Investigators identify several potential first time risk factors of long-term outcomes in patients with HER2-positive breast cancer with or without a pathologic complete response.
Factors such as tumor size, nodal status, and hormone receptor status may help in predicting relapse in complete responders with early breast cancer, according to findings from an analysis published in the Journal of Clinical Oncology.
Patients who experienced a pathologic complete response had better event-free survival (EFS; HR, 0.39; 95% CI, 0.34-0.46; P <.001) and overall survival (HR, 0.32; 95% CI, 0.26-0.41; P <.001) than those who didn’t. Among this population, both tumor size (HR, 0.67; 95% CI, 0.50-0.90; P = .007) and nodal status (HR, 0.72; 95% CI, 0.53 to 0.98; P = .039) were found to be independent predictors of EFS, whereas only tumor size was a significant predictor of OS (HR, 0.55; 95% CI, 0.34-0.87; P = .011).
Among patients without a complete response, tumor size predicted for both EFS (HR, 0.62; 95% CI, 0.53-0.73; P <.001) and OS (HR, 0.47; 95% CI, 0.37-0.60; P <.001); nodal status was also prognostic for both EFS (HR, 0.66; 95% CI, 0.55-0.79; P <.001) and OS (HR, 0.75; 95% CI, 0.58-0.96; P <.025). Notably, hormone receptor status was also found to be predictive in this population for both EFS (HR, 0.59; 95% CI, 0.50-0.68; P = .005) and OS (HR, 0.44; 95% CI, 0.36-0.55; P <.001).
“[Many] trials are selecting patients with high risk of relapse, and pathologic complete response is commonly used as a prognostic marker in the postneoadjuvant setting,” the investigators wrote. “However, on the basis of the results presented here, patients with a pathologic complete response after neoadjuvant systemic treatment but with unfavorable clinicopathologic features at primary diagnosis have a higher risk of relapse and this should be considered by clinicians when initiating postneoadjuvant treatment and in the future when designing new trials.”
Investigators extracted data from 3710 enrolled patients across 11 randomized clinical trials to derive these findings. The median age of these patients was 49 years old (range, 18-81 years). The overall median follow-up was 61.2 months (range, 37.6-81.7).
Nodal involvement existed at diagnosis in 64.9% of patients, 56.7% of patients were diagnosed with a tumor size of 1 or 2, and 54.9% of patients had hormone receptor–positive disease.
A minority of patients (n = 1497; 40.4%) in this population had experienced a complete response; the remainder (n = 2213; 59.6%) had residual disease following neoadjuvant therapy. This latter group included 176 patients who did not undergo surgery for various reasons and were therefore considered to have no pathologic complete response.
Other findings included a lower EFS rate among patients with a complete response, hormone receptor–positive disease, clinically positive lymph nodes, and tumor size of 3 or 4 vs those with negative lymph nodes and a tumor size of 1 or 2 (HR, 0.46; 95% CI, 0.25-0.85). Among patients without nodal involvement, 5-year EFS rates were similar regardless of tumor size (HR, 0.84; 95% CI, 0.53-1.35).
Investigators moreover developed a prognostic scoring system based on the examined factors and found that a greater quantity of risk factors predicted worse EFS and OS outcomes across all analyzed patient subsets (P <.001 for all subsets).
“A prognostic score consisting of the number of risk factors present was developed and demonstrated that patients with a higher number of risk factors present, regardless of the achievement of pathologic complete response, had a significantly worse EFS and OS,” investigators wrote. “This simple scoring system could help clinicians when considering treatment options after neoadjuvant systemic therapy and counseling patients.”
van Mackelenbergh MT, Loibl S, Untch M, et al. Pathologic complete response and individual patient prognosis after neoadjuvant chemotherapy plus anti-human epidermal growth factor receptor 2 therapy of human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. Published online April 19, 2023. doi:10.1200/JCO.22.02241