Triple-Negative Breast Cancer Update
by Lisa A. Carey, MD
Breast cancer is not one disease; it is a family of diseases that differ from one another in biology and in their behavior. While scientists have an increasing array of tools to identify subtypes of breast cancer at the molecular level, doctors rely on three tools to help make treatment decisions: 1) measurement of the estrogen receptor (ER), 2) the related protein progesterone receptor (PR), and 3) a separate protein, HER2.
These three proteins are important because they help us identify the different types of breast cancer, and because they are drug targets that we use to determine what kind of treatment is appropriate for each person.
About 80 percent of breast cancers are positive for ER and PR. This signals that the cancer is sensitive to hormones. For these people, anti-estrogen pills, like tamoxifen or aromatase inhibitors, are the keys to treating the cancer or preventing its recurrence.
Excess HER2 expression (or the genetic abnormality responsible for this excess) is found in about 20 percent of tumors. It means that a cancer may be sensitive to drugs designed to attack HER2, like trastuzumab (Herceptin®).
For the 15 percent of breast cancers that are triple negative, chemotherapy is the mainstay of treatment and the primary means of keeping these tumors from recurring.
When none of these three proteins is present, the tumor is called triple negative. For the 15 percent of breast cancers that are triple negative, chemotherapy is the mainstay of treatment and the primary means of keeping these tumors from recurring.
There are several myths about triple negative breast cancer. Myth number one is that these tumors are destined to recur. While triple-negative breast cancer generally has a poorer prognosis than most other kinds of breast cancer, the majority of these cancers do not recur if they are treated effectively with surgery (with or without radiation) and chemotherapy.
The second common myth is that triple-negative breast cancer only affects African-American women. Several studies, the most famous of which was the Carolina Breast Cancer Study, have consistently shown that the triple-negative subtype is more common in black women (and young women). However, the truth is that any woman can develop triple-negative breast cancer and that most African-American women who are diagnosed have other types of breast cancer. Part of the Carolina Breast Cancer Study suggests that risk factors may be different for triple-negative breast cancer than for other more common breast cancers. While this still needs to be confirmed, there is early evidence that breast-feeding and weight control may be effective in preventing this disease.
Dr. Larry Norton
“The great revolution in the management of infections happened when medical scientists knew enough about these diseases to shift their attention from the organ involved – lung for pneumonia, kidney for pyelonephritis, etc. – to the bacteria actually causing the illness: streptococcus, staphylococcus, and so on. A similar revolution is now happening in cancer medicine; we are learning to focus less on the organ from which the tumor originates and more on the abnormalities in DNA, RNA, and other molecules that make the cancer behave as it does.
“In her article addressing triple-negative breast cancer, Dr. Lisa Carey – one of the world leaders in breast cancer research – describes the biology of these diseases, outlining exciting developments aimed toward prevention, as well as treatment. She also sets the record straight about some common myths, illustrating how scientific study can dispel misconceptions and point the way to a better future.” – Larry Norton, MD, Deputy Physician-in-Chief for Breast Cancer Programs at Memorial Sloan-Kettering Cancer Center in New York, NY.
Myth number three is that triple-negative breast cancer does not respond to standard treatments. In fact, the triple-negative subtype is quite sensitive to chemotherapy, and advances in chemotherapy have benefited women with this disease.
We would love to find a targeted therapy for triple-negative breast cancer, but at this point, we do not yet have treatments beyond chemotherapy for this disease. The most recent excitement surrounded a group of drugs called PARP inhibitors. Sadly, despite early enthusiasm and evidence that these drugs work in women with familial breast cancer (the kind that women who inherit mutations in the genes BRCA1 or BRCA2 get), it does not look like they will be effective in the majority of triple-negative cases.
At the same time, many other drugs targeting various abnormalities in how triple-negative cancer cells grow or survive are in clinical trials, and women should ask their oncologist about trials available near them to help improve treatment for women in the future.
What we all hope for the future is a better understanding of the causes of all subtypes of breast cancer, thanks to today’s ongoing studies. We also want to be able to give lifestyle and healthy behavior recommendations for breast cancer prevention that are backed by scientific evidence. We count on developing more effective treatments, including realizing the promise of targeted therapy for triple-negative breast cancer, so that chemotherapy for breast cancer becomes a distant memory.
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Dr. Lisa Carey is the Preyer Distinguished Professor of Breast Cancer Research at the University of North Carolina School of Medicine and associate director of Clinical Research at UNC Lineberger Comprehensive Cancer Center in Chapel Hill, NC.
This article was originally published in Coping® with Cancer magazine, September/October 2012.