Neoadjuvant Versus Adjuvant Therapy in TNBC

Sarah S. Mougalian, MD:Neoadjuvant chemotherapy for triple-negative breast cancer is being used more and more commonly. Traditionally, the use of neoadjuvant therapy was limited to breast cancers that were not surgically resectable. However, more and more research has been done in this setting, and more and more providers are using neoadjuvant chemotherapy to try to get patients to breast conservation. There are a number of additional benefits of the use of neoadjuvant chemotherapy, particularly in triple-negative breast cancer.

First, it gives us a glimpse into the activity of the agents being used. For example, if a patient has a palpable breast mass that shrinks in size, presumably that affect is also taking place on any micrometastatic disease. Secondly, we know that prognosis is largely dependent on the pathologic response to treatment. Patients who have a complete pathologic response after neoadjuvant chemotherapy have excellent long-term outcomes. Finally, we know that patients who do have residual disease after neoadjuvant chemotherapy may benefit from the addition of adjuvant therapy—for example, the use of capecitabine as per the CREATE-X clinical trial.

The use of neoadjuvant chemotherapy also affords us a couple of additional benefits. It’s an optimal setting for studying novel agents, novel combinations of agents, with the use of pathologic response as an outcome. And also, it allows us to select for the most high-risk patients for the study of adjuvant therapies in patients who have had neoadjuvant chemotherapy and have residual disease at the time of surgery.

Outside of clinical trials, the standard of care for the treatment of triple-negative breast cancer includes an anthracycline and a taxane. The role of platinum agents is not well-defined at this point. However, there are 2 large randomized clinical trials—CALGB 40603 and GeparSixto—both of which studied the addition of carboplatin to standard chemotherapy in the neoadjuvant setting. In both studies, the combination of chemotherapy with a platinum resulted in higher pathologic complete response rates.

The use of platinum in the adjuvant setting is actively under investigation with the NRG-BR003 study, which is examining the addition of carboplatin to standard third-generation chemotherapy; and in EA1131, which is examining carboplatin versus capecitabine in the adjuvant setting for women who have residual disease after neoadjuvant chemotherapy.

In my practice, I reserve the use of carboplatin, or a platinum agent to the neoadjuvant setting in those patients who are at highest risk of recurrence.

Transcript edited for clarity.