New data from the Million Women Study indicates that adiposity at different life stages is likely to affect the risk of postmenopausal breast cancer through distinct mechanisms.
Being overweight as an adult has consistently been associated with a decreased risk of breast cancer before the menopause, but an increased risk after the menopause, with these associations being stronger for hormone-sensitive cancers. However, up to now there has been less evidence about how body size in early life affects the risk of postmenopausal breast cancer.
In a new study led by Oxford Population Health’s Cancer Epidemiology Unit (CEU), researchers investigated this using data from over 342,000 UK women who were recruited to the Million Women Study between 1996 and 2001. The results have been published today in BMC Cancer.
Information about the participants’ body size at age 10, clothes size at age 20, and body mass index (BMI)* at recruitment (around age 60) were combined with data from national registries for cancers and deaths. None of the women in the analysis had a prior history of cancer at recruitment, or used menopausal hormone therapy during the study period. The data were adjusted to account for differences in 15 potential confounding variables, including education, social deprivation, reproductive history, alcohol consumption, and smoking status.
After an average follow-up period of 14 years:
- There were 15,506 diagnoses of breast cancer among the study population.
- Greater BMI at around age 60 was associated with an increased risk of postmenopausal breast cancer, with the risk increasing by 20% for each 5kg/m2 increase in BMI.
- Greater body size at age 10 and 20 were associated with a decreased risk of postmenopausal breast cancer. For each 5 kg/m2 increase in BMI, the risk of postmenopausal breast cancer decreased by 30% and 8%, respectively.
- The positive association with BMI at age 60 and postmenopausal breast cancer was largely confined to hormone-sensitive cancers which were both oestrogen-receptor and progesterone-receptor positive.
- The negative association between body size at age 10 and 20 was evident for all breast cancer subtypes considered, regardless of oestrogen or progesterone receptor status.
According to the research team, the fact that the association between adult body size and postmenopausal breast cancer was restricted to hormone-sensitive cancers supports the theory that this is driven by greater serum levels of oestrogen among women of higher BMI, since adipose tissue takes over from the ovaries as the main source of oestrogen after the menopause. In premenopausal women, however, increased adiposity is thought to disrupt the normal menstrual cycle and consequently lower exposure to oestrogen.
In contrast, the fact that the inverse association with body size at age 10 and 20 was not restricted to hormone-sensitive breast cancers suggests that a different mechanism may well be responsible. For example, it has been suggested that adiposity in early life may be related to growth hormone profiles or breast tissue development which could, in turn, affect breast cancer risk.
Lead researcher Dr Owen Yang (CEU) said: ‘To our knowledge, this is the largest study to date of early life body size and the risk of postmenopausal breast cancer. Our findings provide strong evidence that, unlike midlife BMI, adiposity in early life, and particularly in childhood, is associated with a substantial reduction in the risk of postmenopausal breast cancer. This apparent protection was evident for hormone-sensitive cancers, and for other cancers, suggesting that early life adiposity may affect risk through pathways that are not directly related to sex hormones.’
Since excess body weight affects many areas of health besides cancer risk, Dr Yang added that the results do not suggest that being overweight as a child is beneficial. ‘However, understanding the mechanisms behind these associations could indicate potential therapeutic targets.’
(*BMI is a measure of body mass relative to a person’s size, calculated by dividing a person’s weight in kilograms by the square of their height in metres.)