Abstract
BackgroundThe incidence of central nervous system (CNS) metastases in breast cancer patients is rising and has become a major clinical challenge. Only few data are published concerning risk factors for the development of CNS metastases as a first site of metastatic disease in breast cancer patients. Moreover, the incidence of CNS metastases after modern neoadjuvant treatment is not clear.MethodsWe analyzed clinical factors associated with the occurrence of CNS metastases as the first site of metastatic disease in breast cancer patients after neoadjuvant treatment in the trials GeparQuinto and GeparSixto (n = 3160) where patients received targeted treatment in addition to taxane and anthracycline-based chemotherapy.ResultsAfter a median follow-up of 61 months, 108 (3%) of a total of 3160 patients developed CNS metastases as the first site of recurrence and 411 (13%) patients had metastatic disease outside the CNS. Thirty-six patients (1%) developed both CNS metastases and other distant metastases as the first site of metastatic disease. Regarding subtypes of the primary tumor, 1% of luminal A-like (11/954), 2% of luminal B-like (7/381), 4% of HER2-positive (34/809), and 6% of triple-negative patients (56/1008) developed CNS metastases as the first site of metastatic disease.In multivariate analysis, risk factors for the development of CNS metastases were larger tumor size (cT3–4; HR 1.63, 95% CI 1.08–2.46, p = 0.021), node-positive disease (HR 2.57, 95% CI 1.64–4.04, p < 0.001), no pCR after neoadjuvant chemotherapy (HR 2.29, 95% CI 1.32–3.97, p = 0.003), and HER2-positive (HR 3.80, 95% CI 1.89–7.64, p < 0.001) or triple-negative subtype (HR 6.38, 95% CI 3.28–12.44, p < 0.001).ConclusionsEspecially patients with HER2-positive and triple-negative tumors are at risk of developing CNS metastases despite effective systemic treatment. A better understanding of the underlying mechanisms is required in order to develop potential preventive strategies.
Highlights
The incidence of central nervous system (CNS) metastases in breast cancer patients is rising and has become a major clinical challenge
Concerning the tumor subtype, 32% (n = 1008) had a triple-negative breast cancer (TNBC), 30% (n = 954) a luminal A-like, 12% (n = 381) a luminal B-like, and 26% (n = 809) human epidermal growth factor receptor 2 (HER2)-positive tumor. Pathologic complete response (pCR) after neoadjuvant treatment was observed in 23% (n = 738) of the patients
Patients with HER2-positive tumors had a pCR rate of 30% (n = 245), and luminal A- and B-like breast cancer patients had pCR rates of 6% (n = 61) and 14% (n = 52), respectively (Table 1)
Summary
The incidence of central nervous system (CNS) metastases in breast cancer patients is rising and has become a major clinical challenge. Few data are published concerning risk factors for the development of CNS metastases as a first site of metastatic disease in breast cancer patients. Central nervous system (CNS) metastases in breast cancer patients are a clinically relevant problem. Survival times of 3.7–15 months after the occurrence of CNS metastases have been described [2]. In a retrospective study by Niikura et al with 1256 patients diagnosed with brain metastases, the median overall survival of TNBC patients after the CNS metastasis diagnosis was 4.9 months and that of human epidermal growth factor receptor 2 (HER2)-positive patients was 11.5 months [3]
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