{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T11:30:20Z","timestamp":1762947020919,"version":"3.45.0"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"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. Oncol."],"abstract":"<jats:p>This case report describes a 45-year-old TNBC patient (cT3N1M0 IIIA) with preexisting parathyroid adenoma who developed multisystem immune-related toxicities after neoadjuvant pembrolizumab chemotherapy. After two cycles, severe hepatotoxicity (ALT 1,090 U\/L), grade 2 dermatitis, hypercalcemic crisis (iPTH 61.99 pmol\/L), and meningeal thickening with intracranial hypertension emerged. Imaging revealed 134% parathyroid adenoma enlargement and diffuse meningeal enhancement. Emergency parathyroidectomy and corticosteroids normalized calcium and reversed neurological symptoms. Pathological complete response (pCR) occurred despite ICI discontinuation. This first-reported case suggests that PD-1 inhibitors may activate parathyroid microenvironments to drive adenoma growth. At the same time, calcium\u2013ICI synergy could impair blood\u2013brain barrier integrity, advocating calcium\/neurological monitoring in ICI-treated endocrine disorder patients.<\/jats:p>","DOI":"10.3389\/fonc.2025.1607957","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T11:26:12Z","timestamp":1762946772000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Accelerated parathyroid adenoma progression and hypercalcemia-driven neurotoxicity following pembrolizumab-based neoadjuvant therapy in triple-negative breast cancer: a case of multisystem immune-related adverse events"],"prefix":"10.3389","volume":"15","author":[{"given":"Yi","family":"Zeng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Qian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31953-X","article-title":"Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial","volume":"396","author":"Mittendorf","year":"2020","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.85433","article-title":"PD-1\/PD-L1 inhibitor - related adverse events and their management in breast cancer","volume":"15","author":"Lei","year":"2024","journal-title":"J Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.665698","article-title":"Case report:Unmasking hypercalcemia in patients with neuroendocrine neoplasms. Experience from six Italian referral centers","volume":"12","author":"Giannetta","year":"2021","journal-title":"Front Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2113128","article-title":"Cancer-associated hypercalcemia","volume":"386","author":"Guise","year":"2022","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2174\/0118715303409910250725043347","article-title":"Severe hypercalcemia following pembrolizumab therapy: A case report and A literature review","author":"Lazzaroni","year":"","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1155\/crom\/8600200","article-title":"Hypercalcemia as an immune-related adverse event in a patient receiving nivolumab and ipilimumab for metastatic melanoma: A case report","volume":"2025","author":"Plessers","year":"2025","journal-title":"Case Rep Oncol Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa092","article-title":"Activating antibodies to the calcium-sensing receptor in immunotherapy-induced hypoparathyroidism","volume":"105","author":"Lupi","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0528-x","article-title":"Inflammation-induced hypoparathyroidism triggered by combination immune checkpoint blockade for melanoma","volume":"7","author":"Trinh","year":"2019","journal-title":"J Immunother Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7459268","article-title":"Hypocalcemia with immune checkpoint inhibitors: the disparity among various reports","volume":"2020","author":"Nalluru","year":"2020","journal-title":"Int J Endocrinol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e235293","DOI":"10.1136\/bcr-2020-235293","article-title":"Microsatellite instability driven metastatic parathyroid carcinoma managed with the anti-PD1 immunotherapy, pembrolizumab","volume":"13","author":"Park","year":"2020","journal-title":"BMJ Case Rep"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13398","article-title":"Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling","volume":"17","author":"Teleanu","year":"2023","journal-title":"Mol Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ24-0126","article-title":"Pembrolizumab with external radiation therapy effectively controlled TMB-high unresectable recurrent parathyroid cancer: a case report with review of literature","volume":"71","author":"Katoh","year":"2024","journal-title":"Endocr J"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-related adverse events associated with immune checkpoint blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2016-0020","article-title":"Immunothera\u2043 peutic implications of IL-6 blockade for cytokine storm","volume":"8","author":"Tanaka","year":"2016","journal-title":"Immunotherapy"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2016.12.019","article-title":"Serum level of interleukin-6 is increased in nivolumab-associated psoriasiform dermatitis and tumor necrosis factor-\u03b1 is a biomarker of nivolumab recativity","volume":"86","author":"Tanaka","year":"2017","journal-title":"J Dermatol Sci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcr\/ytab061","article-title":"Progressive valvular calcifications with critical aortic stenosis in a 25-year-old woman with end-stage renal disease on haemodialysis: a case report","volume":"5","author":"Oxlund","year":"2021","journal-title":"Eur Heart J Case Rep"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1097\/XCE.0000000000000220","article-title":"Rapid progression of aortic stenosis after initiation of teriparatide treatment: a case report","volume":"10","author":"Solomon","year":"2020","journal-title":"Cardiovasc Endocrinol Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-020-05676-7","article-title":"Hypercalcemia upon denosumab withdrawal in primary hyperparathyroidism: a case report and literature review","volume":"31","author":"Camponovo","year":"2020","journal-title":"Osteoporos Int"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017-01249","article-title":"CDC73-related disorders: clinical manifestations and case detection in primary hyperparathyroidism","volume":"102","author":"van der Tuin","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0000000000000161","article-title":"myasthenia gravis after nivolumab therapy for squamous cell carcinoma of the bladder","volume":"40","author":"Chang","year":"2017","journal-title":"J Immunother"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000503","article-title":"Neurological toxicities associated with immune-checkpoint inhibi\u2043 tors","volume":"30","author":"Touat","year":"2017","journal-title":"Curr Opin Neurol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2017.07.014","article-title":"Immune mediated neuropathy following checkpoint immunotherapy","volume":"45","author":"Gu","year":"2017","journal-title":"J Clin Neurosci"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01440","article-title":"Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: ASCO guideline update","volume":"39","author":"Schneider","year":"2021","journal-title":"J Clin Oncol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e000687","DOI":"10.1136\/jitc-2020-000687","article-title":"Calcium-sensing receptor autoantibody-mediated hypoparathyroidism associated with immune checkpoint inhibitor therapy: diagnosis and long-term follow-up","volume":"8","author":"Dadu","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajem.2017.02.048","article-title":"Acute symptomatic hypocalcemia from immune checkpoint therapy-induced hypoparathyroidism","volume":"35","author":"Win","year":"2017","journal-title":"Am J Emerg Med"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1607957\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T11:26:13Z","timestamp":1762946773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1607957\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":25,"alternative-id":["10.3389\/fonc.2025.1607957"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1607957","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]},"article-number":"1607957"}}