1. Home>
2. Specialties>
3. Oncology and Hematology>
4. Meeting Report

The 2011 San Antonio Breast Cancer Symposium

Highlights include adjuvant bisphosphonates, endocrine therapy, treatment of HER2-positive breast cancer, and genomic scores for predicting risk for recurrence of ductal carcinoma in situ.

Presentations at the 2011 San Antonio Breast Cancer Symposium (SABCS; December 6–10, 2011) encompassed bisphosphonates as adjuvant therapy, use of biological mechanisms to enhance endocrine therapy, treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and genomic assays for ductal carcinoma in situ (DCIS). Key findings are summarized below; for more information, readers are encouraged to visit the SABCS website.

Benefits of Bisphosphonates
Several reports focused on the role of bisphosphonates for lowering recurrence risk in patients with early breast cancer. The ABSCG-12 trial of adjuvant endocrine therapy (ovarian suppression plus tamoxifen or anastrozole) with or without zoledronic acid (ZA) was updated with long-term follow-up (Abstract S1-2). At initial publication of the study (JW Oncol Hematol Feb 11 2009), results showed that ZA provided no overall survival (OS) benefit but did confer disease-free survival (DFS) benefit in postmenopausal patients (probably because of their low estrogen levels). Now, at median follow-up of 84 months, DFS was improved in patients who received ZA (hazard ratio, 0.71; P=0.011) as was OS (HR, 0.63; P=0.049). The added benefit of ZA occurred regardless of primary tumor size, axillary nodal status, or whether patients received tamoxifen or anastrozole. The effect of ZA was most striking in women older than 40.

The ZO-FAST trial (Abstract S1-3) was designed to determine whether ZA has greater benefit for bone-mineral density (BMD) when given immediately versus after a delay (duration determined based on postbaseline bone health) in postmenopausal patients with early breast cancer. The initial report showed that immediate use of ZA had greater beneficial effects on BMD than did delayed use. Now, 5-year follow-up has confirmed these findings and also showed a 34% improvement in DFS with immediate ZA versus delayed ZA (absolute difference in risk for a DFS event, 3.6%). The greater benefit of immediate therapy was observed in patients with low estrogen levels resulting from ovarian suppression, in those who were older than 60, and in those who were naturally postmenopausal at study entry.

The NSABP B-34 trial (Abstract S2-3) involved oral clodronate rather than ZA in patients with early breast cancer, but findings were similar to those of the ABSCG-12 and ZO-FAST trials: Results showed no benefit for DFS or OS with clodronate in the overall study population, but benefit was seen in postmenopausal participants (risk for distant metastases was lowered by 20% to 39% in women 50 or older). Although results of other trials have been inconsistent, the body of evidence points to an anticancer effect from bisphosphonate therapy, leading clinicians to reconsider this class of agents as a component of adjuvant therapy.

Honing Endocrine Therapy
Our better understanding of downstream signaling pathways in hormone receptor–positive breast cancer has yielded new agents that are effective against hormone-resistant disease. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor that enhances the activity of preoperative endocrine therapy. The BOLERO-2 trial of exemestane plus everolimus or placebo involved postmenopausal patients with metastatic breast cancer whose disease had progressed on letrozole or anastrozole (N Engl J Med 2011 Dec 7; [e-pub ahead of print]). Now, updated results (Abstract S3-7) showed that median progression-free survival more than doubled with the addition of everolimus (3.2 months vs. 7.4 months by investigator assessment; 11.0 months vs. 4.1 months by independent radiologic review). All subgroups of patients benefited from everolimus; however, adverse events included stomatitis, rash, diarrhea, hyperglycemia, fatigue, and pnuemonitis. The clinical benefit of adding everolimus to exemestane seems clear, but the adverse events associated with this doublet move the experience of receiving endocrine therapy closer to that of chemotherapy.

A New Agent, Pertuzumab, Joins Trastuzumab
The number of options for treating HER2-positive breast cancer continues to grow, leveraged by elucidation of the underlying biology of tumor-cell receptors and downstream signaling pathways. Investigators presented the results of the CLEOPATRA study (Abstract S5-5), a phase III trial involvong 800 patients with HER2-positive, metastatic breast cancer who were randomized to receive docetaxel plus trastuzumab with or without pertuzumab (a monoclonal antibody that prevents HER2 from dimerizing with other HER subtypes, particularly the most potent signaling partner, HER3). A full report of these findings was recently published (N Engl J Med 2012; 366:109). The results are expected to lead to regulatory approval of pertuzumab in 2012.

Predictive Value of Genomic Assays for DCIS
In a biomarker validation study (Abstract S4-6), researchers reported that the Oncotype DX DCIS Score (calculated based on a 12-gene subset of the 21-gene Oncotype DX assay for invasive breast cancer) can predict risk for an ipsilateral breast event (either a new invasive breast cancer or a DCIS recurrence) in women who have undergone breast-conserving surgery. DCIS scores from 0 to 100 were generated and were classified as predictive of low (<39), intermediate (39–54), and high (55) risk for recurrence. The assay's predictive value was assessed in 327 participants in the prospective ECOG E5194 study. Rates of any ipsilateral breast event and of invasive breast cancer were directly related to DCIS risk scores. The Oncotype DX DCIS assay is now commercially available and could inform clinical decision making about the need for radiation therapy, additional surgery, or both treatments.

— William J. Gradishar, MD

Published in Journal Watch Oncology and Hematology January 24, 2012

Image Gallery