Certain biomarkers identified risk for subsequent invasive cancer

Among patients with initial ductal carcinoma in situ lesions, expression of the biomarkers p16, Cox-2 and Ki67 positive, or the ability for lesions to be detected by palpation were the most important factors for predicting higher risk for subsequent invasive cancer.

Using the SEER program of North California, researchers examined data from 1,162 women diagnosed with DCIS and treated with lumpectomy alone between January 1983 and December 1994. They gathered information on 324 women who developed a subsequent breast tumor more than six months after initial treatment.

The risk for subsequent invasive cancer was higher among women whose initial DCIS was detected by palpation vs. mammography (HR=2.0; 95% CI, 1.3-2.9).

Women with lesions that were p16 positive, p16 and Ki67 positive or p16, Cox-2 and Ki67 positive were at increased risk (19.6%; 95% CI, 18.0-21.3) for subsequent cancer vs. women with initial lesions that were detected by mammography and were p16, Cox-2 and Ki67 triple negative (4.1%; 95% CI, 3.4-5.0).

Risk was also increased for women aged 40 to 49 years vs. women aged at least 70 years (HR=2.2; 95% CI, 1.4-3.4). Risk was elevated for initial lesions that were more than 10 mm, had positive or uncertain margins, were of high nuclear grade or had extensive necrosis.

Women with lesions that were ER negative, ERBB2 positive or Ki67 positive among individual markers, or ER negative and ERBB2 positive or ER negative and Ki67 positive among marker combinations were at increased risk.

In multivariable analysis, lesions that were triple positive or detected by palpation were associated with the development of invasive cancer; nuclear grade showed no link.

Eight-year risk was highest among women with disease-free margins at least 1 mm combined with ER negative, ERBB2 positive and Ki67 positive or p16 positive, COX-2 negative and Ki67 positive status (23.6%; 95% CI, 18.1-34.0).

“Overall, this is a thought-provoking study that addresses an important issue,” D. Craig Allred, MD, consulting pathologist, department of pathology and immunology, Washington University School of Medicine, St. Louis, wrote in an accompanying editorial.

“The threats of recurrent ductal carcinoma in situ or invasive breast cancer both elicit substantial and essentially identical efforts to prevent them,” Allred said.

Kerlikowske K. J Natl Cancer Inst. 2010;102:627-637.