Abstract P6-05-07: Improving personalized management of primary breast cancer: Mammaprint® risk stratification and blueprint® molecular subtyping
Authors: Mikkilineni L , Austin LK , Limentani K , Jaslow RJ , Avery TP , Palazzo J , Cristofanilli M 
Published: May 2016

Abstract
Background:
Historically, breast cancer (BC) patients were offered cytotoxic or endocrine therapy based on factors such as tumor size, stage, and immunohistochemistry (IHC) markers for estrogen receptor (ER) and HER2-positivity. In 2010 the College of American Pathologists revised the breast cancer guidelines on endocrine therapy (ET) to include a lower threshold of ER positivity by immunohistochemistry, changing the definition from 10% to 1% [Hammond et al]. As a result, although a larger number of patients are offered ET, not all may benefit from this expanded definition of ER positivity if their disease is not truly estrogen driven. More recently, sensitive gene profiling assays, such as Blueprint®, can determine intrinsic molecular subtype which may be more sensitive in predicting which patients will benefit from ET. Additionally, Mammaprint® provides risk stratification which can aid in determining which patients could benefit from neoadjuvant therapy.
Methods
This is an observational analysis of 60 patients with stage I-IV BC. Tissue analysis for ER, PR and HER2 status were determined by IHC/FISH. mRNA expression profiles of 80 genes for Blueprint® (Agendia) analysis provided molecular subtyping: luminal, basal or her2. Moreover, Mammaprint® (Agendia) analysis of 70 genes subdivided patients into low risk or high risk providing further stratification for Luminal-type.
Results
By IHC staining, 48% of patients were ER+/HER2-, 10% were ER+/HER2+, 8.3% were ER-/HER2+, and the remaining patients (20%) were triple negative (TN) BC. By comparison, molecular profiling classified 21% as luminal A, 18% luminal B, 11.6% Her2 and 35% basal subtype. The 35 ER+ patients were heterogeneous by subtype: 13 were classified as molecular luminal A, 16 were luminal B, 4 were reclassified as HER2 and 2 were basal-like (one of whom had 40% ER positivity). Of the ER+ patients whose IHC quantitative staining was known, 29% with low positivity (less than 10%) were reclassified as basal subtype. Of the 5 patients who are ER+/HER2+, 2 were luminal B and 3 were of the HER2-subtype. Two patients who were TN were reclassified as luminal B, and an ER-/HER2+ was classified as a basal subtype. One patient with ER+/HER2- disease had evidence of both HER2 and luminal B subtype. Of the patients who received neo-adjuvant therapy, pCR was obtained in 33% of luminal, 60% of HER2 and 50% of basal-type patients.
Conclusions
BluePrint® and Mammaprint® Molecular profiling are useful diagnostic tools which further characterize tumors to predict risk of recurrence and response to treatment. About one third of ER+ patients with low positivity (less than 10%) were reclassified as basal subtype, suggesting that there is a proportion of patients who are exposed to the morbidity of hormonal therapy with little therapeutic benefit. Additionally, the test is predictive of pCR, with the highest rates in the basal and Her2 subtypes, thus enabling clinicians to predict and improve clinical outcomes through more personalized treatment decisions.
Citation Format: Mikkilineni L, Austin LK, Limentani K, Jaslow RJ, Avery TP, Palazzo J, Cristofanilli M. Improving personalized management of primary breast cancer: Mammaprint® risk stratification and blueprint® molecular subtyping. [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 P6-05-07.