TAKE-HOME POINTS■ The Oncotype DX is a 21-gene reverse transcriptasepolymerase chain reaction assay that can predict the risk of relapse and likelihood of response to chemotherapy for patients with early-stage breast cancer.
■ Physician-patient treatment discussions and decisions are significantly enhanced by the results of the assay.
■ Treatment decisions based on the assay are efficacious, safe, and potentially or actually cost-effective.
Breast cancer is a complex and heterogeneous disease at both the clinical and molecular levels. In breast oncology, defining risk and predicting response to therapy is an inexact science, at best. The Oncotype DX (Genomic Health, Inc; Redwood City, California), a 21-gene reverse transcriptase-polymerase chain reaction (RT-PCR) assay, is a validated tool that defines risk and predicts therapy response.1 Using a fixed, paraffin-embedded sample of breast-tumor tissue, the assay can predict risk of relapse and the likelihood of response to chemotherapy. Assay results are reported as a recurrence score (RS) of 1 to 100. Patients are stratified by score as low risk (RS <18), intermediate risk (RS 18-30), or high risk (RS ≥31). This knowledge can allow therapy to be tailored to the molecular biology of a breast tumor and represents a pivotal step that has the potential to minimize overtreatment of patients at low risk and avoid undertreatment of patients at high risk.
IMPROVED PROGNOSTICS AND
TAILORED TREATMENT
Breast cancer affects more than 200,000 women annually in the United States. Approximately 40,000 women will die from their disease.2 Estrogen receptor-positive (ER+) early-stage breast cancer (ESBC) accounts for approximately 50% of all breast cancer cases each year. Deciding which patients will benefit from hormone therapy and/or chemotherapy is traditionally based on such clinical parameters as patient age, tumor size, nodal involvement, histologic features, and hormone-receptor status. These criteria remain limited, and patients continue to be under- or overtreated at a considerable cost in patient morbidity and economic burden. The benefit of chemotherapy for patients with ER+ ESBC is difficult to predict. Some patients can achieve a cure with surgery and radiation therapy; others will have a relapse of disease despite therapy. The likelihood of disease recurrence 10 years after treatment with surgery and hormone therapy is approximately 15%. Therefore, if all patients with ER+ ESBC were offered chemotherapy, at least 85% of them would be overtreated.
The Oncotype DX assay allows for optimal and individualized treatment planning. Studies show that the assay outperforms using standard clinicopathologic features to predict risk and response to therapy. The assay report also provides expanded information, including quantitative ER, progesterone receptor (PR), and HER2 expression, which may permit further clarification of cases in which quantification by local laboratories is equivocal or nonconcordant with clinicopathologic features.
WHAT PRIMARY CARE PAs NEED TO KNOW
Patients with newly diagnosed breast cancer are often fearful of the potential need for chemotherapy and its attendant toxicity. Certain patients, such as those with ER-, PR-, and HER2-negative (referred to as triple negative) tumors or HER2+ breast cancer will require chemotherapy. But for those with ER+ ESBC, use of the 21-gene assay substantially reduces the number of patients for whom chemotherapy is recommended.
Postmarketing clinical research shows that treatment recommendations were influenced by the RS in 25% to 30% of patients with ER+/lymph node-negative (LN−) ESBC.3,4 Most often, this resulted in treatment sparing, or a change from chemotherapy with hormone therapy to hormone therapy alone, for those patients with a favorable genomic profile.
The assay results are reported in a manner that facilitates the physician-patient discussion of risk and options. Patients appreciate and understand the visual graphics of recurrence risk and chemotherapy benefit. Anecdotally, physicians and patients report that the RS increased their confidence in the appropriateness of the chosen treatment plan. Lo and colleagues reviewed 93 cases from one community practice and three academic practices.4 The most frequent change in treatment based on the RS was from chemotherapy to hormone therapy. The 15 participating medical oncologists indicated that the RS results increased their confidence in the treatment decisions made in 76% of cases. Ninety percent of the patients felt the assay influenced their overall confidence in the treatment decision.
The current health care crisis highlights the importance of integrating molecular markers in a cost-effective way. Although the assay is costly, extensive economic analyses demonstrated that RS-guided treatment decisions provide significant net savings compared with routine administration of chemotherapy.5,6 Identifying those patients who will not benefit from chemotherapy can potentially conserve the health care dollars absorbed by chemotherapy and its associated morbidity.