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Purpose: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need., Methods: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1. Correlative analyses included the HER2DX genomic tool, multiomic evaluations of HER2 heterogeneity, and predictors of thrombocytopenia., Results: After a median follow-up of 5.8 years, 11 iDFS events were observed in the T-DM1 arm, consistent with a 5-year iDFS of 97.0% (95% CI, 95.2 to 98.7). At 5 years, the recurrence-free interval (RFI) was 98.3% (95% CI, 97.0 to 99.7), the overall survival was 97.8% (95% CI, 96.3 to 99.3), and the breast cancer-specific survival was 99.4% (95% CI, 98.6 to 100). Comparable iDFS was observed with T-DM1 irrespective of tumor size, hormone receptor status, centrally determined HER2 immunohistochemical score, and receipt of T-DM1 for more or less than 6 months. Although ATEMPT was not powered for this end point, the 5-year iDFS in the TH arm was 91.1%. Among patients with sufficient tissue for HER2DX testing (n = 187), 5-year outcomes significantly differed according to HER2DX risk score, with better RFI (98.1% v 81.8%, hazard ratio [HR], 0.10, P = .01) and iDFS (96.3% v 81.8%, HR, 0.20, P = .047) among patients with HER2DX low-risk versus high-risk tumors, respectively., Conclusion: Adjuvant T-DM1 for 1 year leads to outstanding long-term outcomes for patients with stage I HER2-positive breast cancer. A high HER2DX risk score predicted a higher risk of recurrence in ATEMPT.

Purpose: Cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6is) are an important component of treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), but it is not known if patients might derive benefit from continuation of CDK4/6i with endocrine therapy beyond initial tumor progression or if the addition of checkpoint inhibitor therapy has value in this setting., Methods: The randomized multicenter phase II PACE trial enrolled patients with hormone receptor-positive/HER2- MBC whose disease had progressed on previous CDK4/6i and aromatase inhibitor (AI) therapy. Patients were randomly assigned 1:2:1 to receive fulvestrant (F), fulvestrant plus palbociclib (F + P), or fulvestrant plus palbociclib and avelumab (F + P + A). The primary end point was investigator-assessed progression-free survival (PFS) in patients treated with F versus F + P., Results: Overall, 220 patients were randomly assigned between September 2017 and February 2022. The median age was 57 years (range, 25-83 years). Most patients were postmenopausal (80.9%), and 40% were originally diagnosed with de novo MBC. Palbociclib was the most common previous CDK4/6i (90.9%). The median PFS was 4.8 months on F and 4.6 months on F + P (hazard ratio [HR], 1.11 [90% CI, 0.79 to 1.55]; P = .62). The median PFS on F + P + A was 8.1 months (HR v F, 0.75 [90% CI, 0.50 to 1.12]; P = .23). The difference in PFS with F + P and F + P + A versus F was greater among patients with baseline ESR1 and PIK3CA alterations., Conclusion: The addition of palbociclib to fulvestrant did not improve PFS versus fulvestrant alone among patients with hormone receptor-positive/HER2- MBC whose disease had progressed on a previous CDK4/6i plus AI. The increased PFS seen with the addition of avelumab warrants further investigation in this patient population.

Background: The impact of abbreviated neoadjuvant regimens for HER2+ breast cancer on rates of breast conservation therapy (BCT) is unclear. We aimed to determine BCT rates in a single-arm prospective trial of neoadjuvant paclitaxel/trastuzumab/pertuzumab (THP) in patients with stage II or III HER2+ breast cancer., Study Design: BCT eligibility was prospectively recorded before and after THP. Pre- and posttreatment mammogram and breast ultrasound were required; breast MRI was encouraged. Patients with a large tumor to breast size ratio were eligible for downsizing. Multifocal/multicentric tumors, extensive calcifications, and contraindications to radiation were considered BCT contraindications., Results: Overall, 92 patients who received neoadjuvant THP on trial were included. At presentation, 39 (42.4%) were considered eligible for BCT and 53 (57.6%) were not. BCT-eligible patients were older (median 54 vs 47 years, respectively; p = 0.006) and had smaller tumors by palpation (median 2.5 vs 3 cm, respectively; p = 0.004). Of 53 BCT-ineligible patients, 28 were candidates for tumor downsizing, whereas 25 had contraindications to BCT. Overall, 51 (55.4%) patients underwent BCT. Of the 28 patients who were candidates for downsizing, 22 (78.6%) became BCT-eligible after THP and 18 of 22 (81.8%) underwent BCT. In total, 44 of 92 (47.8%) patients experienced breast pathologic complete response (ypT0), including 11 of 25 (44.0%) patients with BCT contraindications at presentation., Conclusions: De-escalated neoadjuvant systemic therapy led to high BCT rates in this cohort. The impact of de-escalated systemic therapy on local therapy and outcomes in early stage HER2+ breast cancer warrants further investigation., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To support shared decision-making, patient-facing resources are needed to complement recently published guidelines on approaches for surveillance mammography in breast cancer survivors aged ≥ 75 or with < 10-year life expectancy. We created a patient guide to facilitate discussions about surveillance mammography in older breast cancer survivors., Methods: The "Are Mammograms Still Right for Me?" guide estimates future ipsilateral and contralateral breast (in-breast) cancer risks, general health, and the potential benefits/harms of mammography, with prompts for discussion. We conducted in-clinic acceptability testing of the guide by survivors and their clinicians at a National Cancer Institute-designated comprehensive cancer center, including two community practices. Patients and clinicians received the guide ahead of a clinic visit and surveyed patients (pre-/post-visit) and clinicians (post-visit). Acceptability was defined as ≥ 75% of patients and clinicians reporting that the guide (a) should be recommended to others, (b) is clear, (c) is helpful, and (d) contains a suitable amount of information. We also elicited feedback on usability and mammography intentions., Results: We enrolled 45 patients and their 21 clinicians. Among those responding in post-visit surveys, 33/37 (89%) patients and 15/16 (94%) clinicians would recommend the guide to others; 33/37 (89%) patients and 15/16 (94%) clinicians felt everything/most things were clear. All other pre-specified acceptability criteria were met. Most patients reported strong intentions for mammography (100% pre-visit, 98% post-visit)., Conclusion: Oncology clinicians and older breast cancer survivors found a guide to inform mammography decision-making acceptable and clear. A multisite clinical trial is needed to assess the guide's impact mammography utilization., Trial Registration: ClinicalTrials.gov-NCT03865654, posted March 7, 2019., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: In early trials, hypersensitivity reactions (HSRs) to paclitaxel were common, thus prompting the administration of antihistamines and corticosteroids before every paclitaxel dose. We tested the safety of omitting corticosteroids after cycle 2 during the paclitaxel portion of the dose-dense (DD) doxorubicin-cyclophosphamide (AC)-paclitaxel regimen., Patients, Materials, and Methods: In this prospective, single-arm study, patients who completed four cycles of DD-AC for stage I-III breast cancer received paclitaxel 175 mg/m 2 every 2 weeks for four cycles. Patients received a standard premedication protocol containing dexamethasone, diphenhydramine, and a histamine H2 blocker prior to the first two paclitaxel cycles. Dexamethasone was omitted in cycles three and four if there were no HSRs in previous cycles. We estimated the rate of grade 3-4 HSRs., Results: Among 127 patients enrolled, 125 received more than one dose of protocol therapy and are included in the analysis. Fourteen (11.2%; 90% confidence interval, 6.9%-20.0%) patients had any-grade HSRs, for a total of 22 (4.5%; 3.1%-6.4%) HSRs over 486 paclitaxel cycles. Any-grade HSRs occurred in 1.6% (0.3%-5.0%), 6.5% (3.3%-11.3%), 7.4% (3.9%-12.5%), and 2.6% (0.7%-6.6%) of patients after paclitaxel cycles 1, 2, 3, and 4, respectively. Dexamethasone use was decreased by 92.8% in cycles 3 and 4. Only one patient experienced grade 3 HSR in cycles 3 or 4, for a rate of grade 3/4 HSR 0.4% (0.02%-2.0%) (1/237 paclitaxel infusions). That patient had grade 2 HSR during cycle 2, and the subsequent grade 3 event occurred despite usual dexamethasone premedication. A sensitivity analysis restricted to patients not known to have received dexamethasone in cycles 3 and 4 found that any-grade HSRs occurred in 2.7% (3/111; 0.7%-6.8%) and 0.9% (1/109; 0.05%-4.3%) of patients in cycle 3 and 4, respectively., Conclusion: Corticosteroid premedication can be safely omitted in cycles 3 and 4 of dose-dense paclitaxel if HSRs are not observed during cycles 1 and 2., Implications for Practice: Because of the potential for hypersensitivity reactions (HSRs) to paclitaxel, corticosteroids are routinely prescribed prior to each dose, on an indefinite basis. This prospective study, including 125 patients treated with 486 paclitaxel cycles, demonstrates that corticosteroids can be safely omitted in future cycles if HSRs did not occur during cycles 1 and 2 of paclitaxel and that this strategy reduces the use of corticosteroids in cycles 3 and 4 by 92.8% relative to current standard of care., (© 2021 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Purpose: The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC)., Methods: Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m 2 IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks). The co-primary objectives were to compare the incidence of clinically relevant toxicities (CRTs) in patients treated with T-DM1 versus TH and to evaluate iDFS in patients receiving T-DM1., Results: The analysis population includes all 497 patients who initiated protocol therapy (383 T-DM1 and 114 TH). CRTs were experienced by 46% of patients on T-DM1 and 47% of patients on TH ( P = .83). The 3-year iDFS for T-DM1 was 97.8% (95% CI, 96.3 to 99.3), which rejected the null hypothesis ( P < .0001). Serially collected patient-reported outcomes indicated that patients treated with T-DM1 had less neuropathy and alopecia and better work productivity compared with patients on TH., Conclusion: Among patients with stage I HER2+ BC, one year of adjuvant T-DM1 was associated with excellent 3-year iDFS, but was not associated with fewer CRT compared with TH., Competing Interests: Sara TolaneyConsulting or Advisory Role: Novartis, Pfizer, Merck, Lilly, Nektar, NanoString Technologies, AstraZeneca, Puma Biotechnology, Genentech, Eisai, Sanofi, Celldex, Bristol Myers Squibb, Paxman, Seattle Genetics, Odonate Therapeutics, AbbVie, Silverback Therapeutics, G1 Therapeutics, OncoPep, Kyowa Hakko Kirin, Samsung Bioepis, CytomX Therapeutics, Daiichi Sankyo, Athenex, Immunomedics/Gilead, Mersana, CertaraResearch Funding: Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, NanoString Technologies, Cyclacel, Nektar, Immunomedics, Odonate Therapeutics, Sanofi, Seattle GeneticsTravel, Accommodations, Expenses: AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Eisai, NanoString Technologies, Puma Biotechnology, Celldex Chau DangHonoraria: Puma Biotechnology, eviCore healthcareConsulting or Advisory Role: Puma Biotechnology, eviCore healthcareResearch Funding: Genentech/Roche, Puma Biotechnology Denise YardleyConsulting or Advisory Role: Novartis, Biotheranostics, Bristol Myers Squibb, G1 Therapeutics, Athenex, Immunomedics, Sanofi/Aventis, R-Pharm, LillySpeakers' Bureau: Novartis, Genentech/Roche, Genentech/RocheResearch Funding: Genentech/Roche, Novartis, MedImmune, Lilly, Medivation, Pfizer, Tesaro, Macrogenics, AbbVie, Merck, Clovis Oncology, Amgen, Biomarin, Biothera, Dana Farber Cancer Hospital, Incyte, Innocrin Pharma, Nektar, NSABP Foundation, Odonate Therapeutics, PolyphorTravel, Accommodations, Expenses: Novartis, Genentech/Roche Steven IsakoffConsulting or Advisory Role: AbbVie, OncoPep, Puma Biotechnology, Seattle Genetics, NovartisResearch Funding: Genentech, PharmaMar, AbbVie, OncoPep, Merck, AstraZeneca/MedImmune, Outcomes4Me Vicente ValeroHonoraria: Genentech/Roche, Merck, NovartisConsulting or Advisory Role: Genentech/Roche, Novartis, MerckTravel, Accommodations, Expenses: Genentech/Roche Therese MulveyConsulting or Advisory Role: Outcomes4Me Ron BoseConsulting or Advisory Role: GenentechResearch Funding: Puma Biotechnology Antonio WolffConsulting or Advisory Role: Ionis PharmaceuticalsResearch Funding: Biomarin, CelldexPatents, Royalties, Other Intellectual Property: Antonio Wolff has been named as inventor on one or more issued patents or pending patent applications related to methylation in breast cancer and has assigned his rights to JHU and participates in a royalty sharing agreement with JHUOpen Payments Link: https://openpaymentsdata.cms.gov/physician/357301/summary Katherine Reeder-HayesResearch Funding: Pfizer Hope RugoHonoraria: Puma Biotechnology, MylanConsulting or Advisory Role: SamsungResearch Funding: Macrogenics, OBI Pharma, Eisai, Pfizer, Novartis, Lilly, Genentech, Merck, Immunomedics, Odonate Therapeutics, Daiichi Sankyo, Seattle Genetics, Sermonix Pharmaceuticals, AstraZenecaTravel, Accommodations, Expenses: Pfizer, Novartis, Macrogenics, Mylan, Daiichi Sankyo, AstraZeneca Spain, MerckOpen Payments Link: https://openpaymentsdata.cms.gov/summary Bhuvaneswari RamaswamyConsulting or Advisory Role: Eisai Lowell HartHonoraria: Novartis, Daiichi Sankyo, AstraZeneca, Seattle Genetics, G1 Therapeutics, Veracyte, Karyopharm TherapeuticsConsulting or Advisory Role: Genentech/Roche, Amgen, G1 Therapeutics, Merck, Seattle GeneticsSpeakers' Bureau: Bristol Myers Squibb, Lilly, Pfizer, Genentech, AstraZeneca, NovartisResearch Funding: Novartis, Genentech/Roche, Bristol Myers Squibb, G1 Therapeutics, Seattle Genetics Vijayakrishna GadiLeadership: SEngine Precision MedicineStock and Other Ownership Interests: Sengine precision medicine, Novilla, 3rdEyeBio, New Equilibrium BiosciencesConsulting or Advisory Role: Seattle Genetics, Puma Biotechnology, Novartis, SanofiSpeakers' Bureau: Seagen, bioTheranosticsResearch Funding: Genentech/Roche, SignalOne Bio, AgendiaTravel, Accommodations, Expenses: NovartisOpen Payments Link: https://openpaymentsdata.cms.gov/physician/2511 Bryan SchneiderHonoraria: Lilly, Research to Practice Paul MarcomConsulting or Advisory Role: Genentech/Roche, ImmunomedicsResearch Funding: Novartis, Genentech/Roche, AstraZeneca, Verily, Glycomimetics, MillenniumOpen Payments Link: https://openpaymentsdata.cms.gov/physician/237508/summary Kathy AlbainConsulting or Advisory Role: Novartis, Pfizer, Myriad Genetics, Genomic Health, Agendia, Genentech/RocheResearch Funding: Seattle GeneticsOther Relationship: Puma Biotechnology Nadine TungResearch Funding: AstraZeneca Rita NandaConsulting or Advisory Role: Merck, Genentech/Roche, Pfizer, Macrogenics, Daiichi Sankyo, Athenex, Aduro Biotech, ION Pharma, Seattle Genetics, ImmunomedicsResearch Funding: Corcept Therapeutics, Celgene, Merck, Seattle Genetics, Genentech/Roche, Odonate Therapeutics, Pfizer, AstraZeneca, AbbVie, ImmunomedicsOther Relationship: G1 Therapeutics Rachel JankowitzHonoraria: EisaiConsulting or Advisory Role: Merck Mothaffar RimawiConsulting or Advisory Role: Macrogenics, Daiichi Sankyo, Seattle Genetics, GenentechResearch Funding: Pfizer Vandana AbramsonEmployment: HCA HealthcareConsulting or Advisory Role: Eisai, Daiichi Sankyo, AbbvieResearch Funding: Genentech/Roche, Lilly Paula PohlmannLeadership: Immunonet BioSciencesStock and Other Ownership Interests: Immunonet BioSciencesHonoraria: Dava Oncology, OncLive/MJH Life Sciences, Frontiers—PublisherConsulting or Advisory Role: Personalized Cancer Therapy, OncoPlex Diagnostics, Immunonet BioSciences, Pfizer, HERON, Puma Biotechnology, Sirtex Medical, Caris Life Sciences, Juniper Pharmaceuticals, Bolt BiotherapeuticsSpeakers' Bureau: Genentech/RocheResearch Funding: Genentech/Roche, Fabre-Kramer, Advanced Cancer Therapeutics, Caris Centers of Excellence, Pfizer, Pieris Pharmaceuticals, Cascadian Therapeutics, Bolt Biotherapeutics, Byondis, SeagenPatents, Royalties, Other Intellectual Property: United States Patent no. 8486413, United States Patent no. 8501417, United States Patent no. 9023362, United States Patent no. 9745377, Patent application Catherine Van PoznakResearch Funding: BayerPatents, Royalties, Other Intellectual Property: UpToDate Andres Forero-TorresEmployment: Seattle GeneticsStock and Other Ownership Interests: Seattle Genetics Minetta LiuResearch Funding: Eisai, Seattle Genetics, Novartis, Roche/Genentech, GRAIL, Merck, Tesaro, Menarini Silicon Biosystems, Genomic HealthTravel, Accommodations, Expenses: GRAIL, Merck, Menarini Silicon Biosystems, Pfizer, Genomic Health, AstraZeneca, Ionis Pharmaceuticals Kathryn RuddyPatents, Royalties, Other Intellectual Property: My husband is a co-inventor of technology licensed by Mayo Clinic to AliveCor (MountainView, CA), which makes a smartphone-enabled remote ECG monitoring system Richard GelberResearch Funding: AstraZeneca, Novartis, Roche, Merck, PfizerTravel, Accommodations, Expenses: Roche, AstraZeneca, Novartis Bill BarryEmployment: Rho Ann PartridgePatents, Royalties, Other Intellectual Property: I receive small royalty payments for co-authoring the breast cancer survivorship section of UpToDateTravel, Accommodations, Expenses: Novartis Eric WinerHonoraria: Genentech/Roche, Genomic HealthConsulting or Advisory Role: Leap Therapeutics, Seattle Genetics, Jounce Therapeutics, GlaxoSmithKline, Carrick Therapeutics, Lilly, G1 Therapeutics, Syros Pharmaceuticals, Genentech/Roche, Gilead Sciences, Zymeworks, AthenexResearch Funding: GenentechOther Relationship: InfiniteMD Ian KropEmployment: AMAG Pharmaceuticals, Freeline TherapeuticsLeadership: AMAG Pharmaceuticals, Freeline TherapeuticsStock and Other Ownership Interests: AMAG Pharmaceuticals, Freeline Therapeutics, VertexHonoraria: Genentech/Roche, AstraZeneca, CelltrionConsulting or Advisory Role: Genentech/Roche, Seattle Genetics, Daiichi Sankyo, Macrogenics, Taiho Pharmaceutical, Context Therapeutics, Novartis, Merck, Ionis Pharmaceuticals, Bristol Myers Squibb, AstraZenecaResearch Funding: Genentech, PfizerNo other potential conflicts of interest were reported.

Purpose: Adverse events (AE) during oncology clinical trials are typically reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), which provides information about the frequency and severity of AEs from the provider's perspective. Instruments that track patient-reported outcomes (PRO) complement the CTCAE and provide additional patient-centered information about the toxicity profile of an anti-cancer drug., Methods: We conducted a single-arm, open-label phase II study of eribulin as first- or second-line therapy for metastatic hormone receptor-positive/HER2-negative (HR+/HER2-) or triple-negative breast cancer (TNBC). Patients were recruited simultaneously into each cohort by tumor subtype. The primary endpoint was overall response rate (ORR). Secondary endpoints included evaluation of toxicity by CTCAE and PRO instruments and agreement between CTCAE and PRO. The study also investigated single-nucleotide polymorphisms (SNPs) associated with treatment-induced neurotoxicity., Results: 83 patients were enrolled: 45 into the HR+/HER2- cohort and 38 into the TNBC cohort. The ORR was 35.6% (90% CI 24-39%) in the HR+/HER2- cohort and 13.2% (90% CI 5-26%) in the TNBC cohort. Stable disease as the best response was recorded in 55.1% of patients with HR+/HER2- disease and 60.5% with TNBC. Toxicity analysis revealed a discordance between CTCAE and PRO assessment in many patients, with a focus on fatigue, alopecia, and neuropathy. Pharmacogenomic analysis identified SNPs associated with treatment-induced peripheral neuropathy., Conclusions: Eribulin is active in HER2- breast cancer. This study reveals that provider-assessed AEs can vary greatly from patient experiences. Future studies should incorporate CTCAE and PRO instruments to improve reporting of treatment-related AEs. ClinicalTrials.gov Registration: NCT01827787.