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 Menicucci, Erin B Yoder, Christine Finn, Kate Corcoran, Lisa E Blumencranz, William Audeh, NBRST Investigators Group, 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 Menicucci, Erin B Yoder, Christine Finn, Kate Corcoran, Lisa E Blumencranz, William Audeh, NBRST Investigators Group
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.
Conflict of interest statement
Pat W. WhitworthEmployment: Integra LifeSciencesLeadership: Integra LifeSciencesStock and Other Ownership Interests: Targeted Medical Education, Inc, Cerebrotech Medical Systems, Medneon, Integra LifeSciencesHonoraria: Puma BiotechnologyConsulting or Advisory Role: ImpediMed, Prelude Therapeutics, Becton DickinsonResearch Funding: Prelude Therapeutics, Agendia, MedneonTravel, Accommodations, Expenses: Targeted Medical Education, Inc Peter D. BeitschEmployment: InVitaeLeadership: Targeted Medical Education, IncStock and Other Ownership Interests: Targeted Medical Education, Inc, InVitaeResearch Funding: InVitaeExpert Testimony: Dune Medical Devices, ImpediMedUncompensated Relationships: Medneon James V. PellicaneStock and Other Ownership Interests: PreludeDxHonoraria: Agendia, PreludeDxSpeakers' Bureau: Agendia, PreludeDx Paul L. BaronHonoraria: Myriad GeneticsConsulting or Advisory Role: Myriad GeneticsSpeakers' Bureau: Myriad GeneticsTravel, Accommodations, Expenses: Myriad Genetics William C. DooleyLeadership: Shaga Medical, LLCStock and Other Ownership Interests: Shaga MedicalResearch Funding: Agendia, XoftPatents, Royalties, Other Intellectual Property: Patent pending: microendoscopy system Kenneth H. CowanStock and Other Ownership Interests: United Health GroupConsulting or Advisory Role: MerckResearch Funding: Merck Beth-Ann LesnikoskiEmployment: HCA HealthcareStock and Other Ownership Interests: HCA HealthcareResearch Funding: Agendia (Inst), Seattle Genetics (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/246359 Beth B. DupreeHonoraria: Medtronic Shiyu WangEmployment: AgendiaStock and Other Ownership Interests: Agendia Andrea R. MenicucciEmployment: Agendia Erin B. YoderEmployment: AgendiaStock and Other Ownership Interests: AgendiaTravel, Accommodations, Expenses: Agendia Kate CorcoranEmployment: Agendia Lisa E. BlumencranzEmployment: Agendia William AudehEmployment: AgendiaLeadership: AgendiaStock and Other Ownership Interests: AgendiaConsulting or Advisory Role: Celanese, Private HealthResearch Funding: AgendiaTravel, Accommodations, Expenses: AgendiaNo other potential conflicts of interest were reported.
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Source: PubMed