Effect of adjuvant/neoadjuvant trastuzumab on clinical outcomes in patients with HER2-positive metastatic breast cancer.

BACKGROUND: The purpose of the current study was to describe the outcomes of patients with human epidermal growth factor receptor 2 (HER2)-overexpressed/amplified (HER2+) early breast cancer who received adjuvant or neoadjuvant trastuzumab-based therapy and were subsequently retreated with trastuzumab for metastatic disease. METHODS: A total of 353 patients with metastatic HER2+ breast cancer who were treated with trastuzumab as part of their first-line treatment for metastatic disease were identified. A total of 75 patients had received adjuvant or neoadjuvant trastuzumab-based therapy for early breast cancer, and 278 had not. Clinical outcomes of patients who had or had not received prior trastuzumab were compared using Cox proportional hazards regression and logistic regression analyses. Survival was estimated using the Kaplan-Meier method. RESULTS: The clinical benefit (complete response, partial response, or stable disease of ≥ 6 months) rates were 71% in the group who did not receive prior trastuzumab and 39% in the group previously treated with trastuzumab. The adjusted odds ratios were 0.28 (95% confidence interval [95% CI], 0.13-0.59; P = .0009) for clinical benefit rates and 0.39 (95% CI, 0.18-0.82; P = .038) for objective (complete or partial) response rates. In the univariate analysis, the median overall survival rate was longer in the group who did not receive prior trastuzumab (36 months vs 28 months) (hazards ratio, 1.47; 95% CI, 1.07-2.01 [P = .022]). The multivariate analysis found no significant difference in overall survival. CONCLUSIONS: When treated with trastuzumab for metastatic disease, patients with HER2+ breast cancer without prior exposure to trastuzumab were found to have superior clinical outcomes to those with prior exposure. Prior trastuzumab exposure should be considered in treatment algorithms and in HER2-targeted clinical trial enrollment for metastatic disease.

Circulating tumor cells in non-metastatic triple-negative breast cancer.

Circulating tumor cells (CTCs) can be identified in approximately 25 % of stage I-III breast cancer patients; CTCs presence is a predictor of poor outcome in metastatic breast cancer, but little is known regarding the prognostic significance of CTCs in non-metastatic triple-negative breast cancer (TNBC) patients. The aim of this study was to determine whether CTCs predict worse outcome in non-metastatic TNBC patients. We evaluated CTCs in 113 patients with stages I-III TNBC at the time of definitive surgery. CTCs were assessed using the CellSearch System®. Progression-free and overall survival were defined as time elapsed between date of diagnosis and either date of clinical disease progression, death, or last follow-up. Log-rank test and Cox regression analysis were used to determine associations of CTCs with progression-free and overall survival. The median follow-up was 40 months. CTCs were identified in 23/113 (20 %) of patients. No primary tumor characteristic or lymph node status predicted the presence of CTCs. The identification of ≥2 CTCs predicted shorter progression-free (log rank P ≤ 0.001; hazard ratio 8.30, 95 % CI 2.61-26.37) and overall survival (log rank P = 0.0004; hazard ratio 7.19, 95 % CI 1.98-26.06) versus survival for patients with <2 CTCs. Two or more CTCs predict shorter progression-free and overall survival in TNBC patients. Larger studies are needed to determine whether CTC assessment provides beneficial information that could be used in stratifying TNBC patients at increased risk for disease progression. Finally, CTCs characterization could facilitate the development of novel treatment approaches for TNBC.