# US 2022/0033912 A1 · Transcriptomic profiling for prognosis of breast cancer to identify subjects who may be spared adjuvant systemic therapy

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- Number: US 2022/0033912 A1
- Document ID: US20220033912A1
- Status: Published application
- Kind: A1
- Application number: 17/311,995
- Filed: 2019-12-06
- Published: 2022-02-03
- Earliest claimed: 2018-12-08
- Assignees: PFS Genomics, Inc.; Decipher Biosciences, Inc.
- Applicants: PFS Genomics Inc; Decipher Biosciences, Inc.
- Inventors: S. Laura Chang; Elai Davicioni; Felix Feng
- Web page: https://patentgrep.com/patent/US20220033912A1

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- C12Q 1/6816: characterised by the detection means (C12Q1/6804 takes precedence)
- G01N 33/575: for cancer
- G01N 33/57515: of the breast
- G16H 20/10: relating to drugs or medications, e.g. for ensuring correct administration to patients
- G16H 20/40: relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
- G16H 50/20: for computer-aided diagnosis, e.g. based on medical expert systems
- G16H 50/30: for calculating health indices; for individual health risk assessment
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/158: Expression markers
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- Y02A 90/10: Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation
- 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
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- G16H: HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Methods, systems, and kits for the diagnosis, prognosis, and treatment of breast cancer in a subject are disclosed. The invention also provides biomarkers and clinically useful classifiers for identifying subjects at low risk of breast cancer recurrence who may be spared from adjuvant chemotherapy and endocrine therapy. Further disclosed herein, in certain instances, are probe sets for use in detecting such biomarkers for determining the risk of breast cancer recurrence in a subject. Methods of treating breast cancer based on expression profiling to determine the risk of breast cancer recurrence are also provided.

## Claims

### Claim 1

A method of treating breast cancer in a subject, comprising:
a) obtaining or having obtained an expression level in a sample from a subject for a plurality of genes, wherein the plurality of genes are selected from Table 2;
b) determining that the subject is at low risk of cancer recurrence based on the expression level, or determining that the subject is not at low risk of cancer recurrence based on the expression level; and
c) administering adjuvant chemotherapy or endocrine therapy if the subject is not identified as being at low risk of cancer recurrence based on the expression level, and not administering adjuvant chemotherapy or endocrine therapy if the subject is identified as being at low risk of cancer recurrence based on the expression level.

### Claim 2 (depends on 1)

The method of claim 1, further comprising calculating an average genomic risk (AGR) score for the subject, wherein adjuvant chemotherapy or endocrine therapy is administered to the subject if the subject is not identified as being at low risk of cancer recurrence based on both the AGR score and the expression levels of the genes selected from Table 2 in the biological sample, and adjuvant chemotherapy or endocrine therapy is not administered to the subject if the subject is identified as being at low risk of cancer recurrence based on both the AGR score and the expression levels of the genes selected from Table 2 in the biological sample.

### Claim 3 (depends on 1)

The method of claim 1, wherein the biological sample is a biopsy or a tumor sample.

### Claim 4 (depends on 1)

The method of claim 1, wherein the subject is a human being.

### Claim 5 (depends on 1)

The method of claim 1, wherein the subject has estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2−) breast cancer and is post-menopausal.

### Claim 6 (depends on 1)

The method of claim 1, wherein the expression levels of all of the genes selected from Table 2 are measured in the biological sample.

### Claim 7 (depends on 1)

The method of claim 1, wherein the levels of expression of one or more of the genes selected from Table 2 are increased or reduced compared to a control.

### Claim 8 (depends on 1)

The method of claim 1, wherein said measuring the levels of expression comprises performing in situ hybridization, a PCR-based method, an array-based method, an immunohistochemical method, an RNA assay method, or an immunoassay method.

### Claim 9 (depends on 8)

The method of claim 8, wherein said measuring the levels of expression comprises using a reagent selected from the group consisting of a nucleic acid probe, one or more nucleic acid primers, and an antibody.

### Claim 10 (depends on 1)

The method of claim 1, wherein said measuring the level of expression comprises measuring the level of an RNA transcript.

### Claim 11 (depends on 1)

The method of claim 1, wherein the method is performed prior to treatment of the subject with the adjuvant chemotherapy or the endocrine therapy.

### Claim 12

A kit for determining a prognosis of a subject having breast cancer and whether or not to treat the subject with adjuvant chemotherapy and endocrine therapy, the kit comprising agents for measuring levels of expression of a plurality of genes selected from Table 2.

### Claim 13 (depends on 12)

The kit of claim 12, wherein the kit comprises agents for measuring the levels of expression of all of the genes listed in Table 2.

### Claim 14 (depends on 12)

The kit of claim 12, wherein said agents comprise reagents for performing in situ hybridization, a PCR-based method, an array-based method, an immunohistochemical method, an RNA assay method, or an immunoassay method.

### Claim 15 (depends on 12)

The kit of claim 12, wherein said agents comprise one or more of a microarray, a nucleic acid probe, a nucleic acid primer, or an antibody.

### Claim 16 (depends on 12)

The kit of claim 12, wherein the kit comprises at least one set of PCR primers capable of amplifying a nucleic acid comprising a sequence of a gene selected from Table 2 or its complement.

### Claim 17 (depends on 12)

The kit of claim 12, wherein the kit comprises at least one probe capable of hybridizing to a nucleic acid comprising a sequence of a gene selected from Table 2 or its complement.

### Claim 18 (depends on 12)

The kit of claim 12, further comprising information, in electronic or paper form, comprising instructions on how to determine the prognosis of a subject having breast cancer and whether or not to treat the subject with adjuvant chemotherapy and endocrine therapy.

### Claim 19 (depends on 12)

The kit of claim 12, further comprising one or more control reference samples.

### Claim 20

A probe set for determining a prognosis of a subject having breast cancer and whether or not to treat the subject with adjuvant chemotherapy and endocrine therapy, the probe set comprising a plurality of probes for detecting a plurality of target nucleic acids, wherein the plurality of target nucleic acids comprises one or more gene sequences, or complements thereof, of genes selected from Table 2.

### Claim 21 (depends on 20)

The probe set of claim 20, wherein the probe set comprises a plurality of probes for detecting a plurality of target nucleic acids comprising gene sequences, or complements thereof, of the genes selected from Table 2.

### Claim 22 (depends on 21)

The probe set of claim 21, wherein at least one probe is detectably labeled.

### Claim 23 (depends on 22)

A kit for determining a prognosis of a subject having breast cancer and whether or not to treat the subject with adjuvant chemotherapy and endocrine therapy, the kit comprising the probe set of claim 22.

### Claim 24 (depends on 22)

A system for determining a prognosis of a subject who has breast cancer and whether or not to treat the subject with adjuvant chemotherapy and endocrine therapy, the system comprising:
a) the probe set of claim 22; and
b) a computer model or algorithm for analyzing an expression level or expression profile of the plurality of target nucleic acids hybridized to the plurality of probes in a biological sample from the subject who has breast cancer and determining if the subject is at low risk of cancer recurrence based on the expression level or expression profile and can be spared treatment with adjuvant chemotherapy and endocrine therapy.

### Claim 25 (depends on 24)

A kit comprising the system of claim 24.

### Claim 26 (depends on 25)

The kit of claim 25, further comprising a computer model or algorithm for designating a treatment modality for the subject.

### Claim 27 (depends on 25)

The kit of claim 25, further comprising a computer model or algorithm for normalizing the expression level or expression profile of the plurality of target nucleic acids.