NEW YORK (GenomeWeb) – A University of California, San Francisco-led research team found that Agendia's MammaPrint 70-gene panel can identify breast cancer patients with ultralow-risk of late recurrence, or patients who might benefit from less endocrine-based treatment than is currently recommended by the breast cancer oncology community.
"We have long suspected that there are tumors that have ultralow-risk, but until we could distinguish them from the rest, we could not act on it," Laura Esserman, corresponding author and surgeon and breast cancer oncologist at the UCSF Carol Franc Buck Breast Care Center, said in an email.
The MammaPrint panel has been previously used to differentiate between breast cancer patients with high or low recurrence risk up to five years after diagnosis. However, the study published today in JAMA Oncology expands the utility of the panel to identify recurrence risk up to 20 years after diagnosis.
"This is the first time that anybody ever looked into [low-risk patients with late recurrence] for such a long follow-up," Laura van't Veer, coauthor on the study and chief research officer at Agendia, said. She noted that most other panels in the space don't have data to support their utility to determine low risk recurrence on such a long time scale.
Van't Veer and her colleagues at Agendia had identified this group of ultralow-risk breast cancer patients in a 2014 study published in Breast Cancer Research and Treatment. However, the current study confirmed that this group could also have ultralow-risk for late recurrence.
The team began by recruiting samples from participants in the Stockholm tamoxifen trial, a randomized clinical trial that ran from 1976 to 1990 and followed 1,780 lymph node-negative, postmenopausal women. The researchers extracted RNA from 652 patients with 70-gene signature classification, based on immunohistochemical analysis. They noted that 313 patients received tamoxifen treatment, and 339 did not, but also stated that most patients (519) had received mastectomy and axillary dissection.
Then they performed Agendia's MammaPrint or the firm's 80-gene BluePrint panel on an Agilent oligonucleotide microarray platform to assess messenger RNA expression. Finally, they assigned tumor subtypes — luminal A, luminal B, ERBB2/HER2, basal, and normal-like — using the PAM50 classifier and performed analysis on SAS statistical software.
The investigators found that the MammaPrint panel scored 42 percent of patients as high risk and 58 percent as low risk. For low-risk patients, this gives an excellent breast cancer-specific survival at five years (greater than 95 percent), but noted that extended follow-up showed that patients' chance of recurrence, and therefore mortality, increased as more years passed. They determined that compared to patients with ultralow-risk tumors, patients with high and low risk assignments had a statistically significant increase in long-term risk of breast cancer-specific death, 4.73 (95 percent CI, 1.38-16.22) and 4.54 (95 percent, 1.40-14.80) respectively.
Only 98 (15 percent) patients were identified as ultralow-risk, but within that group, there were no breast cancer-specific deaths at 15 years among patients who received tamoxifen, and breast-cancer-specific survival was 97 percent at 20 years. Ultralow-risk patients who did not receive any systemic therapy had a 97 percent and 94 percent breast cancer-specific survival at 10 and 20 years, respectively.
The team concluded that the MammaPrint panel "reliably identifies women with minimal risk of death [from] cancer out to 20 years in the absence of any systemic therapy and negligible risk of death with two or more years of tamoxifen therapy alone."
"We know that about 20 to 25 percent of cancer might be classified as ultralow-risk," Esserman said. "This test suggests that, in a postmenopausal woman with node-negative disease, that this test would allow me to tell her not to worry about this, that her cancer will not kill her."
For Agendia, this confirms that their 70-gene panel can identify this ultralow-risk, late recurrence patient group, which is something that they have identified previously but had not confirmed with a randomized trial, van't Veer said. She added that "the finding of late recurrence, low-risk [tumors] will help position patients to further discuss their [treatment] options."
Esserman noted that while there is more harm that can be done than good by looking for ductal carcinoma in situ in ultralow-risk cancers early, identifying the precursors of ultralow-risk tumors is an important target to work toward. She added that the researchers are currently conducting a large-scale screening study, called the WISDOM study, that will help them determine who is at risk for what kind of tumor that will further this type of research.