Expert Point of View: Eun-Sil Shelley Hwang, MD, MPH

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Eun-Sil Shelley Hwang, MD, MPH, of Duke University Medical Center, Durham, North Carolina, who discussed both papers on ductal carcinoma in situ at the ASCO Annual Meeting, noted that better risk stratification and treatments are substantially changing the outlook for DCIS. “We are getting close to the point where patients treated for DCIS have a local recurrence risk that is just as low as, and perhaps lower than, their risk for contralateral breast cancer,” she said.

The positive results of the RTOG trial, she suggested, may be due to several factors. “There was a lower recurrence rate in the excision-only group than had been predicted, but what drove the positive findings was the much lower rate in the radiation therapy group,” she said.

The low rate of recurrence—only 3% even without radiation therapy—might also have been influenced by the administration of tamoxifen in two-thirds of the women, and perhaps by the short follow-up, she suggested, emphasizing that further follow-up of these women is required.

“Although the reduction in recurrence is low, the baseline recurrence risk is also extremely low,” Dr. Hwang told The ASCO Post. “Would most women want to undergo 6 weeks of radiation to reduce their risk from 3% to below 1%? And there is still contralateral risk as well,” she added.

“I am also worried that the overall risk is very low—much lower than anticipated. We know that low-risk disease takes longer to recur. Longer follow-up may reveal that the benefit of radiation is really not significant in this low-risk group…. In the meantime, the goal is to be smarter about whom we give treatment to, not to give treatment to everyone with negligible risk,” she said.

Risk-stratification Tools

Commenting on the DCIS score, Dr. Hwang agreed with the investigators: “The DCIS score gives additional information above and beyond traditional pathologic variables,” she said.

She said the observed weak association between nuclear grade and recurrence answers some of the “often-heard criticism” that the DCIS score and Oncotype DX score “may just be surrogates—very expensive surrogates—for proliferative index or Ki-67.”

But while the DCIS score is “an interesting molecular tool,” Dr. Hwang said that other risk-stratification tools are in development, including one that combines Ki-67, Cox-2, and P16, and if validated, these should also be useful. Additionally, next-generation sequencing, further molecular characterization with epigenomics and proteomics, and better characterization of stromal factors should lead to even greater refinement of risk stratification in breast cancer.

“But none of this is important unless we can implement them in the treatment of patients,” she cautioned. “And in this increasingly resource-constrained environment, cost-effectiveness issues will also be very important to analyze as we go forward.” ■

Disclosure: Dr. Hwang has served as a consultant or advisor for Genomic Health and receives research funding from Merck.

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