Use of Oncotype Dx® Testing Breast SSG meeting 10 th July 2015 Dr Rebecca Bowen

Prognostic and predictive markers used in breast cancer management Prognostic (recurrence risk) Axillary node status Histologic type/grade Tumour size Patient age Lymphatic/Vascular invasion ER/PR status HER2 status NPI/ Adjuvant Online/ NHS Predict Genomic assays: Endopredict Prosigna uPA PAI1 Oncotype DX ® Predictive (treatment benefit) ER/PR status HER2 neu status Oncotype DX ® test Predict treatment benefit Estimate the risk of disease recurrence

Summary 2004 Paik et al NEJM publication on validation of Recurrence Score April 2010: first conversation with NICE Two UK decision impact studies set up Private health insurance companies start to reimburse May 2011: NICE diagnostics assessment commenced September 2013: NICE recommendation (DG10) April 2015: NHS patients can access!

The Onco type DX ® Assay The only multi-gene assay incorporated into all major guidelines to predict adjuvant chemotherapy benefit in ER+, HER2- EBC Quantifies risk of recurrence as a continuous variable and predicts responsiveness to both tamoxifen and chemotherapy NCCN Guidelines ®1 >0.5cm, node negative, N1mi Predicts the risk of recurrence and may be used to identify patients likely to benefit from tamoxifen or chemotherapy ASCO ® Guidelines 2 Node negative Provides additional prognostic and/or predictive information to complement pathology assessment and to predict response to adjuvant chemotherapy ESMO 3 Node negative Provides not only prognostic but also predictive information regarding the utility of cytotoxic therapy in addition to endocrine therapy St Gallen Consensus 4 Node negative, node positive Recommended as an option for guidance of chemotherapy decisions in patients at intermediate risk* of distant recurrence NICE 5 Node negative 1.NCCN Practice Guidelines in Oncology. V Harris L, et al. J Clin Oncol Senkus E Ann Oncol Goldhirsch A, et al. Ann Oncol NICE Diagnostics Guidance DG by other decision making tools or protocols ASCO is a trademark of the American Society of Clinical Oncology. NCCN and NCCN Guidelines are trademarks of the National Comprehensive Cancer Network. The guidelines do not endorse products or therapies. *Intermediate risk of distant recurrence is defined as NPI score ≥3.4 or at intermediate risk

The Onco type DX ® assay process Genomic Health has processed >500,000 tests from >70 countries; >3,800 tests from the UK Results generation Billing 2-3 weeks Report delivery Secure online portal Extraction Quantitation gDNA detection Reverse transcription QPCR Order entry Online Specimen retrieval Specimen accessioning Request FedEx Materials return Order entry ShippingPathology Analytical laboratory Report fulfilment Material return Pathology review Histopath 7-10 days

Triple-neg Node-negative or with *1 to 3 positive nodes Newly diagnosed early stage invasive breast cancer Newly diagnosed early stage invasive breast cancer Metastatic or locally advanced breast cancer with 4+ positive nodes HER2-pos ER-pos, HER2-neg The patient is assessed as being at intermediate risk; the decision to prescribe chemotherapy remains unclear, so that information on the biological features of the cancer provided by the Oncotype DX ® assay is likely to help in a predicting the course of the disease *Use of the Oncotype DX ® breast cancer assay in the N+ setting validated for post-menopausal patients Accessed 14 Jan 2014HER2: Human Epidermal Growth Factor Receptor 2 NICE guidance DG Oestrogen receptor Clinical indicationNICE guidance Node-negative, ER-positive, HER2-negative Which patients may benefit from the Onco type DX ® Test?

Recurrence Score ® results and patient discussion prior to the Oncotype DX ® test Eligible: Intermediate risk NPI >3.4 ≤ 5.4 Low Benefit of CT on Adjuvant! or ≥3% on PREDICT RS <18: Chemotherapy not recommended. Endocrine alone RS 18-30: Treatment recommendation discussed prior to testing based on individual score RS >30: Chemotherapy recommended

Eligible Patient Summary All node negative, ER positive, HER2 negative: – Grade 1: > 70mm – Grade 2:> 20mm – Grade 3:Any size

Change in Recommendations – Choice Study Oncologists recommendation changed in 55 (42%) patients 43 chemotherapy to no chemotherapy 12 no chemotherapy to chemotherapy Oncologists recommended chemotherapy in 51% patients pre Oncotype DX and 28% post Oncotype DX Changes in recommendation were consistent with the Recurrence Score