Brain metastases after breast-conserving therapy and systemic therapy: incidence and characteristics by biologic subtype

Abstract

The characteristics of brain metastases (BM) that develop after breast-conserving therapy (BCT) for early-stage breast cancer (BC) remain incompletely defined. We examined 1,434 consecutive patients with stage I/II invasive BC who received BCT from 1997 to 2006, 91 % of whom received adjuvant systemic therapy, according to BC subtype. Median follow-up was 85 months. Overall 5-year cumulative incidence of BM was 1.7 %; 0.1 % for luminal A, 3.3 % for luminal B, 3.2 % for luminal-HER2, 3.7 % for HER2, and 7.4 % for triple negative (TN). Women who developed BM were more likely at BC diagnosis to be younger (P < .0001) and have node-positive (P < .0001), grade 3 (P < .0001), hormone receptor-negative (P = .006), and HER2-positive (P = .01) tumors. Median time from BC diagnosis to BM was 51.4 months (range, 7.6-108 months), which was longer among luminal versus non-luminal subtypes (P = .0002; median, 61.4 vs. 34.5 months). Thirty-four percent of patients who developed distant metastases (DM) eventually developed BM. Median time from DM to BM was 12.8 months but varied by subtype, including 7.4 months for TN, 9.6 months for luminal B, and 27.1 months for HER2. Eighty-one percent of all BM patients presented with neurologic symptoms. Median number of BM at diagnosis was two, and median BM size was 15 mm, with TN (27 mm) and luminal B (16 mm) exhibiting the largest median sizes. In conclusion, the risk of BM after BCT varies significantly by subtype. Given the large size and symptomatic presentation among luminal B and TN subtypes, earlier BM detection might improve quality of life or increase eligibility for non-invasive treatments including stereotactic radiosurgery. Women with DM from these two BC subtypes have a high incidence of BM with a short latency, suggesting an ideal target population for trials evaluating the utility of MRI screening.

Antidepressant use and risk of central nervous system metastasis

“…Leptomeningeal involvement differs by subtype in breast cancer patients, with the majority of the disease occurring in luminal A subtypes followed by HER2 and triple negative cancers. Also differing by subtype, the median parenchymal brain metastases at diagnosis was highest among luminal A subtypes and decreased to luminal B, with the lowest number of parenchymal metastases in the HER2, and triple negative subtypes [153].…”

“…In breast cancer, this size differs by subtype, with triple negative tumors resulting in the largest median brain metastases [153]. In the parenchyma, these lesions tend to displace the tissue as opposed to permeating it.…”

“…Metastatic CNS tumors should be in the differential diagnosis if a cancer patient reports neurological symptoms such as headaches, nausea, cognitive problems, seizures, dysphasia, motor weakness, or sensory disturbances, since these metastases are usually symptomatic [139,145,153,[156][157][158]. CNS metastasis symptoms can either be generalized or focal.…”

“…One of the most common symptoms of brain metastasis is a headache, developing in about 23% to 38% of patients [153,[156][157][158]. These headaches generally transpire in patients with multiple metastases or metastasis located in the posterior fossa [4].…”

“…Occurring as frequently as headaches, altered mental status appeared in almost 25% of patients with brain metastasis [153,157]. Another study reported motor weakness and convulsion as the most frequent symptoms of brain metastases with almost a quarter of all clinically diagnosed breast cancer cases reporting each of these symptoms [145].…”