Abstract P1-13-04: Impact of hormone receptor status in HER2-Positive early breast cancer in the trastuzumab era: Results of a National multi-institutional study
Authors: de Nonneville A , Gonçalves A , Cohen M , Reyal F , Classe JM , Giard S , Colombo PE , Muracciole X , Chopin N , Lambaudie E , Houvenaeghel G 
Published: February 2018

Background: Recent updated analysis of the HERA (HERceptin Adjuvant) trial indicate that tumor hormone receptor status (HR)remains a major determinant of outcome in HER2-positive (HER2+) early breast cancer (BC) patients, with higher rates of recurrence and death in women with HR-negative (HR-) disease, even after 11 years' median follow-up. Furthermore, data reported from the HERA trial suggest that the timing of recurrences is different, with an initial higher frequency of disease-free survival (DFS) events in patients with HR- disease than those with HR-positive disease (HR+). No evidence of a different trastuzumab efficacy according to the HR of the primary tumor was found. In this study, we examined the impact of HR on outcome in a large, multicenter, “real-world”, retrospective cohort of HER2+ early breast cancer patients

Methods: HER2+ BC were retrospectively identified from a large cohort of 23,375 consecutive patients who underwent primary surgery at 17 French centers between Dec 1987 and Jan 2014. A multivariate Cox model was built including age, tumor size, SBR grade, lymphovascular invasion, lymph node involvement, hormonal receptors status, adjuvant chemotherapy, adjuvant hormone therapy, trastuzumab, radiotherapy and type of surgery.

Results: A total of 1308 cases were identified, including 829 (63%) HR+ and 479 (47%) HR- patients. Median follow-up was 52 months (range 0 to 201). Compared with HR+, HR- patients had significantly smaller tumors (37 vs. 31% ≤ 10mm, p=0.027; information for multifocal tumors was not available), with higher SBR grade (58 vs. 40% grade 3, p&lt;0.001) and had more lymph nodes involvement (41 vs. 32% pN+, p=0.001). HR- patients were more frequently treated by mastectomy (41 vs. 31%, p&lt;0.001), received more trastuzumab (63 vs. 53%, p&lt;0.001) and less radiotherapy (85 vs. 89%, p=0.020). Endocrine therapy was administered in 90% (744) of HR+ patients. No other significant difference in patient, tumor or treatment characteristics was found. HR status impacted DFS, metastasis free-survival (MFS) and BC-Specific survival (BC-SS) (hazard ratios: 0.46 [0.32-0.66]; p&lt;0.001, 0.52 [0.33-0.82]; p=0.004 and 0.56 [0.34-0.90]; p=0.017, respectively), log-rank test) in overall population with higher rates of recurrence and death in women with HR- disease. In multivariate analysis, lymph node involvement and use of trastuzumab but not HR status impacted significantly DFS, MFS and BC-SS. Considering patients by treatment groups (with or without trastuzumab), HR status was not predictive of survival outcomes in the trastuzumab group, as opposed to the group without trastuzumab. Regarding the timing of recurrences, we observed an increased tendency for later relapse in patients with HR+ disease compared with HR- disease, for both DFS and MFS events.

Conclusions: Our results suggest that HR status remains a major determinant of outcome in HER2+ BC, including the timing of recurrence. Yet, this prognostic impact appears to be mitigated by trastuzumab-based adjuvant treatment.

Citation Format: de Nonneville A, Gonçalves A, Cohen M, Reyal F, Classe JM, Giard S, Colombo PE, Muracciole X, Chopin N, Lambaudie E, Houvenaeghel G. Impact of hormone receptor status in HER2-Positive early breast cancer in the trastuzumab era: Results of a National multi-institutional study [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 P1-13-04.