Breast cancer has been considered the most common type of cancer among women in 161 countries and the most common cause of cancer deaths in 98 countries. Known and established risk factors for breast cancer include age, family history, breast tissue density, parity, overweight, alcohol consumption and genetic risk factors such as BRCA mutations. Recently, vitamin D receptor (VDR) genes have been reported to increase the risk of breast cancer. Several subtypes of molecular breast carcinoma have been identified: luminal A and B (representing 50-60% of cases), basal or triple negative (10-20% of cases) and HER2-enriched (10-15% of cases). Vitamin D exerts its effects through VDR, which is found in breast epithelial cells. The vitamin D receptor was first identified in a breast cancer cell line in 1979 and subsequently identified in human breast cancer tissues. It has a receptor within cells that binds to 1.25 (OH) 2D and interacts with its target genes. Vitamin D regulates the transcription of over 60 genes that are responsible for antiproliferative, differentiating, antimetastatic and lethal effects on cells. The vitamin D receptor gene from vitamin D plays an important role in the mammary gland, through the regulation of calcium transport during lactation, hormone differentiation and milk production. Many studies have examined the association between the vitamin D level and the risk of breast cancer, which generally show an inverse association.
Vitamin D levels in blood ≥45 ng / mL can protect against breast cancer and chemotherapeutic drugs that alternate the process of carcinogenesis, such as tamoxifen, raloxifene and aromatase inhibitors, have high toxicity and are not effective in negative negative receptor (ER-) of estrogen breast tumors. A massive meta-analysis with 11 nested and retrospective cases-controls and 10 case-controls was published by Chen et al. (2010), which evaluated the association between vitamin VD intake, blood levels and calcium intake in breast cancer risk. The highest levels of circulating VD were associated with a 45% reduction in breast cancer compared to lower levels. Dose-response meta-analysis by Bauer et al. (2013) studied the association between circulating VD and breast cancer risk, in 5206 cases and 6450 stratified menopausal controls. A gradual inverse association was observed in postmenopausal women over a threshold of 27 ng / mL, but with flattening of effects over 35 ng / mL. An interesting case-control research by Grant et al. verified the association between vitamin D and breast cancer risk among the Asian population. They evaluated in particular the association between serum VD and stratified breast cancer risk based on the state of menopause and hormone receptor (HR) status of the tumor. It appears that concentration values of VD are useful only for short follow-up times for rapidly developing breast cancer.
Although most of the case-controlled studies, meta-analyzes and joint reviews found that the VD concentration was inversely related to breast cancer risk, only a few randomized controlled trials (RCTs) of vitamin D support this result. Bolland et al. in their Study of the Women’s Health Initiative, a randomized study showed that among 15646 women (43%) who did not take calcium or vitamin D supplements at random, concomitant administration of calcium and vitamin D significantly reduced the risk of total and invasive mammary carcinoma within 14% to 20%. McDonnell et al. in their aggregated analysis of the randomized study and of the prospective cohort study, it supports this inverse association between the concentration of VD and the risk of breast cancer. They reported that women with a VD concentration greater than 20 ng / mL had 67% lower risk of any invasive cancer than VD serum below 20 ng / mL. Low levels of vitamin D were recorded among breast cancer patients compared to healthy controls. Furthermore, low levels of vitamin D were common in the diagnosis of breast cancer and were associated with a poor prognosis.
About 94% of women with a vitamin D level below 20 ng / mL develop metastasis and 73% die from advanced disease. VD levels are significantly higher in patients with early-stage breast cancer compared to those with locally advanced or metastatic disease. Therefore, most of the studies on vitamin D support the inverse association between vitamin D level and breast cancer risk and retrospective and prospective epidemiological studies have revealed that vitamin D deficiency is associated with an increased risk of breast cancer. Nonetheless, there is an urgent need for better designed and randomized clinical trials. Previous research indicates that vitamin D can be effective in treating most forms of breast cancer, even negative ones for estrogen receptors or triple negative. The latter takes into account 11 of 15 out of 100 positive patients and is very unreactive to therapy. Exploring the possibility of using VD in breast cancer therapy is a natural form of chemo that may be free of side effects.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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