Which Breast Cancer Type Has Greatest Risk of Brain Metastasis?

Nearly one in seven patients with metastatic breast cancer will need radiotherapy to treat brain metastases, but patients with certain subtypes are much more likely to develop brain metastases, recent analysis shows.

Specifically, about one third of women with ERBB2-positive disease and nearly one in four with triple-negative breast cancer (TNBC) will develop brain metastases that require radiotherapy. Those with TNBC also developed intracranial involvement in the shortest time from diagnosis of metastatic disease.

The findings potentially justify “screening for intracranial metastatic disease in these patient populations,” senior author Katarzyna Jerzak, Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada, and colleagues conclude.

The study was published online in JAMA Network Open.

Brain metastases remain a significant cause of morbidity and mortality in women with breast cancer but currently guidelines do not recommend patients undergo neuroimaging to screen for brain involvement in women with early or metastatic breast cancer.

The researchers reviewed Ontario-wide health administrative data to identify the cumulative probability of patients receiving radiotherapy for brain metastases among women with de novo metastatic breast cancer as well as the time to develop brain metastases following their diagnosis.

Overall, 3916 women were identified as having de novo metastatic breast cancer between 2009 and 2018. Among these patients, 14% underwent stereotactic radiosurgery or whole brain radiotherapy to treat brain metastases.

Looking at breast cancer subtype, the cumulative incidence of brain metastases was highest among patients with ERBB2-positive/HR-negative disease at nearly 35%, followed by 28% for those with ERBB2-positive/HR-positive breast cancer, and 22% with TNBC.

The median time from the diagnosis of metastatic breast cancer to brain radiotherapy was about 15 months but varied by breast subtype. The time ranged from 7.5 months for patients with TNBC to 19.8 months for those with ERBB2-positive/HR-positive breast cancer.

Median survival also varied by breast cancer subtype. Overall survival from diagnosis of metastatic breast cancer was 19.3 months overall, but survival was lowest for patients with TNBC (8.8 months) and highest for those with ERBB2-positive/HR-positive breast cancer (27.8 months).

This analysis can help inform brain metastases screening programs. For instance, patients with ERBB2-positive metastatic breast cancer may be “ideal candidates” for brain metastases screening programs, the authors suggest.

However, the authors note that even though patients with metastatic TNBC have a high cumulative incidence of brain metastases, “it is unclear whether these patients would benefit from early detection and treatment of intracranial metastatic diseases given their typically aggressive disease biology.”

The work was supported by a research grant from Eli Lilly. Jerzak reported receiving grants from Eli Lilly, AstraZeneca, and Seagen, and personal fees from Amgen, AstraZeneca, Pfizer, Novartis, Eli Lilly, and other companies.

JAMA Network Open. Published online August 12, 2022. Full text.

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