ABSTRACT
BACKGROUND: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. METHODS: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34-16.66) compared with 18 months (95% CI: 14.46-21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71-44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). CONCLUSION: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes.
Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/secondary , Breast Neoplasms/epidemiology , Receptor, ErbB-2/metabolism , Adult , Aged , Aged, 80 and over , Austria/epidemiology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Disease-Free Survival , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lung Neoplasms/secondary , Middle Aged , Neoplasm Staging , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Retrospective StudiesABSTRACT
BACKGROUND: Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit. METHODS: Eighty patients with BM from HER2-positive breast cancer were identified. Karnofsky Performance Score (KPS) of at least 70 was required. We included a control group of 37 patients treated before 2003, when continuation of trastuzumab after diagnosis of BM was not yet recommended. Remainders received either trastuzumab or lapatinib and trastuzumab (either concomitantly or sequentially) with or without chemotherapy. RESULTS: Median overall survival (OS) in patients receiving trastuzumab after diagnosis of BM was 13 months; corresponding numbers were 9 months in patients treated with chemotherapy, and 3 months with radiotherapy alone. Median OS was not reached in the lapatinib group. Addition of lapatinib prolonged OS over trastuzumab alone (P=0.002). After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival (HR 0.279; P=0.012). INTERPRETATION: This retrospective single-centre study suggests that the introduction of lapatinib improved survival in patients with BM from HER2-positive breast cancer. Patients with KPS ≥70 may benefit when treated with lapatinib in addition to trastuzumab after completion of local therapy.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/therapeutic use , Brain Neoplasms/secondary , Breast Neoplasms/drug therapy , Receptor, ErbB-2/antagonists & inhibitors , Survival Analysis , Adult , Aged , Breast Neoplasms/pathology , Female , Humans , Karnofsky Performance Status , Middle Aged , TrastuzumabABSTRACT
INTRODUCTION: Erlotinib and Gefitinib (EGFRi) are small molecules specifically inhibiting epidermal growth factor receptor (EGFR). We present here data of an exploratory study evaluating EGFRi monotherapy in patients with recurrent or progressive malignant glioma. PATIENTS: 21 patients with recurrent or progressive malignant glioma were included in this study. EGFRi treatment was started at a median of 1.8 years (range 0.54 to 10.95) after initial surgery. 20/21 patients had undergone radiotherapy and all patients had received at least one (range 1 to 5, median 2) line of systemic antineoplastic therapy. Patients received 100 or 150 mg Erlotinib or 250 mg Gefitinib orally per day. RESULTS: Median age at primary diagnosis was 47.9 years (range 31.9 to 76 years). 18 patients received a total of 92.8 months (median 3.03) of Erlotinib treatment and 3 patients received a total of 16.1 months (median 6.06) of Gefitinib treatment. The best responses were partial remission in one patient receiving Erlotinib and in two patients receiving Gefitinib, respectively. Median time to progression was 3.05 months. Six months after start of EGFRi treatment, 4/21 (19%) patients were progression-free and 6/21(29%) patients were alive. Expression of EGFRwt, EGFRvIII, PTEN, phospho-Akt or EGFRvIII/PTEN co-expression in tumor cells did not significantly associate with time to progression or survival time. In one patient EGFRi administration had to be discontinued due to toxicity (grade 3 rash). CONCLUSION: EGFRi monotherapy is associated with therapeutic efficacy in only a small fraction of patients with malignant gliomas. Biomarkers reliably predicting tumor response to EGFRi need to be identified.
