Clinical characteristics, tumor-infiltrating lymphocytes, and prognosis in HER2-low breast cancer: A comparison study with HER2-zero and HER2-positive disease

Introduction: HER2-low breast cancer is a gradually recognized and unexplored group of diseases. We aimed to investigate the clinical and prognosis features and to identify the role of stromal tumor-infiltrating lymphocytes (sTILs) in this population. Methods: Consecutive primary breast cancer patients treated between January 2009 to June 2013 were retrospectively reviewed. HER2-low was defined as immunohistochemistry (IHC) 1+, or 2+ and fluorescence in situ hybridization (FISH) negative. sTILs were scored following the international guidelines. Clinicopathologic features and survival were compared according to HER2 and sTILs category. Results: A total of 973 breast cancer patients were enrolled, including 615 (63.2%) HER2-low patients. HER2-low patients shared more similarity with HER2-0 cases in clinicopathological features. sTILs in HER2-Low patients was comparable to HER2-0 patients (p = 0.064), both significantly lower than HER2-positive ones (p < 0.001). Meanwhile, tumors with sTILs >= 50% accounted for the least proportion of HER2-low cases (p < 0.001). HER2 status had no significant influence on recurrence-free survival (RFS, p = 0.901) in the whole population. However, in the estrogen receptor (ER)-negative subgroup, HER2-low was related to worse RFS (p = 0.009) and OS (p = 0.001) compared with HER2-positive ones. sTILs increment was an independent favorable prognostic factor in the whole (OS, p = 0.003; RFS, p = 0.005) and HER2-low population (OS, p = 0.007; RFS, p = 0.009) after adjusted to clinicopathological parameters. Conclusions: HER2-low patients shared similar clinicopathological features with HER2-0 rather than HER2-positive cases and had relatively low sTILs. ER-negative/HER2-low patients had significantly inferior survival. sTILs increment was independently associated with favorable survival in the HER2-low group, suggesting a potential benefit from a novel treatment strategy.