Patients with inflammatory breast cancer at high risk for brain metastases
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Patients with inflammatory breast cancer exhibited higher risk for central nervous system metastasis, according to study results published in Cancer.
The risk appeared highest among those with metastasis elsewhere, particularly at a younger age, and/or triple-negative breast cancer, researchers noted.
Background and methods
“This research was prompted by earlier studies showing a relatively high risk for brain metastases in patients with inflammatory breast cancer,” Laura E.G. Warren, MD, EdM, radiation oncologist in the department of radiation oncology at Dana-Farber Cancer Institute, told Healio. “We wanted to examine the risk for brain metastases in a larger cohort of patients with inflammatory breast cancer, explore the risk factors for brain metastases and report on the treatment approaches to date.”
The retrospective review included 531 patients (median age, 51 years; range, 24-91) diagnosed with inflammatory breast cancer between 1997 and 2019. Among them, 372 (70%) had been diagnosed with stage III disease and 159 had de novo stage IV disease at diagnosis.
Researchers defined CNS metastasis-free survival time as the date from inflammatory breast cancer diagnosis to the date of CNS metastasis or death — whichever occurred first. They used a competing risks hazard model to evaluate risk factors for CNS metastasis.
Findings
Among all patients, 124 (23%) developed CNS metastasis.
At median follow-up of 5.6 years, researchers observed a CNS metastasis incidence of 5% at 1 year, 9% at 2 years and 18% at 5 years among patients with stage III disease. Among those with stage IV disease, researchers observed a CNS metastasis incidence of 17% at 1 year, 30% at 2 years and 42% at 5 years at median follow-up of 1.8 years.
Median OS after diagnosis of CNS metastasis was 0.6 years (95% CI, 0.5-0.8).
Results of multivariate analysis that included 343 patients with stage III disease showed triple-negative disease (subdistribution HR [sHR] = 1.98; 95% CI, 1.02-3.84) as a significant risk factor for CNS metastasis compared with hormone receptor-positive, HER2-negative disease.
Modeling for 309 patients with metastatic disease who did not present with CNS metastasis showed significantly higher risk for CNS metastasis among those with viscera vs. bone as first metastatic site (sHR = 1.96; 95% CI, 1.08–3.58) and triple-negative vs. HER2-positive disease (sHR = 2.31; 95% CI, 1.25-4.13). Older patients had a lower likelihood of being diagnosed with CNS metastasis than younger patients (sHR = 0.97; 95% CI, 0.96-0.99).
“The majority of patients were diagnosed with brain metastases when they presented with neurologic symptoms concerning for brain metastases and received whole-brain radiation therapy for treatment of their brain metastases,” Warren said. “It is important to note that because screening or surveillance MRI was not used routinely in these patients, likely the true incidence of brain metastases is even higher than this study reports.”
Implications
The relatively high incidence of brain metastases observed in the study population highlights the need for future research on the potential role of surveillance brain imaging for high-risk patients and whether surveillance imaging improves quality of life and/or allows for more focused treatment with fewer side effects than whole-brain radiation therapy, Warren said.
“It also emphasizes the need to obtain brain imaging in patients with inflammatory breast cancer presenting with neurologic symptoms, given the high incidence of brain metastases in this population,” Warren continued. “An open, phase 2, single-arm study at our institution will examine the question of surveillance brain MRI among patients presenting with stage III inflammatory breast cancer. This study will provide prospective data on the incidence of brain metastases in this patient population, which is critical, as our study likely underreported the incidence.”
The study highlighted the high incidence of brain metastases among patients with inflammatory breast cancer and the poor prognosis after diagnosis, and raised the question of whether routine screening brain MRIs should be implemented to detect metastatic breast cancer earlier in patients with inflammatory breast cancer, according to an accompanying editorial by Ajay Dhakal, MBBS, assistant professor in the department of medicine at University of Rochester Medical Center, and Carey K. Anders, MD, professor of medicine in the department of medicine at Duke Cancer Institute.
“Importantly, will earlier detection lead to improvement in both survival and quality of life? We eagerly await the results of ongoing trials to investigate the feasibility and/or benefit of the implementation of screening MRIs in patients with metastatic breast cancer, which may help us answer this important question,” the editorial authors wrote.
References :
- Dhakal A, et al. Cancer. 2022;doi:10.1002/cncr.34442.
- Warren LEG, et al. Cancer. 2022;doi:10.1002/cncr.34441.
For more information:
Laura E.G. Warren, MD, EdM, can be reached at laura_warren@dfci.harvard.edu.
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