2011 SABCS, San Antonio Breast Cancer Symposium, 6-10 December, San Antonio, USA

Link between vitamin D levels and breast cancer

Dr Eitan Amir – Princess Margaret Hospital, Toronto, Canada


My name is Dr Eitan Amir, I’m a medical oncologist at Princess Margaret Hospital in Toronto, Canada. This was actually a follow-on study from one that we did previously which has been presented earlier on in the ASCO meeting. What struck us really is that many of the more recent data with regards to trying to assess whether vitamin D is associated with breast cancer have been negative, compared to some of the earlier studies which suggested an association between low levels of vitamin D and increased risk of breast cancer.

So what we did is we conducted a systematic review and meta-analysis where we tried to extract all of the published and presented data that we were aware of that assessed different levels of blood concentrations of 25-hydroxyvitamin D and the risk of subsequently developing breast cancer. We found two specific groups of studies, those in which the blood was taken from patients before the cancer diagnosis and then another group where the blood was actually taken from patients after they developed breast cancer. When we pooled all these studies together what we actually found was that in those studies where blood was taken remotely from the diagnosis of breast cancer, usually a number of years prior to the diagnosis of breast cancer, the likelihood of the association between low levels of vitamin D and breast cancer risk was very marginal, there was only a 10% increase for being in the low quartile of vitamin D which just met statistical significance. Because this is a meta-analysis this is a very highly powered assessment.

The more interesting element, from our point of view, is that amongst those studies where blood was actually measured after cancer diagnosis, there was a much higher risk, almost a 280% increase in the risk of breast cancer, which suggests that the timing of measuring vitamin D levels in blood is important with regards to assessment of risk. This is something that in clinical epidemiological circles is called reverse causation bias because it may well be that the presence of breast cancer somehow influences the concentration of vitamin D.

So what these data show is that perhaps the association between vitamin D levels and breast cancer is not quite as substantial as previously thought, if there is any association it’s likely extremely small, our data would suggest only a 10% relative increase. So that would, in most patients, be a very, very small absolute increase in risk and would suggest that any association is probably not directly related to vitamin D but perhaps some other measure which may correlate with it.

We have tried to look into it in other kinds of cancers and this work is on-going. I think that there are stronger data with some gastrointestinal tumours, whether it be pancreatic and others. There has also been some work looking at it with gynaecological malignancies, they appear quite varied and probably there doesn’t appear to be a huge effect. We’ve always known, obviously, about the association of vitamin D and skin cancers, whether they be non-melanoma or melanoma, but of course there the association is that of sun exposure, leading to a higher risk of the cancers as well as higher vitamin D levels in blood. So those are the ones really where there is the most evidence for.

Are there any on-going trials now?

Every few months there are studies that are on-going that look at it, that try and look for associations. It’s something that’s reasonably easy to do because there are many prospectively collected cohorts of patients out there that have had blood stored at some point in the past and these analyses can very easily be done. So there are probably a substantial number, although unlike clinical trials these are not registered so it’s very difficult to know how many are going on, but clearly we see these not infrequently, both in cancer journals as well as through review processes.

So what’s your opinion on the relationship between vitamin D levels and breast cancer risk?

If you look at the current data and split it the way that we’ve done in the way that we think is probably more appropriate, there doesn’t appear to be a substantial influence of vitamin D levels. Of course we didn’t look at what might be clinically certainly more relevant, which is the effect of supplementation, that’s a different thing altogether, but I think that the rationale for that kind of clinical trial appears to be small.