Use of adjuvant regimens with single-cytotoxic agents among women with stage II-III HER2-positive breast cancer.
Authors: Joan Marie Neuner, Noel Estrada-Merly, Brahmendra Reddy Viyyuri, John A. Charlson, Sneha Deepak Phadke, Dana McDougall, Kara Gavin, Mary C. Schroeder
Journal: Journal of Clinical Oncology (2025)

e12526 Background: Use of paclitaxel alone with trastuzumab leads to excellent survival with T1 HER2+ breast cancer. The role of de-escalation of cytotoxic agents in higher-stage HER2+ patients is not as clear, but older patients and patients with comorbid diseases have particularly high toxicity risks with multiagent regimens. We examined patterns of de-escalation of cytotoxic chemotherapy in Stage II-III HER2+ breast cancer. Methods: We used data from the Greater Plains Collaborative Reusable Observable Unified Study Environment, a Patient Centered Outcomes Research (PCOR)net-funded clinical research network in Central and Mountain West states. Electronic health records (EHR) from each member health system were linked with North American Association of Central Cancer Registries-formatted data in a deidentified data resource. Following a federally funded, IRB-approved protocol, we identified women ≥18 years diagnosed 2014-2022 with a first, stage II-III, breast cancer who initiated chemotherapy within 4 months of diagnosis (neoadjuvant) or surgery (adjuvant chemotherapy-only) at ten health systems. We examined up to 2 years of post-diagnosis EHR data for chemotherapy agent codes and administration dates. Descriptive statistics were used to characterize the study sample, agents in each cycle and number of cycles. Multivariate models were used to examine factors associated with use of single-cytotoxic agents. Information regarding clinical trial enrollment was not available. Thus, we performed a sensitivity analysis that excluded years 2021-22 when large de-escalation trials were enrolling. Results: Among a cohort of 1,433 subjects with Stage II-III HER2+ cancer receiving a targeted therapy, (9.6% age ≥70, 9.0% non-Hispanic Black, 8.9% ≥3 comorbid conditions), 15.1% received an initial regimen with a single cytotoxic agent. These regimens included paclitaxel (including nab-paclitaxel) (59.4%), docetaxel (25.3%) or carboplatin (15.2%) alone. Over 33% of paclitaxel patients received ≤10 doses. Single-agent use varied from 6.3 to 25.3% across health systems, from 7.7% for age &gt; 40 to 41.0% for ³70, and from 17% with Stage 2 to 10% with Stage 3. In models including race/ethnicity, comorbidity, and HR status, only site, age 60-69 (Adjusted Odds Ratio 1.61, 95% Confidence Interval 1.02, 2.56), age ≥70 (AOR 5.72, 95% CI 3.39, 9.73), stage II vs III (AOR 2.17, 95% CI 1.44, 3.33), and diagnosis after 2020 were associated with increased single cytotoxic use. In sensitivity analyses excluding 2021-22, overall use was lower (12%) but model results were similar. Conclusions: Over 15% of women with Stage II-III HER2+ breast cancers received single-agent cytotoxic chemotherapy, with use increasing substantially with older age and comorbidity. Our findings could inform future strategies to foster evidence-based adoption if ongoing de-escalation trial results are positive.