# Molecular markers of risk of subsequent invasive breast cancer in women wth ductal carcinoma in situ

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $1,225,240

## Abstract

ABSTRACT
Ductal carcinoma in situ (DCIS) is considered to be a non-obligate precursor of invasive breast
cancer (IBC). Use of screening mammography has led to a substantial increase in detection of
DCIS over the past 2-3 decades. About 5-14% of patients diagnosed with DCIS and treated with
breast-conserving therapy, with or without radiation, develop an ipsilateral IBC and 1-6% develop a
contralateral IBC over a period of 10 years. However, natural history studies have shown that, in
the absence of treatment, 14-53% of DCIS cases develop IBC if followed for up to ~30 years.
Treatment of DCIS is variable, and many DCIS patients are either under- or over-treated.
Elucidation of the molecular changes detectable in DCIS lesions that are associated with risk of IBC
development is critically needed, as this may help not only to reduce risk of development of IBC but
also to prevent overtreatment of patients with lower risk of IBC. In this regard, a multigene
expression assay, consisting of genes related to proliferation, as well as PR and GSTM1, was
recently shown to predict risk of subsequent ipsilateral IBC in women with DCIS. Similarly,
immunohistochemically-detected expression of p16, COX-2, and Ki67 has also been associated
with increased risk of IBC development. However, these findings require confirmation. Furthermore,
novel prognostic (and ultimately predictive) markers may emerge from assessment of gene
expression patterns on a global scale. In this regard, microRNAs (miRNAs), which are noncoding
RNAs that are master regulators of gene expression, are thought to contribute to the development
of invasive cancer. Against this background, our overarching goal is to facilitate early detection of
patients with DCIS at risk of IBC development. To this end, building upon our previous work, we
propose to use clinical data and archived formalin-fixed paraffin-embedded (FFPE) tissue from a
large, population-based multi-center cohort of 7,275 patients initially diagnosed with DCIS in
community-based health plans and followed for subsequent IBC development, to identify and then
validate miRNA expression changes associated with risk of subsequent IBC, to evaluate risk of IBC
in association with 2 previously identified sets of markers (Oncotype DX DCIS score; positivity for
p16, COX-2, and Ki67 protein expression), and to examine the association between clinical factors
and risk of subsequent IBC in the largest such study to date. Our molecular epidemiologic study,
which proposes to apply state-of-the art technologies to archived DCIS FFPE specimens for the
detection of molecular changes associated with risk of IBC development in a large, multi-center
population-based cohort of women initially diagnosed with DCIS, has the potential to lead to
approaches that will help to refine identification of women who need enhanced surveillance and
early aggressive treatment.

## Key facts

- **NIH application ID:** 9981666
- **Project number:** 5R01CA218429-05
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Olivier Loudig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,225,240
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981666

## Citation

> US National Institutes of Health, RePORTER application 9981666, Molecular markers of risk of subsequent invasive breast cancer in women wth ductal carcinoma in situ (5R01CA218429-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9981666. Licensed CC0.

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