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More Body Fat = Less Breast Cancer Risk Before Menopause

Discussion in 'Oncology' started by Dr.Scorpiowoman, Jun 25, 2018.

  1. Dr.Scorpiowoman

    Dr.Scorpiowoman Golden Member

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    Adiposity in young adulthood or childhood could be critical factor, investigators said

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    A higher body-mass index (BMI) was associated with lower breast cancer risk in premenopausal women, according to a pooled analysis of 19 large prospective cohort studies.

    The analysis found an age-related linear association, with the greatest risk reduction in women 18-24 years old (hazard ratio per 5 kg/m2 0.77; 95% CI 0.73-0.80) and less of a reduction in older women, with the weakest association in women 45-54 (HR per 5 kg/m20.88; 95% CI 0.86-0.90), said Minouk Schoemaker, PhD, of the Institute of Cancer Research in London, and colleagues.

    "Obesity is linked with a higher risk of breast cancer in older women and is one of the leading causes of cancer worldwide," said Schoemaker in a statement. "But our study shows that the link with breast cancer is more complicated than we thought, and that younger women with higher BMIs are at lower risk of the disease before the menopause."

    The inverse association with BMI was found even in normal-weight and underweight women, with more than a fourfold risk gradient between the highest BMI category (35 and higher) and the lowest (less than 17) in women ages 18-24 (HR 0.24; 95% CI 0.14-0.40), the researchers reported in JAMA Oncology.

    The investigators adjusted for risk factors including age at menarche, age at first birth, and family history of breast cancer. The association was stronger for estrogen receptor (ER)-positive and progesterone receptor (PR)-positive breast cancer than for hormone receptor–negative cancer at every age group. For example, in women age 18-24, the risk reduction associated with ER-positive and PR-positive tumors was 24% per 5 kg/m2 (HR 0.76; 95% CI 0.70-0.81) and only 15% for hormone receptor–negative tumors (HR 0.85; 95% CI 0.76-0.95), the study found.

    "The observed inverse associations are unlikely to be attributable to bias, given that they were present in multiple studies and across strata of birth cohort and risk factors for breast cancer. The stronger inverse associations of risk with BMI at younger than older ages suggest that adiposity in young adulthood or earlier ... is the critical factor," the study authors wrote.

    "Obesity has many adverse effects on general health, and we do not advocate weight gain as a preventative measure against premenopausal breast cancer. However, understanding the mechanistic action underlying the inverse association of premenopausal adiposity with breast cancer risk could potentially identify modifiable pathways. Because the association with BMI at ages 18 to 24 is significant for ER-positive and ER-negative tumors, hormonal and non-hormonal mechanisms might be involved," the authors wrote.

    The researchers explained that breast tissue is particularly susceptible to carcinogens between menarche and first childbirth, and this susceptibility may be influenced by childhood adiposity. Greater adiposity has a strong association with early onset of puberty but also with slower pubertal tempo, including slower peak growth, and rapid adolescent growth has been associated with increased breast cancer risk.

    The estrogenic effects of being overweight in childhood, when adipose tissue is the major site of estrogen release, have been proposed to induce early breast differentiation or to increase the expression of tumor-suppressor genes, said Schoemaker et al. In contrast, being underweight during adolescence might result in immature differentiation due to lack of breast fat and/or low levels of ovarian hormones during breast development.

    "After the menopause, obese women have an increased risk of breast cancer, which is likely due to estrogen hormones produced by fat cells," said Schoemaker. "We now need follow-up research to understand why this effect seems to be reversed in younger women."

    Study Details

    The analysis pooled data on 758,592 women from 19 prospective cohort studies: nine in North America, seven in Europe, two in Asia, and one in Australia. Participants were recruited from 1963 through 2013. The median age was 40.6, and median follow-up per participant was 9.3 years. Follow-up ended at breast cancer diagnosis, menopause, death, or age 55, whichever came first. There were 13,082 incident cases of breast cancer before menopause during follow-up.


    Information on height and weight was sometimes self-reported, and sometimes measured. The study authors used Cox proportional hazards regression analysis to look for associations between BMI and breast cancer risk at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54.

    Limitations of the study, the authors said, included that weight was often self-reported, and participants sometimes over- or under-report their weight. In addition, BMI was used as a measure of adiposity, but women with the same BMI can have different body fat distribution and overall levels of body fat, and this was not taken into account.

    "The results of our study suggest that increased BMI is inversely associated with the risk of breast cancer diagnosis before menopause, to a greater magnitude than suggested in previous analyses, and with the strongest associations for BMI at young ages. Understanding the biological mechanism underlying this association could have important implications for breast cancer prevention."

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