Breast Cancer brain metastases are associated with short survival once diagnosed.
Breast-cancer brain metastases are the second most frequent secondary CNS metastases following those from non-small cell lung cancer.
Up to 1/3 of patients with breast cancer are diagnosed with CNS disease.
In the ESME cohort, the risk of developing brain metastasis during metastatic disease was 34% for patients with ER positive and HER2 positive breast cancer and 49% for patients with ER negative and HER2 positive breast cancer.
An estimated 10-30% of all breast cancer patients eventually develop brain metastases.
Breast cancer brain metastasis occur in almost half of the patients with triple negative and HER2 positive metastatic breast cancer.
Brain metastases is associated with short survival compared to metastases at other sites of spread.
The cumulative incidence rates of brain metastases with breast cancer are highest patients with HER-2 positive and triple negative breast cancer, and his lowest in patients with ER positive disease.
Breast cancer brain metastasis typically are multifocal and intracerebral, and less commonly solitary and leptomeningeal.
Breast Cancer brain metastases arise as a function of the primary tumor biology and the metastatic environment.
The metastatic environment includes the blood brain barrier, pericytes, astrocytes, and the glial cells, which create the microenvironment in the brain that impacts the ability for metastases to develop and limits therapeutic response.
The 15 year cumulative incidence rates of brain metastasis are highest in HER2 positive and triple negative breast cancer (TNBC) subtypes of breast cancer and lowest in the luminal subtypes (Kennecke H et al).
The breast Cancer brain metastases rate in HER2 positive and TNBC subtypes is 15-44% and 25-46% respectively.
Patients with HER2 positive disease and estrogen receptor negative status have a higher likelihood of breast cancer brain metastases.
In an analysis of 213 patients with breast cancer brain metastases the median brain metastasis free survival was 34, 18, and 12 months in ER positive, HER2 positive and TNBC subtypes, respectively.
For HER2 positive breast cancer brain metastasis combinations of capecitabine and lapatinib, and neratinib are effective agents.
For HER2 positive disease to continue in combination with trastusumab and capecitabine demonstrated response rates from 20 to 47% in brain metastases.
Trastusumab deruxtecan is active in HER positive brain metastases.
Trastuzumab is associated with an increased time to the development of brain metastasis and improve survival after development of brain metastasis in HER2 positive BC.
HER2 positive breast cancer with brain metastasis is usually treated with a taxane plus trastuzumab and pertuzumab.
Tucatinib in combination with the trastusumab and capecitabine improved the overall survival, while reducing the risk of developing new brain metastasis in patients with ERBB2 positive metastatic breast cancer