Breast cancer and leptomeningeal disease (LMD): hormone receptor status influences time to development of LMD and survival from LMD diagnosis

Abstract

Leptomeningeal disease (LMD) occurs in 5 % of breast cancer patients. The aim of this study was to identify risk factors related to survival and time to development of LMD in breast cancer patients. A retrospective analysis of breast cancer patients with LMD, evaluated in MDACC between 1995 and 2011. 103 patients with diagnosis of breast cancer and LMD were identified (one male). The median age at LMD diagnosis was 49.2 years. 78.2 % had invasive ductal carcinoma. Hormone receptors (HRs) were positive in 55.3 % of patients, 47.4 % were human epidermal growth factor receptor 2-positive and 22.8 % were triple negative. 52 % of the patients were treated with WBRT, 19 % with spinal radiation, 36 % with systemic chemotherapy and 55 % with intrathecal chemotherapy. Estimated median overall survival from time of breast cancer diagnosis was 3.66 years. Median survival from time of LMD diagnosis was 4.2 months. Time from breast cancer diagnosis to LMD was 2.48 years. In multivariate analysis, HR status and stage at diagnosis were significantly associated with time to LMD diagnosis (p < 0.05). In triple negative patients, time to LMD was shorter. In patients who were HR positive, time to LMD was longer. Survival from LMD diagnosis was significantly associated with both treatment, as well as positive HR status (multivariate analysis p < 0.05). In conclusion LMD has dismal prognosis in breast cancer patients. HR status contributes to time to LMD diagnosis and survival from LMD diagnosis. The impact of treatment aimed at LMD cannot be ascertained in our retrospective study due to the inherent bias associated with the decision to treat.

Management of isolated leptomeningeal metastasis as the initial and sole site of recurrence in a patient with early-stage breast cancer

“…Patients with hormone receptor (HR)-positive disease were also noted to have longer progression-free survival and overall survival in comparison to HR-negative cases [4]. Despite our patient having luminal subtype disease, GD recurred only three years post adjuvant therapy likely due to her high nodal burden of sixteen positive nodes.…”

Treatment of leptomeningeal carcinomatosis: Current challenges and future opportunities

“…Outside of performance status (PS), no consistent set of prognostic or predictive indicators have been elucidated to guide management. PS has demonstrated prognostic significance in a number of studies [7,10,11,20,21]. Pre-treatment CSF markers for prognostication have not definitively been shown to correlate with outcomes [2,4,5,7,11,12].…”

“…The importance of receptor status in breast cancer LM mirrors its importance in breast cancer in both systemic disease as well as brain metastases [22]. Some studies show that HER2+ LM has a better OS while triple-negative patients have poorer OS [20]. However, other studies suggest that patients with triple-negative disease may only appear to have worse outcomes because they have shorter time until diagnosis of LM [8].…”

“…Early studies combining patients with various primary tumors suggested that those with LM and breast cancer primaries have a higher response to treatment (up to 60% improving or stabilizing with chemotherapy and/or radiation therapy) and longer median survivals than those with other primaries (7 months versus 8-30 weeks) [2,4,11,20,24].…”

“…This may be because trastuzumab does not effectively cross the BBB, or because of loss of HER2 amplification in the breast cancer cells that metastasize to the brain. However, patients with HER2 amplified breast cancer and CNS metastases, both in brain parenchyma and CSF, fare better than those who are HER2 negative [20,22]. This may be due to more favorable natural history, better CNS response to therapies, better extra-CNS response to therapy, or a combination of these factors.…”