Abstract:
Objective This study aimed to analyze the proportion, clinicopathological characteristics, and response to neoadjuvant anti-HER2 targeted therapy in HER2-positive breast cancer patients with BRCA1/2 pathogenic variants. Methods A total of 531 breast cancer patients with germline BRCA1/2 pathogenic variants were included (201 BRCA1, 330 BRCA2). Clinicopathological data were collected. Results Among the 201 BRCA1 and 330 BRCA2 carriers, 17 (8.5%) and 42 (12.7%) HER2-positive breast cancer cases were identified, respectively, accounting for 11.1% of all BRCA1/2-mutated breast cancers. Compared to BRCA1/2-mutated HR-positive/HER2-negative patients, HER2-positive patients showed no significant differences in clinicopathological features. However, compared to triple-negative breast cancer patients, HER2-positive patients had later onset age and lower tumor grades. Among the 17 BRCA1/2-mutated HER2-positive breast cancer patients who received neoadjuvant anti-HER2 targeted therapy, 10 achieved pCR (58.8%), while 7 did not (41.2%). Conclusion HER2-positive breast cancer accounts for over 10% of BRCA1/2-mutated patients. Approximately 40% of these patients fail to achieve pCR after neoadjuvant targeted therapy, highlighting the possibility for combination therapy of anti-HER2 targeted agents with poly (adenosine diphosphate-ribose) polymerase inhibitors.
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