January 22, 2020

expert reaction to study looking at vitamin D and breast cancer in women in Karachi

A study of Pakistani women, published in the journal PLOS ONE, reports that vitamin D deficiency may be associated with breast cancer occurrence.

Dr Bernard Khoo, Senior Clinical Lecturer in Endocrinology at UCL, and Member of the Society for Endocrinology, said:

“The new study is consistent with some studies in the past that have shown associations between low vitamin D levels and the new diagnosis of cancer, in this case breast cancer.  However, this is only an association and does not scientifically show a causal relationship between lack of vitamin D and cancer.

“I do not think the title given in the press release is justified by the data in the paper, in particular I take issue with the last part of the title: “supplements might protect against breast cancer” as this study does not support this assertion.  I would consider a randomised controlled trial of vitamin D supplementation in patients at risk of breast cancer in a properly powered trial to be adequate information to support this sentence and this study is not one of these.  Currently, the data from randomised controlled trials does not support a major role for vitamin D supplementation in preventing cancer, for example the VITAL trial which did not show any effect of vitamin D supplementation on the risk of developing breast cancer.

“The research is moderate quality.  Although there is a statistically significant relationship between low vitamin D levels and the diagnosis of breast cancer, it is clear that there are other factors which influence vitamin D levels (e.g. socioeconomic status) which are known to be associated with cancer diagnosis.  I appreciate that the researchers did try to adjust for socioeconomic status and other factors which are known to influence breast cancer incidence, but I think it is still more likely that there are many confounding factors that influence the likelihood of vitamin D deficiency and simultaneously the risk of breast cancer.”

Dr Andrea Darling, Postdoctoral Research Fellow, Department of Nutritional Sciences, University of Surrey, said:

“The study is reasonably well thought out and is novel in that little research has studied vitamin D and breast cancer in women living in Pakistan.  Importantly, the researchers of the current study did check for the influence of some factors which could alternatively explain the results seen (e.g. socioeconomic status, body mass index) and it was found that the association between vitamin D levels and breast cancer risk still existed after these were controlled for in the analysis.  However, we must remember that this is an observational study and so we cannot disentangle cause and effect in this research.  Ideally, we need more vitamin D supplementation trials, following women up for years, to truly be able to say whether higher vitamin D levels reduce the risk of breast cancer.”

Dr Zaki Hassan-Smith, Consultant Endocrinologist at the University Hospitals Birmingham, and Member of the Society for Endocrinology said:

“The authors of this study set out to investigate associations between vitamin D status (25-hydroxyvitamin D) and breast cancer in women in Karachi, Pakistan.  Previous observational studies have shown there to be associations between vitamin D status and cancer incidence.

“Although study is interesting, I would be very cautious with the findings.  The clinical significance of vitamin D deficiency is not addressed by the study design.  It is unable to assess whether vitamin D supplementation would prevent breast cancer or improve outcomes.  This is a relatively small observational study.  Well-designed large scale randomised control trials would address this question.  However these studies are expensive to carry out.  A number of recent large scale studies looking at the impact of vitamin D non-skeletal disease outcomes have failed to show benefit.

“A potential confounder with this type of study is that patients undergoing treatment for a disease may be more likely to have vitamin D deficiency for other reasons such as reduced sun exposure or nutritional changes.

“The general vitamin D advice in the real-world, though not about breast cancer, is outlined by Public Health England and the Special Advisory Council on Nutrition reports.  In this those with risk factors for vitamin D deficiency (including low sunlight exposure) should consider maintenance supplementation.  Vitamin D supplementation can be helpful in children to prevent rickets.  People with conditions such as osteoporosis are also advised to ensure that vitamin D status is optimised.”

Dr Inez Schoenmakers, Senior Lecturer, Department of Medicine, Norwich Medical School, UEA, said:

“This is a well conducted retrospective case-control study.

“It is surprising that supplement use was highly significant in a model that also included a marker for vitamin D status (plasma 25OHD).  This may suggest a specific effect of supplement use and/or additional confounding that was not accounted for by the variables (the confounders) included in the models.

“Unique about this study is that vitamin D status of the women was low compared to many other studies and that the study was conducted in women with a relatively low sunshine exposure due to their dress style.  As a result of the latter, these women will be have been mostly dependent on oral sources of vitamin D.  This may differ from studies in more Western populations, where the vitamin D produced in the skin under the influence of sunshine is – for many – an important contributor to their vitamin D supply.

“As for all studies of this type of design, this needs to be replicated in a randomised placebo controlled trial.  We therefore need to be conservative in our interpretation of the relevance of these findings for health policy.”

‘A multicenter case control study of association of vitamin D with breast cancer among women in Karachi, Pakistan’ by Uzma ShamsiI author et al. was published in PLOS ONE at 19:00 UK time on Wednesday 22 January 2020.

DOI: 10.1371/journal.pone.0225402

Declared interests

Dr Andrea Darling: “No conflicts of interest to disclose.”

Dr Zaki Hassan-Smith: “No conflicts of interest.”

Dr Inez Schoenmakers: “None.”

None others received.