Better Outcomes in Breast Cancer With Complete Response After Neoadjuvant Therapy

LAS VEGAS—Pathologic complete response (pCR) after neoadjuvant systemic therapy (NST) is associated with better recurrence and survival outcomes in breast cancer patients compared with those who have residual disease, particularly in those with more specific tumor subtypes, according to new research.

For a comparison of clinicopathologic variables and outcomes between patients with pCR and those with residual disease after NST and breast-conserving surgery, researchers consulted their institutional database at The University of Texas MD Anderson Cancer Center, looking at all patients treated with both NST and breast-conserving surgery for nonmetastatic, invasive breast cancer between 1999 and 2015.

They identified 764 patients, 33% of whom overall experienced pCR. “Greater proportions of patients with high-grade disease and ductal histology experienced pCR; no patients with lobular histology had pCR,” said Victoria Huynh, MD, an assistant professor of surgery at the University of Alabama at Birmingham, presenting the research at the 2025 annual meeting of the American Society of Breast Surgeons.

Among tumor subtypes, pCR rates differed significantly; pCR occurred in 44% and 46% of patients with HER2-positive and triple-negative breast cancer (TNBC), respectively, but in only 15% of patients with hormone receptor (HR)-positive/HER2-negative disease. “Amongst patients with HER2-positive disease, those with HR-negative tumors had significantly higher rates of pCR than those with HR-positive disease,” Dr. Huynh said.

At a median follow-up of about seven years, patients who experienced pCR had significantly longer overall survival (OS) and disease-free survival (DFS). “They also had significantly improved distance recurrence-free survival (DRFS), but we did not observe significant differences in locoregional recurrence-free survival in patients with pCR versus those with residual disease,” she said.

Image: 2012 Sommer R. Gunia et al.

Stratified further by tumor subtype, patients with TNBC and residual disease had locoregional recurrence estimates of 14% at five years, while those with other tumor subtypes had low rates of locoregional recurrence regardless of pCR status. There were no locoregional recurrences in patients with HR-positive/HER2-negative disease who experienced pCR.

“In summary, pCR is associated with improved OS, DFS, and DRFS. While systemic therapies have certainly changed over time, rates of locoregional recurrence are low after breast-conserving surgery regardless of pCR in all tumor subtypes except for TNBC, demonstrating that the effect of pCR on outcomes depends on tumor biology,” Dr. Huynh said.

Due to the study’s time period and retrospective nature, the researchers were not able to document the effect of residual cancer burden, “which is a more quantitative measure of the amount of residual disease,” observed Carla S. Fisher, MD, the chief of the Division of Breast Surgery at the Indiana University Health School of Medicine, in Indianapolis.

“The study shows excellent outcomes for LRR [locoregional recurrence] with rates under 6% for most of the cohort at five years depending on pCR and receptor subtypes. One of their interesting findings is a high rate of LRR in TNBC patients—14% in patients with residual disease compared with less than 4% in patients with pCR.”

This raises the question: Should patients with TNBC who undergo NST and lumpectomy and have residual disease be encouraged to undergo mastectomy or even bilateral mastectomy?

“I would say no, not based on these data,” Dr. Huynh said.

Dr. Fisher agreed. “Given the time period studied—some of these patients were treated 25 years ago—we cannot recommend changes in current protocols based on these findings. We know that patients with TNBC who have residual disease after NST represent a high-risk group of patients for both local disease and distant recurrence. But with immunotherapy and adjuvant capecitabine, we’ve seen significant advances for these patients in the last 25 years,” she said.

Any patient with residual disease after NST should be followed closely for signs of recurrence, “knowing that while their recurrence rates may be higher than those in patients with pCR, they are still favorable and improving overall.”