1. Review Article
Int. J. Chem. and LifeSci.
ISSN: 2234-8638
OPEN ACCESS
*Corresponding Author:
Jasmeet Singh,
Demonstrator,
Department of Biochemistry,
G.G.S. Medical College and Hospital,
Faridkot, Punjab, India.
1309
Vitamin D and Breast Cancer! A Close Correlation
Panag KMDS, Anil Batta, Gitanjali Goyal and Jasmeet Singh*
Department of Biochemistry, G.G.S. Medical College & Hospital, Faridkot, Punjab, India.
Received for publication: March 12, 2014; Accepted: March 22, 2014
Introduction
Breast cancer is a malignant tumor which is
a group of cancerous cells that grow into other areas
around it. Breast cancer starts in the cells of the
breast and it can spread to other areas of the body
which is known as metastasis. Tumors in the breast
can either be benign or malignant. Benign tumors or
lump are usually not harmful whereas malignant
tumors are cancerous and can spread to other body
parts.1,2
What is Breast Cancer
The normal female breast is made up mainly
of lobules, ducts, nipple and stroma. Mostly breast
cancer begins in the cells that line the ducts and
some begin in the cells that line the lobules. Breast
cancer can be defined as a cancerous growth that
inhabits the tissues in the breast. In this type of
cancer, the cells in the breast grow abnormally in an
uncontrolled way and they can grow into (invade)
surrounding tissues or spread (metastasize) to
distant areas of the body. When the breast cancer
cells spread, they usually first spread to underarms
and above the collar bone, to lymph nodes.3
Risk factors for Breast Cancer
Risk factors for developing breast cancer
include obesity, lack of physical exercise, drinking
alcohol, hormone replacement therapy during
menopause, ionizing radiations, early age at first
menstruation, and having children late or not at all.4
Symptoms of Breast Cancer
Symptoms of breast cancer include lump in
the breast, a change in breast shape, dimpling of the
skin, fluid coming from the nipple, or a red scaly
patch of skin and advanced symptoms include bone
pain, swollen lymph nodes, shortness of breath, or
yellow skin and noticeable changes in the size and
shape of the mature breast.5
What is Vitamin D
Vitamin D is the name given to a group of
fat-soluble prohormones (substance that usually
have little hormonal activity by themselves but the
body can turn into hormones). Vitamin D helps the
body to use calcium and phosphorous to make
strong bones and teeth. There are two sources of
vitamin D, one is dietary and the other is sunlight
exposure. Vitamin D deficiency causes rickets in
children and osteomalacia in adults.
Vitamin D Metabolism
There are two major forms of Vitamin D, one
is Vitamin D2 (ergocalciferol) and the other is Vitamin
D3 (cholecalciferol). The Vitamin D2 is made naturally
by plants and vitamin D3 is formed by skin exposure
to sunlight. Both these forms are converted to 25-
hydroxy vitamin D in the liver.25-hydroxy vitamin D
then travel through the blood to the kidney, where it
is further modified to 1, 25-dihydroxy Vitamin D, or
calcitriol, the active form of Vitamin D in the body.
The most accurate method of evaluating a person’s
Vitamin D status is to measure the level of 25-
hydroxy Vitamin D in the blood.6,7
Mechanism of Action of Vitamin D
The proposed mechanisms of action of
Vitamin D in the prevention of breast cancer can be
discussed as following:
1. Induced morphological changes associated with
apoptosis in breast cancer cells are arrested by
1,25(OH)2D as it causes increased expression of
cyclin dependent kinase inhibitors such as p21
and p27 in MCF-7 breast cancer cell lines.8
Abstract: Breast cancer strikes more than one-quarter of a million women in the US. An estimated 15%
of women fall victim due to genetic susceptibility. Current treatment options include surgery,
chemotherapy, radiotherapy, immune therapy and vaccine therapy. Vitamin D has been found to have
an important role in stimulating apoptosis and reducing angiogenesis1. Keeping in mind the proposed
role of Vitamin D in the prevention of breast cancer this review has been written.
Key Words: Breast cancer, Vitamin D

2. Panag KMDS et al., Int. J. Chem. and LifeSci., 2014, 3 (04), 1309-1311
www.ijcls.com 1310
2. 1,25(OH)2D can suppress the estrogen pathway
by reducing the expression of gene coding
aromatase activity which converts androgens to
estrogens9
and it can also down regulate the
estrogen receptor10
. Hence it inhibits breast
cancer by estrogen pathway inhibition.
3. Vitamin D inhibits prostaglandin synthesis by
increasing the expression of 15-hydroxy-
prostaglandin to inactive keto-derivatives by
down-regulating the expression of
cyclooxygenase-2. In this way it inhibit
prostaglandin production which is well known
factor for tumor progression, tumor cell invasion
and angiogenesis in human breast cancer cell
lines by being anti- inflammatory in action.9
4. Vitamin D can inhibit the activity of matrix
metallo-proteinases (MMP’s) and urokinase-type
plasminogen activators. It can also increase the
production of their inhibitors (MMP inhibitor-1
and Plasminogen activator inhibitor) which are
mediators of invasion and metastasis. 11
5. By treating breast cancer cells with a potent
form of vitamin D it was found that half of the
cancer cells shrived up and died. It was also
postulated that vitamin D has the same effect as
the drug used in the treatment of breast cancer
that is tamoxifen. It was also found that Vitamin
D entered the cells and triggered the cell death
process in a similar way to the drug
tamoxifen.12
6. BRCA 1 is a well-known tumor suppressor gene,
as it helps repair DNA double strand breaks,
helping to prevent the initial phase of breast
cancer lines. Loss of the BRCA 1 gene repairing
ability greatly increased the risk of developing
cancer. It was identified that a critical DNA repair
factor known as 53BP1 becomes impaired with
BRCA 1 gene degradation and it was found that
when BRCA1 deficient tumor cell treated with
Vitamin D restored high level of 53BP 1 which
resulted in increased genomic instability and
reduced proliferation. It was concluded that
treatment in combination with Vitamin D and
PARP inhibitors could represent a novel
therapeutic strategy for the treatment of breast
cancer with poor prognosis.2
7. Vitamin D receptors are found on the surface of
a cells where they receive chemical signals. By
attacking themselves to a receptor, these
chemical signals direct a cell to do something,
for example to act in a certain way, or to divide
or die. There are also Vitamin D receptors in
breast tissue, and Vitamin D can bind to these
receptors. This can cause cell like oncogenes to
die or stop growing and can stop the cancer
cells from spreading to other parts of the body.
Therefore, it is thought that vitamin D may help
in protecting against breast cancer by making
cells in the breast smarter.13,14,15
Thus, Vitamin D has been found to have
several activities that might slow or prevent the
developing of cancer, including promoting cellular
differentiation, decreasing cancer cell growth,
stimulating cell death (apoptosis) and reducing
tumor blood vessels formation (angiogenesis).
Recent Observational Research Done In Different
Subcontinents Shows That:
1. An observational study was done in Canada
which looked at early stage of breast cancer and
followed them for a period of 12 years which
revealed that women with low levels of vitamin
D almost double the risk of cancer spread, worst
tumor and death.16
2. A study conducted in Belgium looked at the
women with early breast cancer and their
Vitamin D levels for a period of 5 years and it
was found that women with low Vitamin D levels
had bigger tumor than women with high
Vitamin D levels and greater risk of death during
the study.17
3. It was also observed that post-menopausal
women with high vitamin D levels were most
likely to have the smallest tumor.
4. A study conducted in America looked at large
group of women taking calcium and vitamin D
supplements. It was observed that women
taking these supplements had 18% lower risk of
developing early stage breast cancer.18,19
5. Another study conducted in post-menopausal
women with higher vitamin D levels had a 12 %
lower chance of developing Breast cancer than
post-menopausal women with low vitamin D
levels.20
Since the above studies are observational
researchers can’t say for sure if low Vitamin D levels
cause worse outcomes in breast cancer.
Summary and Conclusions
Extensive research over the past decade has
clearly shown that sub-optimal level of Vitamin D
greatly increases the risk of many forms of cancer, as
the pro-hormone unlocks the necessary blue print to
the accurate cellular application and elimination of
mutations. This important review is among the latest
to identify Vitamin D as an important key to prevent
and even treat breast cancer in resistant cases.

3. Panag KMDS et al., Int. J. Chem. and LifeSci., 2014, 3 (04), 1309-1311
www.ijcls.com 1311
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Source of support: Nil,
Conflict of interest: None Declared