Correlation between vitamin D deficiency and fibrocystic mastopathy

Introduction

Fibrocystic dystrophy is one of the most frequent and common non-neoplastic pathologies whose symptomatology is represented by the appearance of painful nodules in the breast. Fibrocystic lesions have as their etiology several factors, the most important being considered the hormonal imbalance between estrogen and progesterone, manifested by excess estrogen that causes proliferations at the connective tissue level (fibrosis)⁽¹⁾.

The most affected age category is between 20 and 40 years old, with the maximum prevalence before menopause⁽²⁾. Most of the patients present menometrorrhagia, are nulliparous, with a history of spontaneous abortions in the past, early menarche and late menopause⁽³⁾. The main symptoms of fibrocystic mastopathy are mastodynia and increased breast sensitivity which can be associated with dysmenorrhea, menometrorrhagia and frequently ovarian cysts (40-60%). The diagnosis of this pathology is based on symptoms and with the help of breast ultrasound, which can also be used in the puncture and drainage of large cysts. The treatment of fibrocystic breast disease is medical, by administering combined oral contraceptives, with a success rate of 70-90%⁽⁴⁾.

Vitamin D was identified by Edward Mellanby, as a fat-soluble substance with antirachitic properties, classically associated with its physiological role of regulating calcium and phosphate in bone metabolism. People can get vitamin D from two main sources: from food and from exposure to the sun. Few foods contain vitamin D in significant amounts, among them being fish, eggs and mushrooms. However, the majority (90% to 95%) of the vitamin D requirement is produced by the skin when exposed to sunlight (ultraviolet B radiation)⁽⁵⁾. The biologically active form of vitamin D – 1a,25-dihydroxyvitamin D3 or 1a,25(OH)2D3 – is synthesized in the kidneys by the mitochondrial enzyme CYP27B1⁽⁶⁾.

Vitamin D is a steroid hormone that exerts most of its biological activities by binding to a specific and high-affinity receptor (vitamin D receptor; VDR). VDR belongs to the superfamily of nuclear receptors for steroid hormones and regulates gene expression by acting as a transcription factor⁽⁷⁾. Vitamin D can also induce VDR-independent effects; the anti-proliferative effects of vitamin D in MCF-7 cells are not solely dependent on the presence of VDR⁽⁸⁾.

It has been shown that vitamin D plays an important role in the development and function of the mammary gland, the VDR receptor being also present in normal breast tissue, through immunohistochemical tests⁽⁹⁾. The main enzymes involved in the metabolism of vitamin D in the normal breast are CYP27B1 and CYP24A1⁽¹⁰⁾, and an imbalance of those can cause the appearance of benign pathology or neoplasia.

Regarding the representation of differences in the expression of vitamin D receptor, CYP27B1 and CYP24A1 during breast carcinogenesis, vitamin D receptor and CYP27B1 expression decreases with breast carcinogenesis, while CYP24A1 expression is increased (the level of brown coloring represents the intensity of gene expression)⁽¹¹⁾ – Figure 1.

In benign breast pathology, the aforementioned three proteins (VDR, CYP27B1 and CYP24A1) are in decreased amount compared to normal breast.

Epidemiological studies suggest that the level of vitamin D (25-hydroxycholecalciferol) below 20 ng/mL is associated with an increased risk of breast, colon and prostate cancer⁽¹²⁾. In young people, vitamin D deficiency is associated with benign pathology (mammary cysts, fibroadenoma)⁽¹³⁾.

Breast ultrasound is an important technique for evaluating breast anatomy, benign and malignant pathology. Fibrocystic mastopathy is most often associated with dense breasts with well-developed breast tissue (Figures 2 and 3).

Fibrocystic mastopathy is highlighted sonographically by multiple anechoic images, well delimited with posterior acoustic accentuation, usually of medium or small size, present in both breasts; the anatomical structure of the breast is preserved and there is no accentuation of the vascularization (Figures 4, 5 and 6).

Materials and method

The study included 50 women, for a period of three years, aged between 30 and 50 years old, all of them being diagnosed by ultrasound with fibrocystic mastopathy and all presenting vitamin D deficiency (below 20 ng/mL of 25-hydroxyvitamin D)⁽¹⁴⁾ at the time of the examination.

After the administration of vitamin D3 (2000 UI) for at least six months and the correction of the vitamin deficiency (above 30 ng/ml of 25-hydroxyvitamin D), the bilateral breast ultrasound was performed again.

At the time of the ultrasound examination, all the cystic images in the four quadrants of the breast were described, measured and numbered.

Results

Thirteen patients (26%) presented an important reduction in the number of breast cystic formations, by more than 50% than in the previous examination, 15 patients (30%) presented a moderate reduction (between 25% and 50% than the previous examination), and six patients (12%) presented a slight decrease, between 10% and 20% compared to the previous examination. Sixteen patients (32%) did not show significant changes, or the number of cystic formations increased.

Conclusions

1. Fifty-six percent of the patients showed a statistically significant reduction in the number of breast cystic formations, this revealing that a correction of vitamin D deficiency has beneficial effects on patients (Figure 7).

2. The sizes of the cysts decreased significantly in the patients who responded to the treatment and even in four patients in the non-responsive group.

3. The fact that 44% of patients were nonresponsive or had a poor response shows that other factors, besides vitamin D deficiency, are involved in fibrocystic breast dystrophy. 
 

Conflict of interest: none declared.

financial support: none declared.

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