IMPAKT News: Prospective comparison of risk assessment tools in early breast cancer

Correlation analysis from the phase III West German Study Group Plan B trial

The St. Gallen Consensus Conference recommended the use of Ki-67 and/or grade for definition of Luminal A and B tumours to indicate adjuvant chemotherapy in hormone receptor positive early breast cancer. Multi-gene based assays e.g. Recurrence Score® are used to support decision regarding adjuvant chemotherapy, and the researchers from the West German Study Group presented the final analysis of risk assessment tools focusing on correlation between central and local pathology assessment and recurrence score at the 4th IMPAKT Breast Cancer Conference (3-5 May 2012, Brussels, Belgium).

The Plan B trial foresaw randomisation between 6 cycles of docetaxel-cyclophosphamide chemotherapy and 4 cycles of epirubicine-cyclophosphamide regimen followed by 4 cycles of docetaxel in locally HER2-negative breast cancer. The Recurrence Score® was used as selection criteria for chemotherapy vs. endocrine therapy alone in hormone receptor positive disease (if recurrence score was < 11 in pN0 or pN1). Central grade, oestrogen-receptor, progesterone-receptor, HER2 and Ki-67 were evaluated by a central pathologist.

An ongoing study

The German researchers led by Dr Gluz, who is the first author of the study, and Dr Harbeck, senior study author, recruited 3196 patients, from whom 2448 have been randomised. The Recurrence Score® was available in 2551 patients with hormone receptor positive tumours. The recurrence score distribution was 0-11 (18%), 12-25 (60%), >25 (22%). In 354 patients, adjuvant chemotherapy was omitted based on low recurrence score. Central grade was available for 3038 samples, immunohistochemistry results are currently available in 1476 cases. Moderate significant correlations were found between recurrence score and both central grade (p<0.001), local grade (p<0.001), Ki-67 (p<0.001) assessment, due to weak correlation within low and intermediate risk group. Weak correlation was found for uPA/PAI-1 and recurrence score. Using Ki-67 cut-off of 14% for Luminal B definition, 55% of patients were defined as Luminal B, for whom chemotherapy was indicated. There was a 68% concordance between local and central grade. The researchers reported that 57% of tumours classified as grade 3 by local board certificated pathologists were grade 3 by central assessment.

The authors concluded that first prospective data from this study shows that high-risk status according to recurrence score is predictive of high risk by uPA/PAI-1, high grade by central pathology, and luminal B subtype by Ki-67. They observed a substantial heterogeneity in risk assessment in the low and intermediate risk recurrence score groups defined by recurrence score, where there are still patients considered as high-risk according to uPA/PAI-1, Ki-67 or central grade. Further follow-up of this study will clarify the significance of these findings regarding patient outcomes.