Abstract P5-13-01: Patterns of Breast Cancer Relapse According to Breast Cancer Subtypes in Lymph Node-Negative Breast Cancer — Results from International Breast Cancer Study Group Trials VIII and IX
Authors: Metzger O , Sun Z , Viale G , Regan MM , Crivellari D , Snyder R , Gelber RD , Coates AS , Goldhirsch A , Cardoso F. 
Published: April 2011

Abstract
Background: To explore the patterns of breast cancer (BC) relapse according to BC subtypes in a lower risk (lymph node (LN)-negative) population we classified pts from two trials according to a molecular classification using IHC surrogates. IBCSG Trial VIII randomized 1109 premenopausal pts with LN-negative BC to sequential treatment with six cycles of CMF followed by 18 months of goserelin, six courses of CMF alone, or 24 months of goserelin alone. The IBCSG Trial IX randomized 1669 postmenopausal pts with LN-negative BC to sequential treatment with 3 courses of CMF followed by tamoxifen for 57 months or tamoxifen alone for 5 years. Retrospective central pathology evaluation including ER, PgR, HER2 and Ki67 was used to define a molecular classification. Patients & Methods: Of the 2778 pts enrolled in both trials the present analysis includes 2033 (824 from trial VIII and 1209 from trial IX) who also had centrally-reviewed pathology data. The BC molecular subtypes were defined as following: Luminal-A (ER and/or PR-present, HER2-negative and Ki67&lt;14%); Luminal-B (ER and/or PR-present, HER2-negative and Ki67 ≥14%); HER2 (HER2-positive independent of ER and PgR status); basal (HER2-, ER-, and PR-negative). Time to the first recurrence in a specific site was calculated from randomization and evaluated using cumulative incidence analysis and competing-risks regression analysis. Wald tests were used to determine the interaction effect of treatment group and molecular subtypes.
Results: In the population analyzed (N = 2033), 25.9% had luminal-A (LA) tumors, 40.3% had luminal B (LB) tumors, 17.7% had HER2-positive tumors, and 16.0% had basal tumors. At 12.7 years median follow-up, a total of 699 (34.4%) pts had BC recurrence or non-BC events (secondary malignancy or death): LA = 152 (28.8%), LB = 291 (35.5%), HER2- positive = 134 (37.2%), and Basal = 122 (37.4%). Among 2033 pts, no significant differences were observed among the molecular subtypes for time to local recurrence (LA 6.1%, LB 6.7%, HER2 7.8%, basal 6.7%, p = 0.98), contralateral BC (LA 3.4%, LB 4.1%, HER2 2.5%, basal 4.9%; p = 0.36), and non-BC events (LA 12%, LB 10%, HER2 8.3%, basal 7.7%; p=0.39). Patients with LB disease had more bone recurrences (LB 5.5%, LA 2.5%, HER2 3.3%, basal 1.8%; p=0.004). The patterns over time of soft tissue nodes and visceral recurrence varied according to the adjuvant treatment received (interaction tests P&lt;0.001 and p=0.007, respectively). Among pts receiving chemotherapy (N = 1139), HER2-positive pts had more and earlier visceral recurrence (HER2 11%, Basal 8%, LB 8.5%, LA 3.1%; p=0.005). Among pts not receiving chemotherapy (N=859), basal and HER2-positive pts had more visceral recurrences than luminal pts (HER2 15.3%, Basal 15.0%, LB 4.2%, LA 4.0%; P&lt;0.001). Conclusion: In this large retrospective analysis we observed a higher incidence of bone recurrence among all LB tumors, while among those allocated chemotherapy LB tumors had a similar incidence of visceral recurrence when compared to basal tumors. Patterns of other DFS events were similar in all subtypes.
Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-13-01.