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A study by researchers from the Dana-Farber Cancer Institute provides novel insights into the high incidence of and risk factors for central nervous system metastases (mCNS) in women with inflammatory breast cancer.

The findings “could have implications for surveillance and prognosis of the disease,” wrote Laura Warren, from the Department of Radiation Oncology and the Inflammatory Breast Cancer Program at the Dana-Farber Cancer Institute, and her colleagues in a paper published recently in the journal Cancer.

Inflammatory breast cancer is a rare subtype of the disease that is estimated to represent less than 5% of invasive breast cancers diagnosed in the United States. Previous studies have demonstrated higher rates of brain metastases in patients with inflammatory breast cancer, but detailed information is lacking.

To address this, Warren and team retrospectively reviewed data for 531 patients diagnosed with stage III or stage IV inflammatory breast cancer between 1997 and 2019.

After a median 5.6 years of follow-up, 66 (17.7%) of the 372 patients with stage III disease at diagnosis developed mCNS. The 1-, 2-, and 5-year cumulative incidence rates of 5%, 9%, and 18%, respectively.

The median follow-up period among the 154 patients with stage IV disease was 1.8 years. In this group, the 1-, 2-, and 5-year cumulative incidence rates of mCNS were a respective 17%, 30%, and 42%.

However, the researchers note that because current guidelines do not recommend brain imaging for people with breast cancer and most (70%) patients in the current study were diagnosed with mCNS during follow-up of neurologic symptoms. It is therefore likely that the true incidence of mCNS is even higher than reported as a result of undetected, asymptomatic disease.

Further analysis revealed that having a triple-negative subtype was associated with double the risk for mCNS compared with a hormone receptor positive, HER2-negative subtype in both the stage III and stage IV patients.

In addition, patients with stage IV disease had twice the risk for mCNS if they had visceral rather than bone metastasis as the first site of metastatic disease, but the risk fell with increasing age. Specifically, each year increase in age at diagnosis was associated with a 3% lower risk for mCNS.

Warren told Inside Precision Medicine that the data “prompt the question of the value of surveillance brain MRI in patients with inflammatory breast cancer.

“One could hypothesize that a risk-adapted surveillance strategy for patients at high risk of brain metastases may allow for earlier detection of brain metastases, detection prior to development of symptoms, decreased utilization of whole brain radiation therapy (and its resultant toxicities), and/or improved quality of life for these patients,” she said.

Warren and team are now recruiting patients to a Phase II, single arm study at the Dana-Farber Cancer Institute that will prospectively examine the question of surveillance brain MRI in patients presenting with stage III inflammatory breast cancer.

While the researchers will await the findings of that trial before recommending routine screening for all patients with inflammatory breast cancer, Warren said that the current study has immediate clinical impact because “it emphasizes the need to obtain brain imaging in patients with inflammatory breast cancer with any symptoms concerning for brain metastases given the high incidence of brain metastases in this population.”

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