When Do Brain Metastases Strike in Breast Cancer Care?

TOPLINE:

In patients with metastatic breast cancer (BC), the prevalence of brain metastases increased with each treatment line, rising the most among patients with hormone receptor (HR)–negative, human epidermal growth factor receptor 2 (HER2)–positive disease and the least among those with HR-positive, HER2-negative disease.

METHODOLOGY:

• Brain metastases indicate a poor prognosis in patients with metastatic BC. Understanding the prevalence of brain metastases with each line of therapy and by tumor subtype could help guide central nervous system screening and treatment strategies.
• The study analyzed data from 18,075 patients with metastatic BC, derived from a deidentified nationwide electronic health record database in the United States. Researchers categorized patients by HR and HER2 status.
• The primary outcome was the first diagnosis of brain metastases. Researchers estimated the risk for brain metastases in patients without them at therapy initiation and evaluated data from patients on as many as five lines of therapy.
• At initiation of first-line therapy, 1102 patients (6.1%) had at least one brain metastasis.

TAKEAWAY:

• The cumulative incidence of brain metastases at 60 months was 10% in patients with HR-positive, HER2-negative disease, 22% in those with triple-negative BC (TNBC), 23% in those with HR-positive, HER2-positive disease, and 34% in those with HR-negative, HER2-positive disease.
• For HER2-positive disease, the prevalence of brain metastases in those who were also HR-positive increased from 9.1% at the start of first-line therapy to 22.9% by third-line therapy. More patients (13.1%) with HR-negative, HER2-positive disease had at least one brain metastasis at first-line therapy, and the incidence rose sharply to 32.4% by second-line therapy and then remained close to 40% for subsequent lines of therapy.
• The prevalence of brain metastases in patients with HR-positive, HER2-negative disease steadily rose with each subsequent line but remained the lowest among the subtypes across lines of therapy, starting at 3.9% at first-line therapy and peaking at 10.7% by the fifth line.
• For TNBC, 12.6% of patients had brain metastases at the start of first-line therapy, and that prevalence peaked at 30.5% by fifth-line therapy. However, the researchers found that HER2-low expression had no effect on brain metastasis incidence in HR-positive, HER2 -negative disease or TNBC.

IN PRACTICE:

“Our findings further demonstrate that brain metastases are frequent in patients with [HR-negative, HER2-positive metastatic BC] and often occur early in the development of the disease,” the authors reported. “Moreover, these findings emphasize the importance of ongoing screening clinical trials (particularly at critical timepoints such as transitions between treatment lines) and have significant clinical implications for the design of screening and prevention trials. Tailored surveillance strategies are warranted” as well.

SOURCE:

The study, led by Sarah L. Sammons, MD, Dana-Farber Cancer Institute, Boston, was published online in the Journal of the National Cancer Institute.

LIMITATIONS:

This study used de-identified data from an electronic health record, which may have inherent limitations in data completeness and standardization.

DISCLOSURES:

The study was supported by F. Hoffmann-La Roche that provided funding for access to the de-identified database. Several authors reported receiving research funding from and having other ties with various pharmaceutical and other organizations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.