SUMMARY: Breast cancer is the most common cancer among women in the US and about 1 in 8 women (12%) will develop invasive breast cancer during their lifetime. Approximately 268,600 new cases of female breast cancer will be diagnosed in 2019 and about 41,760 women will die of the disease. Carcinoma in situ of the breast also known as Ductal Carcinoma In Situ (DCIS) is defined as a malignant proliferation of ductal epithelial cells that are confined to the milk ducts without invasion of the basement membrane, and is a precursor lesion to invasive carcinoma. DCIS accounts for approximately 25% of all newly diagnosed breast cancers. Patients with small, screening-detected lesions, are often treated with breast-conserving surgery (to prevent the development of invasive breast cancer), followed by adjuvant radiation and hormonal therapy, although neither of the latter two interventions have been shown to improve survival outcomes. As such, a significant number of patients are overtreated. There remains a large unmet need, to distinguish relatively benign DCIS from DCIS that will develop into invasive breast cancer.
The authors in this study performed a systematic review from 1970 to 2018, with meta-analyses of 1,781 articles from the PubMed database, to summarize current knowledge on prognostic factors for invasive disease, after a diagnosis of DCIS. The number of patients in the included studies ranged from 52 to 37,692. Of all the articles reviewed, 40 articles met the inclusion criteria. Eligible studies assessed 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 mean follow up time ranged from 3.2 to 15.8 years. Quality in Prognosis Studies (QUIPS) tool was used for risk-of-bias assessment (A working group comprising epidemiologists, statisticians, and clinicians developed this tool based on previous research and this tool can inform judgements of risk-of-bias in prognostic research). Meta-analyses were performed to estimate the average effect size of the prognostic factors.
The researchers identified six prognostic factors in the meta-analyses that were statistically significant and were associated with a 36% to 84% increase in the relative risk of recurrence of invasive disease after a DCIS diagnosis. These six factors included-
1) African American race (43% higher risk)
2) Premenopausal status (59% higher risk)
3) Detection by palpation (84% higher risk)
4) Positive margins (63% higher risk)
5) High histologic grade (36% higher risk)
6) High p16 expression (51% higher risk).
Further, the authors identified frequently occurring biases in studies on invasive recurrence after DCIS and the highest risk of bias was attributable to insufficient handling of confounders and poorly described study groups. They added that avoiding these common methodological pitfalls can improve future study designs.
It was concluded that this study results may help clinicians distinguish indolent from potentially aggressive DCIS and prevent overtreatment.
Predictors of an Invasive Breast Cancer Recurrence after DCIS: A Systematic Review and Meta-analyses. Visser LL, Groen EJ, van Leeuwen FE, et al. Cancer Epidemiol Biomarkers Prev. 2019;28:835-845
