Results from a new study are providing information to potentially improve the clinical management of women diagnosed with ductal carcinoma in situ (DCIS). A systematic review with meta-analyses to summarize current knowledge on prognostic factors for invasive disease after a diagnosis of DCIS has found that among 26 prognostic factors, 6 were associated with a 36% to 84% increase in the relative risk of progression to invasive disease. The 6 factors include African American race, premenopausal status, detection by palpation, involved margins, high histologic grade, and high p16 protein expression. In addition, the study identified frequently occurring biases in studies on invasive disease after a DCIS diagnosis. The study by Visser et al was published in Cancer Epidemiology, Biomarkers & Prevention.
Although some cases of DCIS will progress into invasive breast cancer, the majority of cases, if left untreated, will not progress and become life-threatening. However, because current guidelines recommend surgical removal of DCIS—usually followed by radiotherapy and sometimes endocrine therapy—many women are overtreated, presenting a large unmet need to distinguish harmless DCIS from DCIS that will develop into invasive breast cancer.
The researchers performed a systematic review of 1,781 studies from the PubMed database from 1970 to 2018. Studies assessed the risk of invasive recurrence in women primarily diagnosed and treated for DCIS, and included at least 10 ipsilateral-invasive breast cancer events and 1 year of follow-up. The Quality in Prognosis Studies (QUIPS) tool was used for risk of bias assessment. Meta-analyses were performed to estimate the average effect size of the prognostic factors.
Of 1,781 articles reviewed, 40 met the inclusion criteria. The number of patients in the included studies ranged from 52 to 37,692, and the mean follow-up time ranged from 3.2 to 15.8 years.
The researchers found that among 26 prognostic factors, they were able to identify 6 that were associated with a 36% to 84% increase in the relative risk of recurrence of invasive disease after a DCIS diagnosis. These factors include African American race [pooled estimate (ES) = 1.43; 95% confidence interval (CI) = 1.15–1.79]; premenopausal status (ES = 1.59; 95% CI = 1.20–2.11); detection by palpation (ES = 1.84; 95% CI = 1.47–2.29); involved margins (ES = 1.63; 95% CI = 1.14–2.32); high histologic grade (ES = 1.36; 95% CI = 1.04–1.77); and high p16 expression (ES = 1.51; 95% CI = 1.04–2.19).
The highest risk of bias was attributable to insufficient handling of confounders and poorly described study groups. “Avoiding these common methodological pitfalls can improve future study designs,” concluded the study authors.
Jelle Wesseling, MD, PhD, of the Netherlands Cancer Institute Department of Pathology, is the corresponding author of this study.
Disclosure: Funding for this study was provided by Cancer Research UK and the Dutch Cancer Society. For full disclosures of the study authors, visit cebp.aacrjournals.org.