This study provides proof of principle that the addition of post-treatment Ki67 to RCB improves the prediction of long-term outcome. Prediction may be further improved by addition of post-treatment grade and ER and warrants further investigation for estimating post-neoadjuvant risk of recurrence. These indices may have utility in stratifying patients for novel therapeutic interventions after neoadjuvant chemotherapy.

Summary Background Malignant melanoma (MM) causes the highest absolute number of deaths among skin cancers. An up‐to‐date analysis of international MM mortality trends is required for assessing the burden of disease, and may support the assessment of the effectiveness of new diagnostic, therapeutic and preventative strategies. Objectives To report MM mortality trends between 1985 and 2015 using the World Health Organization (WHO) Mortality Database. Materials and methods We used country‐level MM mortality data from the WHO Mortality Database for all countries with high usability death registration data. Mortality trends were described using Joinpoint regression modelling. Results Thirty‐one countries met the inclusion criteria. All countries, except the Czech Republic, demonstrated increased age‐standardized death rates (ASDRs) in males over the observation period. More countries exhibited decreased or stable MM mortality in females. The median mortality rate for 2013–2015 was 2·57 deaths per 100 000 for males and 1·55 per 100 000 for females. Australia and Norway had the highest ASDRs for males (5·72 per 100 000 and 4·55 per 100 000, respectively). Norway and Slovenia had the highest ASDRs for females (3·02 per 100 000 and 2·58 per 100 000, respectively). MM mortality was greater for males than females in all countries, with sex disparity increasing across the period. Disparity in mortality between older and younger cohorts in several countries was also found. Conclusions An overall increase in MM mortality over the past 30 years was observed. However, there was notable variation in mortality trends between countries, as well as between males and females, and between different age groups.

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.