Genetic Makeup of Triple-Negative Breast Cancer Explored
Study presents two main subtypes of triple-negative disease
A genetic analysis of triple-negative tumors cataloged in The Cancer Genome Atlas found that triple-negative breast cancers can be broken down into two main groups: those that are basal-like, and those that are non-basal-like.
This finding indicates the need for clinical trials that explore triple-negative breast cancer and its treatments based on whether the tumor is basal-like.
Triple-negative breast cancer, breast cancer lacking estrogen, progesterone and HER2 receptors, and basal-like breast cancer, cancer in which tumor cells are similar to the outer (basal) cells of the ducts of the breast, are often considered the same. However, it is known that not all triple-negative tumors are basal-like, and not all basal-like tumors are triple-negative.
In 2000, research findings confirmed four main gene-specific subtypes of breast cancer exist, one of which is the basal-like subtype. More recent studies further subdivided breast cancer into 6 main groups. Knowing more about the genetic makeup of each type of cancer may eventually impact future treatments. Treatment decisions are currently made based on a tumor’s hormonal status, HER2 status, grade and size, but not on its molecular subtype. However, the tumor’s molecular subtype may control how it behaves – and be the key to creating targeted treatments.
The basal-like breast cancer subtype is highly associated with “triple negative” tumor status, but these are not one and the same. Further studies have shown that “triple negative” tumors consist of six subtypes of their own, one of which is basal-like.
The current investigators studied a group of triple-negative tumors and a group of basal-like tumors, to compare the degree of overlap and the molecular characteristics that differ between them.
Genetic information used in this study was taken from publically-available data sets recorded by the Cancer Genome Atlas Network. In total, the researchers analyzed 412 triple-negative tumors and 473 basal-like tumors. To determine the cancer subtypes, researchers used PAM50, a 50-gene subtype predictor.
Only samples with known hormonal status (estrogen receptor, progesterone receptor and HER2 status) were included in the analysis.
Overall, the study showed triple-negative breast cancer has two specific subtypes, and those subtypes can be further broken down by their individual genetic makeup. The two main subtypes are:
- Non-basal-like, which includes
- Luminal A and B subtypes
- HER2 enriched (HER2E) subtypes
- Basal-like, which includes
- Claudin-low subtypes
- Basal-like subtypes
Comparing triple-negative tumors to basal-like tumors, they found that:
- 31.5 percent of basal-like tumors were not triple-negative
- 21.4 percent of triple-negative tumors were not basal-like
The researchers believe identifying the subtypes of triple-negative breast cancer may eventually allow for more individualized treatment options. More research is needed, but they suggest that non-basal-like cancers may respond better to certain hormonal or targeted therapies, while basal-like cancers may respond better to chemotherapies.
What This Means for You
This research will not immediately impact your care, but will allow scientists to design further studies of how subtypes of triple-negative breast cancer respond to different treatments. Understanding breast cancer at the molecular level may lead to more targeted, individualized therapy. This may mean more effective medicines with fewer side effects in the future.
Clinical trials are an important part of understanding how triple-negative breast cancer works and can be treated. If you are interested in participating in a clinical trial, talk with your doctor about open trials for which you may be eligible.
Prat, A, Adamo, B, Cheang, MCU, Anders, CK, Carey, LA, Perou, CM. Molecular characterization of basal-like and non-basal-like triple-negative breast cancers.The Oncologist. 2013; 18(2):123-133.