Familial breast cancer

Recent developments in molecular genetics and the identification of a number of breast cancer predisposition genes (BRCA1, BRCA2 and TPS3) have done much to stimulate interest in this fascinating area. Yet women whose breast cancer is due to an inherited generic change actually account for less than 5 per cent of all breast cancers — that is about 1250 cases per year in the UK and 9000 cases in the USA. A much larger number of women will have a risk elevated above normal due to an as yet unspecified familial inheritance. These women have a risk of developing breast cancer two to 10 times above baseline.

The risks associated with family history are summarised in Table 46.8.

The BRCAI gene has been cloned and is located on the long arm of chromosome 17 (17q). The gene frequency in the population is approximately 0.0006. BRCA2 is located on chromosome 13q. Women who are thought to be gene carriers may be offered breast screening (and ovarian screening in the case of BRGA1, which is known to impart a 50 per cent lifetime risk of ovarian cancer), usually as part of a research programme, or may be offered generic counselling and mutation analysis. Those who prove to he ‘gene positive’ have an 80 per cent risk of developing breast cancer, predominantly whilst premenopausal. Many will opt for prophylactic mastectomy, although this does not completely eliminate the risk.

For,those with a positive family history who are unlikely to be carriers of a breast cancer gene, which will comprise the great majority of women, there is no currently proven preventive or screening manoeuvre, although these are under investigation. Thus these women are best served by being assessed and followed up, if necessary, in a properly organised research family history clinic.

Pregnancy

The effects of pregnancy on breast cancer are not well studied but it is thought that breast cancer presenting during pregnancy or lactation tends to be at a later stage — presumably because the symptoms are masked by the pregnancy — but in other respects it behaves in a similar way to breast cancer in a nonpregnant young woman, and should be treated accordingly. Thus treatment is similar with some provisos:

radiotherapy should be avoided during pregnancy, making mastectomy a more frequent option than breast conservation surgery; chemotherapy should he avoided during the first trimester but is probably safe subsequently; most tumours are hormone receptor negative and so hormone treatment, which is potentially teratogenic, is not required. Becoming pregnant subsequent to a diagnosis of breast cancer appears not to alter likely outcome, hut women are usually advised to wait at least 2 years, as it is within this time that recurrence most often occurs.

The risk of developing breast cancer with oral contraceptive use is only slight, and disappears 10 years after stopping the Pill.