{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T20:38:57Z","timestamp":1792269537105,"version":"4.4.0"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Everolimus, an inhibitor of the mechanistic target of rapamycin (mTOR), is used with endocrine therapy for endocrine-resistant hormone receptor\u2013positive, human epidermal growth factor receptor 2 (HER2)\u2013negative advanced breast cancer. Although diarrhea is a recognized adverse effect, severe inflammatory colitis accompanied by gastrointestinal bleeding is rare and remains insufficiently characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Presentation<\/jats:title>\n                    <jats:p>A 60-year-old woman with metastatic estrogen receptor\u2013positive, progesterone receptor\u2013positive, HER2-negative breast cancer involving the bone and liver presented with a 2-day history of severe abdominal pain, bloody diarrhea, and hematochezia approximately 6\u00a0months after starting exemestane, everolimus, and zoledronic acid. Contrast-enhanced computed tomography demonstrated marked circumferential wall thickening and submucosal edema involving predominantly the cecum, ascending colon, and proximal transverse colon, with pericolic fat stranding and mild free fluid. Colonoscopy showed diffuse mucosal erythema and edema, and colonic biopsy demonstrated moderate chronic active non-specific colitis with focal surface epithelial erosion and preserved mucosal architecture. No viral cytopathic changes or evidence of inflammatory bowel disease, dysplasia, or malignancy were identified. Cytomegalovirus testing of colonic tissue and peripheral blood was negative, and available stool investigations identified no infectious etiology. Everolimus was permanently discontinued. Management included bowel rest, intravenous fluids, initial antibiotics, intravenous methylprednisolone, transfusion of two units of packed red blood cells for symptomatic anemia, and nutritional support. Follow-up computed tomography demonstrated complete resolution of the colonic inflammatory abnormalities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The diagnosis rested on the temporal relationship with everolimus exposure, multimodal objective evidence of colitis, structured assessment of competing diagnoses, and sustained recovery following permanent drug withdrawal and medical management. The event was retrospectively classified as Common Terminology Criteria for Adverse Events Grade 3 colitis, and a Naranjo score of five supported a probable adverse drug reaction. Histopathology confirmed active colitis but was non-specific and did not independently establish everolimus causality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Probable everolimus-associated severe colitis should be considered when patients receiving mTOR inhibitors develop acute abdominal pain, diarrhea, or gastrointestinal bleeding. Because histopathological findings may be non-specific, diagnosis requires integration of drug exposure, objective evidence of intestinal inflammation, careful exclusion of competing etiologies, and clinical evolution following withdrawal of the suspected agent.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1871050","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:35:55Z","timestamp":1789450555000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Probable everolimus-associated severe colitis with hematochezia in a patient with metastatic hormone receptor\u2013positive, HER2-negative breast cancer: a case report"],"prefix":"10.3389","volume":"17","author":[{"given":"Ahmad","family":"Fatayer","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Palestine Medical Complex","place":["Ramallah, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem K.","family":"Qupp","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Al-Quds University","place":["Jerusalem, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"Morcos","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Al-Quds University","place":["Jerusalem, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ZainEdeen","family":"Zyadah","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Al-Quds University","place":["Jerusalem, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Alresheq","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Palestine Medical Complex","place":["Ramallah, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahed","family":"Bushnaq","sequence":"additional","affiliation":[{"name":"Internal Medicine, Washington University of Health and Science","place":["San Pedro, Belize"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"Qubaja","sequence":"additional","affiliation":[{"name":"Anatomical Pathology Department, Augusta Victoria Hospital","place":["Jerusalem, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ola Abu","family":"Laban","sequence":"additional","affiliation":[{"name":"Cancer Care Center, Augusta Victoria Hospital","place":["Jerusalem, Palestine"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"108094","DOI":"10.1016\/j.ijscr.2023.108094","article-title":"Multiple ulcers and perforation of small intestine with everolimus use in a patient with rectal neuroendocrine tumor: a case report","volume":"106","author":"Abe","year":"2023","journal-title":"Int. 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