What treatment is suitable for HER2 positive breast cancer that has spread to the brain?

This paper studied methods of treatment in breast cancer brain metastasis. 

Breast cancer brain metastasis is cancer that has spread from the breast to the brain and is associated with poor prognosis (outlook). The overexpression of human epidermal growth factor receptor 2 (HER2, a protein on cells) increases the risk of brain metastasis. Trastuzumab (Herceptin; a drug that targets HER2) is used with chemotherapy as treatment. However, the blood-brain barrier (barrier that prevents certain substances from entering the brain) makes it difficult for trastuzumab to enter the brain. Hence, new techniques are being developed to enhance delivery of trastuzumab. 

Trials have shown that HER2 positive (HER2 present) patients are two to four times more likely than HER2 negative (HER2 absent) patients to develop brain metastases. The data suggests that trastuzumab itself does not increase the risk of brain metastasis.

Studies have shown that trastuzumab improves survival. Among HER2 positive patients, the average overall survival was 9-26 months in patients who received trastuzumab compared to 2-9 months in patients who did not receive trastuzumab. The time to development of brain metastasis and survival was longer in patients treated with trastuzumab compared to patients who did not receive trastuzumab.

Tumor growth and cancer therapy in the brain can compromise the blood brain barrier. A study showed that in patients with metastatic breast cancer, there was greater uptake of trastuzumab in those with brain tumors compared to normal brain tissue. Another study showed that average survival was 13.6 months patients who had received trastuzumab after brain metastasis compared with 4 months in patients who received trastuzumab before brain metastasis diagnosis and 5.5 months in patients who did not receive trastuzumab.

There are different methods of delivering drugs to cross the blood brain barrier. These include intraventricular administration (administration to spinal fluid at the base of the neck) and intracerebral drug delivery (administered directly to the brain). However, these are invasive techniques. Drug manipulation is another technique which is hard for large drus. Drugs can also be coupled to transporters. Another method involves physically disrupting the blood brain barrier. One study used ultrasound to disrupt the barrier and deliver trastuzumab directly. Future methods to cross the blood brain barrier may improve the effectiveness of trastuzumab in breast cancer that has metastasized to the brain. 

The authors concluded that trastuzumab is the standard treatment for HER2 positive breast cancer metastasis to the brain and can extend survival. 

Results were taken from several studies.