Molecular Profiling Helps Determine Use of New Therapeutic Agents in Breast Cancer

Howard A. Burris, III, MD

For locally advanced breast cancer, molecular profiling may be an effective way to determine which patients respond better to certain therapies.

At the 9th Annual Northern New Jersey Breast Cancer Conference, which took place at John Theurer Cancer Center at Hackensack University Medical Center in February, Howard A. Burris, III, MD, chief medical officer and executive director of Drug Development at the Sarah Cannon Research Institute in Nashville, Tennessee, discussed a number of studies that examined pathological complete response (pCR) in patients with certain clinical characteristics.

A phase II study in which Burris was one of the authors, looked at the use of ixabepilone and cyclophosphamide as neoadjuvant therapy in HER2-negative breast cancer patients whose recurrence score (RS) was determined through Oncotype DX assessments. Of the 108 patients assessed with the Oncotype DX test, 0 patients out of 19 with a low RS <18 achieved pCR, and 0 patients out of 17 with an intermediate RS between 18 and 30 achieved pCR. However, pCR was achieved in 19 out of 72 patients (26%) with a high RS >31.

Paired baseline and posttreatment recurrence scores were also obtained. These showed that 13 of 40 tumors (33%) with a high RS at baseline had residual tumor or low or intermediate RS after neoadjuvant chemotherapy, while none of the tumors with low or intermediate RS had high-risk RS after neoadjuvant chemotherapy, suggesting that tumors maintain the same molecular characteristics.

“It fits along the adage that those tumors that are highly proliferating are more responsive to the chemotherapy,” Burris said. “Whether in fact the biologics would make a difference in that setting is something that needs to be explored in clinical trials.”

Burris reviewed the results of a number of high-profile trials that studied the effects of various therapies delivered in the adjuvant setting. One such trial, BOLERO-2, examined a PI3K/mTOR inhibitor called everolimus in a randomized, double-blind study involving more than 700 postmenopausal women from 195 sites worldwide. Each participant in the study had estrogen receptor—positive, human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer, whose disease had already progressed despite endocrine therapy with nonsteroidal aromatase inhibitors. Patients were randomized 2:1 to receive exemestane plus everolimus or exemestane and placebo. The addition of everolimus resulted in a median progression-free survival of 7.4 months compared with 3.2 months in the control arm.

“It’s the basis of [BOLERO-2] that will now lead to first-line trials in adjuvant studies to understand just how extensive the impact of a PI3K/mTOR inhibitor could be in the treatment of breast cancer,” Burris said.

Burris also discussed the NeoSphere study, a phase II study that looked at neoadjuvant pertuzumab and trastuzumab in breast cancer patients. The study showed a significantly higher pCR rate (63.2%) in patients who were ER- and progesterone receptor-negative who received trastuzumab and pertuzumab combined with docetaxel. The authors found excellent tolerability of these agents.

Burris said trials like this can help determine whether these new agents should be used in a primary, adjuvant, or neoadjuvant setting and the role of maintenance therapy for these patients. “These initial clinical trial results are just really the first peek in the door of how we should best use these promising agents,” Burris said.