Clinical significance of progesterone receptor and HER2 status in estrogen receptor-positive, operable breast cancer with adjuvant tamoxifen.

PURPOSE: To evaluate prognostic factors in estrogen receptor (ER)-positive, operable breast cancer focusing on the progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). PATIENTS AND METHODS: A total of 819 patients with ER-positive, operable breast cancer were enrolled. All patients received upfront adjuvant tamoxifen, as stipulated by eligibility criteria. Prognostic values of the PR status and HER2 status were evaluated using Cox regression. RESULTS: Of all patients enrolled, 72% were PR positive and 20% were HER2 positive. PR and HER2 status were inversely correlated (P = 0.014). PR-negative tumors were associated with older age over 50 years (P < 0.001) and higher histologic grade (P = 0.024). HER2 overexpression correlated with older age over 50 years (P = 0.007), higher T stage (P = 0.010), and higher histologic grade (P = 0.047). For recurrence, PR negativity was a poor prognostic factor before 5 years postsurgery (hazard ratio = 1.57; P = 0.049) and HER2 overexpression was a consistent poor prognostic factor over all time periods (hazard ratio = 1.93; P = 0.001) in the multivariate model adjusted by age, T/N stage, and histologic grade. CONCLUSIONS: In ER-positive, operable breast cancer, PR negativity may provide additional information on poor prognosis or tamoxifen resistance during adjuvant tamoxifen therapy within 5 years postsurgery. HER2 overexpression was a poor prognostic factor consistently throughout time. This suggests that an alternative adjuvant strategy, possibly incorporating prolonged HER2-targeted therapy, needs to be evaluated for HER2-overexpressing tumors.ope