29 September 2015
One of the most common questions asked by a newly diagnosed cancer patient is “Will I need chemotherapy?”. Almost everyone is aware of the toxicity related to chemotherapy, and the fact that it is a common component of cancer treatment. A recent study sheds some light on which patients can safely avoid chemotherapy.
We have known for many years that not all patients who receive chemotherapy will benefit from it – in some cases, less than 3% of patients benefit. We traditionally used measures such as tumor stage, tumor grade, and receptor status such as ER/ PR and Her2/neu. Since 2004, many of us have relied on the OncotypeDx test. This assay, which is performed on the tumor, analyzes 21 genes (of the cancer – different from genetic testing of the patient) that have to do with cell growth and proliferation. The score, which is reported as low, intermediate, or high, is used to help determine whether or not a patient will benefit from chemotherapy.
The initial studies leading to widespread use of the OncotypeDx test were retrospective. Many of the large national breast cancer trials had tissue saved from the original procedures. The OncotypeDx test was run on these tissue samples, and then was analyzed with respect to patient outcomes. Based on these studies, patients with low risk scores were advised not to undergo chemotherapy; chemotherapy targets rapidly dividing cells, and low-risk tumors simply will not respond. Conversely, patients with high risk scores were advised to undergo chemotherapy treatment. Based on these studies, we discovered that our traditional methods of determining who should receive chemotherapy were not very accurate.
A new study published in the New England Journal of Medicine is the report of the first prospective trial involving OncotypeDx testing. Dr. Joseph Sparano and colleagues reported on the Prospective Validation of a 21-Gene Expression Assay in Breast Cancer. In this study, patients with hormone-receptor positive, Her2/neu negative breast cancers, 1.5 – 5.0 cm in size, had OncotypeDx testing on their tumors. Patients with low-risk tumors received endocrine therapy (tamoxifen or aromatase inhibitors). Patients with high-risk tumors received chemotherapy. Patients with intermediate-risk tumors were randomized to either hormonal therapy or chemotherapy, as prior studies did not demonstrate a clear benefit from either class of treatment.
The current study reports on the low-risk group, which included 1626 women. At 5 years, fewer than 2% of patients experienced a local-regional (breast or lymph nodes) or distant / metastatic (spread to other areas of the body) recurrence.
The authors concluded that endocrine therapy is perfectly appropriate for patients with low-risk tumors, and chemotherapy would not add any significant benefit in terms of recurrence or overall survival. A criticism of the study was that follow up was only 5 years, but the authors note that the primary benefit of chemotherapy is in reducing recurrences within the first 5 years of treatment. Endocrine therapy is recommended for longer-term reduction in recurrence in these patients.
Dr. Clifford Hudis, of the Memorial Sloan Kettering Cancer Center in New York, wrote an accompanying editorial: Biology Before Anatomy in Early Breast Cancer – Precisely the Point. He noted that “this assay is the most rigorously tested option and provides proof of the principle that we can develop reproducible predictive results to select patients who should not receive chemotherapy. In that regard, it is one more step towards precision. There are more steps ahead.”