Adjuvant ovarian function suppression and aromatase inhibitors in premenopausal patients with hormone receptor and HER2 positive breast cancer, by timing of chemotherapy and trastuzumab and response to neoadjuvant therapy.

backgroundThe benefit of adjuvant ovarian function suppression (OFS) and aromatase inhibitors (AI) in premenopausal patients with hormone receptor positive, HER2 positive (HR+/HER2+) breast cancer (BC) is unclear. We aimed to investigate this question in a retrospective cohort, stratified by timing (adjuvant or neoadjuvant) of chemotherapy and trastuzumab and by response to neoadjuvant therapy.

methodsPatients aged <45Y at diagnosis, with stage I-III HR + HER2+ BC, treated with (neo)adjuvant chemotherapy and trastuzumab ( ± pertuzumab) and endocrine therapy were included. LHRH-agonists and oophorectomy were considered OFS. We compared distant disease-free survival (DDFS) with tamoxifen, OFS + tamoxifen and OFS + AI in three cohorts: neoadjuvant-pathologic complete response (pCR), neoadjuvant-residual disease (RD) and adjuvant. Endocrine therapy (ET) was modeled as a time dependent covariate in cox logistic regression analyses.

resultsThe study included 1124 patients with median follow-up of 72.6 months (range:0-205 months). DDFS rates at 5 years were 83.9 %, 86.8 % and 92.1 % with tamoxifen, OFS + tamoxifen and OFS + AI respectively in the RD group, 94.3 %, 97.6 % and 96.5 % in the pCR group, and 94.3 %, 93.4 % and 98.6 % in the adjuvant group. OFS + AI was associated with better DDFS compared to tamoxifen in the RD group (n = 366) (multivariable weighted HR 0.28. 95 % CI 0.11-.069, p = 0.006), but associations of ET with DDFS in the pCR (n = 307, p = 0.59) and adjuvant (n = 451, p = 0.18) cohorts were not detected. Stage III was associated with worse DDFS in all groups.

conclusionOFS + AI were associated with better DDFS in patients with RD after neoadjuvant therapy. Our findings can assist shared decision-making on adjuvant endocrine therapy of these patients.