Molecular markers predict risk for invasive breast cancer years before the tumor develops

A team of scientists from the University of California San Francisco has identified distinct molecular markers that predict whether or not a woman is likely to develop subsequent invasive cancer after initial diagnosis with a noninvasive form of early breast cancer.

The research, published by Cell Press in the November issue of Cancer Cell, provides critical information that can be used to determine whether a woman should receive more or less aggressive therapy.

Approximately 12-15% of women diagnosed with ductal carcinoma in situ (DCIS), a tumor limited to milk ducts, develop a subsequent invasive cancer event within the first decade after surgical lumpectomy. However, due to the absence of reliable predictors to identify those women that will develop future tumors formation, all women diagnosed with DCIS tend to be offered similar treatment options. “Identification of biomarkers that predict future tumor development would allow us to stratify a women's individual risk for subsequent invasive tumors and avoid over- and under- treatment,” says lead author Dr. Thea D. Tlsty and clinician, Dr. Karla Kerlokowske, both from the Comprehensive Cancer Center at the University of California San Francisco.

Dr. Tlsty, Gauthier and Berman hypothesized that cells capable of activating pathways linked to stress-induced cell death would not form subsequent tumors while cells that bypass stress signals would be more likely to eventually progress to tumor formation. The researchers evaluated molecular characteristics and their association with outcome in a group of women diagnosed with DCIS and found that expression of biomarkers indicative of a short-circuited response to cellular stress predicts DCIS with a worse outcome and is a defining characteristic of an aggressive phenotype called basal-like tumors. Conversely, a disease-free prognosis is associated with an intact response to cellular stress.

Mechanistic studies indicated that deregulation of the tumor suppressor Rb pathway is linked with the highly proliferative basal-like subtype of breast cancer and cancer recurrence. “The combination of stress-activation and deregulation of p16/Rb signaling may represent a defining signature of basal-like carcinogenesis that can be assayed far in advance to the development of invasive disease and present clinical opportunities for appropriate aggressive intervention,” concludes Dr. Tlsty.

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