Abstract P4-05-10: Comparative analysis of genomic landscape reveals heterogeneity in HER2-positive primary breast cancers and residual disease following neoadjuvant therapy

Background: Neoadjuvant therapy is currently standard of care for patients with HER2-positive (HER2+) breast cancer. Patients with residual disease after neoadjuvant therapy have a higher risk of metastatic recurrence compared to patients achieving pathologic complete response (pCR). While both primary breast cancer and residual disease may harbor cancer cell subpopulations with high metastatic potential, residual disease after neoadjuvant targeted therapy may include larger subpopulations of therapy-resistant cells. A better understanding of the differences in genomic aberrations in residual disease following neoadjuvant therapy in comparison to primary breast cancer is essential to choice of novel post-neoadjuvant treatment strategy for HER2+ patients with residual disease. Methods: We are currently building a large ethnically diverse, breast cancer cohort with integrated genomic data. We analyzed clinical data of stage 1-3, HER2+ breast cancer. pCR after neoadjuvant therapy was defined as ypT0N0 or ypTisNo. Using the xT 595-gene panel (Tempus Labs, Inc.) with matched tumor-normal samples in a subset of the cohort, we evaluated genomic heterogeneity between HER2+ primary breast cancers and residual disease following neoadjuvant therapy. Results: There were 469 HER2+ early stage invasive breast cancer patients in the study cohort with a median follow-up of 6.0 years. The mean age at diagnosis was 53.6 (SD=13.4) years. 52.7% are European Americans and 39.2% are African Americans. 61.8% were hormone receptor-positive (HR+)/HER2+ and 37.7% were HR-/HER2+. Although patients undergoing neoadjuvant chemotherapy (n=191) had lager tumor and more nodal positive disease compared to patients undergoing adjuvant therapy (n=213), the two groups have similar recurrence-free survival rate (adjusted hazard ratio 0.88, 95% CI 0.50-1.55). In patients undergoing neoadjuvant therapy, 72 (37.7%) achieved pCR. Women with HR-/HER2+ tumors had higher pCR rate (58.9%), compared with 24.6% in women with HR+/HER2+ tumors (p Citation Format: Masaya Hattori, Dezheng Huo, Nike Beaubier, Padma Sheila Rajagopal, Toshio Yoshimatsu, Yonglan Zheng, Elisabeth Sveen, Galina Khramtsova, Fang Liu, Taylor Abboushi, Kevin White, Olufunmilayo Olopade. Comparative analysis of genomic landscape reveals heterogeneity in HER2-positive primary breast cancers and residual disease following neoadjuvant therapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-05-10.