Re: Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer.

Data in the article of Cheang et al. (1) help to define relatively high- and low-risk estrogen receptor–positive breast cancers by using human epidermal growth factor receptor 2 (HER2) and Ki67 expression. We suggest that quantitative progesterone (PR) and/or estrogen receptor expression may provide similar or even superior prognostic information in their patient populations, given the prognostic impact of the steroid receptors from central pathology review of large randomized studies (2,3).The small difference in number of PR-negative tumors reported by Cheang et al. (32.5% for luminal B vs 25.4% for luminal A) is surprising, given that the heatmap of the centroid models for the PAM50 classifier demonstrated clear differences in PR RNA expression in luminal A and luminal B tumors (4). This observation suggests that a cut point between positive and negative values of 1% of cell nuclei for estrogen receptor and PR, as used in their study, may not be ideal. Even so, the absence of PR expression when this cut point was used has been shown previously to be associated with high Ki67 expression (5). We would ask the authors to reexamine their data by using PR and estrogen receptor expression as continuous variables in their multivariable survival analyses to determine whether Ki67 retains independent prognostic value and whether the relative expression levels of either steroid receptor is superior in differentiating between the two luminal subgroups.This matter is of particular importance when one considers recent UK guidelines from the National Institute for Clinical Excellence, suggesting that the PR status of breast cancers should no longer be assessed routinely (6). We suggest that the PR has sufficient prognostic value to warrant continued routine testing and that the study by Cheang et al. can provide further insight into this issue.