Clinicopathological Characteristics, Prognosis, and Survival of HER2-Low Breast Cancer Patients Based on a Retrospective Cohort Study of 14,642 Patients

Background and purpose: With the emergence of HER2 antibody–drug conjugates, new treatment options have been provided to patients with breast cancer, especially those with low HER2 expression. The biology of HER2-low breast cancer is not yet well understood. This study included the largest sample size thus far to explore the different clinicopathological characteristics, pathological complete responses (pCRs), and prognoses of HER2-low cancers compared with those of HER2-0 and HER2-high cancers. Methods: This study included 14,642 female breast cancer patients and 544 female patients with breast cancer from the TCGA. A logistic regression model was used to determine predictive factors for pCR. K–M curves and log-rank tests were applied to determine OS and DFS. Results: Compared with HER2-0 and HER2-high patients, the HER2-low group had a greater proportion of members in the N1–2 group and with grade I–II disease, a tumor size ≤ 20 mm, a Ki-67 index ≤ 14%, and invasive cancer. Among the HR+ subtypes of the HER2-low subgroup, the distribution of pathological types, pN stages, Ki-67 values, and tumor sizes significantly differed. In the triple-negative breast cancer subtypes of HER2-low patients, the distributions of age, pathological type, histological grade, and Ki-67 index were significantly different. The Ki-67 index and pathological type were independent factors that affected the pCR of the axillary lymph nodes. HER2 expression was mostly driven by patients who switched to or from HER2-low expression after neoadjuvant chemotherapy. The pCR rate and survival did not differ markedly across the three HER2 subtypes. Conclusions: HER2-low breast cancer is distinct from HER2-0 and HER2-high breast cancer with respect to clinicopathological characteristics. HER2-low breast cancer is highly unstable during chemotherapy; therefore, reevaluating HER2 expression may provide new treatment strategies for some patients after neoadjuvant therapy.