Abstract P5-18-19: The 2006 Adjuvant Trastuzumab Convention in Belgium: 5 years later

Abstract

Abstract Background: Outside clinical trials, long term follow-up data from large series of women treated with adjuvant trastuzumab are lacking. We here report such data from a Belgian cohort for premature trastuzumab discontinuation and 5 year outcome. Patients and Methods: A year prior to its reimbursement (June 1st 2007), the Belgian health authorities offered adjuvant trastuzumab to women with a HER-2 amplified breast cancer as given in HERA: following completion of loco-regional therapy, at least 4 cycles of chemotherapy (CT) (neo-adjuvant or adjuvant) or radiotherapy whichever was last. Demographics, histopathologic features, baseline (≥55%) and follow-up left ventricular ejection fraction (LVEF) together with 5 yr breast cancer related events (BCRE) were centrally recorded. Outcome was reported by grade (< or > grade 3), lymph node (pN) status (neg/pos), hormone receptor (HR) status (neg/pos) and timing of CT (adjuvant/neo-adjuvant). Results: 917 pts were included. Files on histopathology, demographics, LVEF and therapy are available for 887 (97%) pts, outcome for 738 (80%). Median age at diagnosis was 53 years (25–81); 56% of tumors were >pT1, 57% pN+, 72% grade 3, 59% HR-positive for estrogen receptor (ER) and/or progesterone receptor (PR). CT was neo-adjuvant in 20% and adjuvant in 80%. Radiotherapy and endocrine therapy were given respectively in 86% and 50%. Median follow-up was 63 (range 8–90) months. Premature (<1 year) treatment discontinuation occurred in 17% of pts mainly because of decrease in LVEF (asymptomatic in 7.2%; symptomatic in 1.2%). A BCRE appeared in 128 pts (17%) on average 31 months (range 4–76) after diagnosis. BCRE was metastatic in 96 pts (13%) and mostly (71%) limited to one organ at diagnosis. Most likely involved were liver (18%), lung (17%), brain (16%) and bone (13%). 7% of patients died of breast cancer. Patients receiving neo-adjuvant CT had more advanced disease and were more likely to develop a distant BCRE (24%) as were patients receiving adjuvant CT (10%); In both populations, the following parameters further affected distant BCRE: lymph node involvement, grade 3, negative HR, and negative PR in ER-positive disease (table 1). We here focus on 636 pts with outcome data. Breast cancer related events (119, 19%) occurred on average 31 months (4–74) after diagnosis and was mainly metastatic, with preference for liver or lungs only (17%), bone only (15%) or brain only (14%). 44 (7%) pts died of breast cancer. Patients who had chemotherapy administered in the neoadjuvant setting (20%) clearly had more advanced disease with more chance to develop a distant relapse (24%) and breast cancer related death (17%). These figures were respectively 11% and 4% when chemotherapy was given in the adjuvant setting (80%). In both populations, the following variables were most prognostic for metastatic relapse: lymph node involvement (28% vs 16% neo; 13% vs 7% adj), grade 3 (24% vs 18% neo; 14% vs 8% adj), a negative HR-status (26% vs 21% neo; 14% vs 9% adj) and a negative PR status (27% vs 16% neo; 13% vs 7% adj). Discussion: Outside a clinical trial, ≥ 80% of patients eligible for adjuvant trastuzumab are able to complete treatment. Outcome at 5 years is favorable with low symptomatic cardiac toxicity and a 13% incidence of metastatic relapse, being lowest in pN−, < grade 3, HR+ and ER+/PR+ tumors. Longer follow-up is needed to differentiate a relapse pattern by HR-status as PR positive cases might relapse at a later moment. This work is funded by the Belgian National Institute for Health and Disability Insurance (INAMI-RIZIV). Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-19.