{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T09:52:57Z","timestamp":1776333177108,"version":"3.51.2"},"reference-count":66,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Vitamin D is a secosteroid that exerts immunomodulatory and anti-proliferative effects through the vitamin D receptor (VDR). Because HER2-targeted therapies substantially improve prognosis in HER2-positive breast cancer and introduces a new mechanism of immunotherapy, we hypothesized that successful correction of vitamin D deficiency would be associated with improved disease-free survival (DFS) in patients treated with curative intent. Methods: We performed a retrospective interventional cohort study of patients with early-stage HER2-positive breast cancer treated at Cancer Treatment Centers of America Midwestern Regional Medical Center from 2008 to 2014. Eligible patients had baseline vitamin D deficiency (25-hydroxyvitamin D or D25 &lt; 30 ng\/mL), received trastuzumab-based therapy, and had \u226512 months follow-up. Patients received vitamin D3 supplementation (typically 2000\u201310,000 IU\/day) with doses adjusted based on D25 level follow-up. Responders were defined as having achieved a mean D25 \u2265 30 ng\/mL during the first year; non-responders remained &lt;30 ng\/mL DFS was analyzed using Kaplan\u2013Meier and Cox models. Results: Of 196 patients, 129 (65.8%) were vitamin D-deficient at baseline. Among these, 76 (60.3%) achieved repletion while 50 (39.7%) remained deficient. Three did not have D25 follow-up obtained. Thirty-one DFS events occurred but no deaths. Responders demonstrated numerically improved outcomes (3-year DFS 90% vs. 85%). Non-responders had a 1.7-fold higher hazard of recurrence, and those who achieved the highest D25 levels (&gt;50 ng\/mL) had the most favorable DFS trends, suggesting a dose response. Conclusions: Failure to correct a vitamin D deficiency was associated with a 1.7-fold higher recurrence risk, although the relationship did not achieve statistical significance. A similar effect size was reported in another retrospective cohort of HER2-positive breast cancer that did achieve statistical significance, and a doubling of pCR rates was seen in two recently completed RCTs in 2025, with benefits particularly seen in the triple-negative and HER2-positive subtypes. Prospective trials evaluating optimized vitamin D repletion in HER2-positive breast cancer are warranted.<\/jats:p>","DOI":"10.3390\/nu18081253","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T09:04:42Z","timestamp":1776330282000},"page":"1253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Retrospective Interventional Study Examining Whether Successful Replacement Therapy After a Confirmed Vitamin D Deficiency Correlates with Improved Disease-Free Survival in the Curative Intent Treatment of HER2+ Breast Cancer"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8639-0477","authenticated-orcid":false,"given":"Eugene R.","family":"Ahn","sequence":"first","affiliation":[{"name":"Cardinal Bernardin Cancer Center, Loyola University, Maywood, IL 60153, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8767-4870","authenticated-orcid":false,"given":"Nandhini","family":"Iyer","sequence":"additional","affiliation":[{"name":"Loyola University Health System, MacNeal Hospital, Berwyn, IL 60402, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel B.","family":"Cothran","sequence":"additional","affiliation":[{"name":"Walter Reed National Military Medical Center, Bethesda, MD 20889, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","unstructured":"American Cancer Society (2026, March 09). 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