Abstract S6-03: The prognosis of small HER2+ breast cancers: A meta-analysis of the randomized trastuzumab trials

Abstract

Background Trastuzumab (T) combined with chemotherapy improves survival of women with HER2-positive breast cancer. Dual therapy with T and other HER-2 targeted agents (lapatinib/pertuzumab) has demonstrated improved efficacy compared to T alone in advanced breast cancer, and is in clinical trials in early stage disease. We hypothesize that subgroups of patients with HER2-positive tumors and limited tumor burden (tumor size and no or few positive lymph nodes) have a favorable outcome and would not be candidates for dual therapy. This study will analyze the disease-free survival (DFS)and overall survival (OS) of patients with early stage breast cancer treated with chemotherapy and T in the seminal randomized studies (RCTs). Methods RCTs were identified by a Medline search from 2004-2013. Trial groups from five phase III RCTs agreed to provide data. TrialNumberEligibilityRegimenNSABP B312130T1-3; pN1, pN2a, or pN3a; M0ACx4 then Tx4 VSACx4 then THx4 then Hx40wkNCCTG N98313505T1-3; pN1-2; M0ACx4 then Tx12wk VS ACTx4 then Hx52wk VS ACx4 then Tx12wk then Hx40wkHERA5102T1-3; pN1-2; M0Any (neo)adjuvant regimen, then H q3wk x1yr VS H q3wk x 2yr VS observationFinHER232T1-4; N0-3; M0Vx3 or T*x3 then FECx3 VS Vx3 or T*x3 with Hx9wk then FECx3PACS043010(528 HER2+)T1-3; pN1-2; M0FE(100)Cx6 VSFE(100)Cx6 then Hx1yr VS T*E(75) x6 VS T*E(75) x6 then Hx1yrA, adriamycin; C, cyclophosphamide; T, paclitaxel; T*, docetaxel; H, trastuzumab; P, carboplatin; F, 5-fluorouracil; E, epirubicin; Treatment regimen also included 5 years of hormonal therapy for ER positive patients. The ER+/HER2+ and the ER-/HER2+ cohorts will be analyzed separately. Patients with tumors 3 cm or smaller (T1a, T1b, T1c and >2 cm- 3cm) and 0, 1, 2 and 3 positive lymph nodes will be included. Initially a log rank test will be used to determine if the survival results are different by study. If there is no difference across studies, Kaplan-Meier survival curves with confidence intervals will be estimated. If there is a difference between studies, individual Kaplan-Meier curves will be estimated and the mean of the curves will be estimated along with confidence intervals using the adjusted standard deviation. Estimates at 3, 5 and 8 years will be presented as well as estimates of the event rates within each subpopulation defined by tumor size, number of positive lymph nodes, and ER status. Survival endpoints of DFS, and OS as defined in the original studies will be analyzed. Results and Conclusion Data from the five trials will be analyzed and an abstract provided prior to the meeting. Subgroups of patients with a very favorable outcome when treated with adjuvant chemotherapy and T will be identified. Our survival estimates might serve as benchmarks for future trials evaluating therapy reduction. Our results will complement those of the Dana Farber single arm multicenter trial in patients with “low risk” HER2-positive disease (APT trial; NCT00542451), being submitted to SABCS 2013. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S6-03.

Small breast cancers: When and how to treat

“…Similarly, patients with small, HR-negative tumors have a favorable outcome when treated with standard adjuvant CT and trastuzumab (5-year DFS 84% and OS 95%). However only 12% of these tumors had size below 1 cm and a focused analysis on this subgroup has not been reported ( Table 2) [21].…”

Systemic therapy for early‐stage HER2‐positive breast cancers: Time for a less‐is‐more approach?

“…In contrast, the results of other studies have indicated that outcomes are more favorable, with low recurrence rates reported in patients with small HER2‐positive breast cancers. Although patients with these cancers were underrepresented in the pivotal adjuvant trials, a recent meta‐analysis of these trials has demonstrated favorable outcomes for patients with small HER2‐positive breast cancers who were treated with adjuvant trastuzumab‐based chemotherapy . The meta‐analysis further demonstrated that the addition of trastuzumab to chemotherapy improves outcomes in these patients compared with chemotherapy alone .…”

“…A recent meta‐analysis specifically addressed outcomes in patients with small HER2‐positive breast cancers who were treated with trastuzumab‐based chemotherapy in the pivotal adjuvant trials . The analysis included patients with cancers measuring ≤2 cm who were treated with trastuzumab and enrolled on the HERA, NCCTG, BCIRG, NSABP B31, PACS‐04, or FinHER trials.…”

“…Favorable outcomes were noted in adjuvant trials that included patients with lymph node‐negative breast cancers (Table ) and in the meta‐analysis of patients with cancers measuring ≤2 cm; thus, a key question is whether a subset of patients with HER2‐positive cancers can be treated with a less aggressive approach. Although this subset has yet to be defined, it may be reasonable to evaluate a less aggressive approach in patients with lymph node‐negative HER2‐positive cancers.…”