Breast cancer and exercise; is this study convincing?

Breast cancer will affect roughly 13% of women in the western world who live to old age, a plague of terror and worry, even when it's eventually cured.  But since cures are only sometimes possible, here's a situation where prevention is worth its weight in....lives.  So any findings could be important -- but it is important to look closely at what might be misleading or false hope.

A recent paper ("Recreational Physical Activity and Leisure-Time Sitting in Relation to Postmenopausal Breast Cancer Risk", Hildebrand et al., in Cancer Epidemiology, Biomarkers and Prevention, Oct, 2013), described on the BBC website, reports that walking an hour a day reduces breast cancer risk in post-menopausal women by 14%.  An association between exercise and lower risk of many diseases, including breast cancer, is often reported, but this paper describes a prospective study by the American Cancer Society of 74,000 women followed for 17 years, a non-trivial study, the results of which we should surely take seriously.

Baseline information on demographic, behavioral, reproductive, medical and environmental factors were collected from women when they enrolled in the study and they answered follow-up questionnaires every 2 years thereafter. This study looked at the association between exercise and risk and found that women who exercised 42 or more MET-hours per week (METs are 'metabolic equivalents', a way to standardize different forms of activity for comparison purposes) were 25% less likely to get breast cancer than the least active women, who reported 0 to 7 MET-hours per week.  Forty seven percent of women reported that walking was their only exercise and among this group, those reporting what the investigators call an intermediate level of exercise, ≥7 hours per week, were at 14% lower risk than women who walked 3 or fewer hours a week.

Nordic walkers; Wikipedia

Other breast cancer risk factors, reported by many earlier studies, include body mass index, weight gain in adulthood, and use of postmenopausal hormones.  Among women in the sample with breast cancer, this study tested whether risk associated with these factors may vary by estrogen receptor (ER) status of tumors.  And, perhaps it's not exercise per se that's important, but time spent sitting, another variable collected for this study, so they looked at that too but of these factors only exercise was found to be associated with risk.

Get out and walk?
What does this all mean?  Should all postmenopausal women now walk 1 hour a day, or more?  Well, as with all studies reporting the effects of purported risk factors as probabilities, the answer isn't clear.  Risk of breast cancer by age 90 is around 13%, as noted earlier.  That is, 1 out of 8 women will develop breast cancer by the age of 90.  So, this means that all women have a 13% risk of breast cancer?  No, that's on average, and cumulative risk is lower at younger ages, increasing with age.  And it isn't even clear what 13% risk means because some women are at no risk, and some at very high risk (women with a high risk BRCA1 or 2 variant, for example, but even these women aren't all at 100% risk, and -- or because -- environmental factors affect risk, though which factors isn't entirely clear).  And, if you are at risk of dying of some other cause before age 90, you need to know the risk by that age, and it will be lower than 13%.

But statistically, a 14% drop in risk, from 13%, would, on average, reduce risk to around 11.2%.  Is that significant?  Should postmenopausal women all start walking an hour a day?  It's up to each woman to decide.  But since no one knows their actual personal risk, and because, based on many findings by numerous other studies over decades, replicated risk factors such as age at menarche, age at first birth, number of births, age at menopause, genetic risk, and various environmental factors such as alcohol use or smoking, and so on, may be more significant than physical activity anyway.

So, given all the other possible risk factors, known and unknown, how much a daily walk would affect a given woman's risk is impossible to predict.  Indeed, one study found that for women with BMI lower than 22 -- thin women -- exercise lowered their risk by 27%, but for women whose BMI was over 30, their risk was lowered by 1%.  The Hildebrand study, however, didn't find any difference in affect of exercise on risk by weight. One can -- should?  must? ask why that is so, and what it means about how epidemiology goes about its business.

Hildebrand et al. also report that 

Physically active women tended to be leaner, more likely to maintain or lose weight during adulthood, more likely to drink alcohol, and less likely to currently smoke. They were also more likely to use PMH and to have had a mammogram in the past year.

These are confounders, variables that may have an effect on risk of breast cancer, but which weren't included in the analysis.  So, it may be that it's because women who walk one hour a day are thinner or don't smoke that their risk is lower than that of less active women, but this study doesn't tease that out.  And how many potential confounders weren't identified specifically, but end up being built into the analysis as if they were due directly to exercise?  This is not an easy question,  nor the fault of any specific study by any means.  But one needs to ask.

The authors state that their study found that "[w]alking on average at least 1 hour/day was modestly associated with lower risk, even in the absence of other recreational physical activities."  Modestly.  But they finally conclude,

Given that breast cancer is the most common cancer affecting women, and that walking is a common activity among postmenopausal women, the finding of a possible lower risk with an average one or more hours/day of walking is of considerable public health interest.

"Considerable"?  In our view, this study doesn't in fact earn that word.  We must ask our usual skeptical question as to whether the investigators may be looking for more funding by promoting this particular finding (and not other risks that might be more surprising but that they didn't find)?  If you do a  huge study, you're naturally compelled to make as much of it as you can....whether or not there is that much to make.

Another side of this is that we already know of the many salubrious effects on health and longevity of exercise.  In that light, this study at best confirms what we already know.  That's good....though if the authors didn't see the connection with body weight, one must wonder about that, and wonder whether such a huge study to find small effects related to something already very well established, was worth doing.  Would smaller, more extensive or focused studies, that could detect specific risks that were really substantial, be a better way? You'll have to answer that for yourself.