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What is Triple Negative Breast Cancer?


Just in recent years, Triple Negative Breast Cancer has sparked interest in the news where instead of calling the tumor as ER-negative, PR-negative, and HER2-negative; researchers began using the shorthand term, "Triple Negative," dubbed the "new type" type of cancer. Being Triple Negative, you don't have a targeted therapy and that your only treatment option is chemotherapy.

Triple Negative is seen in about 15% of all breast cancers. Triple Negative is a very aggressive cancer that tends to strike younger women, pre-menopause, especially among African-American women and women who have BRCA1 mutations. The tumor tends to be fast growing and is less likely to show up on an annual mammogram. TN is more likely to metastasis early on; has a high rate of recurrence in the first 2-3 years from diagnosis and has a poorer prognosis than other types of breast cancer due to lack of specific, targeted treatment for TNBC.

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Tuesday, May 3, 2011

April 2011 Ask The Expert: Research And Treatment Options For Triple-Negative Breast Cancer

Hope S. Rugo, MD
2011-04 - Triple-Negative Breast Cancer - Living Beyond Breast Cancer
Your questions, your answers...

Dr. Hope S. Rugo is a clinical professor of medicine and director of the Breast Medical Oncology Clinical Trials Program in the division of hematology and oncology at the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center.

Question: I have been diagnosed with triple-negative, grade 3, invasive breast cancer, 5.5 cm x 4.0 cm, and have had mastectomy with axillary surgery. No metastases found in nodes, but large tumor with necrosis. I am having FEC chemotherapy right now, probably followed by radiotherapy. Is there any targeted treatment coming up soon for this condition? I am concerned whether this standard treatment will be enough. I am a retired health professional. Thank you.
Dr. Rugo: Triple-negative breast cancer is often high grade, or grade 3, which is what I think you mean. High grade refers to the way the cancer looks under the microscope and includes several features. There are only three grades, and grade 3 cancers are usually faster growing, more aggressive types. Interestingly, this type of cancer is also very sensitive to chemotherapy, as chemotherapy targets rapidly dividing cells. So adjuvant or neoadjuvant chemotherapy is very important for triple-negative disease and can prevent many recurrences.
The behavior of your cancer is important. The fact that the cancer got to be very big without spreading to the lymph nodes means something important. For example, a small cancer that has spread to many nodes is acting more aggressively than a large tumor without positive nodes, regardless of being triple-negative.
For adjuvant treatment of these cancers, we recommend something like FEC or an Adriamycin regimen followed by a taxane. Depending on the agent we give it weekly for 12 weeks, or every 2 to 3 weeks for 4 doses. I think the addition of the taxane is really important in triple-negative disease, and this has been shown in a number of trials. I would only give 4 cycles of the FEC or AC type treatment.
There is intense interest in finding active targeted agents for triple-negative disease. It turns out to be more difficult than we first thought. Because the disease is not one type, but many, one targeted agent is unlikely to work for all triple-negative tumors. Biologically we have identified different subgroups, but this work is still evolving.
The most exciting therapy in the last couple of years was adding agents that blocked the ability of the cancer to repair DNA to standard chemotherapy. These agents are called PARP inhibitors. One very promising study did not have the same benefits when repeated in a larger population of patients, and we are still trying to figure out which tumors benefit the most from this type of treatment. All of the trials reported so far have been done in advanced cancer, and one trial giving these agents before surgery does not yet have results.
In addition to PARP inhibitors, many agents are being tested that target different pathways including angiogenesis, or new blood vessel growth.
That said, you should receive an anthracyline (like FEC or AC) for 4 cycles followed by a taxane, as outlined above. That treatment has very good success rates in a cancer like yours.
Question: I am 8 years out from my triple-negative breast cancer. The label did not even exist at that time, as little was known. I would like to learn more about ongoing studies, or clinical trials that are focused on preventing recurrence of triple-negative cancers. How can I find out if such trials exist?
Dr. Rugo: First, congratulations on being 8 years out!
The majority of recurrences for this disease occur in the first 3-5 years after diagnosis. There are many ongoing studies; these can be accessed at the NCI patient data query site online, as everyone is required to register and list all clinical trials now.
For prevention, there are a number of ongoing investigations, both in the clinic and in the laboratory. Much of the work has been focused on testing for BRCA1 mutations and looking at diet and lifestyle factors that could contribute to the development of this subtype of breast cancer.
Question: What is the 5-year survival rate for triple-negative metastatic cancer?
Dr. Rugo: This is very much dependent on how much tumor was present at the time of diagnosis. Due to the diversity of this type of cancer, as well as the impact of extent of disease at diagnosis and the type and intensity of treatment, it is impossible to give an overall value across the board.
If treatment was given before surgery (neoadjuvant), then response to therapy is a useful predictor of both risk of recurrence and survival. Because this cancer is very sensitive to chemotherapy, adjuvant treatment has a big impact on survival.
Question: Since triple-negative breast cancer returns often, and to other vital organs such as the liver and lungs, how often and what testing should be done?
Dr. Rugo: There is no data that routine testing impacts outcome. In other words, it is not helpful to obtain routine scans looking for recurrence. Scans should be done as needed based on symptoms, findings on blood tests or physical examination. Clearly, symptoms should not be ignored. However, finding metastases “early,” by scan alone, does not change survival from or treatment for this disease. Recurrence in other sites in the body is treatable but not curable regardless of when the disease is discovered.
Question: When I was diagnosed with triple-negative breast cancer, I was told that if it came back, there would not be anything else that they could do for me. Are you finding this true for other TNBC patients?
Dr. Rugo: This global statement is not true. If the disease recurs in distant sites (metastatic breast cancer), it is true that we do not know of a treatment option that will cure it. However, we have a number of chemotherapy and clinical trial options that can extend survival and control the cancer. Unfortunately this is not the case in all patients, but it certainly is in the great majority. In addition to standard therapy, there are many agents in clinical trials that appear quite promising. Information about these trials can be found on the NCI clinical trials website.
Question: Is breast conversation surgery a safe choice for triple-negative cancers?
Dr. Rugo: Yes, if the surgical margins are clear and radiation is given after chemotherapy, this is a safe surgical option for TNBC. One caveat is in patients with BRCA mutations—these women are at higher risk for new cancers, particularly in the unaffected breast, and should discuss surgical options with their surgeon and a genetic counselor.
Question: Is there a size tumor you'd want to stay below to recommend breast conservation surgery?
Dr. Rugo: There is not a specific size. The size issue impacts the cosmetics of the resulting surgery, however this is all related to the size of the breast and where the tumor is located in the breast. If you are large breasted, you have more leeway. Breast conservation, in general, is influenced by the size of the tumor, its location in the breast and the size and shape of the breast.
Question: I'd like to know the doctor’s thoughts on chemo treatments, large doses vs. smaller daily doses. Is one more effective for TNBC?
Dr. Rugo: The answer to this question is dependent on whether this applies to early- or late-stage disease.
Based on current knowledge, it appears that weekly paclitaxel is as effective as but significantly less toxic than larger doses of paclitaxel or docetaxel given less frequently. Any study that has demonstrated improved outcome with one treatment compared to another has shown that this is also true in the more rapidly growing tumor subtypes like TNBC.
Question: Is there any research relating specifically to triple-negative DCIS?
Dr. Rugo: DCIS is noninvasive—in other words, it has not yet invaded blood or lymph vessels. There is research directed toward preventing new cancers after a diagnosis of DCIS and reducing the extent of treatment for lower risk disease.
Other work is focusing on developing a predictive model to estimate an individual’s risk for subsequent invasive cancer. Overall, the appropriate treatment for this disease is excision with clear margins, radiation following breast conserving surgery and surveillance for new cancers.
Question: How should a patient gauge her likelihood of recurrence/metastasis when she has an early-stage diagnosis?
Dr. Rugo: Risk of recurrence is affected by a number of factors. The two most important are the biology and stage of the tumor, followed closely by the age and health of the patient and extent of adjuvant or neoadjuvant chemotherapy. However, triple-negative breast cancer is often very sensitive to chemotherapy, so even higher risk cancers still can be cured.
For an individual who has surgery first followed by chemotherapy, risk is estimated based on the clinical features of the cancer.
Question: My oncologist said that there are studies indicating that there are different types of triple-negative disease—some types are very aggressive, and some types are less aggressive. Can you comment?
Dr. Rugo: Yes, it appears that there are subtypes within triple-negative disease that vary based on some biologic features, sensitivity to chemotherapy and behavior in the body. Very few triple-negative cancers are slow growing; the majority are more aggressive and rapidly growing. Most are very sensitive to chemotherapy, but some are quite resistant.
Laboratory research is now directed toward trying to better understand differences between triple-negative breast cancers, with the goal of trying to find the right treatment for these specific cancer subsets. We understand, for example, that triple-negative cancers associated with BRCA1 mutations have specific sensitivity to PARP inhibitors and to agents that damage DNA. So even within triple-negative disease, it is clear that one size does not fit all in terms of the most effective therapy.
Question: Are there any new treatment options for triple-negative breast cancer patients beside the PARP Inhibitor?
Dr. Rugo: Yes, there are a number of new agents that are being tested in triple-negative disease, some with very promising early results. Trials are listed on the NCI’s clinical trial database, as investigators are now required to list all trials on that site. One exciting area for investigation in the near future is targeting the body’s immune response to cancer, as the immune response may promote resistance to chemotherapy.
Question: I am 30 years old. Diagnosed last year with TNBC. Bilateral mastectomies, chemo. No lymph node involvement. Stage 2. Should I ask my doctor about getting into trials? Do you recommend getting into trials? Could it cause problems?
Dr. Rugo: If you have not seen a genetic counselor for counseling and BRCA testing, I would strongly encourage you to consider this. Presumably you received chemotherapy after your surgery? As you are now likely to be done with your adjuvant therapy, trial participation depends on availability of a post adjuvant study. Usually these trials randomize to treatment or placebo.
One such trial is studying a drug called metformin to see if this will reduce recurrence (not just in triple-negative disease). Metformin is a drug used to treat diabetes that may have anti-cancer effects. This trial, run by our colleagues in Canada, is not yet open in the United States but should be soon.

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