Association of low HER2 expression with specific mortality risk in early-stage breast cancer: A competing risk analysis of 2645 patients

The current study aimed to evaluate the HER2 status and clinicopathological characteristics of patients with early stage breast cancer (BC) accounting for competing risks. We reviewed the prospectively maintained database of our institution to identify adult women with HER2-negative BC diagnosed between January 2010 and December 2019. We calculated the cumulative incidence function (CIF) for breast cancer-specific death (BCSD) and constructed the Fine and Gray’s proportional subdistribution hazard model, as well as a joint analysis to predict the risk of cause specific death in each combination. Of the 2645 patients with HER2-negative BC identified, 1945 (73.5 %) had low HER2 expression and 700 (26.5 %) were completely HER2 negative (HER2-zero). The proportion of luminal-type (HR-positive) BC was significantly higher in patients with HER2-low tumors than in those with HER2-zero tumors (91.9 % vs 78.4 %, p < 0.001). Predictors of BCSD include older age, advanced stage, HER2-zero, HR-negative, recurrence and positive axillary lymph node. HR-negative alone was associated with BCSD, with an adjusted subdistribution hazard ratio (sHR) of 4.21 (95 % CI: 1.70–10.40; p = 0.002). The adjusted sHR of BCSD increased to 10.94 for HR-negative patients who had HER2-zero status and axillary lymph node dissection (ALND) compared with patients who had a luminal subtype with HER2-low status and sentinel lymph node biopsy (SLNB). The findings of the present study indicate that HER2-zero is a distinct biomarker for poor prognosis in comparison with HER2-low, with a difference that is especially prominent in the HR-negative subgroup.