Clinicopathological features among patients with advanced human epidermal growth factor-2-positive breast cancer with prolonged clinical benefit to first-line trastuzumab-based therapy: A retrospective cohort study

The relationship between clinicopathological features and long-term benefit to trastuzumab-based therapy was evaluated in 164 HER2-positive metastatic breast cancer patients. Treatment duration was associated with hormone receptor status and use of adjuvant trastuzumab; however, with low predictive value. With growing availability of targeted treatments for HER2-positive disease, a major clinical priority is identifying molecular predictors of benefit of anti-HER2 therapies. Background: The magnitude of benefit of trastuzumab for the treatment of advanced HER2-positive breast cancer varies widely. In this retrospective study, we investigated the clinicopathological features associated with prolonged first-line trastuzumab-based treatment duration. Patients and Methods: A total of 164 patients diagnosed with advanced HER2-positive breast cancer and treated with first-line trastuzumab-based therapy from 1999 to 2009 were identified. Duration of treatment was classified according to tertiles. Different logistic regression models including age, disease-free interval, number of metastatic sites, visceral disease, hormone receptor, and adjuvant trastuzumab were fitted to investigate associations with benefit of prolonged trastuzumab-based therapies. The predictive value of each model was assessed using C-statistics. Results: At a median follow-up of 5.8 years (range, 0.7-22.1 years), patients in the short-, intermediate-, and long-term treatment duration groups were given first-line trastuzumab-based therapy for < 7.2 months, 7.2 to 14 months, and > 14 months, respectively. In the multivariate analysis, patients with long-term clinical benefit had a higher likelihood of having hormone receptor-positive tumors (odds ratio [OR]positive vs. negative = 2.39 [95% confidence interval (CI), 1.08-5.31]; P =.032); and a lower likelihood of having received adjuvant trastuzumab (OR _{adjuvant trastuzumab vs. no adjuvant trastuzumab} = 0.30 [95% Cl 0.10-0.96]; p =.043]. C-statistics varied between 0.634 and 0.699. Conclusion: Long-term benefit of trastuzumab-based therapy is associated with hormone receptor positivity and the absence of previous adjuvant trastuzumab. Nevertheless, clinicopathological features had a low predictive value for prolonged treatment duration. The validation of the current findings and the identification of molecular features associated the magnitude of trastuzumab benefit should be encouraged.