Abstract P1-10-21: Intrathecal therapy in invasive lobular carcinoma with non-bulky leptomeningeal disease: case report

Abstract Introduction: Leptomeningeal disease (LMD) is a challenging complication of breast cancer (BC) with limited treatment options and a prognosis of three to four months in most cohorts. This case report describes the treatment of a patient with LMD at her initial diagnosis, evaluating its indication and clinical evolution. Case report: Female, 68y at BC diagnosis, post-menopausal. Previous history: hysterectomy at 43y; hormone implants replacement therapy until diagnosis; pleuropulmonary fibrolastosis. Family history: a sister died of ovarian cancer at 40y, NGS for 25 germline mutations negative. In 2018, the patient experienced bloating. Upper digestive endoscopy: normal. In April 2018, she was hospitalized due to ascites, with positive oncotic cytology. A biopsy confirmed peritoneal carcinomatosis (GATA3 and estrogen/progesterone receptors [ER/PR] positive; CDX-2 and HER2 negative). At initial staging, diffuse gastric thickening compatible with carcinomatosis. In the right breast, nodule measuring 1.6x1.0x0.8cm, biopsy confirmed invasive lobular carcinoma (ER 95%, PR 95%, HER2 negative, Ki67 15%). In May 2018, she received 5 cycles of Carboplatin + Paclitaxel with reduction in ascites and partial response at restaging. She then came to our institution and was started on Tamoxifen (as her estradiol levels were high due to hormone implants that were not able to be removed) and Palbociclib in August 2018. However, at this time, diplopia was present, and she reported it had started before chemotherapy. Cerebrospinal fluid (CSF) cytology was positive for neoplastic cells, and there were suspicious findings on cranial MRI: heterogeneous contrast uptake in the right cingulate gyrus with no parenchymal brain metastases (BM). She received 9 cycles of intrathecal (IT) methotrexate (12mg) from August 2018 until January 2019, with improvement of diplopia. CSF after 8 weeks of IT therapy was still positive, but it was negative in February 2019, with no suspicious findings on new cranial MRI. She remained on Tamoxifen and Palbociclib with stable disease (SD) in the breast, with no other measurable site. In January 2021, she developed epigastric pain. An endoscopy showed an area of infiltration in the duodenum, biopsy confirmed lobular BC. She underwent radiotherapy with resolution of her symptoms. Palbociclib was maintained and Tamoxifen was switched to Letrozole as her estradiol levels were indetectable. In October 2021, she presented a new progression of duodenal disease, and liposomal doxorubicin was administered for 6 cycles until April 2022 with partial response. Afterwards, she continued hormonal treatment with Fulvestrant and Alpelisib (PIK3Ca mutation on NGS). Due to pneumonitis, Alpelisib was suspended in June 2022. In November, Fulvestrant was also suspended due to continued worsening of pneumonitis. She was maintained on treatment holiday due to previous toxicities. In April 2023, she had SD, measurable only in the breast, being maintained with no oncological treatment. However, she continued to worsen her previous pulmonary condition (pleuropulmonary fibrolastosis) and died in August 2023. Discussion: The patient above presented non-bulky LMD, with no hydrocephalus, and with no parenchymal BM, deriving clinical benefit with improvement in diplopia and survival of 59 months after the diagnosis of LMD. No relapse was observed in the central nervous system after IT therapy. The patient died from non-oncological causes with no disease activity while on drug holiday. Conclusion: This patient with invasive lobular carcinoma and non-bulky LMD, no hydrocephalus and no parenchymal BM had a longer survival than most patients with LMD. She received both IT and systemic therapy. This case reinforces the importance of seeking appropriate criteria for selecting patients with potential benefit from treatment. Citation Format: Daniel Sobral Filho, Aniceto Lopes da Silva Neto, Giulia Mazaro de Oliveira, Rafaela Lopes da Silva Naves, Raelson Rodrigues Miranda, Laura Testa. Intrathecal therapy in invasive lobular carcinoma with non-bulky leptomeningeal disease: case report [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-10-21.