Reproductive Factors

As early as 1926, the proposal was made that a breast never used for lactation is more likely to become cancerous. This hypothesis is consistent with knowledge of breast physiology and breast carcinogenesis, as well as with patterns of international variation in breast cancer incidence: Rates are lower in populations in which breast-feeding is both common and of long duration. The overall evidence from case control and cohort studies supports a reduction in risk with longer duration of breast-feeding, but the findings have varied substantially in the level of risk reduction. A review of 32 studies published through 1998 (R. Blum and G. Colditz, personal communication, 1998) showed that only 2 were prospective,and only 16 of 32 demonstrated a statistically significant lower risk with longer duration of breast-feeding.51 The strongest results supported at least a 50% reduction in risk for women who breast-fed for 2 or more years, but this was in the setting of extremely high parity. Some of the differences may relate to the pattern of breast-feeding, for example, whether feeding was exclusively from the breast or supplemented with other food; this needs to be evaluated further.

Social norms regarding parity and breast-feeding in American culture have limited the ability even to study this potential preventive behavior; the population that breast-feeds at all is small, and the group that breast-feeds over an extended period is even smaller. For example, despite the strong recommendation of the American Academy of Pediatrics that infants be breast-fed through the first 6 months of life because of unequivocal benefit to the infant, in 1988 breast-feeding was practiced by only 32% of new mothers. Although low, this still represents a doubling since 1970.

Spontaneous and Induced Abortion
Close to one-quarter of all clinically identified pregnancies in the United States end as induced abortions, and for women whose pregnancies continue for 8 to 28 weeks, the probability of spontaneous abortion ranges from 8% to 12%. It has been suggested that breast cells are the most vulnerable to mutation when breast tissue consists of rapidly growing and undifferentiated cells, such as during adolescence and pregnancy. In early pregnancy, the number of undifferentiated cells increases as rapid growth of the breast epithelium takes place. If the pregnancy continues to term, these cells differentiate by the third trimester; thus, the number of cells susceptible to malignancy decreases.

The interruption of the differentiation of breast cells that takes place as a result of spontaneous and induced abortions has been hypothesized to increase a woman’s risk of developing breast cancer. This hypothesis appears to be supported by a meta-analysis that included data from 28 published reports on induced abortion and breast cancer incidence. This analysis, however, based largely on case control studies, contains the underlying serious potential for bias in retrospective studies of the relationship between abortion and breast cancer. Induced abortion can be an extremely sensitive topic, and reporting on abortion history by women with a life-threatening condition such as breast cancer may be more complete than reporting by women without breast cancer.

Other studies provide a different picture of the association between breast cancer and abortion. In a hospital-based case control study including 1,803 women with breast cancer, the relative risk among parous women was 1.1 (95% confidence interval of 0.9 to 1.5) for women with a history of any induced abortion compared with women who had never had induced or spontaneous abortion. The relative risk associated with induced abortions in nulliparous women was 1.3 (95% confidence interval, 0.9 to 1.9). Spontaneous abortions similarly were not associated with increased breast cancer risk. Although selection bias could not be ruled out, this large study provided little support for an increase in breast cancer risk in association with spontaneous or induced abortion. In another large case control study, only abortions performed before they were legal in the United States were associated with risk of breast cancer, thus supporting the likelihood of bias in case control studies. Given these concerns regarding recall bias in case control studies of induced abortion and risk of breast cancer, greater weight must be placed on the results from prospective studies that are by design free from such recall bias.

By far the strongest study on the association between breast cancer and abortion was a population-based cohort study made up of 1.5 million Danish women born April 1, 1935 through March 31, 1978. Of these women, 280,965 (18.4%) had had one or more induced abortions. After adjusting for potential confounders of age, parity, age at delivery of first child, and calendar period, the risk of breast cancer for women with a history of induced abortion was no different from that for women who had not had an induced abortion (relative risk, 1.0; 95% confidence interval, 0.94 to 1.06). The number of induced abortions in a woman’s history also had no significant relation to risk of breast cancer. A statistically significant increase in risk was found among the very small number of women with a history of second-trimester abortion. Results from this population-based prospective cohort thus provide strong evidence against an increase in risk of breast cancer among women with a history of induced abortion during the first trimester. Taken as a whole, and accounting for the limitations of the case control study design, the available evidence does not support any important relation between induced abortion and risk of breast cancer.

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