Breast cancer classification turns to gene expression

Ali Conlin, M.D.
Medical oncologist
Providence Cancer Center

Published December 2012

As the most common cancer in women worldwide, breast cancer is a constant “hot spot” of research and investigation. Charles Perou, Ph.D., at the University of North Carolina has led research for classifying breast cancer using gene expression profiling.

In 2000 he published a novel way of examining breast cancers using gene expression. This work in the journal Nature classified breast cancer into four distinct subtypes that transcended the usual staging or prognostic indicators that we currently use.

In September 2012, Dr. Perou and colleagues published a similar paper in Nature that further explored this new classification system. Using multiple “platforms” of gene expression analysis, including microRNA sequencing and DNA methylation, the researchers examined several hundred primary breast tumors for mutations.

Again, four main subtypes of breast cancer emerged: luminal A and luminal B, HER2 overexpression, and the basal-like subtype. Luminal A and luminal B subtypes encompass most hormone-receptor-positive breast cancers, while the basal-like subtype predominantly is composed of triple-negative breast cancers.

So what does this all mean? Do we have a new language to talk about breast cancer? At the cancer research base meetings and in new clinical research protocols, this classification system is slowly creeping into place.

This doesn’t mean, however, that tumors are routinely examined by gene expression profiling, nor have we stopped reporting estrogen-receptor or HER2 tumors. Yet these technologies exist now with new assays, such as the mammoprint and blueprint from Agendia, and gene expression profiling could be in our near future.

We are reaching a point where it’s no longer enough to talk about an estrogen-receptor-positive breast cancer. Clinicians and even patients now want to know if the cancer is luminal A, meaning they may need only anti-estrogen therapy, or luminal B, which means that chemotherapy might be an important part of adjuvant therapy.

We are not there yet, but I suspect this will be breast cancer classification 2.0. Stay tuned.

Clinical articles by Ali Conlin, M.D.