In the United States, more than 200,000 women receive a breast cancer diagnosis annually. Early detection offers patients the best chance for a cure, but may also lead to treatment dilemmas in some patients. Oncology Net Guide (ONG) had the opportunity to interview Richard Bender, MD, FACP, chief medical officer of Agendia, about MammaPrint, a breast cancer recurrence assay that can help oncologists determine the metastatic potential of their early-stage breast cancer patients’ tumors.ONG: How does MammaPrint work and what is its clinical utility? Dr Bender:
The MammaPrint test is performed on a fresh tumor tissue sample, and measures the gene expression profile of the 70 genes that constitute the test. MammaPrint classifies tumors as either high risk or low risk for recurrence, and when used in conjunction with other risk factors, helps identify patients who will benefit from adjuvant therapy. Compared with standard risk-assessment factors, MammaPrint significantly reduces the number of patients traditionally classified as having a poor prognosis, while at the same time identifying those patients who may be at increased risk for recurrence despite their clinical pathological findings.Which patients with breast cancer benefit from MammaPrint testing? Or is screening a more appropriate word?
MammaPrint is not a screening device or service; rather, it is a gene expression profile. A breast cancer patient should meet the following criteria to be eligible:
What are advantages to using MammaPrint versus other types of molecular screening and how do physicians choose?
Stage 1 or stage 2 breast cancer
Invasive carcinoma (infi ltrating carcinoma)
Tumor size <5.0 cm
Lymph node negative
Estrogen receptor positive (ER+) or estrogen receptor negative(ER-)
MammaPrint is a true next-generation breast cancer recurrence assay. Developed and validated on untreated patient samples, it is equally prognostic for patients who are either ER+ or ER- and avoids therapy requirements assumed by other tests. Based on extensive clinical discussions about early-stage breast cancer treatment thresholds—who may safely forego adjuvant therapy versus who may benefit from more aggressive therapy—MammaPrint was designed to provide a binary “low-risk” or “high-risk” result, thereby ensuring every patient result is clinically relevant and useful. With MammaPrint, physicians and their patients have an FDA-cleared test which aides in therapeutic decision- making every time, compared with other assays which often provide an ambiguous “intermediate” result. MammaPrint’s added value is supported by these differentiators, which competing assays do not provide.The FDA has given four clearances to MammaPrint. What uses has the FDA cleared?
In February 2007, the FDA cleared MammaPrint as a prognostic tool for patients less than 61 years with stage 1 or stage 2 breast cancer, invasive carcinoma (infiltrating carcinoma), tumor size <5.0 cm, negative lymph nodes, and ER+ or ER- tumors. In June 2007, the FDA cleared the MammaPrint fresh tissue transport methodology with RNARetain®, allowing for room- temperature shipping. In July 2008, MammaPrint was cleared to be run on a new high-density microarray, and in December 2009, FDA clearance was expanded for use in women of all ages.How does using formalin-fixed, paraffin-embedded tissue (like OncotypeDX) affect results compared with using fresh or frozen tissue samples, like MammaPrint
The benefit of working with fresh tissue is that mRNA integrity is preserved. Using formalin-fixed, paraffin-embedded tissues, on the other hand, damages mRNA, leaving truncated pieces. Since genomic tests such as these rely on measuring mRNA expression levels, maintaining mRNA integrity is vital. The National Institutes of Health (NIH) Biorepository, moreover, recommends fresh tissue sampling. NIH has recently launched
the landmark I-SPY 2 trial in collaboration with the FDA, the National Cancer Institute (NCI), and a host of leading pharmaceutical and biotechnology companies. The use of MammaPrint is one of the key pivots for the study.Risk assessments are often performed using online questionnaires, such as Adjuvant! Online and the NCI’s Breast Cancer Risk Assessment Tool based on the Gail Model. Are these tests useful and do you have anyconcerns about them?
While such assessments are generally useful, attention should be paid to the fact that one criterion is often more heavily weighted at the expense of another. It is, therefore, crucial to understand how these tools were developed and use them correctly to help inform treatment decisions. For instance, MammaPrint is FDA-cleared to be used in conjunction with other clinical pathological criteria.Is insurance coverage a problem with MammaPrint?