015 (4 week follow-up cohort) to patients treated between January 1, 2016, and August 31, 2018 (2 week follow-up cohort). Analyses included a multivariable model that adjusted for other factors known to correlate with toxicity. We prospectively defined acute toxicity as maximum breast pain (moderate or severe rating) and/or occurrence of moist desquamation reported 7 days before the completion of radiation therapy (RT) until 42 days after completion., Results: A total of 2689 patients who received postlumpectomy radiation and boost were analyzed; 1862 patients in the 2-week follow-up cohort and 827 in the 4-week follow-up cohort. All acute toxicity measures assessed were statistically similar between follow-up cohorts when compared in an unadjusted fashion. Overall acute composite toxicity was 26.4% and 27.7% for patients in the 4-week follow-up and 2-week follow-up cohorts, respectively. Overall acute composite toxicity remained similar between follow-up cohorts in a multivariable, adjusted model and was significantly related to patient's age, body mass index, smoking status, and treatment technique (intensity-modulated RT vs 3-dimensional conformal radiation therapy) but not follow-up cohort., Conclusions: An earlier posttreatment follow-up for HF-WBI patients did not reveal a significant increased incidence of acute toxicities at 2 weeks compared with 4 weeks. This study provides physicians and patients with additional data on the safety and tolerability of HF-WBI for early stage breast cancer., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Our purpose was to assess whether an association exists between surgical localization technique and lumpectomy cavity size on radiation therapy planning computed tomography (CT) scan., Methods and Materials: A single-institution retrospective review was conducted of women undergoing breast conserving surgery with wire or magnetic seed guided lumpectomy followed by adjuvant radiation therapy from 2018 to 2021. Patients of a surgeon only performing 1 localization technique or undergoing bracketed localization were excluded. The primary outcome was lumpectomy cavity size on simulation CT. Confounding due to imbalance in patient and tumor factors was addressed with overlap weights derived from a propensity score analysis and used in a weighted multivariable analysis. Secondary outcomes included positive margins, total pathologic volume, boost delivery, and boost modality., Results: Of 617 women who received lumpectomy during the study period, 387 were included in final analysis. Tumors of patients undergoing seed localization were more likely unifocal, assessable by ultrasound, and smaller. Seed use rates ranged from 27.7% to 70.7% per surgeon. There was no difference in positive margins (6.4 vs 5.4%, P = .79) or second surgeries (9.4 vs 8.1%, P = .79) between groups. Close margin rates were similar for ductal carcinoma in situ (P = .35) and invasive carcinoma (P = .97). In unadjusted bivariable analyses, wire localization was associated with larger total pathology volume (P = .004), but localization technique showed no association with CT cavity volume (P = .15). After adjusting for potentially confounding variables, multivariable analysis failed to show an association between localization technique and either CT cavity (P = .35) or total path volume (P = .08). There was no difference in indicated-boost delivery (P = .15) or electron boost (P = .14) by localization technique., Conclusions: There was no significant difference in CT cavity size by localization technique, suggesting choice between surgical techniques does not impede radiation therapy boost delivery., Competing Interests: Disclosures Michael Dykstra, Jessica Thompson, Jessica Aldous, Shannon Jiang, Tasha Hughes, James Hayman, Aleksandar Dragovic, Jennifer Shah, Alfred Chang, Michael Sabel, and Lesly Dossett have no disclosures. Corey Speers receives consulting fees from Exact Sciences and has received honoraria for presentations unrelated to the current work. He is also on the DSMB for a head and neck radiosensitizer and is on the ASCO Cancer Communications Committee. Matthew Schipper receives consulting fees from Innovative Analytics. Reshma Jagsi has stock options as compensation for her advisory board role in Equity Quotient, a company that evaluates culture in health care companies; she has received personal fees from the Greenwall Foundation, Doris Duke Charitable Foundation, and the National Institutes of Health and grants or contracts for unrelated work from the National Institutes of Health, the Doris Duke Charitable Foundation, the American Cancer Society, the Greenwall Foundation, the Susan G. Komen Foundation, and Genentech. She has served as an expert witness for Kleinbard, LLC., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of interests CEC reports grants from Breast Cancer Now, Cancer Research UK (CRUK), Addenbrooke's Charitable Trust, and the National Institute for Health and Care Research (NIHR); participation in the Independent Data Monitoring Committees for the UK PivotalBoost trial (chair), the PROTIS phase III sinonasal proton versus IMRT trial (member), the TORPEdO Proton Beam Therapy trial (member); and a leadership role for the Lancet Breast Cancer Commission (chair). CHB reports grants and research support from AbbVie, Nektar Therapeutics, Pfizer, Polyphor, Amgen, Daiichi Sankyo, Sanofi, Exelixis, Regeneron, Novartis, Henlius, Shanghai Henlius Biotech, GSK, Janssen, OBI Pharma, Eli Lilly, Seagen, Checkpoint Therapeutics, Roche, Bristol Myers Squibb, MSD, Merck Serono, AstraZeneca, Novocure, Aveo Oncology, Takeda Pharmaceuticals, TRIO Pharmaceuticals, PharmaMar, Celgene, Myovant, PPD, Syneos Health, DOCS, Labcorp, ICON, IQVIA, Parexel, Nuvisan, PSI, and Medpace; ownership or stocks in Tummi and MEDSir; and participation in advisory boards and consulting activities for Boehringer Ingelheim, GSK, Novartis, Pfizer, Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Eli Lilly, Sanofi, and Daiichi Sankyo. DAC reports research grants and support from Exact Sciences and Novartis; consulting fees from Eli Lilly, Novartis, Seagen, Daiichi Sankyo, Erytech Pharma, Carnall Farrar, Sapience, and Sanofi; payment or honoraria for lectures and presentations from Exact Sciences, Gilead, Eli Lilly, and Pfizer; participation on data safety monitoring or advisory boards for Novartis, AstraZeneca, and Grail; unremunerated leadership roles for Make Seconds Count (chair of charity trustees) and the Breast International Group (chair of board of not-for-profit research organisation); and receipt of funding for analysis and medical writing for Eli Lilly and Novartis. FC reports payment or honoraria for lectures and presentations and support for attending meetings and travel from Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, Gilead, GSK, IQVIA, Macrogenics, Medscape, MSD, Merus, Mylan, Mundipharma, Novartis, Pfizer, Pierre Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva Pharmaceuticals, and Touch Independent Medical Education; institutional financial support for clinical trials from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eisai, Fresenius, Genentech, Gilead, GSK, Ipsen, Incyte, Nektar Therapeutics, Nerviano, Novartis, Macrogenics, MediGene, MedImmune, MSD, Millenium, Pfizer, Pierre Fabre, Roche, Sanofi, Sonus, Tesaro, Tigris, Wilex, and Wyeth; a leadership role for the ABC Global Alliance and ABC Consensus Conference and Guidelines (president); and membership of ESMO, ESO, EORTC-BCG, IBCSG, SOLTI, ASCO, AACR, EACR, SIS, and ASPIC. WC reports honoraria from AstraZeneca, Pfizer, MSD, and Eisai. PAF reports a former role in the scientific advisory committee of Breast Cancer Trials Australia and New Zealand cooperative group (chair). RJ reports support from the Susan G Komen Foundation; grants from the National Institutes of Health (NIH), the Doris Duke Charitable Foundation, the Greenwall Foundation, and the American Cancer Society; serving as an expert witness for Kleinbard and Hawks Quindel Law; roles in the Board of Directors of ASCO (former member), ASTRO's Ethics Committee (chair), and the Women in Radiation Oncology Affinity Group (chair); membership on the Medical Advisory Board for Blue Cross Blue Shield Association; stock options for their advisory board role in Equity Quotient; and personal fees from the NIH, Doris Duke Charitable Foundation, and the Greenwall Foundation. FMK reports research grants from the ABC Global Alliance, Breast Cancer Now, Merck Serono WHO, MSD, Avon Cosmetics, the US Cancer Pain Relief Committee, and the Medical Research Council; consulting fees from Merck Serono and Instituto Tecnológico y de Estudios Superiores de Monterrey Mexico; and leadership roles for the Board of Directors of Women in Global Health (unpaid member), Tómatelo a Pecho (unpaid president and founder), the Mexican Health Foundation (unpaid Senior Economist), and the Board of Directors of the International Association for Hospice and Palliative Care (unpaid member). SAMcI reports grant funding from the NIHR, CRUK, and Breast Cancer Now; honoraria from Roche, MSD, AstraZeneca, Becton, Dickinson and Company; travel and conference support from Roche, Eli Lilly, and MSD; membership of advisory boards for Eli Lilly, MSD, Roche, and Novartis; and roles for the UK National Cancer Research Institute Breast Research Group (unpaid chair) and the Royal College of Surgeons Breast Surgical Specialty Lead (unpaid). K-AP reports clinical trial funding from AstraZeneca (paid to institution) and unremunerated previous participation in AstraZeneca advisory boards. LR reports grants from the European Commission Horizon 2020 and the German Research Foundation and a role in the International Association for Hospice and Palliative Care (Chair of Board of Directors). MKT reports grants from Addenbrooke's Charitable Trust and CRUK. FA reports grants from Novartis, Pfizer, AstraZeneca, Eli Lilly, Daiichi Sankyo, and Roche and consulting fees from MedImmune, Gilead, Relay Therapeutics, and Guardant Health. JEA reports speaker honoraria from AstraZeneca, Pfizer, Novartis, and Eisai and conference travel support from AstraZeneca. ISB reports participation in the Roche advisory board for ESMO. JMB reports research grants from Breast Cancer Now, AstraZeneca, MSD, Puma Biotechnology, Clovis Oncology, Pfizer, Janssen-Cilag, Novartis, Eli Lilly, Roche, CRUK, and the NIHR. MAF is funded by a Conquer Cancer Breast Cancer Research Foundation Career Development Award for Diversity and Inclusion supported by the Breast Cancer Research Foundation and reports financial support from the WeShare project. AF reports consultancy work for Oxford Immune Algorithmics; grants from Addenbrooke's Charitable Trust and the Ann McLaren Building Preclinical Imaging Suite of the University of Cambridge; and travel support from the University of Cambridge. DIR reports support from the University of Chicago Center for Global Health. DN reports research support from Cepheid; a grant from the US National Cancer Institute; and an unpaid leadership role with the WHO Global Breast Cancer Initiative. WER reports grants from the Cambia Health Foundation, the Robert Wood Johnson Foundation, and the Rita and Alex Hillman Foundation; and book royalties from Springer Publishing and Jones & Bartlett Learning. JR reports funding from the NIHR and support from AstraZeneca for attendance at a teaching event. DS reports a leadership role at the Jamaica Cancer Care and Research Institute (co-director). HS reports membership of the Breast Cancer Now Tissue Bank Advisory Board and voluntary patient membership of the Independent Cancer Patients' Voice charity; an honorarium from the CRUK Precision Grand Challenge; and support for travel expenses from Breast Cancer Now, CRUK, the Association of Breast Surgeons UK, and Breast International Group. IV-L reports grants from Resilience; consulting fees from Novartis, AstraZeneca, and Amgen; payment or honoraria for lectures and presentations from Novartis, Sandoz, Amgen, AstraZeneca, and Pfizer; and support for travel and attending meetings from Novartis. CV-G reports grants from AstraZeneca and Roche; consulting fees from Roche, Novartis, Pfizer, and Eli Lilly; honoraria from Roche, Myriad Genetics, and Novartis; and support for attending meetings and travel from Roche, MSD Oncology, and Pfizer. All other authors declare no competing interests.

Purpose: Breast and skin changes are underrecognized side effects of radiation therapy for breast cancer, which may have long-term implications for quality of life (QOL). Racial and ethnic disparities in breast cancer outcomes, including long-term QOL differences after breast radiation therapy, are poorly understood., Methods and Materials: We conducted a cross-sectional survey study of patients from the Texas Cancer Registry who received diagnoses of stage 0-II breast cancer from 2009 to 2014 and treated with lumpectomy and radiation therapy; 2770 patients were sampled and 631 responded (23%). The BREAST-Q Adverse Effects of Radiation overall score and subindices measured the effect of radiation therapy on breast tissue. Multivariable logistic regression evaluated associations of demographic and treatment characteristics with outcomes., Results: The median age was 57 years (IQR, 48-65), median time from diagnosis to survey response 9 years (IQR, 7-10), and the cohort included 62 Asian American or Pacific Islander (9.8%), 11 American Indian or Alaskan Native (AIAN) (1.7%), 161 Black (25.5%), 144 Hispanic (22.8%), and 253 White (40.1%) patients. Mean BREAST-Q Adverse Effects of Radiation score was worse for AIAN patients (-22.2; 95% CI, -39.9 to -4.6; P = .01), Black patients (-10.8; 95% CI, -16.1 to -5.5; P < .001), and Hispanic patients (-7.8; 95% CI, -13.0 to -2.5; P = .004) compared with White patients, age <50 compared with ≥65 (effect size -8.6; 95% CI, -14.0 to -3.2; P = .002), less than a college education (-5.8; 95% CI, -10.0 to -1.6; P = .01), bra cup size of D/E versus A/B (-5.3; 95% CI, -9.9 to -0.65; P = .03), and current smokers (-11.3; 95% CI, -18.3 to -4.2; P = .002). AIAN, Black, and Hispanic patients reported worse changes in skin pigmentation, telangiectasias, dryness, soreness, and/or irritation compared with White patients., Conclusions: AIAN, Black, and Hispanic patients reported substantially worse long-term breast and skin QOL outcomes after radiation therapy. Additional work is needed to understand these differences and how to alleviate them., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Multiple studies have shown a low risk of ipsilateral breast events (IBEs) or other recurrences for selected patients age 65-70 years or older with stage I breast cancers treated with breast-conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy. We sought to evaluate whether younger postmenopausal patients could also be successfully treated without radiation therapy, adding a genomic assay to classic selection factors., Methods: Postmenopausal patients age 50-69 years with pT1N0 unifocal invasive breast cancer with margins ≥2 mm after BCS whose tumors were estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-negative with Oncotype DX 21-gene recurrence score ≤18 were prospectively enrolled in a single-arm trial of radiotherapy omission if they consented to take at least 5 years of ET. The primary end point was the rate of locoregional recurrence 5 years after BCS., Results: Between June 2015 and October 2018, 200 eligible patients were enrolled. Among the 186 patients with clinical follow-up of at least 56 months, overall and breast cancer-specific survival rates at 5 years were both 100%. The 5-year freedom from any recurrence was 99% (95% CI, 96 to 100). Crude rates of IBEs for the entire follow-up period for patients age 50-59 years and age 60-69 years were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall recurrence were 5.0% (3/60) and 3.6% (5/140), respectively., Conclusion: This trial achieved a very low risk of recurrence using a genomic assay in combination with classic clinical and biologic features for treatment selection, including postmenopausal patients younger than 60 years. Long-term follow-up of this trial and others will help determine whether the option of avoiding initial radiotherapy can be offered to a broader group of women than current guidelines recommend.

Purpose: Up to 50% of women treated for localized breast cancer will experience some degree of arm or shoulder morbidity. Although radiation is thought to contribute to this morbidity, the mechanism remains unclear. Prior studies have shown biologic and radiographic changes in the pectoralis muscles after radiation. This study thus aimed to investigate the relationship between radiation to the pectoralis muscles and referrals for rehabilitation services posttreatment for arm and shoulder morbidity., Methods and Materials: A retrospective 1:1 matched case-control study was conducted for patients with breast cancer who were and were not referred for breast or shoulder rehabilitation services between 2014 and 2019 at a single academic institution. Patients were included if they had a lumpectomy and adjuvant radiation. Patients who underwent an axillary lymph node dissection were excluded. Cohorts were matched based on age, axillary surgery, and use of radiation boost. Muscle doses were converted to equivalent dose in 2 Gy fractions assuming an α:β ratio of 2.5 and were compared between the 2 groups., Results: In our cohort of 50 patients of a median age 60 years (interquartile range, 53-68 years), 36 patients (72%) underwent a sentinel lymph node biopsy in addition to a lumpectomy. Although pectoralis muscle doses were generally higher in those receiving rehabilitation services, this was not statistically significant. Pectoralis major V20-40 Gy reached borderline significance, as did pectoralis major mean dose (17.69 vs 20.89 Gy; P = .06)., Conclusions: In this limited cohort of patients, we could not definitively conclude a relationship between pectoralis muscle doses and use of rehabilitation services. Given the borderline significant findings, this should be further investigated in a larger cohort., Competing Interests: Disclosures None., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: For early stage breast cancer (BC), the choice of radiation therapy duration (1 vs 3 weeks) is highly debated. Cost and financial toxicity are major concerns that patients with BC face. Nonetheless, there remain limited discussions providing granular details of the role of insurance in the aggregate cost of 1 week versus 3 weeks of radiation therapy for patients. This project aims to disaggregate costs by plan to increase transparency of out-of-pocket (OOP) cost estimates in radiation therapy., Methods and Materials: Treatment procedures were determined through the National Comprehensive Cancer Network guidelines. OOP treatment costs, deductibles, and copays/coinsurance were calculated by using Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D prescription plans. The medicare.gov, medicaid.oh.gov, aarpmedicareplans.com, and the physician fee schedule from cms.gov were used to determine costs by treatment. Price estimates reflect actual costs per insurance plan rather than costs estimated from claims data. All procedures were considered to be performed in an Ohio hospital setting. One-week radiation therapy was defined as 5 fractions without boost, and 3-week radiation therapy was defined as 15 fractions without boost., Results: Medicare beneficiaries with Original Medicare coverage face an OOP treatment charge of $649.24 for 1 week of radiation therapy and $1006.20 for 3 weeks of radiation therapy. Assuming the deductible is met postlumpectomy, Medigap Plan G beneficiaries are faced with no additional charges for both lengths of radiation therapy. Similarly for Medicaid beneficiaries (assuming treatment is approved by Medicaid), all expenses are covered without limit, resulting in no OOP expense., Conclusions: Considerations of 1 and 3 weeks of radiation therapy for postlumpectomy early-stage BC are often dependent on cancer characteristics and patient preferences. This model (based on actual cost estimates per insurance plan rather than claims data) compares OOP costs across Medicaid and Medicare plans, which more holistically informs providers and patients in radiation therapy duration decision making., Competing Interests: Disclosures Reshma Jagsi has stock options as compensation for her advisory board role in Equity Quotient, a company that evaluates culture in health care companies; she has received personal fees from the National Institutes of Health as a special government employee (in her role as a member of the Advisory Committee for Research on Women's Health), the Greenwall Foundation, and the Doris Duke Charitable Foundation. She has received grants for unrelated work from the National Institutes of Health, the Doris Duke Foundation, the Greenwall Foundation, the American Cancer Society, the Komen Foundation, and Blue Cross Blue Shield of Michigan for the Michigan Radiation Oncology Quality Consortium. She had a contract to conduct an investigator-initiated study with Genentech. She has served as an expert witness for Sherinian and Hasso, Dressman Benzinger LaVelle, and Kleinbard LLC. Shearwood McClelland III serves as a consultant for Gilmartin Capital (a company that evaluates surgically targeted radiation therapies), receives travel funding from GT Medical Technologies Inc, and research funding from the University Hospitals Minority Faculty Career Development Award, the American Society of Radiation Oncology Emerging Investigator Award, the Robert Winn Diversity in Clinical Trials Career Development Award, and the National Cancer Institute Paul Calabresi K12 Clinical Oncology Research Career Development Program., (Copyright © 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Objective: To compare long-term quality of life (QOL) outcomes in breast cancer survivors who received breast-conserving surgery with radiotherapy (BCS+RT) with those who received a mastectomy and reconstructive surgery (Mast+Recon) without radiotherapy and identify other important factors., Background: The long-term differences in patient-reported QOL outcomes following BCS+RT and Mast+Recon are not well understood., Methods: We identified patients from the Texas Cancer Registry with stage 0-II breast cancer diagnosed in 2009-2014 after BCS+RT or Mast+Recon without radiotherapy. Sampling was stratified by age and race and ethnicity. A paper survey was sent to 4800 patients which included validated BREAST-Q and PROMIS modules. Multivariable linear regression models were implemented for each outcome. Minimal clinically important difference for BREAST-Q and PROMIS modules, respectively, was 4 points and 2 points., Results: Of 1215 respondents (25.3% response rate), 631 received BCS+RT and 584 received Mast+Recon. The median interval from diagnosis to survey completion was 9 years. In adjusted analysis, Mast+Recon was associated with worse BREAST-Q psychosocial well-being (effect size: -3.80, P =0.04) and sexual well-being (effect size: -5.41, P =0.02), but better PROMIS physical function (effect size: 0.54, P =0.03) and similar BREAST-Q satisfaction with breasts, physical well-being, and PROMIS upper extremity function ( P >0.05) compared with BCS+RT. Only the difference in sexual well-being reached clinical significance. Older (≥65) patients receiving BCS+RT and younger (<50) patients receiving autologous Mast+Recon typically reported higher QOL scores. Receipt of chemotherapy was associated with detriments to multiple QOL domains., Conclusions: Patients who underwent Mast+Recon reported worse long-term sexual well-being compared with BCS+RT. Older patients derived a greater benefit from BCS+RT, while younger patients derived a greater benefit from Mast+Recon. These data inform preference-sensitive decision-making for women with early-stage breast cancer., Competing Interests: B.D.S. receives salary support from Varian Medical Systems that is unrelated to the current project. He also has a royalty and equity interest in Oncora Medical. R.J.’s time on this work was supported by the Susan G. Komen Foundation. Outside the current work, she has stock options as compensation for her advisory board role in Equity Quotient, a company that evaluates culture in health care companies; she has received personal fees from the Greenwall Foundation, Doris Duke Charitable Foundation, and the National Institutes of Health and grants or contracts for unrelated work from the National Institutes of Health, the Doris Duke Charitable Foundation, the American Cancer Society, the Greenwall Foundation, and Genentech. She has served as an expert witness for Dressman Benzinger LaVelle and Kleinbard LLC. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Little is known about regional nodal irradiation (RNI) practice patterns or rates of locoregional recurrence (LRR) with and without RNI in patients with limited nodal disease and favorable biology treated with modern surgical and systemic therapy, including approaches that de-escalate those latter treatments., Objective: To investigate how often patients with low-recurrence score breast cancer with 1 to 3 nodes involved receive RNI, incidence and predictors of LRR, and associations between locoregional therapy and disease-free survival., Design, Setting, and Participants: In this secondary analysis of the SWOG S1007 trial, patients with hormone receptor-positive, ERBB2-negative breast cancer, and a Oncotype DX 21-gene Breast Recurrence Score assay result of no more than 25, were randomized to endocrine therapy alone vs chemotherapy then endocrine therapy. Prospectively collected radiotherapy information was collected from 4871 patients treated in diverse settings. Data were analyzed June 2022 to April 2023., Exposure: Receipt of RNI (targeting at least the supraclavicular region)., Main Outcome(s) and Measure(s): Cumulative incidence of LRR was calculated by locoregional treatment received. Analyses were assessed for associations between invasive disease-free survival (IDFS) and locoregional therapy, adjusted for menopausal status, treatment group, recurrence score, tumor size, nodes involved, and axillary surgery. Radiotherapy information was recorded in the first year after randomization, so survival analyses were landmarked as starting at 1 year among those still at risk., Results: Of 4871 female patients (median [range] age, 57 [18-87] years) with radiotherapy forms, 3947 (81.0%) reported radiotherapy receipt. Of 3852 patients who received radiotherapy and had complete information on targets, 2274 (59.0%) received RNI. With a median follow-up of 6.1 years, the cumulative incidence of LRR by 5 years was 0.85% among patients who received breast-conserving surgery and radiotherapy with RNI; 0.55% after breast-conserving surgery with radiotherapy without RNI; 0.11% after mastectomy with postmastectomy radiotherapy; and 1.7% after mastectomy without radiotherapy. Similarly low LRR was observed within the group assigned to endocrine therapy without chemotherapy. The rate of IDFS did not differ by RNI receipt (premenopausal: hazard ratio [HR], 1.03; 95% CI, 0.74-1.43; P = .87; postmenopausal: HR, 0.85; 95% CI, 0.68-1.07; P = .16)., Conclusions and Relevance: In this secondary analysis of a clinical trial, RNI use was divided in the setting of biologically favorable N1 disease, and rates of LRR were low even in patients who did not receive RNI. Disease-free survival was not associated with RNI receipt; omission of chemotherapy among patients similar to those enrolled in the S1007 trial is not an independent indication for use of RNI.

Purpose: The COVID-19 pandemic has profoundly affected cancer care worldwide, including radiation therapy (RT) for breast cancer (BC), because of risk-based resource allocation. We report the evolution of international breast RT practices during the beginning of the pandemic, focusing on differences in treatment recommendations between countries., Materials and Methods: Between July and November 2020, a 58-question survey was distributed to radiation oncologists (ROs) through international professional societies. Changes in RT decision making during the first surge of the pandemic were evaluated across six hypothetical scenarios, including the management of ductal carcinoma in situ (DCIS), early-stage, locally advanced, and metastatic BC. The significance of changes in responses before and during the pandemic was examined using chi-square and McNemar-Bowker tests., Results: One thousand one hundred three ROs from 54 countries completed the survey. Incomplete responses (254) were excluded from the analysis. Most respondents were from the United States (285), Japan (117), Italy (63), Canada (58), and Brazil (56). Twenty-one percent (230) of respondents reported treating at least one patient with BC who was COVID-19-positive. Approximately 60% of respondents reported no change in treatment recommendation during the pandemic, except for patients with metastatic disease, for which 57.7% (636/1,103; P < .0005) changed their palliative practice. Among respondents who noted a change in their recommendation during the first surge of the pandemic, omitting, delaying, and adopting short-course RT were the most frequent changes, with most transitioning to moderate hypofractionation for DCIS and early-stage BC., Conclusion: Early in the COVID-19 pandemic, significant changes in global RT practice patterns for BC were introduced. The impact of published results from the FAST FORWARD trial supporting ultrahypofractionation likely confounded the interpretation of the pandemic's independent influence on RT delivery.

Purpose: Phyllodes tumors of the breast are rare fibroepithelial lesions that are classified as benign, borderline or malignant. There is little consensus on best practice for the work-up, management, and follow-up of patients with phyllodes tumors of the breast, and evidence-based guidelines are lacking., Methods: We conducted a cross-sectional survey of surgeons and oncologists with the aim to describe current clinical practice in the management of phyllodes tumors. The survey was constructed in REDCap and distributed between July 2021 and February 2022 through international collaborators in sixteen countries across four continents., Results: A total of 419 responses were collected and analyzed. The majority of respondents were experienced and worked in a university hospital. Most agreed to recommend a tumor-free excision margin for benign tumors, increasing margins for borderline and malignant tumors. The multidisciplinary team meeting plays a major role in the treatment plan and follow-up. The vast majority did not consider axillary surgery. There were mixed opinions on adjuvant treatment, with a trend towards more liberal regiments in patients with locally advanced tumors. Most respondents preferred a five-year follow-up period for all phyllodes tumor types., Conclusions: This study shows considerable variation in clinical practice managing phyllodes tumors. This suggests the potential for overtreatment of many patients and the need for education and further research targeting appropriate surgical margins, follow-up time and a multidisciplinary approach. There is a need to develop guidelines that recognize the heterogeneity of phyllodes tumors., (© 2023. The Author(s).)

Introduction: National guidelines recommend against routine axillary staging with sentinel lymph node biopsy (SLNB) and adjuvant radiotherapy (RT) in women ≥70 y with early-stage, hormone receptor-positive, HER2-negative breast cancer and clinically negative axilla; however, these practices remain common., Methods: We conducted a prospective pilot study from August 2021 to 2022 using an intervention targeting breast surgeons and radiation oncologists in Michigan that aimed to reduce SLNB and RT in eligible patients. The intervention consisted of (1) a geriatric assessment, (2) an assessment of the patient's medical maximizing-minimizing preferences, and (3) a tailored script with counterpoints to reasons patients commonly seek SLNB or RT. At the end of the study period, participants completed a survey providing feedback with the primary outcomes being: acceptability, appropriateness, feasibility, and intention and motivation to use the materials based on validated measures., Results: Participants (n = 23) included 15 breast surgeons and 8 radiation oncologists. Collectively, the materials were used with 115 patients. Considering all materials holistically, acceptability, appropriateness, and feasibility of the intervention were high; participants also intended and were motivated to use the intervention. Scores across all measures were highest for the geriatric assessment and lowest for the tailored script. The major barriers to using the intervention were limited time and instances of disagreement on treatment recommendations among surgeons and radiation oncologists., Conclusions: The omission of SLNB and adjuvant RT should be discussed in appropriately selected patients. A multifaceted provider-level deimplementation strategy may be an effective means for achieving this goal., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Radiotherapy (RT) is a common and often essential treatment for breast cancer, but has been associated with pectoralis major (PM) muscle fibrosis and atrophy. In an initial prospective evaluation, we assessed muscle stiffness and muscle thickness of the sternocostal and clavicular regions of the PM with ultrasound shear wave elastography and B-mode imaging. Changes in PM muscle stiffness and thickness following RT can be detected within the first twelve months of RT completion. These parameters may potentially be useful for screening of patients who would benefit from post-RT physical therapy. Further studies with larger sample sizes that include patients who receive nodal radiation are necessary to confirm these findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Advances in precision medicine have given oncologists new evaluative tools to better individualize treatments for patients with curable breast cancer. These innovations have revealed a need to improve patient understanding of novel, often complex information related to breast cancer treatment decisions. Ensuring patients have the emotional support to face consequential treatment decisions, as well as the opportunity to engage and discuss with their clinicians, is key to improving patient-centered communication and patient understanding., Methods/design: This study will implement a multilevel intervention with patient and clinician components as a NCORP Cancer Care Delivery Research (CCDR) trial within the Alliance for Clinical Trials in Oncology Research Base (Alliance). The two interventions in this study, the Shared Decision Engagement System (SharES), include (1) two versions of an evidence-based patient-facing breast cancer treatment decision tool (iCanDecide +/- an emotional support module) and (2) a clinician-facing dashboard (Clinician Dashboard) that is reviewed by surgeons/clinicians and summarizes ongoing patient needs. The design is a near minimax, hybrid stepped wedge trial of SharES where both interventions are being evaluated in a crossed design over six 12-week time periods. The primary outcome (knowledge) and key secondary outcomes (i.e., self-efficacy and cancer worry) are assessed via patient report at 5 weeks after surgery. Secondary outcomes are also assessed at 5 weeks after surgery, as well as in a second survey 9 months after registration. We anticipate recruiting a total of 700 breast cancer patients (600 evaluable after attrition) from 25 surgical practices affiliated with Alliance., Discussion: Upon study completion, we will have better understanding of the impact of a multilevel intervention on patient-centered communication in breast cancer with a specific focus on whether the intervention components improve knowledge and self-efficacy and reduce cancer worry., Trial Registration: ClinicalTrials.gov NCT04549571 . Registered on 16 September 2020., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Racial disparities in survival of patients with cancer motivate research to quantify treatment disparities and evaluate multilevel determinants. Previous research has not evaluated cardiac radiation dose in large cohorts of breast cancer patients by race nor examined potential causes or implications of dose disparities., Methods: We used a statewide consortium database to consecutively sample 8750 women who received whole breast radiotherapy between 2012 and 2018. We generated laterality- and fractionation-specific models of mean heart dose. We generated patient- and facility-level models to estimate race-specific cardiac doses. We incorporated our data into models to estimate disparities in ischemic cardiac event development and death. All statistical tests were 2-sided., Results: Black and Asian race independently predicted higher mean heart dose for most laterality-fractionation groups, with disparities of up to 0.42 Gy for Black women and 0.32 Gy for Asian women (left-sided disease and conventional fractionation: 2.13 Gy for Black women vs 1.71 Gy for White women, P < .001, 2-sided; left-sided disease and accelerated fractionation: 1.59 Gy for Asian women vs 1.27 Gy for White women, P = .002). Patient clustering within facilities explained 22%-30% of the variability in heart dose. The cardiac dose disparities translated to estimated excesses of up to 2.6 cardiac events and 1.3 deaths per 1000 Black women and 0.7 cardiac events and 0.3 deaths per 1000 Asian women vs White women., Conclusions: Depending on laterality and fractionation, Asian women and Black women experience higher cardiac doses than White women. This may translate into excess radiation-associated ischemic cardiac events and deaths. Solutions include addressing inequities in baseline cardiac risk factors and facility-level availability and use of radiation technologies., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Acquired mutations in the ligand-binding domain (LBD) of the gene encoding estrogen receptor α (ESR1) are common mechanisms of endocrine therapy resistance in patients with metastatic ER+ breast cancer. The ESR1 Y537S mutation, in particular, is associated with development of resistance to most endocrine therapies used to treat breast cancer. Employing a high-throughput screen of nearly 1,200 Federal Drug Administration-approved (FDA-approved) drugs, we show that OTX015, a bromodomain and extraterminal domain (BET) inhibitor, is one of the top suppressors of ESR1 mutant cell growth. OTX015 was more efficacious than fulvestrant, a selective ER degrader, in inhibiting ESR1 mutant xenograft growth. When combined with abemaciclib, a CDK4/6 inhibitor, OTX015 induced more potent tumor regression than current standard-of-care treatment of abemaciclib + fulvestrant. OTX015 has preferential activity against Y537S mutant breast cancer cells and blocks their clonal selection in competition studies with WT cells. Thus, BET inhibition has the potential to both prevent and overcome ESR1 mutant-induced endocrine therapy resistance in breast cancer.

Advances in our understanding of tumor biology now permit greater personalization of radiotherapy for early-stage breast cancer. De-escalation of radiotherapy is an important opportunity that exists due to improvements in breast imaging, surgery, pathology, and systemic therapy. These modern tools, in addition to molecular subtype and prediction assays, have allowed us to select certain patients with breast cancer based on favorable biology who are at sufficiently low-risk of local recurrence that they may reasonably consider the omission of radiotherapy to reduce toxicity and burden. For decades, clinical trials have been conducted to try to identify the population of patients in whom the risk of recurrence in the absence of radiotherapy is sufficiently small that omission of adjuvant radiotherapy might acceptably be considered after breast conserving surgery. Trials to date have largely included patients with estrogen receptor-positive breast cancer selected based upon clinicopathologic characteristics alone and have yet to identify a patient population for whom radiotherapy is not effective. They have, however, identified women with lower absolute risks of locoregional recurrence with radiotherapy omission, and current guidelines do recognize this patient population as candidates for radiotherapy omission after breast conserving surgery. Studies that assess not just clinicopathologic features but predictive molecular biomarkers of the underlying biology are currently ongoing. This manuscript will briefly review historical trials evaluating the role of radiotherapy after breast conserving surgery as well as discuss the exciting ongoing trials in hormone receptor-positive disease leveraging our growing appreciation of tumor biology and molecular prediction to identify a population of patients who may reasonably consider omitting radiotherapy after breast conserving surgery., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: We investigated whether the use of chemotherapy before whole breast irradiation (WBI) using either conventional fractionation (CWBI) or hypofractionation (HWBI) is associated with increased toxic effects or worse cosmetic outcome compared with WBI alone., Methods and Materials: We identified 6754 patients who received WBI alone (without a third field covering the superior axillary and supraclavicular nodal regions) with data prospectively collected in a statewide consortium. We reported rates of 4 toxic effects: physician-reported acute moist desquamation, patient-reported acute moderate/severe breast pain, a composite acute toxic effect measure (including moist desquamation and either patient- or physician-reported moderate/significant breast pain), and physician-reported impaired cosmetic outcome at 1 year after WBI. Successive multivariable models were constructed to estimate the effect of chemotherapy on these outcomes., Results: Rates of moist desquamation, patient-reported pain, composite acute toxic effects, and impaired cosmetic outcome were 23%, 34%, 42%, and 10% for 2859 patients receiving CWBI and 13%, 28%, 31%, and 11% for 3895 patients receiving HWBI. Receipt of chemotherapy before CWBI was not associated with higher rates of patient-reported pain, composite acute toxic effects, or impaired cosmetic outcome compared with CWBI without chemotherapy but was associated with more moist desquamation (odds ratio, 1.32 [1.07-1.63]; P = .01). Receipt of chemotherapy before HWBI was not associated with higher rates of any of the 4 toxic effects compared with HWBI alone., Conclusions: In this cohort, use of chemotherapy before WBI was generally well tolerated. CWBI with chemotherapy but not HWBI with chemotherapy was associated with higher rates of moist desquamation. Rates of acute breast pain and impaired cosmetic outcome at 1 year were comparable in patients receiving chemotherapy before either CWBI or HWBI. These data support the use of HWBI after chemotherapy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: Treatment options for early breast cancer include breast-conserving surgery with radiation therapy (RT) or mastectomy and breast reconstruction without RT. Despite marked differences in these treatment strategies, little is known with regard to their association with long-term quality of life (QOL)., Objective: To evaluate the association of treatment with breast-conserving surgery with RT vs mastectomy and reconstruction without RT with long-term QOL., Design, Setting, and Participants: This comparative effectiveness research study used data from the Texas Cancer Registry for women diagnosed with stage 0-II breast cancer and treated with breast-conserving surgery or mastectomy and reconstruction between 2006 and 2008. The study sample was mailed a survey between March 2017 and April 2018. Data were analyzed from August 1, 2018 to October 15, 2021., Exposures: Breast-conserving surgery with RT or mastectomy and reconstruction without RT., Main Outcomes and Measures: The primary outcome was satisfaction with breasts, measured with the BREAST-Q patient-reported outcome measure. Secondary outcomes included BREAST-Q physical well-being, psychosocial well-being, and sexual well-being; health utility, measured using the EuroQol Health-Related Quality of Life 5-Dimension, 3-Level questionnaire; and local therapy decisional regret. Multivariable linear regression models with weights for treatment, age, and race and ethnicity tested associations of the exposure with outcomes., Results: Of 647 patients who responded to the survey (40.0%; 356 had undergone breast-conserving surgery, and 291 had undergone mastectomy and reconstruction), 551 (85.2%) confirmed treatment with breast-conserving surgery with RT (n = 315) or mastectomy and reconstruction without RT (n = 236). Among the 647 respondents, the median age was 53 years (range, 23-85 years) and the median time from diagnosis to survey was 10.3 years (range, 8.4-12.5 years). Multivariable analysis showed no significant difference between breast-conserving surgery with RT (referent) and mastectomy and reconstruction without RT in satisfaction with breasts (effect size, 2.71; 95% CI, -2.45 to 7.88; P = .30) or physical well-being (effect size, -1.80; 95% CI, -5.65 to 2.05; P = .36). In contrast, psychosocial well-being (effect size, -8.61; 95% CI, -13.26 to -3.95; P < .001) and sexual well-being (effect size, -10.68; 95% CI, -16.60 to -4.76; P < .001) were significantly worse with mastectomy and reconstruction without RT. Health utility (effect size, -0.003; 95% CI, -0.03 to 0.03; P = .83) and decisional regret (effect size, 1.32; 95% CI, -3.77 to 6.40; P = .61) did not differ by treatment group., Conclusions and Relevance: The findings support equivalence of breast-conserving surgery with RT and mastectomy and reconstruction without RT with regard to breast satisfaction and physical well-being. However, breast-conserving surgery with RT was associated with clinically meaningful improvements in psychosocial and sexual well-being. These findings may help inform preference-sensitive decision-making for women with early-stage breast cancer.

Importance: Understanding whether physicians accurately detect symptoms in patients with breast cancer is important because recognition of symptoms facilitates supportive care, and clinical trials often rely on physician assessments using Common Toxicity Criteria for Adverse Events (CTCAE)., Objective: To compare the patient-reported outcomes (PROs) of patients with breast cancer who received radiotherapy from January 1, 2012, to March 31, 2020, with physicians' CTCAE assessments to assess underrecognition of symptoms., Design, Setting, and Participants: This cohort study included a total of 29 practices enrolled in the Michigan Radiation Oncology Quality Consortium quality initiative. Of 13 725 patients with breast cancer who received treatment with radiotherapy after undergoing lumpectomy, 9941 patients (72.4%) completed at least 1 PRO questionnaire during treatment with radiotherapy and were evaluated for the study. Of these, 9868 patients (99.3%) were matched to physician CTCAE assessments that were completed within 3 days of the PRO questionnaires., Exposures: Patient and physician ratings of 4 symptoms (pain, pruritus, edema, and fatigue) were compared., Main Outcomes and Measures: We used multilevel multivariable logistic regression to evaluate factors associated with symptom underrecognition, hypothesizing that it would be more common in racial and ethnic minority groups., Results: Of 9941 patients, all were female, 1655 (16.6%) were Black, 7925 (79.7%) were White, and 361 (3.6%) had Other race and ethnicity (including American Indian/Alaska Native, Arab/Middle Eastern, and Asian), either as self-reported or as indicated in the electronic medical record. A total of 1595 (16.0%) were younger than 50 years, 2874 (28.9%) were age 50 to 59 years, 3353 (33.7%) were age 60 to 69 years, and 2119 (21.3%) were 70 years or older. Underrecognition of symptoms existed in 2094 of 6781 (30.9%) observations of patient-reported moderate/severe pain, 748 of 2039 observations (36.7%) of patient-reported frequent pruritus, 2309 of 4492 observations (51.4%) of patient-reported frequent edema, and 390 of 2079 observations (18.8%) of patient-reported substantial fatigue. Underrecognition of at least 1 symptom occurred at least once for 2933 of 5510 (53.2%) of those who reported at least 1 substantial symptom. Factors independently associated with underrecognition were younger age (younger than 50 years compared with 60-69 years: odds ratio [OR], 1.35; 95% CI, 1.14-1.59; P < .001; age 50-59 years compared with 60-69 years: OR, 1.19; 95% CI, 1.03-1.37; P = .02), race (Black individuals compared with White individuals: OR, 1.56; 95% CI 1.30-1.88; P < .001; individuals with Other race or ethnicity compared with White individuals: OR, 1.52; 95% CI, 1.12-2.07; P = .01), conventional fractionation (OR, 1.26; 95% CI, 1.10-1.45; P = .002), male physician sex (OR, 1.54; 95% CI, 1.20-1.99; P = .002), and 2-field radiotherapy (without a supraclavicular field) (OR, 0.80; 95% CI, 0.67-0.97; P = .02)., Conclusions and Relevance: The results of this cohort study suggest that PRO collection may be essential for trials because relying on the CTCAE to detect adverse events may miss important symptoms. Moreover, since physicians in this study systematically missed substantial symptoms in certain patients, including younger patients and Black individuals or those of Other race and ethnicity, improving symptom detection may be a targetable mechanism to reduce disparities.

Background: Despite mandated insurance coverage for breast reconstruction following mastectomy, health care costs are increasingly passed on to women through cost-sharing arrangements and high-deductible health plans. In this population-based study, the authors assessed perceived financial and employment declines related to breast reconstruction following mastectomy., Methods: Women with early-stage breast cancer (stages 0-II) diagnosed between July 2013 and May 2015 who underwent mastectomy were identified through the Surveillance, Epidemiology, and End Results registries of Georgia and Los Angeles and were surveyed. Primary outcome measures included patients' appraisal of their financial and employment status after cancer treatment. Multivariable models evaluated the association between breast reconstruction and primary outcomes., Results: Among 883 patients with breast cancer who underwent mastectomy, 44.2% did not undergo breast reconstruction, and 55.8% underwent reconstruction. Overall, 21.9% of the cohort reported being worse off financially since their diagnosis (25.8% with reconstruction vs 16.6% without reconstruction; P = .002). Women who underwent reconstruction reported higher out-of-pocket medical expenses (32.1% vs 15.6% with expenses greater than $5000; P < .001). Reconstruction was independently associated with a perceived decline in financial status (odds ratio, 1.92; 95% confidence interval, 1.15-3.22; P = .013). Among women who were employed at the time of their diagnosis, there was no association between reconstruction and a perceived decline in employment status (P = .927)., Conclusions: In this diverse cohort of women who underwent mastectomy, those who elected to undergo reconstruction experienced higher out-of-pocket medical expenses and self-reported financial decline. Patients, providers, and policymakers should be aware of the potential financial implications related to reconstruction despite mandatory insurance coverage., (© 2021 American Cancer Society.)

Purpose: Questions remain about whether moderately hypofractionated whole-breast irradiation is appropriate for patients with triple-negative breast cancer., Methods and Materials: Using the prospective database of a multicenter, collaborative quality improvement consortium, we identified patients with node-negative, triple-negative breast cancer who received whole-breast irradiation with either moderate hypofractionation or conventional fractionation. Using inverse probability of treatment weighting (IPTW), we compared outcomes using the Kaplan-Meier product-limit estimation method with Cox regression models estimating the hazard ratio for time-to-event endpoints between groups., Results: The sample included 538 patients treated at 18 centers in 1 state in the United States, of whom 307 received conventionally fractionated whole-breast irradiation and 231 received moderately hypofractionated whole-breast irradiation. The median follow-up time was 5.0 years (95% confidence interval [CI], 4.77-5.15 years). The 5-year IPTW estimates for freedom from local recurrence were 93.6% (95% CI, 87.8%-96.7%) in the moderate hypofractionation group and 94.4% (95% CI, 90.3%-96.8%) in the conventional fractionation group. The hazard ratio was 1.05 (95% CI, 0.51-2.17; P = .89). The 5-year IPTW estimates for recurrence-free survival were 87.8% (95% CI, 81.0%-92.4%) in the moderate hypofractionation group and 88.4% (95% CI 83.2%-92.1%) in the conventional fractionation group. The hazard ratio was 1.02 (95% CI, 0.62-1.67; P = .95). The 5-year IPTW estimates for overall survival were 96.6% (95% CI, 92.0%-98.5%) in the moderate hypofractionation group and 93.4% (95% CI, 88.7%-96.1%) in the conventional fractionation group. The hazard ratio was 0.65 (95% CI, 0.30-1.42; P = .28)., Conclusions: Analysis of outcomes in this large observational cohort of patients with triple-negative, node-negative breast cancer treated with whole-breast irradiation revealed no differences by dose fractionation. This adds evidence to support the use of moderate hypofractionation in patients with triple-negative disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Simple intensity modulation of radiation therapy reduces acute toxicity compared with 2-dimensional techniques in adjuvant breast cancer treatment, but it remains unknown whether more complex or inverse-planned intensity modulated radiation therapy (IMRT) offers an advantage over forward-planned, 3-dimensional conformal radiation therapy (3DCRT)., Methods and Materials: Using prospective data regarding patients receiving adjuvant whole breast radiation therapy without nodal irradiation at 23 institutions from 2011 to 2018, we compared the incidence of acute toxicity (moderate-severe pain or moist desquamation) in patients receiving 3DCRT versus IMRT (either inverse planned or, if forward-planned, using ≥5 segments per gantry angle). We evaluated associations between technique and toxicity using multivariable models with inverse-probability-of-treatment weighting, adjusting for treatment facility as a random effect., Results: Of 1185 patients treated with 3DCRT and conventional fractionation, 650 (54.9%) experienced acute toxicity; of 774 treated with highly segmented forward-planned IMRT, 458 (59.2%) did; and of 580 treated with inverse-planned IMRT, 245 (42.2%) did. Of 1296 patients treated with hypofractionation and 3DCRT, 432 (33.3%) experienced acute toxicity; of 709 treated with highly segmented forward-planned IMRT, 227 (32.0%) did; and of 623 treated with inverse-planned IMRT, 164 (26.3%) did. On multivariable analysis with inverse-probability-of-treatment weighting, the odds ratio for acute toxicity after inverse-planned IMRT versus 3DCRT was 0.64 (95% confidence interval, 0.45-0.91) with conventional fractionation and 0.41 (95% confidence interval, 0.26-0.65) with hypofractionation., Conclusions: This large, prospective, multicenter comparative effectiveness study found a significant benefit from inverse-planned IMRT compared with 3DCRT in reducing acute toxicity of breast radiation therapy. Future research should identify the dosimetric differences that mediate this association and evaluate cost-effectiveness., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Radiation therapy (RT) can increase the risk of cardiac events in patients with breast cancer (BC), but biomarkers predicting risk for developing RT-induced cardiac disease are currently lacking. We report results from a prospective clinical trial evaluating early magnetic resonance imaging (MRI) and serum biomarker changes as predictors of cardiac injury and risk of subsequent cardiac events after RT for left-sided disease., Methods: Women with node-negative and node-positive (N-/+) left-sided BC were enrolled on 2 institutional review board (IRB)-approved protocols at 2 institutions. MRI was conducted pretreatment (within 1 week of starting radiation), at the end of treatment (last day of treatment ±1 week), and 3 months after the last day of treatment (±2 weeks) to quantify left and right ventricular volumes and function, myocardial fibrosis, and edema. Perfusion changes during regadenoson stress perfusion were also assessed on a subset of patients (n = 28). Serum was collected at the same time points. Whole heart and cardiac substructures were contoured using CT and MRI. Models were constructed using baseline cardiac and clinical risk factors. Associations between MRI-measured changes and dose were evaluated., Results: Among 51 women enrolled, mean heart dose ranged from 0.80 to 4.7 Gy and mean left ventricular (LV) dose from 1.1 to 8.2 Gy, with mean heart dose 2.0 Gy. T1 time, a marker of fibrosis, and right ventricular (RV) ejection fraction (EF) significantly changed with treatment; these were not dose dependent. T2 (marker of edema) and LV EF did not significantly change. No risk factors were associated with baseline global perfusion. Prior receipt of doxorubicin was marginally associated with decreased myocardial perfusion after RT (P = .059), and mean MHD was not associated with perfusion changes. A significant correlation between baseline IL-6 and mean heart dose (MHD) at the end of RT (ρ 0.44, P = .007) and a strong trend between troponin I and MHD at 3 months post-treatment (ρ 0.33, P = .07) were observed. No other significant correlations were identified., Conclusions: In this prospective study of women with left-sided breast cancer treated with contemporary treatment planning, cardiac radiation doses were very low relative to historical doses reported by Darby et al. Although we observed significant changes in T1 and RV EF shortly after RT, these changes were not correlated with whole heart or substructure doses. Serum biomarker analysis of cardiac injury demonstrates an interesting trend between markers and MHD that warrants further investigation., (Published by Elsevier Inc.)

Background: Despite awareness regarding financial toxicity in breast cancer care, little is known about the financial strain associated with breast reconstruction. This study aims to describe financial toxicity and identify factors independently associated with financial toxicity for women pursuing post-mastectomy breast reconstruction., Methods: A 33-item electronic survey was distributed to members of the Love Research Army. Women over 18 years of age and at least 1 year after post-mastectomy breast reconstruction were invited to participate. The primary outcome of interest was self-reported financial toxicity due to breast reconstruction, while secondary outcomes of interest were patient-reported out-of-pocket expenses and impact of financial toxicity on surgical decision making., Results: In total, 922 women were included (mean age 58.6 years, standard deviation 10.3 years); 216 women (23.8%) reported financial toxicity from reconstruction. These women had significantly greater out-of-pocket medical expenses. When compared with women who did not experience financial toxicity, those who did were more likely to have debt due to reconstruction (50.9% vs. 3.2%, p < 0.001). Younger age, lower annual household income, greater out-of-pocket expenses, and a postoperative major complication were independently associated with an increased risk for financial toxicity. If faced with the same decision, women experiencing financial toxicity were more likely to decide against reconstruction (p < 0.001) compared with women not experiencing financial toxicity., Conclusions: Nearly one in four women experienced financial toxicity from breast reconstruction. Women who reported higher levels of financial toxicity were more likely to change their decisions about surgery. Identified factors predictive of financial toxicity could guide preoperative discussions to inform decision making that mitigates undesired financial decline., (© 2021. Society of Surgical Oncology.)

Background: Screening mammography guidelines do not explicitly consider racial differences in breast cancer epidemiology, treatment, and survival., Objective: To compare tradeoffs of screening strategies in Black women versus White women under current guidelines., Design: An established model from the Cancer Intervention and Surveillance Modeling Network simulated screening outcomes using race-specific inputs for subtype distribution; breast density; mammography performance; age-, stage-, and subtype-specific treatment effects; and non-breast cancer mortality., Setting: United States., Participants: A 1980 U.S. birth cohort of Black and White women., Intervention: Screening strategies until age 74 years with varying initiation ages and intervals., Measurements: Outcomes included benefits (life-years gained [LYG], breast cancer deaths averted, and mortality reduction), harms (mammographies, false positives, and overdiagnoses), and benefit-harm ratios (tradeoffs) by race. Efficiency (benefits per unit resource), mortality disparity reduction, and equity in tradeoffs were evaluated. Equitable strategies for Black women were defined as those with tradeoffs closest to benchmark values for screening White women biennially from ages 50 to 74 years., Results: Biennial screening from ages 45 to 74 years was most efficient for Black women, whereas biennial screening from ages 40 to 74 years was most equitable. Initiating screening 10 years earlier in Black versus White women reduced Black-White mortality disparities by 57% with similar LYG per mammogram for both populations. Selection of the most equitable strategy was sensitive to assumptions about disparities in real-world treatment effectiveness: The less effective treatment was for Black women, the more intensively Black women could be screened before tradeoffs fell short of those experienced by White women., Limitation: Single model., Conclusion: Initiating biennial screening in Black women at age 40 years reduces breast cancer mortality disparities and yields benefit-harm ratios that are similar to tradeoffs of White women screened biennially from ages 50 to 74 years., Primary Funding Source: National Cancer Institute at the National Institutes of Health.

Bolus serves as a tissue equivalent material that shifts the 95-100% isodose line towards the skin and subcutaneous tissue. The need for bolus for all breast cancer patients planned for postmastectomy radiation therapy (PMRT) has been questioned. The work was initiated by the faculty of the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer courses and represents a multidisciplinary international breast cancer expert collaboration to optimize PMRT. Due to the lack of randomised trials evaluating the benefits of bolus, we designed a stepwise project to evaluate the existing evidence about the use of bolus in the setting of PMRT to achieve an international consensus for the indications of bolus in PMRT, based on the Delphi method., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Financial toxicity from cancer treatment is a growing concern. Its impact on patients requires refining our understanding of this phenomenon. We sought to characterize patients' experiences of financial toxicity in the context of an established framework to identify knowledge gaps and strategies for mitigation., Methods: Semistructured interviews with patients with breast cancer who received financial aid from a philanthropic organization during treatment were conducted from February to May 2020. Interviews were transcribed and coded until thematic saturation was reached, and findings were contextualized within an existing financial toxicity framework., Results: Thirty-two patients were interviewed, of whom 58% were non-Hispanic White. The mean age was 46 years. Diagnoses ranged from ductal carcinoma in situ to metastatic breast cancer. Concordant with an established framework, we found that direct and indirect costs determined objective financial burden and subjective financial distress stemmed from psychosocial, behavioral, and material impact of diagnosis and treatment. We identified expectations as a novel theme affecting financial toxicity. We identified knowledge gaps in treatment expectations, provider conversations, identification of resources, and support-finding and offer strategies for mitigating financial toxicity on the basis of participant responses, such as leveraging support from decision aids and allied providers., Conclusion: This qualitative study confirms an existing framework for understanding financial toxicity and identifies treatment expectations as a novel theme affecting both objective financial burden and subjective financial distress. Four knowledge gaps are identified, and strategies for mitigating financial toxicity are offered. Mitigating patients' financial toxicity is an important unmet need in optimizing cancer treatment., Competing Interests: Susan GooldPatents, Royalties, Other Intellectual Property: A simulation exercise (CHAT) I coinvented, when others pay to use it, results in royalties to me, my coinventor, and our institutions. My own royalty receipts in the past 2 years have been less than $1,000 US dollars Grace SmithResearch Funding: Varian Medical SystemsOther Relationship: Oncora Medical Reshma JagsiEmployment: University of MichiganStock and Other Ownership Interests: Equity QuotientResearch Funding: GenentechExpert Testimony: Baptist Health/Dressman Benziger Lavalle Law, Kleinbard LLCTravel, Accommodations, Expenses: AmgenOther Relationship: JAMA OncologyOpen Payments Link: https://openpaymentsdata.cms.gov/physician/373670/summaryhttps://openpaymentsdata.cms.gov/physician/373670/summaryNo other potential conflicts of interest were reported.

Purpose: Post mastectomy radiation therapy (PMRT) reduces locoregional recurrence (LRR) and breast cancer mortality for selected patients. Bolus overcomes the skin-sparing effect of external-beam radiotherapy, ensuring adequate dose to superficial regions at risk of local recurrence (LR). This systematic review summarizes the current evidence regarding the impact of bolus on LR and acute toxicity in the setting of PMRT., Results: 27 studies were included. The use of bolus led to higher rates of acute grade 3 radiation dermatitis (pooled rates of 9.6% with bolus vs. 1.2% without). Pooled crude LR rates from thirteen studies (n = 3756) were similar with (3.5%) and without (3.6%) bolus., Conclusions: Bolus may be indicated in cases with a high risk of LR in the skin, but seems not to be necessary for all patients. Further work is needed to define the role of bolus in PMRT., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Accrual to clinical trials that challenge well-established treatment paradigms represents a unique challenge. Physician opinions on investigation of a novel approach to breast cancer treatment, in which patients with complete response to neoadjuvant chemotherapy are offered omission of lumpectomy, are unknown. NRG-CC006 sought to describe physician attitudes toward a novel approach to breast cancer treatment., Methods: We recruited 18 participants in the fields of surgery, medical oncology, and radiation oncology to participate in the semi-structured telephone interviews. Main outcomes are qualitative themes associated with omission of surgery., Results: Of 18 interview participants, specialty and gender were evenly represented across surgery, medical oncology, and radiation oncology. Qualitative themes included general attitudes toward treatment de-escalation, stakeholder considerations, and trial/protocol considerations. The vast majority of participants expressed interest in investigation of omission of surgery, with all participants endorsing need for further investigation into treatment de-escalation. Stakeholder considerations in opening such a trial emphasized need for multidisciplinary involvement and, particularly, the unique role of surgeons as gatekeepers in breast cancer treatment. Finally, participants endorsed a need for further foundational studies to develop ways to predict complete pathologic response to chemotherapy without surgical intervention., Conclusions: Physicians expressed interest in investigating a novel approach to breast cancer treatment that would omit surgery in complete responders to neoadjuvant chemotherapy. Multidisciplinary input, and specifically surgeon engagement, will be key to the success of future investigations. Ongoing work to develop approaches to predict pathologic complete response accurately is needed to achieve the promise of this idea. ClinTrials #: BR005: NCT03188393 June 13, 2017.

Purpose: Scales for rating acute radiation dermatitis (ARD) have not been validated despite decades of clinical use, and little is known regarding the relationship between toxicity scores and patient-reported symptoms. Skin tone also complicates assessment of ARD, and as such we sought to design an illustrated scale to consistently describe ARD across several skin tone types in breast cancer patients undergoing radiation (RT)., Methods and Materials: Patients undergoing RT for breast cancer were enrolled on a prospective study with photographs obtained at 2-week intervals. Photographs were clustered according to the apparent severity of acute radiation dermatitis and a descriptive photonumeric scale was developed. Four clinically experienced raters used both the illustrated photonumeric scale and the Common Terminology Criteria for Adverse Events to independently score the collection of photographs in 2 independent sessions., Results: Among 80 unique patients with 192 photographs, 47 patients (59%) completed questionnaires about their symptoms during RT. Physicians completed toxicity forms at the point-of-care for 52 patients (65%). Photonumeric ratings compared against patient reports of dry and moist desquamation demonstrated high specificity (95% and 93%, respectively) and negative predictive value (84% and 92%), indicating correct identification of patients who did not report dry or moist desquamation. The sensitivity and positive predictive value for separate measures of dry and moist desquamation were considerably lower. A combined measure of any desquamation (dry or moist) portrayed higher diagnostic accuracy, resulting in 72% sensitivity, 93% specificity, 75% positive predictive value, and 92% negative predictive value. Photonumeric ratings of dry or moist desquamation were significantly associated with patient reports of itching, burning or stinging, hurting, and swelling., Conclusions: The Michigan scale for acute radiation dermatitis is a simple grading rubric that is distinguished by characterization of its intra- and interrater reliability and diagnostic accuracy, correlation with patient-reported symptoms of bother and pain, and applicability across the spectrum of skin pigmentation., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Importance: There is currently no guidance on how to approach surveillance mammography for older breast cancer survivors, particularly when life expectancy is limited., Objective: To develop expert consensus guidelines that facilitate tailored decision-making for routine surveillance mammography for breast cancer survivors 75 years or older., Evidence: After a literature review of the risk of ipsilateral and contralateral breast cancer events among breast cancer survivors and the harms and benefits associated with mammography, a multidisciplinary expert panel was convened to develop consensus guidelines on surveillance mammography for breast cancer survivors 75 years or older. Using an iterative consensus-based approach, input from clinician focus groups, and critical review by the International Society for Geriatric Oncology, the guidelines were refined and finalized., Findings: The literature review established a low risk for ipsilateral and contralateral breast cancer events in most older breast cancer survivors and summarized the benefits and harms associated with mammography. Draft mammography guidelines were iteratively evaluated by the expert panel and clinician focus groups, emphasizing a patient's risk for in-breast cancer events, age, life expectancy, and personal preferences. The final consensus guidelines recommend discontinuation of routine mammography for all breast cancer survivors when life expectancy is less than 5 years, including those with a history of high-risk cancers; consideration to discontinue mammography when life expectancy is 5 to 10 years; and continuation of mammography when life expectancy is more than 10 years. Individualized, shared decision-making is encouraged to optimally tailor recommendations after weighing the benefits and harms associated with surveillance mammography and patient preferences. The panel also recommends ongoing clinical breast examinations and diagnostic mammography to evaluate clinical findings and symptoms, with reassurance for patients that these practices will continue., Conclusions and Relevance: It is anticipated that these expert guidelines will enhance clinical practice by providing a framework for individualized discussions, facilitating shared decision-making regarding surveillance mammography for breast cancer survivors 75 years or older.

Background: Multiple studies have demonstrated the safety of omitting therapies in older women with breast cancer. Despite de-implementation guidelines, up to 65% of older women continue to receive one or more of these low-value services. Previous work has investigated the role of both provider and patient attitudes as barriers to de-implementation; however, the importance of the patient's maximizing-minimizing preferences within this context remains unclear., Methods: In this qualitative study, we conducted 30 semi-structured interviews with women ≥ 70 years of age without a previous diagnosis of breast cancer to elicit perspectives on breast cancer treatment in relation to their medical maximizing-minimizing preferences, as determined by the single-item maximizer-minimizer elicitation question (MM1). We used an interpretive description approach in analysis to produce a thematic survey., Results: Participants were relatively evenly distributed across the MM1 (minimizer, n = 8; neutral, n = 13; maximizer, n = 9). Despite being told of recommendations allowing for the safe omission of sentinel lymph node biopsy and post-lumpectomy radiotherapy, maximizers consistently stated preferences for more medical intervention and aggressive therapies over minimizers and neutral individuals., Conclusion: Medical maximizing-minimizing preferences in older women correspond with preferences for breast cancer treatment options that guidelines identify as potentially unnecessary. Increased awareness of patient-level variability in maximizing-minimizing preferences may be valuable in developing optimal intervention strategies to reduce utilization of low-value care.

Background: For women older than 70 years with early-stage breast cancer, the routine use of sentinel lymph node biopsy (SLNB) and adjuvant radiotherapy offers no overall survival benefit and may be perceived as undesirable by many women. National guidelines allow possible omission of these practices for older women. This study aimed to assess the availability of web-based educational materials targeting older women and their age-specific treatment recommendations., Methods: The study systematically assessed the websites of the top 25 "Best Hospitals for Cancer" ranked by the U.S. News & World Report, as well as the websites of four prominent national cancer organizations., Results: Websites for the leading cancer hospitals and national cancer organizations contain extremely limited information directed toward older patients with breast cancer. Both SLNB and adjuvant radiotherapy are described as treatments "typically," "most often," or "usually" used in combination with breast-conserving surgery without circumstances noted for possible omission. Specifically, no hospital website and only one national organization in this study included information on the recommendation to avoid routine SLNB. Only two hospitals and two national organizations included information suggesting possible omission of adjuvant radiotherapy for patients older than 70 years., Conclusion: The absence of online material for older patients with breast cancer represents a gap potentially contributing to overtreatment by framing SLNB and adjuvant radiotherapy as necessary. Informational resources available to women aged 70 years or older may aid in informed physician-patient communication and decision-making, which may reduce SLNB and adjuvant radiotherapy for patients who might opt out of these procedures if fully informed about them.

Purpose: Understanding acute toxicities after whole-breast radiotherapy is important to inform patients, guide treatment decisions, and target supportive care. We evaluated patient-reported outcomes prospectively collected from a cohort of patients with breast cancer., Methods: We describe the maximal toxicity reported by 8,711 patients treated between 2012 and 2019 at 27 practices. Multivariable models identified characteristics associated with (1) breast pain, (2) bother from itching, stinging/burning, swelling, or hurting of the treated breast, and (3) fatigue within 7 days of completing whole-breast radiotherapy., Results: Moderate or severe breast pain was reported by 3,233 (37.1%): 1,282 (28.9%) of those receiving hypofractionation and 1,951 (45.7%) of those receiving conventional fractionation. Frequent bother from at least one breast symptom was reported by 4,424 (50.8%): 1,833 (41.3%) after hypofractionation and 2,591 (60.7%) after conventional fractionation. Severe fatigue was reported by 2,008 (23.1%): 843 (19.0%) after hypofractionation and 1,165 (27.3%) after conventional fractionation. Among patients receiving hypofractionated radiotherapy, younger age ( P < .001), higher body mass index (BMI; P < .001), Black ( P < .001) or other race ( P = .002), smoking status ( P < .001), larger breast volume ( P = .002), lack of chemotherapy receipt ( P = .004), receipt of boost treatment ( P < .001), and treatment at a nonteaching center predicted breast pain. Among patients receiving conventionally fractionated radiotherapy, younger age ( P < .001), higher BMI ( P = .003), Black ( P < .001) or other race ( P = .002), diabetes ( P = .001), smoking status ( P < .001), and larger breast volume ( P < .001) predicted breast pain., Conclusion: In this large observational data set, substantial differences existed according to radiotherapy dose fractionation. Race-related differences in pain existed despite controlling for multiple other factors; additional research is needed to understand what drives these differences to target potentially modifiable factors. Intensifying supportive care may be appropriate for subgroups identified as being vulnerable to greater toxicity.

Purpose: Although many studies clearly demonstrate disparities in cancer clinical trial enrollment, there is a lack of consensus on potential causes. Furthermore, virtually nothing is known about associations between patients' decision-making style and their participation in clinical trials., Methods: Women with newly diagnosed, stage 0-II breast cancer reported to the Georgia and Los Angeles County Surveillance, Epidemiology, and End Results (SEER) registries in 2013-2014 were surveyed approximately seven months after diagnosis. We investigated two primary outcome variables: (1) invitation to participate in a clinical trial, (2) participation in a clinical trial. We evaluated bivariate associations using Chi-squared tests and used multivariable logistic regression models to investigate associations between patient variables, including decision-making style, and the primary outcomes., Results: 2578 patients responded (71% response rate); 30% were > age 65, 18% were black, 18% were Latina, 29% had ≤ high school education. 10% of patients reported invitation to participate in a clinical trial; 5% reported participation in a clinical trial. After adjustment younger age, receipt of chemotherapy or radiation, disease stage, and a more rational (versus more intuitive) decision-making style were associated with a higher odds of invitation to participate. Being married was associated with a higher odds of participation; having an annual family income ≥ $40,000 was associated with a lower odds of participation., Conclusions: 10% of patients reported invitation to participate in a clinical trial, and half of these reported participation. Invitation to participate varied by age and decision-making style, and participation varied by marital status and income.

Importance: Women aged 70 years or older with hormone receptor-positive breast cancer have an excellent prognosis, but because of their age and comorbidities, they are at higher risk for treatment-related adverse events. Despite studies demonstrating the safety of omitting previously routine therapies, including sentinel lymph node biopsy (SLNB) and postlumpectomy radiotherapy, these treatments continue to be used at high rates. Physicians cite patient preference as one factor associated with overuse. However, little is known about how women view potential de-escalation of therapies., Objective: To evaluate older women's preferences for SLNB and radiotherapy in the setting of guidelines recommending them or allowing for their omission., Design, Setting, and Participants: This qualitative study was performed from October 2019 to January 2020. Midwestern women aged 70 years and older who had never received a diagnosis of breast cancer were recruited online and interviewed. Guided by an interpretive description approach, interviews were analyzed to produce a thematic description. Data analysis was performed from January to March 2020., Exposures: Participants were presented with hypothetical scenarios in which they received a diagnosis of low-risk, hormone receptor-positive breast cancer and were given treatment options in accordance with current guidelines., Main Outcomes and Measures: The interviews elicited perspectives on breast cancer treatment, including surgery, SLNB, chemotherapy, and postlumpectomy radiotherapy., Results: The median (interquartile range) age of the 30 participants was 72.0 (71.0-76.5) years. Most of the women were White (26 participants [87%]), lived in metropolitan areas (29 participants [97%]), and were college educated (20 participants [67%] had a 4-year degree or higher). Overall, women expressed the belief that age-based guidelines were appropriate on the basis of decreased recurrence risk and increased frailty in older patients. However, many participants stated that these guidelines should not apply to healthy older women with a long life expectancy. Some participants struggled to understand that the basis for treatment de-escalation in older patients is a favorable, not poor, prognosis. Women who said they would undergo SLNB (12 participants [40%]) perceived the procedure as low risk and providing peace of mind. Most participants (22 participants [73%]) expressed a preference for omitting postlumpectomy radiotherapy because of the perceived risks, lack of benefit, and inconvenience., Conclusions and Relevance: Positive reframing of the excellent prognosis driving national recommendations for de-escalation may reduce breast cancer overtreatment in older women. Strategies for reducing SLNB use will likely require education on the risks vs benefits and addressing patient preferences for peace of mind. In contrast, efforts to reduce radiotherapy use may need to address clinician or organizational factors.

Purpose: Hypofractionated radiation therapy is a less burdensome and less costly approach that is efficacious for most patients with early-stage breast cancer. Concerns about racial disparities in adoption of medical advances motivate investigation of the use of hypofractionated radiation in diverse populations. The goal of our study was to determine whether hypofractionated whole breast radiation therapy after breast-conserving surgery was being similarly used across racial groups in the state of Michigan., Methods and Materials: A prospectively collected statewide quality consortium database from 25 institutions was queried for patients with breast cancer who completed hypofractionated (HF) or conventionally fractionated whole breast radiation therapy from January 2012 to December 2018. We used patient-level multivariable modeling to evaluate associations between HF use and race, controlling for patient and facility factors, and multilevel modeling to account for patient clustering within facilities., Results: Of 9634 patients analyzed, 81% self-reported race as white, 17% as black, and 2% as Asian, similar to statewide and national distributions. In addition, 31.7% of whites were treated at teaching centers compared with 66.7% of blacks and 64.8% of Asians. In 2018, HF was used in 72.7% of whites versus 56.7% of blacks and 67.6% of Asians (P = .0411). On patient-level multivariable analysis, black and Asian races were significantly associated with a lower likelihood of HF receipt (P < .001), despite accounting for treatment year, age, laterality, body mass index, breast volume, comorbidities, stage, triple-negative status, intensity modulated radiation therapy use, teaching center treatment, and 2011 American Society for Radiation Oncology Hypofractionation Guideline eligibility. On multilevel analysis, race was no longer significantly associated with HF receipt., Conclusions: We observed that black and Asian patients receive hypofractionated whole breast radiation therapy less often than whites, despite more frequent treatment at teaching centers. Multilevel modeling eliminated this disparity, suggesting that differences in facility-specific HF use appear to have contributed. Further inquiry is needed to determine whether reduction of facility-level variation may reduce disparities in accessing HF treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: To address overuse of unnecessary practices, several surgical organizations have participated in the Choosing Wisely ® campaign and identified four breast cancer surgical procedures as unnecessary. Despite evidence demonstrating no survival benefit for all four, evidence suggests only two have been substantially de-implemented. Our objective was to understand why surgeons stop performing certain unnecessary cancer operations but not others and how best to de-implement entrenched and emerging unnecessary procedures., Methods: We sampled surgeons who treat breast cancer in a variety of practice types and geographic regions in the United States. Using a semi-structured guide, we conducted telephone interviews (n = 18) to elicit attitudes and understand practices relating to the four identified breast cancer procedures in the Choosing Wisely ® campaign. Interviews were recorded, transcribed, and anonymized. Transcripts were analyzed using inductive and deductive thematic analysis., Results: For the two procedures successfully de-implemented, surgeons described a high level of confidence in the data supporting the recommendations. In contrast, surgeons frequently described a lack of familiarity or skepticism toward the recommendation to avoid sentinel-node biopsy in women ≥ 70 years of age and the influence of other collaborating oncology providers as justification for continued use. Regarding contralateral prophylactic mastectomy, surgeons consistently agreed with the recommendation that this was unnecessary, yet reported continued utilization due to the value placed on patient autonomy and preference., Conclusions: With a growing focus on the elimination of ineffective, unproven or low value practices, it is imperative that the behavioral determinants are understood and targeted with specific interventions to decrease utilization rapidly.

Background: Whether to irradiate the tissue expander before implant exchange or to defer irradiation until after exchange in immediate, two-stage expander/implant reconstruction remains uncertain. The authors evaluated the effects of irradiation timing on complication rates and patient-reported outcomes in patients undergoing immediate expander/implant reconstruction., Methods: Immediate expander/implant reconstruction patients undergoing postmastectomy radiation therapy at 11 Mastectomy Reconstruction Outcomes Consortium sites with demographic, clinical, and complication data were analyzed. Patient-reported outcomes were assessed with BREAST-Q, Patient-Reported Outcomes Measurement Information System, and European Organisation for Research and Treatment of Cancer Breast Cancer-Specific Quality-of-Life Questionnaire surveys preoperatively and 2 years postoperatively. Survey scores and complication rates were analyzed using bivariate comparison and multivariable regressions., Results: Of 317 patients who met inclusion criteria, 237 underwent postmastectomy radiation therapy before expander/implant exchange (before-exchange cohort), and 80 did so after exchange (after-exchange cohort). Timing of radiation had no significant effect on risks of overall complications (OR, 1.25; p = 0.46), major complications (OR, 1.18; p = 0.62), or reconstructive failure (OR, 0.72; p = 0.49). Similarly, radiation timing had no significant effect on 2-year patient-reported outcomes measured by the BREAST-Q or the European Organisation for Research and Treatment of Cancer survey. Outcomes measured by the Patient-Reported Outcomes Measurement Information System showed less anxiety, fatigue, and depression in the after-exchange group. Compared with preoperative assessments, 2-year patient-reported outcomes significantly declined in both cohorts for Satisfaction with Breasts, Physical Well-Being, and Sexual Well-Being, but improved for anxiety and depression., Conclusions: Radiation timing (before or after exchange) had no significant effect on complication risks or on most patient-reported outcomes in immediate expander/implant reconstruction. Although lower levels of anxiety, depression, and fatigue were observed in the after-exchange group, these differences may not be clinically significant., Clinical Question/level of Evidence: Therapeutic, II.

Importance: The 21-gene assay recurrence score is increasingly used to personalize treatment recommendations for systemic therapy in postmenopausal women with estrogen receptor (ER)- or progesterone receptor (PR)-positive, node-positive breast cancer; however, the relevance of the 21-gene assay to radiotherapy decisions remains uncertain., Objective: To examine the association between recurrence score and locoregional recurrence (LRR) in a postmenopausal patient population treated with adjuvant chemotherapy followed by tamoxifen or tamoxifen alone., Design, Setting, and Participants: This cohort study was a retrospective analysis of the Southwest Oncology Group S8814, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy. Patients at North American clinical centers were enrolled from June 1989 to July 1995. Medical records from patients with recurrence score information were reviewed for LRR and radiotherapy use. Primary analysis included 316 patients and excluded 37 who received both mastectomy and radiotherapy, 9 who received breast-conserving surgery without documented radiotherapy, and 5 with unknown surgical type. All analyses were performed from January 22, 2016, to August 9, 2019., Main Outcomes and Measures: The LRR was defined as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes. Time to LRR was tested with log-rank tests and Cox proportional hazards regression for multivariate models., Results: The final cohort of this study comprised 316 women with a mean (range) age of 60.4 (44-81) years. Median (interquartile range) follow-up for those without LRR was 8.7 (7.0-10.2) years. Seven LRR events (5.8%) among 121 patients with low recurrence score and 27 LRR events (13.8%) among 195 patients with intermediate or high recurrence score occurred. The estimated 10-year cumulative incidence rates were 9.7% for those with a low recurrence score and 16.5% for the group with intermediate or high recurrence score (P = .02). Among patients who had a mastectomy without radiotherapy (n = 252), the differences in the 10-year actuarial LRR rates remained significant: 7.7 % for the low recurrence score group vs 16.8% for the intermediate or high recurrence score group (P = .03). A multivariable model controlling for randomized treatment, number of positive nodes, and surgical type showed that a higher recurrence score was prognostic for LRR (hazard ratio [HR], 2.36; 95% CI, 1.02-5.45; P = .04). In a subset analysis of patients with a mastectomy and 1 to 3 involved nodes who did not receive radiation therapy, the group with a low recurrence score had a 1.5% rate of LRR, whereas the group with an intermediate or high recurrence score had a 11.1% LRR (P = .051)., Conclusions and Relevance: This study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes. This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision-making.

Background: The effect of surgeon factors on patient-reported quality-of-life outcomes after breast-conserving therapy (BCT) is unknown and may help patients make informed care decisions., Methods: We performed a survey study of women aged ≥ 67 years with non-metastatic breast cancer diagnosed in 2009 and treated with guideline-concordant BCT, to determine the association of surgeon factors with patient-reported outcomes. The treating surgeon was identified using Medicare claims, and surgeon factors were identified via the American Medical Association Physician Masterfile. The primary outcome was patient-reported cosmetic satisfaction measured by the Cancer Surveillance and Outcomes Research Team (CanSORT) Satisfaction with Breast Cosmetic Outcome instrument, while secondary outcomes included BREAST-Q subdomains. All patient, treatment, and surgeon covariables were included in a saturated multivariable linear regression model with backward elimination applied until remaining variables were p < 0.1., Results: Of 1650 women randomly selected to receive the questionnaire, 489 responded, of whom 289 underwent BCT. Median age at diagnosis was 72 years and the time from diagnosis to survey was 6 years. The mean adjusted CanSORT score was higher for patients treated by surgical oncologists than patients treated by non-surgical oncologists (4.01 [95% confidence interval [CI] 3.65-4.38] vs. 3.53 [95% CI 3.28-3.77], p = 0.006). Similarly, mean adjusted BREAST-Q Physical Well-Being (91.97 [95% CI 86.13-97.80] vs. 83.04 [95% CI 80.85-85.22], p = 0.006) and Adverse Radiation Effects (95.28 [95% CI 91.25-99.31] vs. 88.90 [95% CI 86.23-91.57], p = 0.004) scores were better among patients treated by surgical oncologists., Conclusions: Specialized surgical oncology training is associated with improved long-term patient-reported outcomes. These findings underscore the value of specialized training and may be useful to patients choosing their care team.

Importance: The increasing use of germline genetic testing may have unintended consequences on treatment. Little is known about how women with pathogenic variants in cancer susceptibility genes are treated for breast cancer., Objective: To determine the association of germline genetic testing results with locoregional and systemic therapy use in women diagnosed with breast cancer., Design, Setting, and Participants: For this population-based cohort study, data from women aged 20 years or older who were diagnosed with stages 0 to III breast cancer between 2014 and 2016 were accrued from the Surveillance, Epidemiology and End Results (SEER) registries of Georgia and California. The women underwent genetic testing within 3 months after diagnosis and were reported to the Georgia and California SEER registries by December 1, 2017., Exposures: Pathogenic variant status based on linked results of clinical germline genetic testing by 4 laboratories that did most such testing in the studied regions., Main Outcomes and Measures: Potential deviation of treatment from practice guidelines was assessed in the following clinical scenarios: (1) surgery: receipt of bilateral mastectomy by women eligible for less extensive unilateral surgery (unilateral breast tumor); (2) radiotherapy: omission in women indicated for postlumpectomy radiotherapy (all lumpectomy recipients except age ≥70 with stage I, estrogen and/or progesterone receptor [ER/PR] positive, ERBB2 [formerly HER2]-negative disease); and (3) chemotherapy: receipt by women eligible to consider chemotherapy omission (stages I-II, ER/PR-positive, ERBB2-negative, and 21-gene recurrence score of 0-30, which was the upper limit of the intermediate risk range during the study years). The adjusted percentage treated and adjusted odds ratio (OR) are reported based on multivariable modeling for each treatment-eligible group., Results: A total of 20 568 women (17.3%) of 119 198 were eligible (mean [SD] age, 51.4 [12.2]). Compared with women whose test results were negative, those with BRCA1/2 pathogenic variants were more likely to receive bilateral mastectomy for a unilateral tumor (61.7% vs 24.3%; OR, 5.52, 95% CI, 4.73-6.44), less likely to receive postlumpectomy radiotherapy (50.2% vs 81.5%; OR, 0.22, 95% CI, 0.15-0.32), and more likely to receive chemotherapy for early-stage, ER/PR-positive disease (38.0% vs 30.3%; OR, 1.76, 95% CI, 1.31-2.34). Similar patterns were seen with pathogenic variants in other breast cancer-associated genes (ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, and TP53) but not with variants of uncertain significance., Conclusions and Relevance: Women with pathogenic variants in BRCA1/2 and other breast cancer-associated genes were found to have distinct patterns of breast cancer treatment; these may be less concordant with practice guidelines, particularly for radiotherapy and chemotherapy.