Abstract P3-03-09: Assessment of Breast Cancer Chemotherapy Dose Reduction in an Integrated Healthcare Delivery System
Authors: Kantor Elizabeth D. , O’Connell Kelli , Ergas Isaac J. , Valice Emily , Roh Janise M. , Bhimani Jenna , Heon Narre , Griggs Jennifer J. , Lee Jean , Bowles Erin J. , Rivera Donna R. , Kolevska Tatjana , Bandera Elisa , Kushi Lawrence H. 
Published: March 2023

Background: Most cytotoxic drugs are dosed according to body surface area (BSA), yet not all patients receive the full BSA-determined dose. Prior work suggests that dose reduction may occur more frequently in obese patients, likely due to concern about inducing toxicity at high doses. Other factors, such as race/ethnicity, have been suggested to be associated with dosing, yet the factors associated with dose reduction remain poorly understood, with little known about dosing patterns in integrated healthcare delivery systems and how such patterns have changed over time. Methods: We examined chemotherapy dosing in 452 women diagnosed with stage I-IIIA primary breast cancer at Kaiser Permanente Northern California. All study participants were a part of the Pathways Study, diagnosed between 2006-2013, and treated with the common breast cancer regimen, ACT (cyclophosphamide and doxorubicin, followed by paclitaxel). We explored the association between obesity and dose reduction, and further explored other factors in relation to dose reduction, including various sociodemographic characteristics, tumor characteristics, and comorbidities. We assessed dosing using first cycle dose proportion (&lt; 90% expected dose) and average relative dose intensity (ARDI, a metric of dose intensity over the entire course of chemotherapy). Results: Overall, 8% of women received a dose reduction &gt;10% in the first cycle of chemotherapy and 21.2% of patients had an ARDI &lt; 90%. Obesity was a strong predictor of dose reduction, both in the first cycle and across all cycles. In the first cycle, 21.9% of severely obese patients (body mass index, BMI: 35+ kg/m2) were dose reduced, whereas no normal weight patients (BMI: 18.5-&lt; 25 kg/m2) experienced a first cycle dose reduction. Across all cycles, 38.4% of severely obese women had an ARDI &lt; 90%, as compared 12.8% of normal weight women. In logistic regression models adjusted for age, race/ethnicity, and white blood cell count, obese women had 4.1-fold higher odds of receiving a dose reduction of 10% or more over the course of chemotherapy than their normal weight counterparts (95% CI: 1.9, 8.9; p-trend: 0.006). Increasing age was positively associated with dose reduction across the course of chemotherapy, as was the presence of comorbidity. Importantly, dose reduction was less common in later calendar years. Sensitivity analyses revealed that the positive association between obesity and dosing was robust to further adjustment for these other significantly associated factors. Impact: These results offer insight on factors associated with variation in chemotherapy dosing for a common breast cancer treatment regimen. Larger studies are required to evaluate relevance of these findings to other treatment regimens. Further work will be needed to determine whether dose reductions impact breast cancer outcomes.

Citation Format: Elizabeth D. Kantor, Kelli O’Connell, Isaac J. Ergas, Emily Valice, Janise M. Roh, Jenna Bhimani, Narre Heon, Jennifer J. Griggs, Jean Lee, Erin J. Bowles, Donna R. Rivera, Tatjana Kolevska, Elisa Bandera, Lawrence H. Kushi. Assessment of Breast Cancer Chemotherapy Dose Reduction in an Integrated Healthcare Delivery System [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-09.