Amulti-gene assay for the clinically useful sub-classification of ductal carcinoma in situ of the breast

Value proposition

About 55,000 breast cancer diagnoses per year in the United States will consist of ductal carcinoma in situ (DCIS) cases, equal to the combined incidence of thyroid, pancreas and bladder cancers in the nation’s women. Approximately 60% of these present as low/intermediate grade DCIS as assessed by biopsy, out of which only a third progress to invasive carcinoma and thereby require aggressive follow-up treatment. However, there is a paucity of reliable, reproducible biomarkers to distinguish these from the indolent cases. Consequently, the majority of DCIS cases currently receive unnecessary extensive surgery such as mastectomy, radiation and/or endocrine therapy in addition to local excision, which affects their quality of life and drastically increases health care costs. Thus, there is a pressing need to uncover molecular biomarkers that can identify women who can be spared the above harsh treatment regimen as opposed to those who require more aggressive therapy.


The inventors have developed a DNA copy number based molecular profile that can accurately distinguish between aggressive and indolent DCIS in low and intermediate grade cases of DCIS, which are most vulnerable to over-treatment. During the course of validating their original 8-gene signature in an independent cohort of DCIS lesions, the inventors were able to develop a multi-gene model for two platforms- qPCR and immunohistochemistry (IHC). It was discovered that a combination of a representative gene from each panel, namely CELSR1 and GRAP2, imparts the strongest differentiating power (p=0.00004) between progressing and non-progressing DCIS lesions. Assays evaluating the expression of either or both of these genes can become powerful adjunctive tests for determining the most appropriate next-steps for DCIS patients.


  • Saves patients and the medical system from unwarranted costs
  • Saves patients from unnecessary anxiety and severe side-effects
  • Available in both PCR and immunohistochemistry assay platforms, with the option of testing only one gene via each platform