Timing of weight gain in relation to breast cancer risk.

Excessive weight gain in women at the time of intense hormonal change can result in metabolic dysfunction. The metabolic/endocrine effect of puberty, pregnancy or menopause on breast tissue 'aging' is likely to be more relevant to a woman's breast cancer risk than is her degree of obesity at the time when the cancer presents. Experimental evidence suggests that the susceptibility of mammary tissue to carcinogenesis is greatest in early adult life, and multiple studies show that a history of weight gain in early adult life is associated with increased breast cancer risk in Western women. Excessive weight gain in that age group is associated with the development of hyperinsulinaemia in individuals with genetic susceptibility to insulin resistance. The insulin resistance syndrome may be a metabolic link between weight gain and breast cancer risk in Western women. Some studies suggest that in postmenopausal women, hyperinsulinaemia is related more to overall obesity, whereas in premenopausal women it is related more to abdominal localisation of fat. This may explain why an increased body mass index is a risk marker for breast cancer in postmenopausal but not premenopausal women. (A premenopausal woman with an average body mass index may have a large intra-abdominal fat mass associated with the presence of hyperinsulinaemia.) It is hypothesised that over-nutrition and inadequate physical exercise favour the development of hyperinsulinaemia and also increase breast cancer risk in women with a genetic susceptibility to both conditions. The hypothesis can be tested by specific intervention studies.