Research article

Predicting for activity of second-line trastuzumab-based therapy in her2-positive advanced breast cancer

Rupert Bartsch¹ , Catharina De Vries¹ , Ursula Pluschnig¹ , Peter Dubsky² , Zsuzsanna Bago-Horvath³ , Simon P Gampenrieder¹ , Margaretha Rudas³ , Robert M Mader¹ , Andrea Rottenfusser⁴ , Christoph Wiltschke¹ , Michael Gnant² , Christoph C Zielinski¹ and Guenther G Steger¹

¹  Department of Medicine 1 and Cancer Centre, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria

²  Department of Surgery, Medical University of Vienna, Vienna, Austria

³  Department of Pathology, Medical University of Vienna, Vienna, Austria

⁴  Department of Radiotherapy, Medical University of Vienna, Vienna, Austria

author email corresponding author email

BMC Cancer 2009, 9:367doi:10.1186/1471-2407-9-367

Published:	17 October 2009

Abstract

Background

In Her2-positive advanced breast cancer, the upfront use of trastuzumab is well established. Upon progression on first-line therapy, patients may be switched to lapatinib. Others however remain candidates for continued antibody treatment (treatment beyond progression). Here, we aimed to identify factors predicting for activity of second-line trastuzumab-based therapy.

Methods

Ninety-seven patients treated with > 1 line of trastuzumab-containing therapy were available for this analysis. Her2-status was determined by immunohistochemistry and re-analyzed by FISH if a score of 2+ was gained. Time to progression (TTP) on second-line therapy was defined as primary study endpoint. TTP and overall survival (OS) were estimated using the Kaplan-Meier product limit method. Multivariate analyses (Cox proportional hazards model, multinomial logistic regression) were applied in order to identify factors associated with TTP, response, OS, and incidence of brain metastases. p values < 0.05 were considered to indicate statistical significance.

Results

Median TTP on second-line trastuzumab-based therapy was 7 months (95% CI 5.74-8.26), and 8 months (95% CI 6.25-9.74) on first-line, respectively (n.s.). In the multivariate models, none of the clinical or histopthological features could reliably predict for activity of second-line trastuzumab-based treatment. OS was 43 months suggesting improved survival in patients treated with trastuzumab in multiple-lines. A significant deterioration of cardiac function was observed in three patients; 40.2% developed brain metastases while on second-line trastuzumab or thereafter.

Conclusion

Trastuzumab beyond progression showed considerable activity. None of the variables investigated correlated with activity of second-line therapy. In order to predict for activity of second-line trastuzumab, it appears necessary to evaluate factors known to confer trastuzumab-resistance.