Relationship of patients' age to histopathological features of breast tumours in BRCA1 and BRCA2 and mutation-negative breast cancer families

INTRODUCTION: Our aim was to evaluate the relationship of patients' age to histopathological features of hereditary breast tumours in a series of breast cancer families not selected for age at diagnosis. In sporadic breast cancer, tumours from premenopausal patients have been shown to differ from those of postmenopausal patients, but this phenomenon has been little studied among familial patients. METHODS: Representative areas of all available breast cancer tissue specimens (n = 262) from 25 BRCA1, 20 BRCA2, and 74 non-BRCA1/2 breast cancer families were punched into a tissue microarray. Immunohistochemical staining of oestrogen receptor, progesterone receptor, ERBB2, and p53 as well as the histology and grade of tumours in these three groups of families were studied in different age groups and compared with each other. RESULTS: We found that only breast cancers from young (<50 years) BRCA1(+ )patients represent features documented as being typical of BRCA1-associated cancers, such as high tumour grade, negativity for oestrogen and progesterone receptors, and overexpression of p53. Among the BRCA2 families, the opposite was found, with a significantly higher frequency of tumours negative for oestrogen and progesterone receptors among the older patients than among the other groups, but no distinctive tumour characteristics among the younger BRCA2 patients. CONCLUSION: Tumours of BRCA1 and BRCA2 carriers aged 50 years or more differed significantly from those of younger carriers. This difference may reflect different biological behaviour and pathways of tumour development among the older and the younger BRCA1 and BRCA2 patients, with impact also on prognosis and survival.