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Expert Analysis Highlights:
Biomarkers are the telltale signature of a cancer that can describe its characteristics, including the capability to grow back or spread to another organ. It is one of the most important areas of cancer research, and is becoming an important component of “personalized cancer medicine”.
The news report on this video describes a major study performed at the University of California at San Francisco Medical Center. Published in the Journal of the National Cancer Institute on May 5, 2010, these investigators performed a study of 1162 women who were diagnosed with Ductal carcinoma in situ (DCIS) and treated by lumpectomy alone between the years 1983-1994. They had long term follow up and standardized pathology review as well as biomarker studies on the pathology specimen. They identified combinations of biomarker expression, size of the tumor, and the surgical margins that were helpful in predicting the risk that a patient with DCIS treated by lumpectomy alone would face: lower risk for recurrence vs. higher risk for recurrence. This information, as it would apply to an individual patient circumstance, may be helpful in the future in counseling women about their options with regard to radiation therapy of the breast or having mastectomy with the option of reconstruction if their risk for recurrence is high. On the other hand, those patients for whom the risk is low might be spared these more aggressive treatments.
Below is the abstract of this study that was published in the Journal of the National Cancer Institute titled, “Biomarker Expression and Risk of Subsequent Tumors After Initial Ductal Carcinoma in situ Diagnosis”
BACKGROUND: Studies have failed to identify characteristics of women who have been diagnosed with ductal carcinoma in situ (DCIS) and have a high or low risk of subsequent invasive cancer. METHODS: We conducted a nested case-control study in a population-based cohort of 1162 women who were diagnosed with DCIS and treated by lumpectomy alone from 1983 to 1994. We collected clinical characteristics and information on subsequent tumors, defined as invasive breast cancer or DCIS diagnosed in the ipsilateral breast containing the initial DCIS lesion or at a regional or distant site greater than 6 months after initial treatment of DCIS (N = 324). We also conducted standardized pathology reviews and immunohistochemical staining for the estrogen receptor (ER), progesterone receptor, Ki67 antigen, p53, p16, epidermal growth factor receptor-2 (ERBB2, HER2/neu oncoprotein), and cyclooxygenase-2 (COX-2) on the initial paraffin-embedded DCIS tissue. Competing risk models were used to determine factors associated with risk of subsequent invasive cancer vs DCIS, and cumulative incidence survival functions were used to estimate 8-year risk. RESULTS: Factors associated with subsequent invasive cancer differed from those associated with subsequent DCIS. Eight-year risk of subsequent invasive cancer was statistically significantly (P = .018) higher for women with initial DCIS lesions that were detected by palpation or that were p16, COX-2, and Ki67 triple positive (p16(+)COX-2(+)Ki67(+)) (19.6%, 95% confidence interval [CI] = 18.0% to 21.3%) than for women with initial lesions that were detected by mammography and were p16, COX-2, and Ki67 triple negative (p16(-)COX-2(-)Ki67(-)) (4.1%, 95% CI = 3.4% to 5.0%). In a multivariable model, DCIS lesions that were p16(+)COX-2(+)Ki67(+) or those detected by palpation were statistically significantly associated with subsequent invasive cancer, but nuclear grade was not. Eight-year risk of subsequent DCIS was highest for women with DCIS lesions that had disease-free margins of 1 mm or greater combined with either ER(-)ERBB2(+)Ki67(+) or p16(+)COX-2(-)Ki67(+) status (23.6%, 95% CI = 18.1% to 34.0%). CONCLUSION: Biomarkers can identify which women who were initially diagnosed with DCIS are at high or low risk of subsequent invasive cancer, whereas histopathology information cannot.
Journal of the National Cancer Institute. 2010 May 5;102(9):627-37. Epub 2010 Apr 28. (Comment in: 2010 May 5;102(9):585-7.)
Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis.
Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington J, Sanchez H, Jimenez C, Stewart K, Chew K, Ljung BM, Tlsty TD.
University of California, San Francisco, CA 94121, USA.