# US 12,215,390 B2 · Integration of tumor characteristics with breast cancer index > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 12,215,390 B2 - Document ID: US12215390B2 - Status: Granted - Kind: B2 - Application number: 18/056,967 - Filed: 2022-11-18 - Published: 2023-03-16 - Granted: 2025-02-04 - Earliest claimed: 2015-11-13 - Assignees: Biotheranostics, Inc. - Applicants: Biotheranostics, Inc. - Inventors: Yi Zhang; Catherine A. Schnabel - Web page: https://patentgrep.com/patent/US12215390B2 ## CPC - C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575) - A61K 31/337: having four-membered rings, e.g. taxol - A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine - A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate - A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)} - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 35/00: Antineoplastic agents - 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 - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Methods of determining risk of recurrence of a breast cancer of a subject are provided. Also provided are methods of predicting responsiveness to a therapy of a breast cancer of a subject. Additionally, methods of recommending treatment for a subject that has breast cancer are provided. Further provided are methods of treating a subject that has breast cancer. Systems for performing described methods are also provided. ## Claims ### Claim 1 A method of treating breast cancer of a subject who is lymph node-positive, the method comprising (i) determining that the subject has an MGIN+ score above an MGIN+ score cut point by: assaying or having assayed a sample of breast cancer cells from the subject for the expression levels of BUB1B, CENPA, NEK2, RACGAP1 and RRM2; summing or having summed the expression levels of BUB1B, CENPA, NEK2, RACGAP1 and RRM2 as a single index into a subject's MGI index; determining or having determined one or more clinicopathological factor selected from tumor size and grade of the subject's breast cancer; calculating or having calculated the MGIN+ score of the subject by combining the subject's MGI index with the one or more clinicopathological factor of the subject using a multivariate Cox-proportional model; comparing or having compared the subject's MGIN+ score to the MGIN+ score cut point, wherein the MGIN+ score cut point has been pre-determined based on the MGIN+ scores calculated for a training set of samples containing breast cancer tissues from patients who had breast cancer recurrence and patients who did not have breast cancer recurrence; and (ii) treating the subject with an MGIN+ score above the MGIN+ cut point with chemotherapy or endocrine therapy. ### Claim 2 (depends on 1) The method of claim 1, wherein the subject has previously been treated for breast cancer with chemotherapy. ### Claim 3 (depends on 1) The method of claim 1, wherein the subject has previously been treated for breast cancer with five years of endocrine therapy. ### Claim 4 (depends on 3) The method of claim 3, wherein the previous endocrine therapy comprised treatment with tamoxifen or anastrozole. ### Claim 5 (depends on 1) The method of claim 1, wherein the subject is treated with (a) endocrine therapy, if the subject has previously been treated for breast cancer, or (b) paclitaxel with 5-fluorouracil, doxorubicin and cyclophosphamide, if the subject has not previously been treated for breast cancer. ### Claim 6 (depends on 5) The method of claim 5, wherein the endocrine therapy comprises tamoxifen or anastrozole. ### Claim 7 (depends on 1) The method of claim 1, wherein combining or having combined the subject's expression levels of BUB1B, CENPA, NEK2, RACGAP1 and RRM2 as a single index into the subject's MGI index uses or has used coefficients determined from a Cox proportional hazards regression, an accelerated failure time model, a parametric survival model, a logistic model, or a linear discriminant analysis. ### Claim 8 (depends on 7) The method of claim 7, wherein the coefficients are or have been determined from a Cox proportional hazards regression. ### Claim 9 (depends on 1) The method of claim 1, wherein the patients from the training set with MGIN+ scores below the cut point have minimal 5-year breast cancer recurrence. ### Claim 10 (depends on 9) The method of claim 9, wherein the recurrence is distant recurrence. ### Claim 11 (depends on 9) The method of claim 9, wherein the recurrence is local recurrence. ### Claim 12 (depends on 1) The method of claim 1, wherein the patients from the training set with MGIN+ scores below the cut point have minimal 10-year residual disease. ### Claim 13 (depends on 1) The method of claim 1, wherein 1 to 3 lymph nodes are positive. ### Claim 14 (depends on 1) The method of claim 1, wherein the subject's breast cancer is estrogen receptor positive. ### Claim 15 A method of treating breast cancer of a subject who is lymph node-positive, the method comprising (i) determining that the subject has an MGIN+ score above 7 by: assaying or having assayed a sample of breast cancer cells from the subject for the expression levels of BUB1B, CENPA, NEK2, RACGAP1 and RRM2; summing or having summed the expression levels of BUB1B, CENPA, NEK2, RACGAP1 and RRM2 as a single index into a subject's MGI index; determining or having determined one or more clinicopathological factor selected from tumor size and grade of the subject's breast cancer; calculating or having calculated the MGIN+ score of the subject by combining the subject's MGI index with the one or more clinicopathological factor of the subject using a multivariate Cox-proportional model; and (ii) treating the subject with an MGIN+ score above 7 with chemotherapy or endocrine therapy. ### Claim 16 (depends on 15) The method of claim 15, wherein the subject is treated with (a) endocrine therapy, if the subject has previously been treated for breast cancer, or (b) paclitaxel with 5-fluorouracil, doxorubicin and cyclophosphamide, if the subject has not previously been treated for breast cancer. ### Claim 17 (depends on 16) The method of claim 16, wherein the endocrine therapy comprises tamoxifen or anastrozole. ### Claim 18 A method of treating breast cancer of a subject who is lymph node-positive, the method comprising (i) determining that the subject has an MGIN+score above an MGIN+score cut point by: assaying or having assayed a sample of breast cancer cells from the subject for the expression levels of BUB1B, CENPA, NEK2, RACGAP1 and RRM2; summing or having summed the expression levels of BUB1B, CENPA, NEK2, RACGAP1 and RRM2 as a single index into a subject's MGI index; determining or having determined one or more clinicopathological factor selected from tumor size and grade of the subject's breast cancer; calculating or having calculated the MGIN+ score of the subject by combining the subject's MGI index with the one or more clinicopathological factor of the subject using a multivariate Cox-proportional model; comparing or having compared the subject's MGIN+ score to the MGIN+ score cut point, wherein the MGIN+ score cut point has been pre-determined based on the MGIN+ scores calculated for a training set of samples containing breast cancer tissues from patients who were responsive to endocrine therapy and patients who were not responsive to endocrine therapy; and (ii) treating the subject with an MGIN+ score above the MGIN+ cut point with endocrine therapy. ### Claim 19 (depends on 18) The method of claim 18, wherein the endocrine therapy comprises tamoxifen or anastrozole. ### Claim 20 (depends on 18) The method of claim 18, wherein the subject's breast cancer is estrogen receptor positive.