One of the most complete portraits of breast cancer yet painted may inspire some new treatment options.
Doctors and researchers have long classified breast cancer into four different types. But those sketches contain information about only one aspect of tumors and do not show all facets of the cancer’s molecular personality, including mutations, protein production and levels of genetic activity. Now, an international consortium of researchers known as the Cancer Genome Atlas Network has combined many different types of data to fill in the picture, including the mutations that probably sparked tumor formation in the first place. The molecular portraits were published online September 23 in Nature.
Breast cancers are usually categorized by which genes are highly active. Tumors with an overactive estrogen receptor gene are known as ER-positive and fall into two groups: the easier-to-treat luminal A group and a more aggressive luminal B group. Another category is based on the activity of the HER2 gene.
The fourth category, basal-like tumors, sometimes called triple-negative tumors, is different from the rest. This type of breast cancer is aggressive, tends to strike younger women, African-Americans and women with a family history of the disease. It is also associated with mutations in the BRCA1 gene, which are associated with a greatly increased risk of breast cancer.
Knowing a tumor’s category has helped doctors advise patients about treatments, but hasn’t offered information about the underlying cause of the disease, says Matthew Ellis, an oncologist and molecular biologist at Washington University School of Medicine in St. Louis. Ellis was one of hundreds of coauthors of the paper.
Information from the new study shows that basal-like breast cancer strongly resembles a type of ovarian tumor called serous ovarian cancer.
“This is what we hoped to find,” says Philip Bernard, a genomics researcher at Huntsman Cancer Institute at the University of Utah, who was not involved in the study. “It was expected…but it still needed to be confirmed.”
So women with these basal-like tumors may benefit from chemotherapy regimens like those given to patients with ovarian cancer, Ellis says. He expects fierce debate and probably some clinical trials to test that conclusion.
In the three other types of breast cancer, a series of biochemical reactions known as the PI3 kinase pathway is overstimulated because of mutations in genes involved at different steps of the process. Some drugs that target specific mutations in genes involved in the PI3 kinase pathway are already being tested against other types of cancer and might be appropriate for some women with breast cancer, the study results suggest.
Ellis professes to worrying that “chaos will ensue unless we get ourselves organized” and decide how best to test drugs developed for other types of cancer in patients with breast cancer. Insurance companies generally will not pay for such off-label use of cancer drugs.
The new study also uncovered new mutations not previously associated with breast cancer. Drugs might be developed to combat some of those newly discovered molecular changes, Ellis says.
