Dynamic risk management for breast cancer with multi-factor genetic testing
Various embodiments disclosed relate to a method of preventive care for breast cancer. A method may include analyzing sequenced genetic data originating from the patient to determine whether the patient has a qualifying variant in any of genes BRCA1, BRCA2, PALB2, ATM, and CHEK2, wherein the qualifying variant can include one or more pathogenic variants, variants of uncertain significance (VUS), or combinations thereof. In an event that the patient does not have a qualifying variant in any of genes BRCA1, BRCA2, PALB2, ATM, and CHEK2, the method can include calculating a polygenic risk score (PRS) of the patient. If the patient has a PRS lower than a predetermined threshold, the method can include classifying the patient as low risk for breast cancer.
1 . A method of determining breast cancer risk level for a patient, the method comprising:
obtaining or having obtained a biological sample from the patient and performing or having performed sequencing on the biological sample to acquire sequenced genetic data for the patient, wherein the sequenced genetic data is accessible via a memory of a genomics server according to at least one file format selected from the group consisting of: a FASTQ format, a browser extensible data (BED) format, a binary alignment map format (BAM), a compressed reference oriented alignment map (CRAM) format, and a variant call format (VCF);
analyzing, by the genomics server, genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 represented in the sequenced genetic data;
determining, by the genomics server, that the patient does not have a qualifying variant in the analyzed genes BRCA1, BRCA2, PALB2, ATM, and CHEK2, wherein the qualifying variant includes at least one of a pathogenic variant, or a variant of uncertain significance (VUS), wherein a memory of the genomics server stores indications of variants included in the analyzed genes, and wherein a memory of the genomics server stores a location of the sequenced genetic data;
in response to determining that the patient does not have a qualifying variant in any of genes BRCA1, BRCA2, PALB2, ATM, and CHEK2, calculating, by the genomics server, a polygenic risk score (PRS) of the patient by analyzing the sequenced genetic data to determine a presence or absence of single nucleotide polymorphisms (SNPs) indicating breast cancer susceptibility that are located at predefined locations within a human genome; and
based on a comparison of the PRS to a predetermined threshold, classifying, by the genomics server, the patient as low risk for breast cancer.
2 . The method of claim 1 , wherein in an event that the patient has a qualifying variant in any of genes BRCA1, BRCA2, PALB2, ATM, and CHEK2, and the qualifying variant is one or more pathogenic variants, classifying the patient as high risk for breast cancer and referring the patient for preventive measures pertaining to breast cancer.
3 . The method of claim 2 , wherein the qualifying variant comprises a pathogenic single nucleotide variant or a pathogenic copy number variant.
4 . The method of claim 1 , wherein in an event that the patient has a qualifying variant in any of genes BRCA1, BRCA2, PALB2, ATM, and CHEK2, and the qualifying variant is a VUS variant but not a pathogenic variant, classifying the patient as average risk for breast cancer, thereby excluding the patient from being classified as low-risk.
5 . The method of claim 1 , wherein if the patient has a PRS above the predetermined threshold, classifying the patient as average risk for breast cancer, thereby excluding the patient from being classified as low-risk.
6 . The method of claim 1 , wherein the genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are analyzed with respect to qualifying variant criteria indicating at least one of one or more Polyphen values or one or more Sorting Intolerant From Tolerant (SIFT) values to classify a variant as a qualifying variant.
7 . The method of claim 1 , further comprising receiving health data for the patient indicating whether the patient is female, and if the patient is not female, foregoing performing the method for male patients.
8 . The method of claim 1 , further comprising receiving health data for the patient indicating whether the patient has a family history of breast cancer.
9 . The method of claim 1 wherein the PRS comprises an aggregate score based on at least three hundred loci.
10 . The method of claim 1 wherein the PRS comprises a weighted sum of values applied to each detected Single Nucleotide Polymorphism (SNP) within a set of predefined loci at the human genome.
11 . The method of determining breast cancer risk level for a patient, the method comprising:
receiving health data indicating whether a patient that is female has a family history of breast cancer;
obtaining or having obtained a biological sample from the patient;
performing or having performed sequencing on the biological sample to acquire sequenced genetic data for the patient, wherein the sequenced genetic data is accessible via a memory of a genomics server according to at least one file format selected from the group consisting of: a FASTQ format, a browser extensible data (BED) format, a binary alignment map format (BAM), a compressed reference oriented alignment map (CRAM) format, and a variant call format (VCF);
analyzing, by the genomics server, the sequenced genetic data to determine whether the patient has a qualifying variant in any of genes ATM or CHEK2, wherein qualifying variants are selected from the group consisting of Loss of Function (LoF) variants and coding variants, wherein a memory of the genomics server stores indications of variants included a number of analyzed genes, and wherein a memory of the genomics server stores a location of the sequenced genetic data; and
in an event that the patient has a qualifying variant in any of genes ATM or CHEK2:
calculating, by the genomics server, a Polygenic Risk Score (PRS) for the patient by analyzing the sequenced genetic data to determine a presence or absence of single nucleotide polymorphisms (SNPs) indicating breast cancer susceptibility that are located at predefined locations within a human genome; and
if the patient has a PRS higher than a first threshold, referring the patient for preventive measures pertaining to breast cancer.
12 . The method of claim 11 , wherein the qualifying variants comprise Loss of Function (LoF) and coding variants.
13 . The method of claim 11 , wherein the PRS comprises an aggregate score based on at least three hundred loci.
14 . The method of claim 11 , wherein the PRS comprises a weighted sum of values applied to each detected Single Nucleotide Polymorphism (SNP) within a set of predefined loci at the human genome.
15 . The method of claim 11 , wherein the first threshold is a median score for a population that the patient belongs to.
16 . The method of claim 11 , wherein the health data indicates the family history of breast cancer via a predefined code.
17 . The method of claim 11 , further comprising, prior to analyzing the sequenced genetic data to determine whether the patient has a qualifying variant in any of genes ATM or CHEK2,
analyzing the sequenced genetic data to determine whether the patient has a qualifying variant in any of genes BRCA1, BRCA2, or PALB2 wherein qualifying variants are selected from the group consisting of Loss of Function (LoF) variants and coding variants; and
in an event that the patient has a qualifying variant in any of genes BRCA1, BRCA2, or PALB2, referring the patient for preventive measures pertaining to breast cancer.
18 . The method of claim 11 , further comprising, prior to analyzing the sequenced genetic data to determine whether the patient has a qualifying variant in any of genes ATM or CHEK2,
analyzing the sequenced genetic data to determine whether the patient has a qualifying variant in a gene BRCA1, wherein qualifying variants are selected from the group consisting of Loss of Function (LoF) variants and coding variants;
analyzing the sequenced genetic data to determine whether the patient has a qualifying variant in a gene BRCA2;
analyzing the sequenced genetic data to determine whether the patient has a qualifying variant in a gene PALB2; and
in an event that the patient has any of a qualifying variant in the gene BRCA1, a qualifying variant in the gene BRCA2, a qualifying variant in the gene PALB2, a qualifying variant in the gene ATM and a PRS higher than a median PRS for a population that the patient belongs to, or a qualifying variant in the gene CHEK2 and a PRS higher than the median PRS for the population:
referring the patient for preventive measures pertaining to breast cancer.
19 . The method of claim 11 , wherein receiving health data comprising obtaining or having obtained health data from an Electronic Health Record (EHR) for a patient that is female and inspecting the health data to determine whether the patient has a family history of breast cancer.
20 . A method of determining breast cancer risk level for a patient, the method comprising:
receiving health data indicating whether a patient that is female has a family history of breast cancer;
obtaining or having obtained a biological sample from the patient;
performing or having performed sequencing on the biological sample to acquire sequenced genetic data for the patient, wherein the sequenced genetic data is accessible via a memory of a genomics server according to at least one file format selected from the group consisting of: a FASTQ format, a browser extensible data (BED) format, a binary alignment map format (BAM), a compressed reference oriented alignment map (CRAM) format, and a variant call format (VCF);
retrieving, by a genomics server, qualifying variant criteria from memory of one or more computing devices, the qualifying variant criteria indicating at least one of one or more Polyphen values or one or more Sorting Intolerant From Tolerant (SIFT) values to classify a variant as a qualifying variant;
analyzing, by the genomics server, the sequenced genetic data with respect to the qualifying variant criteria to determine that, regardless of family history, the patient has a qualifying variant in any of genes BRCA1, BRCA2, PALB2, ATM, and CHEK2, wherein a memory of the genomics server stores indications of variants included a number of analyzed genes, and wherein a memory of the genomics server stores a location of the sequenced genetic data; and
in an event that the patient has a qualifying variant in any of genes BRCA1, BRCA2, PALB2, ATM, or CHEK2: referring the patient for preventive measures pertaining to breast cancer.