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Purpose: This study aimed to assess whether physical functional decline in older women with early-stage breast cancer is driven by cancer, chemotherapy, or a combination of both., Methods: We prospectively sampled three groups of women aged ≥ 65: 444 with early-stage breast cancer receiving chemotherapy (BC Chemo), 98 with early-stage breast cancer not receiving chemotherapy (BC Control), and 100 non-cancer controls (NC Control). Physical function was assessed at two timepoints (T1 [baseline] and T2 [3, 4, or 6 months]) using the Physical Functioning Subscale (PF-10) of the RAND 36-item Short Form. The primary endpoint was the change in PF-10 scores from T1 to T2, analyzed continuously and dichotomously (Yes/No, with "yes" indicating a PF-10 decline > 10 points, i.e., a substantial and clinically meaningful difference)., Results: Baseline PF-10 scores were similar across all groups. The BC Chemo group experienced a significant decline at T2, with a median change in PF-10 of -5 (interquartile range [IQR], -20, 0), while BC Control and NC Control groups showed a median change of 0 (IQR, -5, 5; p < 0.001). Over 30% of BC Chemo participants had a substantial decline in PF-10 vs. 8% in the BC Control and 5% in the NC Control groups (p < 0.001)., Conclusion: In this cohort of older adults with early-stage breast cancer, the combination of breast cancer and chemotherapy contributes to accelerated functional decline. Our findings reinforce the need to develop interventions aimed at preserving physical function, particularly during and after chemotherapy., Implications for Cancer Survivors: The high prevalence of accelerated functional decline in older women undergoing breast cancer chemotherapy underscores the urgency to develop interventions aimed at preserving physical function and improving health outcomes., Clinical Trial: NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Colorectal cancer (CRC) screening utilization is low among low-income, uninsured, and minority populations that receive care in community health centers (CHCs). There is a need for evidence-based interventions to increase screening and follow-up care in these settings., Methods: A multilevel, multi-component pragmatic cluster randomized controlled trial is being conducted at 8 CHCs in two metropolitan areas (Boston and Los Angeles), with two arms: (1) Mailed FIT outreach with text reminders, and (2) Mailed FIT-DNA with patient support. We also include an additional CHC in Rapid City (South Dakota) that follows a parallel protocol for FIT-DNA but is not randomized due to lack of a comparison group. Eligible individuals in participating clinics are primary care patients ages 45-75, at average-risk for CRC, and overdue for CRC screening. Participants with abnormal screening results are offered navigation for follow-up colonoscopy and CRC risk assessment., Results: The primary outcome is the completion rate of CRC screening at 90 days. Secondary outcomes include the screening completion rate at 180 days and the rate of colonoscopy completion within 6 months among participants with an abnormal result. Additional goals are to enhance our understanding of facilitators and barriers to CRC risk assessment in CHC settings., Conclusions: This study assesses the effectiveness of two multilevel interventions to increase screening participation and follow-up after abnormal screening in under-resourced clinical settings, informing future efforts to address CRC disparities., Trial Registration: NCT05714644., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Folasade P. May: Exact Sciences: Advisory Board Sapna Syngal: inventor of the PREMM model (the intellectual property of which is owned by Dana-Farber Cancer Institute); research funding by Exact Sciences, Biological Dynamics, Inc.; consultant for Natera, Inc., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The antibody-drug conjugate (ADC) sacituzumab govitecan (SG) comprises the topoisomerase 1 (TOP1) inhibitor (TOP1i) SN-38, coupled to a monoclonal antibody targeting trophoblast cell surface antigen 2 (TROP-2). Poly(ADP-ribose) polymerase (PARP) inhibition may synergize with TOP1i and SG, but previous studies combining systemic PARP and TOP1 inhibitors failed due to dose-limiting myelosuppression. Here, we assess the proof-of-mechanism and clinical feasibility for SG and talazoparib (TZP) employing an innovative sequential dosing schedule., Patients and Methods: In vitro models tested pharmacodynamic endpoints, and in a phase 1b clinical trial (NCT04039230), 30 patients with metastatic triple-negative breast cancer (mTNBC) received SG and TZP in a concurrent (N = 7) or sequential (N = 23) schedule. Outcome measures included safety, tolerability, preliminary efficacy, and establishment of a recommended phase 2 dose., Results: We hypothesized that tumor-selective delivery of TOP1i via SG would reduce nontumor toxicity and create a temporal window, enabling sequential dosing of SG and PARP inhibition. In vitro, sequential SG followed by TZP delayed TOP1 cleavage complex clearance, increased DNA damage, and promoted apoptosis. In the clinical trial, sequential SG/TZP successfully met primary objectives and demonstrated median progression-free survival (PFS) of 7.6 months without dose-limiting toxicities (DLT), while concurrent dosing yielded 2.3 months PFS and multiple DLTs including severe myelosuppression., Conclusions: While SG dosed concurrently with TZP is not tolerated clinically due to an insufficient therapeutic window, sequential dosing of SG followed by TZP proved a viable strategy. These findings support further clinical development of the combination and suggest that ADC-based therapy may facilitate novel, mechanism-based dosing strategies., (©2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: Gastric sleeve stenosis (GSS) is an increasingly common adverse event following sleeve gastrectomy for which objective diagnostic criteria are lacking. Impedance planimetry measurements show promise in characterizing GSS, though normal and abnormal benchmark values have never been established., Methods: This was a retrospective analysis of upper endoscopies performed with impedance planimetry for suspected GSS. A bariatric endoscopist, blind to impedance planimetry measurements, assessed gastric sleeve anatomy and graded GSS severity. Impedance planimetry of diameter and distensibility index (DI) were obtained using 3 different balloon volumes (30, 40, and 50 mL)., Results: A total of 110 upper endoscopies were included. Distribution of GSS was graded as none, mild, moderate, and severe in 19 (17%), 27 (25%), 34 (31%), and 30 (27%) procedures, respectively. In normal gastric sleeve anatomy, mean (±SD) diameter and DI measurements using consecutive balloon volumes ranged from 19.1 (±5.5) to 23.2 (±1.7) and 16.8 (±4.9) to 23.1 (±10.9), respectively. In severe GSS, mean diameter and DI measurements ranged from 10.3 (±3.0) to 16.6 (±2.1) and 7.5 (±2.4) to 7.7 (±2.4), respectively. When stratified by severity, impedance planimetry measurements of diameter and DI were significantly lower with each subsequent increase in GSS grade regardless of balloon fill volumes ( P ≤ 0.001)., Discussion: Impedance planimetry measurements provide objective assessment in the diagnosis of GSS and correlate with luminal narrowing. A diameter ≥20 mm and a DI ≥15 mm 2 /mm Hg, as measured by impedance planimetry, are predictive of normal gastric sleeve anatomy. This study provides new benchmark values for the diagnosis and severity of GSS., (Copyright © 2024 by The American College of Gastroenterology.)

Background: Older women with breast cancer frequently experience toxicity-related hospitalizations during adjuvant chemotherapy. Although the geriatric assessment can identify those at risk, its use in clinic remains limited. One simple, low-cost marker of vulnerability in older persons is fall history. Here, the authors examined whether falls prechemotherapy can identify older women at risk for toxicity-related hospitalization during adjuvant chemotherapy for breast cancer., Methods: In a prospective study of women >65 years old with stage I-III breast cancer treated with adjuvant chemotherapy, the authors assessed baseline falls in the past 6 months as a categorical variable: no fall, one fall, and more than one fall. The primary end point was incident hospitalization during chemotherapy attributable to toxicity. Multivariable logistic regression was used to examine the association between falls and toxicity-related hospitalization, adjusting for sociodemographic, disease, and geriatric covariates., Results: Of the 497 participants, 60 (12.1%) reported falling before chemotherapy, and 114 (22.9%) had one or more toxicity-related hospitalizations. After adjusting for sociodemographic, disease, and geriatric characteristics, women who fell more than once within 6 months before chemotherapy had greater odds of being hospitalized from toxicity during chemotherapy compared to women who did not fall (50.0% vs. 20.8% experienced toxicity-related hospitalization, odds ratio, 4.38; 95% confidence interval, 1.66-11.54, p = .003)., Conclusions: In this cohort of older women with early breast cancer, women who experienced more than one fall before chemotherapy had an over 4-fold increased risk of toxicity-related hospitalization during chemotherapy, independent of sociodemographic, disease, and geriatric factors., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Exploration is an important feature for successfully learning motor skills. However, game rules such as one attempt to serve in volleyball could discourage exploration due to an individual's fear of making a mistake and forfeiting a point. The constraints-led approach is a coaching methodology that encourages exploration by selectively manipulating task constraints such as rules. Therefore, the aim of this study was to examine whether the addition of the task constraint of a second serve would encourage volleyball players to use their first serve to explore their action capabilities. Forty male high school students competed in two volleyball games; a regulation (single serve) game and a modified (2-serve) game. Participants reported that having a second chance at serving allowed them to feel more confident and relaxed which facilitated the exploration of their serving capability. In the 2-serve game, participants attempted a more powerful ( M  = 60.3 km/hr), and complex ( M  = 44.5% jump topspin serves) first serve, compared to the regulation game ( M  = 55.6 km/hr; M  = 25.2% jump topspin serves). Findings suggest that to facilitate learning of motor skills, it is important to manipulate the practice environment using task constraints to address the factors that restrict exploration.

Purpose: To guide clinicians and policymakers in three global resource-constrained settings on treating patients with metastatic breast cancer (MBC) when Maximal setting-guideline recommended treatment is unavailable., Methods: A multidisciplinary, multinational panel reviewed existing ASCO guidelines and conducted modified ADAPTE and formal consensus processes., Results: Four published resource-agnostic guidelines were adapted for resource-constrained settings; informing two rounds of formal consensus; recommendations received ≥75% agreement., Recommendations: Clinicians should recommend treatment according to menopausal status, pathological and biomarker features when quality results are available. In first-line, for hormone receptor (HR)-positive MBC, when a non-steroidal aromatase inhibitor and CDK 4/6 inhibitor combination is unavailable, use hormonal therapy alone. For life-threatening disease, use single-agent chemotherapy or surgery for local control. For premenopausal patients, use ovarian suppression or ablation plus hormone therapy in Basic settings. For human epidermal growth factor receptor 2 (HER2)-positive MBC, if trastuzumab, pertuzumab, and chemotherapy are unavailable, use trastuzumab and chemotherapy; if unavailable, use chemotherapy. For HER2-positive, HR-positive MBC, use standard first-line therapy, or endocrine therapy if contraindications. For triple-negative MBC with unknown PD-L1 status, or if PD-L1-positive and immunotherapy unavailable, use single-agent chemotherapy. For germline BRCA1 / 2 mutation-positive MBC, if poly(ADP-ribose) polymerase inhibitor is unavailable, use hormonal therapy (HR-positive MBC) and chemotherapy (HR-negative MBC). In second-line, for HR-positive MBC, Enhanced setting recommendations depend on prior treatment; for Limited, use tamoxifen or chemotherapy. For HER2-positive MBC, if trastuzumab deruxtecan is unavailable, use trastuzumab emtansine; if unavailable, capecitabine and lapatinib; if unavailable, trastuzumab and/or chemotherapy (hormonal therapy alone for HR-positive MBC).Additional information is available at www.asco.org/resource-stratified-guidelines. It is ASCO's view that healthcare providers and system decision-makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Purpose: There is a demand for improved care delivery surrounding genomic testing and clinical trial enrollment among patients with metastatic breast cancer (MBC). We sought to improve the current process via real-time informal consultation and prescreening assessment for patients with MBC treated by community and academic medical oncologists by implementing a virtual molecular and precision medicine (vMAP) clinic., Methods: The vMAP program used a virtual referral system directed to a multidisciplinary team with precision medicine expertise. Providers contacted vMAP regarding patients with MBC, and on receipt of referral, the vMAP team engaged in discussion to identify if further diagnostics were needed (including genomic testing) and to identify potential clinical trials or standard treatment options. Recommendations were then sent to the referring provider within 72 hours. Pre-/postsurveys were issued to network physicians to assess for barriers, clinical trial access, and vMAP referral experience. Program implementation was evaluated with the Squire 2.0 reporting guidelines for quality improvement in health care as a framework., Results: Eighty-one cases from 22 providers were referred to vMAP over a 26-month period. The average response time to the referring provider with a finalized recommendation was 1.90 ± 1.82 days. A total of 86.4% of cases had clinical trial options on vMAP prescreen, with 40.7% initiating formal screening assessments and 27 patients (33.3%) ultimately enrolling on trials. On resurvey, 92% of survey responses across community oncology referring providers said that they were very likely to use vMAP again., Conclusion: In the initial 2-year period, vMAP demonstrated an efficient means to offer real-time interpretation of genomic testing and identification of clinical trials for patients with MBC, with effective clinical trial enrollment and high rates of referring provider satisfaction.

Breast cancer remains a leading cause of cancer-related death in women despite screening and therapeutic advances. Early detection allows for resection of local disease; however, patients can develop metastatic recurrences years after curative treatment. There is no reliable blood-based monitoring after curative therapy, and radiographic evaluation for metastatic disease is performed only in response to symptoms. Advances in circulating tumor DNA (ctDNA) assays have allowed for a potential option for blood-based monitoring. The detection of ctDNA in the absence of overt metastasis or recurrent disease indicates molecular evidence of cancer, defined as molecular residual disease (MRD). Multiple studies have shown that MRD detection is strongly associated with disease recurrence, with a lead time prior to clinical evidence of recurrence of many months. Importantly, it is still unclear whether treatment changes in response to ctDNA detection will improve outcomes. There are currently ongoing trials evaluating the efficacy of therapy escalation in the setting of MRD, and these studies are being conducted in all major breast cancer subtypes. Additional therapies under study include CDK4/6 inhibitors, PARP inhibitors, HER2-targeted therapies, and immunotherapy. This review will summarize the underlying scientific principles of various MRD assays, their known prognostic roles in early breast cancer, and the ongoing clinical trials assessing the efficacy of therapy escalation in the setting of MRD., (©2023 American Association for Cancer Research.)

The assessment of plasma for circulating tumor DNA (ctDNA) via liquid biopsy has revolutionized our understanding of breast cancer pathogenesis and evolution. Historically, genotyping evaluation of breast cancer required invasive tissue biopsy, limiting potential for serial evaluation over the treatment course of advanced breast cancer, and not allowing for assessment for residual disease in early breast cancer after resection. However, technological advances over the years have led to an increase in the clinical use of ctDNA as a liquid biopsy for genotype-matched therapy selection and monitoring for patients undergoing treatment for advanced breast cancer. Furthermore, increasingly sensitive assays are being developed to facilitate detection of molecular evidence of residual or recurrent disease in localized breast cancer after definitive therapy. In this review, we discuss the current and future applications of ctDNA in breast cancer. Rational applications of ctDNA offer the potential to further refine patient-centered care and personalize treatment based on molecularly defined risk assessments for patients with breast cancer., Competing Interests: Disclosure Dr. Medford has consulted for Guardant Health, Illumina and Natera. Dr. Parsons has advised for Caris, Illumina, and SAGA. Institutional research funding has been provided by Puma Biotechnology. Dr. Bardia has consulted for Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics/Gilead, Sanofi, Daiichi Pharma/Astra Zeneca, Phillips, Eli Lilly, and Foundation Medicine. Contracted research/grant to the institution has been provided by Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/Astra Zeneca, and Eli Lilly., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Patients with breast cancer (BC) face complex medical information and decisions. The Outcomes4Me mobile app provides evidence-based BC education, symptom management tracking and clinical trial matching. This study sought to evaluate the feasibility of introducing this app into routine BC care., Methods: In this pilot study among BC patients undergoing therapy at an academic cancer center, patients were followed for 12 weeks with survey administration and electronic health record (EHR) abstraction at baseline and completion. Feasibility was defined as 40% of patients engaging with the app 3 or more times during the study. Additional endpoints included app usability (system usability scale), patient care experience, symptom evaluation, and clinical trial matching., Results: The study enrolled 107 patients from 6/01/2020 to 3/31/2021. Utilization of the app was deemed feasible with 60% of patients engaging with the app at least 3 times. SUS score of 70 indicated above average usability. New diagnosis and higher education level was associated with greater app engagement, with usability similar across all age groups. 41% of patients found the app helped track symptoms. Cognitive and sexual symptoms were infrequently reported, but were more frequently captured in the app than in the EHR. After using the app, 33% of patients reported increased interest in clinical trial enrollment., Conclusion: Introducing the Outcomes4Me patient navigation app into routine BC care is feasible and may improve the patient experience. These results support further evaluation of this mobile technology platform to improve BC education, symptom management, and decision making., Clinical Trial Registry: Clinicaltrials.gov registration #: NCT04262518., (© 2023. The Author(s).)

Background: ExteNET showed that neratinib, an irreversible pan-HER tyrosine kinase inhibitor, given for 1 year after trastuzumab-based therapy significantly improved invasive disease-free survival in women with early-stage HER2-positive breast cancer. We report the final analysis of overall survival in ExteNET., Methods: In this international, randomised, double-blind, placebo-controlled, phase 3 trial, women aged 18 years or older with stage 1-3c (amended to stage 2-3c) HER2-positive breast cancer who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab were eligible. Patients were randomly assigned to oral neratinib 240 mg/day or placebo for 1 year. Randomisation was stratified according to hormone receptor (HR) status (HR-positive vs. HR-negative), nodal status (0, 1-3 or 4+), and trastuzumab regimen (sequentially vs. concurrently with chemotherapy). Overall survival was analysed by intention to treat. ExteNET is registered (Clinicaltrials.gov: NCT00878709) and is complete., Results: Between July 9, 2009, and October 24, 2011, 2840 women received neratinib (n = 1420) or placebo (n = 1420). After a median follow-up of 8.1 (IQR, 7.0-8.8) years, 127 patients (8.9%) in the neratinib group and 137 patients (9.6%) in the placebo group in the intention-to-treat population had died. Eight-year overall survival rates were 90.1% (95% CI 88.3-91.6) with neratinib and 90.2% (95% CI 88.4-91.7) with placebo (stratified hazard ratio 0.95; 95% CI 0.75-1.21; p = 0.6914)., Conclusions: Overall survival in the extended adjuvant setting was comparable for neratinib and placebo after a median follow-up of 8.1 years in women with early-stage HER2-positive breast cancer., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SD declares institutional grants from Puma Biotechnology Inc. during the conduct of the study, institutional grants from Pfizer, Novartis, AstraZeneca, RocheGenentech, Lilly, Myriad, Orion, Amgen, Sanofi, Genomic Health, GE, Servier, MSD, Bristol Myers Squibb, Pierre Fabre, Seagen, Exact Sciences, Rappta, Besins, European Commission, French Government, Fondation ARC, Taiho, and Elsan, and non-financial support from Pfizer, AstraZeneca, and RocheGenentech outside the submitted work. BE is a Medical Director of the Danish Breast Cancer Group, and has received a personal grant from the Danish Cancer Society, and institutional grants from Samsung Bioepis, MSD, Pfizer, and AstraZeneca. HI declares institutional grants from Chugai, Eli Lilly, Nihon Kayaku, Daiichi Sankyo, AstraZeneca, Taiho, Pfizer, MSD, Sanofi, Novartis, Bayer, and Boehringer Ingelheim, personal consulting fees from Chugai, Kyowa Hakko Kirin, AstraZeneca, Eli Lilly, Pfizer, and Daiichi Sankyo, and personal payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chugai, AstraZeneca, Eli Lilly, Pfizer, Taiho, Daiichi Sankyo, Eisai, and Kyowa Kirin. MG has received consulting fees from Lifebrain, Daiichi Sankyo, AstraZeneca, Eli Lilly, Veracyte, Novartis, and MSD, payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from AstraZeneca, Eli Lilly, and Pierre Fabre, support for attending meetings and/or travel from Eli Lilly, and declares that his spouse is employed by Sandoz. MB is a stockholder of the International Drug Development Institute. CHB declares support from Puma Biotechnology for work completed for the present manuscript, institutional grants or contracts from Abbvie, Nektar, Pfizer, Polyphor, Amgen, Daiichi Sankyo, Sanofi, Exelixis, Regeneron, Novartis, Henlius, Shanghai, GSK, Janssen, OBI Pharma, Lilly, Seagen, Checkpoint Therapeutics, Roche, BMS, MSD, Merck Serono, AstraZeneca, Novocure, Aveo Oncology, Takeda, TRIO, PharmaMar, Celgene, Myovant, PPD, Syneos Health, Docs, Labcorp, ICON, IQVIA, Parexel, Nuvisan, PSI, and Medpace, advisory board or consulting fees from Boehringer Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi, and Daiichi Sankyo, payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Boehringer Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi, and Daiichi Sankyo, support for attending meetings and/or travel from Daiichi Sankyo, participation on a Data Safety Monitoring Board or Advisory Board for Roche/Genentech, and is a member of the BIG Executive Board. TS received payments for lectures, presentations and educational events from Novartis, Pfizer, Eli Lilly, Roche, Amgen, Sandoz, Abbot, and AstraZeneca, support for attending symposia from Novartis, Pfizer, and Roche, and received drugs for patient treatment through market access programmes from Novartis, Pfizer, and Puma Biotechnology Inc. RŠ received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Pfizer, Novartis, Roche, and Astellas, and support for attending meetings and/or travel from Novartis and Roche. AGZ reports an institutional grant from Pfizer, consulting fees from AstraZeneca, Pierre Fabre, Novartis, Exact Sciences, and Lilly, payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Novartis, Pfizer, AstraZeneca, and Exact Sciences, support for attending meetings and/or travel from Novartis, Pfizer, and Lilly, and a leadership or fiduciary role in GEICAM. ND declares support for the present manuscript, grants or contracts from the US Oncology Network, support for attending meetings and/or travel for a Seattle Genetics advisory board, participation on a Data Safety Monitoring Board or Advisory Board for Alliance, leadership or fiduciary role at the Arlington Free Clinic, and stock or stock options with AstraZeneca (employee currently). DP declares a leadership or fiduciary role on the Board of Directors, Community Oncology Alliance. EG has received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from BMS, Pfizer, Roche, Novartis, AstraZeneca, Janssen, Amgen, Gilead, Lilly, Astellas, and GEN Ilac Ve Saglik Urunleri Sanayi Ve Ticaret, payment for expert testimony from BMS, Pfizer, Roche, Novartis, AstraZeneca, Amgen, Gilead, and Lilly, support for attending meetings and/or travel from BMS, Roche, Pfizer, Astellas, and Abdi Ibrahim, participation on a Data Safety Monitoring Board or Advisory Board for BMS, Pfizer, Roche, Novartis, AstraZeneca, Janssen, Amgen, Gilead, Lilly, and Astellas. IG declares funding for the trial, provision of study drug and manuscript support from Puma Biotechnology Inc., clinical trial support from Pfizer and AstraZeneca, and stock or stock options for Pfizer and Merck. SL declares institutional grants or contracts from Abbvie, AstraZeneca, Celgene, Daiichi Sankyo, Gilead, Novartis, Pfizer, and Roche, royalties or licenses paid to institution from VM Scope GmbH, payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events paid to institution from AstraZeneca, Daiichi Sankyo, Gilead, Novartis, Pfizer, and Roche, patents pending and issued paid to institution (EP14153692.0, EP21152186.9, EP15702464.7, EP19808852.8), participation on Data Safety Monitoring Boards or Advisory Boards paid to institution for Abbvie, Amgen, AstraZeneca, BMS, Celgene, Daiichi Sankyo, Eirgenix, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, and Seagen, and medical writing (non-financial) for Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, and Seagen. NM declares grants or contracts from Chugai, Eli Lilly, Astra Zeneca, Pfizer, Daiichi Sankyo, MSD, Eisai, Novartis, Sanofi, Kyowa-Kirin, and Nippon-Kayaku, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Chugai, Pfizer, AstraZeneca, Eli Lilly, and Eisai, and is a representative director (unpaid) of JBCRG (Japan Breast Cancer Research Group). KP has received consulting fees from Eli Lilly, Pfizer, Novartis, Pierre Fabre, AstraZeneca, and MSD, payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Eli Lilly, MSD, Novartis, Pfizer, and AstraZeneca, and support for attending meetings and/or travel from Gilead. DDP is a full-time employee at Puma Biotechnology Inc., and has ownership interest (stock, stock options) in Puma Biotechnology Inc. AW is a full-time employee at Puma Biotechnology Inc., and has ownership interest (stock, stock options) in Puma Biotechnology Inc. MM declares an institutional grant from Puma Biotechnology Inc. for work completed for the present manuscript, consulting fees from Roche, Novartis, AstraZeneca, Daiichi Sankyo, Seagen, Lilly, and Sanofi, payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Seagen, Lilly, AstraZeneca, Pfizer, Daiichi Sankyo, and Roche, and that he is Chairman of GEICAM, and Member of Board of Directors of TRIO. All remaining authors have declared no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: For patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), first-line treatment is endocrine therapy (ET) plus cyclin-dependent kinase 4/6 inhibition (CDK4/6i). After disease progression, which often comes with ESR1 resistance mutations (ESR1-MUT), which therapies to use next and for which patients are open questions. An active area of exploration is treatment with further CDK4/6i, particularly abemaciclib, which has distinct pharmacokinetic and pharmacodynamic properties compared with the other approved CDK4/6 inhibitors, palbociclib and ribociclib. We investigated a gene panel to prognosticate abemaciclib susceptibility in patients with ESR1-MUT MBC after palbociclib progression., Methods: We examined a multicenter retrospective cohort of patients with ESR1-MUT MBC who received abemaciclib after disease progression on ET plus palbociclib. We generated a panel of CDK4/6i resistance genes and compared abemaciclib progression-free survival (PFS) in patients without versus with mutations in this panel (CDKi-R[-] v CDKi-R[+]). We studied how ESR1-MUT and CDKi-R mutations affect abemaciclib sensitivity of immortalized breast cancer cells and patient-derived circulating tumor cell lines in culture., Results: In ESR1-MUT MBC with disease progression on ET plus palbociclib, the median PFS was 7.0 months for CDKi-R(-) (n = 17) versus 3.5 months for CDKi-R(+) (n = 11), with a hazard ratio of 2.8 ( P = .03). In vitro, CDKi-R alterations but not ESR1-MUT induced abemaciclib resistance in immortalized breast cancer cells and were associated with resistance in circulating tumor cells., Conclusion: For ESR1-MUT MBC with resistance to ET and palbociclib, PFS on abemaciclib is longer for patients with CDKi-R(-) than CDKi-R(+). Although a small and retrospective data set, this is the first demonstration of a genomic panel associated with abemaciclib sensitivity in the postpalbociclib setting. Future directions include testing and improving this panel in additional data sets, to guide therapy selection for patients with HR+/HER2- MBC.

We compared cell-free DNA (cfDNA) results at MBC diagnosis in patients who developed brain metastases (BM) vs those without (non-BM) to understand genomic predictors of BM. Patients with cfDNA testing at MBC diagnosis (Guardant360®, 73 gene next generation sequencing) were identified. Clinical and genomic features of BM and non-BM were compared (Pearson's/Wilcoxon rank sum tests). Eighteen of 86 patients (21%) with cfDNA at MBC diagnosis developed BM. Comparing BM vs non-BM, a higher prevalence of BRCA2 (22% vs 4.4%, p = 0.01), APC (11% vs 0%, p = 0.005), CDKN2A (11% vs 1.5%, p = 0.05), and SMAD4 (11% vs 1.5%, p = 0.05) was observed. Seven of 18 BM had ≥1 of the following 4 mutations in baseline cfDNA: APC, BRCA2, CDKN2A or SMAD4 vs 5/68 non-BM (p = 0.001). Absence of this genomic pattern had a high negative predictive value (85%) and specificity (93%) in excluding BM development. Baseline genomic profile varies in MBC that develops BM., (© 2023. The Author(s).)

Background: We aimed to report on long-term outcomes of patients with small, node-negative, HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab and to establish potential biomarkers to predict prognosis., Methods: In this open-label, single-arm, phase 2 study, patients aged 18 years or older, with small (≤3 cm), node-negative, HER2-positive breast cancer, and an Eastern Cooperative Oncology Group performance status of 0-1, were recruited from 16 institutions in 13 cities in the USA. Eligible patients were given intravenous paclitaxel (80 mg/m 2 ) with intravenous trastuzumab (loading dose of 4 mg/kg, subsequent doses 2 mg/kg) weekly for 12 weeks, followed by trastuzumab (weekly at 2 mg/kg or once every 3 weeks at 6 mg/kg) for 40 weeks to complete a full year of trastuzumab. The primary endpoint was 3-year invasive disease-free survival. Here, we report 10-year survival outcomes, assessed in all participants who received protocol-defined treatment, with exploratory analyses using the HER2DX genomic tool. This study is registered on ClinicalTrials.gov, NCT00542451, and is closed to accrual., Findings: Between Oct 29, 2007, and Sept 3, 2010, 410 patients were enrolled and 406 were given adjuvant paclitaxel and trastuzumab and included in the analysis. Mean age at enrolment was 55 years (SD 10·5), 405 (99·8%) of 406 patients were female and one (0·2%) was male, 350 (86·2%) were White, 28 (6·9%) were Black or African American, and 272 (67·0%) had hormone receptor-positive disease. After a median follow-up of 10·8 years (IQR 7·1-11·4), among 406 patients included in the analysis population, we observed 31 invasive disease-free survival events, of which six (19·4%) were locoregional ipsilateral recurrences, nine (29·0%) were new contralateral breast cancers, six (19·4%) were distant recurrences, and ten (32·3%) were all-cause deaths. 10-year invasive disease-free survival was 91·3% (95% CI 88·3-94·4), 10-year recurrence-free interval was 96·3% (95% CI 94·3-98·3), 10-year overall survival was 94·3% (95% CI 91·8-96·8), and 10-year breast cancer-specific survival was 98·8% (95% CI 97·6-100). HER2DX risk score as a continuous variable was significantly associated with invasive disease-free survival (hazard ratio [HR] per 10-unit increment 1·24 [95% CI 1·00-1·52]; p=0·047) and recurrence-free interval (1·45 [1·09-1·93]; p=0·011)., Interpretation: Adjuvant paclitaxel and trastuzumab is a reasonable treatment standard for patients with small, node-negative, HER2-positive breast cancer. The HER2DX genomic tool might help to refine the prognosis for this population., Funding: Genentech., Competing Interests: Declaration of interests SMT has received grant support (paid to institution) from AstraZeneca, Merck, Nektar, Novartis, Pfizer, Genentech (Roche), Gilead, Exelixis, BMS, Eisai, NanoString, Cyclacel, Sanofi, Seagen, and Eli Lilly; and has received consulting or advisory board fees (paid to self) from AstraZeneca, Eli Lilly, Merck, Novartis, Pfizer, Genentech (Roche), Gilead, BMS, Eisai, Sanofi, SeaGen, Daiichi-Sankyo, Athenex, OncoPep, Kyowa Kirin Pharma, CytomX, Certara, Mersana Therapeutics, Ellipses Pharma, 4D Pharma, OncoSec, Infinity Therapeutics, BeyondSpring Pharma, OncXerna, Zymeworks, Zentalis, ARC Therapeutics, Reveal Genomics, Blueprint Medicines, Myovant, Umoja Biopharma, Stemline (Menarini), and Artios Biopharma. PT has received consulting or advisory board fees from AstraZeneca, Daiichi-Sankyo, and Lilly and has received payment or honoraria for educational events from AstraZeneca and Daiichi-Sankyo. NT has received honoraria for a Clinical Research Workshop at the San Antonio Breast Cancer Symposium. LP is an employee of Reveal Genomics and has a patent (EP 20 382 679.7—in vitro method for the prognosis of patients suffering from HER2-positive breast cancer). GV has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from MSD, GSK, Pierre Fabre, and Pfizer and has participated on a data safety monitoring board or advisory board for AstraZeneca. CTD has received research funding from Genentech (Roche) and Puma and has received consulting fees from Daiichi-Sankyo, Novartis, Pfizer, Gilead, Seagen, and Genentech (Roche). DAY has received funding (paid to institution) for the present manuscript from Dana-Farber Cancer Institute; grant support (paid to institution) from Ambrx, Amgen, BIOMARIN, Biothera Pharmaceuticals, Clovis Pharma, Dana-Farber Cancer Institute, Lilly, Genentech (Roche), G1 Therapeutics, Gilead Sciences, Incyte, Innocrin Pharmaceuticals, Macrogenics, MedImmune, Medivation, Merck, Merrimack Pharmaceuticals, Nektar Therapeutics, Novartis, the National Surgical Adjuvant Breast and Bowel Project, Pfizer, and Polyphor; and has received consulting fees (paid to institution) from AstraZeneca, Athenex, bioTheranostics, G1 Therapeutics, Gilead Sciences, Immunomedics, Merck, Novartis, Pfizer, and Sanofi-Aventis. PKM has received support (paid to institution) for the present manuscript from Genentech; has participated on a data safety monitoring board for Genentech (Roche); has stock or stock options in Veracyte; and was a full-time employee of Veracyte at time of manuscript submission. KSA has received funding (paid to institution) for the present manuscript from Dana-Farber Cancer Institute for data management support. HSR has received grant funding (paid to UC Regents only) from Ambrx, Astellas Pharma, AstraZeneca, Daiichi-Sankyo, Genentech (Roche), Gilead Sciences, GSK, Lilly, Merck & Co, Novartis Pharmaceuticals, OBI Pharma, Pfizer, Pionyr Immunotherapeutics, Seattle Genetics, Sermonix Pharmaceuticals, Taiho Oncology, and Veru; has received consulting fees from Puma, Napo Pharmaceuticals, and Blueprint; and has received support for attending meetings and travel from Merck, AstraZeneca, and Gilead. MJE has reported a PAM50 Bioinformatics for Prosigna royalty-bearing license to Veracyte; and and has been an employee of AstraZeneca since March 7, 2022 (AstraZeneca had no role in this study and the author's involvement in this study preceded his employment with AstraZeneca). LAC has received research funding (paid to institution) from Syndax, Novartis, NanoString Technologies, Seattle Genetics, Veracyte, and AstraZeneca and declares participation in uncompensated consulting activities for Eisai (to self), Sanofi (to self), Lilly (to self), Seagen (to self), Novartis (to institution), G1 Therapeutics (to institution), Genentech (Roche; to institution), GSK (to institution), AstraZeneca (to institution), and Daiichi-Sankyo (to institution). RBS has received consulting fees from AstraZeneca, Libbs, Daiichi-Sankyo, Eli Lilly, Pfizer, Novartis, MSD, and Roche; has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or education events from AstraZeneca, Libbs, Daiichi-Sankyo, Eli Lilly, Pfizer, Novartis, MSD, and Roche; has received support for attending meetings and travel from Daiichi-Sankyo, Eli Lilly, MSD, and Roche; has participated on a data safety monitoring board or advisory board for AstraZeneca, Daiichi-Sankyo, and Roche; and is a member of the Clinical Research Committee of the Brazilian Society of Clinical Oncology. JGTZ has stock or stock options in Loncar Cancer Immunotherapy ETF, iShares Genomics Immunology and Healthcare ETF, iShares Biotechnology ETF, SPDR S&P Biotech ETF, Adaptive Biotechnologies, 2seventy bio, and bluebird bio. NW has received grant support from AstraZeneca; has received consulting fees from Relay Therapeutics, Flare Therapeutics, Eli Lilly, and Section 32; has received payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Genentech; and has stock or stock options in Relay Therapeutics and Flare Therapeutics. AHP has received royalties from UpToDate. AGW has received grant support (paid to institution) from Macrogenics, Genentech, and Merck and has received consulting fees (paid to self) from AstraZeneca. CAH is Chief Executive Officer at the American Society of Clinical Oncology, which pays 100% of the author's personal annual earned income. IEK has received support for the present manuscript from Genentech (Roche); has received grant support from Macrogenics and Pfizer; has received consulting fees from Daiichi-Sankyo, Macrogenics, Roche, Seagen, and AstraZeneca; and has participated on a data safety monitoring board or advisory board for Novartis, Merck, Daiichi-Sankyo, Macrogenics, Roche, Seagen, and AstraZeneca. AP has received funding for the present manuscript from Reveal Genomics; has received grants (paid to institution) from Roche, Daiichi-Sankyo, and Reveal Genomics; has received royalties or licenses from Reveal Genomics (paid to institution); has received consulting fees (paid to self) from Roche, Novartis, Daiicki-Sankyo, and AstraZeneca; has patents licensed to Reveal Genomics: HER2DX, ERBB2, and DNADX genomic tools; and has stock or stock options in Reveal Genomics and Oncolytics Biotech. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options.

Background: Most metastatic recurrences of triple negative breast cancer (TNBC) occur within five years of diagnosis, yet late relapses of TNBC (lrTNBC) do occur. Our objective was to develop a risk prediction model of lrTNBC using readily available clinicopathologic and sociodemographic features., Methods: We included patients diagnosed with stage I-III TNBC between 1998 and 2012 at ten academic cancer centers. lrTNBC was defined as relapse or mortality greater than 5 years from diagnosis. Features associated with lrTNBC were included in a multivariable logistic model using backward elimination with a p < 0.10 criterion, with a final multivariable model applied to training (70%) and independent validation (30%) cohorts., Results: A total 2210 TNBC patients with at least five years follow-up and no relapse before 5 years were included. In final multivariable model, lrTNBC was significantly associated with higher stage at diagnosis (adjusted Odds Ratio [aOR] for stage III vs I, 10.9; 95% Confidence Interval [CI], 7.5-15.9; p < 0.0001) and BMI (aOR for obese vs normal weight, 1.4; 95% CI, 1.0-1.8; p = 0.03). Final model performance was consistent between training (70%) and validation (30%) cohorts., Conclusions: A risk prediction model incorporating stage, BMI, and age at diagnosis offers potential utility for identification of patients at risk of development of lrTNBC and warrants further investigation., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The single-arm phase II APT trial established trastuzumab and paclitaxel (TH) as the standard adjuvant regimen for small human epidermal growth factor receptor 2 (HER2+) tumors. However, paclitaxel causes alopecia and has high rates of neuropathy and hypersensitivity reactions. In patients with metastatic HER2+ breast cancer (BC), the combination of trastuzumab and vinorelbine (TV) is effective and well tolerated. There is a need for alternative non-anthracycline/taxane-based regimens for patients with HER2+ early-stage BC, especially for those with contraindications or who wish to avoid side effects of taxane-based regimens. Here we describe our institutional experience with adjuvant TV for patients with early-stage HER2+ BC., Methods: Clinicopathological characteristics, treatment details, and outcomes of patients with localized HER2+ BC treated with adjuvant TV from 2007 to 2021 at a large academic medical institution were collected. Study endpoints included invasive disease-free survival (IDFS), overall survival (OS), and safety/tolerability. IDFS and OS were measured from start date of TV treatment to date of event/last follow-up and date of death/last follow-up, respectively., Results: A total of 30 patients were treated with TV. All patients received trastuzumab at standard dosing and vinorelbine at a starting dose of 25 mg/m 2 either on days 1/8 or on days 1/8/21 (weekly) of a 21-day cycle with four planned cycles. Median age at diagnosis was 59 years (range: 36-81). 90.3% of patients had anatomic pathologic stage IA BC and 9.7% stage IIA BC. Of the 30 patients, 24 of them opted to pursue TV due to concerns related to alopecia, neuropathy, and other toxicities, and 6 switched from treatment with TH to TV due to toxicities. Eight patients experienced neutropenia with no cases of febrile neutropenia. No patients experienced alopecia or long-term neuropathy. With a median follow-up of 68 months (5.7 years), the 5-year IDFS rate was 90.9%, with one local and one distant recurrence. The 5-year OS was 100%., Conclusions: Trastuzumab in combination with vinorelbine in the adjuvant, early-stage setting for low-risk HER2+ BC demonstrated clinical efficacy and appeared to be well tolerated. TV warrants further evaluation as an alternative regimen to TH for patients with early-stage HER2+ BC., Competing Interests: Shannon MacLaughlin: No COI Erika Nakajima: No COI Yael Bar: No COI Jennifer Hutchinson: Advisory board participant for Novartis Jennifer Shin: No COI Beverly Moy: No COI Steven J. Isakoff: SJI declares the following relationships: institutional research funding from Genentech, PharmaMar, Abbvie, OncoPep, Merck, and AstraZeneca/MedImmune Aditya Bardia: AB declares the following relationships: Consultant/advisory board: Genentech/Roche, Immunomedics, Novartis, Pfizer, Merck, Radius Health, Spectrum Pharma, Taiho Pharm, Diiachi, Sanofi, Puma Biotechnology; Research Grant (self): Biothernostics; Research Grant (Institution): Genentech/Roche, Immunomedics, Novartis, Pfizer, Merck, Radius Health, Sanofi, Mersana AB is supported by Department of Defense Breast Cancer grant and National Comprehensive Cancer Network grant. Irene Kuter: No COI Laura M. Spring: LMS has served as a compensated consultant or received honoraria from Novartis, Puma Biotechnology, G1 Therapeutics, Daiichi Sankyo, AstraZeneca; institutional research support from Merck, Gilead, Lilly, and Phillips Dr. Spring is supported by the National Cancer Institute (grant number K12CA087723) and a National Comprehensive Cancer Network grant., (© The Author(s), 2023.)

Purpose: Older women with high-risk early breast cancer (EBC) benefit from adjuvant chemotherapy, but their treatment is frequently complicated by toxic side effects, resulting in dose reductions and delays. This makes it challenging for oncologists to maintain a relative dose intensity (RDI) ≥ 85%, as recommended for optimal curative-intent treatment. Understanding which women are at risk of receiving suboptimal RDI may inform treatment discussions and guide early, targeted supportive care or geriatric comanagement interventions., Methods: This was a prespecified secondary analysis of the HOPE trial, which enrolled women age ≥ 65 years with EBC initiating neoadjuvant or adjuvant chemotherapy. RDI was calculated as the ratio of delivered to planned chemotherapy dose intensity. The primary outcome was low RDI, defined as RDI < 85%. Multivariable logistic regression with stepwise selection was used to evaluate the association between baseline variables (demographic, clinical, and geriatric assessment) and low RDI. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used to compare overall survival., Results: Three hundred twenty-two patients (median age at diagnosis, 70 years; range, 65-86 years) were included. The median follow-up was 4 years. Sixty-six patients (21%) had a low RDI. Age ≥ 76 years (odds ratio [OR], 2.57; 95% CI, 1.12 to 5.91; P = .03), lower performance status (OR, 4.32; 95% CI, 1.98 to 9.42; P < .001), and use of anthracycline-based or cyclophosphamide, methotrexate, and fluorouracil regimens (OR, 3.47; 95% CI, 1.71 to 7.05; P < .001) were associated with low RDI. The 5-year overall survival probability was 0.80 versus 0.91 in patients with RDI < 85 versus ≥ 85%, respectively (log-rank P = .02)., Conclusion: One in five older patients with EBC treated with standard chemotherapy received low RDI and had inferior survival outcomes. Older patients at risk for low RDI should be identified and targeted upfront before initiating chemotherapy.

Introduction: Cancer clinical trials represent the "gold standard" for advancing novel cancer therapies. Optimizing trial participation is critical to ensuring the generalizability of findings across patients, yet trial enrollment rates, particularly among minority and socioeconomically disadvantaged populations, remain suboptimal., Methods: We conducted in-depth interviews with oncologists at a large academic medical center to explore their (1) attitudes and perceived barriers to offering clinical trials to minority and socioeconomically disadvantaged patients, and (2) recommendations for improving the enrollment of minority and socioeconomically disadvantaged patients in cancer clinical trials., Results: Of 23 medical oncologists approached, 17 enrolled (74% response rate; mean age = 47; female = 42%; White = 67%). Content analysis revealed several barriers to enrollment: (1) ethical dilemmas; (2) ambivalence about trial risks and benefits; and (3) concern about patient well-being. Concerns about the legitimacy of informed consent, perceived lack of equipoise, and fear of personal bias influenced clinicians' decisions to recommend trials during treatment discussions. Concerns about creating an imbalance between trial risks and benefits among patients with high-level needs, including patients with literacy, psychiatric, and other socioeconomic vulnerabilities, impacted clinicians' enthusiasm to engage in trial discussions. Clinicians identified patient, provider, and system-level solutions to address challenges, including increasing patient and clinician support as well as involving external personnel to support trial enrollment., Conclusion: Findings reveal multi-level barriers to offering cancer clinical trials to underrepresented patients. Targeted solutions, including system level changes to support clinicians, patient financial support, and implementation of clinical trial navigation programs were recommended to help reduce access barriers and increase enrollment of underrepresented patients into cancer clinical trials.

Background: Approximately half of patients with high-risk HER2-positive early-stage breast cancer (ESBC) do not have pathologic complete response (pCR) after neoadjuvant therapy. The residual burden of disease among this population has not been previously quantified., Materials and Methods: We used decision-modeling techniques to simulate recurrence, progression from locoregional to distant cancer, breast cancer-related mortality, and mortality from other causes over a 10-year period in a hypothetical cohort. We derived progression probabilities primarily from the KATHERINE trial of T-DM1 (ado-trastuzumab emtansine) and mortality outcomes from the published literature. Modeled outcomes included recurrences, breast cancer deaths, deaths from other causes, direct medical costs, and costs due to lost productivity. To estimate the residual disease burden, we compared outcomes from a cohort of patients treated with T-DM1 versus a hypothetical cohort with no disease recurrence., Results: We estimated that 9,300 people would experience incident high-risk HER2-positive ESBC in the United States in 2021 based on cancer surveillance databases, clinical trial data, and expert opinion. We estimated that, in this group, 2,118 would experience disease recurrence, including 1,576 distant recurrences, and 1,358 would experience breast cancer deaths. This residual disease burden resulted in 6,435 life-years lost versus the recurrence-free cohort, and healthcare-related costs totaling $644 million, primarily associated with treating distant cancers., Conclusion: Patients with HER2-positive ESBC who do not achieve pCR after neoadjuvant therapy are at ongoing risk of recurrence despite the effectiveness of neoadjuvant treatment. There is substantial clinical and economic value in further reducing the residual disease burden in this population., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Neonatal cerebral hypoxia-ischemia (HI) results in symptomatic seizures and long-term neurodevelopmental disability. The Rice-Vannucci model of rodent neonatal HI has been used extensively to examine and translate the functional consequences of acute and chronic HI-induced encephalopathy. Yet, longitudinal electrophysiological characterization of this brain injury model has been limited by the size of the neonatal mouse's head and postnatal maternal dependency. We overcome this challenge by employing a novel method of longitudinal single-mouse electroencephalography (EEG) using chronically implanted subcranial electrodes in the term-equivalent mouse pup. We characterize the neurophysiological disturbances occurring during awake and sleep states in the acute and chronic phases following newborn brain injury., Methods: C57BL/6 mice underwent long-term bilateral subcranial EEG and electromyographic electrode placement at postnatal day 9 followed by unilateral carotid cauterization and exposure to 40 minutes of hypoxia the following day. EEG recordings were obtained prior, during, and intermittently after the HI procedure from postnatal day 10 to weaning age. Quantitative EEG and fast Fourier transform analysis were used to evaluate seizures, cortical cerebral dysfunction, and disturbances in vigilance states., Results: We observed neonatal HI-provoked electrographic focal and bilateral seizures during or immediately following global hypoxia and most commonly contralateral to the ischemic injury. Spontaneous chronic seizures were not seen. Injured mice developed long-term asymmetric EEG background attenuation in all frequencies and most prominently during non-rapid eye movement (NREM) sleep. HI mice also showed transient impairments in vigilance state duration and transitions during the first 2 days following injury., Significance: The functional burden of mouse neonatal HI recorded by EEG resembles closely that of the injured human newborn. The use of single-mouse longitudinal EEG in this immature model can advance our understanding of the developmental and pathophysiological mechanisms of neonatal cerebral injury and help translate novel therapeutic strategies against this devastating condition., (© 2022 International League Against Epilepsy.)

Purpose: Polygenic risk scores (PRS) for breast cancer may help guide screening decisions. However, few studies have examined whether PRS are associated with risk of short-term or poor prognosis breast cancers. The study purpose was to evaluate the association of the 313 SNP breast cancer PRS with 2-year risk of poor prognosis breast cancer., Methods: We evaluated the association of breast cancer PRS with breast cancer overall, ER + and ER- breast cancer, and poor prognosis breast cancer diagnosed within 2 years of a negative mammogram among a cohort of 3657 women using logistic regression adjusted for age, breast density, race/ethnicity, year of screening, and genetic ancestry principal components. Breast cancers were considered poor prognosis if they were metastatic, positive lymph nodes, ER/PR + HER2- and > 2 cm, ER/PR/HER2-, or HER2 + and > 1 cm., Results: Of the 308 breast cancers, 137 (44%) were poor prognosis. The overall breast cancer PRS was significantly associated with breast cancer diagnosis within 2 years (OR 1.39, 95% CI 1.23-1.57, p < 0.001). The breast cancer PRS was also associated specifically with diagnosis of poor prognosis disease (OR 1.24, 95% CI 1.03-1.49, p = 0.018), but was more strongly associated with good prognosis cancer (OR 1.52 95% CI 1.29-1.80 p = 3.60 × 10 -7 ) The ER + PRS was significantly associated with ER/PR + breast cancer (OR 1.41, 95% CI 1.24-1.61, p < 0.001) and the ER- PRS was significantly associated with ER- breast cancer (OR 1.48, 95% CI 1.08-2.02, p = 0.015)., Conclusion: Breast cancer PRS was independently and significantly associated with diagnosis of both breast cancer overall and poor prognosis breast cancer within 2 years of a negative mammogram, suggesting PRS may help guide decisions about screening intervals and supplemental screening., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To update the ASCO Biomarkers to Guide Systemic Therapy for Metastatic Breast Cancer (MBC) guideline., Methods: An Expert Panel conducted a systematic review to identify randomized clinical trials and prospective-retrospective studies from January 2015 to January 2022., Results: The search identified 19 studies informing the evidence base., Recommendations: Candidates for a regimen with a phosphatidylinositol 3-kinase inhibitor and hormonal therapy should undergo testing for PIK3CA mutations using next-generation sequencing of tumor tissue or circulating tumor DNA (ctDNA) in plasma to determine eligibility for alpelisib plus fulvestrant. If no mutation is found in ctDNA, testing in tumor tissue, if available, should be used. Patients who are candidates for poly (ADP-ribose) polymerase (PARP) inhibitor therapy should undergo testing for germline BRCA1 and BRCA2 pathogenic or likely pathogenic mutations to determine eligibility for a PARP inhibitor. There is insufficient evidence for or against testing for a germline PALB2 pathogenic variant to determine eligibility for PARP inhibitor therapy in the metastatic setting. Candidates for immune checkpoint inhibitor therapy should undergo testing for expression of programmed cell death ligand-1 in the tumor and immune cells to determine eligibility for treatment with pembrolizumab plus chemotherapy. Candidates for an immune checkpoint inhibitor should also undergo testing for deficient mismatch repair/microsatellite instability-high to determine eligibility for dostarlimab-gxly or pembrolizumab, as well as testing for tumor mutational burden. Clinicians may test for NTRK fusions to determine eligibility for TRK inhibitors. There are insufficient data to recommend routine testing of tumors for ESR1 mutations, for homologous recombination deficiency, or for TROP2 expression to guide MBC therapy selection. There are insufficient data to recommend routine use of ctDNA or circulating tumor cells to monitor response to therapy among patients with MBC.Additional information can be found at www.asco.org/breast-cancer-guidelines.

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options., Competing Interests: Beverly MoyConsulting or Advisory Role: MOTUS (I)Research Funding: Puma Biotechnology (Inst) Lisa A. CareyResearch Funding: Syndax (Inst), Novartis (Inst), NanoString Technologies (Inst), Seattle Genetics (Inst), Veracyte (Inst), AstraZeneca (Inst)Patents, Royalties, Other Intellectual Property: Royalty-sharing agreement, investorship interest in licensed IP to startup company, Falcon Therapeutics, that is designing neural stem cell-based therapy for glioblastoma multiforme (I)Uncompensated Relationships: Novartis (Inst), G1 Therapeutics (Inst), Genentech/Roche (Inst), GlaxoSmithKline (Inst), AstraZeneca/Daiichi Sankyo (Inst), Exact Sciences (Inst), Eisai, Sanofi, Lilly, Seattle GeneticsOpen Payments Link: https://openpaymentsdata.cms.gov/physician/179671No other potential conflicts of interest were reported.

Purpose: Cancer clinical trial (CCT) participants are at risk for experiencing adverse associations from financial toxicity, but these remain understudied., Methods: From July 2015 to July 2017, we prospectively enrolled CCT participants referred for financial assistance and a group of patients matched by age, sex, cancer type, trial, and trial phase. We assessed financial burden of cancer care, cost concerns about CCTs, physical (Edmonton Symptom Assessment Scale [ESAS]) and psychologic (Patient Health Questionnaire-4 [PHQ-4]) symptoms, illness perceptions (Brief Illness Perception Questionnaire), and communication confidence (Perceived Efficacy in Patient-Physician Interactions). Adjusting for age, sex, race, performance status, marital status, income, insurance, and disease status, we examined associations of financial burden and cost concerns with patients' symptoms, illness perceptions, and communication confidence., Results: Of 198 patients, 112 (56.6%) reported financial burden and 82 (41.4%) reported cost concerns. Higher ESAS-total (odds ratio [OR] = 1.03; 95% CI, 1.01 to 1.06; P = .001), PHQ-4 depression (OR = 1.58; 95% CI, 1.20 to 2.08; P < .001), PHQ-4 anxiety (OR = 1.26; 95% CI, 1.02 to 1.55; P = .025), and more negative illness perceptions (OR = 1.04; 95% CI, 1.00 to 1.07; P = .029) were associated with financial burden, but not communication confidence (OR = 0.98; 95% CI, 0.02 to 1.05; P = .587). Higher ESAS-total (OR = 1.03; 95% CI, 1.01 to 1.05; P = .004), PHQ-4 depression (OR = 1.36; 95% CI, 1.08 to 1.71; P = .03), PHQ-4 anxiety (OR = 1.26; 95% CI, 1.03 to 1.53; P = .018), more negative illness perceptions (OR = 1.06; 95% CI, 1.02 to 1.10; P = .001), and decreased communication confidence (OR = 0.93; 95% CI, 0.86 to 1.00; P = .029) were associated with cost concerns., Conclusion: In this study of CCT participants, greater symptom burden, more negative illness perceptions, and lower communication confidence were associated with financial toxicity, underscoring the importance of addressing these issues when seeking to alleviate adverse associations of financial toxicity.

Purpose: To explore the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with breast cancer based on type of anticancer treatment., Methods: Patients with breast cancer had anti-spike antibody concentrations measured ⩾14 days after receiving a full SARS-CoV-2 vaccination series. The primary endpoint was IgA/G/M anti-spike antibody concentration. Multiple regression analysis was used to analyze log 10 -transformed antibody titer concentrations., Results: Between 29 April and 20 July 2021, 233 patients with breast cancer were enrolled, of whom 212 were eligible for the current analysis. Patients who received mRNA-1273 (Moderna) had the highest antibody concentrations [geometric mean concentration (GMC) in log 10 : 3.0 U/mL], compared to patients who received BNT162b2 (Pfizer) (GMC: 2.6 U/mL) (multiple regression adjusted p  = 0.013) and Ad26.COV2.S (Johnson & Johnson/Janssen) (GMC: 2.6 U/mL) ( p  = 0.071). Patients receiving cytotoxic therapy had a significantly lower antibody titer GMC (2.5 U/mL) compared to patients on no therapy or endocrine therapy alone (3.0 U/mL) ( p  = 0.005). Patients on targeted therapies (GMC: 2.7 U/mL) also had a numerically lower GMC compared to patients not receiving therapy/on endocrine therapy alone, although this result was not significant ( p  = 0.364). Among patients who received an additional dose of vaccine ( n  = 31), 28 demonstrated an increased antibody response that ranged from 0.2 to >4.4 U/ mL., Conclusion: Most patients with breast cancer generate detectable anti-spike antibodies following SARS-CoV-2 vaccination, though systemic treatments and vaccine type impact level of response. Further studies are needed to better understand the clinical implications of different antibody levels, the effectiveness of additional SARS-CoV-2 vaccine doses, and the risk of breakthrough infections among patients with breast cancer., Competing Interests: Competing interests: Elyssa Denault: No COI Erika Nakajima: No COI Vivek Naranbhai: No COI Jennifer Hutchinson: Advisory board participant for Novartis Lindsey Mortensen: No COI Elizabeth Neihoff: No COI Caroline Barabell: No COI Amy Comander: No COI Dejan Juric: Consulting: Novartis, Genentech, Inc., EMD Serono, Eisai, Ipsen, Syros, Vibliome Therapeutics, Relay Therapeutics, MapKure, Petra Pharma, Silverback Therapeutics, PIC Therapeutics; Research Funding (To the institution): Novartis, Genentech, Inc., Eisai, EMD Serono, Pfizer, Syros, Takeda, Amgen, InventisBio, Dizal Pharma, Celgene, Infinity Pharmaceuticals. Irene Kuter: No COI Theresa Mulvey: No COI Jeffrey Peppercorn: Employment (spouse): GlaxoSmithKline, Consulting (self) Abbott Labs Aron S Rosenstock: No COI Jennifer Shin: No COI Neelima Vidula: Research funding to the institution (MGH): Daehwa, Pfizer, Merck, Novartis, and Radius, Advisory board participation: AbbVie, OncoSec Seth A Wander: Consulting/Advisory board: Foundation Medicine, Veracyte, Eli Lilly, Hologic, Biovica; institutional research funding from Genentech. Beverly Moy: No COI Leif W. Ellisen: No COI Steven J. Isakoff: Institutional research funding from Genentech, PharmaMar, Abbvie, OncoPep, Merck, and AstraZeneca/MedImmune A. John Iafrate: Invitae (royalties); Consulting (Paige.ai, Kinnate, Oncoclinicas Brasil, Repare); Funding from Peter and Ann Lambertus Family Foundation Justin F. Gainor: Served as a compensated consultant or received honoraria from Bristol-Myers Squibb, Takeda, Loxo/Lilly, Blueprint, Oncorus, Regeneron, Gilead, Moderna, AstraZeneca, EMD Serono, Pfizer, Novartis, iTeos, Karyopharm, Silverback Therapeutics, Merck, and GlydeBio; research support from Novartis; institutional research support from Bristol-Myers Squibb, Tesaro, Moderna, Blueprint, Jounce, Array Biopharma, Merck, Adaptimmune, Novartis, and Alexo; and has an immediate family member who is an employee with equity at Ironwood Pharmaceuticals. Aditya Bardia: Consultant/advisory board: Genentech/Roche, Immunomedics, Novartis, Pfizer, Merck, Radius Health, Spectrum Pharma, Taiho Pharm, Diiachi, Sanofi, Puma Biotechnology; Research Grant (self): Biothernostics; Research Grant (Institution): Genentech/Roche, Immunomedics, Novartis, Pfizer, Merck, Radius Health, Sanofi, Mersana. Dr. Bardia is supported by Department of Defense Breast Cancer grant and National Comprehensive Cancer Network grant. Laura M. Spring: Compensated consultant or received honoraria from Novartis, Puma Biotechnology; institutional research support from Merck, Gilead, Lilly Dr. Spring is supported by the National Cancer Institute [grant number K12CA087723] and a National Comprehensive Cancer Network grant., (© The Author(s), 2022.)

Background: Guidelines support comparable treatment for women diagnosed with breast cancer during pregnancy (PrBC) and nonpregnant women with limited case-specific modifications to ensure maternal-fetal safety. Experience during pregnancy with modern agents, such as taxanes or granulocyte colony-stimulating factors (GCSF), is limited., Patients and Methods: We retrospectively identified a multi-institutional cohort of PrBC between 1996 and 2020. Propensity score analyses with multiple imputation for missing variables were applied to determine the associations between chemotherapy exposures during pregnancy, with or without taxanes or GCSF, and a compound maternal-fetal outcome including spontaneous preterm birth, preterm premature rupture of membranes, chorioamnionitis, small for gestational age newborns, congenital malformation, or 5-min Apgar score < 7., Results: Among 139 PrBC pregnancies, 82 (59.0%) were exposed to chemotherapy, including 26 (31.7%) to taxane and 18 (22.0%) to GCSF. Chemotherapy use, in general, and inclusion of taxane and/or GCSF, specifically, increased over time. Pregnancies resulting in live singleton births (n = 123) and exposed to chemotherapy were as likely to reach term as those that were not (59.5% vs. 63.6%, respectively, p unadjusted  = 0.85). Among women treated with chemotherapy, propensity score-matched odds ratios (OR) for the composite maternal-fetal outcome were not significantly increased with taxane (OR 1.24, 95% CI 0.27-5.72) or GCSF (OR 2.11, 95% confidence interval (CI) 0.48-9.22) with similar effects in multiple imputation and sensitivity models., Conclusion: The judicious increased use of taxane chemotherapy and/or growth factor support during pregnancy was not associated with unfavorable short-term maternal-fetal outcomes. While these findings are reassuring, case numbers remain limited and continued surveillance of these patients and progeny is warranted., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We define cancer equity as all people having as the same opportunity for cancer prevention, treatment, and survivorship care. However, marginalized populations continue to experience avoidable and unjust disparities in cancer care, access to clinical trials, and cancer survival. Racial and ethnic minorities, and individuals with low socioeconomic status, Medicaid insurance, limited health literacy, disabilities, and mental health disorders are more likely to experience delays to cancer diagnosis and less likely to receive guideline-concordant cancer care. These disparities are impacted by the social determinants of health including structural discrimination, racism, poverty, and inequities in access to healthcare and clinical trials. There is an urgent need to develop and adapt evidence-based interventions in collaboration with community partners that have potential to address the social determinants of health and build capacity for cancer care for underserved populations. We established the Virtual Equity Hub by developing a collaborative network connecting a comprehensive cancer center, academic safety net hospital, and community health centers and affiliates. The Virtual Equity Hub utilizes a virtual tumor board, an evidence-based approach that increases access to multi-specialty cancer care and oncology subspecialty expertise. We adapted the tumor board model by engaging person-centered teams of multi-disciplinary specialists across health systems, addressing the social determinants of health, and applying community-based research principles with a focus on populations with poor cancer survival. The virtual tumor board included monthly videoconferences, case discussion, sharing of expertise, and a focus on addressing barriers to care and trial participation. Specifically, we piloted virtual tumor boards for breast oncology, neuro-oncology, and individuals with cancer and serious mental illness. The Virtual Equity Hub demonstrated promise at building capacity for clinicians to care for patients with complex needs and addressing barriers to care. Research is needed to measure the impact, reach, and sustainability of virtual equity models for patients with cancer., (© The Author(s) 2022. Published by Oxford University Press.)

Cancer displays some of the largest health-equity concerns of all diseases. This paper draws attention to how health economics research can assess strategies to reduce or even eliminate health disparities and provides pivotal examples of existing research as well as areas for future contributions. The paper also highlights critical data limitations that currently restrain the impact health economics research could have. We then explore new areas of inquiry where economic research is sparse but could have an important impact on health equity, particularly in topics involving Medicare and Medicaid policies that expand reimbursement and generosity of coverage. Health economics studies are notably absent from policies and practices surrounding clinical trials, representing an opportunity for future research. We urge health economics researchers to consider experiments, interventions, and assessments through primary data collection; we further encourage the formulation of multidisciplinary teams to ensure that health economics skills are well melded with other areas of expertise. These teams are needed to maximize novelty and rigor of evidence. As policies are promulgated to address disparities in cancer, involvement of economics in a multidisciplinary context can help ensure that these policies do not have unintended impacts that may deepen inequities., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: Retrospective analysis of nightly fasting among women with breast cancer suggests that fasting < 13 h may be associated with a higher risk of breast cancer recurrence. We sought to evaluate prolonged overnight fasting (POF), an accessible nonpharmacological intervention, in a prospective feasibility study., Methods: We designed a single-arm, pilot study to evaluate the feasibility of fasting for 13 h overnight for 12 weeks among women with a history of early-stage breast cancer survivors. Baseline and end of study assessments included measurements of body mass index (BMI), blood biomarkers, quality of life (QOL), mood, fatigue, and physical activity. Patient-reported outcome questionnaires were also administered at 6 weeks. Feasibility was defined as ≥ 60% of participants documenting fasting for 13 h on at least 70% of nights during the study period., Results: Forty women with a history of breast cancer were enrolled with a median age of 60 (range 35-76) and median time since diagnosis of 4.5 years (range 0.8-20.7). At baseline, BMI was ≥ 25 in 37.5%. Ninety-five percent of participants fasted ≥ 13 h for at least 70% of study days (95% CI 83-99%). There was a statistically significant improvement in anxiety (p = 0.0007) at 6 weeks and BMI (p = 0.0072), anxiety (p = 0.0141), depression (p = 0.0048), and fatigue (p = 0.0105) at 12 weeks. There was no significant change in overall QOL, physical activity levels, or blood biomarkers at 12 weeks., Conclusions: POF is feasible among patients with a history of breast cancer and may potentially improve BMI, mood, and fatigue without detrimental effects on overall QOL., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Healthcare systems contribute to disparities in breast cancer outcomes. Patient navigation is a widely cited system-based approach to improve outcomes among populations at risk for delays in care. Patient navigation programs exist in all major Boston hospitals, yet disparities in outcomes persist. The objective of this study was to conduct a baseline assessment of navigation processes at six Boston hospitals that provide breast cancer care in preparation for an implementation trial of standardized navigation across the city., Methods: We conducted a mixed methods study in six hospitals that provide treatment to breast cancer patients in Boston. We administered a web-based survey to clinical champions (n = 7) across six sites to collect information about the structure of navigation programs. We then conducted in-person workflow assessments at each site using a semi-structured interview guide to understand site-specific implementation processes for patient navigation programs. The target population included administrators, supervisors, and patient navigators who provided breast cancer treatment-focused care., Results: All sites offered patient navigation services to their patients undergoing treatment for breast cancer. We identified wide heterogeneity in terms of how programs were funded/resourced, which patients were targeted for navigation, the type of services provided, and the continuity of those services relative to the patient's cancer treatment., Conclusions: The operationalization of patient navigation varies widely across hospitals especially in relation to three core principles in patient navigation: providing patient support across the care continuum, targeting services to those patients most likely to experience delays in care, and systematically screening for and addressing patients' health-related social needs. Gaps in navigation across the care continuum present opportunities for intervention., Trial Registration: Clinical Trial Registration Number NCT03514433, 5/2/2018., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To update recommendations of the American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario [CCO]) adjuvant bone-modifying agents in breast cancer guideline., Methods: An Expert Panel conducted a systematic review to identify new, potentially practice-changing data., Results: Four articles met eligibility criteria and form the evidentiary basis for revision of the previous recommendations., Recommendations: Adjuvant bisphosphonate therapy should be discussed with all postmenopausal patients (natural or therapy-induced) with primary breast cancer, irrespective of hormone receptor status and human epidermal growth factor receptor 2 status, who are candidates to receive adjuvant systemic therapy. Adjuvant bisphosphonates, if used, are not substitutes for standard anticancer modalities. The benefit of adjuvant bisphosphonate therapy will vary depending on the underlying risk of recurrence and is associated with a modest improvement in overall survival. The NHS PREDICT tool provides estimates of the benefit of adjuvant bisphosphonate therapy and may aid in decision making. Factors influencing the decision to recommend adjuvant bisphosphonate use should include patients' risk of recurrence, risk of side effects, financial toxicity, drug availability, patient preferences, comorbidities, and life expectancy. When an adjuvant bisphosphonate is used to prevent breast cancer recurrence, the therapeutic options recommended by the Panel include oral clodronate, oral ibandronate, and intravenous zoledronic acid. The Panel supports starting bisphosphonate therapy early, consistent with the points outlined in the parent CCO-ASCO guideline; this is a consensus recommendation. The Panel does not recommend adjuvant denosumab to prevent breast cancer recurrence, because studies did not show a consistent reduction of breast cancer recurrence in any subset of those with early-stage breast cancer.Additional information can be found at www.asco.org/breast-cancer-guideline., Competing Interests: Andrea EisenOther Relationship: Cancer Care Ontario Melissa K. AccordinoHonoraria: Sermo (I), M3 (I), Charter Oak Research, ExpertConnect, Medscape, Deerfield Management, Incrowd, Massive BioOther Relationship: Onclive Mark J. ClemonsHonoraria: PfizerConsulting or Advisory Role: Cornerstone Research Group, ApotexTravel, Accommodations, Expenses: Pfizer Sukhbinder Dhesy-ThindHonoraria: PfizerConsulting or Advisory Role: Novartis Canada Pharmaceuticals Inc, Seattle Genetics Melissa S. DillmonStock and Other Ownership Interests: Johnson & Johnson (I), Bristol Myers Squibb (I)Consulting or Advisory Role: Puma Biotechnology Elizabeth S. FrankHonoraria: AstraZenecaTravel, Accommodations, Expenses: Roche Sigrun HallmeyerLeadership: Association of Community Cancer Centers (ACCC)Honoraria: Cardinal HealthConsulting or Advisory Role: Bristol Myers Squibb, Cardinal Health, Array PharamceuticalSpeakers' Bureau: Bristol Myers SquibbTravel, Accommodations, Expenses: Cardinal Health, Bristol Mers SquibbUncompensated Relationships: Society for Immunotherapy of Cancer Beverly MoyConsulting or Advisory Role: MOTUS (I)Research Funding: Puma Biotechnology (Inst) Alia ThawerHonoraria: Knight Pharmaceuticals, Novartis Canada Pharmaceuticals Inc, Pfizer, GlaxoSmithKline Canada, AbbVie, AstraZeneca CanadaConsulting or Advisory Role: Ipsen, Amgen, Novartis, Lilly, Sandoz-Novartis, Pfizer, EisaiResearch Funding: Novartis, AstraZeneca Joy Y. WuResearch Funding: Radius Health Catherine H. Van PoznakResearch Funding: Bayer (Inst)Patents, Royalties, Other Intellectual Property: UpToDateNo other potential conflicts of interest were reported.

Background: Studies show that early, integrated palliative care (PC) improves quality of life (QoL) and end-of-life (EoL) care for patients with poor-prognosis cancers. However, the optimal strategy for delivering PC for those with advanced cancers who have longer disease trajectories, such as metastatic breast cancer (MBC), remains unknown. We tested the effect of a PC intervention on the documentation of EoL care discussions, patient-reported outcomes, and hospice utilization in this population., Patients and Methods: Patients with MBC and clinical indicators of poor prognosis (n=120) were randomly assigned to receive an outpatient PC intervention (n=61) or usual care (n=59) between May 2, 2016, and December 26, 2018, at an academic cancer center. The intervention entailed 5 structured PC visits focusing on symptom management, coping, prognostic awareness, decision-making, and EoL planning. The primary outcome was documentation of EoL care discussions in the electronic health record (EHR). Secondary outcomes included patient-report of discussions with clinicians about EoL care, QoL, and mood symptoms at 6, 12, 18, and 24 weeks after baseline and hospice utilization., Results: The rate of EoL care discussions documented in the EHR was higher among intervention patients versus those receiving usual care (67.2% vs 40.7%; P=.006), including a higher completion rate of a Medical Orders for Life-Sustaining Treatment form (39.3% vs 13.6%; P=.002). Intervention patients were also more likely to report discussing their EoL care wishes with their doctor (odds ratio [OR], 3.10; 95% CI, 1.21-7.94; P=.019) and to receive hospice services (OR, 4.03; 95% CI, 1.10-14.73; P=.035) compared with usual care patients. Study groups did not differ in patient-reported QoL or mood symptoms., Conclusions: This PC intervention significantly improved rates of discussion and documentation regarding EoL care and delivery of hospice services among patients with MBC, demonstrating that PC can be tailored to address the supportive care needs of patients with longer disease trajectories. ClinicalTrials.gov identifier: NCT02730858.

Purpose: This guideline updates recommendations of the ASCO guideline on chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) that is either endocrine-pretreated or hormone receptor (HR)-negative., Methods: An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations., Results: The Expert Panel reviewed abstracts from the literature review and retained 14 articles., Recommendations: Patients with triple-negative, programmed cell death ligand-1-positive MBC may be offered the addition of immune checkpoint inhibitor to chemotherapy as first-line therapy. Patients with triple-negative, programmed cell death ligand-1-negative MBC should be offered single-agent chemotherapy rather than combination chemotherapy as first-line treatment, although combination regimens may be offered for life-threatening disease. Patients with triple-negative MBC who have received at least two prior therapies for MBC should be offered treatment with sacituzumab govitecan. Patients with triple-negative MBC with germline BRCA mutations previously treated with chemotherapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. Patients with HR-positive human epidermal growth factor receptor 2-negative MBC for whom chemotherapy is being considered should be offered single-agent chemotherapy rather than combination chemotherapy, although combination regimens may be offered for highly symptomatic or life-threatening disease. Patients with HR-positive MBC with disease progression on an endocrine agent may be offered treatment with either endocrine therapy with or without targeted therapy or single-agent chemotherapy. Patients with HR-positive MBC with germline BRCA mutations no longer benefiting from endocrine therapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. No recommendation regarding when a patient's care should be transitioned to hospice or best supportive care alone is possible.Additional information is available at www.asco.org/breast-cancer-guidelines., Competing Interests: Beverly MoyConsulting or Advisory Role: MOTUSResearch Funding: Puma Biotechnology Steven E. ComeResearch Funding: AstraZenecaOpen Payments Link: https://openpaymentsdata.cms.gov/physician/163830/summary Angelo Di LeoHonoraria: Roche, Novartis, Pfizer, AstraZeneca, Eisai, Lilly, Celgene, AmgenConsulting or Advisory Role: Roche, Novartis, Pfizer, AstraZeneca, Lilly, Celgene, Puma Biotechnology, Ipsen, Genentech, Amgen, Seattle Genetics, Genomic Health, Athenex, Daiichi SankyoTravel, Accommodations, Expenses: Roche, Pfizer, Celgene, Novartis Julie R. GralowConsulting or Advisory Role: Genentech, AstraZeneca, Hexal, Puma Biotechnology, Roche, Novartis, Seagen, Genomic Health Gabriel N. HortobagyiConsulting or Advisory Role: NovartisResearch Funding: NovartisTravel, Accommodations, Expenses: Novartis Douglas YeeStock and Other Ownership Interests: Apogen BiotechnologiesHonoraria: Puma Biotechnology, Daiichi Sankyo, Boehringer IngelheimConsulting or Advisory Role: Martell diagnosticResearch Funding: Boehringer IngelheimOpen Payments Link: https://openpaymentsdata.cms.gov/physician/636443/summary Ian E. SmithStock and Other Ownership Interests: Perci HealthHonoraria: Eisai, AstraZeneca, Genomic Health, PfizerConsulting or Advisory Role: Roche, AstraZeneca, Eisai, Pfizer, Genomic HealthTravel, Accommodations, Expenses: Genomic Health Mariana Chavez-MacGregorEmployment: MD Anderson Physician's NetworkHonoraria: Pfizer, EisaiConsulting or Advisory Role: Roche/Genentech, AstraZeneca, Novartis, Pfizer, Asofar, Genomic Health, Roche/GenentechResearch Funding: NovartisExpert Testimony: Abbott Laboratories, PfizerTravel, Accommodations, Expenses: PfizerOther Relationship: RocheUncompensated Relationships: Legacy Healthcare Services, The Hope Foundation Rita NandaConsulting or Advisory Role: Merck, Genentech/Roche, Pfizer, Macrogenics, Aduro Biotech, Ionis Pharmaceuticals, Immunomedics, OncoSec, Cardinal Health, Seattle Genetics, Fujifilm, Clovis Oncology, G1 TherapeuticsResearch Funding: Corcept Therapeutics, Celgene, Merck, Seattle Genetics, Genentech/Roche, Odonate Therapeutics, Pfizer, AstraZeneca, Immunomedics, OncoSec, Arvinas, Taiho OncologyOther Relationship: G1 Therapeutics Heather L. McArthurConsulting or Advisory Role: Merck, Lilly, Immunomedics, Pfizer, Genentech, Bristol Myers Squibb, AstraZeneca , Daiichi Sankyo, Seattle Genetics, Genomic Health, Puma BiotechnologyResearch Funding: Bristol Myers Squibb, ZIOPHARM Oncology, Lilly, MerckTravel, Accommodations, Expenses: Merck, Spectrum Pharmaceuticals, Lilly, Amgen, Puma Biotechnology, Immunomedics, Genentech, Pfizer, AstraZeneca, Bristol Myers Squibb, DAVA PharmaceuticalsOther Relationship: Lilly, Genomic Health Laura SpringConsulting or Advisory Role: Novartis, Puma Biotechnology, Lumicell, AvrobioResearch Funding: Tesaro, MerckTravel, Accommodations, Expenses: Merck, Tesaro Katherine E. Reeder-HayesResearch Funding: Pfizer Kathryn J. RuddyResearch Funding: MedtronicPatents, Royalties, Other Intellectual Property: Spouse and Mayo Clinic have filed patents related to the application of artificial intelligence to the electrocardiogram for diagnosis and risk stratification, and Spouse and Mayo Clinic are involved in a potential equity/royalty relationship with AliveCor Shaveta VinayakConsulting or Advisory Role: OncoSecResearch Funding: OncoSec, Seattle Genetics, PfizerTravel, Accommodations, Expenses: OncoSec William J. Irvin JrResearch Funding: Merck, Altor BioScience, Odonate Therapeutics, Boston Biomedical, Novartis, Pfizer, Seattle Genetics, AstraZeneca Michael A. DansoHonoraria: AmgenConsulting or Advisory Role: Novartis, Pfizer, Immunomedics, Seattle Genetics Natalie DicksonEmployment: Tennessee OncologyConsulting or Advisory Role: Via Oncology, AbbVie, CignaResearch Funding: Bristol Myers SquibbTravel, Accommodations, Expenses: Flatiron Health Sophie S. TurnerEmployment: IQVIA Cheryl PerkinsEmployment: Medscape Lisa A. CareyResearch Funding: Syndax, Immunomedics, Novartis, NanoString Technologies, AbbVie, Seattle Genetics, VeracytePatents, Royalties, Other Intellectual Property: Royalty-sharing agreement, investorship interest in licensed IP to startup company, Falcon Therapeutics, that is designing neural stem-cell–based therapy for glioblastoma multiformeUncompensated Relationships: Sanofi, Novartis, G1 Therapeutics, Genentech/Roche, GlaxoSmithKline, AstraZeneca/Daiichi Sankyo, Aptitude Health, Exact Sciences, EisaiOpen Payments Link: https://openpaymentsdata.cms.gov/physician/179671No other potential conflicts of interest were reported.

Introduction: The CREATE-X study, conducted in Japan and South Korea, established capecitabine as an adjuvant treatment option for patients with triple negative breast cancer (TNBC) who have residual disease (RD) following neoadjuvant anthracycline or taxane-based chemotherapy. However, there are no reports on the tolerability and outcomes of adjuvant capecitabine in the US setting following publication of the CREATE-X data., Methods: We retrospectively collected treatment and tolerability data from the medical records of the first 23 TNBC patients who received adjuvant capecitabine for RD post neoadjuvant chemotherapy at our institution. Disease-free survival was assessed using the Kaplan-Meier method., Results: The median starting dosage of capecitabine was 1871 mg/m 2 /day, most commonly divided into two daily doses on days 1-14 of each 21 day cycle. 34.8% of patients completed the treatment as prescribed. Side effects associated with treatment were common with 69.6% of patients experiencing hand-foot syndrome, 39.1% of patients experiencing diarrhea, and 13.0% of patients requiring hospitalization for side effects. Of 23 patients treated with adjuvant capecitabine, 34.8% completed the planned dose, 30.4% completed with dose reduction, and 34.8% discontinued early. At a median follow-up time of 14 months, the median disease-free survival was 22 months, with 30.4% of patients experiencing recurrence., Conclusion: Tolerability was poor overall compared to the CREATE-X cohort. Administering adjuvant capecitabine for TNBC patients with residual disease in the United States is challenging given differences in tolerability. More research is needed to understand how poor tolerability will affect the efficacy of this approach in the US population.

Background: Phase 1 trials are increasingly important in the molecularly driven era of oncology, but few studies have examined phase 1 participation disparities. The authors of this study investigated factors associated with phase 1 versus phase 2/3 trial enrollment., Methods: They authors conducted a cross-sectional study using serial samples of patients age ≥18 years enrolling on cancer trials from October 2011 to November 2014 at an academic cancer center. They used univariable and multivariable logistic regression models to analyze sociodemographic and clinical associations with phase 1 versus phase 2/3 trial enrollment., Results: Among 3103 patients enrolled in cancer trials, 2657 unique patients participated in phase 1/2/3 trials. For patients enrolled in phase 1 (n = 1401) versus phase 2/3 (n = 1256) trials, we found no significant differences by age, insurance status, marital status, and income. Overall, 1216 (93%) White, 72 (6%) Asian, and 21 (2%) Black patients enrolled on phase 1 trials, whereas 1068 (93%) White, 40 (3%) Asian, and 43 (4%) Black patients enrolled on phase 2/3 trials. Adjusting for age, sex, race, ethnicity, insurance status, marital status, income, cancer type, disease status, travel distance, and trial year, compared with White patients, Black patients had lower phase 1 enrollment (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.25-0.82), as did Hispanic/Latino (OR, 0.25; 95% CI, 0.08-0.79) and male patients (OR, 0.77; 95% CI, 0.62-0.94). Asian patients had higher phase 1 enrollment (OR, 1.38; 95% CI, 0.88-2.16)., Conclusions: Disparities in phase 1 versus phase 2/3 cancer clinical trial enrollment underscore the urgent need for interventions addressing inequities in early-phase trial participation., Lay Summary: Phase 1 trials are of increasing importance in oncology. The authors of the study analyzed all patients enrolling on cancer clinical trials at a large academic cancer center from October 2011 to November 2014. Among the 2657 trial participants, when age, sex, race, ethnicity, insurance status, marital status, income, cancer type, disease status, travel distance, and trial year were taken into account, Black, Hispanic/Latino, and male patients were less likely to enroll on phase 1 trials versus phase 2/3 trials. These findings suggest a need for targeted interventions to improve access to and education about phase 1 trials for Black and Hispanic/Latino patients., (© 2021 American Cancer Society.)

Purpose: Neratinib plus capecitabine (N+C) demonstrated significant progression-free survival (PFS) benefit in NALA (NCT01808573), a randomized phase III trial comparing N+C with lapatinib + capecitabine (L+C) in 621 patients with HER2-positive (HER2 + ) metastatic breast cancer (MBC) who had received ≥2 prior HER2-directed regimens in the metastatic setting. We evaluated correlations between exploratory biomarkers and PFS., Patients and Methods: Somatic mutations were evaluated by next-generation sequencing on primary or metastatic samples. HER2 protein expression was evaluated by central IHC, H-score, and VeraTag/HERmark. p95 expression (truncated HER2) was measured by VeraTag. HRs were estimated using unstratified Cox proportional hazards models., Results: Four hundred and twenty samples had successful sequencing: 34.0% had PIK3CA mutations and 5.5% had HER2 (ERBB2) mutations. In the combined patient populations, PIK3CA mutations trended toward shorter PFS [wild-type vs. mutant, HR = 0.81; 95% confidence interval (CI), 0.64-1.03], whereas HER2 mutations trended toward longer PFS [HR = 1.69 (95% CI, 0.97-3.29)]. Higher HER2 protein expression was associated with longer PFS [IHC 3+ vs. 2+, HR = 0.67 (0.54-0.82); H-score ≥240 versus <240, HR = 0.77 (0.63-0.93); HERmark positive vs. negative, HR = 0.76 (0.59-0.98)]. Patients whose tumors had higher HER2 protein expression (any method) derived an increased benefit from N+C compared with L+C [IHC 3+, HR = 0.64 (0.51-0.81); H-score ≥ 240, HR = 0.54 (0.41-0.72); HERmark positive, HR = 0.65 (0.50-0.84)], as did patients with high p95 [p95 ≥2.8 relative fluorescence (RF)/mm 2 , HR = 0.66 (0.50-0.86) vs. p95 < 2.8 RF/mm 2 , HR = 0.91 (0.61-1.36)]., Conclusions: PIK3CA mutations were associated with shorter PFS whereas higher HER2 expression was associated with longer PFS. Higher HER2 protein expression was also associated with a greater benefit for N+C compared with L+C., (©2021 The Authors; Published by the American Association for Cancer Research.)