In general , single-agent chemotherapy is not recommended for the adjuvant treatment of breast cancer in any patient population .
Anthracycline-taxane-based polychemotherapy regimens are , overall , considered superior to earlier-generation regimens and have the most significant impact on patient survival outcomes .
Regimens with varying anthracycline and taxane doses and schedules are options ; in general , paclitaxel given every 3 weeks is inferior .
Evidence does not support the use of bevacizumab in the adjuvant setting ; other systemic therapy agents such as metformin and vaccines remain investigatory .
BACKGROUND The Program in Evidence -Based Care ( pebc ) of Cancer Care Ontario recently created an evidence -based consensus guideline on the systemic treatment of early breast cancer .
The evidence for the guideline was compiled using a systematic review to answer the question " What is the optimal systemic therapy for patients with early-stage , operable breast cancer , when patient and disease factors are considered ? "
The question was addressed in three parts : cytotoxic chemotherapy , endocrine treatment , and human epidermal growth factor receptor 2 (her2)-directed therapy .
Predictive markers of anthracycline benefit: a prospectively planned analysis of the UK National Epirubicin Adjuvant Trial (NEAT/BR9601).
BACKGROUND The NEAT/BR9601 trial showed benefit for addition of anthracyclines to cyclophosphamide , methotrexate , and fluorouracil ( CMF ) as adjuvant treatment for early breast cancer . We investigated prospect ively predictive biomarkers of anthracycline benefit including HER2 and TOP2A . METHODS 1941 tumours from 2391 women recruited to NEAT/BR9601 were analysed on tissue microarrays for HER2 and TOP2A amplification and deletion , HER1 - 3 and Ki67 expression , and duplication of chromosome 17 centromere enumeration probe ( Ch17CEP ) . Log-rank analyses identified factors affecting relapse-free and overall survival , and regression models tested independent prognostic effect of markers , with adjustment for known prognostic factors ( age , nodal status , oestrogen-receptor status , grade , and tumour size ) . The predictive value of markers was tested by treatment interactions for relapse-free and overall survival . FINDINGS 1762 patients were analysed . 21 % of tumours ( n=367 ) were HER2 amplified , 10 % were TOP2A amplified ( n=169 ) , 11 % showed TOP2A deleted ( n=191 ) , 23 % showed Ch17CEP duplication ( n=406 ) , and 61 % had high ( > 13.0 % ) Ki67 ( n=1136 ) . In univariate analyses , only HER2 amplification and TOP2A deletion were significant prognostic factors for relapse-free ( hazard ratio [ HR ] 1.59 , 95 % CI 1.32 - 1.92 , p<0.0001 ; and 1.52 , 1.20 - 1.92 , p=0.0006 , respectively ) and overall survival ( 1.79 , 1.47 - 2.19 , p<0.0001 ; and 1.62 , 1.26 - 2.08 , p=0.0002 respectively ) . We detected no significant interaction with anthracycline benefit for Ki67 , HER2 , HER1 - 3 , or TOP2A . By contrast , in multivariate analyses , Ch17CEP duplication was associated with significant improvements in both relapse-free ( HR 0.92 , 95 % CI 0.72 - 1.18 for tumours with normal Ch17CEP vs 0.52 , 0.34 - 0.81 for tumours with abnormal Ch17CEP ; p for interaction=0.004 ) and overall survival ( 0.94 , 0.72 - 1.24 vs 0.57 , 0.36 - 0.92 ; p for interaction=0.02 ) with anthracycline use . INTERPRETATION In women with early breast cancer receiving adjuvant chemotherapy  , the most powerful predictor of benefit from anthracyclines is Ch17CEP duplication . In view of the location of HER2/TOP2A on chromosome 17 , Ch17CEP duplication might explain the inconsistencies in previous studies of factors predicting benefit from anthracyclines . FUNDING Cancer Research UK and the Scottish Breast Cancer Clinical Trials Group
In general , single-agent chemotherapy is not recommended for the adjuvant treatment of breast cancer in any patient population .
Anthracycline-taxane-based polychemotherapy regimens are , overall , considered superior to earlier-generation regimens and have the most significant impact on patient survival outcomes .
Regimens with varying anthracycline and taxane doses and schedules are options ; in general , paclitaxel given every 3 weeks is inferior .
Evidence does not support the use of bevacizumab in the adjuvant setting ; other systemic therapy agents such as metformin and vaccines remain investigatory .
BACKGROUND The Program in Evidence -Based Care ( pebc ) of Cancer Care Ontario recently created an evidence -based consensus guideline on the systemic treatment of early breast cancer .
The evidence for the guideline was compiled using a systematic review to answer the question " What is the optimal systemic therapy for patients with early-stage , operable breast cancer , when patient and disease factors are considered ? "
The question was addressed in three parts : cytotoxic chemotherapy , endocrine treatment , and human epidermal growth factor receptor 2 (her2)-directed therapy .