Background

Ideally classification by subtype predicts treatment response and overall outcome. BluePrint 80-gene functional molecular subtype is based on mRNA expression (as is intrinsic subtype) associated with intact translation to protein (unlike intrinsic subtype). BluePrint (BP) classifies patients into Luminal, HER2 or Basal-type. Presently subtype is approximated using conventional immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) ("conventional subtype") or assigned by gene expression profiling. The aim of the prospective NBRST study was to compare chemosensitivity as defined by pathological Complete Response (pCR), or endocrine sensitivity as defined by partial response (PR) using 80-gene functional subtype vs. conventional IHC/FISH subtyping. In this analyses we present the results of all IHC/FISH Hormone Receptor (HR) positive/Her2 negative patients.

Methods

The neo-adjuvant NBRST study enrolled over 1000 US patients between June 2011 and December 2014. Women aged 18–90 with histologically proven breast cancer, who were scheduled to start neo-adjuvant chemotherapy (NCT) or neo-adjuvant endocrine therapy (NET), and who provided written informed consent were included. Additional inclusion criteria were no excision biopsy or axillary dissection, no confirmed distant metastatic disease, and no prior therapy for breast cancer. Treatment was at the discretion of the physician adhering to NCCN approved or other peer-reviewed, established regimens. BluePrint in combination with MammaPrint classifies patients into four molecular subgroups: Luminal A, Luminal B, HER2 and Basal. pCR is defined as T0/isN0 and PR is according to RECIST and defined as at least a 30% decrease in the tumor bed.

Results

418 IHC/FISH HR+/Her2- T1-4, N0-3, patients were enrolled (median age 54, range 22-87).

MammaPrint and BluePrint (MP/BP) classified 28% as Luminal A, 54% as Luminal B, and 18% as Basal-type. The distribution of locally assessed ER% in BP Luminal tumors was 2% ER 0-10%; 3% ER 11-50%; and 95% ER>50% compared to 45% ER 0-10%; 28% ER 11-50%; and 27% ER >50% in BP Basal tumors. Tumors classified as BP Luminal 370 (89%) received NCT and the overall pCR rate was 9%. There was a significantly higher (p<0.0001) pCR rate of 26% in BP Basal tumors compared to the pCR rate in BP/MP Luminal A and B tumors (3% and 6%). 43 (10%) patients received neo-adjuvant ET and 72% had a PR.

Conclusions

Molecular subtyping using MammaPrint and BluePrint classified 1 out of 5 pathological luminal patients as BP Basal-type with a significant higher response rate to NCT compared to BP Luminal patients. BP Luminal patients have an excellent partial response rate to NET.

Citation Format: Pellicane JV, Whitworth P, Beitsch P, Baron P, Beatty J, Murray MK, Dul CL, Mislowsky AM, Nash CH, Richards PD, Lee LL, Stork-Sloots L, de Snoo F, Untch S, Gittleman M, Akbari S, Rotkis MC. Chemosensitivity and endocrine sensitivity predicted by MammaPrint and BluePrint in clinical luminal patients in the prospective NBRST study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-67.