Triple-negative breast cancer (TNBC) makes up approximately 15% of all breast cancer cases, but is typically more aggressive and has a higher risk of early relapse. TNBC is characterized by the aberrations it lacks—no HER2 amplification and no hormone receptor expression.
Because of a current lack of targets for triple-negative disease, the main course of treatment is chemotherapy. Lisa Carey, MD, professor of medicine, medical director of the University of North Carolina (UNC) Breast Center and associate director for clinical research at UNC Lineberger Comprehensive Cancer Center, presented the major questions in managing triple-negative breast cancer, both in the early and advanced setting, at the 30th Annual Miami Breast Cancer Conference, held March 7–10 in Miami Beach, Florida.
In the early breast cancer setting, one key question is whether a subset of TNBC patients has a good enough prognosis and does not need adjuvant chemotherapy. One misconception about TNBC is that it is a lethal disease at all stages. But, most stage I breast cancers, including TNBC, are in fact cured. “This message has somehow been lost for patients, and one goal is to better educate the patient to understand that clinical factors are just as important as the molecular and biological ones,” said Carey. “There is no breast cancer biology that is predestined to recur.”
In the adjuvant setting, another major question is still whether local therapy for TNBC should be different from other breast cancer subtypes. Like other breast cancers, TNBC is currently managed with breast-conserving surgery followed by adjuvant radiotherapy or a mastectomy. In most cases, there is currently a lack of evidence that TNBC patients should be treated differently in terms of surgery and radiotherapy.
Another question is whether TNBC requires a different type of chemotherapy treatment compared with other breast cancer types in the adjuvant setting. Typically, clinicians treat TNBC patients with chemotherapy earlier and with a more aggressive chemotherapy regimen in order to mitigate the risk of recurrence. “I would argue that there are patients who may not need to receive chemotherapy, but that have TNBC,” said Carey. These are patients with very small, node-negative tumors for which the 5-year risk of recurrence is typically low (less than 10%). “It is perfectly appropriate to consider not treating these patients [with chemotherapy], and I typically draw the line at a 5-mm tumor,” said Carey. However, there is still only a small dataset of long-term results for these patients that have not been treated.
The other question is whether the chemotherapy type should differ for treatment of TNBC? There is no robust data to suggest this, according to Carey. Platinum-based chemotherapy is considered more aggressive, and studies are ongoing to understand whether TNBC patients may benefit more from these regimens. “I do not use platinum-based regimens outside of a clinical trial for the adjuvant setting,” said Carey. Carey highlighted the Cancer and Leukemia Group B (CALGB) 40603 trial that is evaluating paclitaxel with or without bevacizumab and with or without carboplatin in the neoadjuvant setting. For now, choice of regimen remains based on assessment of risk of recurrence, as well as any comorbidities of the patient. To treat high-risk TNBC, Carey says she uses a combination regimen of anthracycline and a taxane-based chemotherapy.
The ultimate question that remains is how to define TNBCs? Molecular subtyping studies are ongoing. A related issue is how to define and best manage those tumors that have a hormone receptor expression that does not meet the threshold to be considered hormone-positive breast cancer. While this subset of tumors, with estrogen-receptor staining in the 1% to 10% range, is generally classified along with TNBC, it may actually be a combination of different subtypes, including luminal tumors. According to Carey, these low estrogen-receptor tumors with no HER2 or progesterone receptor expression should be treated with adjuvant endocrine therapy, as guided by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP).
“TNBC is not a unique subset, but made up of different molecular subtypes,” said Carey. Still, the commonality of the breast cancers that make up what are called the triple-negative class is their higher rate of both local and distant metastasis and earlier rate of relapse. Many more translational and comprehensive studies are needed to understand the subtypes that make up TNBC for targeted treatment options to be developed.
What is the overall conclusion? For now, breast cancer surgery, radiotherapy, and chemotherapy options remain individualized to the patient and similar to the way that other breast tumor types are treated.