Developments in Ki67 and other biomarkers for treatment decision making in breast cancer.

Estrogen receptor (ER) and HER2 are well established as predictive markers for treatment benefit, although methodological deficiencies can still affect their predictive accuracy. The shift towards earlier diagnosis poses a challenge in identifying those low-risk patients who may safely avoid adjuvant chemotherapy for early breast cancer. Therefore, recent research has focused on developing biomarkers to quantify residual risk on adjuvant endocrine therapy. For widespread adoption into clinical practice, these must be validated in well-designed clinical trials and provide additional information to current standards using reproducible and cost-effective methodologies. Furthermore, evidence from preoperative studies indicates that on- or post-treatment biomarkers can be more predictive than at baseline. In particular, Ki67 has recently emerged as an intermediate marker of long-term outcome. The power of Ki67 to predict treatment benefit from endocrine therapy has facilitated the design of studies where Ki67 is the primary end-point. This has also led to investigations into the predictive power of Ki67 to determine benefit from signal transduction inhibitors and chemotherapy in several recent and ongoing trials.