Prediction of Benefit From Adjuvant Pertuzumab by 80-Gene Signature in the APHINITY (BIG 4-11) Trial
- Author(s)
- Krop, IE; Mittempergher, L; Paulson, JN; Andre, F; Bonnefoi, H; Loi, S; Loibl, S; Gelber, RD; Caballero, C; Bhaskaran, R; Dreezen, C; Menicucci, AR; Bernards, R; van 't Veer, LJ; Piccart, MJ; APHINITY Steering Committee and Investigators;
- Journal Title
- JCO Precision Oncology
- Publication Type
- Research article
- Abstract
- PURPOSE: At the primary analysis, the APHINITY trial reported a statistically significant but modest benefit of adding pertuzumab to standard adjuvant chemotherapy plus trastuzumab in patients with histologically confirmed human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer. This study evaluated whether the 80-gene molecular subtyping signature (80-GS) could identify patients within the APHINITY population who derive the most benefit from dual anti-HER2 therapy. METHODS: In a nested case-control study design of 1,023 patients (matched event to control ratio of 3:1), the 80-GS classified breast tumors into functional luminal type, HER2 type, or basal type. Additionally, 80-GS distinguished tumor subtypes that exhibited a single-dominant functional pathway versus tumors with multiple activated pathways. The primary end point was invasive disease-free survival (IDFS). Hazard ratios (HRs) were evaluated by Cox regression. After excluding patients without appropriate consent and those with missing data, 964 patients were included. RESULTS: The 80-GS classified 50% (n = 479) of tumors as luminal type, 28% (n = 275) as HER2 type, and 22% (n = 209) as basal type. Most luminal-type tumors (86%) displayed a single-activated pathway, whereas 49% of HER2-type and 42% of basal-type tumors were dual activated. There was no significant difference in IDFS among different conventional 80-GS subtypes (single- and dual-activated subtypes combined). However, basal single-subtype tumors were significantly more likely to have an IDFS event (hazard ratio, 1.69 [95% CI, 1.12 to 2.54]) compared with other subtypes. HER2 single-subtype tumors displayed a trend toward greater beneficial effect on the addition of pertuzumab (hazard ratio, 0.56 [95% CI, 0.27 to 1.16]) compared with all other subtypes. CONCLUSION: The 80-GS identified subgroups of histologically confirmed HER2-positive tumors with distinct biological characteristics. Basal single-subtype tumors exhibit an inferior prognosis compared with other subgroups and may be candidates for additional therapeutic strategies. Preliminary results suggest patients with HER2-positive, genomically HER2 single-subtype tumors may particularly benefit from added pertuzumab, which warrants further investigation.
- Publisher
- American Society of Clinical Oncology
- Keywords
- Humans; Female; Case-Control Studies; Trastuzumab/therapeutic use; *Antibodies, Monoclonal, Humanized/therapeutic use; *Breast Neoplasms/drug therapy/genetics/metabolism
- Department(s)
- Medical Oncology
- Publisher's Version
- https://doi.org/10.1200/po.22.00667
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-02-20 12:40:59
Last Modified: 2024-02-20 12:45:33