The Clinicopathological and Prognostic Significance of HER2-Low Breast Cancer: A Comparative Analysis Between HER2-Low and HER2-Zero Subtypes

HER2-low breast cancer (BC) is a newly defined subset of HER2-negative BC. However, it is still uncertain whether HER2-low BC can be categorized as a distinct biological/clinical subgroup with any prognostic significance. Invasive BC cases (n = 10,215) with Stage I-III were retrospectively analyzed to determine the HER2 status. The HER2 status was then divided into 3 groups: HER2-0, HER2-low, and HER2-positive. The HER2 status was classified as HER2-0 in 1,227 cases (12.0%), HER2-low in 7,209 cases (70.6%), and HER2-positive in 1779 cases (17.4%). HER2-low cases had more positive nodes and were significantly associated with positive ER/PgR, lower nuclear grade, and lower Ki-67 index. HER2-0 had the lowest OS rate in the primary cases and after recurrence. HER2-0 in the node positive group had the lowest OS and was significantly different from HER2-low in the same group. The pathological complete response (pCR) rate for NAC was lowest in the HER2-low group. The DFS after NAC was significantly better in all the pCR cases, regardless of the HER2 status. However, the DFS was significantly lower in the HER2-low non-pCR cases. HER2-low accounted for 70% of the cases and correlated with favorable biological markers. The HER2-low group had a significantly better OS than the HER2-0 group. However, the response to NAC was low in the HER2-low group, and this group had the poorest prognosis among all the non-pCR cases. These findings indicate that HER2-low may have a different biology and prognosis and therefore should be classified as a new entity. A retrospective study of 10,215 cases in the field of breast cancer research was conducted to determine whether HER2-low is a distinct subtype. HER2-low accounted for 70% of the cases and correlated with favorable biological markers and prognosis. The findings indicate that HER2-low may have a different biology and prognosis and therefore should be classified as a new entity.