{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:05:56Z","timestamp":1784696756318,"version":"3.55.0"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"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:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>HER2-positive breast cancer is an aggressive subtype associated with high rates of early recurrence and brain metastasis. Standard adjuvant therapy, including anti-HER2 targeted agents, significantly improves outcomes. This case illustrates the natural history of untreated HER2-positive breast cancer and documents an exceptionally rare metastatic site.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We report a case of a 63-year-old woman with HER2-positive (3+, FISH amplified), ER-positive (80-90%), PR-negative, Ki-67 15% invasive ductal carcinoma of the left breast (pT1cN2aM0, 7\/12 axillary lymph nodes positive).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The patient refused all standard adjuvant therapies (chemotherapy, radiotherapy, endocrine therapy, and anti-HER2 therapy) and opted for sole Chinese herbal medicine. After seven years of follow-up (with a disease-free interval of approximately four years, she developed a right cerebellar hemisphere metastasis (2.3\u00d72.7 cm with extensive edema), widespread lymphadenopathy, and a pathologically confirmed thyroid metastasis\u2014an extremely rare event in breast cancer. Fine-needle aspiration of the thyroid nodule demonstrated atypical cells, and subsequent immunohistochemistry confirmed breast cancer origin (GATA3+, GCDFP-15+, HER2 3+, ER+, TTF-1-, TG-).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This case provides compelling\n                      <jats:italic>in vivo<\/jats:italic>\n                      evidence of the aggressive natural history of untreated HER2-positive breast cancer. The development of brain metastasis underscores the critical importance of anti-HER2 agents that penetrate the blood-brain barrier. The rare thyroid metastasis adds to the literature on unusual metastatic patterns. This report serves as a powerful warning of the consequences of abandoning evidence-based adjuvant therapy in high-risk breast cancer.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1861088","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:45:21Z","timestamp":1784695521000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: From standard therapy refusal to rare metastases: a case of untreated HER2-positive breast cancer progressing to brain and thyroid metastases after seven years of follow-up during which the patient received only Chinese herbal medicine"],"prefix":"10.3389","volume":"16","author":[{"given":"Qing","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Pathology, Deyang People\u2019s Hospital","place":["Deyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Deyang People\u2019s Hospital","place":["Deyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, Deyang People\u2019s Hospital","place":["Deyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, Deyang People\u2019s Hospital","place":["Deyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32417-5","article-title":"HER2-positive breast 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