US 2022/0044819 A1 · DIAGNOSTIC AND THERAPEUTIC METHODS FOR THE TREATMENT OF BREAST CANCER

Abstract

Provided herein, inter alia, are predictive diagnostic, pharmacodynamic, and therapeutic methods for the treatment of breast cancer. In embodiments, the methods and compositions are based, at least in part, on the discovery that the estradiol (E2)-induced score or estrogen receptor (ER) pathway activity score determined from a sample (e.g., a tissue sample, e.g., a tumor tissue sample, e.g., a FFPE, a FF, an archival, a fresh, or a frozen tumor tissue sample) from an individual can be used in methods of determining whether the individual having breast cancer is likely to respond to a treatment including an endocrine therapy, selecting a therapy for an individual having breast cancer; treating an individual having breast cancer; and monitoring therapeutic efficacy of an endocrine therapy, as well as related kits.

Claims25

Dependent claims

1-95. (canceled)

A method of identifying an individual having a breast cancer who may benefit from a treatment comprising an endocrine therapy, the method comprising determining an estrogen receptor (ER) pathway activity score from a sample from the individual;

wherein the ER pathway activity score is calculated by subtracting an E2-repressed score, determined from the average z-scored expression of at least 4 of the E2-repressed genes selected from the group consisting of BAMBI, BCAS1, CCNG2, DDIT4, EGLN3, FAM171B, GRM4, IL1R1, LIPH, NBEA, PNPLA7, PSCA, SEMA3E, SSPO, STON1, TGFB3, TP53INP1, and TP53INP2, from an E2-induced score, determined from the average z-scored expression of 23 of the E2-induced genes selected from the group consisting of AGR3, AMZ1, AREG, C5AR2, CELSR2, CT62, FKBP4, FMN1, GREB1, IGFBP4, NOS1AP, NXPH3, OLFM1, PGR, PPM1J, RAPGEFL1, RBM24, RERG, RET, SGK3, SLC9A3R1, TFF1, and ZNF703;
and
wherein an ER pathway activity score from the sample that is at or above a reference ER pathway activity score identifies the individual as one who may benefit from a treatment comprising an endocrine therapy.

A method for monitoring the response of an individual having a breast cancer to treatment with an endocrine therapy, the method comprising:

(a) determining a first ER pathway activity score from a sample from the individual at a first time point, wherein the first ER pathway activity score is calculated by subtracting an E2-repressed score, determined from the average z-scored expression of at least 4 of the E2-repressed genes selected from the group consisting of BAMBI, BCAS1, CCNG2, DDIT4, EGLN3, FAM171B, GRM4, IL1R1, LIPH, NBEA, PNPLA7, PSCA, SEMA3E, SSPO, STON1, TGFB3, TP53INP1, and TP53INP2, from an E2-induced score, determined from the average z-scored expression of 23 of the E2-induced genes selected from the group consisting of AGR3, AMZ1, AREG, C5AR2, CELSR2, CT62, FKBP4, FMN1, GREB1, IGFBP4, NOS1AP, NXPH3, OLFM1, PGR, PPM1J, RAPGEFL1, RBM24, RERG, RET, SGK3, SLC9A3R1, TFF1, and ZNF703;
(b) following step (a), determining a second ER pathway activity score, wherein the second ER pathway activity score is calculated by subtracting an E2-repressed score, determined from the average z-scored expression of at least 4 of the E2-repressed genes selected from the group consisting of BAMBI, BCAS1, CCNG2, DDIT4, EGLN3, FAM171B, GRM4, IL1R1, LIPH, NBEA, PNPLA7, PSCA, SEMA3E, SSPO, STON1, TGFB3, TP53INP1, and TP53INP2, from an E2-induced score, determined from the average z-scored expression of 23 of the E2-induced genes selected from the group consisting of AGR3, AMZ1, AREG, C5AR2, CELSR2, CT62, FKBP4, FMN1, GREB1, IGFBP4, NOS1AP, NXPH3, OLFM1, PGR, PPM1J, RAPGEFL1, RBM24, RERG, RET, SGK3, SLC9A3R1, TFF1, and ZNF703 from a sample from the individual at a second time point following administration of an endocrine therapy;
and
(c) comparing the first ER pathway activity score with the second ER pathway activity score, wherein a decrease in the second ER pathway activity score relative to the first ER pathway activity score is predictive of an individual who is likely to respond to treatment with an endocrine therapy.

1 more element

A method for monitoring the response of an individual having a breast cancer to treatment with an endocrine therapy, the method comprising:

(a) determining a first E2-induced score from a sample from the individual at a first time point wherein the first E2-induced score is determined from the average z-scored expression of all of the E2-induced genes selected from the group consisting of AGR3, AMZ1, AREG, C5AR2, CELSR2, CT62, FKBP4, FMN1, GREB1, IGFBP4, NOS1AP, NXPH3, OLFM1, PGR, PPM1J, RAPGEFL1, RBM24, RERG, RET, SGK3, SLC9A3R1, TFF1, and ZNF703;
(b) following step (a), determining a second E2-induced score from a sample from the individual at a second time point following administration of an endocrine therapy, wherein the second E2-induced score is determined from the average z-scored expression of all of the E2-induced genes selected from the group consisting of AGR3, AMZ1, AREG, C5AR2, CELSR2, CT62, FKBP4, FMN1, GREB1, IGFBP4, NOS1AP, NXPH3, OLFM1, PGR, PPM1J, RAPGEFL1, RBM24, RERG, RET, SGK3, SLC9A3R1, TFF1, and ZNF703;
and
(c) comparing the first E2-induced score with the second E2-induced score, wherein a decrease in the second E2-induced score relative to the first E2-induced score is predictive of an individual who is likely to respond to treatment with an endocrine therapy.

1 more element

Dependencies are inferred from the claim text.

Diagnostic and therapeutic methods for the treatment of breast cancer

Life of this patent

Diagnostic and therapeutic methods for the treatment of breast cancer

Life of this patent

Abstract

Claims25