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April 2012 Ask the Expert: Research and Treatment Options for Triple-Negative Breast Cancer

During the month of April, Living Beyond Breast Cancer experts Edith P. Mitchell, MD, FACP, and Ruth O'Regan, MD, answered your questions about research and treatment options for triple-negative breast cancer.

You may also be interested in our April teleconference on Triple-Negative Breast Cancer: Medical Update.

One surgeon recommends chemo followed by surgery, and another recommends surgery followed by chemo. What should I do?

My surgeon suggested a lumpectomy, but I want a bilateral mastectomy. Should I listen to my surgeon or do what would make me feel less anxious?

Is there research on what activates triple-negative breast cancer?

What diet or exercise might prevent a recurrence of triple-negative disease?

What treatment options are available after chemo, surgery and radiation?

What is the association between triple-negative disease and BRCA1 and 2?

What do we know about triple-negative? Is it one category, or can it be many different types? 

Is there any link between TNBC and previous estrogen receptor-positive breast cancer?

What is the current research to address African-American women and Latinas?

Are the PARP inhibitors still looking like a viable treatment for triple-negative breast cancer? 

What special problems do women with triple-negative breast cancer experience? Emotional, physical, cognitive, etc.?

Am I more at risk for recurrence no matter how many years out from my diagnosis?

Question: I got two opinions from two different surgeons. One said to do chemo first to reduce the size of the tumor, then do surgery. The other said surgery first, then chemo. My tumor is just under 1 cm and triple-negative. I don't know what to do.  

Dr. Mitchell: They are both correct. The standard treatment for triple-negative breast cancer is surgery followed by chemotherapy. However, because triple-negative breast cancer has a tendency to metastasize (spread to other parts of the body) and recur within the first five years after diagnosis, many doctors recommend chemotherapy before surgery. The goal of chemotherapy is to prevent the breast cancer from coming back and spreading to other parts of the body (metastasis).

Question: Both of my surgeons suggested a lumpectomy. I want a bilateral mastectomy. Should I listen to my surgeon or do what would make me feel less anxious? 

Dr. Mitchell: You should make your decision carefully after talking with not only your breast surgeon, but also a plastic and reconstructive surgeon, medical oncologist and geneticist. Be sure to review all the information and work with your doctor or nurse to develop the best plan.

Question: Is there any research on what activates triple-negative breast cancer? 

Dr. Mitchell: Unfortunately, we do not yet know the cause of triple-negative disease or the factors that initiate the process.

Question: Are there any recommendations on what diet or exercise might prevent a recurrence of triple-negative breast cancer?  

Dr. Mitchell: In general, a healthy diet low in fat and high in vegetables and fruits, maintaining an ideal body weight and moderate exercise are important. You should discuss your follow-up care and plan of action for your post-treatment care, also called a survivorship care plan, with your doctor.

Question: Are there any new treatment options available for TNBC survivors after chemo, surgery and radiation?

Dr. Mitchell: There are currently no standard treatment options available after chemotherapy, surgery and radiation. You should discuss your follow-up and surveillance plan with your doctor.

Question: How much association is there between triple-negative breast cancer and BRCA1 and 2?

Dr. Mitchell: Approximately 7 percent of breast cancer cases are associated with an autosomal dominant pattern of inheritance, which means you only need to get the abnormal gene from one parent in order for you to inherit the disease. One of the parents may often have the disease. Approximately 80 percent of BRCA1-associated tumors will be triple-negative.

Question: Triple-negative seems like an unknown category more defined by what it isn't. Is triple-negative one category, or can it be many different types? What do we know about triple-negative?

Dr. O’Regan: Triple-negative breast cancers lack three “receptors” known to fuel most breast cancers: estrogen receptors, progesterone receptors and human epideral growth factor receptor 2 (HER2). The most successful treatments for breast cancer target these receptors.

Triple-negative breast cancer is an umbrella term, as there are multiple subtypes of triple-negative breast cancer that are not completely defined. It is likely that each subtype may ultimately require a different treatment approach.

Recent data from Vanderbilt researchers identified six distinct types of triple-negative breast cancers by evaluating the expression of key genes. They demonstrated that each of these subtypes responds differently to chemotherapy and other targeted agents. For example, one subtype of triple-negative breast cancer expresses androgen receptors and can respond to agents that are used to decrease androgen levels in people diagnosed with prostate cancer.

The presence of these different subtypes suggests that we will have to develop unique therapeutic approaches for each subtype. Given that triple-negative breast cancer accounts for 15 to 20 percent of breast cancers (30,000 to 40,000 cases annually in the U.S.), therapeutic trials in each of these subtypes will require extensive collaborations between investigators throughout the U.S. and the rest of the world.

Question: Is there any link between TNBC and previous estrogen receptor-positive breast cancer?

Dr. O’Regan: Anyone who has been diagnosed with breast cancer is at higher risk of a second breast cancer. Additionally, there is an association between mutations of the BRCA1 gene and estrogen receptor-negative breast cancer, though women who have this mutation can also develop ER-positive breast cancers. Beyond this, I am not aware of an association between prior ER-positive breast cancer and subsequent triple-negative disease.

Question: What is the current research to address African-American women and Latinas?

Dr. O’Regan: Both African-American and Latina women are at higher risk for triple-negative breast cancer, but the reasons for this remain unclear. Diet and other health issues as well as genetics are being investigated to explain this disparity.

Although information on diet and the prevention of breast cancer is inconclusive, following a low-fat diet has been shown to decrease recurrence and improve survival in women who have been diagnosed with ER-negative breast cancer.

Question: Are the PARP inhibitors still looking like a viable treatment for triple-negative breast cancer? Tell us more about this research.

Dr. O’Regan: The PARP (polyadenosinedisposphate-ribose polymerase) enzyme fixes DNA breaks in both healthy and cancerous cells. The goal of PARP inhibitors is to prevent DNA from fixing its mistakes.

So far, PARP inhibitors appear to be effective only when the cancer has an underlying defect in how it repairs DNA, such as in BRCA mutation carriers. The effectiveness of PARP inhibitors in women diagnosed with triple-negative breast cancer but who do not have a BRCA mutation is unclear. 

A randomized trial using iniparib in combination with chemotherapy in women with triple-negative breast cancer did not demonstrate positive results, but this is probably because iniparib does not inhibit PARP at the doses used in humans. Ongoing research should focus on identifying which women benefit from PARP inhibitors by looking at the molecular makeup of the cancer.

Question: What special problems do women with triple-negative breast cancer experience? Emotional, physical, cognitive, etc.?

Dr. O’Regan: A triple-negative breast cancer diagnosis is scary given the bad press these cancers get on the Internet. I tell my patients that all breast cancers, triple-negative or not, are curable if diagnosed at an early stage. I also tell them that they are unlikely to recur after five years.

Joining a support group for women with triple-negative breast cancer may be worthwhile, given that these cancers often occur in young women and almost always need chemotherapy. Ask members of your oncology team to guide you to area resources.

Question: I have heard that those of us who have had triple-negative breast cancer cannot let down our guard as this disease can return anytime. Is this true? Am I more at risk no matter how many years out from my diagnosis?

Dr. O’Regan: It is clear that most triple-negative breast cancers recur within five years if they are destined to recur. After five years the rate of recurrence is very low in contrast to estrogen receptor-positive cancers that can recur many years after diagnosis.

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