30 novembre, 2006 18:38
High Body Mass Index at Age 18 Linked to Lower Risk for Breast Cancer
http://www.medscape.com/viewarticle/548568
News Author: Laurie Barclay, MD
CME Author: Désirée Lie, MD, MSEd
November 30, 2006 — High body mass index (BMI) at age 18 years is linked to lower risk for breast cancer in premenopausal women, according to the results of a longitudinal study reported in the November 27 issue of the Archives of Internal Medicine.
"A high body mass index (BMI) has been related to a reduced risk of breast cancer in premenopausal women," write Karin B. Michels, ScD, PhD, of Harvard Medical School in Boston, Massachusetts, and colleagues. "A high BMI can be associated with irregular or long menstrual cycles or with polycystic ovary syndrome (PCOS), and it has been suggested that anovulation, which is associated with such characteristics and with decreased estradiol and progesterone levels, may explain the lower risk of breast cancer in these women. However, few studies have explored whether these or other factors provide mechanistic insights into the unexpected protection that a high body mass confers on the premenopausal breast."
The investigators determined whether factors affecting ovulation could explain the inverse association between BMI and breast cancer in 113,130 premenopausal women enrolled in the Nurses' Health Study II (NHS II).
During 1,225,520 person-years of prospective follow-up between 1989 and 2003, there were 1398 diagnosed cases of invasive breast cancer. Follow-up data included weight, height, ovulatory infertility, menstrual cycle patterns, and other covariates.
There was a linear inverse trend between current BMI and breast cancer incidence (P < .001) that was unexplained by menstrual cycle characteristics or infertility caused by an ovulatory disorder (covariate-adjusted hazard ratio for breast cancer in women with a BMI of 30 kg/m2 or higher vs 20.0 to 22.4 kg/m2 was 0.81; 95% confidence interval [CI], 0.68 - 0.96). BMI at age 18 years was the best predictor of breast cancer incidence (covariate-adjusted hazard ratio for breast cancer in women at age 18 years with a BMI of ≥ 27.5 vs 20.0 - 22.4 kg/m2 was 0.57; 95% CI, 0.41 - 0.81).
Study limitations include possible detection bias because obese women are less likely to seek breast cancer screening than normal-weight women.
"Body size during the early phases of adult life seems to be particularly important in the development of premenopausal breast cancer," the authors write. "Factors other than anovulation are likely to mediate the protection conferred by a high BMI."
The National Cancer Institute, National Institutes of Health, US Department of Health and Human Services supported NHS II. The Massachusetts Breast Cancer Research Grants Program of the Massachusetts Department of Public Health supported this project. The authors have disclosed no relevant financial relationships.
Arch Intern Med. 2006;166:2395-2402.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
Describe the association between BMI and risk for breast cancer.
Identify factors modifying the association between BMI and breast cancer risk.
Clinical Context
According to the current authors, an inverse relationship has been described between BMI and breast cancer risk in premenopausal women, and anovulation is one of the mechanisms postulated for this association. However, it is not clear if the effect is mediated by factors such as PCOS or infertility. This is a large cohort study within the NHS II, involving 116,609 nurses aged 25 to 42 years at baseline who returned a self-administered questionnaire and who were followed up for an average of 14 years, to examine the association between current BMI and BMI at age 18 years and risk for breast cancer in premenopausal women.
Study Highlights
Included were women aged 25 to 42 years living in one of 14 US states.
Excluded were postmenopausal women, those with cancer, those missing the date of diagnosis of breast cancer, or those with missing information on their height or weight.
Information on weight at age 18 years, height, and current weight was obtained from the baseline questionnaire at enrollment.
Participants reported characteristics of their menstrual cycle: length and pattern, and infertility status was determined.
A diagnosis of probable PCOS was made if participants had at least 3 of 4 characteristics: hirsutism, BMI of 27 kg/m2 or higher, irregular menstrual cycles, and infertility due to anovulation.
Infertility was defined as 1 year of attempting to become pregnant without success. Participants were asked for the cause of infertility.
Confounding variables controlled for included age at menarche, age at first birth, benign breast disease, family history of breast cancer, oral contraceptive use, and physical activity.
New cases of breast cancer were identified through biennial questionnaires, and deaths were reported by family members or traced through the National Death Index.
Primary study endpoint was invasive breast cancer.
Analysis was stratified by menstrual cycle length and use of oral contraceptives (current, past, or never).
During 1,225,520 person-years of follow-up, 1398 incident cases of invasive breast cancer were diagnosed in the 113,130 premenopausal women.
Women with a higher BMI were older, had a higher BMI at age 18 years, were less likely to have benign breast disease, were more likely to report menstrual irregularity, and had a history of ovulatory infertility.
Women on both ends of the BMI spectrum were more likely to be nulliparous.
Mean age was 38 years, 20% had a family history of breast cancer, 13% had a history of benign breast disease, mean age at menarche was 12 years, 23% were nulliparous, the mean number of births in parous women was 2.2, and the mean age at first birth was 26 years.
There was a significant inverse trend between current BMI and breast cancer incidence (P < .001).
Women with a BMI of 30.0 kg/m2 or higher had a hazard ratio for breast cancer of 0.79 (95% CI, 0.67 - 0.94) vs women with a BMI between 20.0 and 22.4 kg/m2.
The inverse association between BMI and invasive breast cancer was strongest for BMI at age 18 years.
Women with a BMI of 27.5 kg/m2 or higher at age 18 years had a covariate-adjusted ratio of 0.57 (95% CI, 0.41 - 0.81) vs women with a BMI between 20.0 and 22.4 kg/m2.
The association between BMI at age 18 years and incident breast cancer was stronger for estrogen-receptor–positive tumors.
Age and oral contraceptive use did not modify the risks.
Women with probable PCOS had a hazard ratio for breast cancer of 0.89 (95% CI, 0.71 - 1.10), but when adjusted for BMI at age 18 years, the hazard ratio was 0.98. Hence, the risk is likely to be associated with BMI rather than with PCOS.
Pearls for Practice
There is a linear inverse association between BMI and risk for invasive breast cancer in premenopausal women.
The inverse association is stronger for estrogen-receptor–positive breast cancer and stronger for BMI at age 18 years.
