Abstract
PurposeHormone receptor-positive (HR+) tumors have heterogeneous biology and present a challenge for determining optimal treatment. In the Neoadjuvant Breast Registry Symphony Trial (NBRST) patients were classified according to MammaPrint/BluePrint subtyping to provide insight into the response to neoadjuvant endocrine therapy (NET) or neoadjuvant chemotherapy (NCT).ObjectiveThe purpose of this predefined substudy was to compare MammaPrint/BluePrint with conventional ‘clinical’ immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) subtyping in ‘clinical luminal’ [HR+/human epidermal growth factor receptor 2-negative (HER2−)] breast cancer patients to predict treatment sensitivity.MethodsNBRST IHC/FISH HR+/HER2− breast cancer patients (n = 474) were classified into four molecular subgroups by MammaPrint/BluePrint subtyping: Luminal A, Luminal B, HER2, and Basal type. Pathological complete response (pCR) rates were compared with conventional IHC/FISH subtype.ResultsThe overall pCR rate for ‘clinical luminal’ patients to NCT was 11 %; however, 87 of these 474 patients were reclassified as Basal type by BluePrint, with a high pCR rate of 32 %. The MammaPrint index was highly associated with the likelihood of pCR (p < 0.001). Fifty-three patients with BluePrint Luminal tumors received NET with an aromatase inhibitor and 36 (68 %) had a clinical response.ConclusionsWith BluePrint subtyping, 18 % of clinical ‘luminal’ patients are classified in a different subgroup, compared with conventional assessment, and these patients have a significantly higher response rate to NCT compared with BluePrint Luminal patients. MammaPrint/BluePrint subtyping can help allocate effective treatment to appropriate patients. In addition, accurate identification of subtype biology is important in the interpretation of neoadjuvant treatment response since lack of pCR in luminal patients does not portend the worse prognosis associated with residual disease in Basal and HER2 subtypes.
Highlights
The overall Pathological complete response (pCR) rate for ‘clinical luminal’ patients to neoadjuvant chemotherapy (NCT) was 11 %; 87 of these 474 patients were reclassified as Basal type by BluePrint, with a high pCR rate of 32 %
Accurate identification of subtype biology is important in the interpretation of neoadjuvant treatment response since lack of pCR in luminal patients does not portend the worse prognosis associated with residual disease in Basal and HER2 subtypes
A total of 474 eligible patients with IHC/FISH HR?/ HER2- tumors were enrolled in the Neoadjuvant Breast Registry Symphony Trial (NBRST) study
Summary
The overall pCR rate for ‘clinical luminal’ patients to NCT was 11 %; 87 of these 474 patients were reclassified as Basal type by BluePrint, with a high pCR rate of 32 %. The Neoadjuvant Breast Registry Symphony Trial (NBRST) is a prospective, phase IV registry study where neoadjuvant chemotherapy (NCT) and neoadjuvant endocrine therapy (NET) regimen outcomes are evaluated, both as response to treatment at the time of surgery and longer term at 5 years.[1] Since tumors are classified by gene expression array with the molecular subtyping profile BluePrint as well as the MammaPrint prognostic profile, response to treatment according to conventional clinical versus molecular classification can be compared. Gallen Expert Consensus considers NET the preferred treatment for Luminal A-type postmenopausal patients.[2] Endocrine therapy can have an important role in the neoadjuvant setting where systemic treatment may be indicated for several months prior to surgery in postmenopausal women with large and/or technically inoperable tumors This treatment is intended to shrink the tumor so that in locally advanced disease surgery becomes possible, and in large operable breast cancers breast-conserving surgery can be performed.[3,4] large, prospective, randomized, neoadjuvant trials in HR? Both ER and PR status were determined by IHC and were considered positive if there was C1 % positive staining
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