The effect of reproductive factors on breast cancer risk was evaluated in a population-based case-control study, including 1,486 breast cancer cases diagnosed over a one-year period in Denmark. They were identified from the files of the nationwide trial of the Danish Breast Cancer Co-operative group and the Danish Cancer Registry. The control group was an age-stratified random sample of 1,336 women from the general population. Data on risk factors were collected by self-administered (mailed) questionnaires. Significantly increased relative risks (RR) were associated with never being pregnant (RR = 1.47), an early terminated first pregnancy (RR = 1.43), and having a natural menopause after the age of 54 (RR = 1.67). Trends of decreasing risk were observed by increasing parity and age at menarche. These findings were independent of age at first full-term pregnancy which overall was not related to breast cancer risk, though a weak association appeared in women less than 50 years at diagnosis. The study confirmed that pregnancies must continue to term to offer protection against breast cancer.
PIP: To evaluate the effect of reproductive factors on breast cancer risk, a case-control study was conducted, which included almost all incident cases over a 1-year period in Denmark. The study included all women, aged less than 70 years, diagnosed with breast cancer between March 1, 1983, and February 29, 1984. The case group comprised 1694 women. The breast cancer diagnosis was histologically confirmed in all but 5 cases. 32 persons had carcinoma in situ; the remainder, 1662 cases, had invasive cancer. As controls, an age-stratified random sample of 1705 women was drawn from the general population. Data on risk factors were collected by self-administered questionnaires, mailed to the cases 1 year after their diagnosis on a monthly basis. To achieve a similar procedure for controls, the preselected pool was divided into monthly batches which were assigned the same date of diagnosis as the cases. There were significant trends of a decreasing breast cancer risk by increasing age at menarche and an increasing risk by increasing age at natural menopause. The latter was supported by the finding of cases more frequently still being premenopausal at the time of diagnosis than equivalently for controls. Compared to women whose 1st pregnancy lasted 28 or more weeks (in the following considered full-term), never pregnant women had a significantly almost 50% increased risk. Women whose 1st pregnancy terminated early, before the 28th week, also had an increased risk. To explain the lack of association between breast cancer and age at 1st full-term pregnancy, several factors were examined. Oral contraceptive (OC) use delayed the 1st childbirth. At the age of 20, practically no OC users had given birth. The delay in 1st pregnancy was more pronounced for controls than cases. While the risk reduction by 4 or more full-term pregnancies persisted after stratification for age at the 1st pregnancy, no consistent pattern was seen for age at 1st full-term pregnancy. Relative to nulliparous women, all age groups showed a reduction in risk by 1 or more childbirths, the trend being most pronounced for women who were diagnosed with breast cancer between the ages of 50-59. Analyzing breast cancer cases by histologic subtype found an increasing risk by increasing age at 1st birth limited to lobular cancers. If a woman who had had an early termination of a 1st pregnancy did not have a subsequent full-term pregnancy, an almost 3-fold increase in risk was observed. The study confirms that full-term pregnancies protect against breast cancer.