Impact of initial chemotherapy dosing on subsequent dosing patterns and treatment completion in early-stage breast cancer.

Abstract

524 Background: While breast cancer treatment guidelines provide dosing recommendations, some patients do not receive the full expected dose at outset. Preemptive dose reduction, often due to toxicity concerns, may influence subsequent reductions or early discontinuation. The impact of initial dose reductions on subsequent care delivery remains unclear. Methods: The Optimal Breast Cancer Chemotherapy Dosing (OBCD) study is a cohort of 34,109 women diagnosed with stage I-IIIA breast cancer at two U.S. integrated healthcare systems between 2004-2019. We examined associations between first-cycle dose proportion (FCDP), categorized as ≥95%, 90-95%, 85-90%, <85%, with average relative dose intensity (ARDI) categories and early discontinuation. Adjusted prevalence ratios (aPRs) were estimated using generalized linear models of the Poisson family to evaluate associations between FCDP (≥95% vs. <95%) and the likelihood of further dose reductions (based on ARDI) and early discontinuation. Analyses were performed overall and stratified by age, body mass index (BMI), and Charlson comorbidity index (CCI), as older age and comorbidities, including obesity, are linked to higher risk of dose reductions. Results: Among 9,724 women receiving adjuvant chemotherapy, 66% of those with FCDP ≥95% remained fully dosed throughout treatment. In contrast, 46% of patients in both the 90–95% and 85–90% FCDP groups stayed in the same category. The highest likelihood of early discontinuation was seen in patients with FCDP <85% (19%) compared to 13% in the FCDP ≥95% group (p <0.01). Multivariable analyses showed that women with FCDP <95% were more likely to experience further dose reductions (aPR 1.34; 95%CI 1.21-1.49), than those with FCDP ≥95%; but interactions with BMI, CCI, or age were not statistically significant. However, the associations between FCDP and early discontinuation (aPR 1.29; 95%CI 1.11-1.50) varied by BMI (p-interaction 0.02) and age (p-interaction 0.03). A lower FCDP was positively associated with early discontinuation in women with BMI 25-30kg/m 2 (aPR 1.62; 95%CI 1.27-2.07) and BMI 30-35kg/m 2 (aPR 1.50; 95%CI 1.16-1.94), but no association was observed for BMI <25 or >35 kg/m 2 . Patients aged ≤49 years (aPR 1.84; 95% CI 1.39–2.45) and 50–64 years (aPR 1.25; 95% CI 1.07–1.46) with FCDP <95% were more likely to discontinue early, with no association observed in older adults. Conclusions: Women with breast cancer who have FCDP <95% are more likely to experience further dose reductions, regardless of age, BMI, or CCI, suggesting that initiating treatment with reduced doses may not prevent subsequent reductions. Early discontinuation was more likely among patients with FCDP <95%, particularly those with BMI 25–30 or 30–35 kg/m² or younger age. These findings may reflect frailty, treatment intolerance, or patient preferences. Understanding the drivers of these decisions is key to guide strategies that balance toxicity concerns with maintaining adequate dosing to reduce treatment cessation in at-risk groups.