DEAR MAYO CLINIC: Why is it that some breast cancers have higher survival rates than others?
ANSWER: The main reason for the difference in survival rates is that breast cancer is not just one disease. It is well accepted that there are four distinct molecular categories of breast cancer. However, new data suggests that there are additional distinct subsets of breast cancer. These subsets have unique characteristics that can influence the long-term outlook associated with each of them.
The most common molecular subset of breast cancer is characterized by its ability to respond to the female hormone estrogen. This type of cancer is characterized by the presence of estrogen receptors. If a tumor is estrogen receptor (ER) positive, that means the breast cancer cells contain receptors that bind to estrogen. Women and men with ER-positive breast cancer tend to have an initial lower risk of the cancer coming back after breast surgery compared with women whose tumors do not have estrogen receptors (known as ER-negative breast cancer).
Information regarding a tumor’s ER status is one of the most important factors that guide breast cancer treatment decisions. When estrogen binds to the estrogen receptors, it may cause these cells to grow. Several types of medication can be used to inhibit the growth of ER-positive breast cancer. These include tamoxifen, which blocks the ER, and aromatase inhibitors, which reduce the amount of estrogen in a person’s body. By preventing estrogen from stimulating the growth of breast cancer, these drugs substantially reduce the risk of recurrence and improve a patient’s chances for long-term survival.
Although the risk of recurrence for estrogen receptor positive breast cancer is lower than estrogen receptor negative breast cancer, some risk for recurrence remains even after taking one of these medications for five years (the most common duration). So, for some women, treatment may be recommended for up to 10 years.
The subset of tumors that are ER-positive can be divided further into two groups: luminal A and luminal B. Luminal A tends to be slower growing, and associated with excellent response to hormonal therapies and a low risk of recurrence. Luminal B responds to estrogen and medications that alter estrogen/estrogen receptors, but this tumor often is more aggressive, and characterized genomically by genes and pathways that can drive the growth of cancer independent of estrogen.
Laboratory testing to identify luminal A and luminal B tumors is available, and this information is already being used to guide decisions about appropriate treatment. For example, in the case of estrogen receptor positive breast cancer, certain tumor gene tests can determine whether tamoxifen alone will be enough to block the growth of the tumor, or whether chemotherapy should also be used as part of a patient’s treatment plan.
Another very important type of breast cancer is the human epidermal growth factor receptor 2, or HER-2 amplified breast cancer subset. In about 20 percent of breast cancer cases, the HER-2 gene is abnormally increased. This genetic change promotes tumor growth, making this subtype of breast cancer more aggressive than others. Survival rates for women with HER-2 breast cancer used to be poor. But development of drugs such as trastuzumab and others, which target the HER-2 protein, have dramatically improved the outcome for those who have this kind of breast cancer.
Finally, the last group of breast cancers are characterized by the lack of expression of all three receptors (ER and HER2), or triple negative breast cancer. This group of breast cancer is the most aggressive, and chemotherapy is the main treatment used.
It is important for doctors to be able to identify and understand these and other specific subtypes of breast cancer. By doing so, the health care team is better able to create an overall treatment plan that fits an individual’s unique needs. — Matthew Goetz, M.D., Medical Oncology, Mayo Clinic, Rochester, Minn.