“The use of adjuvant tamoxifen should be considered for patients with DCIS,” Dr. D. Craig Allred from Washington University in St. Louis, Missouri and colleagues conclude in a report online April 2 in the Journal of Clinical Oncology.
Today, DCIS accounts for 20% to 30% of all breast cancers and lumpectomy and radiation are now standard of care. The NSABP B-24 study found a significant benefit with adjuvant tamoxifen after lumpectomy and radiation in DCIS. (Fisher et al. Lancet 1999;353:1993-2000)
But the B-24 protocol was initiated before it became widely known that the benefit of tamoxifen in treating invasive breast cancer is essentially restricted to ER-positive and/or progesterone receptor (PgR)-positive disease. Women in the B-24 protocol were enrolled without knowledge of hormone receptor status.
Dr. Allred and colleagues did the current analysis to evaluate, retrospectively, the relationship between receptor status and response to tamoxifen in 732 women from the B-24 study, “with the expectation that the results would be similar to those in invasive breast cancer.”
Indeed, only the ER-positive group seemed to benefit from adjuvant tamoxifen. Women with ER-positive DCIS treated with adjuvant tamoxifen (vs placebo) showed significant decreases in subsequent breast cancer at 10 years (hazard ratio 0.49; p<0.001) and during overall follow up lasting a median of 14.5 years (HR 0.60; p=0.003), which remained significant in multivariable analysis (overall HR 0.64; p=0.003).
“Results were similar, but less significant, when subsequent ipsilateral and contralateral, invasive and noninvasvie, breast cancers were considered separately,” the investigators say. No significant benefit was observed in ER-negative DCIS, “emphasizing that tamoxifen must bind to functional ER to exert its beneficial effect on pre-existing residual tumor cells,” they note.
Adjuvant tamoxifen in ER-positive DCIS “offers an additional therapeutic option for patients and physicians to consider,” Dr. Allred and colleagues conclude.
In a JCO podcast on the journal's web site, Dr. Michael Baum of University College London in the United Kingdom, who specializes in the research, diagnosis and treatment of breast cancer, notes that 80% of the DCIS in this study were screen detected. The increasing rate of detection of DCIS is “a penalty we pay for screening,” he says.
He further notes that, “As the increasing incidence of DCIS has not accompanied by a fall in the incidence of invasive cancer, than many of these cases have to be considered an overdiagnose. If that is the case, then maybe instead of looking for cases of DCIS that might or might not respond to tamoxifen we should be looking for cases using histological and molecular variables that might allow us to decide whether or not to offer any treatment in the first place. The ER-status doesn't seem to fit that bill,” Dr. Baum said, “as the overall recurrence-free survival is very similar (26% and 30%, respectively) at 14 years in the placebo control ER-negative and the ER-positive group.”
J Clin Oncol 2012.