Pathologic Complete Response to Neoadjuvant Chemotherapy May Guide Escalation and De-escalation Treatment Strategies in Localized Breast Cancer

February 2019, Vol 9, No 2

Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy correlates with significantly improved event-free survival (EFS) and overall survival (OS) in patients with localized breast cancer, according to the results of a large comprehensive meta-analysis presented at the 2018 San Antonio Breast Cancer Symposium.

Survival was improved across different types of breast cancer in patients treated with neoadjuvant therapy who achieved pCR, and was particularly robust in triple-negative and HER2-positive breast cancer. EFS and OS rates were similar regardless of whether patients were treated with additional adjuvant chemotherapy, suggesting that adjuvant chemotherapy may be omitted in some patients with early breast cancer who achieve pCR with neoadjuvant chemotherapy.

“Similar outcomes with or without adjuvant chemotherapy in patients who attain pCR on neoadjuvant chemotherapy…suggests that adjuvant chemotherapy could potentially be omitted under certain circumstances. These important findings suggest that further research is needed to evaluate the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on neoadjuvant response,” said Laura M. Spring, MD, Breast Medical ­Oncologist, Massachusetts General Hospital Cancer Center, Boston.

“Additional adjuvant chemotherapy…adds to toxicity and may represent overtreatment for some patients who get to pCR on neoadjuvant therapy. Neoadjuvant chemotherapy offers several additional advantages over adjuvant therapy, including rapid assessment of response using surrogate markers like pCR,” Dr Spring stated.

The meta-analysis included published studies of localized breast cancer with 25 or more patients featuring neoadjuvant chemotherapy that reported pCR results as well as recurrence and/or survival based on pathologic outcome. A PubMed search identified 3209 potential studies, but only 52 met the criteria for inclusion; the total number of patients included in these studies was 27,895.

pCR as a Predictive Marker

pCR was achieved in 21.1% of all patients included in the meta-analysis, and varied by subtype, with approximately 30% of triple-negative and HER2-positive patients who were treated with neoadjuvant therapy attaining pCR compared with <20% of hormone receptor (HR)-­positive patients.

Patients who achieved pCR after neoadjuvant chemotherapy had significantly better EFS versus patients with residual disease. EFS was improved by 69% in those with pCR. The 5-year EFS was 88% for patients with pCR versus 67% for those with residual disease.

A similar relationship was observed between pCR and OS. Five-year OS was 94% for patients with pCR versus 75% for those with residual disease.

The relationship between pCR and survival was strongest for triple-negative and HER2-positive breast cancer, although survival was improved to a lesser extent by pCR versus residual disease in HR-positive/HER2-negative breast cancer.

The 5-year EFS was improved in pCR patients who received treatment with adjuvant chemotherapy as well as in those who did not: 86% versus 88%, respectively.

One of the study’s strengths was that pCR was highly predictive of EFS and OS regardless of the type of neoadjuvant regimens the patients received.

“This suggests that the path taken to attain pCR may not be critical,” Dr Spring noted.

Commenting from the audience about Dr Spring’s presentation, Laura J. Esserman, MD, MBA, Director, Carol Franc Buck Breast Cancer Center, University of California San Francisco, stated, “This is a fantastic job of presenting complex data. The data show that however you get to pCR, you have a good outcome. This study supports de-escalation of therapy in localized breast cancer.”

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