Study Analyzes Breast Cancer Genetics, Finds Four Classes of Disease

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Researchers have done the most thorough analysis of breast cancer genetics to date and found that there are four genetically distinct classes of the disease. The research will likely lead to new, more precise treatments for breast cancer, but developing and testing these new treatments is likely to take many years.

The research was published online by the journal Nature on Sept. 23, 2012. Read “Comprehensive molecular portraits of human breast tumours.”

Genes contain the recipes for the various proteins a cell needs to stay healthy and function normally. Some genes and the proteins they make can influence how a breast cancer behaves and how it might respond to a specific treatment. Cancer cells from a tissue sample can be tested to see which genes are normal and abnormal. The proteins they make also can be tested.

In the study, researchers analyzed the genes in breast cancer tumors from 825 women diagnosed with early-stage breast cancer. The study is part of a larger national project, the Cancer Genome Atlas, which aims to build maps of the genetic abnormalities in common cancers, including breast, lung, and colon cancers.

The study confirmed that there are four main subtypes of breast cancer:

  • luminal A, which is hormone-receptor-positive (either estrogen- and/or progesterone-positive) and HER2-negative
  • luminal B, which is hormone-receptor-positive (either estrogen- and/or progesterone-positive) and HER2-positive
  • basal-like, which is hormone-receptor-negative and HER2-negative (also called triple-negative breast cancer); the researchers found that basal-like breast cancer is much different from the other three types of breast cancer and more closely resembles ovarian cancer and a type of lung cancer
  • HER2-enriched, which is hormone-receptor-negative and HER2-positive

Luminal A breast cancer is the most common type of breast cancer and tends to have a better prognosis than the other three types. Luminal B breast cancer tends to have a worse prognosis than luminal A, but better than basal-like and HER2-enriched. The researchers suggested that women diagnosed with luminal A breast cancer might do well with only hormonal therapy treatment, while women diagnosed with luminal B breast cancer might benefit from a treatment plan that includes both hormonal therapy and chemotherapy.

Basal-like or triple-negative breast cancers tend to have the worst prognosis of all the types. Women diagnosed with basal-like breast cancer are more likely to be younger, African American, and have abnormal BRCA1 or BRCA2 genes compared to women diagnosed with the other types of breast cancer.

Because basal-like breast cancers seem to be more closely related to ovarian cancer, the researchers suggested that some standard treatments for ovarian cancer should be tested as treatments for that type of breast cancer. Also, PARP inhibitors, a new type of targeted therapy medicine, have been used to successfully treat some ovarian cancers. The researchers also suggested that PARP inhibitors be tested as a treatment for basal-like breast cancer.

The PARP (poly ADP-ribose polymerase) enzyme fixes DNA damage in cells, including DNA damage caused by chemotherapy medicines. Scientists developed PARP inhibitors based on the idea that a medicine that interferes with or inhibits the PARP enzyme might make it harder for cancer cells to fix damaged DNA. This would make the cancer more susceptible to chemotherapy and make it harder for cancer to become resistant to chemotherapy.

HER2-enriched breast cancers tend to have a worse prognosis than cancers that are hormone-receptor positive. Women diagnosed with HER2-enriched breast cancers are more likely to be younger compared to women diagnosed with the other types.

Herceptin (chemical name: trastuzumab) is a targeted therapy medicine used to treat HER2-positive breast cancer. Still, some HER2-positive cancers don’t respond to or stop responding to Herceptin. The researchers found that there are at least two types of HER2-positive breast cancers, based on the genetics of the cancer. This means that the two types of HER2-positive breast cancers had different abnormal genes in them. This could be part of the reason why some HER2-positive breast cancers respond to Herceptin and some don’t.

This study offers more evidence that the genetic errors that cause breast cancer are usually different from cancer to cancer, even between two people who’ve been diagnosed with the same type of cancer. Each breast cancer is unique and seems to be controlled by its own set of genetic abnormalities.

The tests available right now, such as estrogen and progesterone receptor tests and HER2 tests, help doctors develop a customized treatment plan for each person diagnosed with breast cancer. This study offers hope for new breast cancer treatments that target a larger number of abnormal genes. Still, it’s important to know that much more research has to be done before these new treatments will be available. A variety of medicines will probably be needed to allow doctors to tailor treatments to the genetic abnormalities in each cancer.

Stay tuned to Breastcancer.org for the latest information on breast cancer genetics and treatments aimed at specific genetic abnormalities.

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