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

Abstract

PURPOSE The 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. METHODS Neoadjuvant 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). RESULTS 80-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. CONCLUSION Significant 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.

Multigene profiles to guide the use of neoadjuvant chemotherapy for breast cancer: a Copenhagen Breast Cancer Genomics Study

“…Furthermore, other assays such as BluePrint and MammaPrint were investigated 23 , 24 with similar outcomes, but a poor concordance of only 59% comparing BluePrint and PAM50 was shown 25 . Several smaller studies have shown a significant association between the Recurrence Score (RS) and pCR following NACT 26 – 30 while a few have not 31 , 32 , and a significant association with pCR after NACT was shown for a high RS (OR 4.87, 95% CI 2.01, 1.82) in 898 ER-positive and HER2-negative breast cancer patients 10 .…”

Genomic Classification of HER2-Positive Patients With 80-Gene and 70-Gene Signatures Identifies Diversity in Clinical Outcomes With HER2-Targeted Neoadjuvant Therapy

“…Biologic diversity of HER2+ breast cancers has been described using BluePrint and other genomic assays such as PAM50, which consistently show a population of IHC/FISHdefined HER2+ patients with functionally activated Luminal or Basal pathways. 8,[23][24][25] Importantly, within this cHER2 NBRST cohort, BluePrint further classified 44.4% as either Luminal-Type or Basal-Type. BluePrint was performed on preoperative core biopsies, suggesting that this genomic diversity is not evident by IHC/FISH methods.…”

Transfer RNAs-derived small RNAs and their application potential in multiple diseases

“…Sex hormones and their receptors are critical in the development and progression of the breast and prostate cancers ( Hayes et al, 2022 ). BC progression can be promoted by sustained exposure of estrogen and at least 70% of BCs are identified as estrogen receptor (ER)-positive luminal type whose development and growth are dependent on the estrogen-activated ERα ( Whitworth et al, 2022 ). In prostate cancer, tumorigenesis is promoted by androgen through androgen receptor (AR)-mediated gene-expression ( Nanda et al, 2020 ).…”