ONCOTYPE CHANGES TREATMENT DECISIONS

January 21, 2010 — Use of a gene assay that provides prognostic information about the likelihood of distant disease recurrence in low-risk, estrogen-receptor (ER)-positive, node-negative breast cancer affects both physician and patient treatment decision making, according to a new study of 89 patients published online January 11 in the Journal of Clinical Oncology.

Results from the 21-gene recurrence-score assay (Oncotype DX, Genomic Health) led medical oncologists to change their treatment recommendations in 28 patients (31.5%); 24 (27%) patients also changed their treatment decision on the basis of test results.

The study is important because it demonstrates the clinical utility of a recurrence-score assay, according to an accompanying editorial by Joseph Sparano, MD, from Albert Einstein College of Medicine and Cancer Center in the Bronx, New York, and Lawrence J. Solin, MD, from Albert Einstein Medical Center in Philadelphia, Pennsylvania.

"There is compelling evidence regarding the clinical validity of these assays in providing prognostic information about distant disease recurrence," write the editorialists. However, "there is little information about their clinical utility."

Specifically, the editorialists ask: How does the test influence clinical decision making, and do patients benefit from a change in treatment decision?

The study provides answers to both questions, suggest the editorialists and the study authors.

With regard to patient benefit, anxiety and decisional conflict were both significantly lower after recurrence-score results, report the study authors, led by Shelly Lo, MD, from Loyola University Stritch School of Medicine in Maywood, Illinois.

With regard to clinical decision marking, the biggest change caused by the test results was conversion from a medical oncologist's pretest recommendation for chemotherapy plus hormone therapy to a posttest recommendation for hormone therapy alone in 20 patients (22%).

The pretest decisions were made on "standard prognostic features," according to the study authors.

Forgoing chemotherapy in these patients is not an easy decision, suggest the editorialists. "There is unequivocal scientific evidence that adjuvant chemotherapy reduces recurrence and mortality in early-stage breast cancer," they note.

However, as Dr. Lo and her coauthors point out, the likelihood of distant recurrence in this patient population who are treated with tamoxifen is only about 15% at 10 years.

Furthermore, given the toxicities of chemotherapy, "it is critical to match each patient with the appropriate therapy for their individual tumor to maximize benefit while minimizing potential side effects," she and her colleagues write.

The test used in the study, the 21-gene recurrence-score assay, has been validated to quantify the risk for distant recurrence in tamoxifen-treated patients with lymph-node-negative, ER-positive breast cancer and to predict the magnitude of chemotherapy benefit, say the study authors.

Controversy Over Gene Expression Assays

Two multiparameter gene expression assays — the Oncotype DX and the 70-gene assay MammaPrint (Agendia BV) — have been commercially available for early-stage breast cancer for about 5 years, note the editorialists.

Several others are also now commercially available. "Some evidence suggests that these assays provide comparable prognostic information," the editorialists write.

There has been controversy about whether or not these tests have been investigated enough for the benefits and harms of the products to be sufficiently established, as reported by Medscape Oncology.

So far, in clinical practice, the use of the multiparameter tests has been limited to making treatment decisions about adjuvant chemotherapy, note Drs. Sparano and Solin.

One of the reasons for the limitation, say the editorialists, is that there are no "clinicopathologic features" obtained from patients that are predictive of chemotherapy benefit, which is not the case for endocrine therapy (i.e., ER and progesterone status) and anti-HER2 therapy (i.e., HER2 status). Also, clinical practice guidelines recommend adjuvant chemotherapy for most patients with operable breast cancer, even those that are at low risk for recurrence, the editorialists add.

Study Design and Other Results

In the study, Dr. Lo and colleagues prospectively surveyed 17 medical oncologists at 1 community and 3 academic centers. Physicians provided their treatment recommendation and patients provided their treatment choice before and after the recurrence-score results.

The average age of the 89 patients was 55 years. Roughly two thirds had intermediate-grade tumors, and the mean tumor size was smaller than 2 cm.

Before the results of the recurrence-score assay were known, the medical oncologists recommended chemotherapy plus hormonal therapy to 42 patients (47%), hormone therapy alone to 46 patients (51.7%), and either one treatment or the other to 1 patient (1.1%).

After obtaining the results of the assay, medical oncologists recommended chemotherapy plus hormonal therapy to 23 patients (25.8%) and hormone therapy alone to 60 patients (67.4%).

Six cases (6.7%) were considered to be a matter of "equipoise" or uncertainty, and patients had equal options for the various treatments. It is "unclear" what the optimal treatment is for these patients, the researchers explain, noting that they all had recurrence scores that were neither high nor low, but instead were intermediate.

The difference between the mean recurrence score on the assay for a recommendation of chemotherapy plus hormonal therapy and for a recommendation of hormonal therapy alone was significant (29 vs 16; P < .0001).

Dr. Lo and colleagues also report that the posttest treatment recommendation from the oncologists was mostly consistent with the recurrence score.

Chemotherapy was recommended to all 9 patients (100%) with high-risk recurrence scores, to 11 patients (26.2%) with intermediate-risk scores, and to 3 patients (7.9%) with low-risk scores.

Hormone therapy alone was recommended to 33 patients (87%) with low-risk scores, 27 patients (64.3%) with intermediate-risk scores, and to 0 patients with high-risk scores.

Patients reported significantly less conflict about the decision for adjuvant treatment after learning their recurrence score. Patients' mean decisional conflict score before testing was 1.99; after testing it decreased to 1.69 (P < .001).

Patients also had significantly decreased situational anxiety immediately after learning the results of the recurrence-score assay. Mean scores for situational anxiety significantly decreased over time; they were 39.6 before testing, 36.0 immediately after testing, and 34.0 a year after testing (P = .007).

Dr. Lo reports receiving research funding from Genomic Health. Dr. Sparano and Dr. Solin have disclosed no relevant financial relationships.

J Clin Oncol. Published before print January 11, 2010. Abstract, Abstract