Vitamin D and breast cancer: A systematic review and meta-analysis of observational studies

Published on Wednesday, 03 December 2025

Abstract

Context: Breast cancer (BC) is the most common malignancy among women in the US. Vitamin D status and intakes are thought to be inversely associated with BC occurrence. Objectives: In our systematic review and meta-analysis, we evaluated evidence linking serum 25(OH)D (both in serum and diet) with breast cancer (BC) occurrence.

Data sources and extraction: Only observational studies from databases such as PubMed and Cochrane (January 1st 2000 through March 15th, 2018) were included using PRISMA guidelines. Publication bias and consistency upon replication were assessed, while harmonizing risk ratios (RR, 95% CI) of BC, per fixed increment of 5 exposures [10 ng/mL of 25(OH)D; 100 IU/d for total/dietary vitamin D intakes; vitamin D deficiency; supplement use). RRs were pooled using random effect models.

Data analysis: Pooled findings from 22 studies suggested a net direct association between 25(OH)D deficiency and BC, with RRpooled = 1.91, 95% CI: 1.51-2.41, P < 0.001). Total vitamin D intake (RRpooled = 0.99, 95% CI: 0.97-1.00, P = 0.022, per 100 IU/d) and supplemental vitamin D (RRpooled = 0.97, 95% CI:0.95-1.00, P = 0.026) were inversely associated with BC. No evidence of publication bias was found; all 5 exposures of interest were consistent upon replication.

Conclusions: 25(OH)D deficiency was directly related to BC while total vitamin D and supplemental vitamin D intakes had an inverse relationship with this outcome. Randomized clinical trials are warranted pending further evidence from primary meta-analyses of observational studies.

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About this publication.

The Di Bella's Method: Use Vitamin D analogues and/or derivatives, Vitamin A/Retinoids (40mg per day Beta-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate), Estrogen therapy (Anastrozole 1 mg tab per day), pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea, Somatostatin/Octreotide analogues and/or derivatives with Cabergoline and/or Bromocriptine (together with others chemical compounds) in Breast Cancer:

- A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- The Di Bella Method (A Fixed Part - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- Beta-Carotene or β-carotene in Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- The Di Bella Method (A Variable Part - Omega 3 Essential/Unsaturated Fatty Acids. From 1.5 grams up to 3.0 grams per day orally);

The Di Bella's Method: Use of Vitamin D analogues and/or derivatives - together with others chemical compounds - in several Oncological Pathologies:

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Pleural Mesothelioma: clinical records on 11 patients treated with Di Bella's Method;

- Malignant pleural mesothelioma, stage T3-T4. Consideration of a case study;

- Excellent result in a Mesothelioma case treated exclusively with Di Bella Method for over 4 years and still treatment with positive results;

- A case of advanced Multiple Myeloma treated with Di Bella Method (DBM) into total remission for 13 years;

- Neuroblastoma: Complete objective response to biological treatment;