Genomic tests predict response to therapy in breast cancer subtypes
New results from the ongoing I-SPY 2 trial showed that the MammaPrint and BluePrint genomic tests can help identify which new drugs or drug combinations are most effective for treating certain breast cancer subtypes, according to a presentation at EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics.
“Effective breast cancer treatment depends on recognizing the biology of the tumor,” Laura J. van’t Veer, PhD, leader of the breast oncology program at University of California, San Francisco, said in a press release. “MammaPrint and BluePrint are two tests that recognize disease that is at risk of early recurrence and the different molecular subtypes.”
The randomized, phase 2 I-SPY 2 trial is testing new drugs, alone or in combination with standard chemotherapy, among women with newly-diagnosed breast cancer and a high risk for early recurrence.
MammaPrint (Agendia), a 70-gene signature assay, is used to predict whether a patient with breast cancer is likely to experience early disease recurrence in the absence of chemotherapy.
Van’t Veer and colleagues analyzed 986 patients from I-SPY 2 who were classified by MammaPrint as “high risk” (MP1) or “ultra-high risk” (MP2) to determine whether those statuses were associated with tumor response to therapy, as well as whether any response might depend on hormone receptor status, HER2 status and treatment received.
Patients in the analysis were classified as MP1 (n = 503) or MP2 (n = 483).
Treatments included paclitaxel alone (or with trastuzumab [Herceptin, Genentech] for HER2-positive disease), or paclitaxel in combination with investigational agents, including veliparib (ABT-888, AbbVie)/carboplatin, neratinib (Nerlynx, Puma Biotechnology), MK-2206 (Merck), ganitumab (AMG 479, NantCell), ganetespib (Aldeyra Therapeutics), AMG 386 (Amgen), ado-trastuzumab emtansine (Kadcyla, Genentech)/pertuzumab (Perjeta, Genentech), and pembrolizumab (Keytruda, Merck).
Patients classified as MP2 were 2.62 times more likely to achieve pathologic complete response than MP1 patients, and 2.43 times more likely after adjustments for hormone receptor status, HER2 status and treatment received.
Further analysis showed that MP2 patients were more likely to achieve pathologic complete response if they were treated with veliparib/carboplatin, neratinib, ganitumab, ado-trastuzumab emtansine/pertuzumab or pembrolizumab in addition to paclitaxel or in combination with trastuzumab.
MP2 patients with hormone receptor-positive and HER2-positive breast cancer were 3.62 times more likely to achieve pathologic complete response than MP1 patients.
MP2 patients with hormone receptor-positive and HER2-negative disease were 3.2 times more likely to achieve pathologic complete response than MP1 patients. However, this trend did not persist among patients with hormone receptor-negative, HER2-postive cancers.
“The most basic message of this study is that a prognostic signature that predicts good outcome in patients with a low-risk signature when foregoing chemotherapy can also, when further stratified, be used to predict response in high-risk signature patients who receive chemotherapy or targeted therapies,” van’t Veer said in the press release. “The clinical implications will need to be further developed, but these data suggest that [MP1 and MP2] status might be a useful adjunct in predicting which patients are likely to respond to which drugs or combinations.”
BluePrint (Agendia), an 80-gene signature test, was used to classify 375 patients with hormone receptor-positive, HER2-negative disease from the I-SPY 2 trial by biological subtypes, including basal (n = 108) or luminal (n = 266).
Van’t Veer and colleagues assessed whether BluePrint subtype was associated with pathologic complete response to neoadjuvant chemotherapy and targeted therapy given before surgery. They also looked at OS by subtype and tumor response.
Patients with basal subtype cancers were more likely to achieve pathologic complete response than patients with luminal cancer regardless of which therapy they received (OR = 4.41; P < .0001).
Researchers also observed an association between the BluePrint subtypes and the MammaPrint MP1 and MP2 classifications. Results showed 77% of patients with basal disease also were MP2.
“These findings suggest that BluePrint can identify a subset of patients with [basal] tumors who are more likely to respond to neoadjuvant chemotherapy,” van’t Veer said in a press release. “The overlap between BluePrint basal subtype and MP2 class suggests that different predictive signatures may identify similar sets of patients who are most likely to respond to a particular investigational drug.” – by John DeRosier
Van’t Veer LJ, et al. Abstract 2. Presented at: EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics; Nov. 13-16, 2018; Dublin.
Van’t Veer LJ, et al. Abstract 3. Presented at: EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics; Nov. 13-16, 2018; Dublin.
Disclosures : Van’t Veer reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.