No abstract

Gene expression profile (GEP) testing in early hormone receptor-positive (HR+) breast cancer can inform adjuvant treatment decisions by providing refined estimates of prognosis and chemotherapy benefit. GEPs may also downshift chemotherapy use, potentially avoiding excess morbidity. Multiple studies have reported racial disparities in access to GEP testing. In this study, we examine the effect of race and GEP testing on chemotherapy utilization in early stage HR+ breast cancer. From The University of North Carolina Cancer Information and Population Health Resource (CIPHR), a statewide linkage of cancer registry and administrative claims data, we studied all women eligible for GEP testing, including those with HR+, T1-2, N0 or N1 unilateral primary breast cancers diagnosed from 2005 to 2012. Separate analyses were performed for N0 and N1 patients. Patients were required to have breast surgery within 6 months of diagnosis and no chemotherapy prior to surgery. Use of GEP testing and chemotherapy treatment were defined from insurance claims, while race was defined using cancer registry data. Propensity score adjustment by standardized mortality ratio weighting (SMRW) was used to control for differences in measured patient characteristics between treatment groups in a non-randomized cohort. Propensity score models included age, race, diagnosis year, co-morbidity, and tumor features. Propensity weighted Poisson models were then used to calculate the adjusted risk of receiving chemotherapy. To investigate differential effects of covariates on chemotherapy across racial groups, we used race-stratified models in the N0 cohort. Due to small sample sizes, race-stratified models were not used for N1 patients. The cohort included 11,958 women of whom 84.5% were non-Hispanic white (NHW), 12.9% black, and 2.6% other race/ethnicity. For stratified analyses, race was dichotomized to NHW versus non-white. In the N0 cohort (n=9,671), 11.5% of untested NHW women, 20.8% of tested NHW, 16.8% of untested non-whites, and 21.9% of tested non-whites received chemotherapy. In SMRW-adjusted models, GEP testing was associated with downshifts in chemotherapy for N0 patients (RR 0.79, 95% CI 0.72-0.86) and N1 patients (RR 0.46, 95% CI 0.40 - 0.54). In race-stratified analyses of N0 patients, use of GEP testing was associated with a decrease in chemotherapy of 19% among NHW women (RR 0.81, 95% CI 0.72 - 0.91) and 25% among non-white women (RR 0.75, 95% CI 0.57 - 0.99). Taxane-based regimens were most common, but a substantial portion of chemotherapy-treated patients (43%) received anthracycline-based regimens with or without a taxane. We conclude that GEP testing was associated with decreases in chemotherapy use after propensity adjustment for patient and tumor factors, with greater reductions among non-white patients and node-positive patients. Possible explanations include over-treatment of black women in the absence of testing due to higher perceived risk, racial differences in provider recommendation or chemotherapy choice among tested women where benefit is uncertain, such as for intermediate recurrence scores. Further studies are underway to evaluate racial differences by recurrence score group and the effect of GEPs on racial disparities in outcome. Citation Format: Reeder-Hayes KE, Meyer A-M, Baggett C, Roberts MC, Zhou X, Meng K, Wheeler SB. Racial variation in effects of gene expression profiling on chemotherapy use [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-10-03.

Rationale: The combination of chemotherapy and the monoclonal antibody trastuzumab is the standard of care for systemic adjuvant therapy of HER2-positive breast cancer, substantially improving patient outcomes. Two regimens have been widely adopted for use in the United States, adriamycin/cyclophosphamide/paclitaxel/trastuzumab (ACTH) and docetaxel/carboplatin/trastuzumab (TCH). While other options are available in the neoadjuvant and low-risk settings, ACTH or TCH remain standard of care for many women with early-stage HER2+ disease. No head-to-head comparison of these regimens has been conducted in a clinical trial, and the clinical trial data have limited generalizability due to the exclusion of older women and the low representation of minorities and those with significant co-morbidities. Research Objectives: We used SEER-Medicare data from 2005-2013 to conduct a comparative effectiveness study of ACTH vs TCH among patients over 65 receiving trastuzumab-based adjuvant chemotherapy. An intent-to-treat analytic design was applied and propensity score matching was used to account for selection bias and to balance cohort characteristics between treatment arms. Outcomes included toxicity-related hospitalization, survival, and regimen completion (receiving ≥ 270 days of trastuzumab). Toxicity was evaluated using inpatient and emergency room claims for chemotherapy-related adverse events in the first six months of therapy, as well as all-cause hospitalization over the same period. Data from 1077 patients with HER2+ disease were analyzed and the propensity-matched sub-sample included 416 women. Results: Over time there was a significant shift in regimen use between ACTH vs TCH, with 88% of patients in 2005 receiving ACTH compared to only 15% by 2011. Using the propensity score-matched patients, we found no difference between regimens in healthcare utilization for chemotherapy-related adverse events or all cause hospitalization. (RR=0.99, 95% CI 0.64-1.51) Patients receiving TCH were significantly more likely to complete trastuzumab (89% for TCH vs 77% for ACTH). There was no difference between regimens in five year breast cancer-specific survival or overall survival. Results of a sensitivity analysis limited to patients who completed trastuzumab were similar to the primary analysis. Conclusions: Among older women with HER2+ breast cancer receiving multi-agent regimens with similar levels of medical comorbidity, ACTH compared to TCH did not appear to be associated with a higher rate of serious adverse events or hospitalizations, but was associated with a lower rate of completion of adjuvant trastuzumab. Ability to evaluate cardiotoxicity in this claims-based analysis was limited. We did not detect a difference in five year survival outcomes for ACTH compared to TCH. In the context of limited evidence in older patients, there appears to be little difference between the two regimens in terms of either toxicity or efficacy. Citation Format: Reeder-Hayes KE, Meyer AM, Hinton SP, Ke M, Carey LA, Dusetzina SB. Comparative toxicity and effectiveness of trastuzumab combined with anthracycline versus platinum chemotherapy regimens for adjuvant therapy of HER2+ breast cancer in older women [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-13.