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Paul Ruff,1,2 Herbert Cubasch,2,3 Maureen Joffe,2,4 Evan Rosenbaum,5 Nivashni Murugan,2,3 Ming-Chih Tsai,2,3 Oluwatosin Ayeni,2 Katherine D Crew,5–7 Judith S Jacobson,6,7 Alfred I Neugut5–7 1Division of Medical Oncology, Department of Internal Medicine, University of the Witwatersrand, Faculty of Health Sciences, 2Noncommunicable Diseases Research Division, Wits Health Consortium, University of the Witwatersrand, Faculty of Health Sciences, 3Department of Surgery, Chris Hani Baragwanath Academic Hospital and University of the Witwatersrand, Faculty of Health Sciences, 4MRC Developmental Pathways of Health Research Unit, Department of Paediatrics, University of Witwatersrand, Faculty of Health Sciences, Johannesburg, South Africa; 5Department of Medicine, College of Physicians and Surgeons, Columbia University, 6Herbert Irving Comprehensive Cancer Center, Columbia University, 7Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA Background: Neoadjuvant (primary) chemotherapy (NACT) is the standard of care for locally advanced breast cancer. It also allows for the short-term assessment of chemotherapy response; a pathological complete responses correspond to improved long-term breast cancer outcomes. In sub-Saharan Africa, many patients are diagnosed with large nonresectable tumors. We examined NACT use in breast cancer patients who visited public hospitals in Johannesburg, South Africa. Methods: We assessed demographic characteristics, tumor stage and grade, hormone receptor status, and human immunodeficiency virus (HIV) status of female patients diagnosed with nonmetastatic invasive carcinoma of the breast at Chris Hani Baragwanath Academic Hospital between January 1, 2009, and December 31, 2011. The patients received neoadjuvant, adjuvant, or no chemotherapy. Trastuzumab was unavailable. We developed logistic regression models to analyze the factors associated with NACT receipt in these patients. Results: Of 554 women with nonmetastatic breast cancer, the median age at diagnosis was 52 years (range: 28–88 years). Only 5.8% of patients were diagnosed with stage I disease; 49.3% and 44.9% were diagnosed with stages II and III, respectively. Most patients had hormone-responsive tumors: luminal A, 38.1%; luminal B1 (human epidermal growth factor receptor 2 [HER2]-negative and high grade), 12.5%, and luminal B2 (HER2-positive any grade), 11.6%; 11.6% had a HER2-enriched tumor and 20.6% a triple-negative tumor. Eighty (14.4%) patients were HIV-positive. In total, 195 patients (35.2%) received NACT, 264 (47.7%) patients received adjuvant chemotherapy, and 95 patients (17.1%) received no chemotherapy, including 62 (11.2%) patients who received only hormonal therapy. Of patients receiving NACT, 125 (64.1%) were evaluable for clinical response. Eighty (64.0%) patients had a clinically significant response; 19 (15.2%) patients had a stable disease, and 26 (20.8%) patients had a progressive disease. Multivariate analysis showed age

BackgroundObservational and experimental data support a potential breast cancer chemopreventive effect of green tea.MethodsWe conducted an ancillary study using archived blood/urine from a phase IB randomised, placebo-controlled dose escalation trial of an oral green tea extract, Polyphenon E (Poly E), in breast cancer patients. Using an adaptive trial design, women with stage I-III breast cancer who completed adjuvant treatment were randomised to Poly E 400 mg (n = 16), 600 mg (n = 11) and 800 mg (n = 3) twice daily or matching placebo (n = 10) for 6 months. Blood and urine collection occurred at baseline, and at 2, 4 and 6 months. Biological endpoints included growth factor [serum hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)], lipid (serum cholesterol, triglycerides), oxidative damage and inflammatory biomarkers.ResultsFrom July 2007-August 2009, 40 women were enrolled and 34 (26 Poly E, eight placebo) were evaluable for biomarker endpoints. At 2 months, the Poly E group (all dose levels combined) compared to placebo had a significant decrease in mean serum HGF levels (-12.7% versus +6.3%, P = 0.04). This trend persisted at 4 and 6 months but was no longer statistically significant. For the Poly E group, serum VEGF decreased by 11.5% at 2 months (P = 0.02) and 13.9% at 4 months (P = 0.05) but did not differ compared to placebo. At 2 months, there was a trend toward a decrease in serum cholesterol with Poly E (P = 0.08). No significant differences were observed for other biomarkers.ConclusionsOur findings suggest potential mechanistic actions of tea polyphenols in growth factor signalling, angiogenesis and lipid metabolism.

Robust methods are needed to efficiently conduct large, multisite, randomized, controlled clinical trials of acupuncture protocols. The Southwest Oncology Group (SWOG) S1200 trial is a randomized, controlled (i.e., sham-controlled and waitlist-controlled) trial of a standardized acupuncture protocol for treating aromatase inhibitor (AI)-associated arthralgias in early-stage breast cancer patients (n=228). The primary objective of this study was to determine whether true acupuncture administered twice weekly for 6 weeks, as compared to sham acupuncture or a waitlist control, reduced AI-associated joint pain at 6 weeks as assessed by patient reports. The study was conducted at 11 institutions across the United States. The true acupuncture protocol was developed using a consensus-based process. The true acupuncture and the sham acupuncture protocols each consisted of 12 sessions administered for 6 weeks, followed by one weekly session for 6 weeks. The true acupuncture protocol used standardized protocol points, and the standardized acupoints were tailored to a patient's joint symptoms. The similarly standardized sham acupuncture protocol utilized superficial needling of nonacupoints. Standardized methods were developed to train and monitor acupuncturists and included online and in-person training, study manuals, monthly phone calls, and remote quality assurance monitoring throughout the study period. The research staff similarly received online and in-person training and monthly phone calls.

Abstract Background: Despite the well-proven efficacy of aromatase inhibitors(AIs) for the treatment of hormone-sensitive breast cancer, a significant number of women suffer from musculoskeletal side-effects which can result in early discontinuation of this important medication. Given the proposed anti-inflammatory effects of omega-3-fatty acid and the paucity of therapeutic options for AI-induced arthralgia, it is therefore reasonable to test the efficacy of omega-3-fatty acid in women with breast cancer who have developed moderate to severe joint symptoms after initiating AIs. Specific aims: To assess if omega-3-fatty acid as compared to placebo causes a reduction in worst joint pain/stiffness in women with AI-associated arthralgias at 12weeks as measured by the modified Brief Pain Inventory (BPI). Additional measures will include the WOMAC, M-SACRAH, FACT-ES and global rating of change, which will be assessed at baseline, 6, 12 and 24 weeks. We will evaluate fasting lipids, hormone levels, serum inflammatory markers (TNF, IL2, CRP), and markers of joint destruction (CTX-II) at baseline, 12 and 24 weeks. Eligibility criteria:Pts. must have histologically-confirmed stages I-III breast cancer, with no evidence of metastatic disease and undergone definitive breast cancer surgery. Pts must be post-menopausal and currently be taking a third-generation AI —anastrazole(Arimidex®), letrozole (Femara®), or exemestane (Aromasin®) for at least the previous 90 days prior to registration with plans to continue for at least an additional 180 days after registration.The patient must have a worse joint pain/stiffness score of 5 or greater on the 10-point scale of the BPI which started or increased after initiation of AI. Pts must not have taken omega-3-fatty acid supplements within the past 3 months prior to registration.Pts will be randomized to receive 6 capsules daily (at 1,000 mg each; ∼600mg combination of ethyl esters EPA/DHA) of omega-3-fattyacid or matching placebo daily for 24 weeks. Statistical methods:We stipulate an alpha=.05 two-sided test, with an estimated 5% non-adherenceand 20% dropout rate at the primary endpoint evaluation time of 12 weeks after randomization. For a two point difference in worst joint pain/stiffness and a 3.5 point SD at 12 weeks, 222 eligible patients would be required for 90% power under a two-arm normal design. To allow ineligibility rate of 10%, 246 total pts will be enrolled. The study should be activated September 2011. Funding: Supported by National Cancer Institute grant CA037429 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-07-02.

Background: While trastuzumab has been shown to improve disease-free and overall survival in patients with HER2-positive breast cancer, it may also cause trastuzumab-induced cardiotoxicity (TIC). Although racial and ethnic minorities are at higher risk for cardiovascular disease (CVD) compared to non-Hispanic Whites (NHW), limited data exists on TIC incidence in diverse multi-ethnic populations. Our objective was to assess racial and ethnic differences in TIC and left ventricular ejection fraction (LVEF) recovery among patients with HER2-positive breast cancer., Methods: We conducted a retrospective cohort study including patients diagnosed with stage I-III HER2-positive breast cancer between 2007 and 2022 who had received adjuvant trastuzumab. We analyzed associations between sociodemographic factors, tumor characteristics, treatment regimens, and CVD risk factors with the primary outcomes of TIC and LVEF recovery, using multivariable logistic regression models. TIC was defined as > 10% decrease in LVEF to an overall LVEF < 50%; LVEF recovery as a return to a LVEF > 50%., Results: Among 496 evaluable patients, median age was 53 years (IQR: 45.0-62.0) with 36.6% NHW, 15.8% non-Hispanic Black (NHB), 27.8% Hispanic, and 19.8% Other. Fifty-three (10.6%) patients developed TIC, half of whom experienced LVEF recovery. Compared to NHW, NHB had a higher rate of TIC (9.3% vs. 17.7%, respectively) and lower rate of LVEF recovery (70.6% vs. 21.4%, respectively), however, race/ethnicity was not a significant predictor of TIC after adjusting for confounders. Increasing age, lower baseline LVEF, anthracycline use, and presence of hypertension or coronary artery disease were significantly associated with TIC in multivariable analysis., Conclusions: TIC was more common among NHB compared to NHW, however, Black race was not consistently associated with TIC after adjustment for CVD risk factors. This suggests that CVD comorbidities (e.g., hypertension) that more frequently affect racial and ethnic minorities and are modifiable may explain differences in TIC incidence and recovery., (© 2024. The Author(s).)

Background: Women with high-risk breast lesions, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have a 4- to tenfold increased risk of breast cancer compared to women with non-proliferative breast disease. Despite high-quality data supporting chemoprevention, uptake remains low. Interventions are needed to break down barriers., Methods: The parent trial, MiCHOICE, is a cluster randomized controlled trial evaluating the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. For this pre-implementation analysis, 25 providers participated in semi-structured interviews prior to accessing decision support tools. Interviews sought to understand attitudes/beliefs and barriers/facilitators to chemoprevention., Results: Interviews with 25 providers (18 physicians and 7 advanced practice providers) were included. Providers were predominantly female (84%), white (72%), and non-Hispanic (88%). Nearly all providers (96%) had prescribed chemoprevention for eligible patients. Three themes emerged in qualitative analysis. The first theme describes providers' confidence in chemoprevention and the utility of decision support tools. The second theme elucidates barriers to chemoprevention, including time constraints, risk communication and perceptions of patients' fear of side effects and anxiety. The third theme is the need for early implementation of decision support tools., Conclusions: This qualitative study suggests that providers were interested in the early inclusion of decision aids (DA) in their chemoprevention discussion workflow. The DAs may help overcome certain barriers which were elucidated in these interviews, including patient level concerns about side effects, clinic time constraints and difficulty communicating risk. A multi-faceted intervention with a DA as one active component may be needed., Trial Registration: This trial was registered with the NIH clinical trial registry, clinicaltrials.gov, NCT04496739., (© 2024. The Author(s).)

Retrospective case studies are one approach to help identify processes underlying the translation of successful health interventions. This case study investigates the development of RealRisks and Breast Cancer Risk Navigation ( BNAV ), decision support tools for breast cancer risk assessment, and risk-stratified prevention. Following a recently developed protocol for retrospective translational science case studies, we examined the career trajectory of Dr Katherine Crew as she expanded from basic science to interdisciplinary, patient-oriented research in oncology and began collaboration with Dr Rita Kukafka, a public health informatician focused on communicating risk. Data collection methods included key informant interviews and examination of peer-reviewed publications, funded grants, and news articles associated with the research. Data were analyzed to identify key milestones in the development of RealRisks and BNAV and to elucidate facilitators and barriers to the translational process. Facilitators to translation included funding and infrastructure provided by a Clinical and Translational Science Award (CTSA), the creation of an interdisciplinary team, and broad support from stakeholders including patient advocacy groups. Barriers to translation included limited mid-career support, ongoing costs for technology, and the time required to establish interdisciplinary, team science efforts. The findings reported here can be used to inform ongoing efforts to develop a more robust science of translation., Competing Interests: Harold Pincus serves on the clinical advisory committee for AbleTo and is a consultant for the National Committee for Quality Assurance. The other authors have no conflicts of interest to declare., (© The Author(s) 2024.)

Background: Breast cancer is the most common malignancy diagnosed among women in South Africa, with the aggressive triple-negative subtype comprising approximately 15% of breast cancers in this population. South Africa has the largest population of people with HIV in the world. This study aims to evaluate the association between HIV status and the proportion of patients with breast cancer with the triple-negative subtype., Methods: We did a cross-sectional analysis of case-only data from the South African Breast Cancer and HIV Outcomes (SABCHO) study, a prospective cohort study recruiting patients with newly diagnosed breast cancer at six public hospitals in South Africa. We analysed data from patients who enrolled in SABCHO between Jan 1, 2015, and Jan 18, 2022. Women aged 18 years or older with newly diagnosed and histologically confirmed invasive breast cancer were eligible. Participants were classified as HIV-positive or HIV-negative by use of an ELISA-based HIV test done at the time of enrolment. We developed multivariable logistic regression models to test for an association between HIV status and the proportion of triple-negative relative to non-triple-negative breast cancers while adjusting for demographic and reproductive risk factors., Findings: Of the 4122 patients enrolled in the SABCHO cohort within our study timeframe, 239 patients were excluded due to unknown breast cancer subtype (n=141), HIV status (n=97), or race (n=1). 3883 women with breast cancer were included in the study, of whom 637 (16·4%) had triple-negative breast cancer, 894 (23·0%) were HIV-positive, and 186 (4·8%) had triple-negative breast cancer and HIV. Triple-negative breast cancer accounted for 186 (20·8%) of 894 breast cancers among women who were HIV-positive and 451 (15·1%) of 2989 breast cancers among women who were HIV-negative (p<0·0001). In the fully adjusted logistic regression model, HIV-positive status was associated with an increased proportion of triple-negative breast cancer (adjusted odds ratio [OR] 1·39, 95% CI 1·12-1·74, compared with women who were HIV-negative). When compared with women who were HIV-negative, the association between HIV-positive status and the proportion of triple-negative breast cancer was strongest among the subgroup of women with a duration of HIV infection of 2 years or longer (1·57, 1·23-2·00) and those on antiretroviral therapy (ART; 1·47, 1·16-1·87)., Interpretation: Patients with breast cancer and chronic HIV who are on ART are more likely to have triple-negative breast cancer than patients with breast cancer without HIV. This association is independent of age, race, and reproductive factors., Funding: US National Institutes of Health, University of the Witwatersrand, South Africa Medical Research Council Common Epithelial Cancers Research Center, Conquer Cancer Foundation, and Varmus Global Scholars Fund., Competing Interests: Declaration of interests AIN reports a consulting or advisory relationship with Otsuka, United Biosource Corp, Hospira, Value Analytics, Merck, Organon, and GSK; is on the Scientific Advisory Board for EHE Intl; and received research funding from Otsuka. YSP reports ownership interest in Pfizer and a consulting or advisory relationship with BMS and Janssen. PR reports clinical trial funding to their institution from Merck, Roche, Pfizer, GSK, Jansen, AstraZeneca, ImmunityBio, and Amgen. All other authors declare no competing interests., (Copyright © 2024 World Health Organization. Published by Elsevier Ltd. This is an Open Access article published under the CC BY NC ND 3.0 IGO license which permits users to download and share the article for non-commercial purposes, so long as the article is reproduced in the whole without changes, and provided the original source is properly cited. This article shall not be used or reproduced in association with the promotion of commercial products, services or any entity. There should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Deep learning-based mammographic evaluations could noninvasively assess response to breast cancer chemoprevention. We evaluated change in a convolutional neural network-based breast cancer risk model applied to mammograms among women enrolled in SWOG S0812, which randomly assigned 208 premenopausal high-risk women to receive oral vitamin D3 20 000 IU weekly or placebo for 12 months. We applied the convolutional neural network model to mammograms collected at baseline (n = 109), 12 months (n = 97), and 24 months (n = 67) and compared changes in convolutional neural network-based risk score between treatment groups. Change in convolutional neural network-based risk score was not statistically significantly different between vitamin D and placebo groups at 12 months (0.005 vs 0.002, P = .875) or at 24 months (0.020 vs 0.001, P = .563). The findings are consistent with the primary analysis of S0812, which did not demonstrate statistically significant changes in mammographic density with vitamin D supplementation compared with placebo. There is an ongoing need to evaluate biomarkers of response to novel breast cancer chemopreventive agents., (© The Author(s) 2024. Published by Oxford University Press.)

Research on polygenic risk scores (PRSs) for common, genetically complex chronic diseases aims to improve health-related predictions, tailor risk-reducing interventions, and improve health outcomes. Yet, the study and use of PRSs in clinical settings raise equity, clinical, and regulatory challenges that can be greater for individuals from historically marginalized racial, ethnic, and other minoritized communities. As part of the National Human Genome Research Institute-funded Electronic Medical Records and Genomics IV Network, we conducted online focus groups with patients/community members, clinicians, and members of institutional review boards to explore their views on key issues, including PRS research, return of PRS results, clinical translation, and barriers and facilitators to health behavioral changes in response to PRS results. Across stakeholder groups, our findings indicate support for PRS development and a strong interest in having PRS results returned to research participants. However, we also found multi-level barriers and significant differences in stakeholders' views about what is needed and possible for successful implementation. These include researcher-participant interaction formats, health and genomic literacy, and a range of structural barriers, such as financial instability, insurance coverage, and the absence of health-supporting infrastructure and affordable healthy food options in poorer neighborhoods. Our findings highlight the need to revisit and implement measures in PRS studies (e.g., incentives and resources for follow-up care), as well as system-level policies to promote equity in genomic research and health outcomes., Competing Interests: Declaration of interests M.S. is a member of the Institutional Review Board of the All of Us Research Program. Wendy Chung is on the Board of Directors for Prime Medicine and Rallybio., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)