Triple-negative breast cancers (TNBC) lack hormone receptors and the human epidermal growth factor receptor (HER2) meaning that they will not respond to, and cannot be treated with hormone therapy or targeted therapies directed at either the hormone or HER2 receptors. Overall about 15-20% of breast cancers will test negative for both hormone receptors and HER2 in the lab. Since the hormone estrogen is not stimulating cancer cell growth, the cancer is unlikely to respond to hormonal therapies, including tamoxifen, Arimidex (anastrozole), Aromasin (exemestane), Femara (letrozole), and Faslodex (fulvestrant). Triple-negative breast cancer also is unlikely to respond to medications that target HER2, such as Herceptin (trastuzumab),Tykerb (lapatinib), and Perjeta® (pertuzumab)
Fortunately early stage TNBC can be treated with standard breast conserving therapy consisting of surgery chemotherapy and radiation therapy and new treatments — such as PARP inhibitors — are showing promise.
What are the defining characteristics of triple-negative breast cancer?
Triple-negative breast cancers account for about 15 percent of all breast cancers and are defined as breast cancers that are estrogen receptor– and progesterone receptor–negative, meaning that these cancers do not depend on estrogen for their growth. In addition, the HER2/neu gene is not amplified in these cancers (when amplified, HER2/neu produces a protein called HER2 that acts as an accelerator for growth when present in an abundance in cancer cells).
What are the risk factors for triple-negative breast cancer?
There are no modifiable risk factors for triple-negative breast cancer. These cancers tend to occur more frequently in young premenopausal women, in African-American women, and in women who carry the abnormal inherited breast cancer susceptibility gene BRCA1.
Why is triple-negative breast cancer such a challenge to treat?
In general, these tumors are more aggressive and grow at a rapid rate. There are two major challenges in treating these tumors. First, because they have no known targets (such as estrogen receptor or HER2/neu), currently the only way to treat them is to use chemotherapy, which generally results in more side effects. Second, even when we treat these tumors with chemotherapy, they may or may not respond; and even when they do, response this is often short-lived.
Are there specific questions that women should ask their healthcare team when they are diagnosed with triple-negative breast cancer?
The key question a woman who is diagnosed with triple-negative breast cancer should ask is whether an appropriate clinical trial exists for her diagnosis. There are some novel approaches to treating these cancers that are still in investigational stages but which hold great promise. It is important that patients make use of these opportunities when possible to increase their treatment options. In addition, patients should be sure to consult their healthcare team to see if genetic testing should be a consideration.
What has been the standard treatment for treating triple-negative breast cancer, and what treatments or innovations are on the horizon for this difficult-to-treat disease?
The standard treatment for early-stage TNBC confined to the breast and the axillary lymph nodes is chemotherapy and surgery. Often chemotherapy is administered before the surgery. At present there are no further treatment options for early-stage triple-negative breast cancer beyond close follow-up care with regular physical exams and mammograms.
For advanced TNBC, the current standard approach is to treat with various chemotherapy regimens. The most recent breakthrough in the treatment of such tumors is the success story of PARP inhibitors. Poly (ADP-ribose) polymerase (PARP) is an enzyme that is required for cells to repair the DNA damage induced by any form of injury (including radiation, UV rays, and chemotherapy). Unfortunately, the cancer cells also use this enzyme to correct the damage induced by chemotherapy, making that treatment less effective. Now researchers have shown that by including with chemotherapy a drug that inhibits the PARP enzyme, they can cause more damage to triple-negative breast cancers than when chemotherapy is delivered alone.
Several clinical trials are currently ongoing at various centers, using different PARP inhibitors with different chemotherapy in triple-negative and genetically inherited breast cancers. At The Ohio State University, we have a clinical trial in which a PARP inhibitor is used along with Paraplatin® (carboplatin) chemotherapy in women with advanced breast cancers.
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