Rare breast cancer case survives 21 months after leptomeningeal spread

A 51-year-old woman with an exceptionally rare form of triple-negative breast cancer survived 21 months after cancer cells spread into the membranes surrounding her brain and spinal cord, according to a case report published in Frontiers in Oncology. The report, from clinicians at Kaohsiung Medical University Chung-Ho Memorial Hospital in Taiwan, describes what the authors believe is the first documented case of leptomeningeal metastasis arising from glycogen-rich clear cell carcinoma of the breast, an uncommon histological subtype that accounts for roughly 1.4 to 3 percent of all breast malignancies. The prolonged survival is notable because leptomeningeal metastasis generally carries a median overall survival of approximately four to six months, and the outlook is even shorter in triple-negative disease.

The patient first presented with a painful, palpable mass measuring approximately 2 centimeters in the upper outer quadrant of her right breast. She had no significant past medical history. Mammography showed a 2.5-centimeter oval, equal-density mass with an obscured margin in the same region, and breast ultrasonography classified the lesion as highly suspicious under the American College of Radiology Breast Imaging Reporting and Data System, category 4c. A core needle biopsy established a histological grade 2 invasive carcinoma with glycogen-rich clear cell features, a morphology defined by tumor cells containing abundant intracytoplasmic glycogen that gives them a clear appearance. Under the World Health Organization classification, more than 90 percent of tumor cells must demonstrate this distinctive pattern for the diagnosis.

Immunohistochemical testing confirmed a triple-negative phenotype: estrogen receptor expression was 0 percent, progesterone receptor expression was 0 percent, and the human epidermal growth factor receptor 2 score was 0. The Ki-67 proliferation index, a measure of how many cells are actively dividing, was approximately 70 percent, indicating a rapidly proliferating tumor. Programmed death-ligand 1 expression was negative, with a tumor proportion score and a combined positive score both below 1 percent. The woman was premenopausal at diagnosis, and germline genetic testing did not identify any pathogenic variants in BRCA1 or BRCA2. Her family history was significant for lung and colorectal cancer but included no known breast or ovarian cancer.

Staging revealed extensive disease. Contrast-enhanced computed tomography showed multifocal tumors in the right breast, the largest measuring 2.4 centimeters, together with metastatic involvement of level I, II, and III axillary lymph nodes and right posterior cervical lymph nodes. Suspicious hepatic nodules prompted further imaging with dynamic contrast-enhanced abdominal magnetic resonance imaging, which demonstrated a small enhancing lesion in segment VII of the liver consistent with metastatic disease. A subsequent 18F-FDG PET/CT scan showed no discernible FDG uptake in that hepatic lesion, but the clinicians noted that the small size of the lesion meant the absence of avidity did not exclude metastasis. No liver biopsy was performed, so the hepatic diagnosis remained radiological. A brain MRI obtained during initial staging showed no evidence of intracranial metastasis. The final diagnosis was stage IV triple-negative breast cancer, classified cT2N3M1, with glycogen-rich clear cell features.

Follow-up chest CT showed a partial response under the Revised Response Evaluation Criteria in Solid Tumors, version 1.1, with shrinking breast tumors and involved lymph nodes. Histopathological examination of the surgical specimen confirmed the glycogen-rich clear cell morphology and triple-negative immunophenotype, with a Ki-67 index of approximately 40 percent. Despite the radiographic shrinkage, multiple foci of residual invasive carcinoma remained, measuring 5.2 centimeters in greatest dimension, and all 13 dissected axillary lymph nodes contained metastatic carcinoma with extranodal extension, indicating a substantial residual disease burden.

Approximately ten months after the initial diagnosis, while still within the planned systemic course but after completing radiotherapy, the patient developed progressive headache, dizziness, left hand numbness, and a transient episode of dysarthria. Neurological examination revealed no focal deficits. Contrast-enhanced brain MRI was initially read as showing no definite leptomeningeal enhancement, although retrospective review suggested subtle meningeal enhancement. Cerebrospinal fluid cytology revealed malignant cells, confirming leptomeningeal metastasis. The planned chemotherapy regimen was discontinued after two cycles, and intravenous sacituzumab govitecan was selected as the next systemic therapy.

Before that drug could begin, her condition deteriorated rapidly. She developed severe headache, intractable vomiting, diplopia, and psychotic manifestations including visual and auditory hallucinations. Repeat brain MRI showed progression of the leptomeningeal disease accompanied by worsening hydrocephalus, an accumulation of fluid within the brain that is a common complication of leptomeningeal metastasis. The intervention produced marked symptomatic improvement.

After the third cycle, MRI demonstrated a partial response by RECIST version 1.1, characterized by reduction in the size of the metastatic lesion in the right hepatic lobe, with no evidence of peritoneal dissemination. However, serial brain MRI during follow-up revealed gradual radiographic progression of both pachymeningeal and leptomeningeal enhancement. In response, the team initiated intrathecal chemotherapy with methotrexate; the patient declined whole-brain radiotherapy. Despite the radiographic progression, she remained clinically stable with an Eastern Cooperative Oncology Group performance status of 1 for the first 20 months after the leptomeningeal diagnosis, experiencing no recurrent headaches or new neurological deficits and remaining independent in activities of daily living. In total, she received eleven cycles of sacituzumab govitecan, two sessions of intrathecal methotrexate at 12 mg, and six cycles of trastuzumab deruxtecan at 5.4 mg/kg, the latter discontinued because of fatigue and financial considerations.

In the final month of her life, she developed frequent transient dysarthria, paresthesia, and vomiting while supine, consistent with clinical progression of the leptomeningeal disease. Resumption of trastuzumab deruxtecan was considered, but she deteriorated before treatment could be given. Following shared decision-making with the patient and her family, care shifted to hospice, and she died 21 months after the leptomeningeal diagnosis. In their discussion, the authors contrast her course with the only previously reported case of sacituzumab govitecan in triple-negative leptomeningeal disease, a patient with a pontine metastasis and extensive craniospinal involvement, repeatedly negative cerebrospinal fluid cytology, who received eight cycles and died seven months after the drug was started. Their patient, by contrast, had no parenchymal brain metastasis, cytology-confirmed disease, and shunt-relieved intracranial pressure. The authors caution that the longer survival may reflect a lower initial neurological burden, pressure relief, longer drug exposure, and multimodal therapy, and cannot be attributed to sacituzumab govitecan alone.

The report also touches on a longstanding concern about shunting. Although peritoneal dissemination is a theoretical risk when a ventriculoperitoneal shunt is placed in a patient with metastatic cancer, prior studies in metastatic breast cancer have not demonstrated shunt-related peritoneal seeding, and no evidence of peritoneal metastasis was observed in this case. The authors raise, explicitly as a speculative hypothesis, the possibility that shunting may influence tumor cell distribution and systemic drug exposure. Because patients with leptomeningeal involvement have been routinely excluded from prospective trials of sacituzumab govitecan, its efficacy in this setting remains largely unexplored, and this represents only the second reported use of the drug in triple-negative leptomeningeal disease. In her own account, the patient described tolerating treatment well, remaining able to work, travel, and carry out her usual activities, including a trip to Turkey lasting more than ten days. The authors conclude that the prolonged clinical course suggests a potential role for the drug and for shunting that warrants further investigation, while emphasizing that conclusions from a single case must remain provisional.

Subject of Research: A case report of leptomeningeal metastasis from triple-negative glycogen-rich clear cell breast carcinoma treated with sacituzumab govitecan and ventriculoperitoneal shunting

Article Title: Case Report: Prolonged survival following multimodal treatment of leptomeningeal metastases in triple-negative glycogen-rich clear cell breast carcinoma

Article References: Lo, Y.-C., Wu, C.-C., Hung, S.-C., Pan, L.-P., & Shih, S.-L. (2026). Case Report: Prolonged survival following multimodal treatment of leptomeningeal metastases in triple-negative glycogen-rich clear cell breast carcinoma. Frontiers in Oncology, 16, Article 1901536. https://doi.org/10.3389/fonc.2026.1901536

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1901536

Keywords: triple-negative breast cancer, leptomeningeal metastases, glycogen-rich clear cell carcinoma, sacituzumab govitecan, ventriculoperitoneal shunt, case report, hydrocephalus, intrathecal methotrexate, trastuzumab deruxtecan, antibody-drug conjugate, brain metastasis, Frontiers in Oncology