A comprehensive study of breast tumors at the molecular level — their genetic makeup — has confirmed that breast cancer can be broken into four different types.
Though researchers have known for many years that the four types exist, this is the first study to show from a genetic standpoint how each type is unique. The hope is that this new knowledge may, in the future, lead to treatments that are better tailored to individual types of breast cancer.
Background and Reason for the Study
All cancers are caused by mutations, or errors, in the DNA of cells. These mutations contribute to the growth of cancer cells. The Cancer Genome Atlas project began in 2006 as a national effort to understand the mutations that drive different kinds of cancer. It is funded by the National Institutes of Health.
These breast cancer findings, published online in Nature, are the product of collaboration among several hundred researchers. They wanted to describe the mutations that drive the growth of breast cancer, and to better understand the differences among breast cancer subtypes.
Tumor and genetic samples from 825 people with breast cancer were analyzed using six different technology platforms. These analyses gave details about the underlying genetic systems that were altered (or abnormal) in each of the tumors. Most samples were analyzed on more than one platform.
The results showed that breast cancer can be viewed as four different genetic types: luminal A, luminal B, HER2 positive and triple-negative. The researchers noted three mutations common in more than 10 percent of all breast cancers. But they found a great deal of molecular diversity within each of the major genetic types.
In clinical practice, breast cancer is broken down into three groups that determine the course of treatment: hormone receptor-positive cancers that are also HER2 negative, HER2 positive cancers (which can be either estrogen receptor positive or negative) and triple-negative tumors. New knowledge about the luminal A and luminal B subtypes, as well as differences within the HER2 positive subtype, may in the future help doctors target each cancer better by explaining why some cancers respond well to certain treatments while others do not. The researchers found that:
Luminal A subtypes
- Are estrogen or progesterone receptor-positive, or both, and HER2 negative
- Have a high survival and low recurrence rate
- Employ different genes and pathways than luminal B
Luminal B subtypes
- Are estrogen or progesterone receptor-positive, or both, and may also be HER2 positive
- Have a high diversity of mutated genes
- Are more aggressive than luminal A cancers
- Employ different genes and pathways than luminal A cancers
HER2 positive subtypes
- Are HER2 positive, and estrogen receptor-positive or -negative
- Have two tumor types: HER2E and luminal
- HER2E tumors are estrogen receptor-negative, have a higher number of certain proteins, including HER2, as well as HER2 DNA
- Luminal HER2 tumors are estrogen receptor-positive, and show mutations associated with luminal subtypes
- Are HER2, estrogen and progesterone receptor-negative
- Are strikingly different than luminal A and B and HER2 subtypes
- Are often basal-like. Basal-like tumor cells are similar to the outer (basal) cells of the ducts ofthe breast
- Are genetically similar to serous ovarian cancers, the most common form of that disease
In most cases, basal-like tumors are negative for HER2 and estrogen and progesterone receptors. However, only about 75 percent of triple-negative breast cancers are basal-like tumors. To look for similarities among basal-like tumors, the researchers excluded triple-negative breast cancers that were not basal-like.
What This Means for You
These findings will not immediately impact your breast cancer care, but they will open new avenues for research. The great many findings from this study will potentially impact future treatment paths. By identifying specific genes and pathways that are active or inactive within the four subtypes, doctors may eventually be better able to prescribe treatments that will target those genes, while avoiding treatments that do not. In the long-term, this could mean more streamlined, individualized treatment.
HER2 positive and triple-negative breast cancers may be more strongly impacted by this study. The finding of two groups of HER2 positive cancers may help researchers study which cancers will respond to anti-HER2 therapies. This finding may also lead to more specific or individualized anti-HER2 therapy.
Triple-negative breast cancer’s remarkable similarity to ovarian cancer suggests that it may benefit from some treatments already approved and in use against ovarian cancer. There are already clinical trials that are completed or are enrolling that address this issue. Researchers will need to conduct clinical trials to make sure existing or new medicines are active against breast cancers.
Though these recent findings may not impact your treatment options today, clinical trials to explore the findings will likely be planned over the coming years. If you are interested in participating in a clinical trial, talk with your doctor about your eligibility.
The Cancer Genome Atlas Network: Comprehensive molecular portraits of human breast tumours. Nature 490, 61-70 (04 October 2012).