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Being able to predict which women diagnosed with ductal carcinoma in situ (DCIS) are likely to develop subsequent invasive breast cancer could prevent a lot of unnecessary treatment, said researchers from the University of California San Francisco (UCSF). In a study published online in the Journal of the National Cancer Institute
, the investigators identified 3 biomarkers highly predictive of an increased likelihood of future DCIS or invasive disease.
Investigators analyzed medical records for 1162 women aged ≥40 years who underwent lumpectomy for DCIS between 1983 and 1994. They identified 324 who developed invasive breast cancer or a second DCIS lesion >6 months after initial treatment. The women had an 11.6% overall risk of developing another DCIS lesion in the next 8 years and an 11.1% risk of developing invasive breast cancer.
Using immunohistochemical staining on tissue samples from the original DCIS tumors for all 1162 women, they found that women whose tumors expressed high levels of p16, Ki67 antigen, and cyclooxygenase-2 (COX-2) had a 19.6% risk (95% confidence interval [CI], 18.0%-21.3%) of developing invasive disease in the 8 years after lumpectomy than women with tumors negative for these biomarkers, who had a 4.1% risk (95% CI, 3.4%- 5.0%). Women whose tumors were found during a physical examination were 17.8% more likely to develop invasive cancer than those whose tumors were identified using mammography in the next 8 years. The authors said these findings were statistically significant (P = .018). Approximately 28% of the women fell into the high-risk category for invasive cancer.
Factors associated with an increased risk of DCIS were not the same as those that conveyed an increased risk of invasive cancer. Women who had DCIS lesions with disease-free margins of ≥1 mm that were positive for estrogen receptor, HER2, and Ki67 or positive for p16, COX-2, and Ki67 had a 23.6% risk of developing a subsequent DCIS in the next 5 to 8 years (95% CI, 18.1%-34.0%).
If the results are validated, lead author Karla Kerlikowske, MD, said, “As many as 44% of patients with DCIS may not require any further treatment and can rely instead on surveillance.” She said the information could also be used to help quantify for women their risk of developing invasive cancer, which was previously grouped together with DCIS as any recurrence. Some women who receive a DCIS diagnosis undergo elective mastectomy, and women who know they have a lower risk of developing invasive breast cancer may forego the procedure.
Half the women in the study who later developed invasive breast cancer did not express the 3 biomarkers, nor had their DCIS been discovered through palpation of a lump. The researchers said this indicates a real need to determine other factors that contribute to disease progression from DCIS. In addition, the standard of care for DCIS has changed since these women were treated, and today women with DCIS typically receive adjuvant radiation and/or hormone therapy following lumpectomy. Adjuvant therapy reduces recurrence rates, and a study conducted today might not produce the same results.
Kerlikowske K, Molinaro AM, Gauthier ML, et al. Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. JNCI
. 2010. [Epub ahead of print]