In this follow-up study of African American women, oral contraceptive use was more strongly associated with an increased risk of ER−PR− breast cancer than of ER+PR+ breast cancer. The incidence of ER−PR− breast cancer increased significantly among recent users as the duration of use increased, with the largest increase, 2.5-fold, among recent users whose duration of use was 10 or more years. However, there were some inconsistencies in that the incidence of ER−PR−cancer was also significantly increased for some shorter-duration and non-recent categories of use. For ER+PR+ cancer, results were null for most categories of interval since last use and duration but there was a significant increase, 1.66-fold, for recent users with 10 or more years of use. Results for ER+PR− tumors were null, but numbers were small.
The present results strengthen evidence that there is a stronger association of oral contraceptive use with ER− cancer than with ER+ cancer (32
). In several case-control studies, odds ratios for oral contraceptive use have been greater for ER− cancer than for ER+ cancer (7
). Specifically, the odds ratio for 20 or more years of oral contraceptive use was 2.23 for ER− cancer and 1.39 for ER+ cancer (7
); for recent use was 3.1 for ER− cancer and 1.6 for ER+ cancer (11
); for ever use was 1.33 for ER− cancer and 0.88 for ER+ cancer (12
); for ever use was 2.0 for ER− cancer and 1.11 for ER+ cancer (13
); and for 10 or more years of use was 1.27 for ER−PR− cancer and 0.76 for ER+PR+ cancer (14
). The Carolina Breast Cancer Study found odds ratios for ever oral contraceptive use to be greater for basal-like breast cancer (which is major component of ER−PR− cancer) than for luminal A breast cancer (which is a major component of ER+PR+ breast cancer).(33
) Other studies of ER+ and ER− breast cancer have not shown differing relations of oral contraceptive use by receptor status (15
). Our study of oral contraceptive use and receptor subtypes is the only study to report separately on black women, and it is also the first follow-up study of the association.
The present results suggest that oral contraceptive preparations used in the last several decades increase the risk of breast cancer in African-American women. Recent formulations have lower doses of estrogen and progestin and different types of progestin than earlier oral contraceptives (21
). In studies of oral contraceptive use and breast cancer diagnosed in the last 15 years, there were positive associations with recent or long-term use in a Scandinavian follow-up study (3
), in the Carolina Breast Cancer Study among African-American women but not among white women (34
), in a hospital-based case-control study in the northeastern U.S. among both African-American and white women (4
), in the Long Island Breast Cancer Study among premenopausal women (5
), in a hospital-based case-control study of nonwhite women in South Africa among women under age 35(6
), and in a case-control study in the southwestern U.S.(7
). There were no associations with breast cancer overall in a study of white women in Los Angeles (14
) or in the largest case-control study of all conducted in several regions of the U.S.(9
Most studies of oral contraceptive use and breast cancer have focused on white women. Among five studies that reported on African-American and white women separately (4
), all but one (9
) reported point estimates of relative risk for breast cancer overall that were greater for African-American women. The higher estimates for African-American women may reflect the greater proportion of ER− cancer in that ethnic group.
Because the prevalence of oral-contraceptive use is similar or perhaps even lower among African-American women than white women (9
), oral-contraceptive use by itself is unlikely to explain the higher proportion of ER− breast cancers among African-American women. Some hormone-related factors, such as nulliparity, delayed childbearing, and early age at menarche have been associated more strongly with increased risk of ER+PR+ breast cancer than of ER−PR− breast cancer.(8
) Higher current body mass index (32
) and use of menopausal female hormone supplements (39
) have also been associated with increased risk of postmenopausal ER+ cancer. If these effects are mediated through hormonal mechanisms that involve both the amounts of estrogen and progesterone and their specific receptors (40
), one might also expect oral contraceptive use to be more strongly associated with ER+ cancer than with ER− cancer. However, the estrogens and progestins in oral contraceptives differ in type and concentration from those in postmenopausal female hormone supplements. It is also possible that non-hormonal mechanisms might be involved (39
A strength of the present study is its focus on African-American women, a group disproportionately affected by ER− breast cancer. The prospective data collection will have eliminated biased recall of oral contraceptive use. Important risk factors for breast cancer were controlled in the analyses. Follow-up rates were sufficiently high to make bias from selective losses an unlikely explanation of the findings. Bias could have resulted from the exclusion of breast cancer cases from the analysis because of lack of information on receptor status. However, the prevalences of breast cancer risk factors were similar in the included and excluded cases.
In summary, the present results strengthen the evidence that oral contraceptive preparations used in recent decades increase the risk of breast cancer and are the first evidence that the increase is larger for ER−PR− than ER+PR+ cancer among African American women.