Germline BRCA-mutated, HER2-negative breast cancer

Germline BRCA-mutated, HER2-negative breast cancer is a biologically distinct subset of breast carcinoma occurring in individuals carrying inherited, deleterious alterations in the *BRCA1* or *BRCA2* tumor suppressor genes whose tumors lack human epidermal growth factor receptor 2 overexpression or gene amplification

Germline BRCA-mutated, HER2-negative breast cancer is a biologically distinct subset of breast carcinoma occurring in individuals carrying inherited, deleterious alterations in the *BRCA1* or *BRCA2* tumor suppressor genes whose tumors lack human epidermal growth factor receptor 2 overexpression or gene amplification Clinically, these tumors can present across disease stages as either hormone receptor–positive or triple-negative phenotypes, frequently manifesting at earlier ages and with higher ...

Pathophysiologically, germline loss of functional BRCA proteins impairs homologous recombination repair of DNA double-strand breaks, creating chromosomal instability and pronounced tumor susceptibility to synthetic lethality from poly(ADP-ribose) polymerase inhibition or DNA-damaging agents

Pathophysiologically, germline loss of functional BRCA proteins impairs homologous recombination repair of DNA double-strand breaks, creating chromosomal instability and pronounced tumor susceptibility to synthetic lethality from poly(ADP-ribose) polymerase inhibition or DNA-damaging agents

Clinically, these tumors can present across disease stages as either hormone receptor–positive or triple-negative phenotypes, frequently manifesting at earlier ages and with higher histologic grade than sporadic breast malignancies