Predicted anti-oestrogen resistance in BRCA-associated familial breast cancers.

There is controversy concerning the prognosis of breast cancers arising in women carrying loss of function mutations in the breast cancer susceptibility genes BRCA1 and BRCA2. This study was carried out to assess the likely hormone dependence of this group of tumours in comparison with an age and grade matched group of control sporadic tumours. We used quantitative immunohistochemical analysis for the oestrogen receptor (ER), progesterone receptor (PgR), cyclin D1 and pS2 on sections of primary tumours and ductal carcinoma in situ (DCIS). Expression of PgR (P < 0.05) and cyclin D1 (P < 0.01) was low in the BRCA1- and BRCA2-associated cancers compared with sporadic cases. The low frequency of expression of ER (9/40), PgR (2/40) cyclin D1 (5/36) and pS2 (5/36) in the familial tumours indicates that the majority of such tumours will be oestrogen insensitive and unlikely to respond to hormonal manipulation even at the in situ stage in their evolution. The low level of PgR (2/40 cases) suggests that there may be some abnormality of transactivating function of the ER in these tumours.