In a retrospective analysis from the neoadjuvant I-SPY2 trial reported in JAMA Surgery, Osdoit et al found that among patients with breast cancer achieving pathologic complete response (pCR), there were no significant differences in treatment outcomes according to the presence or absence of residual ductal carcinoma in situ (DCIS).
As stated by the investigators, “pCR after neoadjuvant chemotherapy in breast cancer strongly correlates with overall survival and has become the standard endpoint in neoadjuvant trials. However, there is controversy regarding whether the definition of pCR should exclude or permit the presence of residual DCIS.”
Study Details
The I-SPY2 trial is an ongoing adaptive neoadjuvant platform trial in patients with breast cancer at high risk of recurrence that is testing novel therapeutics against a background of standard of care for early breast cancer. In the trial, women with stage II/III breast cancer at high risk of recurrence are randomly assigned to receive taxane and anthracycline-based neoadjuvant therapy with or without 1 of 10 investigational agents, followed by definitive surgery. The current analysis compared 3-year event-free survival, distant recurrence–free survival, and locoregional recurrence among patients with pCR with vs without residual DCIS.
Key Findings
Among 933 patients with complete pathology and follow-up data, 337 (36%) had no residual invasive disease (residual cancer burden 0, or pCR), with 70 (21%) of these having residual DCIS. Among the patients with pCR, residual DCIS was identified in 8.5% of triple-negative tumors, 15.6% of hormone receptor–positive tumors, and 36.6% of HER2-positive tumors.
At 3 years, among patients with pCR with vs without residual DCIS, event-free survival was 89.2% vs 95.6% (hazard ratio [HR] = 2.08, 95% confidence interval [CI] = 0.83–5.20, P = .12), distant recurrence–free survival was 90.6% vs 96.0% (HR = 1.91, 95% CI = 0.72–5.08, P = .20), and freedom from locoregional recurrence was 97.0% vs 97.0% (HR = 1.27, 95% CI = 0.26–6.28, P = .77).
The investigators concluded, “The analysis supports the definition of pCR as the absence of invasive disease after neoadjuvant chemotherapy regardless of the presence or absence of DCIS.”
They noted, “The finding that the prevalence of residual DCIS varied significantly by receptor subtype is intriguing and raises the possibility that a residual in situ component could have different prognostic significance in subtype specific analyses. Such an evaluation would require an even larger data set but should be explored.”
Rita A. Mukhtar, MD, of the University of California, San Francisco, is the corresponding author for the JAMA Surgery article.
Disclosure: The study was supported by the Quantum Leap Healthcare Collaborative, Foundation for the National Institutes of Health, National Cancer Institute, and others. For full disclosures of the study authors, visit jamanetwork.com.
