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Induced and Spontaneous Abortion and Breast Cancer Risk
Abstract & Commentary
By Leon Speroff, MD, Editor, Professor of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.
Synopsis: The Nurses' Health Study reports no association between the incidence of breast cancer and induced or spontaneous abortions.
Source: Michels KB, et al. Induced and spontaneous abortion and incidence of breast cancer among young women. A prospective cohort study. Arch Intern Med. 2007;167:814-820.
Michels and colleagues from the Nurses' Health Study searched for a link between the incidence of breast cancer and either induced or spontaneous abortions in their prospective cohort of 105,716 women.1 During the 14 years of follow-up, there were 1458 newly diagnosed cases of invasive breast cancer. The important hazard ratios (relative risks) after adjustment for breast cancer risk factors are the following:
|Induced abortion||HR=1.01 (CI=0.88-1.17)|
|Spontaneous abortion||HR=0.89 (CI=0.78-1.01)|
No trend was observed with number of induced or spontaneous abortions or age at first induced or spontaneous abortion. No association was found with parity. The authors concluded that neither spontaneous nor induced abortions were associated with the incidence of breast cancer, predominantly premenopausal breast cancer in this population.
This subject has been controversial for more than a decade because of opposite findings reported in over 20 epidemiologic studies. Why is it plausible that abortion might increase the risk of breast cancer? The argument goes like this. A full-term pregnancy before age 35 reduces the lifetime risk of breast cancer. It is believed that the exposure to the high levels of estrogen and progesterone for the length of a normal pregnancy produces a full differentiation of breast cells conferring protection against malignant transformation. A pregnancy that is terminated early, either spontaneously or by induced abortion, results in a hormonal exposure that is harmful because it only produces stimulation and does not persist long enough to produce the beneficial differentiation.
A meta-analysis in 1996 of the world's literature on this subject concluded that induced abortion increased the risk of breast cancer, largely in premenopausal women.2 This meta-analysis is still referred to today. After the publication of this meta-analysis, responsible epidemiologists re-considered this subject and raised the real possibility that the healthy control women in the case-control studies were reluctant to reveal that they had induced abortions. Subsequently, studies that avoided this recall bias by deriving data from national registries instead of personal interviews failed to find an increased risk of breast cancer associated with induced abortions.3-5 This was followed by more carefully conducted case-control studies that also failed to find a link between abortions and breast cancer risk.6, 7 Similarly, newer prospective cohort studies yielded reassuringly negative results.6, 8
The Nurses' Health Study investigators point out that it is difficult to control for all breast cancer risk factors in retrospective studies. They criticize the prospective studies as having insufficient data collection (eg, information on abortion was obtained only once at baseline). Hence, the value of the Nurses' Health Study with updated data-gathering throughout the follow-up. Although the women in this prospective cohort were predominantly premenopausal, 34% were postmenopausal. The Danish cohort study found no association across both premenopausal and postmenopausal age groups.4
This study adds to the impressive list of epidemiologic reports that fail to find an association between induced or spontaneous abortions and the risk of breast cancer. A link has been reported only in some studies that collected data retrospectively by personal interviews. The misleading findings in the retrospective studies almost assuredly resulted from the inclination of women who developed breast cancer to disclose previous induced abortions more frequently than the healthy women in the control group. This is also another great example of how a meta-analysis of observational data can produce incorrect conclusions.