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Redefining therapeutic landscapes: clinicopathological insights into low and ultra-low HER2 expression in male breast cancer

Diagn Pathol. 2025 Apr 15;20(1):43. doi: 10.1186/s13000-025-01632-3.

ABSTRACT

OBJECTIVE: With the emergence of new antibody coupled drugs, the treatment decisions of patients with low and ultra-low HER2 expression have been reshaped. However, the epidemiological characteristics of relatively rare male breast cancer are still unclear. This study discusses the clinicopathological and immunophenotypic characteristics of male invasive breast cancer with low and ultra-low HER2 expression.

METHODS: The clinicopathological and immunophenotypic features of 106 cases of male invasive breast cancer were retrospectively analyzed. HER2 was evaluated according to ASCO/CAP guidelines. The cutoff value of HER2 positive cell staining was > 10%. HER2 negative cases were divided into HER2 low expression (IHC = 1+/2 + and ISH without amplification) and HER2-0 (IHC-0, HER2 null and < 10% weak staining of cell membrane). The clinicopathological characteristics and prognosis of the cases were collected.

RESULTS: 106 male patients with invasive breast cancer from 2015 to 2024 were included in this study, and more than 85% of male breast cancer histological types were invasive ductal carcinoma. Immunophenotype: There were 23 cases of HER2-zero (including 13 cases of HER2 ultra-low), 72 cases of HER2 low, 11 cases of HER2 positive, and the HER2 positive rate was 10.38%, and the incidence of low expression was 67.93%; The incidence of HER2 low in male breast cancer was significantly higher than that in female breast cancer, and the difference was statistically significant (P < 0.05). In terms of prognosis, there was no statistical difference between HER2 low male breast cancer and female breast cancer (P > 0.05). There was no statistical difference in survival prognosis between different HER2 status in the male breast cancer cohort.

CONCLUSION: Male invasive breast cancer is rare, and it is more common in the elderly over 60 years old. The positive rate of ER and PR is high, and the incidence of HER2 low is high. The high HER2 low expression rate of male breast cancer can provide a new anti-HER2 treatment decision.

PMID:40234892 | DOI:10.1186/s13000-025-01632-3

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