GENE SIGNATURES IN BREAST CANCER

Results of a 70-gene signature assay (70-GS) can influence recommendations about adjuvant treatment for patients with early breast cancer classified as intermediate risk by a 21-gene assay (21-GA), researchers say.

“The use of genomic assays in early stage ER-positive, HER2-negative breast cancer has become a standard practice for determining who should get adjuvant chemotherapy,” Dr. Hatem Soliman of Moffitt Cancer Center in Tampa, Florida, told Reuters Health.

“There are still some situations where the initial genomic test doesn't provide a clear answer. In these cases, the provider and patient may require additional information - almost like a second opinion - to guide them,” he said by email.

“However,” he added, “this is costly and should be done only in cases where the clinicopathologic information and initial genomic test are equivocal.”

To investigate, Dr. Soliman and colleagues enrolled 840 patients (mean age, 59; 87% white) with early-stage breast cancer and a 21-gene assay recurrence score of 18 to 30 (intermediate risk). All patients also were classified with the 70-GS, and results were given to physicians before adjuvant treatment was started.

As reported in JAMA Oncology, online October 26, on the basis of 21-GA result (before 70-GS assessment), 382 patients (45.5%) were recommended to receive adjuvant chemotherapy and 458 (54.5%) were recommended not to receive it.

The 70-GS reclassified the intermediate-risk patients as low-risk in 374 cases (44.5%) and high-risk in 466 cases (55.5%).

Receiving the 70-GS classifications significantly influenced adjuvant treatment assessment. Among the low-risk patients, 108 (28.9%) had chemotherapy removed from their treatment recommendation, whereas 171 (36.7%) high-risk patients had chemotherapy added.

The 70-GS results were significantly associated with the physician’s adjuvant treatment recommendation: 88% of high-risk patients were recommended to receive adjuvant chemotherapy, and 91% of low-risk patients were recommended not to receive it.

After receiving the 70-GS results, physicians reported having greater confidence in their treatment recommendation in 79% of cases.

Dr. Soliman said, “The information provided by the 70-GS assay had a significant clinical impact on adjuvant therapy recommendations. So in cases where there is initial uncertainty regarding the use of adjuvant chemotherapy, the 70-GS assay can aid in identifying patients with an excellent prognosis using endocrine therapy alone.”

Experts in cancer genetics weighed in on the findings in emails to Reuters Health.

Dr. Sofia Merajver, Scientific Director of the Breast Cancer Program and Director of the Breast and Ovarian Cancer Risk Evaluation Program at the UM Comprehensive Cancer Center in Ann Arbor said, “It is unknown whether survival would be improved by the change in therapy for those patients, and that is the gold standard.”

“Plus, the total expression of proteins is not sufficient to define the signaling processes inside cells, nor is a single static measure robust enough to predict long-term survival or time to recurrence, the outcome variables patients are truly interested in,” she observed.

“In essence, this paper just proves what doctors and patients are willing to do. The hope is that the value of adjusting the therapy was not overstated during this research, since so much (outcomes) data still needs to be collected.”

Dr. Dana Zakalik, Director of the Beaumont Cancer Genetics Program at Beaumont Hospital in Royal Oak, Michigan, commented, “The 70-gene assay seems to ‘simplify’ the genomic risk score into two categories (high vs. low) and addresses the uncertainty of the ‘intermediate’ risk score of the 21-gene assay, for which we still await data.”

“We need more data and validation to answer whether this is a better assay or whether it merely simplified it by just having a high versus a low group,” he added.

“There has not been a head-to-head comparison between the different assays, so we need more research and longer follow-up. Hopefully,” he said, “we will soon have data on the ‘intermediate’ group of the 21-gene assay, and perhaps that will resolve some questions.”

Dr. Glenn Gerhard, Chair of the Department of Medical Genetics and Molecular Biochemistry at Temple University in Philadelphia said, “Risk stratification for breast cancer for the significant number of patients classified as intermediate risk by the 21-GA assay is problematic; thus, other approaches are needed.”

“More comprehensive genomic testing using the 70-GS assay provides important additional information in a setting in which physicians use limited clinical data and other more traditional information to guide decision making,” he added.

Like Dr. Merajver, Dr. Gerhard noted that “recurrence and survival data were not collected as part of the study; thus, whether the changes in treatment decisions altered outcomes has not yet been determined.”

“The results were also restricted to patients with ER-positive, HER2-negative cancers, to those with a designated range of 21-GA results, and to a largely white population,” noted. “Thus, the extent of generalizability is not known.”

The study was sponsored by Agendia, a molecular diagnostics company that employs four of the authors.