Breast cancer and migraines–what is risk, anyway?

ResearchBlogging.orgOne of the questions most often asked in the medical literature is “what is the risk of x?”  It’s a pretty important question.  I’d like to be able to tell my patient with high blood pressure what their risk of heart attack is, both with and without treatment.  And risk is a sexy topic—the press loves it.  Whether it’s cell phones and the “risk” of brain cancer, or vaccines and the “risk” of autism, risk makes for cool headlines.  Take this one for example:

Migraines cut breast cancer risk 30 percent: study

What does this mean?  Should I tell my wife to go out and find some migraines?  I have a feeling one or more of my colleagues will give a more detailed critique of this study, but I’d like to talk to you a bit about what we mean by “risk”.

Risk, in the most basic sense, is a causal association.  If, for example, I find that members of the “Thunderstorm-lovers Golf Association” have a higher incidence of being struck by lightning than golfers who don’t belong to this odd club, I may have stumbled upon a measurable risk.  There is both a measurable association, and a plausible reason to causally link the associated variables.   If I find that members of the National Association of Philatelists have a higher incidence of heart disease than other folks, I may or may not have stumbled on a risk.  Is there a reason that philatelists should have more heart disease?  Is it a coincidence?  Is it worth investigating further?  Is there a confounding variable, e.g. are philatelists in general older, and did I fail to control for this?

Then there is the question of the degree of risk.  How strong is the risk observed?

Statisticians have ways of measuring risk, but many of these terms—such as relative risk, absolute risk reduction, odds ratio—are not intuitive concepts.

Let’s take the study in question.  The premise is interesting.  Migraines and breast cancer are both associated with estrogen.   Many breast cancers are estrogen-dependent, and the risk of developing breast cancer correlates with exposure to estrogen.

Migraines appear to be associated with estrogen as well, but negatively.  This is a much more tenuous connection.  It has been observed that migraines tend to wax during estrogen-poor times, and wane during estrogen-rich times—high estrogen, fewer migraines; low estrogen, more migraines. Or so it’s been observed.

The authors of this study invoked migraine as a negative risk factor for breast cancer.  The English meaning of “risk” is a bit lost here—what they are saying is that women who have migraines are less likely to develop breast cancer than women who don’t have migraines. This shouldn’t be all that surprising, as migraines and breast cancer are both associated with, well, womanhood.

But all this aside, it’s the “30%” headline annoys me.  That a big number!  Get me a migraine, stat! But thirty percent is an “odds ratio“, which is a mathematical way of describing an association in a case-control study such as this one.  Odds ratios are not intuitive, and as a measure of risk, they tend to break down when looking at common occurrences, such as migraines.

If we look directly at the data from the study, the data used to calculate the odds ratio, we see something else.  In this study, the control group was post-menopausal women without breast cancer.  The case group was women with breast cancer.  Among women without breast cancer, 19% had ever had a migraine.  Among women with breast cancers, 14-15% had ever had a migraine.  So, there was about a 4-5% difference in migraine rates between women with and without breast cancer.  Does that still sound like a big number?

Statistics are non-intuitive.  I have to work pretty hard to try to dig out the clinical meaning from stats, and I still get it wrong sometimes.  The press gets it wrong much more often.  Be very wary of banner headlines about risk.  Besides the difficulty of understanding the difference between risk reduction and odds ratios,  what does it mean in the real world?


R. W. Mathes, K. E. Malone, J. R. Daling, S. Davis, S. M. Lucas, P. L. Porter, C. I. Li (2008). Migraine in Postmenopausal Women and the Risk of Invasive Breast Cancer Cancer Epidemiology Biomarkers & Prevention, 17 (11), 3116-3122 DOI: 10.1158/1055-9965.EPI-08-0527

Posted in: Science and Medicine, Science and the Media

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16 thoughts on “Breast cancer and migraines–what is risk, anyway?

  1. HCN says:

    Wait… does this mean that because I don’t get migraines that I should have my boobs removed to prevent cancer?!

    Yeah, I noticed you wanted your wife to find more migraines instead of the other more traditional approach to avoiding breast cancer (though usually happens only if a woman possesses the BRCA1 or BRCA2 gene).

    Oh wait, you wrote “So, there was about a 4-5% difference in migraine rates between women with and without breast cancer.”

    Actually, anything under 5% is commonly considered statistical noise, or in other words: not statistically significant.

    Thank you, I’m keeping the boobs, even though they make fitting jackets and shirts difficult (I’m middle aged, things move… that is life!).

    By the way, my experience with migraines mostly has to do with hubby and and son. I know what to do and what not to do when a person has a migraine. What are they to do? (well, actually hubby’s migraines have reduced significally since his early thirties, that may be the pattern with our 20 year old son)

  2. Harriet Hall says:

    Women with migraines are less likely to be prescribed birth control pills or hormone replacement therapy, and HRT is associated with a higher risk of breast cancer. Did this study control for exogenous estrogen?

  3. daedalus2u says:

    The connection may be through nitric oxide. Estrogen does activate nitric oxide synthase through the estrogen receptor, so periods of high estrogen are also periods of high NO (as during a woman’s cycle and during pregnancy).

    Migraines can be pretty reliably triggered by Viagra (which I think is due to a low NO rebound due to feedback inhibition from supraphysiologic levels of cGMP). Also nitroglycerine triggers migraine. Some people consider nitroglycerine to be an NO donor (it isn’t). Migraine from nitroglycerine comes multiple hours after taking nitroglycerine (not the drug profile if it were due to NO).

    There is considerable thought that migraines are the same as “spreading depression”, which appears to be very much like hypoxic spreading depression which occurs during ischemia, but spreading depression occurs during non-hypoxia and O2 levels go up (I think due to reduced consumption due to ischemic preconditioning). Spreading depression propagates in nervous tissue, though not along axons, but across the bulk at a very slow speed (few mm/minute). Low NO is one of the triggers of ischemic preconditioning. I suspect that NO might be the diffusible signal that is causing the spreading depression to propagate.

    The breast cancer connection probably is due to estrogen and the migraine connection due to low NO secondary to low estrogen. Men can get migraines too, and they have very different estrogen physiology than do women. Presumably the fundamentals of migraine don’t necessarily involve estrogen.

    Pregnancy cuts breast cancer risk by a lot. If estrogen is involved, that would seem to be an effect in the opposite direction. However it is my understanding that maternal estrogen levels go very low following delivery. Since the effect on tumor cells is non-linear (as is everything in physiology), the level and the timing are important.

    In my recent blog on vascular effects of NO I talk some about the connections of NO with migraines. I think that increasing NO levels will reduce migraines without the use of estrogen (for both women and men).

  4. medstudt says:

    HCN, I’m confused by your comments. A 5% reduction in risk may be both statistically and clinically significant. Are you talking about p values?

  5. Peter Lipson says:

    yes, it may be…or may not be

    much depends on the incidence of the disease in question

  6. wjawja says:

    All I can say is “GIVE ME A BREAK”! I suffered with migraines from the age of 13. And yet, I was diagnosed with breast cancer with estrogen and progesterone receptors. So forgive me if I don’t put any credence in this study! The good news is that the chemo induced menopause put an end to my migraines!

  7. HCN says:

    Pretty much, yes (see ). It also depends on the size of the study and other variables which cannot be controlled (as noted in other comments). Remember, this was not a clinical study.

    Seriously, the bit about 5% was part of a talk on alternative medicine I went to recently given by Dr. Harriet Hall (Hi!). Which is why it is stuck in my head right now. It was a great presentation where the 5% comes up in several homeopathy and acupuncture studies (the “Snake Oil Science” book that she reviewed on this blog also mentions it… though I read a copy from the library and cannot review the actual verbage — it is worth reading).

    (I have used statistics only as an engineer, things are much easier if one can control all the variables. Yes, there are variations in the properties of aluminum, but they are not as extreme as people.)

    My knowledge of migraines comes from marrying into a family where migraines are fairly common. My husband is the first person I ever knew who got migraines regularly (more as a young adult, lesser as he has gotten older). His father also suffered from migraines, as did his maternal grandmother. His sister developed a chronic migraine condition about a year after I met my husband (this has caused lots of other medical/mental issues, see the books “All in My Head” by Paula Kamen and “Migraine” by Dr. Oliver Sacks). One of my sons has migraines (he is also the one who got neonatal seizures, and seizures while dehydrated during an illness — I have been assured that there is no relationship between seizures and migraines, but that counters what I read in Dr. Sacks’ book). There seems to be a genetic factor.

    There is no history of breast cancer in either family. Anecdotally, there does not seem to be a casual connection between migraines and breast cancer. Now smoking relating cancer, that has been a factor in both of our families in the last decade (including a hubby cousin who died in his mid-40s).

    By the way, Dr. Lipson, your writing was almost as flippant as Dr. Crislip. I was mixing you two up! This is not a criticism, but more an explanation of why I responded the way I did.

  8. HCN says:

    I thought my response would come right after Dr. Lipson’s… I was responding to medstudt.

    I didn’t know that wjawja was also responding. I support whatever she says. It was a silly comparison.

    For review Dr. Lipson wrote: “Among women without breast cancer, 19% had ever had a migraine. Among women with breast cancers, 14-15% had ever had a migraine. ”

    Okay, that means that there were close to 1/6 of the women who had breast cancer had migraines. This includes wjawja.

    Of the women who did not have breast cancer, less than 1/5 had migraines.

    Big whoop.

  9. daedalus2u says:

    This study does give cover to men who act in ways that give their wife/GF migraines and/or headaches. They can simply say they are trying to reduce her risk of breast cancer. ;)

  10. Peter Lipson says:

    HCN, I’m flattered that you should conflate Crislip an me, but he’s a much more entertaining writer.

    I try to save some of my snarkiness for my other blog, but it does leak through.

    These headlines of “risk” really get my goat and overload my phone lines. Quoting odds ratios is very problematic, especially when the meaning of odds ratio is sometimes quite different from relative risk. NNT/NNH cannot be calculated from OR’s, and they are not in any way intuitive. And they tend to produce big-sounding numbers.

  11. First of all, cancer involves exclusively with Oncological Terrain “AND” OT.-dependent Inherited Real Risk in the biological system, wherein malignancy will occur.
    Secondly, Oncological Terrain and thus OT.-dependent Inherited Real Risk are based on a mitochondrial cytopathy, I termed Congenital Acidosic Enzyme-Metabolic Histangiopathy,conditio sine qua non of all human disorders, including diabetes, hypertension, rheumatisms…and migraine!
    As a consequence, there are people suffering from CANCER with or whitout migraine.
    For further information, See, for instance,
    http://www.nature,com, About Biophysical Semeiotic Constitutions

  12. wertys says:

    Whaa ??

  13. James Fox says:

    Whaa?? X 2

  14. My answer to whaa?? and whaa?? X2, easy and clear-cut, so that also he (she, or…) will be able to understand! In a few words, I forecast that all women (and men, of couse?) involved unfortunately by breast cancer, are POSITIVE for Oncological Terrain (Such as statement ALL give a large number of information, from episthemological view-point). It’s sufficient to falsify my theory if whaa?? and whaa?? X2 will find a cancer diseased human… negaitve for Oncological Terrain!

    “Viviamo tutti in una fogna, ma io guardo le stelle!”
    Only for ANONIMOUS whaa?? and whaa?? X2, if they will not be able to understand what I mean…

    Sergio Stagnaro MD
    Via Erasmo Piaggio 23/8
    16039 Riva Trigoso (Genoa) Europe
    Founder of Quantum Biophysical Semeiotics
    Who’s Who in the World (and America)
    since 1996 to 2009
    Ph 0039-0185-42315
    Cell. 3338631439

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