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’
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.