An NCDB-based investigation on predictors of upgrade to invasive disease in patients with ductal carcinoma in situ: Does hormone receptor status play a role?

Abstract Introduction The management of ductal carcinoma in situ (DCIS) is evolving as clinical trials investigate active surveillance. Identifying risk factors for upstaging to invasive disease must be understood for safe de-escalation of care. This study examined risk factors associated with upgrade to invasive disease, focusing on hormone receptor (HR) status. Methods The National Cancer Database (NCDB) was queried for female patients > 18 years with DCIS who underwent curative-intent surgery from 2004-2020. HR positive (HR+) DCIS was defined as estrogen and/or progesterone receptor positive (immunohistochemical stain >1%). Upstaging to invasive disease was defined as > pT1 or >pN0 on final pathology. Univariate and multivariable logistic regression were performed to identify risk factors predictive of upstaging to invasive disease. Results Among 226,837 patients, median age was 60 years old (IQR 50-68) and 85.1% had HR+ disease. Overall, 17.2% (n=39,086) were upstaged to invasive carcinoma. HR - DCIS had higher odds of upstaging than HR+ DCIS on univariate analysis (OR 1.45; 95%CI 1.41-1.50, p<0.001). After controlling for factors such as grade and tumor size on multivariate analysis, HR negative status remained predictive of upgrade to invasive disease (OR 2.51; 95%CI: 2.42-2.60, p<0.001). Conclusions In this large national cohort, 17.2% of patients with DCIS were upstaged to invasive cancer. Hormone receptor-negative status is independently associated with increased risk of upstaging to invasive disease. As we continue to redefine the management of DCIS, understanding how hormone receptor status influences upgrade risk, may help clinicians to risk-stratify patients and inform treatment decision-making.