Breakthroughs in TNBC: Expert insights on neoadjuvant vs adjuvant therapy

In an early morning session on the last day of the Miami Breast Cancer Conference, Hyo Han, MD, Research Director, Department of Breast Oncology at Moffitt Cancer Center, discussed the best practices for neoadjuvant and adjuvant therapy in early triple-negative breast cancer (TNBC). 

What makes a patient a good candidate for neoadjuvant therapy?

Dr. Han noted patients who are inoperable or those who have locally advanced disease—such as inflammatory breast cancer or bulky and/or matted cN2 or cN3, or cT4—are potential candidates for neoadjuvant therapy. Other candidates include those with TNBC and HER2+ with > cT2 or cN1, those with “a large primary tumor relative to breast size who [also] desire breast conservation, or those who have delayed definite surgery.

There are some pros and cons to neoadjuvant therapy, Dr. Han said. Among them, it can downstage the tumor and improve outcomes in breast-conserving surgery. There’s also an opportunity to optimize local therapy in patients with N+ to N0. It allows time for genetic testing and to plan reconstruction or lymphovenous bypass. However, the risks are “possible overtreatment if clinical stage is underestimated, and possible undertreatment locoregionally with radiation if clinical stage is underestimated,” according to Dr. Han.

She highlighted pembrolizumab in combination with chemotherapy, which was approved in 2022 as a neoadjuvant treatment and as a single agent for adjuvant therapy following surgery for patients with high-risk, early stage TNBC; approval was based on the KEYNOTE-522 findings. “I would like to point out that ‘high-risk’ wasn’t defined here, so it’s something to think about,” Dr. Han said.

For neoadjuvant therapy, “It’s important to get diagnostic staging correct,” Dr. Han says.

Adjuvant therapy candidates, explained

“Adjuvant therapy is for some patients who declined neoadjuvant [or] patients with worse disease,” Dr. Han said. She pointed to a phase III study published in JAMA Oncology, which found that a paclitaxel and carboplatin regimen is an effective alternative adjuvant chemotherapy choice for patients with operable TNBC. “Carboplatin is shown to improve human survival,” Dr. Han said.

“Current data supports the use of post--neoadjuvant therapy for high risk TNBC patients without pCR following neoadjuvant therapy,” Dr. Han said, including capecitabine and olaparib. She also recommended continued pembrolizumab in an adjuvant setting. “Combination therapy with pembrolizumab and capecitabine or olaparib can be considered for high-risk patients (non-pCR) despite lack of randomized trials,” said Dr. Han. The take home message, she impressed, is that this kind of treatment protocol requires a “multidisciplinary approach with shared decision making.”