{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:30:16Z","timestamp":1790807416678,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Triple-negative breast cancer (TNBC) is an aggressive malignancy that disproportionately affects young women. The integration of immune checkpoint inhibitors (ICIs) has significantly improved outcomes in both early-stage and metastatic TNBC, shifting attention toward long-term survivorship issues, particularly endocrine function and fertility. However, the reproductive safety profile of ICIs remains insufficiently characterized. This narrative review synthesizes current preclinical and clinical evidence on ICI-associated reproductive toxicity, focusing on both direct immune-mediated gonadal injury and indirect disruption of the hypothalamic\u2013pituitary\u2013gonadal axis. Experimental models consistently demonstrate immune cell infiltration of ovarian and testicular tissue, cytokine-driven inflammatory cascades, follicular atresia, impaired spermatogenesis, and altered steroidogenesis following PD-1\/PD-L1 and CTLA-4 blockade. Emerging clinical data report cases of immune-related orchitis, azoospermia, testosterone deficiency, diminished ovarian reserve, and premature ovarian insufficiency. Secondary hypogonadism due to immune-mediated hypophysitis represents an additional and frequently underdiagnosed mechanism. We further discuss the oncofertility challenges faced by young patients with TNBC treated with chemoimmunotherapy, emphasizing the uncertainty of fertility risk stratification and the importance of early fertility counseling and individualized fertility preservation strategies. To illustrate the potential clinical impact, we present the case of a 34-year-old nulliparous woman who developed premature ovarian insufficiency two years after neoadjuvant chemoimmunotherapy including atezolizumab, despite ovarian suppression. In conclusion, while ICIs have transformed the therapeutic landscape of TNBC, their potential long-term impact on reproductive and endocrine health represents a clinically significant concern. A precautionary, multidisciplinary oncofertility approach and prospective clinical registries are essential to define the true incidence and mechanisms of ICI-associated reproductive toxicity.<\/jats:p>","DOI":"10.3390\/diseases14020051","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T14:35:46Z","timestamp":1769783746000},"page":"51","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Reproductive Toxicity of Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer: A Case Report with a Literature Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0353-131X","authenticated-orcid":false,"given":"Cristina","family":"Tanase-Damian","sequence":"first","affiliation":[{"name":"Faculty of Medicine, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, Victor Babes 8, 400347 Cluj Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7497-5578","authenticated-orcid":false,"given":"Nicoleta Zenovia","family":"Antone","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, Victor Babes 8, 400347 Cluj Napoca, Romania"},{"name":"Department of Oncology, The Oncology Institute \u201cProf. Dr. Ion Chiricuta\u201d, Republicii 34-36, 400015 Cluj Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Loreta","family":"Paun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, Eroii Sanitari 8, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2625-344X","authenticated-orcid":false,"given":"Ioan","family":"Tanase","sequence":"additional","affiliation":[{"name":"Department of Surgery, \u201cCarol Davila\u201d University of Medicine and Pharmacy, Eroii Sanitari 8, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9928-5883","authenticated-orcid":false,"given":"Patriciu Andrei","family":"Achima\u0219-Cadariu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, Victor Babes 8, 400347 Cluj Napoca, Romania"},{"name":"Department of Gynecology-Oncology, The Oncology Institute \u201cProf. Dr. Ion Chiricuta\u201d, Republicii 34-36, 400015 Cluj Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1093\/jnci\/djab121","article-title":"Determining PD-L1 Status in Patients with Triple-Negative Breast Cancer: Lessons Learned From IMpassion130","volume":"114","author":"Badve","year":"2022","journal-title":"J. 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