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Presentations at the 2012 San Antonio Breast Cancer Symposium (SABCS; December 4–8, 2012) addressed the role of sentinel lymph node surgery, eribulin versus capecitabine for heavily pretreated breast cancer, development of a new cyclin-dependent kinase inhibitor, and chemotherapy for completely resected local recurrence. Key findings are summarized below; for more information, please visit the SABCS website.
Previous guidelines have suggested that axillary dissection should still be performed in those patients who present with positive axillary nodes before preoperative systemic therapy. Randomized trials designed to compare preoperative versus postoperative adjuvant therapy in axillary node–positive breast cancer patients have shown that as many as 40% of patients who receive preoperative therapy will have negative axilla at the time of axillary lymph node dissection (ALND). This finding indicates that preoperative chemotherapy could allow a substantial proportion of patients with axillary node–positive disease to avoid axillary dissection. Now, investigators have sought to determine if sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy permits identification of a group of patients in whom ALND can be averted (Abstract S2-1).
A total of 756 participants with axillary node–positive breast cancer received neoadjuvant chemotherapy followed by surgery; of these, 637 underwent both SLN surgery and ALND. SLN surgery correctly identified nodal status in 91% of patients, including 255 patients with node-negative disease and 326 with residual node positivity. The false-negative rate was 12.6%, but the success rate for identifying the SLN was highest when both blue-dye and radioactive colloid tracer were used (false-negative rate, 10.8%). Removing more sentinel nodes, placement of a surgical clip near the positive node, and nodal pathologic evidence of chemotherapeutic effectiveness all predicted greater success in identifying the SLN. These data require confirmation, but suggest that certain women with axillary node–positive disease can be spared ALND following neoadjuvant chemotherapy.
As is true with any anticancer drug's development, the goal is to administer the drug as early as possible during disease course. When eribulin was approved for metastatic breast cancer, the agent was determined to be active in patients with heavily pretreated metastatic disease: Those who received eribulin achieved a statistically significant survival benefit (2.5 months). Now, investigators report the results of an industry-sponsored, phase III trial (Abstract S6-6) of eribulin versus capecitabine in 1102 patients with locally advanced or metastatic disease who had received ≤3 prior chemotherapy regimens (≤2 for advanced disease). Progression-free survival (PFS), overall survival, and response rates were not statistically different between the two treatment groups; however, eribulin may have offered greater therapeutic benefit in certain prespecified subgroups (i.e., triple-negative, estrogen receptor–negative, or human epidermal growth factor receptor 2 [HER2]–negative). The overall results are disappointing in that earlier use of eribulin did not translate into an advantage for all patients with metastatic disease; however, further work should be focused on these specific patient groups.
Cyclin-dependent kinases (CDKs) regulate cell-cycle progression by interacting with specific cyclin proteins. PD0332991 is an oral, highly selective inhibitor of CDK 4/6 kinase that prevents tumor cell-cycle progression from G1 to S phase. Preclinical studies have shown that ER-positive breast cancer (luminal subtype) is particularly sensitive to PD0332991. In a two-part, phase II study (Abstract S1-6), patients with ER+ metastatic breast cancer were randomized to letrozole alone or with PD0332991 as first-line therapy. The first part of the study included only ER+ patients, while the second part enriched for patients having ER+ tumors with loss of p16 and/or amplification of CCND1 (markers of sensitivity to PD0332991). The study's first phase previously showed that PD332991 significantly improved PFS. Now, data from the second phase continue to show a statistically significant improvement in median PFS (7.5 months to 26.1 months) that favors the doublet over letrozole alone. Manageable neutropenia was the most common adverse event. Based on these encouraging results, a randomized, phase III trial of similar design is planned.
A troubling clinical dilemma arises when a patient who has previously received adjuvant systemic therapy develops a local recurrence that is completely resected. Clinicians recognize that such patients are at excess risk for systemic relapse, yet little data support using additional, nonendocrine, systemic therapy. Now, results of the Chemotherapy as Adjuvant for Locally Recurrent Breast Cancer (CALOR) trial provide guidance (Abstract S3-2). A total of 162 patients who developed first ipsilateral local and/or regional recurrences (in the absence of supraclavicular nodes or evidence of metastatic disease) that had been completely excised were randomized to 3 to 6 months of chemotherapy or no chemotherapy, with endocrine therapy or anti-HER2 therapy as appropriate. Radiation therapy was recommended for all patients. Most patients had developed ipsilateral recurrence in a conserved breast; one third had recurrence on the chest wall or in the mastectomy scar. Fewer than 10% of patients received anti-HER2 therapy, and >90% of patients eligible for endocrine therapy received some form of it. More than two thirds of chemotherapy patients received polychemotherapy. Five-year disease-free survival improved with the addition of chemotherapy (69% vs. 57%, P=0.045) and was most striking in the patients with ER-negative recurrences (67% vs. 35%, P=0.007). Overall survival also improved with the addition of chemotherapy. Although this study was substantially smaller than planned (original accrual goal, 974), another such trial is unlikely. As such, chemotherapy should be strongly considered in this clinical situation, particularly for patients with ER-negative recurrences.