Biomarkers linked to DCIS outcomes

(14 January 2008: VIDYYA MEDICAL NEWS SERVICE) -- Ductal carcinoma in situ (DCIS), where abnormal cells are found in the lining of a breast duct, is usually treated with surgical lumpectomy, followed by radiation, chemotherapy, a combination of the two, or surveillance. Most women undergoing these treatments will not experience a recurrence, but in 15 to 30 percent of women, a new tumor will develop within 10 years, and about half of these will be invasive breast cancers. To help clinicians determine whether DCIS is likely or unlikely to follow this course, researchers at the University of California, San Francisco, and the Bay Area Breast Cancer Specialized Program of Research Excellence (SPORE) have identified biomarkers associated with invasiveness. Their results appear in the November 12, 2007, Cancer Cell.

Using lumpectomy samples from 70 women who were diagnosed with DCIS and then followed for more than 10 years (180 months), the researchers looked at several markers associated with stress-induced senescence or proliferation. They compared the profiles of these markers in women whose DCIS did not progress to those in women for whom the DCIS did progress.

The results showed that in samples containing proliferating cells identified using Ki67 proliferation marker, overexpression of stress-activated p16 and/or COX-2 proteins reflects abnormal response to cellular stress and predicts subsequent tumor events within the first decade after the initial DCIS diagnosis. Low expression of Ki67 (regardless of the p16 and COX-2 status) usually indicates favorable prognosis. Other findings include observation of post-transcriptional rather than transcriptional regulation of COX-2 expression in a subset of HER-2-positive tumors.

The authors conclude that when tissue shows stress activation and deregulation of p16 and Rb signaling, this "may represent a defining signature of basal-like carcinogenesis that can be assayed [before] the development of invasive disease," with opportunities for prevention years before an invasive tumor actually occurs.

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