Longitudinal study on the role of body size in premenopausal breast cancer.

BACKGROUND A high body mass index (BMI) has been related to a reduced risk of breast cancer in premenopausal women. The mechanisms underlying this association have not been elucidated. METHODS We explored whether factors affecting ovulation may explain the inverse association between BMI (calculated as weight in kilograms divided by the square of height in meters) and breast cancer in 113,130 premenopausal participants in the Nurses' Health Study II. During 1,225,520 person-years of prospective follow-up between 1989 and 2003, 1398 incident cases of invasive breast cancer were diagnosed. Weight, height, ovulatory infertility, menstrual cycle patterns, and a multitude of covariates were assessed throughout follow-up. Cox proportional hazards regression was used to compute hazard ratios and 95% confidence intervals (CIs). RESULTS We observed a significant linear inverse trend between current BMI and breast cancer incidence (P<.001) that was not explained by menstrual cycle characteristics or infertility due to an ovulatory disorder (covariate-adjusted hazard ratio for breast cancer in women with a BMI > or =30 vs 20.0-22.4, 0.81; 95% CI, 0.68-0.96). We found BMI at age 18 years to be the strongest predictor of breast cancer incidence (covariate-adjusted hazard ratio for breast cancer in women with a BMI at age 18 years > or =27.5 vs 20.0-22.4, 0.57; 95% CI, 0.41-0.81). CONCLUSIONS Body size during the early phases of adult life seems to be particularly important in the development of premenopausal breast cancer. Factors other than anovulation are likely to mediate the protection conferred by a high BMI.

[1]  Roger B. Davis,et al.  Obesity and breast cancer screening , 2004, Journal of General Internal Medicine.

[2]  W. Willett,et al.  A prospective study of infertility due to ovulatory disorders, ovulation induction, and incidence of breast cancer. , 2006, Archives of internal medicine.

[3]  M. Dowsett,et al.  Birthweight and Body Size throughout Life in Relation to Sex Hormones and Prolactin Concentrations in Premenopausal Women , 2006, Cancer Epidemiology Biomarkers & Prevention.

[4]  K. Michels,et al.  Role of birthweight in the etiology of breast cancer , 2006, International journal of cancer.

[5]  D. Spiegelman,et al.  Endogenous steroid hormone concentrations and risk of breast cancer among premenopausal women. , 2006, Journal of the National Cancer Institute.

[6]  A. Aalborg,et al.  Barriers to routine gynecological cancer screening for White and African-American obese women , 2006, International Journal of Obesity.

[7]  W. Willett,et al.  Menstrual Cycle Characteristics and Incidence of Premenopausal Breast Cancer , 2005, Cancer Epidemiology Biomarkers & Prevention.

[8]  J. Chang-Claude,et al.  Serum Sex Steroids in Premenopausal Women and Breast Cancer Risk Within the European Prospective Investigation into Cancer and Nutrition (EPIC) , 2005 .

[9]  R. Kay,et al.  Influence of height, weight, and obesity on breast cancer incidence and recurrence in Auckland, New Zealand , 2005, Breast Cancer Research and Treatment.

[10]  F. Clavel-Chapelon,et al.  C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC) , 2005, Cancer Causes & Control.

[11]  W. Willett,et al.  Body fatness during childhood and adolescence and incidence of breast cancer in premenopausal women: a prospective cohort study , 2005, Breast Cancer Research.

[12]  W. Willett,et al.  Breast cancer--early life matters. , 2004, The New England journal of medicine.

[13]  F. Clavel-Chapelon,et al.  Body size and breast cancer risk: Findings from the European prospective investigation into cancer and nutrition (EPIC) , 2004, International journal of cancer.

[14]  H. Pijl,et al.  Prolactin release is enhanced in proportion to excess visceral fat in obese women. , 2004, The Journal of clinical endocrinology and metabolism.

[15]  B. Ambrosi,et al.  Anthropometric, hormonal and biochemical differences in lean and obese women before and after menopause , 2004, Journal of endocrinological investigation.

[16]  F. Berrino,et al.  Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women. , 2004, European journal of endocrinology.

[17]  T. Key,et al.  Lifestyle determinants of serum insulin-like growth-factor-I (IGF-I), C-peptide and hormone binding protein levels in British women , 2003, Cancer Causes & Control.

[18]  M. Inoue,et al.  Association of Family History and Other risk factors with Breast Cancer Risk among Japanese Premenopausal and Postmenopausal Women , 2001, Cancer Causes & Control.

[19]  L. Kolonel,et al.  Anthropometric predictors of breast cancer incidence and survival in a multi-ethnic cohort of female residents of Hawaii, United States , 1998, Cancer Causes & Control.

[20]  C. Nagata,et al.  Association of body mass index, physical activity, and reproductive histories with breast cancer: a case-control study in Gifu, Japan , 1997, Breast Cancer Research and Treatment.

[21]  H. Adami,et al.  Anthropometric measures and breast cancer in young women , 1990, Cancer Causes & Control.

[22]  T. Key,et al.  Circulating levels of sex hormones and their relation to risk factors for breast cancer: a cross-sectional study in 1092 pre- and postmenopausal women (United Kingdom) , 2004, Cancer Causes & Control.

[23]  D. Albanes,et al.  The relation of body size to plasma levels of estrogens and androgens in premenopausal women (Maryland, United States) , 2004, Cancer Causes & Control.

[24]  W. Thompson,et al.  Early adult body weight, body mass index, and premenopausal bilateral breast cancer: data from a case-control study , 2004, Breast Cancer Research and Treatment.

[25]  C. Rotimi,et al.  Obesity and height in urban Nigerian women with breast cancer. , 2003, Annals of epidemiology.

[26]  Nanette Santoro,et al.  Reproductive hormones in the early menopausal transition: relationship to ethnicity, body size, and menopausal status. , 2003, The Journal of clinical endocrinology and metabolism.

[27]  C. Rotimi,et al.  Waist–hip ratio and breast cancer risk in urbanized Nigerian women , 2002, Breast Cancer Research.

[28]  J. Samet,et al.  Associations of weight, weight change, and body mass with breast cancer risk in Hispanic and non-Hispanic white women. , 2002, Annals of epidemiology.

[29]  J. Potter,et al.  Association of body size and fat distribution with risk of breast cancer among Chinese women , 2001, International journal of cancer.

[30]  R. Kraemer,et al.  Effect of estrogen on serum DHEA in younger and older women and the relationship of DHEA to adiposity and gender. , 2001, Metabolism: clinical and experimental.

[31]  R. Sichieri,et al.  Height, weight, weight change and risk of breast cancer in Rio de Janeiro, Brazil. , 2001, Sao Paulo medical journal = Revista paulista de medicina.

[32]  C. Friedenreich.  Review of anthropometric factors and breast cancer risk , 2001, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[33]  J R Marshall,et al.  Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. , 2000, American journal of epidemiology.

[34]  L. Bernstein,et al.  Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[35]  C. Land,et al.  A prospective study of estradiol and breast cancer in Japanese women. , 2000, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[36]  Christina Wee,et al.  Screening for Cervical and Breast Cancer: Is Obesity an Unrecognized Barrier to Preventive Care? , 2000, Annals of Internal Medicine.

[37]  R. Millikan,et al.  Body size and breast cancer risk in black women and white women: the Carolina Breast Cancer Study. , 2000, American journal of epidemiology.

[38]  C. la Vecchia,et al.  Risk factors for breast cancer in women under 40 years. , 1999, European journal of cancer.

[39]  D. Brogan,et al.  Risk of breast cancer in young women in relation to body size and weight gain in adolescence and early adulthood , 1999, British Journal of Cancer.

[40]  A. Oshima,et al.  Risk factors for breast cancer in Japan, with special attention to anthropometric measurements and reproductive history. , 1999, Japanese journal of clinical oncology.

[41]  S. Yen,et al.  Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management , 1999 .

[42]  S. Peacock,et al.  Relation between obesity and breast cancer in young women. , 1999, American journal of epidemiology.

[43]  A. Buzdar,et al.  Inflammatory breast cancer and body mass index. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[44]  E. Riboli,et al.  Breast‐cancer incidence in relation to height, weight and body‐fat distribution in the Dutch “DOM” cohort , 1998, International journal of cancer.

[45]  I. Prpić-Križevac,et al.  Hyperinsulinemia and sex hormones in healthy premenopausal women: relative contribution of obesity, obesity type, and duration of obesity. , 1998, Metabolism: clinical and experimental.

[46]  Chiun-Sheng Huang,et al.  Body size as a factor in different ages and breast cancer risk in Taiwan. , 1998, Anticancer research.

[47]  G A Colditz,et al.  Dual effects of weight and weight gain on breast cancer risk. , 1997, JAMA.

[48]  C. Nagata,et al.  Factors associated with serum levels of estradiol and sex hormone-binding globulin among premenopausal Japanese women. , 1997, Environmental health perspectives.

[49]  M. Dowsett,et al.  Re: Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. , 1996, Journal of the National Cancer Institute.

[50]  M. Dowsett,et al.  A prospective study of endogenous serum hormone concentrations and breast cancer risk in post-menopausal women on the island of Guernsey. , 1997, British Journal of Cancer.

[51]  M. Dowsett,et al.  A prospective study of endogenous serum hormone concentrations and breast cancer risk in premenopausal women on the island of Guernsey. , 1997, British Journal of Cancer.

[52]  R. Giorgino,et al.  Body fat accumulation is possibly responsible for lower dehydroepiandrosterone circulating levels in premenopausal obese women. , 1996, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[53]  J. Palmgren,et al.  Body‐size indicators and risk of breast cancer according to menopause and estrogen‐receptor status , 1996, International journal of cancer.

[54]  H. Zacur,et al.  Predictors of ovarian steroid secretion in reproductive-age women. , 1996, American journal of epidemiology.

[55]  D. Amadori,et al.  Body size indices and breast cancer risk before and after menopause , 1996, International journal of cancer.

[56]  R. Hoover,et al.  Reversal of relation between body mass and endogenous estrogen concentrations with menopausal status. , 1996, Journal of the National Cancer Institute.

[57]  E. Wynder,et al.  A case-control study on breast cancer and body mass , 1995 .

[58]  B. Pasternack,et al.  Premenopausal estradiol levels and the risk of breast cancer: a new method of controlling for day of the menstrual cycle. , 1994, American journal of epidemiology.

[59]  R. Mayberry.  Age-specific patterns of association between breast cancer and risk factors in black women, ages 20 to 39 and 40 to 54. , 1994, Annals of epidemiology.

[60]  J. Carstensen,et al.  Relationship between Quetelet's index and cancer of breast and female genital tract in 47,000 women followed for 25 years. , 1994, British Journal of Cancer.

[61]  C. Longcope,et al.  A prospective study of endogenous hormones and breast cancer. , 1994, Cancer detection and prevention.

[62]  C. Cirrincione,et al.  Is Body Fat Topography a Risk Factor for Breast Cancer? , 1993, Annals of Internal Medicine.

[63]  K. Namboodiri,et al.  Breast Cancer Risk: Effects of Estrogen Replacement Therapy and Body Mass , 1992 .

[64]  L. Brinton,et al.  Height and weight at various ages and risk of breast cancer. , 1992, Annals of epidemiology.

[65]  J. Battermann,et al.  Body measurements, estrogen availability and the risk of human breast cancer: A case‐control study , 1992, International journal of cancer.

[66]  L. Vatten,et al.  Prospective study of height, body mass index and risk of breast cancer. , 1992, Acta oncologica.

[67]  P. Wingo,et al.  The relationship between body mass and breast cancer among women enrolled in the Cancer and Steroid Hormone Study. , 1991, Journal of clinical epidemiology.

[68]  J. Potter,et al.  Increased incidence of carcinoma of the breast associated with abdominal adiposity in postmenopausal women. , 1990, American journal of epidemiology.

[69]  E. Negri,et al.  Anthropometric variables and risk of breast cancer , 1990, International journal of cancer.

[70]  S. Haffner,et al.  Relationship of sex hormone binding globulin to overall adiposity and body fat distribution in a biethnic population. , 1989, International journal of obesity.

[71]  M. Pike,et al.  The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. , 1988, European journal of cancer & clinical oncology.

[72]  R. Pasquali,et al.  Sex hormones in obese premenopausal women and their relationships to body fat mass and distribution, B cell function and diet composition , 1987, Journal of endocrinological investigation.

[73]  D. Wysowski,et al.  Sex hormone levels in serum in relation to the development of breast cancer. , 1987, American journal of epidemiology.

[74]  S. Shapiro,et al.  Risk factors for breast cancer in black women. , 1987, Journal of the National Cancer Institute.

[75]  T. Rönnemaa,et al.  Sex steroid, gonadotropin, cortisol, and prolactin levels in healthy, massively obese women: correlation with abdominal fat cell size and effect of weight reduction. , 1986, The Journal of clinical endocrinology and metabolism.

[76]  R. J. Marshall,et al.  Hypothesis testing in the polychotomous logistic model with an application to detecting gastrointestinal cancer. , 1985, Statistics in medicine.

[77]  B. Macmahon,et al.  Obesity, serum cholesterol, and estrogens in premenopausal women. , 1983, Oncology.

[78]  B. Zumoff.  Relationship of obesity to blood estrogens. , 1982, Cancer research.

[79]  P. Kopelman,et al.  ABNORMAL SEX STEROID SECRETION AND BINDING IN MASSIVELY OBESE WOMEN , 1980, Clinical endocrinology.

[80]  M. Renaer.  Reproductive endocrinology physiology, pathophysiology and clinical management , 1979 .

[81]  David R. Cox,et al.  Regression models and life tables (with discussion , 1972 .