Great question Dr. Aroon. The controversies surrounding this topic are endless and have been going on for a very long time. It is clear that our understanding of the predictive power of PR receptor expression in breast cancer is incomplete.
Your statement is absolutely correct for breast cancer in the metastatic setting. Indeed, measurement of PR improves the predictive power for obtaining a response in ER positive tumors. Metastatic patients that express both ER and PR are associated with a 70% response rate to hormonal therapy. While ER+/PR- or ER-/PR+ have a 40% chance of response. Those with both ER and PR negativity respond in less than 10% of cases. There is also some evidence that HER2 positivity may affect hormonal response in ER/PR positive patients.
It’s a different story when we discuss PR status in the adjuvant setting. Initial reports from the ATAC trial (9366 patients) which randomized patients to receive either initial tamoxifen or anastrazole, suggested better outcome in ER+/PR- as compared to ER+/PR+. This benefit was not confirmed in follow up data or in another important trial, the BIG 1-98, which tested a different aromatase inhibitor (letrozole) against standard tamoxifen. Here there was clearly no difference between ER+/PR- and ER+/PR+ groups.
Again, you are right in saying that the PR status has been overshadowed by ER status. This was later overshadowed by the role that HER-2 status played in modulating response to hormonal therapy. Currently, the focus is on genetic profiling, with Luminal A patients showing superior responses compared to Luminal B hormone positive tumors, which is probably why your point is not mentioned in this review.
Thanks again for this important question.