Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies.

The current study was conducted to investigate survival and the response to radiotherapy among patients with molecular subtypes of breast cancer brain metastases treated with or without targeted therapies. Patients diagnosed with breast cancer brain metastases at a single tertiary care institution were included. The primary outcome was overall survival, whereas secondary outcomes included the cumulative incidences of distant intracranial failure, local failure, and radiation necrosis. Competing risks regression was used to model secondary outcomes. Within the study period, 547 patients presented with 3224 brain metastases and met inclusion criteria. Among patients with human epidermal growth factor receptor 2 (HER2)-amplified disease, 80% received HER2 antibodies and 38% received HER2/epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The median survival was significantly shorter in the basal cohort (8.4 months), and progressively increased in the luminal A (12.3 months), HER2-positive (15.4 months), and luminal B (18.8 months) cohorts (P<.001). Among patients with HER2-amplified disease, the median survival was extended with the use of both HER2 antibodies (17.9 months vs 15.1 months; P = .04) and TKIs (21.1 months vs 15.4 months; P = .03). The 12-month cumulative incidences of local failure among molecular subtypes were 6.0% in the luminal A cohort, 10.3% in the luminal B cohort, 15.4% in the HER2-positive cohort, and 9.9% in the basal cohort (P = .01). Concurrent HER2/epidermal growth factor receptor TKIs with stereotactic radiosurgery significantly decreased the 12-month cumulative incidence of local failure from 15.1% to 5.7% (P<.001). Molecular subtypes appear to be prognostic for survival and predictive of the response to radiotherapy. TKIs were found to improve survival and local control, and may decrease the rate of distant failure. To preserve neurocognition, these results support a paradigm of upfront radiosurgery and HER2-directed therapy in the HER2-amplified population, reserving whole-brain radiotherapy for salvage. Cancer 2017;123:2283-2293. © 2017 American Cancer Society.

Miller JA ，Kotecha R ，Ahluwalia MS ，Mohammadi AM ，Chao ST ，Barnett GH ，Murphy ES ，Vogelbaum MA ，Angelov L ，Peereboom DM ，Suh JH ... -  《-》

Stereotactic radiosurgery with concurrent lapatinib is associated with improved local control for HER2-positive breast cancer brain metastases.

Parsai S ，Miller JA ，Juloori A ，Chao ST ，Kotecha R ，Mohammadi AM ，Ahluwalia MS ，Murphy ES ，Barnett GH ，Vogelbaum MA ，Angelov L ，Peereboom DM ，Suh JH ... -  《-》

Prognostic factors of brain metastases from breast cancer: impact of targeted therapies.

Brain metastases (BM) from breast cancer are associated with poor prognosis. This study was made to determine the prognostic influence of breast cancer biological subtypes, and to define the best therapeutic options in this setting, with a special focus on the HER2-positive population. Breast cancer patients with known hormone receptors (HR) and HER2 status presenting with BM treated between 1995 and 2010 in our two institutions were considered for this retrospective study. 250 patients were included. The study population consisted of 25.6% patients categorized as triple-negative (HR-/HER2-), 30.8% as HR+/HER2- and 43.6% as HER2+ breast cancer. Median overall survival (OS) was 8.9 months (95% CI, 6.9-10.3 months). Cerebral progression remained the most frequent cause of death (57.1%). On multivariate analysis, HER2 positivity and the RPA score were the two most important prognostic factors. Local treatment (surgery or stereotactic radiotherapy) and chemotherapy were significantly associated with an increased survival. On multivariate analysis of the RPA1-2 population, local treatment and chemotherapy were independent prognostic factors in addition to biological subtypes, RPA class, liver metastases and clinical signs of intra-cranial hypertension. Anti-HER2 therapies administered after BM diagnosis significantly and independently increased OS. Median OS in patients receiving both trastuzumab and lapatinib after BM diagnosis was significantly better than that the one of patients receiving only one of the 2 targeted therapies (25.7 vs. 9.6 months, p < 0.001). Biological subtypes are independent prognostic determinants. Chemotherapy and targeted therapies positively affect the prognosis after first BM.

Braccini AL ，Azria D ，Thezenas S ，Romieu G ，Ferrero JM ，Jacot W ... -  《-》

Stereotactic radiosurgery with concurrent HER2-directed therapy is associated with improved objective response for breast cancer brain metastasis.

Patients with breast cancer positive for human epidermal growth factor receptor 2 (HER2) remain at high risk of intracranial relapse following treatment and experience increased rates of intracranial failure after stereotactic radiosurgery (SRS). We hypothesized that the addition of concurrent lapatinib to SRS would improve intracranial complete response rates. Patients with newly diagnosed HER2-amplified breast cancer brain metastases from 2005-2014 who underwent SRS were included and divided into 2 cohorts based on timing of treatment with lapatinib. Outcome variables included the proportion of patients who achieved an intracranial complete response or progressive disease according to the RECIST 1.1 criteria, as well as individual lesion response rates, distant intracranial failure, and radiation necrosis. Eighty-four patients with 487 brain metastases met inclusion criteria during the study period. Over 138 treatment sessions, 132 lesions (27%) were treated with SRS and concurrent lapatinib, while 355 (73%) were treated with SRS without lapatinib. Compared with patients treated with SRS alone, patients treated with concurrent lapatinib had higher rates of complete response (35% vs 11%, P = 0.008). On a per-lesion basis, best objective response was superior in the concurrent lapatinib group (median 100% vs 70% reduction, P < 0.001). Concurrent lapatinib was not associated with an increased risk of grade 2+ radiation necrosis (1.0% with concurrent lapatinib vs 3.5% without, P = 0.27). Lapatinib had no protective effect on distant intracranial failure rates (48% vs 49%, P = 0.91). The addition of concurrent lapatinib to SRS was associated with improved complete response rates among patients with HER2-positive brain metastases.

Kim JM ，Miller JA ，Kotecha R ，Chao ST ，Ahluwalia MS ，Peereboom DM ，Mohammadi AM ，Barnett GH ，Murphy ES ，Vogelbaum MA ，Angelov L ，Abraham J ，Moore H ，Budd GT ，Suh JH ... -  《-》

Impacts of HER2-overexpression and molecular targeting therapy on the efficacy of stereotactic radiosurgery for brain metastases from breast cancer.

Yomo S ，Hayashi M ，Cho N 《-》