Consumption of Meat, Animal Products, Protein, and Fat and Risk of Breast Cancer: A Prospective Cohort Study in New York.
Toniolo P, Riboli E, Shore RE, Pasternack BS. Epidemiology 1994; 5 (4): 391-397.
Epidemiologic studies have focused on the association between diet and breast cancer with conflicting results. Whereas a majority of case-control studies indicate a role for the intake of total fat and saturated fat, most prospective cohort studies either are negative or indicate very modest associations. Only a few authors have examined the role of meat intake in relation to breast cancer risk. The aim of this study was to examine the relation between risk of breast cancer and dietary intake of meat, animal products, fat, and protein. Between 1985 and 1991, we recruited 14,291 New York City women in a prospective cohort study of endogenous hormones, diet, and cancer, in which they reported on their recent diet using a food frequency questionnaire self-administered at enrollment. From the cohort, 180 invasive breast cancer cases diagnosed before December 1990 and five times as many controls, individually matched by age, calendar time at enrollment, menopausal status, and, if premenopausal, phase of menstrual cycle, were included in a nested case-control study. There was an evident increase in the relative risk (RR) of breast cancer for increasing consumption of meat. Women in the upper quintile of total and saturated fat and no apparent association for other types of fat, protein, dairy products, poultry, or fish. The study indicates that the elevated consumption of certain foods of animal origin, such as red meat, may be a factor in explaining the postulated role of diet in breast cancer etiology.
A Prospective Study of Endogenous Estrogens and Breast Cancer in Postmenopausal Women.
Toniolo PG, Levitz M, Zeleniuch-Jacquotte A, Banerjee S, Koenig KL, Shore RE, Strax P, Pasternack BS. Journal of the National Cancer Institute 1995; 87 (3): 190-197.
Background: Circumstantial Evidence links endogenous estrogens to increased risk of breast cancer in women, but direct epidemiologic support is limited. In particular, only a few small prospective studies have addressed this issue.
Purpose: Our purpose was to assess breast cancer risk in relation to circulating levels of the two major endogenous estrogens, estrone and estradiol, measured before the clinical onset of the disease.
Methods: The association between serum levels of estrogens and the risk of breast cancer was examined in a prospective cohort study of 14,291 New York City women, 35-65 years of age, who received screening for breast cancer at the time of blood sampling and who had not been diagnosed with breast cancer. During the first 5? years of the study, we identified 130 breast cancers among the postmenopausal group (7063 women, 35,509 person years). The case subjects and twice as many postmenopausal control subjects were included in a case-control study nested within the cohort. Biochemical analyses for percent free estradiol, percent estradiol bound to sex hormone-binding globulin (SHBG), total estradiol, estrone, and follicle-stimulating hormone were performed on sera that had been kept at -80ÌC since sampling.
Results: For increasing quartiles of total estradiol, the odds ratio (ORs) of breast cancer, as adjusted for Quetelet index (weight in kilograms divided by the square of the height in meters), were 1.0, 0.9, 1.8, and 1.8 (P value for trend = .06); the ORs for increasing quartiles of estrone were 1.0, 2.2, 3.7, and 2.5 (P value for trend = .06). For increasing quartiles of free estradiol, defined as the fraction of estradiol that is not bound to proteins, the Quetelet index-adjusted ORs of breast cancer were 1.0, 1.4, 3.0, and 2.9 (P value for trend <.01). When we considered the percent of estradiol bound to SHBG, the Quetelet index-adjusted ORs were 1.0, 0.70, 0.40, and 0.32 (P value for trend <.01), thus suggesting a protective effect. These associations persisted or became even stronger when analyses were restricted to women whose samples had been drawn two or more years before breast cancer diagnosis.
Conclusions: These data represent the first confirmation in a large prospective epidemiologic study of a link between circulating estrogens and breast cancer risk. Although estrogen levels appeared to fall within the conventional limits of normality in all women under study, those who subsequently developed breast cancer tended to show higher levels of estrone, total estradiol, and free estradiol, and a lower percent of estradiol bound to SHBG than women who remained free of cancer.
Implications: Factors that increase endogenous estrogen production or reduce the binding of estradiol to SHBG may increase a woman's risk of developing breast cancer later in life.
Endogenous Estrogens and Risk of Breast Cancer by Estrogen Receptor Status: a Prospective Study in Postmenopausal Women.
Zeleniuch-Jacquotte A, Toniolo P, Levitz M, Shore RE, Koenig KL, Banerjee S, Strax P, Pasternack BS. Cancer Epidemiology, Biomarkers & Prevention 1995; 4: 857-860.
A positive association between postmenopausal serum levels of total estradiol, percent free estradiol and percent estradiol not bound to sex-hormone binding globulin (SHBG) and breast cancer risk was recently reported by the New York University Women's Health Study (J Natl Cancer Inst 1995; 87:190-197) (abstract). Data from this prospective study are used to assess whether the observed associations differ according to estrogen receptor (ER) status of the tumor. Between 1985 and 1991, 7063 postmenopausal women donated blood and completed questionnaires at a large breast cancer screening clinic in New York City. Prior to 1991, 130 cases of first primary breast cancer were identified by active follow-up of the cohort. For each case, two controls were selected, matching the case on age at first blood donation and length of storage of specimens. Biochemical analyses were performed on sera that had been stored at -80Ì since sampling. ER information was abstracted from pathology reports. Separate statistical analyses were conducted for ER+, ER- and ER unknown groups (53, 23, and 54 matched sets, respectively). In each of the 3 groups, the mean estradiol and the mean percent free estradiol were greater (21 to 28% and 6 to 7%, respectively) in cases than in controls. Conversely, the mean percent of estradiol bound to SHBG was 9 to 12% lower in cases than in controls. The logistic regression coefficients measuring the strength of the association between estradiol and its free and SHBG-bound fractions and breast cancer risk were similar in the ER+, ER- and ER unknown groups. These data suggest that in postmenopausal women, the association of endogenous estrogens with breast cancer risk is independent of the ER status of the tumor. This result is more compatible with the hypothesis of a progression from ER+ to ER- tumors than with the hypothesis that ER status identifies two distinct types of breast cancer.
