From the Guidelines
The prognosis for leptomeningeal carcinomatosis (LC) secondary to breast cancer is generally poor, with median survival typically ranging from 3-6 months with treatment, and patients with HER2-positive disease may have slightly better outcomes with median survival extending to 10-12 months in some cases when treated with HER2-directed therapies. When considering treatment options, it is essential to prioritize the patient's quality of life and morbidity, given the challenging prognosis. Treatment approaches may include:
- Intrathecal chemotherapy, such as methotrexate 10-15mg twice weekly or liposomal cytarabine 50mg every 2 weeks 1
- Systemic chemotherapy, particularly high-dose methotrexate 3-8g/m² if the patient can tolerate it
- Whole-brain radiation therapy, typically 30-40 Gy in 10-20 fractions
- Targeted therapies for HER2-positive disease, such as trastuzumab or T-DM1 1 Prognostic factors that may indicate a somewhat better outcome include:
- Good performance status (KPS >70)
- Limited systemic disease
- Hormone receptor positivity
- HER2 positivity (due to targeted treatment options)
- Absence of neurological deficits at diagnosis Supportive care is essential throughout treatment, including management of increased intracranial pressure with corticosteroids (dexamethasone 4-16mg daily), pain control, and addressing neurological symptoms 1. Early palliative care involvement is recommended to optimize quality of life given the challenging prognosis. According to the latest European Association of Neuro-Oncology (EANO)-ESMO guidelines, current treatments recommended for patients with LMD include systemic pharmacotherapy, intrathecal pharmacotherapy, and radiotherapy 1. The tucatinib, trastuzumab, and capecitabine combination has been included as a potential treatment option in the latest EANO-ESMO guidelines, with a median OS of 11.9 months in patients with LMD 1. Recent data also suggest that T-DXd could have a role in the treatment of patients with LMD, with a median OS of 13.3 months in patients with HER2-positive or HER2-low breast cancer and LMD 1.
From the Research
Prognosis of Leptomeningeal Carcinomatosis (LC) Secondary to Breast Cancer
- The prognosis of patients with leptomeningeal carcinomatosis (LC) secondary to breast cancer is poor, with a median overall survival time of less than 6 months 2.
- A study reported a case of a young woman with breast cancer who presented with LC and was treated with two lines of intrathecal chemotherapy, resulting in a prolonged response lasting 10 months 2.
- The 6-month survival rate for patients with LC secondary to breast cancer treated with intravenous thiotepa was 69%, and the 1-year survival rate was 31% 3.
- Patients with triple-negative breast cancer, concomitant brain metastases, or LC involving both the brain and spinal cord have the poorest prognosis 4.
- The median progression-free survival (PFS) from diagnosis of LC was 3.9 months, and the median overall survival (OS) was 5.4 months 4.
- Treatment options for LC, including radiotherapy, systemic therapy, and intrathecal treatment, aim to maintain the quality of life of patients by correcting neurological deficits and arresting neurological degeneration 5.
Treatment Options and Challenges
- Intrathecal chemotherapy is considered a standard of care for LC, although no randomized trial has demonstrated that it actually prolongs survival 2.
- Systemic therapy has been shown to have the longest OS compared to other treatment modalities, with a median OS of 8.8 months 4.
- The blood-brain barrier and the aggressive nature of the disease pose significant challenges to the treatment of LC 6.
- There is a lack of standardized therapy for LC due to the absence of randomized trials on this condition 5.