Using Epigenetic Changes to Stratify DCIS Biopsies

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Investigator: Thea D. Tlsty, PhD
Sponsor: California Breast Cancer Research Program

Location(s): United States

Description

Ductal carcinoma in situ (DCIS) is known as a “pre-cancer”, also called “Stage 0” or premalignant, which means that cancer cells stay in the milk duct of the breast. Unfortunately, most women with DCIS feel they have cancer, since “carcinoma” is in the name and since they receive many of the same treatments as women with invasive breast cancer. Most women with DCIS do well, only 15% of them developing invasive breast cancer; unfortunately, these cancers often spread quickly. This means that most women diagnosed with DCIS get the same type of surgery (mastectomy or partial mastectomy, i.e. full or partial breast removal) or partial mastectomy followed by radiotherapy and/or hormone drugs as women with invasive breast cancer. Thus, 39,000 women are treated unnecessarily with radiation, hormonal therapy, and/or mastectomy in order to prevent an invasive cancer that may not, in fact, happen, causing unnecessary suffering and side effects in otherwise-healthy women and causing a healthcare burden.

Using this and other funding we plan to develop a rapid, inexpensive prognostic clinical test that will incorporate “epigenomic markers” (i.e., changes in gene expression or cellular phenotype by mechanisms other than DNA sequence alone) and provide individual risk information for as many women as possible diagnosed with DCIS. We will evaluate selected epigenetic markers in a retrospective cohort of women diagnosed with pure DCIS in the 1980-90’s, treated by lumpectomy alone. We published descriptions of this cohort, methods for histological staining, statistical analysis, epigenetic analysis, proper controls and validation (J Natl Cancer Inst. 2010 102:627–637). Our current biomarker panel predicts with a high probability future tumor formation for 45% of DCIS patients. The addition of a panel of epigenomic biomarkers would translate within 3 years into a clinical test that would provide a better individual probability assessment of subsequent tumor events for women diagnosed with DCIS.

Stratifying risk of future tumor formation for women diagnosed with DCIS is an urgent clinical need. Validated criteria are needed to help women decide whether to have adjuvant therapy after lumpectomy based on their risk of subsequent invasive cancer.