Vitamin D Supplementation in Women With DCIS and/or LCIS

In vitro, calcitriol, the most potent metabolite of vitamin D, inhibits a variety of cellular
pathways that promote cell proliferation and survival. Vitamin D has been shown to reduce the
growth of breast cancer precursor cells in cell culture studies. In animal models Vitamin D
has been shown to prevent the growth and progression of transplanted cell lines MCF710A,
which is a model of pre-invasive cancer. Serum Vitamin D level deficiency correlates with an
increased risk of breast cancer, and reduced survival of breast cancer patients. Vitamin D is
also recognized to have effects on immune cell function and autoimmunity. The safety profile
of oral Vitamin D, and its metabolite calcitriol, was well established for moderate term and
acute therapy worldwide. Potential additional primary and secondary benefits of vitamin D are
a) the suppression of carcinogen-induced transformation or progression of breast epithelium,
and b) the enhancement of innate immune defense of pre-invasive breast cancer lesions, and c)
its qualification as a combination therapy when combined with other neoadjuvant therapies for
DCIS.

Patients who have been diagnosed by core biopsy with carcinoma in situ, ductal or lobular,
will be evaluated for vitamin d supplementation. Patients with vitamin d levels less than 50
will be eligible for participation. They will receive a one month (30 days) schedule of
vitamin D supplementation and then proceed with the standard of care of surgical excision.
Immunohistochemistry studies will be performed on the diagnostic core biopsy and the surgical
specimen to evaluate the impact of vitamin d supplementation on: the proliferative
index-ki67, proliferative marker- PCNA, proteins of the autophagy pathway (LC3B, ATG7), her2
localization, and levels of PMCA2 - calcium efflux channel.

Inclusion Criteria:

- Subjects must have a tissue diagnosis of lobular carcinoma in situ or ductal carcinoma
in situ and being scheduled to undergo excision of their cancer

- Subjects must be female at least 18 years of age

- Subjects must have a signed consent

- Normal liver function based on (total bilirubin and AST <1.5 x Upper Limit of Normal)

- Serum creatinine < 2.0 mg/dL

- Serum 25 (OH) D levels < 50 ng/ml

- Calcium within the normal range (8.5-10.2 mg/dL)

- ECOG performance status 0-2

- Are able to swallow and retain oral medication

- Subjects should be willing to abstain from use of hormonal therapies (e.g. hormone
replacement therapy, oral contraceptive pills, hormone-containing IUDs, and E-string)

Exclusion Criteria:

- Patient desires not to participate in the study

- Inability to give consent

- Current use of hormone-containing forms of birth control such as implants (i.e.
Norplants, or injectables (i.e. depo-provera)

- Currently lactating

- Patients with history of renal or hepatic insufficiency

- Used an investigational drug within 30 days or 5 half-lives, whichever is longer,
preceding the first dose of study medication

- History of granulomatous disease such as tuberculosis or sarcoidosis

- History of Vitamin D supplementation > 2000 IU/day within the last 2 months

- History of hypoparathyroidism