Endocrine therapy for the treatment of leptomeningeal carcinomatosis in luminal breast cancer: a comprehensive review

Abstract

Leptomeningeal disease (LMD) represents a devastating complication of advanced breast cancer (ABC), with survival of <5 months with multimodal treatment. The role of endocrine therapy (ET), due to its favorable toxicity profile and first-line indication in luminal ABC, appears promising in the setting of LMD, where symptom stabilization and quality-of-life preservation are the main goals; however, evidenced-based data are lacking. We conducted a thorough review of published evidence, aiming to investigate the role of ET in LMD treatment in luminal ABC. Twenty-one of 342 articles, evaluating 1302 patients, met inclusion criteria. ET use was rarely reported. New targeted agents show CNS activity. Research is lacking on the role of ET and targeted agents in BC-LMD treatment.

Radiological response of leptomeningeal metastases according to revised RANO criteria is associated with overall survival in breast cancer patients

“…In accordance with literature data, we also confirmed the prognostic impact of PS 15–19 and HER2 status, 20 while a positive CSF was not confirmed as a negative prognostic factor in our population, despite what recently reported 13 . In addition, in the selected cohort of patients with a follow‐up MRI, the prognostic impact of treatment modalities was also evaluated, and we confirmed the prognostic impact of systemic chemotherapy 17–20 and hormone therapy 15,21 …”

“…13 In addition, in the selected cohort of patients with a follow-up MRI, the prognostic impact of treatment modalities was also evaluated, and we confirmed the prognostic impact of systemic chemotherapy [17][18][19][20] and hormone therapy. 15,21 The major limitation of the present study is represented by its retrospective nature. For this reason, only radiological data could be accurately collected and assessed, while neurological and CSF assessments were unfortunately not always available.…”

Leptomeningeal Metastases: New Opportunities in the Modern Era

“…Despite the uncertainty regarding tumor-directed efficacy of hormonal agents in LM, it is worth noting that the use of endocrine therapy after brain or leptomeningeal metastasis diagnosis has been associated with prolonged survival, with no difference identified between choice of endocrine therapy employed [121]. This finding is supported also by a number of case reports suggesting durable response of LM to several hormonal agents, with most cases describing success with letrozole, exemestane, and tamoxifen [122][123][124][125][126].…”

Leptomeningeal Carcinomatosis from Solid Tumor Malignancies: Treatment Strategies and Biomarkers

“…It has limited CNS penetration in that studies have shown that CSF levels are 1-3% compared with those of serum. However, a study by Bowman and Kumthekar found that in 13 patients with LMD from breast cancer, treatment with pemetrexed leads to an mOS of 7.3 mo 25,37 Tamoxifen, letrozole, and anastrozole These have all been reported as at least moderately efficacious in hormone receptorþ breast cancer LMD case reports 25,53 Temozolomide þ/À irinotecan Reports in melanoma and breast cancer: temozolomide may be given alone 25 or in combination with Irinotecan 54 Tucatinib HER2þ breast cancer, ongoing clinical trials for LMD patients as well as in patients with HER2þ cancers Abbreviations: BEEP, bevacizumab, etoposide, and cisplatin; CNS, central nervous system; CSF, cerebrospinal fluid; EGFR, epidermal growth factor receptor; LMD, leptomeningeal disease; mOS, median overall survival; RT, radiotherapy.…”