Breast cancer is the most prevalent form of cancer in women worldwide. The medications and hormone therapies used to treat breast cancer can result in several side effects, usually due to modification of estrogen production in the body. Similar to the consequences of decreased estrogen production in women going through menopause, breast cancer patients undergoing hormone therapy can experience musculoskeletal symptoms such as joint pain, stiffness, bone pain, muscle pain and muscle weakness.
Aromatase inhibitors (AI) suppress estrogen levels in postmenopausal women with breast cancer by inhibiting the enzyme that activates estrogen production in fat tissue. Letrozole is a type of AI used in breast cancer hormone therapy treatment. Previous studies have shown that musculoskeletal symptoms worsened in patients taking letrozole as a result of vitamin D deficiency and decreased estrogen production. Researchers conducted a recent study to investigate the role that vitamin D3 and calcium supplementation might have on musculoskeletal symptoms in breast cancer patients taking letrozole.
Prieto-Alhambra, M.K. Javaid, S. Servitja, N.K. Arden, M. Martinez-García, A. Diez-Perez, J. Albanell, I. Tusquets, X. Nogues. Vitamin D threshold to prevent aromatase inhibitor-induced arthralgia: a prospective cohort study . Breast Cancer Res. Treat., 125 (2011), pp. 869–878
A total of 82 postmenopausal breast cancer patients taking letrozole for at least two months were divided into three different groups: vitamin D sufficient (>30 ng/ml), insufficient (10-30 ng/ml) and deficient (<10 ng/ml).
For 6 weeks, the vitamin D deficient group received 4,000 IU D3 and 1,000 mg calcium, and the insufficient group received 2,000 IU D3 and 1,000 mg calcium. The vitamin D sufficient group did not receive supplements. At the end of the 6 weeks, serum 25(OH)D concentrations were measured, and the patients were reassigned supplementation regimens based on the test results. Supplementation continued for another 6 weeks, and serum 25(OH)D levels were measured again at the end of this time period. In addition, the participants were assessed using the Health Assessment Questionnaire- II (HAQ-II), which is a standardized set of 10 questions used to determine musculoskeletal symptoms, at baseline and at the end of the 12 week period.
Here is what the study found:
- Baseline vitamin D levels revealed that 13.4% of patients were deficient (<10 ng/ml) and 73.2 % of patients were insufficient in 25-hydroxy vitamin D (10-30 ng/ml).
- There was a negative correlation between duration of letrozole treatment (p= 0.031), BMI (p = 0.001), and serum 25 (OH) vitamin D concentrations.
- There was a positive correlation between serum vitamin D levels and calcium (p<0.001) as well as between serum vitamin D levels and phosphorus (p<0.001).
- Patients who had low serum 25-hydroxy vitamin D concentrations experienced significantly more musculoskeletal symptoms, which was improved following supplementation (p<0.001).
The researchers concluded that in patients with breast cancer undergoing letrozole treatment, vitamin D supplementation should be administered to those with deficient or insufficient levels to compensate for the declining levels. Furthermore, the researchers suggest that vitamin D supplementation may play an important role in reducing musculoskeletal symptoms among patients with breast cancer who are taking letrozole.
While the study possessed several key strengths, the study also contained a few limitations worth acknowledging. First, the sample size was relatively small, and a larger population is needed in order to further prove the association between vitamin D and this specific breast cancer treatment. Second, estrogen concentration was not estimated in the patients, which could have been an important factor in the causation of musculoskeletal pain. They noted that in order to further prove association between vitamin D and letrozole treatment, further studies are needed.
Vitamin D supplementation is important for those who do not spend much time outside in the noonday sun, or at times when your shadow is shorter than you are. For those who require supplementation, the Vitamin D Council recommends a minimum of 5,000 IU of vitamin D3 per day, and checking vitamin D levels about every 6 months to ensure you are at optimum levels.
Peterson, R. & Cannell, JJ. Vitamin D supplementation may reduce musculoskeletal pain in breast cancer patients . The Vitamin D Council Blog & Newsletter, 2016.
Arul Vijaya Vani S, Ananthanarayanan PH, Kadambari D, Harichandrakumar KT, Niranjjan R, Nandeesha H. Effects of vitamin D and calcium supplementation on side effects profile in patients of breast cancer treated with letrozole. Clin Chim Acta Int J Clin Chem. 2016 May 21;459:53–6.