# US 12,180,551 B2 · Method of using biomarkers and clinical variables for predicting chemotherapy benefit > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,180,551 B2 - Document ID: US12180551B2 - Status: Granted - Kind: B2 - Application number: 17/966,689 - Filed: 2022-10-14 - Published: 2023-04-13 - Granted: 2024-12-31 - Earliest claimed: 2017-09-08 - Assignees: Myriad International GmbH - Applicants: Myriad Genetics, Inc. - Inventors: Alexander Gutin; Julia Reid; Ralf Kronenwett; Marsel Scheer - Web page: https://patentgrep.com/patent/US12180551B2 ## CPC - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - G16B 20/00: ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations - G16B 25/10: Gene or protein expression profiling; Expression-ratio estimation or normalisation - G16B 40/20: Supervised data analysis - G16H 20/10: relating to drugs or medications, e.g. for ensuring correct administration to patients - G16H 50/20: for computer-aided diagnosis, e.g. based on medical expert systems - G16H 70/60: relating to pathologies - C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism - C12Q 2600/118: Prognosis of disease development - C12Q 2600/158: Expression markers - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES - G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY - G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA ## Abstract Provided herein are methods for predicting chemotherapy benefit. The invention predicts chemotherapy benefit based on the expression analysis of biomarkers, e.g., RNA biomarker transcription analysis, taken from a tumor sample. The biomarker expression data can be combined with clinical variables, e.g., tumor size and nodal status, to generate a profile that predicts the benefit of including chemotherapy as a treatment decision. ## Claims ### Claim 1 A method for detecting a responder to chemotherapy comprising: (a) measuring RNA expression level values of four or more of the following 8 genes in a tumor sample from a patient suffering from or at risk of developing recurrent neoplastic disease: UBE2C, BIRC5, DHCR7, STC2, AZGP1, RBBP8, IL6ST and MGP; or (b) measuring the RNA expression levels of four or more of the following 8 genes in a tumor sample from the patient: UBE2C, RACGAP1, DHCR7, STC2, AZGP1, RBBP8, IL6ST and MGP, wherein a combined score generated by combining an expression score with a clinical values score is indicative of a prognosis for the patient, and wherein the expression score was generated by combining the expression level values for the genes of the mentioned set recited in (a) or the mentioned set recited in (b). ### Claim 2 (depends on 1) The method of claim 1, wherein the neoplastic disease is a cancer. ### Claim 3 (depends on 2) The method of claim 2, wherein the cancer is breast cancer. ### Claim 4 (depends on 3) The method of claim 3, wherein the breast cancer is an estrogen receptor-positive and HER2-negative breast cancer. ### Claim 5 (depends on 1) The method of claim 1, wherein the chemotherapy is a neoadjuvant therapy. ### Claim 6 (depends on 1) The method of claim 1, wherein the prognosis is correlated to one or more distant metastases. ### Claim 7 (depends on 1) The method of claim 1, wherein the chemotherapy is adjuvant chemotherapy. ### Claim 8 (depends on 1) The method of claim 1, wherein the chemotherapy includes an anthracyclin-based therapy. ### Claim 9 (depends on 1) The method of claim 1, wherein the chemotherapy is 5-fluorouracil, epirubicin, and cyclophosphamide (FEC). ### Claim 10 (depends on 1) The method of claim 1, wherein the RNA expression levels have at least in part not been normalized before the combination. ### Claim 11 (depends on 1) The method of claim 1, wherein the clinical values score was generated by processing information regarding nodal status of the patient, the tumor size, or a combination thereof. ### Claim 12 (depends on 11) The method of claim 11, wherein the patient is node positive. ### Claim 13 (depends on 1) The method of claim 1, wherein the expression level is measured by at least one of a PCR-based method, a microarray-based method, a hybridization-based method, or a sequencing and/or next generation sequencing approach. ### Claim 14 (depends on 1) The method of claim 1, wherein the measuring of expression levels is in a formalin-fixed paraffin-embedded tumor sample or in a fresh-frozen tumor sample. ### Claim 15 (depends on 1) The method of claim 1, wherein the expression level of the at least one marker gene is measured as a pattern of expression relative to at least one reference gene or to a computed average expression value. ### Claim 16 (depends on 1) The method of claim 1, wherein combining the expression score with the clinical values score comprises applying an algorithm to values representative of an expression level of a given gene, wherein the algorithm is a linear combination of the values representative of an expression level of a given gene or wherein a value for a representative of an expression level of a given gene is multiplied with a coefficient. ### Claim 17 (depends on 1) The method of claim 1, wherein one or more thresholds are determined for the combined score and wherein the thresholds are discriminated into high and low risk, high, intermediate and low risk, or more risk groups by comparing the combined score to the determined one or more thresholds. ### Claim 18 (depends on 1) The method of claim 1, wherein a high combined score indicates a benefit from a more aggressive therapy. ### Claim 19 (depends on 1) The method of claim 1, wherein the four or more genes comprises UBE2C, BIRC5, DHCR7, STC2, AZGP1, RBBP8, IL6ST and MGP. ### Claim 20 (depends on 1) The method of claim 1, wherein the four or more genes comprises UBE2C, RACGAP1, DHCR7, STC2, AZGP1, RBBP8, IL6ST and MGP.