History of Menstrually-Related Migraine May Protect Against ER-/PR- Breast Cancer

“Has a doctor or other health professional ever told you that you had migraine headaches?”

If “yes”, then “Have you ever noticed a pattern where your migraine headaches got worse at certain times of your menstrual cycles?”

These were the questions asked of participants in a baseline questionnaire to examine the possible associations between breast cancer and migraine. Migraines may be sensitive to hormones, which may explain why approximately 50% of women with migraines report that attacks tend to occur with their menstrual cycle. Typically, a headache may begin within a day or two before menses onset, which coincides with the decrease in estrogen levels at the end of the cycle. Hormones may also be linked to risk of breast cancer. Higher rates of breast cancer are seen in women with early age at menarche, late age at first birth, and late age at menopause. Shi and colleagues conducted a study to determine whether migraines were associated with the risk of breast cancer and if that association differed by tumor subtype or migraine subtype, as it relates to menstruation.1 The investigators further evaluated the association with ductal carcinoma in situ (DCIS) and invasive breast cancer, with the latter further divided into tumor-based estrogen receptor/progesterone receptor (ER/PR) status subtypes.

Data were taken from a cohort study of 50,884 women whose sister had breast cancer (Sister Study) and a sister-matched-control study including 1,418 young-onset (<50 years) breast cancer cases (Two Sister Study). The Sister Study was a prospective, population-based study in the United States and Puerto Rico that required participants aged 35 to 74 at enrollment to have never been diagnosed with breast cancer, but had a sister with breast cancer. Incident breast cancer cases were identified over a mean follow-up of 5.34 years. The Two Sister Study was a retrospective, family-based, case-controlled study that included participants under the age of 50 who had been diagnosed with breast cancer within 4 years. Participants from both studies completed the same risk factor questionnaires. Women who responded as having migraines during both menstrual and non-menstrual cycles were categorized as having menstrual migraines.

Study results showed that similar percentages of women in the Sister (20.7%) and Two Sister (18.5%) studies reported migraine history. In addition, similar percentages reported their migraine to coincide with their menstrual cycle (Sister, 44.5%; Two Sister, 45.5%), referred to as menstrually-related migraine.

The key findings reported by the study authors were as follows:

  • A history of migraine was not associated with breast cancer overall.
  • There was an inverse association between migraines and DCIS (HR = 0.77; 95% CI (0.62, 0.96)).
  • Women with non-menstrually-related migraine had an increased risk (HR = 1.30, 95% CI (0.93, 1.81)) of hormone-receptor-negative (ER-/PR-) cancer.
  • Women with menstrually-related migraine had decreased risk (HR = 0.63, 95% CI (0.42, 0.96)) of hormone-receptor-negative (ER-/PR-) cancer.

Some limitations to the study included the self-reported method of information collected on migraine history and on whether the participants’ migraine attacks were timed with their menstrual cycle. Migraines that coincided with the menstrual cycle were considered “menstrually-related migraines”, instead of using the stricter category of “menstrual migraine” defined by the International Headache Society. Also, investigators could not distinguish between women with only menstrual migraine and women with both types. Finally, for the Sister Study only baseline information was used and participant data was not updated during the approximate 5 year follow-up period.

It is believed that migraines and breast cancer are both estrogen-sensitive disorders that primarily affect women. Effective therapeutic regimens have been developed to address ER+ breast tumors, because of its sensitivity to estrogen. In contrast, therapeutic options for hormone-receptor-negative tumors remain a clinical challenge. Data from this study suggests that women with hormone-insensitive migraine are at relatively increased risk for the more aggressive hormone-receptor-negative breast cancer. It is worth noting that this finding was reproduced in both the Sisters and the Two Sisters studies, each with very different study designs. This provided statistically independent and reproducible results.

To date, the existing literature on migraine and breast cancer is inconclusive. Four studies have reported a negative association2-5, while two studies reported no association6,7. As of this study, the inverse association that a history of menstrually-related migraine may be protective against ER-/PR- breast cancer has now been independently observed twice, this study and a study by Lowry and colleagues5. However, additional studies are needed to support these findings.

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