A comprehensive review of current treatment modalities for leptomeningeal carcinomatosis in breast cancer.

Leptomeningeal carcinomatosis (LC) is a metastatic complication of breast cancer that imparts a very poor prognosis and distressing neurologic symptoms in affected patients. While the incidence of LC has risen with improving survival rates for cancer patients, there remains no established treatment protocol for LC and clinical trial data comparing available therapies is limited. Here, a comprehensive literature search of the pubmed and Cochrane databases was performed. Current treatment modalities and their safety/ efficacy profiles are summarized for LC in breast cancer. Roles for emerging therapies in LC are discussed, including targeted agents, CAR-T, immune checkpoint inhibitors, CDK inhibitors and novel antibody conjugates. A treatment pathway for LC is also proposed to guide clinicians through management of this severe metastatic complication of breast cancer.

A Pilot Study of the Combination of Entinostat with Capecitabine in Advanced Breast Cancer.

Background: Breast cancer has an unacceptably high recurrence rate when any residual disease is found following neoadjuvant treatment of high-risk disease. Based on clinical data suggesting an adjuvant role for epigenetic modifying agents in breast cancer and preclinical data suggesting synergistic activity of entinostat combined with capecitabine, we conducted a phase I, open-label study of these agents in metastatic breast cancer (MBC). Both agents have published doses for use in combination therapy, but the agents had not previously been combined with each other in a human trial. Methods: A multisite phase I dose escalation study was performed at two academic centers. Patients with pretreated, HER2-negative MBC, and measurable disease were enrolled. Dual dose escalation was performed via a Bayesian partial order continual assessment method. Dose levels ranged from entinostat 3 mg to 5 mg and capecitabine 800 mg/m2 to 1000 mg/m2. Results: Thirteen patients with MBC and a median of 4 lines of prior therapy were enrolled across four dose level combinations. The most common toxicities were neutropenia, thrombocytopenia, and palmar-plantar dysesthesia, which were expected toxicities. No new safety signals were observed. One dose-limiting toxicity was observed, which did not exceed a prespecified toxicity rate of 25%. The median treatment duration was 2.37 months. No partial nor complete responses were observed. The study was halted early prior to entering an expansion phase, due to drug supply limitations. Conclusion: The tested dosing combinations of entinostat and capecitabine are likely safe in heavily pretreated metastatic breast cancer. This study's clinical investigation of entinostat in breast cancer was halted, but drug development of this agent continues outside the US. There remains a need for postoperative adjuvant drug therapy for the subpopulation of breast cancer patients with high-risk residual cancer after curative therapy. This trial is registered with NCT03473639.

Primary tumor resection in de novo stage IV breast cancer patients.

Breast and axillary surgery in Stage IV disease is outside current national guidelines but has been a topic of ongoing debate. A single institution retrospective study identified women with de novo stage IV BC from 2011-2016 to evaluate the rate and goals of primary site surgery. Only 10.2% (n = 27/265patients) had primary site surgery. The goal of surgery was most often treatment intent (n = 23, 85.1%) not palliation (n = 4, 14.8%). There was no 30-day mortality and low (n = 1, 3.7%) 30-day morbidity. Multi-disciplinary patient care pathways based on modern evidence may help identify patients potentially suitable for primary site surgery.