Oral Contraceptives and Breast Cancer in Young Women
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: American case-control study finds no increase in premenopausal lobular breast cancer associated with oral contraceptive use.
Source: Nyante SJ, et al. The association between oral contraceptive use and lobular and ductal breast cancer in young women. Int J Cancer. 2007;epub Oct 23, 2007.
A team of epidemiologists from several institutions in the US performed a case-control study of the association between oral contraceptive use and lobular and ductal breast cancer occurring in young women (under age 44).1 Cases included 100 lobular cancers and 1164 ductal cancers. The results were as follows:
| Lobular Ca | Ductal Ca | |
| Ever use of OCs | 1.10 (0.68-1.78) | 1.21 (1.01-1.45) |
The authors concluded that the use of oral contraceptives has no meaningful effects on breast cancer according to histologic subtype.
Commentary
Lobular cancer (15% of all breast cancers) has been increasing in the US in recent years, prompting these investigators to ask whether this reflects exposure to exogenous hormones. According to their data, the answer is no. This is very reassuring because it is well-recognized that lobular cancer is more hormonally sensitive than ductal breast cancer.
It is disappointing that the article gives a biased point of view, stating that "it has been consistently shown that oral contraceptive use is associated with an increased risk of breast cancer in young women." To support that claim, they site 14 studies with only one in opposition. Two of the 14 are the same study, and one is the collaborative reanalysis of previous studies, published in 1996. That leaves 11 studies. The 11 studies date from 1981 to 1991, thus reflecting old, high-dose oral contraceptives no longer used. The negative study was reported in 2006 with data derived from users of low-dose oral contraceptives.
Most importantly, the authors ignore other recent studies that reflect low-dose oral contraceptives. In the largest case-control study by far, the Centers for Disease Control and Prevention found no increase in risk, even with initiation at a young age and with increasing duration of use.2 A large study using cases from 3 different countries focused on premenopausal breast cancer and could not detect an increase in risk in current oral contraceptive users.3
Finally, all of the studies that have reported small increases in premenopausal breast cancer have been unable to avoid being confounded by a very likely possibility: early and recent use of oral contraceptives may affect the growth of a preexisting malignancy. This is supported by the fact that those studies with positive findings find an increase limited to current and recent use, and the increase has been largely localized disease (in many studies, only localized disease).
Another consideration is the fact that most premenopausal breast cancers are estrogen-receptor negative. Hormone-responsive breast cancers in premenopausal women are more likely to be lobular cancers. For this reason, this negative report on lobular cancer gives more reason to believe that low-dose oral contraceptives have little, if any, effect on breast cancer risk.
I think the following conclusions are appropriate: Even if there is a small increase in premenopausal breast cancer associated with oral contraceptives, this would be a very small number of cases because most cases of breast cancer occur after age 40. Well-done and large case-control studies of modern low-dose oral contraceptives have been consistently negative and reassuring. Older positive studies cannot escape the possibility of detection/surveillance bias because of an effect on preexisting tumors.
References
- Nyante SJ, et al. The association between oral contraceptive use and lobular and ductal breast cancer in young women. Int J Cancer. 2007;epub Oct 23, 2007.
- Marchbanks PA, et al. Oral contraceptives and the risk of breast cancer. New Engl J Med. 2002;346:2025-2032.
- Milne RL, et al. Oral contraceptive use and risk of early-onset breast cancer in carriers and noncarriers of BRCA1 and BRCA2 mutations. Cancer Epidemiol Biomarkers Prev. 2005;14:350-356.
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