Can Molecular Biomarkers Help Reduce the Overtreatment of DCIS?

Abstract

Ductal carcinoma in situ (DCIS), especially in the era of mammographic screening, is a commonly diagnosed breast tumor. Despite the low breast cancer mortality risk, management with breast conserving surgery (BCS) and radiotherapy (RT) is the prevailing treatment approach in order to reduce the risk of local recurrence (LR), including invasive LR, which carries a subsequent risk of breast cancer mortality. However, reliable and accurate individual risk prediction remains elusive and RT continues to be standardly recommended for most women with DCIS. Three molecular biomarkers have been studied to better estimate LR risk after BCS—Oncotype DX DCIS score, DCISionRT Decision Score and its associated Residual Risk subtypes, and Oncotype 21-gene Recurrence Score. All these molecular biomarkers represent important efforts towards improving predicted risk of LR after BCS. To prove clinical utility, these biomarkers require careful predictive modeling with calibration and external validation, and evidence of benefit to patients; on this front, further research is needed. Most trials do not incorporate molecular biomarkers in evaluating de-escalation of therapy for DCIS; however, one—the Prospective Evaluation of Breast-Conserving Surgery Alone in Low-Risk DCIS (ELISA) trial—incorporates the Oncotype DX DCIS score in defining a low-risk population and is an important next step in this line of research.

Tools to Guide Radiation Oncologists in the Management of DCIS

“…In addition, HER2 overexpression predicts a more effective response to RT for in situ LRs rather than for invasive ones [55,107,110].…”

Is it Time to Retire the Term of Low-Grade Ductal Carcinoma in Situ and Replace it With Ductal Neoplasia?

“…In addition, it can adversely affect cosmesis, quality of life, development of second cancer, and heart disease, not to mention the risk of financial toxicity for patients and their families. 55,56 Similarly, the use of endocrine therapy in the management of DCIS is inconsistent, which may be related to its lack of survival benefit and associated adverse effects 57 In an effort to use biomarkers to help de-escalate the treatment of DCIS, up to date, 3 molecular marker assays have been clinically evaluated in DCIS cases. [58][59][60][61][62] Oncotype DX DCIS Score Recognized as the first molecular expression assays evaluated for DCIS, Oncotype Dx is comprised of 12 of 21 genes of the Oncotype DX recurrence score.…”

“…Breast radiotherapy can be associated with significant effects such as fatigue, skin erythema and desquamation, breast pain, skin telangiectasia, ulceration, and hyperpigmentation. In addition, it can adversely affect cosmesis, quality of life, development of second cancer, and heart disease, not to mention the risk of financial toxicity for patients and their families 55,56 . Similarly, the use of endocrine therapy in the management of DCIS is inconsistent, which may be related to its lack of survival benefit and associated adverse effects 57 …”

The Coming of Age of Breast Radiotherapy

“…Purswani et al [4] reviewed not only multi-gene profiling but also the classical low-tech parameters (e.g., age and tumor sub-type) considered when attempting to determine the cases for which omission is a reasonable strategy. Meanwhile, Hahn et al [5] wondered whether or not molecular biomarkers (three were evaluated in their review) could prevent the over-treatment of intraductal carcinoma of the breast. The authors observed that, in contrast to the case of invasive disease, very few protocols have been designed to pursue this type of research with DCIS.…”