Nurses’ Health Study II: No Inverse Association Between Migraine and Breast Cancer
The results of a cohort study and meta-analysis shed further light on the relation between migraines and breast cancer.1 Data suggesting that migraines might be inversely related to breast cancer come from three earlier studies—two case-control studies and one prospective cohort study. However, in 2013, a large prospective cohort study found no association between the two disorders. Despite speculation that pathways involving female sex hormones might link migraine and breast cancer, no mechanism has been elucidated so far.
Cohort study results: No association between breast cancer and migraines
Winter and colleagues sought to evaluate the association between migraine and breast cancer using data from the Nurses’ Health Study II.1 This ongoing cohort study, which began in 1989, includes 116,430 US nurses aged 25 to 42 years at the start. Data are collected via questionnaires every 2 years, with high follow-up rates.
Women were asked whether they had ever been diagnosed with migraine by a physician at baseline, 1993, and 1995. At baseline, 15.3% of women reported migraine; 6% more had been diagnosed by 1995. Breast cancer cases were identified based on the questionnaires and death records. Medical records were available to confirm 90% of the self-reported cases and provide additional information on the hormone receptor status and histologic subtype of the tumors. The primary outcome was invasive or in situ breast cancer. Women diagnosed with cancer before 1989 were excluded, leaving 115,378 women in the analysis.
With one exception, no association was found between any breast cancer subtype and migraine. The only significant association was an increase in the risk of tumors that were both ductal and lobular.
The authors point out that their findings are consistent with results from the Women’s Health Study, in which no association was found between breast cancer and any migraine or active migraine with or without aura.2 A similarly designed analysis of data from the Women’s Health Initiative Observational Study showed that migraine was significantly associated with an 11% lower risk of breast cancer.3
Meta-analysis: Study design matters
Data from four studies were pooled with the results of the Nurses’ Health Study II for meta-analysis.
In the overall pooled analysis, migraine was associated with a significantly lower risk of invasive breast cancer (RR, 0.84; 95% CI, 0.73-0.98) and breast cancer harboring ER+/PR+ tumors (RR, 0.80; 95% CI, 0.68-0.94).
Interestingly, when analyzed by study design, the association between breast cancer and migraine was significant in the case-control studies (RR, 0.72; 95% CI, 0.66-0.79), but not the prospective cohort studies (RR, 0.98; 95% CI, 0.87-1.10). The authors speculated that the results of the case-control studies may have been biased by underreporting of migraine history among breast cancer patients or over-reporting by controls. They also note that unmeasured confounding, selection bias, and chance may have played a role.
The authors concluded that results from the Nurses’ Health Study, a large prospective cohort study, do not provide evidence that migraineurs have a lower risk of breast cancer. No association found when these results were pooled with data from two other prospective cohort studies. In contrast, meta-analysis of data from case-control studies suggests an inverse association may exist between migraine and breast cancer.