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 .
A phase III randomized trial of metformin versus placebo on recurrence and survival in early-stage breast cancer (BC) (NCIC Clinical Trials Group MA.32).
TPS103 Background : There has been a recent convergence of epidemiologic , clinical and pre clinical evidence suggesting metformin ( a biguanide used to treat type 2 diabetes ) may lower BC risk and improve BC outcomes . This evidence raises the intriguing possibility that metformin may act ( i ) indirectly by lowering circulating insulin levels ( secondary to reduced hepatic gluconeogenesis ) leading to reduced insulin/IGF-I receptor mediated PI3 K signaling in BC cells or ( ii ) directly on tumor cells , largely via an AMPK mediated mechanism , leading to mTOR inhibition . METHODS NCIC CTG led , CTEP sponsored , r and omized , phase III trial of metformin 850 mg po bid vs placebo bid for 5 years . Eligibility criteria : pTIcNO ( and > one : grade 3 , ER/PR- , HER2Neu+ , lymphovascular invasion , Oncotype DX recurrence score>25 , Ki67>14 % ) or pT2/T3 N0 or pT1 - 3 N1 - 3 . St and ard adjuvant therapy ( chemotherapy , hormone , biologics ) Adequate organ function and PS Age 18 - 75 Endpoints : Primary : invasive disease free survival ( IDFS ) . Secondary : overall survival , distant disease free survival , BC free survival , adverse events , new diabetes , cardiovascular hospitalizations , BMI , insulin resistance syndrome attributes ( ATP III criteria ) , Quality of Life , diet and physical activity . Correlative studies : Embedded correlative research examines prognostic factors and targets and predictors of metformin benefit . Variables include : Fasting Insulin , glucose , Homeostasis Model Assessment ( HOMA ) ( baseline , 6 months , end of treatment ) : genomic/gene expression analysis of blood and tumour , tumor insulin receptor ( IR ) , IGF-IR , tumor molecular markers of target pathways ( LKBI , PI3 K ( STMN1 ) , PKB/Akt ( P-PKB/Akt , ) mTOR ( P-4E-BP1 ) and IRS-1 ( P-IRS-1 ) ; Fatigue sub- study with biological correlates ( NSABP led ) . Statistical design : Planned accrual is 3,582 subjects over 3 years with 3 more years follow-up . Target hazard ratio is 0.76 ( 5 year IDFS of 88.4 % vs 85 % , power 0.80 , 2-tail type 1 error of 0.05 ) . Two interim analyses are planned . Conduct to Date : Study activation : June 2010 . Enrollment : 145 subjects . In Nov 2010 a DSMC review supported trial continuation
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 .