July 2015 Ask the Expert: Medical Updates, Treatment Options and Follow-Up Care for Triple-Negative Breast Cancer

July 1, 2015

About 15 to 25 percent of breast cancers are triple-negative, meaning that unlike other breast cancers, they do not grow because of estrogeninfo-icon, progesteroneinfo-icon or a proteininfo-icon called HER2.

This July, Living Beyond Breast Cancer expert Rita Nanda, MD, answered your questions about triple-negative breast cancerinfo-icon – how it's different from other types of breast cancer, what treatments are available, what research is happening and how it applies to you.

Remember: we cannot provide diagnoses, medical consultations or specific treatment recommendations. This service is designed for educational and informational purposes only. The information is general in nature. For specific healthcare questions or concerns, consult your healthcare providerinfo-icon because treatment varies with individual circumstances. The content is not intended in any way to substitute for professional counselinginfo-icon or medical advice.

Question: Since triple-negative breast cancer is not hormonally fed, what went wrong in the body that caused it, especially if there is no family history? Is research getting closer to figuring out the cause?

Dr. Nanda: One in eight women in the US will develop breast cancer in her lifetime and about 20 percent are triple-negative. While there are a number of risk factors that are known to increase risk, such as having a BRCA1info-icon or BRCA2info-icon mutationinfo-icon, up to 80 percent of women who develop breast cancer have no identifiable risk for developing breast cancer. And it is not well understood why some women develop triple-negative breast cancerinfo-icon versus other types of breast cancer.

Question: What is the risk of recurrence for triple-negative breast cancer? How does stage at diagnosis, number of lymph nodes removed or other factors affect it?

Dr. Nanda: The risk of recurrenceinfo-icon of triple-negative breast cancerinfo-icon (as is the case for other forms of breast cancer) is related to the size of the tumorinfo-icon, the number of lymphinfo-icon nodes that are positive for cancer, and the gradeinfo-icon of the tumor. In general, the larger the tumor and/or the higher the number of involved lymph nodes, the higher the risk of recurrence.

Question: It is my understanding that triple-negative breast cancer is more likely to recur in the first 2 years. Is that true? Am I at a lesser risk at 5 years and beyond?

Dr. Nanda: For those people who develop triple-negative breast cancerinfo-icon, the risk of a recurrenceinfo-icon is highest within the first 3 years after diagnosisinfo-icon. While late recurrences (those after 3 years) can still occur, they are much less common.

Question: Does sugar (processed foods, white sugar, white rice, pasta, etc.) feed cancer, especially triple-negative breast cancer? If so, is there a specific diet that people should follow?

Dr. Nanda: Processed foods do not selectively feed cancer cells. We do advise patients to follow a heart-healthy diet and some studies suggest that such a diet can reduce the risk of recurrenceinfo-icon. General recommendations are for a low fat, high fiber diet, focusing on lean sources of proteininfo-icon (grains, fish, turkey, chicken over more fatty sources of protein; baked foods over fried) and plenty of fresh vegetables and fruits. In addition, reducing or limiting alcohol consumption to under three alcoholic beverages (on average) a week has also been show to help reduce the risk of breast cancer recurrence. Rich foods, sweets and alcohol are fine in moderation.

Question: If you were obese at diagnosis and are working on losing weight, does that lower your risk of recurrence of triple-negative breast cancer, or are your odds the same because you were already obese?

Dr. Nanda: Maintaining a healthy body weight, following a heart-healthy diet and exercising regularly have all been associated with a reduction in the risk of recurrenceinfo-icon of breast cancer in a number of different studies. While it is hard to know to what degree these lifestyle changes reduce the risk, a number of studies have demonstrated a benefit and it is never too late to start healthy habits!

Question: Can stress cause TNBC?

Dr. Nanda: Psychologicalinfo-icon stressinfo-icon describes what people feel when they are under mental, physical, or emotional pressure. Although it is normal to experience some stress from time to time, people who experience high levels of stress over a long period of time may be at increased risk for developing health problems. However, there are no clear data linking stress to the development of cancer.

People who have cancer may have increased stress related to the diagnosisinfo-icon and treatment of the disease. People who are able to use effective coping strategies to deal with stress, such as relaxation and stress management techniques, have been shown to have lower levels of depressioninfo-icon, anxietyinfo-icon and symptoms related to the cancer and its treatment. Although there is still no strong evidence that stress directly affects cancer outcomes, studies suggest that patients can develop a sense of hopelessness when stress becomes overwhelming. It is therefore important for those who are experiencing symptoms of stress to seek help.

Question: Are today's chemotherapy medicines any better than previous versions when it comes to side effects?

Dr. Nanda: The chemotherapyinfo-icon drugs that are routinely used to treat TNBC are drugs that have been around since the 1980s and 1990s. These drugs are generally well-tolerated, with manageable side effects. While our treatments haven’t significantly changed for the past 2 decades, our ability to manage the side effects has. Anti-nauseainfo-icon medications have improved and the vast majority of women who receive chemotherapy these days have little to no nausea. While fatigueinfo-icon, decreased blood counts and hair loss do occur with most regimens, these side effects are manageable.

Question: My oncologist has recommended infusions with zoledronic acid (Zometa) to help prevent recurrence of my triple-negative breast cancer. I was diagnosed 2 years ago at age 49. After chemotherapy and radiation, I am now in menopause. Do you have any feedback about this treatment option?

Dr. Nanda: Zoledronic acidinfo-icon is a bisphosphonateinfo-icon, and bisphosphonates are routinely used to prevent or treat osteoporosisinfo-icon. Bisphosphonates do this by limiting the activity of certain bone cells, called osteoclasts, which help cause the bone weakening and breakdown that leads to osteoporosis. Investigators have also studied if bisphosphonates can reduce the risk of breast cancer recurrenceinfo-icon. The studies performed to date have had mixed results, with some demonstrating a reduction in the risk of recurrence and others showing no reduction. A meta-analysisinfo-icon (an analysis of all of the studies lumped together) suggested that there is a modest reduction in the risk of relapseinfo-icon when bisphosphonates are given to women who are postmenopausalinfo-icon. While the use of bisphosphonates in this setting is somewhat controversial (given the conflicting results of the many studies performed), it is reasonable to consider its use, particularly in individuals who are postmenopausal and at high risk of recurrence.

Question: I have been diagnosed with TNBC and am awaiting a mastectomy and reconstruction. If the lymph nodes are clear why would I want to do chemo?

Dr. Nanda: The risk of recurrenceinfo-icon from breast cancer is based on the size of the cancer and lymph nodeinfo-icon status. While those who do not have lymph node involvement are at lower risk, there is still a risk of disease recurrence (your oncologistinfo-icon can help assess what your risk is based on your personal history and the features of your cancer). Chemotherapyinfo-icon can reduce this risk of recurrence by 50 percent. Therefore, even in the setting of negative lymphinfo-icon nodes, chemotherapy is routinely recommended for TNBC.

Question: Given that TNBC has a high recurrence rate, why would I NOT go for a double mastectomy?

Dr. Nanda: The risk of recurrenceinfo-icon after a diagnosisinfo-icon of breast cancer is related to the stageinfo-icon of the breast cancer (which is dependent on the size and the lymph nodeinfo-icon status). If TNBC recurs, the most common sites of recurrence include the lungs, the liver and the bones. Choosing to have a mastectomyinfo-icon or a double mastectomy does nothing to impact this risk of a recurrence. The primary medical reason for a person to consider prophylacticinfo-icon removal of both breasts is if she is found to be at high risk for developing a new breast cancer (e.g. if she has a BRCA1info-icon or BRCA2info-icon mutationinfo-icon).

Question: Immunotherapy seems to be a hot topic in treatment of cancer. Is there any information on using immunotherapy to treat triple-negative breast cancer that is regionally advanced but not metastatic?

Dr. Nanda: Immune checkpoint inhibitors have shown promise for women with advanced triple-negative breast cancerinfo-icon and studies exploring these agents alone or in combination with chemotherapyinfo-icon in the advanced cancer setting are ongoing. These drugs are purely investigationalinfo-icon at this point, are not yet FDAinfo-icon approved for breast cancer, and thus not recommended outside of a clinical trialinfo-icon. Immune checkpoint inhibitors are being incorporated into therapyinfo-icon for early-stageinfo-icon disease in the neoadjuvant setting, and many studies for advanced cancer do allow patients with regionally advanced disease or locally recurrent disease that has not responded to standard chemotherapy.

Question: I have received different biomarker results from my first biopsy (triple-positive) and my mastectomy (triple-negative). Can I trust these results? Should I request to have the tests redone?

Dr. Nanda: Breast cancers can be very heterogeneous and biopsies only sample a small area of the tumorinfo-icon, so they might not be representative of the entire tumor. I do think, however, that it would be reasonable to have both the first biopsyinfo-icon and the mastectomyinfo-icon specimen restained for ERinfo-icon, PRinfo-icon, and HER2 to confirm the result, given the differences between the two samples.

Question: A recent study indicates that copper depletion might prevent recurrence in triple-negative breast cancer. Can you discuss the status of this research on the drug tetrathiomolybdate and how to get involved (if possible) in the phase III clinical trial that is being developed? And is tetrathiomolybdate available outside of a clinical trial for the purpose of preventing cancer?

Dr. Nanda: Results from an early phase trial has suggested that targeting the tumorinfo-icon microenvironment with a copper-depleting agent, tetrathiomolybdate, creates an inhospitable environment for tumor progressioninfo-icon in patients with breast cancer, with the effect most striking in those with triple-negative disease. The results were presented at the 2015 American Society of Clinicalinfo-icon Oncologyinfo-icon (ASCO) Annual Meeting. Study investigators are currently developing a phase III randomized study of tetrathiomolybdate in breast cancer patients, but this study is not yet recruiting. Once it is, it will be listed on ClinicalTrials.gov. Tetrathiomolybdate is not FDAinfo-icon approved and is not available outside of a clinical trialinfo-icon.

Question: I was diagnosed with stage I triple-negative breast cancer. I am not BRCA-positive and I had a breast MRI prior to surgery that showed no other abnormality. I had a lumpectomy, chemotherapy and radiation. The only additional scans I have had are repeat mammograms. Why is it that other tests (PET/bone scans etc.) are not done? How can I be sure there are no metastases in my liver, lung, bones or brain?

Dr. Nanda: The American Society of Clinicalinfo-icon Oncologyinfo-icon (ASCO) has guidelines for follow-up care of breast cancer patients. After treatment is completed, patients should follow up with their physicians for physical examinations every 3-6 months for the first 3 years, every 6-12 months for years 4 and 5, and annually thereafter.

For women who have undergone breast-conserving surgeryinfo-icon, a post-treatment mammograminfo-icon should be done 1 year after the initial mammogram and at least 6 months after completion of radiation therapyinfo-icon. Unless otherwise indicated, a yearly mammographic evaluation should be performed.

The use of complete blood counts, chemistry panels, bone scans, chest x-rays, CT scans, PET scans, MRIs, and/or tumorinfo-icon markers (CA 15-3 and CA 27.29) is not recommended for routine follow-up in a patient with no symptoms and no specific findings on clinical examination. Some medical oncologists perform follow-up scans and tumor markers after the completion of treatment to monitor for a recurrenceinfo-icon, however, intense surveillance has not been shown to improve outcomes for women with breast cancer, and I personally follow the ASCO guidelines. In fact, in many cases, intense surveillance can be quite detrimental as it can increase anxietyinfo-icon and lead to additional and oftentimes invasive and unnecessary testing.

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