biomarker predicts risk of invasive breast cancer years before tumor develops

[Lani]

Biomarkers Predict Risk For Invasive Breast Cancer Years Before The Tumor Develops [ScienceDaily]
ScienceDaily (Nov. 13, 2007) — A specific biological response to cellular stress may predict the likelihood of future tumor formation of the most common, non-invasive form of pre-malignant breast cancer— ductal carcinoma in situ, or DCIS.
This information could potentially be used in a clinical setting to determine which women should receive more or less aggressive therapy when initially diagnosed with DCIS, according to a study led by researchers from the University of California, San Francisco.
The research results are also significant because traditional tests available today are not strong enough to predict whether or not a woman will develop a future cancer after diagnosis with DCIS. By identifying this particular biological response in patients, physicians may now be able to predict subsequent tumor formation years before it actually occurs.
The study is the cover story of the November 13, 2007 issue of "Cancer Cell." It is a translational study that brings together an integrated team of basic and clinical scientists in an attempt to find molecular markers to aid women and their physicians in determining the best treatment option following a diagnosis of DCIS.
"We were very excited by the results," said senior author Thea Tlsty, PhD, professor of pathology and co-leader of the Cell Cycling and Signaling Program of the UCSF Comprehensive Cancer Center. "Until now, little has been known about the molecular pathways that may cause a differential risk in women diagnosed with this type of breast pre- malignancy."
DCIS is a type of breast cancer where cancer cells form inside the milk ducts of the breast but have not spread to surrounding breast tissue. DCIS accounts for nearly 25 percent of all breast cancer diagnoses, according to the American Cancer Society.
In the absence of this new information, the researchers said, women diagnosed with DCIS today are often offered a gamut of treatment options that extend from a full mastectomy to watchful waiting. A majority of women usually opt for a lumpectomy with or without additional treatments such as radiation, hormonal therapy or chemotherapy. However, since the majority of DCIS lesions are not associated with formation of subsequent invasive tumors, it is likely that many women diagnosed with DCIS are being over treated.
"Conversely, since some women still get subsequent invasive carcinomas following these therapies, we may be under-treating a group of women diagnosed with DCIS," said Tlsty. Approximately 12-15 percent of women diagnosed with DCIS develop a subsequent invasive tumor within 10 years after undergoing surgical lumpectomy.
As noted in the study, it is well recognized that normal cellular responses to stress are important barriers to cancer formation and therefore also provide researchers with molecular candidates to help identify lesions that will not progress to a malignancy. To determine if stress-associated biomarkers in this response could provide insight into the likelihood of subsequent tumor formation in DCIS, the researchers examined several biomarkers in biopsies of DCIS tissue both in isolation and in conjunction to determine their effects.
They found that the presence of high amounts of two biomarkers, p16 and COX-2, played a critical role in the biological response to cellular stress. In particular, they found that tumors with high p16 and/or high COX-2 in the absence of cell proliferation reflected correct stress activation and a protective response to cellular stress.
"This phenotype begins to identify women less likely to have a subsequent tumor event after a diagnosis of DCIS," said Tlsty. "It supports the hypothesis that the senescent program is a barrier to tumor growth."
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ABSTRACT: Abrogated Response to Cellular Stress Identifies DCIS Associated with Subsequent Tumor Events and Defines Basal-like Breast Tumors [Cancer Cell]
Approximately 15%-30% of women diagnosed with ductal carcinoma in situ (DCIS) develop a subsequent tumor event within 10 years after surgical lumpectomy. To date, little is known about the molecular pathways that confer this differential risk for developing subsequent disease. In this study, we demonstrate that expression of biomarkers indicative of an abrogated response to cellular stress predicts DCIS with worse outcome and is a defining characteristic of basal-like invasive tumors. Mechanistic studies identify the Rb pathway as a key regulator of this response. Conversely, biomarkers indicative of an intact response to cellular stress are strongly associated with a disease-free prognosis. Assessment of these biomarkers in DCIS begins to allow prediction of tumor formation years before it actually occurs.