A large comprehensive patient-level meta-analysis showed that achieving pathologic complete response after neoadjuvant chemotherapy correlates with significantly improved event-free survival and overall survival in patients with localized breast cancer. These findings were particularly robust in triple-negative breast cancer and HER2-positive breast cancer. Event-free and overall survival were similar regardless of whether patients received additional adjuvant chemotherapy. The findings suggest that adjuvant chemotherapy can be abbreviated or even omitted in some patients if they achieve pathologic complete response to neoadjuvant chemotherapy.
Similar outcomes with or without adjuvant chemotherapy in patients who attain pathologic complete response on neoadjuvant chemotherapy likely reflects tumor biology and support the clinical utility of escalation and de-escalation strategies in the adjuvant setting based on the neoadjuvant response,” said lead author Laura M. Spring, MD, a medical oncologist at Massachusetts General Hospital Cancer Center, Boston. Dr. Spring presented these results at the 2018 San Antonio Breast Cancer Symposium,1. They were in keeping with several other presentations suggesting that de-escalation of breast cancer treatment may be possible.
Breast cancer trials have traditionally added additional systemic therapies to reduce recurrence risk, but this adds to toxicity and may represent overtreatment for some patients. Neoadjuvant chemotherapy offers several additional advantages over adjuvant therapy, including rapid assessment of response using surrogate markers like pathologic complete response,” she told listeners.
Objectives and Implications
The study Dr. Spring presented examined the impact of subsequent adjuvant therapy following pathologic complete response in the neoadjuvant setting and long-term outcomes. She and her co-researchers also examined the relationship between the magnitude of change in pathologic complete response and corresponding changes in event-free survival. Senior author of this paper, Aditya Bardia, MD, MPH, Director of Precision Medicine at the Center for
Breast Cancer at Massachusetts General Hospital and Harvard Medical School, Boston, said: “Overall, the study findings highlight the potential importance of a Hologic complete response (or lack thereof) in clinical decision-making. For example, if a patient does not have pathologic -complete response, they are at higher risk of recurrence, and extended therapy could potentially lower risk, such as demonstrated by large adjuvant trials in this setting—e.g., CREATE-X (capecitabine for triple-negative breast cancer)
KATHERINE (T-DM1 for HER2-positive breast cancer). The decision to include adjuvant chemotherapy requires individual discussion on a case-by-case basis, factoring in baseline risk, type of neoadjuvant therapy, and other factors. The study highlights how pathologic complete response could be utilized to personalize the ‘right amount of therapy for a patient with localized breast cancer.
Methods and Findings
Dr. Spring and her team conducted a comprehensive patient-level meta-analysis of studies in localized breast cancer. Relevant studies were identified by a PubMed search of published studies of localized breast cancer with 25 or more patients featuring neoadjuvant chemotherapy that reported pathologic complete response results and recurrence and/or survival based on pathologic outcome. The search identified 3,209 studies; 52 of these studies with 27,895 patients met the full criteria for selection for the analysis. Pathologic complete response was determined to be an important and independent predictor of outcomes.
To account for treatment differences in our statistical approach, we used a random-effects model, which is more conservative than other approaches, and we also performed several sensitivity analyses to confirm results,” Dr. Spring explained. Overall, pathologic complete response was achieved in 21.1% of patients in the meta-analysis. Pathologic complete response varied by subtype. About 30% of patients with triple-negative and HER2-positive disease have a pathologic complete response compared with less than 20% of those with hormone receptor-positive disease. Patients who achieved a pathologic complete response after neoadjuvant chemotherapy had significantly better event-free survival than patients with residual disease. Event-free survival was improved by 69% among those with a pathologic complete response.