It’s All in the Genes:
Prognosis of BRCA-positive and HER2-positive Breast Cancer Patients
DELRAY BEACH, FL – A recent multicenter observational study was conducted to evaluate the clinicopathological characteristics and prognosis of women with breast cancer based on their HER2 and BRCA status. The study found that HER2-positive status, characterized by the overexpression or gene amplification of the HER2 protein, is associated with higher aggressiveness in breast cancers. While anti-HER2 therapies are effective for HER2-positive breast cancer, resistance to these drugs can occur. The study aimed to investigate the clinical outcome of HER2-positive breast cancers in patients with BRCA mutations, which are known to be associated with hereditary breast and ovarian cancer syndrome. The results showed that the co-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer.
The study evaluated 115 cases of HER2-positive/BRCA mutated breast cancer and compared them to three control groups: HER2-positive/BRCA wild type, HER2-negative/BRCA mutated, and HER2-negative/BRCA wild type. It was observed that HER2-positive/BRCA mutated cases were more frequently associated with BRCA2 mutations, while HER2-negative/BRCA mutated controls more commonly had BRCA1 mutations. Patients with HER2-positive breast cancer had higher histologic grade and proliferation rates compared to HER2-negative tumors, regardless of BRCA mutation status. Treatment with trastuzumab-based neoadjuvant and/or adjuvant therapy was more common in HER2-positive cases, while less than half of HER2-negative patients received neo- or adjuvant chemotherapy. Importantly, HER2-positive/BRCA mutated cases had poorer 5-year overall survival rates compared to the control groups.
The study highlights the negative prognostic impact of co-occurring BRCA mutations and HER2-positive status in early or locally advanced breast cancer. It adds to the existing knowledge on the association between HER2-positive breast cancer and BRCA mutations, which are commonly associated with hereditary breast and ovarian cancer syndrome. The findings suggest that patients with HER2-positive/BRCA mutated breast cancer may have a worse prognosis compared to other subgroups, emphasizing the importance of identifying predictive factors of response and resistance to anti-HER2 therapies in this population. Further research is needed to better understand the underlying mechanisms and potential targeted treatment approaches for this high-risk group of patients.
- Viansone A, Pellegrino B, Omarini C, et al. Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer. Breast. 2022;65:145-150. doi:10.1016/j.breast.2022.07.012