Genomic Classification of Patients With HER2+ Breast Cancer Identifies Diversity in Clinical Outcomes With HER2-Targeted Neoadjuvant Therapy
abstract
This abstract is available on the publisher's site.
Access this abstract nowPURPOSE
The prospective Neoadjuvant Breast Registry Symphony Trial compared the 80-gene molecular subtyping signature with clinical assessment by immunohistochemistry and/or fluorescence in situ hybridization in predicting pathologic complete response (pCR) and 5-year outcomes in patients with early-stage breast cancer.
METHODS
Standard-of-care neoadjuvant chemotherapy combined with trastuzumab or trastuzumab plus pertuzumab was given to patients with human epidermal growth factor receptor 2 (HER2)-positive tumors (n = 295). pCR was the primary end point, with secondary end points of distant metastasis-free survival and overall survival at 5 years.
RESULTS
Among clinically defined HER2-positive (cHER2) tumors, the 80-gene assay identified 29.5% (87 of 295) as Luminal-Type (cHER2/gLuminal), 14.9% (44 of 295) as Basal-Type (cHER2/gBasal), and 55.6% (164 of 295) as HER2-Type (cHER2/genomically classified as HER2 [gHER2]). Patients with cHER2/gHER2 tumors had a higher pCR rate (61.6%) compared with non-gHER2 tumors (26.7%; P < .001). Dual targeting for cHER2/gHER2 tumors yielded a higher pCR rate (75%) compared with those treated with single HER2-targeted therapy (54%; P = .006). For cHER2/gBasal tumors, the 42.9% pCR rate observed with dual targeting was not different from that with trastuzumab alone (46.4%; P = .830). Among those with cHER2/gBasal tumors, 5-year distant metastasis-free survival (68.6%; 95% CI, 49.1 to 81.9) was significantly worse than in patients with cHER2/gLuminal tumors (88.9%; 95% CI, 78.0 to 94.6) and cHER2/gHER2 tumors (87.4%; 95% CI, 80.2 to 92.2; P = .010), with similar corresponding overall survival differences.
CONCLUSION
The 80-gene assay identified meaningful genomic diversity in patients with cHER2 disease. Patients with cHER2/gHER2 tumors, who benefitted most from dual HER2-targeted therapy, accounted for approximately half of the cHER2 cohort. Genomically Luminal tumors had low pCR rates but good 5-year outcomes. cHER2/gBasal tumors derived no benefit from dual therapy and had significantly worse 5-year prognosis; these patients merit special consideration in future trials.
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Additional Info
Genomic Classification of HER2-Positive Patients With 80-Gene and 70-Gene Signatures Identifies Diversity in Clinical Outcomes With HER2-Targeted Neoadjuvant Therapy
JCO Precis Oncol 2022 Sep 01;6(2022)e2200197, PW Whitworth, PD Beitsch, MK Murray, PD Richards, A Mislowsky, CL Dul, JV Pellicane, PL Baron, RL Rahman, LA Lee, BB Dupree, PR Kelemen, AY Ashikari, RJ Budway, C Lopez-Penalver, W Dooley, S Wang, P Dauer, AR Menicucci, EB Yoder, C Finn, LE Blumencranz, W AudehFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.