Background: Pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT) for early-stage breast cancer is prognostic, but not the sole surrogate marker for long-term outcome at a trial level, given that recurrence risk persists in patients who achieve pCR. This study aimed to investigate factors affecting the outcome of patients who achieve pCR.
Methods: This population-based cohort study prospectively enrolled patients who received NACT for nonmetastatic breast cancer between 2007 and 2020 in the Stockholm-Gotland region, which comprises 25% of the entire Swedish population. The primary endpoint was distant relapse-free survival (DRFS), defined as time from surgery to distant recurrence or death from any cause.
Results: Median follow-up from surgery was 5.9 years. Among 2,487 patients, 661 (26.6%) attained pCR. Several factors were independently associated with DRFS in patients with pCR, including increasing age (adjusted hazard ratio [aHR], 1.04; 95% CI, 1.01-1.06), T3/T4 stage (aHR, 2.02; 95% CI, 1.05-3.87), and HER2 positivity (aHR, 0.34; 95% CI, 0.17-0.68). Node positivity predicted distant recurrence during the first year postsurgery (aHR, 2.84; 95% CI, 1.16-6.94), whereas estrogen receptor positivity predicted distant recurrence at 5 to 10 years (aHR, 4.30; 95% CI, 1.06-17.49). The rate of central nervous system relapse as the first site of recurrence was not affected by pCR status (5.3% vs 4.1%; P=.21).
Conclusions: In this population-based study, our findings suggest that patients achieving pCR after NACT are a heterogeneous group in terms of long-term prognosis. Baseline tumor characteristics should be considered when investigating post-neoadjuvant therapy approaches.
Trial registration: ClinicalTrials.gov NCT04675827 NCT05812807) (NCT05232916 NCT04457596 NCT04622319.