LM is a rare but lethal complication of BC, with extremely low incidence rate of 2–5% on average. However, this percentage is supposed to be underestimated. On the other hand, incidence of LM-BC is increasing due to improvements in the survival of BC and poor blood-brain-barrier (BBB) penetration[4]. Considering the huge population base, China has a large number of patients with LM-BC.
Even more unfortunately, there are barely systematic studies of treatment for LM-BC[4, 5]. In addition, The diagnosis of LM always means resistant to endocrinotherapy. There are a great number of studies on the therapy of LM from HER2 + BC, but management of LM from ER + HER2 − ABC remains challenging[6]. In the face of specific treatment, the median overall survival (OS) is limited and the 1-year-survival rate is less than 15% worldwide. Palliative treatment is recommended by National Comprehensive Cancer Network (NCCN) and European Association of Neuro-Oncology/European Society for Medical Oncology (EANO/ESMO). However, it hardly improves neurologic symptoms without extending patients’ survival.
Molecular targeted therapy have been proved to be medicable for molecular-selected patients with non-small cell lung cancer (NSCLC) or breast cancer[7–10]. However, only less than 10% patients have the opportunity to achieve molecular targeted therapy[11]. The treatment for most LM patients lack of specific therapeutic targets, ER + HER2 − ABC, is still limited.
As shown by multivariate analysis, performance status at diagnosis of LM is the most important prognostic factor[1], other prognostic factors include subtype of cancer, CSF protein levels, administration of combined modality treatment, systemic treatment or intrathecal treatment and clinical or CSF responses to treatment.
LM with adverse prognostic factors, such as multiple and severe neurologic deficits, KPS score of < 60, concomitant brain metastasis, whose prognosis is extremely poor. Their CSF circulation is blocked by cancer cells, and the dispersion of intrathecal chemotherapy drugs is poor. IC alone has no survival benefit, and may even cause fearful central toxicity due to local drug accumulation.
Radiotherapy can directly kill the cancer cells and improve the symptoms of LM. It also can reconstruct the blocked CSF flow and reduce the symptoms of severe intracranial hypertension caused by poor CSF flow. In addition, the re-established CSF flow improves the diffusion of drugs in the CSF, improves the efficacy, and reduces the adverse toxicities in case of CSF flow obstruction[12–13].
However, the role of concurrent IC and radiotherapy in LM from solid tumors remained unproven. Prospective clinical trials of concurrent radiotherapy and IC performed in LM from solid tumors is few and far between. More than 30 years ago, two studies showed clinical benefit in patients who received concomitant IC and CNS radiotherapy, but further systematic studies have been lacking. For the past few years, Pan, Z. et al.[14] revealed a survival benefit from the regimen of concurrent radiotherapy and intrathecal MTX. Iglseder, S. et al.[15] retrospective analysis revealed WBRT combined intrathecal liposomal cytarabine showed an acceptable safety profile and may indicate a trend towards improved efficacy. Pan, Z. et al.[16] further confirmed concurrent involved-field radiotherapy and intrathecal MTX or Ara-C should be a feasible treatment option with an acceptable safety profile for LM from a common tumor entity, even for patients with adverse prognostic factors, which suggested that the concomitant therapeutic modality could be an optimal option for LM from patients lack of specific therapeutic targets.
In this article, we reported a ER + HER2 − LM-BC with adverse prognostic factors, including poor KPS and severe dysneuria, whose neurological function and the quality of life were completely improved while survival was significantly prolonged by concurrent WBRT and intrathecal MTX. It provides the light of prolonged survival for ER + HER2 − LM-BC.
In conclusion, this case indicates that to provide longer and better survival benefits for ER + HER2 − LM-BC, concurrent WBRT and intrathecal MTX has been proved to be a feasible option with an acceptable safety profile. But further trials are urgently needed to explore the precise therapeutic schedule, including therapeutic timing, cycle, order and dose of radiotherapy or intrathecal chemotherapy.