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Epidemiol Rev. 1993;15(1):98-107.

Exogenous progestins and breast cancer.

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  • 1Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.


More research on the effect of exogenous progestins on breast cancer risk is clearly needed. Biologic evidence that progestins may act synergistically with estrogen to enhance proliferation of breast epithelial cells emphasizes the importance of further exploration of this issue, particularly given the increasing prevalence of exposure to contraceptive and noncontraceptive progestins. No specific type or dose of progestin in monophasic combination oral contraceptives has been linked to breast cancer. Based on the few epidemiologic studies of progestin-only oral contraceptives, there also is no evidence that they increase risk of breast cancer. Two studies found that longer-term use of progestin-only pills was associated with a decreased risk of breast cancer. However, given the low prevalence of use of minipills, it is unlikely that this exposure substantially affects the incidence of breast cancer in the population as a whole. Use of the injectable contraceptive DMPA has been positively associated with risk of breast cancer in some subgroups of women, although no significant overall adverse effect has been observed in the two largest studies conducted to date. There is suggestive evidence that use at an early age or prior to a first term birth and recent use may increase risk of breast cancer. It remains unclear, however, whether or not surveillance bias may explain the positive association observed in recent users. Additional research on DMPA and breast cancer incidence is needed, since studies published to date have lacked sufficient power to evaluate risk in relation to long-term use. Future studies of breast cancer in relation to use of other long-acting progestational agents such as Norplant will also be important. There is concern about the relation between breast cancer incidence and use of combined estrogen-progestin replacement therapy, especially extended periods of use. At the present time, only one study (45) has estimated risk according to duration of use, and it remains uncertain whether the reported elevation in risk seen in long-term users of combined therapy is due to enhanced surveillance for breast cancer among exposed women. Further research will be required before any definitive conclusions can be reached about the potential effect of estrogen-progestin replacement regimens on breast cancer incidence. Future studies should attempt to determine the circumstances under which progestins may alter risk of breast cancer and whether such effects vary by duration of use, dosage, type of preparation, concomitant use of estrogens, regimen of exposure, and the timing of progestin use in relation to age and menstrual and reproductive events.(ABSTRACT TRUNCATED AT 400 WORDS)


No study has yet linked use of oral contraceptives (OCs) containing progestin (monophasic combined OCs and progestin only OCs) with increased risk of breast cancer. On the other hand, use of the injectable contraceptive. Depo-Provera, may be linked to an increased risk of breast cancer in women who use it at an early age or before a 1st term birth and those who have used it recently. Surveillance bias may explain the positive association, however. Insufficient power makes it difficult to evaluate risk linked to longterm use of the injectable. 1 study has found an increased risk of breast cancer among longterm users of combined estrogen-progestin replacement therapy. Surveillance bias may also be responsible for this association. Biologic evidence suggests that progestins work synergistically with estrogen to increase mitotic activity of breast epithelial cells, thus more research in their role is needed. This need is especially important since more and more women are exposed to progestins. Future research should investigate how progestins may change the risk of breast cancer and whether these changes differ by duration of use, dosage, type of preparation, concurrent use of estrogens, regimen of exposure, and the timing of progestin use in relation to age and menstrual and reproductive events. Research should also examine breast cancer risk in the presence or absence of other risk factors for breast cancer, e.g., family history of breast cancer. This type of research may identify high risk subgroups of women whom physicians should advise not to take progestins. If women at high risk of breast cancer choose to use progestins, physicians should monitor them more closely. Other areas of inquiry are progestins' effect on breast cancer risk according to stage of disease at diagnosis or other markers of tumor aggressiveness (e.g., hormone receptor status).

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