Anees B. Chagpar

Abstract P6-06-37: Predicting improvements in survival based on improvements in pathologic response rate to neoadjuvant chemotherapy in different breast cancer subtypes

Background: Individuals with excellent pathologic response (complete response or minimal residual cancer burden, pCR+RCB-I) to neoadjuvant chemotherapy have prolonged survival, and several chemotherapy regimens have resulted in improved pathologic response rates. However, how to estimate expected improvements in disease free survival (DFS) in a clinical trial based on improvement in pathologic response remains uncertain. The purpose of this study was to develop a statistical tool to estimate improvements in DFS based in improvements in pCR/RCB-I in triple negative (TNBC) and HR+/HER2- breast cancer subtypes. Methods: 387 clinical stage II (73%) and III (23%) breast cancers who received neoadjuvant T/FAC chemotherapy at MD Anderson Cancer Center were included in this analysis (N = 127 TNBC, N = 260 HR+/HER2-). Patients received adjuvant endocrine therapy if HR+. To evaluate the association between pCR rate and survival we used within-subtype stratified bootstrap analysis with biased resampling from the two response groups (pCR and RCB-I) to generate 500 bootstrapped populations with a range of different response rates. Survival was based on the Kaplan-Meier estimator with its variance obtained from the bootstrap standard error. Power was estimated as the probability of no overlap in the 95% log confidence intervals of survival in 500 bootstrap replicates of populations of different sizes and response rates. Results: Excellent pathologic response (pCR or RCB-I), was observed in 50% and 23% in the TNBC and ER+/HER2- cohorts respectively. The median follow-up was 7.6 years (range 0.1 to 13.4 years); 48 and 59 relapses occurred in the TNBC and HR+ subtypes, respectively. Bootstrap analysis showed a linear dependence of the 5-year DFS on the pCR/RCB-I rate, with a slope of 0.472 for TNBC suggesting a 4.7% improvement in DFS for every 10% increase in response rate. A more modest slope of 0.129 was observed for ER+/HER2- cancers. The sample size of a randomized 2-arm study required to show with 80% power a statistically significant improvement in 5-year DFS that corresponds to 75% response rate compared to baseline response rate of 50% and 23% in TNBC and ER+/HER2- would be 1144 and 1688 cases respectively. We are providing an open-access web-based calculator to estimate improvements in DFS and for sample size calculations for randomized clinical trials with combined endpoints of pCR/RCB-I and survival. Conclusions: We observed a linear increase in DFS with increase in pathologic response rate in the evaluated cohort. The slope depends on breast cancer subtype - it is greater in TNBC than in ER+ cancers - and expected to be influenced by the stage distribution in the study population. These results could help provide a basis for powering studies with combined response and survival endpoints. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-37.

Abstract P1-09-01: African American women have lower pathologic complete response rates to neoadjuvant chemotherapy compared to white women for triple negative and HER 2 positive breast cancer

Introduction Although racial disparities in breast cancer treatment have been well documented, data regarding differences in response to neoadjuvant chemotherapy are few. In 2010 the National Cancer Database (NCDB) included a new variable, documenting pathologic complete response (pCR) after neoadjuvant chemotherapy. The purpose of this study was to explore racial differences in the rates of pCR by molecular subtype. Methods The NCDB was queried to identify women diagnosed with invasive, stage 1-3 breast cancer in 2010 -2011 who received neoadjuvant chemotherapy. Univariate and multivariate logistic regression was performed to determine factors associated with likelihood of pCR. Results Out of 278,815 patients with known race and ethnicity, 27,300 (10%) received neoadjuvant chemotherapy. Of 17,970 where the outcome was known, 5,944 (33%) had a pCR. As seen in the table, there were no differences in response rate for ER/PR+ tumors, but compared to whites, non-hispanic black women had a lower rate of pCR for ER/PR- Her2+ and triple negative tumors. This difference persisted when adjusted for patient age, clinical T stage, clinical N stage, histology, grade, comorbidity index, facility type, geographic region, insurance status, and census-derived median income and education for the patient9s zip code (OR 0.84, 95% CI: 0.77-0.93). Conclusions Non-hispanic black women have a lower likelihood of pCR after neoadjuvant chemotherapy compared to white women for triple negative and Her 2 positive breast cancer. It is unknown whether this is due to biologic differences in chemosensitivity or whether it represents treatment or socioeconomic differences that cannot be adjusted for in the current analysis. Citation Format: Killelea BK, Chagpar AB, Horowitz NR, Pusztai L, Wang S, Mougalian S, Lannin DR. African American women have lower pathologic complete response rates to neoadjuvant chemotherapy compared to white women for triple negative and HER 2 positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-09-01.

Abstract P3-14-02: Patterns of the use of primary systemic therapy in the United States

Background: Primary systemic therapy (PST) is an accepted alternative to adjuvant systemic therapy of breast cancer. It provides equivalent survival, increased breast conservation rates, and prognostic information. Methods: This analysis assesses patterns of PST use based on information collected by the National Cancer Database (NCDB), a joint project of the American College of Surgeons and the American Cancer Society which captures data on over 70% of all diagnosed breast cancer patients in the U.S. Using the b-participant use file of the NCDB, we evaluated regional, patient, and tumor factors associated with PST use. Results: The NCDB captured 621,319 patients treated with PST from 2006 to 2010. Of these, 7.4% received systemic therapy pre-operatively, and 3.6% in both the pre- and post-operative settings. Factors correlating with timing of therapy are shown in the table. PST use increased steadily from 7.0% to 7.8% (p<0.001) from 2006 to 2010. PST was significantly more frequently used in younger, African-American, Hispanic, low-income, uninsured patients with larger, node positive tumors, living in large metropolitan areas in the West and treated in academic centers. These factors remained significantly and independently associated with PST on multivariate analysis. View this table: Conclusion: PST appears to be underutilized, received by only 7.8% of all patients, 36% of T3-T4 tumors, and 26.0% of clinically node positive patients. However, its rate of use has increased over the past years. There is also significant regional variation in the use of PST, independent of patient and tumor factors. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-02.