What need does the Oncotype DX® assay address?
In 2008, the National Cancer Institute estimated that approximately 200,919 new cases of breast cancer are expected to be diagnosed in the United States. Almost half of the new cases are lymph-node-negative (LN-), estrogen-receptor-positive (ER+) tumors.1 Approximately 17% (tumor size 0.1-1.0 cm) to 34% (tumor size 2.6-3.0 cm) of women with LN-, ER+ tumors are at risk of distant recurrence within 10 years with no adjuvant therapy. The landmark NSABP B-14 study indicated that tamoxifen can halve that recurrence rate to 15%.2 A later study conducted by Paik et al. found that in a group of 651 tamoxifen-treated patients, the proportion of patients without distant recurrence at 10 years increased just 4.4%, from 87.8% to 92.2%, with the addition of chemotherapy to the treatment regimen.3
For each patient, this benefit must be weighed against the risk of adverse events. Chemotherapy-related adverse events occur in almost all patients and more than 1 in 10 women experience a serious or life-threatening event.4 Between 1 in 100 to 1 in 500 women actually die from side effects related to the administration of chemotherapy. Late adverse effects of chemotherapy also occur, including development of second primary cancers in more than 1 in 20 women and cognitive dysfunction, or so-called “chemo-fog.” Other adverse effects include ovarian failure, cardio-toxicity, nausea and hair loss. As Paik et al. concluded, “the likelihood of 10-year distant recurrence in patients treated with tamoxifen alone is about 15%, at least 85% of patients would be over-treated with chemotherapy if it were offered to everyone.”2
Clinical guidelines exist (based on clinical markers such as tumor size, age of the patient and tumor histology) to guide the decision of who should undergo chemotherapy. Guidelines define most women with LN-, ER+ breast cancer as having higher risk of recurrence than ER-negative women, thus more than 60%–70% of LN-, ER+ women receive adjuvant chemotherapy, and at least 1 in 2 women that receive adjuvant chemotherapy experience early and late adverse events without a clear sub-group defined with predicted benefit.5
Large clinical trials, such as the landmark National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (B-14 and B-20), have demonstrated the benefit of tamoxifen and adjuvant chemotherapy in women who have LN-, ER+ breast cancer.2,3 Because the likelihood of distant recurrence in patients treated with tamoxifen alone after surgery exceeds 10% at 10 years, the results from these trials have supported a treatment trend toward use of adjuvant chemotherapy across this population.
A more reliable method of identifying those patients likely to receive benefit from chemotherapy could provide both better treatment outcomes and potentially save many from the adverse effects of chemotherapy.
Risks of Adjuvant Chemotherapy
Chemotherapy is associated with serious early and late adverse events (AEs).6 In the following Figure 1, Hassett and colleagues display the difference between hospital admission and emergency room visit rates among breast cancer patients with and without chemotherapy.7 Chemotherapy-related adverse events were more common among chemotherapy recipients (infections, neutropenia, thrombocytopenia, anemia, nausea, emesis, diarrhea, malnutrition and dehydration) whereas chemotherapy-unrelated adverse events (hip fractures, etc.) were not, after adjusting for age, co-morbidities, metastatic status and other factors. Approximately 51% of chemotherapy patients visited the ER or were admitted to the hospital within the first 6 months of treatment compared to 23% of women not receiving chemotherapy. Chemotherapy-related adverse events occur in almost all chemotherapy patients and more than 1 in 10 women experience a serious or life-threatening event.4
Figure 1. Hospital Admissions and Emergency Room Visits Among Breast Cancer Patients, Grouped by Chemotherapy Usage
From Hassett et al. 2005
When the absolute benefits of chemotherapy are small, the associated toxicities of chemotherapy may outweigh any potential benefit. Therefore, accurate and reliable information is needed to help physicians and their patients weigh the potential benefits and risks of adjuvant chemotherapy.