San Antonio, TX—The following are 5 topics that you may have missed from the San Antonio Breast Cancer Symposium, which was held December 10-14, 2013:
A meta-analysis of individual patient data from 36 randomized controlled clinical trials of bisphosphonate therapy in women with early breast cancer showed a 17% reduction in the risk of breast cancer mortality in estrogen-deprived women, but no effect on this end point in premenopausal women. The Early Breast Cancer Trialists’ Collaborative Group conducted the meta-analysis, the findings of which were reported by Rob Coleman, MD, Academic Unit of Clinical Oncology, Weston Park Hospital, University of Sheffield, United Kingdom. The meta-analysis included data from 17,709 women, and the 17% reduction in the risk of breast cancer mortality found in estrogen-deprived women randomized to a bisphosphonate relative to placebo or to open control was highly significant (P = .004).
HER2-positive breast cancer appears to be an immunogenic cancer type, and trastuzumab’s activity in this cancer involves not only the direct killing of tumor cells, but also the relief of suppression of antitumor immunity. The evidence comes from the evaluation of lymphocytic infiltration of HER2-positive breast tumors. Some of these cancers were found to exhibit high levels of tumor-infiltrating lymphocytes that contain the immunosuppressive genes programmed death 1 and cytotoxic T-lymphocyte–associated protein 4. Women with breast tumors with a high number of tumor-infiltrating lymphocytes had better outcomes with trastuzumab (Herceptin) in a retrospective analysis of the FinHer trial, said Sherene Loi, MD, PhD, a medical oncologist and Head of the Translational Breast Cancer Genomics Laboratory at the Peter MacCallum Cancer Centre in Melbourne, Australia.
The nonsteroidal aromatase inhibitor anastrozole (Arimidex) may prevent breast cancer in women at significant risk of the disease. In the International Breast Cancer Intervention Study II, 3864 postmenopausal women at high risk of developing breast cancer based on family history were randomly assigned to placebo or to anastrozole for 5 years. At a median follow-up of 5 years, women assigned to anastrozole had a 53% reduction in incident breast cancer compared with women who received placebo, reported Jack Cuzick, PhD, Head of the Cancer Research Centre for Cancer Prevention and Director of the Wolfson Institute of Preventive Medicine, Queen Mary University, London.
Pathologic complete response (pCR) predicted “significantly better event-free survival [EFS] and overall survival [OS] compared with no pCR” in women with HER2-positive, hormone receptor-negative breast cancer in a trial known as NeoALTTO, said Martine Piccart-Gebhart, MD, PhD, Chair of the Breast International Group, Brussels, Belgium. As a result, pCR might be an appropriate end point for drug approval by the US Food and Drug Administration. In a 30-week landmark analysis, the 3-year EFS rate among patients who achieved a pCR was 86% compared with 72% for patients who did not have a pCR (P = .003). The 3-year OS rate was also significantly higher in patients who achieved pCR with neoadjuvant therapy versus patients wgo did not reach a pCR (94% vs. 87%, respectively; P = .005). In NeoALTTO, dual HER2 blockade with trastuzumab and lapatinib (Tykerb) was superior to either monotherapy with either drug in achieving pCR.
- An adaptive phase 2 trial design has yielded a drug, veliparib, for phase 3 testing in the neoadjuvant setting in women with triple-negative breast cancer. Veliparib, a poly ADP ribose polymerase inhibitor, advanced to phase 3 on the basis of a 52% pathologic response rate when combined with carboplatin (Paraplatin) and standard chemotherapy, or twice the pathologic response rate achieved in controls who were treated with standard neoadjuvant therapy. A total of 38 patients with triple-negative cancer were enrolled in this arm of the phase 2 study (1 of 7 experimental treatment arms to be evaluated to date) and were treated for 6 months. In an adaptive design, several drugs can be studied in small groups of patients, and during the trial patients with higher probabilities of response can be assigned to therapies that perform better in their subtype of disease, said Hope S. Rugo, MD, Professor of Medicine, and Director of Breast Oncology and Clinical Trials Education, University of California, San Francisco. On the basis of this trial, statisticians estimate a 92% Bayesian predictive probability that adding veliparib and carboplatin would be statistically superior to standard therapy for women with triple-negative breast cancer in a 300-patient randomized phase 3 clinical trial.