Women diagnosed with localized breast cancer face difficult decisions with their doctors. What kind of neoadjuvant (before surgery) treatment to choose? Should chemotherapy follow surgery? Based on the subtype of breast cancer, should specific chemotherapy drugs be used?
Several molecular tests are designed to help answer these questions, and the choice of testing options is growing. Tests are geared towards different populations of patients, and some are more established than others. What follows is a brief description of which tests are used most often and which are just entering the clinic.
Only one test, Oncotype DX, is supported by clinical guidelines from the National Comprehensive Cancer Center Network (NCCN). Oncotype DX is only relevant for women with early-stage breast cancer that is estrogen receptor (ER)-positive, and is therefore of no use to women with ER-negative cancers. Some patients with early-stage ER+ cancers should get chemotherapy because their tumors are deemed to be at a high risk for recurrence. Others really do not need chemotherapy, and will do well on hormonal therapy alone.
Oncotype DX classifies tumors in terms of risk factors by analyzing the expression of 21 select genes in tumor biopsies. This helps to gauge the need for chemo- or radiotherapy after the tumor is removed by surgery. The test uses a ‘numerical recurrence score’ (1 to 100) that divides tumors into three categories: low, intermediate, or high risk of recurrence. Oncotype DX is covered by most insurance plans.
The competing MammaPrint test helps to estimate the risk of recurrence or distant metastases in early-stage breast cancer patients, whether their tumors are ER+ or ER-. Thus, it has broader applicability than Oncotype DX. MammaPrint is performed in patients who are younger than age 61 years and have stage I or II, lymph node-negative cancer, with a tumor size of less than 5 cm. It measures the expression of 70 genes in tumors—a lot more than Oncotype DX measures. MammaPrint classifies tumors as high- versus low risk of recurrence, and helps to decide if and what type of treatment is needed after surgery.
MammaPrint is not yet endorsed by NCCN, being newer than Oncotype DX, but it already has substantial insurance coverage. Because it is applicable for diverse types of breast cancer, MammaPrint may become more widely used once more evidence for its accuracy is available. The U.S. Food and Drug Administration (FDA) recently approved MammaPrint for testing of archival (paraffin-embedded) tissues, which may broaden its applicability as well.
Agendia, the maker of MammaPrint, is now promoting a new test, BluePrint, that reclassifies breast tumors based on what are called ‘functional’ subtypes. Agendia says BluePrint is both a diagnostic test that allows for a better definition of breast cancer subtype, and, based on this, a guide to the optimal choice of neoadjuvant treatment.
Agendia reports that BluePrint might help guide the choice of neoadjuvant therapy for HER2-positive cancers. Most HER2+ cancers that need neoadjuvant treatment are treated with chemotherapy and trastuzumab (Herceptin), the mainstay HER2-targeted drug. However, not all patients respond as well as hoped, and many do not achieve pCR (pathologic complete response—no signs of cancer), the aim of neoadjuvant treatment.
A large study followed the outcomes of neoadjuvant treatment in HER2+ cancers and their correlation with BluePrint test results. Agendia reported that BluePrint reclassified about 22% of HER2+ tumors from the initial diagnosis. BluePrint identified a subtype (‘luminal’) within these cancers that turned out to be resistant to neoadjuvant therapy with chemotherapy and Herceptin. However, this subtype has a better response when pertuzumab (Perjeta—a newer HER2-targeted drug) is added to the Herceptin.
These data show that BluePrint could identify which patients with HER2+ should receive Perjeta as part of their neoadjuvant treatment. The data also support coverage of Perjeta by health insurance agencies.