This study combined data from two previous observational studies. It is unable to show conclusively that breast cancer development in individual women can be directly affected by the frequency of migraine or by treatments for migraine. Further research will be needed to investigate this association, and to determine whether hormone variations are to blame.

Where did the story come from? Dr Robert W. Mathes from the Division of Public Health Sciences at the Fred Hutchinson Cancer Research Center and colleagues from the University of Washington conducted this research. It was published in the peer reviewed Journal of Cancer Epidemiology and Biomarkers Prevention and funded by grants from the National Cancer Institute.

What kind of scientific study was this? This was an analysis of the combined data from two previous case-control studies. The study’s aim was to investigate if there is a reduced frequency of migraine in women who develop breast cancer (and therefore if the presence of migraine is linked to a reduced risk of breast cancer).

The researchers note that the frequency of migraine headaches that women get changes throughout their lifetime. They say this could be related to the fluctuating oestrogen levels during the menstrual cycle, during pregnancy and approaching the menopause. Most women experience an increase in migraines as oestrogen levels fall, for example, just before periods start for the first time and in the pill-free-week of oral contraception. Conversely, during pregnancy when oestrogen levels are high, most women who get migraines report a reduction in attacks.

The researchers used the results from two studies that had used similar methods and contained “cases” of two different types of breast cancer and a number of “control” women without cancer. In total, this gave the researchers 1,199 cases of ductal carcinoma, 739 cases of lobular carcinoma, and 1,474 controls. The women were 55 to 79 years of age.

The first study included women in western Washington who had been diagnosed with invasive breast cancer between 1997 and 1999 regardless of histologic type (that is, what kind of cancer it was, based on looking at the cancerous tissue under a microscope). Of 1,210 eligible cases identified, 975 (81%) were interviewed. The cases were matched in five year age groups, year, and county of residence to the controls. Of the 1,365 eligible controls identified, 1,007 (74%) were enrolled and interviewed.

In the second study, women diagnosed with invasive breast cancer were enrolled between 2000 and 2004. As the purpose of this study was to evaluate the cause of lobular carcinomas (one type of breast cancer), sampling of cancer cases differed by histologic type. A Cancer Surveillance System was used to identify 1,251 eligible cases and of these 83% (501 ductal and 543 lobular cases) were subsequently enrolled in the study and interviewed. The researchers identified controls who were the same age as the cases by randomly dialling numbers from a phonebook. A total of 9,876 telephone numbers were identified and 87% of those contacted were successfully screened for eligibility. Of the 660 eligible controls identified, 469 (71%) were enrolled and interviewed.

Both studies also recorded if the women with breast cancer had oestrogen and progesterone receptor positive or negative disease. These receptors are found on the cancer cells and indicate whether or not the tumour is sensitive to the hormones oestrogen and progesterone.

In both studies, each woman was given a personal interview about their migraine history. This included asking them if they had ever been clinically diagnosed with migraine, their age at diagnosis, and if they had ever used prescription medications to control migraine. Information on specific medications used to treat migraine, including the name, dose, and duration, was not collected. The researchers used statistical methods to control for other factors that might be influencing the link and to test if any association found was significant.

What were the results of the study? The researchers say that women who reported a clinical diagnosis of migraine had reduced risks of ductal carcinoma and lobular carcinoma. These associations were primarily limited to hormone receptor–positive tumours, and migraine was associated with a reduced risk of oestrogen receptor positive and progesterone receptor positive ductal carcinoma. There was a reduction in risk whether or not the women took prescription medication to treat their migraine.

What interpretations did the researchers draw from these results? The researchers say that a history of migraine is associated with a decreased risk of breastcancer. They note that because this is the first study to address an association between migraine history and breast cancer risk, “additional studies are needed to confirm the finding”.

What does the NHS Knowledge Service make of this study? Although the researchers say that women who reported a clinical diagnosis of migraine had reduced risks of ductal carcinoma and lobular carcinoma, this is better explained the other way around. In other words, that woman who had a diagnosis of breast cancer had a reduced risk of reporting a clinical diagnosis of migraine. An understanding of this difference is the basis of assessing the reliability of case control designs.

The researchers point out several limitations, which mean that a certain level of caution has to be taken when interpreting its results.

Information on migraine was based on self-report from patients who may already have developed cancer. This means that there may have been some bias due to cases and controls recalling their migraine history differently. However, the researchers suggest that, given the severity of migraine, it is likely that recall of migraine history will be accurate.They only information on migraine that was captured was that it was diagnosed by a health professional. As it has been estimated that 27% to 59% of migraine sufferers are never clinically diagnosed, this may have led to misclassification.The lack of data on migraine characteristics (whether the migraine was a type linked to menstrual periods or not) and a lack of data on the treatments used for migraine means that there may also be other factors not measured in the study that could be influencing the rate of breast cancer. For example, non-steroidal anti-inflammatory drugs (NSAIDs), which might be used by women to treat their migraine, are also thought to be associated with a modest reduction in breast cancer risk.There is plausible mechanism (hormone levels) which could explain this link and the researchers say that other lines of evidence also support the association between falling oestrogen levels and migraine occurrence. However, on their own, case control studies such as these cannot be used to prove a “cause and effect” relationship. More studies of a prospective design are needed to get a clearer picture.

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