Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature

Pat W. Whitworth, Peter D. Beitsch, James V. Pellicane, Paul L. Baron, Laura A. Lee, Carrie L. Dul, Mary K. Murray, Mark A. Gittleman, Raye J. Budway, Rakhshanda Layeequr Rahman, Pond R. Kelemen, William C. Dooley, David T. Rock, Kenneth H. Cowan, Beth Ann Lesnikoski, Julie L. Barone, Andrew Y. Ashikari, Beth B. Dupree, Shiyu Wang, Andrea R. MenicucciErin B. Yoder, Christine Finn, Kate Corcoran, Lisa E. Blumencranz, William Audeh

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSEThe 80-gene molecular subtyping signature (80-GS) reclassifies a proportion of immunohistochemistry (IHC)-defined luminal breast cancers (estrogen receptor-positive [ER+], human epidermal growth factor receptor 2-negative [HER2-]) as Basal-Type. We report the association of 80-GS reclassification with neoadjuvant treatment response and 5-year outcome in patients with breast cancer.METHODSNeoadjuvant Breast Registry Symphony Trial (NBRST; NCT01479101) is an observational, prospective study that included 1,069 patients with early-stage breast cancer age 18-90 years who received neoadjuvant therapy. Pathologic complete response (pCR) and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed in 477 patients with IHC-defined ER+, HER2- tumors and in a reference group of 229 patients with IHC-defined triple-negative breast cancer (TNBC).RESULTS80-GS reclassified 15% of ER+, HER2- tumors (n = 73) as Basal-Type (ER+/Basal), which had similar pCR compared with TNBC/Basal tumors (34% v 38%; P =.52), and significantly higher pCR than ER+/Luminal A (2%; P <.001) and ER+/Luminal B (6%; P <.001) tumors. The 5-year DMFS (%, [95% CI]) was significantly lower for patients with ER+/Basal tumors (66% [52.6 to 77.3]), compared with those with ER+/Luminal A tumors (92.3% [85.2 to 96.1]) and ER+/Luminal B tumors (73.5% [44.5 to 79.3]). Importantly, patients with ER+/Basal or TNBC/Basal tumors that had a pCR exhibited significantly improved DMFS and OS compared with those with residual disease. By contrast, patients with ER+/Luminal B tumors had comparable 5-year DMFS and OS whether or not they achieved pCR.CONCLUSIONSignificant differences in chemosensitivity and 5-year outcome suggest patients with ER+/Basal molecular subtype may benefit from neoadjuvant regimens optimized for patients with TNBC/Basal tumors compared with patients with ER+/Luminal subtype. These data highlight the importance of identifying this subset of patients to improve treatment planning and long-term survival.

Original languageEnglish (US)
JournalJCO Precision Oncology
Volume6
Issue number1
DOIs
StatePublished - Apr 1 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients with Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature'. Together they form a unique fingerprint.

Cite this