Best Use of Genomic Assays Debated at Miami Session

Norman Wolmark, MD

Should genomic profiles be used routinely to determine which breast cancer patients receive adjuvant chemotherapy?

That question was the subject of a lively debate at the Miami Breast Cancer Conference in Florida, where the challenge of translating scientific advances into clinical practice was among the dominant themes. The conference was held March 9-12.

In the “Pro” Corner: The Power of the Gene Assay

The Oncotype DX® test, with its 21-gene recurrence score (RS) assay, has proved its value as a prognostic tool and should be used regularly to evaluate treatment options for breast cancer patients, argued Norman Wolmark, MD.

Wolmark, professor and chairman of the Department of Human Oncology at Allegheny General Hospital in Pittsburgh, Pennsylvania, said the test is an accurate and practical method of quantifying the likelihood of recurrence in early-stage, node-negative, estrogen receptor-positive breast cancer, and of predicting which patients will benefit from chemotherapy.

He said >120,000 patients have undergone the test since it was introduced 7 years ago.

The professor, who also chairs the National Surgical Adjuvant Breast and Bowel Project, said the assay delivers results superior to those derived from the standard algorithm, which considers tumor grade and size and the age of the patient. He also noted that it has made other evaluative methods such as immunohistochemistry “an anachronism.”

Notably, Wolmark said, the RS method has shed light on which patients will benefit from chemotherapy. “It appears the entire benefit of chemotherapy is restricted to the one-third of patients [defined as] high risk,” he said, although he noted more study is needed for patients who fall between the high- and low-risk categories.

As a result of the test’s accuracy, Wolmark said, some nations have mandated the test be administered to all appropriate patients. He cited one estimate that predicts $100 million in savings for the US healthcare system as patients avoid futile treatments.

“It’s remarkable to me that pathologists have not really embraced this assay,” Wolmark said. “This is prime time. We have certainly crossed the threshold.”

J. Michael Dixon, MD

In the “Con” Corner: Skepticism About Value in Individual Treatment Choices

The predictive conclusions of genomic signature testing represent another way of looking at established trends and generally are not helpful to individuals facing treatment decisions, contended J. Michael Dixon, MD, clinical director of the Breakthrough Research Unit at the Edinburgh Breast Unit in the United Kingdom. He said they should not be made part of the routine practice for all patients.

“In reality, what comes out is what you expect,” said Dixon, who also is a professor of Surgery and a consulting surgeon. “They measure what we already know.”

Dixon said there are 2 commonly used genomic profiles, MammaPrint® and Oncotype DX, and that both have disadvantages: MammaPrint uses only frozen tissue and does not account for the HER2 gene, while Oncotype DX may not add to information available through routine immunohistochemistry.

When Should Oncotype DX Be Used?

Genomic Health, Inc, which developed the Oncotype DX

assay, diagrams its place on the treatment timetable.

He said both tests measure proliferation, which can predict the benefits of chemotherapy. Current methods, however, also measure proliferation, Dixon said. In addition, he said, the results are meaningful for groups but not individuals. “It gives us a percentage, but actually the individual patient isn’t interested.”

Dixon also said, “The concern about all of the tests is that the confidence intervals for predicting outcome for an individual patient are wide. What patients want is much greater certainty about their individual outcome and how treatment can influence that outcome.”

“Molecular markers are on the right track, but they’re stuck on the goal line and they’ve not yet scored,” he told the conference audience.