While hormone receptor-positive (HR+) and negative (HR-) HER2+ breast cancers (BC) are thought to be distinct diseases, only few studies have investigated the impact of HR status in the context of trastuzumab (TRZ)-treated BC. We evaluated the impact of HR status on outcomes of HER2+ early BC, before and after generalization of TRZ.
Patients were identified from a cohort of 23,374 women who underwent primary surgery in 18 centers between 2000 and 2017. Since the year 2005 marked the generalization of TRZ, we conducted distinct analyses in patients treated between 2000 and 2004 and those treated between 2005 and 2017. Impact of HR status analyses were done with censorship of events occurring after 5 years in both cohorts. Proportionality tests included all events.
Of 970 HER2+ patients, 349 were treated between 2000 and 2004 without TRZ, and 621 between 2005 and 2017, with TRZ-based adjuvant chemotherapy. Endocrine therapy was received by 92 and 94% of HR+ patients, respectively. In the first group, HR status impacted disease-free survival (DFS) in univariate analysis (Hazard ratio: 2.44 [1.43-4.19]; p < 0.001, log-rank test). Conversely, HR status did not significantly impact DFS in the cohort with TRZ (1.34 [0.66-2.71], p = 0.414). Overall survival was also impacted by HR status in the group without TRZ (Hazard ratio: 2.49 [1.23-5.04]; p = 0.009), but not in the TRZ group (0.68 [0.23-2.00]; p = 0.482). These results were maintained in multivariate analysis including age, LVI, lymph node involvement, histology, grade and tumor size. Evolution of Hazard ratio over time for cumulative incidence of first recurrence according to HR status in patients without TRZ showed a non-proportionality of risks on metastatic (p = 0.027, AD-test) recurrences, with a decreasing risk for HR- over time. Conversely, the analysis of cumulative incidence of first recurrence did not show such a trend in patients treated with TRZ, suggesting the proportionality of the risks over time for HR status.
Instead patients treated without TRZ, HR status was no longer determinant of outcomes when patients received TRZ. These observations are supported by the analysis of Hazard ratio’s evolution over time for cumulative incidence of first metastatic recurrence.
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All authors have declared no conflicts of interest.