Poor Survival Outcomes in Elderly HER2 Positive Breast Cancer Patients.
Authors: S. Tovey, J. Edwards, S. Brown, E. Mallon, J. Doughty
Journal: Cancer Research (2009)

Abstract IntroductionIncreasing age is a major risk factor for breast cancer. The majority of breast cancers in Europe and USA are in women over 65 and with an aging population this will become an increasing concern. Despite this, there are suggestions of bias in allocating treatment based on chronological rather than physiological age, with adverse effects on survival (1). In addition, women over 70 are usually excluded from randomised clinical trials. One particular area of controversy is the treatment of HER2 positive elderly women with trastuzumab +/- concurrent chemotherapy, particularly with the concerns over cardiac toxicity in these patients.MethodsWe analysed a cohort of 255 patients older than 70 years to assess the impact of HER2 positivity (IHC Herceptest 3+ or FISH positive) on survival in elderly women with breast cancer. These patients were selected from a database of 1400 breast cancers diagnosed between 1980-2002 which contains all clinicopathological details and full follow-up (median 5.3yrs). The group were 81% ER positive, 74% grade I or II, and 49% node positive. Only 2.7% received chemotherapy but 82% received endocrine therapy (tamoxifen).SPSS version 12 was used to calculate univariate Kaplan Meier Survival Curves and multivariate cox regression analysis using breast cancer specific death as an endpoint.ResultsThe HER2 positivity rate was 5.9% which is substantially lower than the 11.9% positive in the original unselected database of 1400 patients.HER2 positive elderly patients (n=15) had significantly poorer breast cancer specific survival rates of 65% compared to 79% at 5 years for the HER2 negative group (p=0.036). In cox regression analysis along side known prognostic variables of grade, size, nodal and ER status the hazard ratio for HER2 positivity was 2.58 (95% CI 1.079-6.147, p&amp;lt;0.033).ConclusionAs previously reported, our cohort of elderly women have low rates of HER2 positive disease, however HER2 status remains a significant predictor of breast cancer specific survival outcome. Whilst no adjuvant trastuzumab trials have directly targeted this age group (with minimal inclusion of patients &amp;gt;70 in any trial), we know that cardiac toxicity increases with age and with anthracycline use (2). This however is generally reversible and treatment certainly should be considered if there is adequate cardiac function. A clinical trial to assess the benefit of adjuvant trastuzumab alone (with endocrine therapy) in this group of patients is suggested in this largely ER positive cohort. The role of the dual inhibitor lapatinib should also be explored with suggestions of less cardiotoxicity with this agent (2).Reference List1. Eaker S, Dickman PW, Bergkvist L, Holmberg L 2006 Differences in management of older women influence breast cancer survival: results from a population-based database in Sweden. PLoS Med 3:e252. Perez EA 2008 Cardiac toxicity of ErbB2-targeted therapies: what do we know? Clin Breast Cancer 8 Suppl 3:S114-S120 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2010.