Exposure to Breast Milk in Infancy and Adult Breast Cancer Risk

Linda Titus-Ernstoff 0 1 Kathleen M. Egan 0 1 Polly A. Newcomb 0 1 John A. Baron 0 1 Meir Stampfer 0 1 E. Robert Greenberg 0 1 Bernard F. Cole 0 1 Jiao Ding 0 1 Walter Willett 0 1 Dimitrios Trichopoulos 0 1 0 Oxford University Press 1 Journal of the National Cancer Institute , Vol. 90, No. 12, June 17, 1998 - Background: There is considerable interest in the possibility of an infectious etiology for human breast cancer. Although studies have shown that certain strains of mice transmit mammary tumor virus via breast milk, few epidemiologic studies have addressed this topic in humans. Methods: We evaluated the relationship between having been breast-fed as an infant and breast cancer risk among 8299 women who participated in a population-based, casecontrol study of breast cancer in women aged 50 years or more. Case women were identified through cancer registries in three states (Massachusetts, New Hampshire, and Wisconsin); control women were identified through statewide drivers license lists (age <65 years) or Medicare lists (ages 6579 years). Information on epidemiologic risk factors was obtained through telephone interview. We used multiple logistic regression to assess having been breast-fed and maternal history of breast cancer in relation to breast cancer occurrence both in premenopausal women (205 case women; 220 control women) and in postmenopausal women ( 3 8 0 3 c a s e w o m e n ; 4 0 7 1 c o n t r o l women). Results: We found no evidence that having been breast-fed increased breast cancer risk in either premenopausal women (odds ratio [OR] = 0.65; 95% confidence interval [CI] = 0.41 1.04) or postmenopausal women (OR = 0.95; 95% CI = 0.851.07). In addition, breast cancer risk was not increased by having been breast-fed by a mother who later developed breast cancer. Conclusion: Our results do not support the hypothesis that a transmissible agent in breast milk increases breast cancer risk. Because premenopausal women were not well represented in our study population, our findings with regard to this group may not be generalizable and should be viewed with caution. [J Natl Cancer Inst 1998;90: 9214] Initial interest in a possible viral etiology for human breast cancer was generated by studies showing that mammary cancer in certain strains of mice can be caused by a tumor virus transmitted via breast milk (1). Early clinical investigators (24) speculated that viral transmission through breast-feeding might also account for the elevated risk observed among women whose mothers had developed breast cancer. Although comprising small numbers of case women, their hospital-based studies provided no evidence of an association. Furthermore, international and temporal patterns are inconsistent with viral transmission through breast milk. Breast cancer rates are low in countries where breast-feeding is common (5,6); in western countries, breast cancer rates have increased over a time when breast-feeding has declined (5,6). Nevertheless, recent studies have produced evidence of viral DNA (7) and viral antigen (8) in human breast cancer tissues, and there is currently substantial interest in a possible viral etiology for human breast cancer (9,10). Although a few case control studies have examined the relationship between exposure to breast milk in infancy and adult breast cancer risk (1115), none have reported whether risk was increased by having been breast-fed by a mother who later developed breast cancer. We evaluated the relationship between exposure to breast milk in infancy and breast cancer risk in a large populationbased, casecontrol study of women aged 50 years and over, who were born during a time period (1911 through 1945) when breast-feeding was relatively common (16). We specifically addressed the hypothesis that an agent might be transmitted via breast milk, by evaluating whether breast cancer risk was increased among women who were breast-fed by a mother who subsequently developed breast cancer. This report is based on an ongoing, U.S. population-based, casecontrol study of breast cancer. We identified case women through population-based cancer registries covering the states of Massachusetts, New Hampshire, and Wisconsin. Potentially eligible case women were of ages 5079 years and were diagnosed with a first invasive breast cancer. Eligibility required a listed telephone number and a drivers license determined by self-report (if <65 years old). We contacted the physician of record named in the cancer registry and requested approval to approach case women for study participation. Of 6839 potential case women, 158 were excluded at their physicians request, 293 had died before contact, 83 could not be located, and 620 declined to participate, providing an overall participation rate of 83%. Of the 5685 case women interviewed, 26 were considered unreliable by the interviewer, leaving 5659 case women for analysis. We selected control women in each state from lists of licensed drivers (women of ages 50 through 64 years) and Medicare beneficiaries (women of ages 65 through 79 years). Control women were selected at random to have an age distribution similar to that of case women. To ensure comparability to the case group, control eligibility required a listed telephone number. Control women who had a personal history of breast cancer were ineligible. Of 7655 potential control women, 183 had died, 124 could not be located, and 1397 declined to participate, providing an overall participation rate of 78%. Of 5951 control women interviewed, 23 were considered unreliable by the interviewer, leaving 5928 control women for analysis. The percentage of participation among case and control women was somewhat higher in Wisconsin than in Massachusetts or New Hampshire (Table 1). Study participants were enrolled during the period from July 1, 1992, through July 31, 1995. Case and control women received a letter of introduction from the study centers principal investigator, followed within a couple of weeks by a telephone call from the study interviewer. The 45-minute telephone interview elicited information concerning physical acEligible Physician refusal Unable to locate Subject refusal Subject deceased Interviewed* % of eligible New Hampshire tivity, alcohol consumption, dietary intake, height, weight, medical history, demographic factors, use of exogenous hormones, reproductive factors, and early life factors, including whether the woman had been breast-fed as an infant. For 87% of case women and 96% of control women, interviewers remained unaware of the participants status until personal medical history was sought at the end of the interview. We evaluated exposures that occurred before a reference date, which was defined for case women as the date of breast cancer diagnosis. For comparability, control women were assigned a reference date that corresponded to the frequency of dates of diagnosis among case women within 5-year age strata (on average, about 1 year prio (...truncated)