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Breast Cancer Mapping Reveals Four Distinct Types

After mapping the genetic features of 800 breast cancer tumors, scientists with The Cancer Genome Atlas (TCGA) program conclude that even given the huge genetic diversity of the disease, there are four main subtypes. They also found a remarkable similarity between one type of breast cancer and ovarian cancer.

The researchers, who write about their findings in a 23 September online issue of Nature, believe they greatly increase the understanding of breast cancer and will lead to more treatment options for patients.

TCGA is an international program led by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) in the US, and involving scientists from around the world in a groundbreaking effort to genetically characterize the entire genome of 20 different cancer types.

One team working on the program is a large group from the University of North Carolina (UNC) School of Medicine that includes the paper's corresponding author, Charles Perou. He told the press:

"This study has now provided a near complete framework for the genetic causes of breast cancer, which will significantly impact clinical medicine in the coming years as these genetic markers are evaluated as possible markers of therapeutic responsiveness."

The work is important for all breast cancer patients, and confirms much of what was already known, said Perou, May Goldman Shaw Distinguished Professor of Molecular Oncology and a member of UNC's Lineberger Comprehensive Cancer Center.

"In particular, we now have a much better picture of the genetic causes of the most common form of breast cancer, namely Estrogen-Receptor positive/Luminal A disease. We also found a stunning similarity between Basal-like breast cancers and ovarian cancers," he added. Four Subtypes For the study, the TCGA researchers analyzed tumors in two ways: first with an unbiased and genome-wide approach. Then they did a new analysis within the context of four previously known molecular sub-types of breast cancer: HER2-enriched, Luminal A, Luminal B and Basal-like.

Both approaches showed that despite the huge genetic diversity of breast cancer, these four main subtypes are observed.

The study is also the first to bring together information from six analytic technologies, helping reveal new insights into the already defined subtypes of breast cancer.

One of these was finding some of the likely genetic causes of the Estrogen-Receptor positive Luminal A subtype, the most common type of breast cancer, and the number one cause of breast cancer deaths in the US.

The study reveals that this subtype has the greatest mutation diversity, and that even specific individual mutations within individual genes, are tied to the Luminal A subtype. This is good news in the sense it may be possible to target some of these mutations with a drug that is already being developed, bringing new treatment options for patients. Basal-like Breast Cancer Similar to Ovarian Cancer Another revelation came when the team compared basal-like breast tumors (also known as triple-negative breast cancers) with high-grade serous ovarian tumors and found the two diseases share many similar molecular characteristics, suggesting their origins are related, and perhaps might be treatable with the same drugs.

In fact, the researchers suggest that the data shows basal-like breast cancer and ovarian cancer are more similar to each other than either is to ER-positive/Luminal breast cancer. Perhaps basal-like breast cancer should even be considered a different disease, as co-author Katherine Hoadley, also from UNC, explains:

"Our ability to compare and integrate data from RNA, microRNA, mutations, protein, DNA methylation, and DNA copy number gave us a multitude of insights about breast cancer."

These methods helped discover, in particular, how different basal-like breast cancers from the other subtypes, she says, adding that:

"These findings suggest that basal-like breast cancer, while arising in the same anatomical location, is potentially a completely different disease."

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