Vitamin D affects breast cancer development and progression in important ways. While the relationship between breast cancer and vitamin D has been studied extensively, it is not fully understood. Vitamin D influences the expression of breast cancer-related gene activity, including cell differentiation, cell growth, and angiogenesis.
Vitamin D regulates the flow of calcium into the bloodstream and is crucial for normal bone development. It also has a role in regulating parathyroid, neuromuscular, immune, and insulin functions. Vitamin D has been found to be associated with lower risks of cardiovascular disease and age-related cognitive impairment. Vitamin D also appears to help prevent esophageal, lung, pancreatic, renal, colorectal, endometrial, prostate and ovarian cancer, as well as Hodgkin and non-Hodgkin lymphoma.
Vitamin D binds to the vitamin D receptor
Vitamin D binds to the vitamin D receptor (VDR). Vitamin D has been shown to inhibit the growth of tamoxifen-resistant breast cancer cells in the laboratory, possibly through a VDR-related mechanism. The impact of vitamin D on breast cancer is influenced by VDR genotype; women can have one of several variants in the VDR gene and these gene polymorphisms influence the potential anticarcinogenic effects of vitamin D.
The effect of vitamin D on breast cancer risk is also modified by the level of calcium consumed. This is because various combinations of calcium and vitamin D can have differing effects on cellular proliferation and differentiation. One study found that certain VDR genotypes are associated with lower risk of breast cancer in women consuming high levels of calcium.
Measuring vitamin D intake is not straightforward
Intake of vitamin D can be difficult to assess since the vitamin is produced in the skin as well as being a component of some foods. The level of vitamin D in the blood is not necessarily proportionate to levels in other tissues such as the breast. In addition, it appears that vitamin D may be more influential in protecting against breast cancer when consumed early in life. Partially as a result, not all population studies have found associations between vitamin D intake or plasma vitamin D and breast cancer.
Forms of vitamin D
Generally speaking, “vitamin D” refers to a set of fat-soluble prosteroids and their metabolites. Vitamin D3 (cholecalciferol) is the form most useful to human beings. Vitamin D3 is made in the skin when skin is exposed to sunlight (as long as the UV index is at least 3). Some vitamin D supplements contain vitamin D2 (ergocalciferol). However, since vitamin D2 is not produced by vertebrates, it makes more sense to take vitamin D3.
Whether obtained from sun exposure to the skin, food, or supplements, vitamin D must undergo chemical reactions to form calcitriol (1,25-Dihydroxycholecalciferol) and thereby become useable in the body. The blood test for vitamin D measures the level of 25-hydroxyvitamin D (25(OH)D, 25OHD, 25-OH-D or 25-OHD), which is the primary metabolic product of vitamin D3 in the blood. Vitamin D deficiency is typically defined as less than either 20 or 25 nmol/L 25(OH)D. In this webpage, by “vitamin D,” we mean vitamin D3 and its metabolites unless otherwise stated.
Vitamin D and risk of breast cancer
Numerous studies have examined the association between vitamin D and breast cancer risk. Most, but not all, have found that suboptimal levels of vitamin D increase risk of breast cancer whereas higher levels are protective, especially among premenopausal women:
- A major 2023 study reported that vitamin D-deficient (less than 20 ng/mL) postmenopausal women had approximately 45% higher risk of breast cancer than women who were not deficient (≥ 30 ng/mL).
- A 2023 Canadian study reported that women with sufficient Vitamin D levels at diagnosis had smaller and lower grade tumors compared to those with insufficient levels, especially among premenopausal women.
- Two 2018 studies reported a reduced risk of breast cancer among women with the highest vitamin D exposure, however this appeared to be confined to premenopausal women in the one study that took menopausal status into account.
- A study with U.S. and Swedish participants found an association between high circulating vitamin D levels and reduced breast cancer risk only in premenopausal women.
- A Japanese study found a reduced risk of breast cancer among women with the highest quartile of vitamin D intake, however this inverse association was confined to premenopausal women.
- A meta-analysis of 11 case-control studies reported that a serum 25(OH)D level of 47 ng/mL was associated with a 50% lower risk of breast cancer. A 2009 meta-analysis of 36 studies also concluded that there was a significant inverse relationship between vitamin D intake and risk of breast cancer. In addition, the study reported a significant decrease in risk of breast cancer for those with the highest calcium consumption.
- A large Swedish prospective study found no significant relationship between risk of breast cancer and sun exposure variables, including annual number of sunburns, skin sun sensitivity, time spent on sunbathing vacations, or solarium use at any age of exposure. There was also no association found between breast cancer incidence and dietary vitamin D intake or supplementary multivitamin use.
- A Canadian case-control study found that while vitamin D intake was most strongly associated with lower risk of ER+/PR+ breast cancer, it also appeared to be associated with lower risks of hormone receptor negative (ER-/PR-) and mixed receptor status (ER+/PR-) tumors.
- A U.S. study reported that breast cancer patients with suboptimal levels of vitamin D were three times more likely to develop triple negative (ER-/PR-/HER2-) breast cancer than patients with optimal levels. In other words, low vitamin D appeared to increase the aggressiveness of the breast cancer that developed.
Vitamin D levels during breast cancer treatment
Levels of vitamin D normally drop during chemotherapy. However this decline is not in itself associated with worse prognosis. Vitamin D supplementation during chemotherapy can raise circulating vitamin D levels and this appears to enhance the treatment effects. The long-term impact on prognosis of taking vitamin D during treatment appears to be favorable:
- A 2023 study found that breast cancer patients were more vitamin D-deficient before chemotherapy than the general population and that this deficiency increased further during treatment. Survival analysis demonstrated significantly longer survival in patients without such deficiency (i.e., >20 ng/mL) at baseline.
- Another 2023 study reported that pretreatment vitamin D insufficiency was a risk factor for peripheral neuropathy in patients with early-stage breast cancer treated with Taxol paclitaxel.
- A 2020 review found that vitamin D is able to help overcome the molecular mechanisms of drug resistance in addition to enhancing the effects of traditional cancer chemotherapy.
- An Irish study reported that breast cancer-specific mortality was 20% lower in women with new post-diagnosis vitamin D prescriptions than those without such prescriptions. The death rate was 49% lower if vitamin D was initiated within six months of breast cancer diagnosis.
- Another study reported that vitamin D had varying effects on triple negative breast cancer cells treated with Taxol, depending on the genetic profile of the cells.
- Over two-thirds of breast cancer patients in one study were found to be vitamin D deficient. Generally speaking, deficiency was higher in non-white patients and patients with later-stage disease. High-dose vitamin D supplementation (at least 50000 IU weekly) resulted in a greater increase in plasma vitamin D (+28 ng/mL; p< 0.01) than low-dose vitamin D (+7 ng/mL; p=0.03) or no supplementation (+2 ng/mL). The authors concluded that conventional low-dose vitamin D was not effective.
- Vitamin D3 was found to increase breast cancer cell death caused by radiotherapy from approximately 30% to 75% in one laboratory study.
- A large Norwegian population study found significant variations in long-term prognosis by season of diagnosis of breast, colon and prostate cancer. The lowest risks of cancer death were associated with diagnoses that had been made during the summer and fall, the seasons with the highest levels of vitamin D3. The authors concluded that a relatively high level of vitamin D3 at the time of diagnosis, and therefore, during cancer treatment, may improve prognosis of the three cancer types studied.
- A phase 2 trial of daily 10000 IU vitamin D supplementation in women with bone metastases reported that vitamin D did not influence bone resorption or reduce pain overall. However, a reduction in the number of pain sites was observed and the treatment reduced elevated parathyroid hormone levels, which presumably had been caused by long-term bisphosphonate use.
Vitamin D and risk of breast cancer recurrence
Vitamin D deficiency at diagnosis appears to be linked to higher risk of breast cancer recurrence. However, there appears to be a benefit to increasing the level of circulating vitamin D once a woman has been diagnosed with breast cancer:
- A large 2021 prospective study reported that women with sufficient vitamin D levels (≥30 ng/mL) had significantly better survival outcomes than those with deficient levels (< 20 ng/mL) at diagnosis.
- A 2021 meta-analysis of previous studies reported that supplementation with vitamin D was associated with lower total mortality, but not lower cancer recurrence, among breast cancer survivors.
- A large 2020 study reported that taking 2000 IU of vitamin D3 per day was associated with reduced risk of advanced (stage IV or fatal) cancer (including breast and other cancers) in those who were cancer-free at baseline. The result was strongest among normal weight individuals (BMI < 25) and did not hold for those who were overweight or obese.
- Another 2020 study found that vitamin D significantly reduced proliferation and levels of pro-angiogenetic markers in both ER+/PR+ and triple negative breast cancer cells.
- A Danish study reported that both high and low levels of vitamin D at diagnosis were associated with inferior breast cancer survival.
- A study of 1,666 women in California found that higher levels of vitamin D at diagnosis were associated with improved survival, especially among premenopausal women.
- A study reported that vitamin D supplementation in women with early stage HER2+ breast cancer was associated with improved relapse-free survival.
- A Belgian study reported that 25(OH)D levels under 30 ng/mL at diagnosis were associated with larger tumor size, but not with positive lymph nodes or tumor grade. Women with levels over 30 ng/mL had better overall survival and breast cancer-free survival than women with lower levels. In addition, levels over 30 ng/mL at diagnosis were associated with a modest favorable effect on disease-free interval (the time between diagnosis and the first recurrence, if any), which became apparent only after the first three years of follow up.
- A prospective study which used stored blood of breast cancer patients to measure Vitamin D levels found that women with deficient vitamin D levels had a significantly increased risk of distant recurrence and death compared with those with sufficient levels. The authors concluded that vitamin D deficiency may be associated with poor outcomes in breast cancer.
- A German prospective study found that low levels of circulating vitamin D at diagnosis were associated with increased risk of recurrence during the first five years.
- Still another prospective study found no association between circulating levels of vitamin D and risk of recurrence among breast cancer survivors overall. However, the same study found that dietary vitamin D intake was protective against recurrence among premenopausal women.
- A study using a mouse model reported that vitamin D deficiency increased the growth of bone metastases. The study examined the intraskeletal growth of the human breast cancer cells in nude mice. Mice weaned onto a vitamin D-free diet developed vitamin D deficiency associated with secondary hyperparathyroidism and accelerated bone turnover. Osteolytic lesions appeared earlier and were significantly larger in vitamin D-deficient mice than in vitamin D-sufficient mice.
How much vitamin D is optimal?
The optimal 25(OH)D level for breast cancer prevention appears to be at least 40 ng/mL — 40 to 50 ng/mL may be an appropriate target range. The optimal vitamin D3 level for women undergoing treatment for breast cancer has not been established.
Increasing vitamin D levels is not necessarily straightforward. Given that most women get little sun exposure and that there are few food sources of vitamin D, supplementation with vitamin D3 is required for most. This is especially true of dark-skinned women for whom vitamin D photosynthesis is less efficient and vitamin D insufficiency is very common. Obesity appears to increase the likelihood of vitamin D deficiency.
Current recommendations of 600 to 1000 units of vitamin D3 per day may not be enough to achieve a 25(OH)D level of 40 ng/mL in a reasonable period of time. Therefore, it might may sense to take 2000 units until 25(OH)D reaches this level and then continue with 1000 units per day.
Some studies have used doses as high as 50000 IU/week, a dosage that appears not to result in vitamin D toxicity (which manifests as high levels of calcium in the blood, as well as bone density and kidney problems) in the short term. However, evidence to date suggests that the adverse event threshold is approximately 4000 IU of vitamin D per day for long-term use. Doses as low as 4000 per day have been found to reduce total volumetric bone mineral density and can cause kidney stones in those with genetic susceptibility. The National Academy of Medicine has set the tolerable upper intake level at 4000 IU per day. In addition, one study reported that individuals with 25(OH)D levels above 100 ng/mL are at increased risk for atrial fibrillation (AF, a type of irregular heartbeat); low vitamin D levels have also been reported to be associated with AF. Furthermore, there is some evidence that high doses of vitamin D could actually promote breast cancer metastasis.
Sources of vitamin D
In addition to exposing the skin to sunlight, the following foods and supplements are significant sources of vitamin D while also having been found to protect against breast cancer:
Vitamin D appears to act synergistically with calcium in the diet to oppose breast cancer. Adequate (but not excessive) levels of calcium are required to maximize the beneficial effects of vitamin D.
Low levels of vitamin D are associated with higher risk of breast cancer and its recurrence. Adequate vitamin D levels at diagnosis, as well as during and after treatment, have the potential to improve long-term survival. Mega-doses of vitamin D appear inadvisable. Please partner with your oncologist or primary care physician to have your vitamin D level tested and develop a plan to increase it, if indicated.
Sources of information provided in this webpage
The information above, which is updated continually as new research becomes available, has been developed based solely on the results of academic studies. Clicking on any of the underlined terms will take you to its tag or webpage, which contain more extensive information.
Below are links to 20 recent studies concerning vitamin D and breast cancer. For a more complete list of studies, please click on the tag vitamin D.
Selected breast cancer studies
The Impact of Vitamin D and Its Dietary Supplementation in Breast Cancer Prevention: An Integrative Review
Torres A, Cameselle C, Otero P, Simal-Gandara J. The Impact of Vitamin D and Its Dietary Supplementation in Breast Cancer Prevention: An Integrative Review. Nutrients. MDPI AG; 2024; 16:573 10.3390/nu16050573
Calcitriol promotes M2 polarization of tumor-associated macrophages in 4T1 mouse mammary gland cancer via the induction of proinflammatory cytokines
Stachowicz-Suhs M, Łabędź N, Anisiewicz A, Banach J, Kłopotowska D, Milczarek M, et al. Calcitriol promotes M2 polarization of tumor-associated macrophages in 4T1 mouse mammary gland cancer via the induction of proinflammatory cytokines. Scientific Reports. Springer Science and Business Media LLC; 2024; 14 10.1038/s41598-024-54433-x
Potential interplay between tumor size and vitamin D receptor (VDR) polymorphisms in breast cancer prognosis: a prospective cohort study
Lindgren H, Ademi D, Godina C, Tryggvadottir H, Isaksson K, Jernström H. Potential interplay between tumor size and vitamin D receptor (VDR) polymorphisms in breast cancer prognosis: a prospective cohort study. Cancer Causes & Control. Springer Science and Business Media LLC; 2024; 10.1007/s10552-023-01845-1
Role of vitamins A, C, D, E in cancer prevention and therapy: therapeutic potentials and mechanisms of action
Talib WH, Ahmed Jum’AH DA, Attallah ZS, Jallad MS, Al Kury LT, Hadi RW, et al. Role of vitamins A, C, D, E in cancer prevention and therapy: therapeutic potentials and mechanisms of action. Frontiers in Nutrition. Frontiers Media SA; 2024; 10 10.3389/fnut.2023.1281879
Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221
Chen C, Zirpoli G, Barlow WE, Budd GT, McKiver B, Pusztai L, et al. Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221. Journal of the National Comprehensive Cancer Network. Harborside Press, LLC; 2023; 21:1172-1180.e3 10.6004/jnccn.2023.7062
Emerging perspectives: unraveling the anticancer potential of vitamin D3
Wakle KS, Mokale SN, Sakle NS. Emerging perspectives: unraveling the anticancer potential of vitamin D3. Naunyn-Schmiedeberg's Archives of Pharmacology. Springer Science and Business Media LLC; 2023; 10.1007/s00210-023-02819-5
Methylation of the Vitamin D Receptor (VDR) gene in human disorders
Gasperini B, Falvino A, Piccirilli E, Tarantino U, Botta A, Visconti VV. Methylation of the Vitamin D Receptor (VDR) gene in human disorders. MDPI AG; 2023; 10.20944/preprints202311.1315.v1
Vitamin D and Its Metabolites Status before and during Chemotherapy in Caucasian Breast Cancer Patients
Kimsa-Furdzik M, Bednarek A, Hibner G, Czajka-Francuz P, Cisoń-Jurek S, Karawasiecka D, et al. Vitamin D and Its Metabolites Status before and during Chemotherapy in Caucasian Breast Cancer Patients. Metabolites. MDPI AG; 2023; 13:996 10.3390/metabo13090996
Low Serum Vitamin D Associated With Increased Tumor Size and Higher Grade in Premenopausal Canadian Women With Breast Cancer
Manocha A, Brockton NT, Cook L, Kopciuk KA. Low Serum Vitamin D Associated With Increased Tumor Size and Higher Grade in Premenopausal Canadian Women With Breast Cancer. Clinical Breast Cancer. Elsevier BV; 2023; 10.1016/j.clbc.2023.06.003
Vitamin D deficiency as a risk factor for breast cancer development.
Mackey JD, Young P, Zimmerer R, Miles B. Vitamin D deficiency as a risk factor for breast cancer development.. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2023; 41:10559-10559 10.1200/jco.2023.41.16_suppl.10559
Combinations of vitamin A and D induced are synergistic in breast cancer cells and alter gene expression in the endoplasmic reticulum stress, unfolded protein and estrogen signaling canonical pathways
Kanabar PN, Los NS, Lawal TO, Patel SM, Raut NA, Maienschein-Cline M, et al. Combinations of vitamin A and D induced are synergistic in breast cancer cells and alter gene expression in the endoplasmic reticulum stress, unfolded protein and estrogen signaling canonical pathways. Functional Foods in Health and Disease. Functional Food Center; 2023; 13:135 10.31989/ffhd.v13i3.1069
The Effect of the Synergistic Combination of Vitamin D and Doxorubicin on the MCF-7 Line Breast Cancer Cells
Sobczak K, Mlicka A, Niewiadomski P, Abramczyk O, Zielińska W, Hałas-Wiśniewska M, et al. The Effect of the Synergistic Combination of Vitamin D and Doxorubicin on the MCF-7 Line Breast Cancer Cells. Cells 2023. MDPI; 2023; 10.3390/blsf2023021020
Association of Body Weight With Response to Vitamin D Supplementation and Metabolism
Tobias DK, Luttmann-Gibson H, Mora S, Danik J, Bubes V, Copeland T, et al. Association of Body Weight With Response to Vitamin D Supplementation and Metabolism. JAMA Network Open. American Medical Association (AMA); 2023; 6:e2250681 10.1001/jamanetworkopen.2022.50681
The Self-Administered Use of Complementary and Alternative Medicine (CAM) Supplements and Antioxidants in Cancer Therapy and the Critical Role of Nrf-2—A Systematic Review
Krejbich P, Birringer M. The Self-Administered Use of Complementary and Alternative Medicine (CAM) Supplements and Antioxidants in Cancer Therapy and the Critical Role of Nrf-2—A Systematic Review. Antioxidants. MDPI AG; 2022; 11:2149 10.3390/antiox11112149
Low baseline vitamin D levels correlate with adverse pathological features and clinical outcomes among patients with breast cancer.
Barakat D, Mohamed R, Elnaggar M, Tarik D, Eid SM. Low baseline vitamin D levels correlate with adverse pathological features and clinical outcomes among patients with breast cancer.. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2022; 40:552-552 10.1200/jco.2022.40.16_suppl.552
Association of Serum 25-Hydroxyvitamin D Concentration with Breast Cancer Risk in Postmenopausal Women in the US
Ganji V, Sukik L, Hoque B, Boutefnouchet L, Shi Z. Association of Serum 25-Hydroxyvitamin D Concentration with Breast Cancer Risk in Postmenopausal Women in the US. Journal of Personalized Medicine. MDPI AG; 2022; 12:944 10.3390/jpm12060944
Vitamin D concentrations and breast cancer incidence among Black/African American and non‐Black Hispanic/Latina women
O’Brien KM, Harmon QE, Jackson CL, Diaz‐Santana MV, Taylor JA, Weinberg CR, et al. Vitamin D concentrations and breast cancer incidence among Black/African American and non‐Black Hispanic/Latina women. Cancer. Wiley; 2022; 10.1002/cncr.34198
Effect of Vitamin D3 Supplements on Development of Advanced Cancer
Chandler PD, Chen WY, Ajala ON, Hazra A, Cook N, Bubes V, et al. Effect of Vitamin D3 Supplements on Development of Advanced Cancer. JAMA Network Open. American Medical Association (AMA); 2020; 3:e2025850 10.1001/jamanetworkopen.2020.25850
Adverse Effects of High‐Dose Vitamin D Supplementation on Volumetric Bone Density Are Greater in Females than Males
Burt LA, Billington EO, Rose MS, Kremer R, Hanley DA, Boyd SK. Adverse Effects of High‐Dose Vitamin D Supplementation on Volumetric Bone Density Are Greater in Females than Males. Journal of Bone and Mineral Research. Wiley; 2020; 35:2404-2414 10.1002/jbmr.4152
Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study
Elliott MJ, Ennis M, Pritchard KI, Townsley C, Warr D, Elser C, et al. Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study. npj Breast Cancer. Springer Science and Business Media LLC; 2020; 6 10.1038/s41523-020-0166-y