Hereditary breast and ovarian cancer syndrome (HBOC) is an autosomal dominant hereditary cancer syndrome caused by germline pathogenic variants in the BRCA1 or BRCA2 tumor suppressor genes. It is characterized by significantly elevated lifetime risks of breast cancer (up to 70-80%) and ovarian cancer (up to 40-50%), as well as increased risks of pancreatic, prostate, and other cancers. HBOC exemplifies the role of DNA double-strand break repair deficiency in tumorigenesis and the therapeutic exploitation of homologous recombination deficiency through PARP inhibitor synthetic lethality.
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name: Hereditary Breast and Ovarian Cancer Syndrome
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-05-03T00:00:00Z'
description: >-
Hereditary breast and ovarian cancer syndrome (HBOC) is an autosomal dominant
hereditary cancer syndrome caused by germline pathogenic variants in the BRCA1
or BRCA2 tumor suppressor genes. It is characterized by significantly elevated
lifetime risks of breast cancer (up to 70-80%) and ovarian cancer (up to 40-50%),
as well as increased risks of pancreatic, prostate, and other cancers. HBOC
exemplifies the role of DNA double-strand break repair deficiency in tumorigenesis
and the therapeutic exploitation of homologous recombination deficiency through
PARP inhibitor synthetic lethality.
categories:
- Hereditary Cancer Syndrome
- Cancer Predisposition Syndrome
parents:
- hereditary cancer-predisposing syndrome
has_subtypes:
- name: BRCA1-Associated HBOC
description: >-
Associated with germline BRCA1 mutations. Higher lifetime risk of breast cancer
(70-80%) and ovarian cancer (40-50%). Breast cancers often triple-negative
(ER-/PR-/HER2-) and high grade. Higher risk of ovarian cancer than BRCA2.
- name: BRCA2-Associated HBOC
description: >-
Associated with germline BRCA2 mutations. Significant lifetime risk of breast
cancer (60-70%) and ovarian cancer (15-30%). Higher risk of male breast cancer
and pancreatic cancer than BRCA1. Also associated with increased prostate
cancer risk.
pathophysiology:
- name: BRCA1/2 Tumor Suppressor Loss
description: >-
Germline heterozygous BRCA1 or BRCA2 mutations result in one functional allele.
Somatic loss or mutation of the remaining wild-type allele (second hit) eliminates
BRCA function, initiating tumorigenesis. This follows Knudson's two-hit hypothesis
for tumor suppressor gene inactivation.
biological_processes:
- preferred_term: DNA repair
modifier: DECREASED
term:
id: GO:0006281
label: DNA repair
downstream:
- target: Homologous Recombination Deficiency
description: BRCA loss impairs error-free DNA double-strand break repair
- name: Homologous Recombination Deficiency
description: >-
BRCA1 and BRCA2 are essential components of the homologous recombination (HR)
pathway for error-free repair of DNA double-strand breaks. Loss of BRCA function
forces cells to rely on error-prone repair pathways such as non-homologous end
joining, leading to genomic instability.
biological_processes:
- preferred_term: homologous recombination
modifier: DECREASED
term:
id: GO:0035825
label: homologous recombination
downstream:
- target: Genomic Instability
description: Error-prone repair mechanisms cause chromosomal rearrangements
evidence:
- reference: PMID:22193408
reference_title: "BRCA1 and BRCA2: different roles in a common pathway of genome protection."
supports: PARTIAL
snippet: "BRCA1 is a pleiotropic DDR protein that functions in both checkpoint \nactivation and DNA repair, whereas BRCA2 is a mediator of the core mechanism of \nhomologous recombination."
explanation: >-
Review distinguishes BRCA1 and BRCA2 roles in DNA damage response and homologous
recombination repair.
- name: Genomic Instability
description: >-
Loss of HR-mediated repair leads to accumulation of chromosomal aberrations,
large-scale genomic rearrangements, and copy number alterations. This pattern
of genomic instability, termed 'BRCAness' or homologous recombination deficiency
(HRD), is characteristic of BRCA-deficient tumors and creates therapeutic
vulnerability to PARP inhibitors.
biological_processes:
- preferred_term: regulation of DNA damage checkpoint
modifier: ABNORMAL
term:
id: GO:2000001
label: regulation of DNA damage checkpoint
downstream:
- target: Tumor Development
description: Accumulated genomic aberrations drive malignant transformation
- name: Tumor Development
description: >-
Progressive accumulation of genomic alterations in BRCA-deficient cells leads
to transformation and tumor development. The tissue specificity (breast, ovary)
may relate to estrogen exposure and proliferative demands on these tissues,
though the precise mechanisms remain incompletely understood. Emerging evidence
identifies serous tubal intraepithelial carcinoma (STIC) in the fallopian tube
as a precursor for BRCA-associated high-grade serous ovarian cancer.
biological_processes:
- preferred_term: cell population proliferation
modifier: INCREASED
term:
id: GO:0008283
label: cell population proliferation
evidence:
- reference: PMID:30424539
reference_title: "Cell Origins of High-Grade Serous Ovarian Cancer."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: indicates that STIC may serve as a precursor for HGSC in high-risk women
explanation: >-
Review summarizes evidence that serous tubal intraepithelial carcinoma in
the fallopian tube is a precursor for high-grade serous ovarian cancer in
BRCA mutation carriers, providing insight into tumor development pathways.
phenotypes:
- category: Neoplastic
name: Breast Cancer
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Breast cancer risk is 70-80% for BRCA1 and 60-70% for BRCA2 mutation carriers.
BRCA1-associated breast cancers are often triple-negative (ER-/PR-/HER2-) and
high grade. BRCA2-associated breast cancers more often express hormone receptors.
Risk of contralateral breast cancer is significantly elevated.
phenotype_term:
preferred_term: Breast carcinoma
term:
id: HP:0003002
label: Breast carcinoma
evidence:
- reference: PMID:28632866
reference_title: "Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: cumulative breast cancer risk to age 80 years was 72% (95% CI, 65%-79%) for
explanation: >-
Prospective cohort study (CARRIERS consortium) provides definitive
penetrance estimates for breast cancer in BRCA1 and BRCA2 mutation carriers.
- category: Neoplastic
name: Triple-Negative Breast Carcinoma
subtype: BRCA1-Associated HBOC
description: >-
BRCA1-associated breast cancers are enriched for triple-negative breast
carcinoma, lacking estrogen receptor, progesterone receptor, and HER2
expression. This phenotype has distinct therapeutic implications because
endocrine and HER2-directed therapies are not applicable.
phenotype_term:
preferred_term: triple-negative breast carcinoma
term:
id: MONDO:0005494
label: triple-negative breast carcinoma
evidence:
- reference: PMID:32029870
reference_title: "Germline mutations of multiple breast cancer-related genes are differentially associated with triple-negative breast cancers and prognostic factors."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: associated with triple-negative breast cancer (TNBC), whereas BRCA2 mutation
explanation: >-
Multigene germline testing cohort supports triple-negative breast
carcinoma as a BRCA1-enriched HBOC phenotype.
- category: Neoplastic
name: Ovarian Cancer
frequency: VERY_FREQUENT
diagnostic: true
description: >-
Ovarian cancer risk is 40-50% for BRCA1 and 15-30% for BRCA2 mutation carriers.
Most are high-grade serous carcinomas. Typically presents at earlier ages than
sporadic ovarian cancer. Risk-reducing salpingo-oophorectomy is often recommended.
phenotype_term:
preferred_term: Ovarian carcinoma
term:
id: HP:0025318
label: Ovarian carcinoma
evidence:
- reference: PMID:28632866
reference_title: "Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: cumulative ovarian cancer risk to age 80 years was 44% (95% CI, 36%-53%) for
explanation: >-
Prospective cohort study provides definitive penetrance estimates for
ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.
- category: Neoplastic
name: Fallopian Tube Carcinoma
description: >-
Fallopian tube carcinoma is part of the formal HBOC cancer spectrum and is
biologically linked to the distal fallopian tube origin model for many
BRCA-associated high-grade serous carcinomas.
phenotype_term:
preferred_term: Fallopian tube carcinoma
term:
id: HP:0030394
label: Fallopian tube carcinoma
evidence:
- reference: DOI:10.3390/genes15020219
reference_title: "Genetic Basis of Breast and Ovarian Cancer: Approaches and Lessons Learnt from Three Decades of Inherited Predisposition Testing."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Germline variants occurring in BRCA1 and BRCA2 give rise to hereditary
breast and ovarian cancer (HBOC) syndrome, predisposing to breast, ovarian,
fallopian tube, and peritoneal cancers marked by elevated incidences of
genomic aberrations that correspond to poor prognoses.
explanation: >-
Review explicitly includes fallopian tube cancer in the BRCA1/2-associated
HBOC cancer spectrum.
- category: Neoplastic
name: Primary Peritoneal Carcinoma
description: >-
Primary peritoneal carcinoma is included in the hereditary breast and ovarian
cancer spectrum and may occur despite risk-reducing surgery, reflecting the
shared high-grade serous carcinoma biology of pelvic serous cancers.
phenotype_term:
preferred_term: Primary peritoneal carcinoma
term:
id: HP:0030406
label: Primary peritoneal carcinoma
evidence:
- reference: DOI:10.3390/genes15020219
reference_title: "Genetic Basis of Breast and Ovarian Cancer: Approaches and Lessons Learnt from Three Decades of Inherited Predisposition Testing."
supports: SUPPORT
evidence_source: OTHER
snippet: >-
Germline variants occurring in BRCA1 and BRCA2 give rise to hereditary
breast and ovarian cancer (HBOC) syndrome, predisposing to breast, ovarian,
fallopian tube, and peritoneal cancers marked by elevated incidences of
genomic aberrations that correspond to poor prognoses.
explanation: >-
Review explicitly includes peritoneal cancer in the BRCA1/2-associated
HBOC cancer spectrum.
- category: Neoplastic
name: Pancreatic Cancer
frequency: OCCASIONAL
description: >-
Lifetime risk of pancreatic cancer is increased to approximately 2-7%, particularly
with BRCA2 mutations. BRCA2 is a recognized pancreatic cancer susceptibility gene.
Surveillance may be considered in families with pancreatic cancer history.
phenotype_term:
preferred_term: Pancreatic adenocarcinoma
term:
id: HP:0006725
label: Pancreatic adenocarcinoma
evidence:
- reference: PMID:10433620
reference_title: "Cancer risks in BRCA2 mutation carriers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: 95% CI = 1. 87-6.58), gallbladder and bile duct cancer (RR = 4.97; 95% CI = 1
explanation: >-
Breast Cancer Linkage Consortium study quantifies the 3.5-fold increased
relative risk of pancreatic cancer in BRCA2 mutation carriers.
- category: Neoplastic
name: Prostate Cancer
frequency: OCCASIONAL
description: >-
BRCA2 mutations confer a 5-8 fold increased risk of prostate cancer, with earlier
onset and more aggressive disease. BRCA1 mutations also increase risk but to a
lesser degree. PARP inhibitors are effective in BRCA-mutated prostate cancer.
phenotype_term:
preferred_term: Prostate cancer
term:
id: HP:0012125
label: Prostate cancer
evidence:
- reference: PMID:10433620
reference_title: "Cancer risks in BRCA2 mutation carriers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: age of 65 years was 7.33 (95% CI = 4.66-11.52)
explanation: >-
Breast Cancer Linkage Consortium study demonstrates a 7.3-fold increased
relative risk of prostate cancer in BRCA2 carriers under age 65.
- category: Neoplastic
name: Male Breast Cancer
frequency: OCCASIONAL
description: >-
Male breast cancer risk is elevated, particularly with BRCA2 mutations
(6-8% lifetime risk). BRCA2 is the most common hereditary cause of male
breast cancer.
phenotype_term:
preferred_term: Breast carcinoma
term:
id: HP:0003002
label: Breast carcinoma
notes: >-
Uses same HP term as female breast cancer. Male breast cancer is specifically
associated with BRCA2 more than BRCA1.
- category: Neoplastic
name: Contralateral Breast Cancer
frequency: FREQUENT
description: >-
BRCA1 and BRCA2 mutation carriers who develop breast cancer have a substantially
elevated risk of contralateral breast cancer compared to sporadic cases. The
cumulative 20-year risk after initial diagnosis is approximately 40% for BRCA1
and 26% for BRCA2 carriers.
phenotype_term:
preferred_term: Breast carcinoma
term:
id: HP:0003002
label: Breast carcinoma
evidence:
- reference: PMID:28632866
reference_title: "Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: cancer, the cumulative risk 20 years after breast cancer diagnosis was 40% (95%
explanation: >-
Prospective data quantifying the high cumulative risk of contralateral
breast cancer in BRCA1 and BRCA2 mutation carriers.
notes: >-
Uses same HP term as primary breast cancer. Contralateral breast cancer risk
is a key consideration in surgical decision-making for BRCA carriers.
- category: Neoplastic
name: Melanoma
frequency: OCCASIONAL
subtype: BRCA2-Associated HBOC
description: >-
BRCA2 mutation carriers have an approximately 2.6-fold increased risk of
malignant melanoma. This association is more clearly established for BRCA2
than BRCA1 mutations.
phenotype_term:
preferred_term: Melanoma
term:
id: HP:0002861
label: Melanoma
evidence:
- reference: PMID:10433620
reference_title: "Cancer risks in BRCA2 mutation carriers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: (RR = 2.58; 95% CI = 1.28-5.17)
explanation: >-
Breast Cancer Linkage Consortium study demonstrates a statistically
significant 2.6-fold increased risk of melanoma in BRCA2 mutation carriers.
biochemical:
- name: BRCA1/2 Genetic Testing
notes: >-
Comprehensive sequencing of BRCA1 and BRCA2 identifies pathogenic variants
including frameshift, nonsense, splice site, and missense mutations, as well
as large deletions/duplications. Founder mutations exist in certain populations
(Ashkenazi Jewish: 185delAG, 5382insC in BRCA1; 6174delT in BRCA2). Variants
of uncertain significance require careful interpretation.
- name: Homologous Recombination Deficiency Testing
notes: >-
Tumor testing for HRD status includes genomic scar assays measuring loss of
heterozygosity, telomeric allelic imbalance, and large-scale state transitions.
HRD-positive tumors may respond to PARP inhibitors even without germline BRCA
mutations.
genetic:
- name: BRCA1
association: Germline Loss-of-Function Mutations
inheritance:
- name: Autosomal Dominant
notes: >-
BRCA1 (17q21.31) encodes a protein essential for DNA double-strand break repair
by homologous recombination. It functions in the RAD51-mediated strand invasion
step and also has roles in cell cycle checkpoint activation. Mutations include
truncating variants, large deletions, and pathogenic missense mutations. Founder
mutations are common in Ashkenazi Jewish (185delAG, 5382insC), Icelandic,
and other populations.
evidence:
- reference: PMID:22193408
reference_title: "BRCA1 and BRCA2: different roles in a common pathway of genome protection."
supports: SUPPORT
snippet: "the proteins work in concert to protect the genome from double-strand DNA \ndamage during DNA replication."
explanation: >-
Review confirms BRCA1 and BRCA2 work together to protect the genome from
DNA double-strand damage.
- name: BRCA2
association: Germline Loss-of-Function Mutations
inheritance:
- name: Autosomal Dominant
notes: >-
BRCA2 (13q13.1) encodes a protein that facilitates RAD51 loading onto single-
stranded DNA at sites of DNA double-strand breaks, enabling homologous
recombination repair. Also known as FANCD1 as biallelic mutations cause Fanconi
anemia. Founder mutations include 6174delT in Ashkenazi Jewish and 999del5 in
Icelandic populations.
- name: Expanded HBOC Panel Genes
association: Additional Hereditary Cancer Predisposition Genes
notes: >-
Although this entry focuses on BRCA1/2-associated HBOC, modern multigene HBOC
panels often include additional clinically actionable genes such as PALB2,
RAD51C, RAD51D, TP53, ATM, CHEK2, and BRIP1.
evidence:
- reference: DOI:10.3390/ijms252312546
reference_title: "Comprehensive Clinical Genetics, Molecular and Pathological Evaluation Efficiently Assist Diagnostics and Therapy Selection in Breast Cancer Patients with Hereditary Genetic Background."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: >-
High-penetrance genes (BRCA1, BRCA2, CDH1, PALB2, PTEN, STK11, TP53) inform
specific clinical surveillance and therapeutic decisions, while
recommendations for moderate-penetrance genes (ATM, BARD1, BRIP1, CHEK2,
MLH1, MSH2, MSH6, PMS2, EPCAM, NF1, RAD51C, RAD51D) are more limited.
explanation: >-
Clinical multigene testing cohort supports noting PALB2 and other expanded
panel genes while keeping the primary disorder scope focused on BRCA1/2.
treatments:
- name: Risk-Reducing Mastectomy
description: >-
Bilateral prophylactic mastectomy reduces breast cancer risk by approximately
90% in BRCA mutation carriers. Timing and decision require careful counseling
about risks, benefits, reconstruction options, and psychological impact.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
evidence:
- reference: PMID:31302855
reference_title: "Survival after bilateral risk-reducing mastectomy in healthy BRCA1 and BRCA2 mutation carriers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: for overall mortality and 0.06 (95% CI 0.01-0.46) for BC-specific mortality
explanation: >-
Dutch multicenter cohort study demonstrates that bilateral risk-reducing
mastectomy is associated with significantly lower overall mortality and
breast cancer-specific mortality in BRCA1 mutation carriers.
- name: Risk-Reducing Salpingo-Oophorectomy
description: >-
Bilateral salpingo-oophorectomy recommended after completion of childbearing
(typically age 35-40 for BRCA1, 40-45 for BRCA2). Reduces ovarian cancer risk
by 80-90% and breast cancer risk by approximately 50% when performed premenopausally.
treatment_term:
preferred_term: surgical procedure
term:
id: MAXO:0000004
label: surgical procedure
evidence:
- reference: PMID:19141781
reference_title: "Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: associated with reductions in the risk of breast, ovarian, and fallopian tube
explanation: >-
Meta-analysis of 10 studies demonstrates that risk-reducing
salpingo-oophorectomy significantly reduces the risk of breast cancer
(HR = 0.49) and ovarian/fallopian tube cancer (HR = 0.21) in BRCA1/2
mutation carriers.
- name: PARP Inhibitors
description: >-
PARP inhibitors (olaparib, rucaparib, niraparib, talazoparib) exploit synthetic
lethality in BRCA-deficient tumors. PARP inhibition blocks single-strand break
repair, causing double-strand breaks that cannot be repaired in HR-deficient
cells. Approved for breast, ovarian, pancreatic, and prostate cancers with
BRCA mutations.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
therapeutic_agent:
- preferred_term: olaparib
term:
id: CHEBI:83766
label: olaparib
evidence:
- reference: PMID:34081848
reference_title: "Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer."
supports: SUPPORT
snippet: "olaparib after completion of local treatment and neoadjuvant or adjuvant \nchemotherapy was associated with significantly longer survival free of invasive \nor distant disease than was placebo."
explanation: >-
OlympiA phase 3 trial demonstrates adjuvant olaparib significantly improves
disease-free survival in high-risk BRCA-mutated breast cancer.
- reference: PMID:28578601
reference_title: "Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: risk of disease progression or death was 42% lower with olaparib monotherapy
explanation: >-
OlympiAD phase 3 trial demonstrates olaparib monotherapy provides
significant progression-free survival benefit over standard chemotherapy in
germline BRCA-mutated metastatic breast cancer.
- reference: PMID:27749330
reference_title: "Targeting DNA Repair: The Role of PARP Inhibition in the Treatment of Castration-Resistant Prostate Cancer."
supports: SUPPORT
evidence_source: OTHER
snippet: Poly(ADP-ribose) polymerase inhibitors have shown to induce significant tumor
explanation: >-
Review supports the use of PARP inhibitors in BRCA-mutated prostate cancer,
with evidence from clinical trials showing significant tumor responses.
- name: Enhanced Surveillance
description: >-
For women who do not undergo prophylactic surgery, enhanced surveillance includes
annual breast MRI (starting age 25-30), mammography (starting age 30), and
clinical breast exam. No proven effective ovarian cancer screening exists.
Consider transvaginal ultrasound and CA-125, though sensitivity is limited.
treatment_term:
preferred_term: cancer screening
term:
id: MAXO:0000126
label: cancer screening
- name: Genetic Counseling
description: >-
Genetic counseling for at-risk family members with cascade testing. Children
of affected parents have 50% risk. Early identification allows risk-reducing
interventions and enhanced surveillance. Prenatal and preimplantation genetic
testing available.
treatment_term:
preferred_term: genetic counseling
term:
id: MAXO:0000079
label: genetic counseling
disease_term:
preferred_term: breast-ovarian cancer, familial, susceptibility to, 1
term:
id: MONDO:0011450
label: breast-ovarian cancer, familial, susceptibility to, 1
references:
- reference: DOI:10.1001/jamaoncol.2024.2185
title: <i>BRCA1, BRCA2</i>, and Associated Cancer Risks and Management for Male Patients
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: ImportanceHalf of all carriers of inherited cancer-predisposing variants in BRCA1 and BRCA2 are male, but the implications for their health are underrecognized compared to female individuals.
supporting_text: ImportanceHalf of all carriers of inherited cancer-predisposing variants in BRCA1 and BRCA2 are male, but the implications for their health are underrecognized compared to female individuals.
evidence:
- reference: DOI:10.1001/jamaoncol.2024.2185
reference_title: <i>BRCA1, BRCA2</i>, and Associated Cancer Risks and Management for Male Patients
supports: SUPPORT
evidence_source: OTHER
snippet: ImportanceHalf of all carriers of inherited cancer-predisposing variants in BRCA1 and BRCA2 are male, but the implications for their health are underrecognized compared to female individuals.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1002/cam4.70321
title: Uptake of Risk‐Reducing Salpingo‐Oophorectomy and Gynaecologic Surveillance Among Germline <scp><i>BRCA</i></scp> Pathogenic Variants Carriers
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Risk‐reducing salpingo‐oophorectomy (RRSO) is recommended by international guidelines in women with BRCA1/2 germline pathogenic variants (PV) to prevent ovarian cancer.
supporting_text: Risk‐reducing salpingo‐oophorectomy (RRSO) is recommended by international guidelines in women with BRCA1/2 germline pathogenic variants (PV) to prevent ovarian cancer.
evidence:
- reference: DOI:10.1002/cam4.70321
reference_title: Uptake of Risk‐Reducing Salpingo‐Oophorectomy and Gynaecologic Surveillance Among Germline <scp><i>BRCA</i></scp> Pathogenic Variants Carriers
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Risk‐reducing salpingo‐oophorectomy (RRSO) is recommended by international guidelines in women with BRCA1/2 germline pathogenic variants (PV) to prevent ovarian cancer.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1007/s10549-024-07283-0
title: Uptake of screening and risk-reducing recommendations among women with hereditary breast and ovarian cancer syndrome due to pathogenic BRCA1/2 variants evaluated at a large urban comprehensive cancer center
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Uptake of screening and risk-reducing recommendations among women with hereditary breast and ovarian cancer syndrome due to pathogenic BRCA1/2 variants evaluated at a large urban comprehensive cancer center
supporting_text: Uptake of screening and risk-reducing recommendations among women with hereditary breast and ovarian cancer syndrome due to pathogenic BRCA1/2 variants evaluated at a large urban comprehensive cancer center
- reference: DOI:10.1007/s10689-024-00412-0
title: 'Risk-reducing salpingectomy with delayed oophorectomy to prevent ovarian cancer in women with an increased inherited risk: insights into an alternative strategy'
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Epithelial ovarian cancer (EOC) is the most lethal type of gynaecological cancer, due to lack of effective screening possibilities and because the disease tends to metastasize before onset of symptoms.
supporting_text: Epithelial ovarian cancer (EOC) is the most lethal type of gynaecological cancer, due to lack of effective screening possibilities and because the disease tends to metastasize before onset of symptoms.
evidence:
- reference: DOI:10.1007/s10689-024-00412-0
reference_title: 'Risk-reducing salpingectomy with delayed oophorectomy to prevent ovarian cancer in women with an increased inherited risk: insights into an alternative strategy'
supports: SUPPORT
evidence_source: OTHER
snippet: Epithelial ovarian cancer (EOC) is the most lethal type of gynaecological cancer, due to lack of effective screening possibilities and because the disease tends to metastasize before onset of symptoms.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1016/j.lanwpc.2024.101017
title: Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants – an Asian study of 572 families
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants – an Asian study of 572 families
supporting_text: Age-specific breast and ovarian cancer risks associated with germline BRCA1 or BRCA2 pathogenic variants – an Asian study of 572 families
- reference: DOI:10.1016/j.rcl.2017.06.011
title: Imaging and Screening of Hereditary Cancer Syndromes
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Imaging and Screening of Hereditary Cancer Syndromes
supporting_text: Imaging and Screening of Hereditary Cancer Syndromes
- reference: DOI:10.1016/j.soncn.2018.12.001
title: 'Hereditary Breast and Hereditary Ovarian Cancer: Implications for the Oncology Nurse'
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: 'Hereditary Breast and Hereditary Ovarian Cancer: Implications for the Oncology Nurse'
supporting_text: 'Hereditary Breast and Hereditary Ovarian Cancer: Implications for the Oncology Nurse'
- reference: DOI:10.1038/s41416-024-02827-z
title: 'BRCA-mutated breast cancer: the unmet need, challenges and therapeutic benefits of genetic testing'
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Mutations in the BRCA1 and/or BRCA2 genes (BRCAm) increase the risk of developing breast cancer (BC) and are found in ~5% of unselected patients with the disease.
supporting_text: Mutations in the BRCA1 and/or BRCA2 genes (BRCAm) increase the risk of developing breast cancer (BC) and are found in ~5% of unselected patients with the disease.
evidence:
- reference: DOI:10.1038/s41416-024-02827-z
reference_title: 'BRCA-mutated breast cancer: the unmet need, challenges and therapeutic benefits of genetic testing'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Mutations in the BRCA1 and/or BRCA2 genes (BRCAm) increase the risk of developing breast cancer (BC) and are found in ~5% of unselected patients with the disease.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1038/s41431-023-01507-5
title: EMQN best practice guidelines for genetic testing in hereditary breast and ovarian cancer
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Hereditary Breast and Ovarian Cancer (HBOC) is a genetic condition associated with increased risk of cancers.
supporting_text: Hereditary Breast and Ovarian Cancer (HBOC) is a genetic condition associated with increased risk of cancers.
evidence:
- reference: DOI:10.1038/s41431-023-01507-5
reference_title: EMQN best practice guidelines for genetic testing in hereditary breast and ovarian cancer
supports: SUPPORT
evidence_source: OTHER
snippet: Hereditary Breast and Ovarian Cancer (HBOC) is a genetic condition associated with increased risk of cancers.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1038/s41467-023-40956-w
title: A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Germline BRCA2 mutation carriers frequently develop luminal-like breast cancers, but it remains unclear how BRCA2 mutations affect mammary epithelial subpopulations.
supporting_text: Germline BRCA2 mutation carriers frequently develop luminal-like breast cancers, but it remains unclear how BRCA2 mutations affect mammary epithelial subpopulations.
evidence:
- reference: DOI:10.1038/s41467-023-40956-w
reference_title: A transcriptional response to replication stress selectively expands a subset of Brca2-mutant mammary epithelial cells
supports: SUPPORT
evidence_source: IN_VITRO
snippet: Germline BRCA2 mutation carriers frequently develop luminal-like breast cancers, but it remains unclear how BRCA2 mutations affect mammary epithelial subpopulations.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1038/s41525-024-00400-4
title: Germline mutations of 4567 patients with hereditary breast-ovarian cancer spectrum in Thailand
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Multi-gene panel testing has led to the detection of pathogenic/likely pathogenic (P/LP) variants in many cancer susceptibility genes in patients with breast-ovarian cancer spectrum.
supporting_text: Multi-gene panel testing has led to the detection of pathogenic/likely pathogenic (P/LP) variants in many cancer susceptibility genes in patients with breast-ovarian cancer spectrum.
evidence:
- reference: DOI:10.1038/s41525-024-00400-4
reference_title: Germline mutations of 4567 patients with hereditary breast-ovarian cancer spectrum in Thailand
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Multi-gene panel testing has led to the detection of pathogenic/likely pathogenic (P/LP) variants in many cancer susceptibility genes in patients with breast-ovarian cancer spectrum.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1038/s41698-024-00741-4
title: Reduced penetrance BRCA1 and BRCA2 pathogenic variants in clinical germline genetic testing
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Prior studies have suggested the existence of reduced penetrance pathogenic variants (RPPVs) in BRCA1 and BRCA2 (BRCA) which pose challenges for patient counseling and care.
supporting_text: Prior studies have suggested the existence of reduced penetrance pathogenic variants (RPPVs) in BRCA1 and BRCA2 (BRCA) which pose challenges for patient counseling and care.
evidence:
- reference: DOI:10.1038/s41698-024-00741-4
reference_title: Reduced penetrance BRCA1 and BRCA2 pathogenic variants in clinical germline genetic testing
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Prior studies have suggested the existence of reduced penetrance pathogenic variants (RPPVs) in BRCA1 and BRCA2 (BRCA) which pose challenges for patient counseling and care.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1093/jnci/djae160
title: Genomic instability in non–breast or ovarian malignancies of individuals with germline pathogenic variants in <i>BRCA1/2</i>
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Genomic instability in non–breast or ovarian malignancies of individuals with germline pathogenic variants in <i>BRCA1/2</i>
supporting_text: Individuals with germline pathogenic variants in BRCA1 or BRCA2 are at a high risk of breast and ovarian carcinomas with BRCA1/2 deficiency and homologous recombination deficiency that can be detected by analysis of genome-wide genomic instability features such as large-scale state transitions, telomeric allelic imbalances, and genomic loss of heterozygosity.
evidence:
- reference: DOI:10.1093/jnci/djae160
reference_title: Genomic instability in non–breast or ovarian malignancies of individuals with germline pathogenic variants in <i>BRCA1/2</i>
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Individuals with germline pathogenic variants in BRCA1 or BRCA2 are at a high risk of breast and ovarian carcinomas with BRCA1/2 deficiency and homologous recombination deficiency that can be detected by analysis of genome-wide genomic instability features such as large-scale state transitions, telomeric allelic imbalances, and genomic loss of heterozygosity.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1158/2767-9764.crc-24-0144
title: MYC is Sufficient to Generate Mid-Life High-Grade Serous Ovarian and Uterine Serous Carcinomas in a p53-R270H Mouse Model
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment are understood.
supporting_text: Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment are understood.
evidence:
- reference: DOI:10.1158/2767-9764.crc-24-0144
reference_title: MYC is Sufficient to Generate Mid-Life High-Grade Serous Ovarian and Uterine Serous Carcinomas in a p53-R270H Mouse Model
supports: SUPPORT
evidence_source: MODEL_ORGANISM
snippet: Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment are understood.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1159/000533391
title: Primary Prevention and Early Detection of Hereditary Breast Cancer
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Primary prevention and early detection of hereditary breast cancer has been one of the main topics of breast cancer research in recent decades.
supporting_text: Primary prevention and early detection of hereditary breast cancer has been one of the main topics of breast cancer research in recent decades.
evidence:
- reference: DOI:10.1159/000533391
reference_title: Primary Prevention and Early Detection of Hereditary Breast Cancer
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Primary prevention and early detection of hereditary breast cancer has been one of the main topics of breast cancer research in recent decades.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1177/09636897241281869
title: 'Ovarian Cancer Patient-Derived Organoids Used as a Model for Replicating Genetic Characteristics and Testing Drug Responsiveness: A Preliminary Study'
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: This study aimed to explore the role of ovarian cancer patient-derived organoids (PDOs) in their replicating genetic characteristics and testing drug responsiveness.
supporting_text: This study aimed to explore the role of ovarian cancer patient-derived organoids (PDOs) in their replicating genetic characteristics and testing drug responsiveness.
evidence:
- reference: DOI:10.1177/09636897241281869
reference_title: 'Ovarian Cancer Patient-Derived Organoids Used as a Model for Replicating Genetic Characteristics and Testing Drug Responsiveness: A Preliminary Study'
supports: SUPPORT
evidence_source: IN_VITRO
snippet: This study aimed to explore the role of ovarian cancer patient-derived organoids (PDOs) in their replicating genetic characteristics and testing drug responsiveness.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1186/s12864-024-10311-4
title: Using Portuguese BRCA pathogenic variation as a model to study the impact of human admixture on human health
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Admixture occurs between different ethnic human populations.
supporting_text: Admixture occurs between different ethnic human populations.
evidence:
- reference: DOI:10.1186/s12864-024-10311-4
reference_title: Using Portuguese BRCA pathogenic variation as a model to study the impact of human admixture on human health
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Admixture occurs between different ethnic human populations.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1186/s13048-023-01222-1
title: Risk-reducing salpingo-oophorectomy among Chinese women at increased risk of breast and ovarian cancer
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women at increased risk of breast and ovarian cancer.
supporting_text: Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women at increased risk of breast and ovarian cancer.
evidence:
- reference: DOI:10.1186/s13048-023-01222-1
reference_title: Risk-reducing salpingo-oophorectomy among Chinese women at increased risk of breast and ovarian cancer
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Risk-reducing salpingo-oophorectomy (RRSO) is recommended for women at increased risk of breast and ovarian cancer.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.1186/s40001-024-01767-x
title: 'Systematic review of the molecular basis of hereditary breast and ovarian cancer syndrome in Brazil: the current scenario'
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: A detailed understanding of the genetic basis of cancer is of great interest to public health monitoring programs.
supporting_text: A detailed understanding of the genetic basis of cancer is of great interest to public health monitoring programs.
evidence:
- reference: DOI:10.1186/s40001-024-01767-x
reference_title: 'Systematic review of the molecular basis of hereditary breast and ovarian cancer syndrome in Brazil: the current scenario'
supports: SUPPORT
evidence_source: OTHER
snippet: A detailed understanding of the genetic basis of cancer is of great interest to public health monitoring programs.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.2147/ott.s353054
title: Hereditary Gynecologic Cancer Syndromes – A Narrative Review
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Hereditary Gynecologic Cancer Syndromes – A Narrative Review
supporting_text: Hereditary Gynecologic Cancer Syndromes – A Narrative Review
- reference: DOI:10.3238/arztebl.2008.0706
title: Hereditary Cancer Syndromes
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Hereditary Cancer Syndromes
supporting_text: Hereditary Cancer Syndromes
- reference: DOI:10.3389/fphar.2024.1460285
title: 'Efficacy and safety of PARP inhibitor maintenance therapy for ovarian cancer: a meta-analysis and trial sequential analysis of randomized controlled trials'
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: The landscape of poly (ADP-ribose) polymerase (PARP) inhibitor treatment for ovarian cancer (OC) is continually evolving.
supporting_text: The landscape of poly (ADP-ribose) polymerase (PARP) inhibitor treatment for ovarian cancer (OC) is continually evolving.
evidence:
- reference: DOI:10.3389/fphar.2024.1460285
reference_title: 'Efficacy and safety of PARP inhibitor maintenance therapy for ovarian cancer: a meta-analysis and trial sequential analysis of randomized controlled trials'
supports: SUPPORT
evidence_source: OTHER
snippet: The landscape of poly (ADP-ribose) polymerase (PARP) inhibitor treatment for ovarian cancer (OC) is continually evolving.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.3390/cancers15133420
title: Overview of the Genetic Causes of Hereditary Breast and Ovarian Cancer Syndrome in a Large French Patient Cohort
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: The use of multigene panel testing for patients with a predisposition to Hereditary Breast and Ovarian Cancer syndrome (HBOC) is increasing as the identification of mutations is useful for diagnosis and disease management.
supporting_text: The use of multigene panel testing for patients with a predisposition to Hereditary Breast and Ovarian Cancer syndrome (HBOC) is increasing as the identification of mutations is useful for diagnosis and disease management.
evidence:
- reference: DOI:10.3390/cancers15133420
reference_title: Overview of the Genetic Causes of Hereditary Breast and Ovarian Cancer Syndrome in a Large French Patient Cohort
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The use of multigene panel testing for patients with a predisposition to Hereditary Breast and Ovarian Cancer syndrome (HBOC) is increasing as the identification of mutations is useful for diagnosis and disease management.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.3390/cancers16010103
title: Prophylactic Interventions for Hereditary Breast and Ovarian Cancer Risks and Mortality in BRCA1/2 Carriers
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Hereditary breast and ovarian cancers (HBOCs) pose significant health risks worldwide and are mitigated by prophylactic interventions.
supporting_text: Hereditary breast and ovarian cancers (HBOCs) pose significant health risks worldwide and are mitigated by prophylactic interventions.
evidence:
- reference: DOI:10.3390/cancers16010103
reference_title: Prophylactic Interventions for Hereditary Breast and Ovarian Cancer Risks and Mortality in BRCA1/2 Carriers
supports: SUPPORT
evidence_source: OTHER
snippet: Hereditary breast and ovarian cancers (HBOCs) pose significant health risks worldwide and are mitigated by prophylactic interventions.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.3390/cancers17010008
title: 'BRCA and Beyond: Impact on Therapeutic Choices Across Cancer'
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Identifying patients with gBRCAm is crucial to facilitate screening strategies, preventive measures and the usage of targeted therapeutics in their management.
supporting_text: Identifying patients with gBRCAm is crucial to facilitate screening strategies, preventive measures and the usage of targeted therapeutics in their management.
evidence:
- reference: DOI:10.3390/cancers17010008
reference_title: 'BRCA and Beyond: Impact on Therapeutic Choices Across Cancer'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Identifying patients with gBRCAm is crucial to facilitate screening strategies, preventive measures and the usage of targeted therapeutics in their management.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.3390/cimb46050281
title: The Molecular Detection of Germline Mutations in the BRCA1 and BRCA2 Genes Associated with Breast and Ovarian Cancer in a Romanian Cohort of 616 Patients
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: The objective of this study was to identify and classify the spectrum of mutations found in the BRCA1 and BRCA2 genes associated with breast and ovarian cancer in female patients in Romania.
supporting_text: The objective of this study was to identify and classify the spectrum of mutations found in the BRCA1 and BRCA2 genes associated with breast and ovarian cancer in female patients in Romania.
evidence:
- reference: DOI:10.3390/cimb46050281
reference_title: The Molecular Detection of Germline Mutations in the BRCA1 and BRCA2 Genes Associated with Breast and Ovarian Cancer in a Romanian Cohort of 616 Patients
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The objective of this study was to identify and classify the spectrum of mutations found in the BRCA1 and BRCA2 genes associated with breast and ovarian cancer in female patients in Romania.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.3390/genes14030684
title: Personalized Systemic Therapies in Hereditary Cancer Syndromes
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population.
supporting_text: Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population.
evidence:
- reference: DOI:10.3390/genes14030684
reference_title: Personalized Systemic Therapies in Hereditary Cancer Syndromes
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Hereditary cancer syndromes are inherited disorders caused by germline pathogenic variants (PVs) that lead to an increased risk of developing certain types of cancer, frequently at an earlier age than in the rest of the population.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.3390/genes15020219
title: 'Genetic Basis of Breast and Ovarian Cancer: Approaches and Lessons Learnt from Three Decades of Inherited Predisposition Testing'
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: 'Genetic Basis of Breast and Ovarian Cancer: Approaches and Lessons Learnt from Three Decades of Inherited Predisposition Testing'
supporting_text: Germline variants occurring in BRCA1 and BRCA2 give rise to hereditary breast and ovarian cancer (HBOC) syndrome, predisposing to breast, ovarian, fallopian tube, and peritoneal cancers marked by elevated incidences of genomic aberrations that correspond to poor prognoses.
evidence:
- reference: DOI:10.3390/genes15020219
reference_title: 'Genetic Basis of Breast and Ovarian Cancer: Approaches and Lessons Learnt from Three Decades of Inherited Predisposition Testing'
supports: SUPPORT
evidence_source: OTHER
snippet: Germline variants occurring in BRCA1 and BRCA2 give rise to hereditary breast and ovarian cancer (HBOC) syndrome, predisposing to breast, ovarian, fallopian tube, and peritoneal cancers marked by elevated incidences of genomic aberrations that correspond to poor prognoses.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.3390/ijms242115507
title: The BRCA1 c.4096+1G>A Is a Founder Variant Which Originated in Ancient Times
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Approximately 30–50% of hereditary breast and ovarian cancer (HBOC) is due to the presence of germline pathogenic variants in the BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) onco-suppressor genes, which are involved in DNA damage response.
supporting_text: Approximately 30–50% of hereditary breast and ovarian cancer (HBOC) is due to the presence of germline pathogenic variants in the BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) onco-suppressor genes, which are involved in DNA damage response.
evidence:
- reference: DOI:10.3390/ijms242115507
reference_title: The BRCA1 c.4096+1G>A Is a Founder Variant Which Originated in Ancient Times
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Approximately 30–50% of hereditary breast and ovarian cancer (HBOC) is due to the presence of germline pathogenic variants in the BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) onco-suppressor genes, which are involved in DNA damage response.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.3390/ijms25020886
title: Human Fallopian Tube-Derived Organoids with TP53 and RAD51D Mutations Recapitulate an Early Stage High-Grade Serous Ovarian Cancer Phenotype In Vitro
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: RAD51D mutations have been implicated in the transformation of normal fallopian tube epithelial (FTE) cells into high-grade serous ovarian cancer (HGSOC), one of the most prevalent and aggressive gynecologic malignancies.
supporting_text: RAD51D mutations have been implicated in the transformation of normal fallopian tube epithelial (FTE) cells into high-grade serous ovarian cancer (HGSOC), one of the most prevalent and aggressive gynecologic malignancies.
evidence:
- reference: DOI:10.3390/ijms25020886
reference_title: Human Fallopian Tube-Derived Organoids with TP53 and RAD51D Mutations Recapitulate an Early Stage High-Grade Serous Ovarian Cancer Phenotype In Vitro
supports: SUPPORT
evidence_source: IN_VITRO
snippet: RAD51D mutations have been implicated in the transformation of normal fallopian tube epithelial (FTE) cells into high-grade serous ovarian cancer (HGSOC), one of the most prevalent and aggressive gynecologic malignancies.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.3390/ijms252312546
title: Comprehensive Clinical Genetics, Molecular and Pathological Evaluation Efficiently Assist Diagnostics and Therapy Selection in Breast Cancer Patients with Hereditary Genetic Background
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: Using multigene panel testing for the diagnostic evaluation of patients with hereditary breast and ovarian cancer (HBOC) syndrome often identifies clinically actionable variants in genes with varying levels of penetrance.
supporting_text: Using multigene panel testing for the diagnostic evaluation of patients with hereditary breast and ovarian cancer (HBOC) syndrome often identifies clinically actionable variants in genes with varying levels of penetrance.
evidence:
- reference: DOI:10.3390/ijms252312546
reference_title: Comprehensive Clinical Genetics, Molecular and Pathological Evaluation Efficiently Assist Diagnostics and Therapy Selection in Breast Cancer Patients with Hereditary Genetic Background
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Using multigene panel testing for the diagnostic evaluation of patients with hereditary breast and ovarian cancer (HBOC) syndrome often identifies clinically actionable variants in genes with varying levels of penetrance.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
- reference: DOI:10.3390/jcm12041422
title: 'Risk-Reducing Breast and Gynecological Surgery for BRCA Mutation Carriers: A Narrative Review'
found_in:
- Hereditary_Breast_and_Ovarian_Cancer_Syndrome-deep-research-falcon.md
findings:
- statement: This narrative review aims to clarify the role of breast and gynecological risk-reduction surgery in BRCA mutation carriers.
supporting_text: This narrative review aims to clarify the role of breast and gynecological risk-reduction surgery in BRCA mutation carriers.
evidence:
- reference: DOI:10.3390/jcm12041422
reference_title: 'Risk-Reducing Breast and Gynecological Surgery for BRCA Mutation Carriers: A Narrative Review'
supports: SUPPORT
evidence_source: OTHER
snippet: This narrative review aims to clarify the role of breast and gynecological risk-reduction surgery in BRCA mutation carriers.
explanation: Deep research cited this publication as relevant literature for Hereditary Breast and Ovarian Cancer Syndrome.
HBOC is a genetic condition characterized by increased risk for breast and ovarian cancers, often with earlier onset than sporadic cancers, and associated risks for other malignancies depending on the causal gene. HBOC is described as an autosomal dominant inherited disorder/cancer predisposition. (bouras2023overviewofthe pages 1-2, mastrodomenico2023personalizedsystemictherapies pages 1-2)
A large French cohort review states that HBOC accounts for ~10–15% of breast cancers and ~25% of ovarian cancers. (bouras2023overviewofthe pages 1-2)
Not retrieved in the available evidence set: MONDO ID for HBOC, Orphanet disease ID, ICD-10/ICD-11 code, and MeSH identifier for the syndrome itself. These identifiers likely exist in aggregated resources (e.g., MONDO/Orphanet/MeSH), but were not directly extractable from the retrieved full-text snippets used here.
Commonly used names in the retrieved literature include: * Hereditary Breast and Ovarian Cancer (HBOC) syndrome (mcdevitt2024emqnbestpractice pages 1-2, bouras2023overviewofthe pages 1-2) * BRCA-associated hereditary breast/ovarian cancer (tan2024brcaandbeyond pages 2-4) * Hereditary breast–ovarian cancer syndrome (kostov2022hereditarygynecologiccancer pages 5-6)
The knowledge summarized here is derived from a mixture of: * Aggregated disease-level resources (reviews, best-practice guidelines, meta-analyses) (mcdevitt2024emqnbestpractice pages 1-2, sun2024efficacyandsafety pages 1-2) * Large clinical cohorts and retrospective/prospective series (e.g., French 4,630-case panel cohort; Hungarian 513-case program; Romanian 616-case cohort; 2024 implementation cohorts) (bouras2023overviewofthe pages 1-2, nagy2024comprehensiveclinicalgenetics pages 1-2, grigore2024themoleculardetection pages 1-2, assad2024uptakeofscreening pages 1-3)
Primary causal mechanism (genetic): HBOC is most frequently caused by heterozygous germline P/LP variants in BRCA1/BRCA2, tumor-suppressor genes essential for homologous recombination (HR) DNA double-strand break repair. (barili2024geneticbasisof pages 1-2, mastrodomenico2023personalizedsystemictherapies pages 2-3)
Other genes (expanded HBOC spectrum): Multigene testing increasingly identifies clinically actionable variants in other genes (e.g., PALB2, RAD51C, RAD51D, TP53, and additional moderate-penetrance genes). (bouras2023overviewofthe pages 1-2, nagy2024comprehensiveclinicalgenetics pages 1-2, mcdevitt2024emqnbestpractice pages 2-3)
Evidence in the retrieved set is limited for specific environmental exposures; however, a meta-analysis synthesis reported a behavioral association: ≥10 lb weight loss between ages 18–30 was associated with 34% lower breast cancer risk in one included study. (liu2023prophylacticinterventionsfor pages 16-17)
Specific gene–environment interaction evidence (e.g., formal GxE interaction terms) was not directly retrieved from the evidence set.
The retrieved evidence supports mapping at least the following phenotypes to HPO: * Breast carcinoma (from evidence of breast cancer risk) (barili2024geneticbasisof pages 1-2, list2021oncogenedxbrca1and pages 1-3) * Ovarian carcinoma / epithelial ovarian cancer (gootzen2024riskreducingsalpingectomywith pages 1-2) * High-grade serous carcinoma (ovary) (katabathina2017imagingandscreening pages 1-2, gootzen2024riskreducingsalpingectomywith pages 1-2) * Triple-negative breast cancer (katabathina2017imagingandscreening pages 1-2) * Fallopian tube carcinoma; primary peritoneal carcinoma (mastrodomenico2023personalizedsystemictherapies pages 1-2, katabathina2017imagingandscreening pages 1-2) * Male breast cancer; prostate cancer; pancreatic cancer (mastrodomenico2023personalizedsystemictherapies pages 1-2, cheng2024brca1brca2and pages 1-3) * Contralateral breast cancer (list2021oncogenedxbrca1and pages 1-3) * STIC (as precursor lesion; while not strictly an HPO phenotype, it can be captured as a pathologic finding) (gootzen2024riskreducingsalpingectomywith pages 1-2)
Frequency among affected individuals: numeric phenotype frequencies are sparse in the retrieved set beyond TNBC (~70% of BRCA1-associated breast cancers) and HGSC predominance (~90% of EOC in BRCA carriers). (katabathina2017imagingandscreening pages 1-2, gootzen2024riskreducingsalpingectomywith pages 1-2)
Quality-of-life impact: evidence is indirect; risk management is characterized as burdensome and lifelong by qualitative work, supporting QoL/psychosocial impact. (bonetti2023omicssciencesand pages 2-3)
Core causal genes and testing panel genes include: * BRCA1/BRCA2 (high penetrance) (barili2024geneticbasisof pages 1-2) * Other high/moderate penetrance genes reported in clinical panels: PALB2, TP53, RAD51C, RAD51D, BRIP1, ATM, CHEK2, and others depending on panel composition. (mcdevitt2024emqnbestpractice pages 2-3, nagy2024comprehensiveclinicalgenetics pages 1-2, bouras2023overviewofthe pages 1-2)
EMQN best-practice guidance emphasizes both tumor (somatic) and germline BRCA testing to inform PARP inhibitor eligibility; ovarian tumor testing detects BRCA1/2 pathogenic variants in ~15% of patients, ~7% somatic-only. (mcdevitt2024emqnbestpractice pages 3-4)
EMQN notes polygenic risk scores (e.g., PRS313 in BOADICEA/CanRisk) exist but require further validation before routine use. (mcdevitt2024emqnbestpractice pages 1-2)
Noncoding mechanisms can contribute: a BRCA1 deep promoter variant (c.-107A>T) is described as causing promoter methylation (“secondary epimutation”) and reduced expression. (barili2024geneticbasisof pages 2-4)
Large rearrangements (CNVs) are an important component; EMQN requires CNV analysis at minimum and notes FFPE CNV calling challenges. (mcdevitt2024emqnbestpractice pages 3-4)
The retrieved evidence base is limited on specific environmental toxins/infections for HBOC. Lifestyle/weight change evidence is noted under Etiology (Section 2). (liu2023prophylacticinterventionsfor pages 16-17)
HR/HRD and genomic scars: JNCI 2024 defines HRD features such as large-scale state transitions, genomic loss-of-heterozygosity and telomeric allelic imbalance. (elze2024genomicinstabilityin pages 1-2)
PARP synthetic lethality: PARP inhibitors inhibit catalytic PARylation and trap PARP on DNA, converting persistent SSBs into DSBs at replication forks; HR-deficient cells cannot repair these DSBs effectively, causing cell death. (mastrodomenico2023personalizedsystemictherapies pages 2-3)
Ontology suggestions (best-effort): * GO Biological Process: homologous recombination; DNA double-strand break repair (supported by BRCA1/2 HR role) (barili2024geneticbasisof pages 1-2) * Cell Ontology (CL): mammary epithelial cell (murine mammary organoid model); fallopian tube epithelial cell (FTE) (najafabadi2023atranscriptionalresponse pages 1-2, dai2024humanfallopiantubederived pages 1-2)
The fallopian tube origin hypothesis is supported by STIC precursor lesions in the distal tube; a 2024 review states STICs are characterized by aberrant p53 and Ki-67 immunohistochemistry and that no precursor lesions have been identified in ovaries. (gootzen2024riskreducingsalpingectomywith pages 1-2)
Mechanistically centered on nuclear DNA repair processes (homologous recombination, DNA damage response; PARP at DNA damage sites). (mastrodomenico2023personalizedsystemictherapies pages 2-3)
HGSC and extrauterine pelvic serous carcinomas are typically aggressive; ovarian cancer is often diagnosed late in the general population (advanced stage common), motivating preventive surgery. (inzoli2024uptakeofrisk‐reducing pages 1-2)
Autosomal dominant inheritance is repeatedly stated for HBOC. (bouras2023overviewofthe pages 1-2, mastrodomenico2023personalizedsystemictherapies pages 1-2)
Risk estimates vary across studies and populations; examples: * By age 70, breast cancer risk: ~60–66% BRCA1, ~55–61% BRCA2; ovarian cancer risk: ~41–58% BRCA1, ~15–16.5% BRCA2 (2024 review). (barili2024geneticbasisof pages 1-2) * Asian family study (Malaysia/Singapore) provides ethnicity- and region-specific cumulative risks by age 80 (e.g., Singapore BRCA1 breast ~57–61%, ovarian ~42%; BRCA2 breast ~43–47%, ovarian ~20%). (ho2024agespecificbreastand pages 1-2)
Panel testing is now routine in many settings due to cost decreases and expanded clinical actionability. EMQN 2024 provides best-practice laboratory guidance for HBOC genetic testing and emphasizes somatic + germline workflows, minimum-gene expectations (BRCA1/2 and PALB2 at minimum), and mandatory CNV analysis capability. (mcdevitt2024emqnbestpractice pages 2-3, mcdevitt2024emqnbestpractice pages 3-4)
Detection rates and yield examples: * French 13-gene panel cohort (n=4,630): 528 P/LP variants detected; BRCA1 and BRCA2 together comprised ~75% of P/LP findings; retesting BRCA-negative cases with expanded panels yielded clinically relevant findings in 5%. (bouras2023overviewofthe pages 1-2) * Hungarian hereditary cancer panel: extended panel doubled detection vs BRCA1/2-only (20.7% vs 12.1%). (nagy2024comprehensiveclinicalgenetics pages 2-4)
Technical confirmation methods: One large cohort confirmed P/LP calls via Sanger for SNVs/indels, MLPA for CNVs, and PCR/RT-PCR for complex/splice variants. (bouras2023overviewofthe pages 2-4)
EMQN notes ovarian tumor testing identifies BRCA1/2 pathogenic variants in ~15% of patients (including ~7% somatic-only), informing PARP inhibitor eligibility. (mcdevitt2024emqnbestpractice pages 3-4)
A radiology review notes BRCA-associated breast cancers may appear well circumscribed and can mimic benign lesions, supporting careful biopsy of detected lesions. (katabathina2017imagingandscreening pages 1-2)
Direct survival/prognosis statistics for HBOC carriers as a group were not comprehensively retrieved; however: * BRCA-associated ovarian tumors (HGSC) are described as sensitive to platinum and PARP inhibitors, influencing outcomes. (katabathina2017imagingandscreening pages 1-2, elze2024genomicinstabilityin pages 1-2)
PARP inhibitors exploit HRD synthetic lethality in BRCA-deficient tumors. (mastrodomenico2023personalizedsystemictherapies pages 2-3)
Breast cancer (adjuvant; 2024 review reporting OlympiA outcomes): 1 year of adjuvant olaparib improved 4-year iDFS 82.7% vs 75.4% (HR 0.63) and 4-year OS 89.8% vs 86.4% (HR 0.68; p=0.009) at median 3.5-year follow-up. (tan2024brcaandbeyond pages 2-4)
Breast cancer (metastatic): * OlympiAD: olaparib vs chemotherapy median PFS 7.0 vs 4.2 months (HR 0.58); ORR 59.9% vs 28.8%; OS not statistically significant (median OS 19.3 vs 17.1 months; HR 0.90). (tan2024brcaandbeyond pages 2-4) * EMBRACA: talazoparib PFS 8.6 vs 5.6 months (HR 0.54); ORR 62.6% vs 27.2%; no significant OS benefit. (tan2024brcaandbeyond pages 2-4)
Ovarian cancer maintenance (2024 meta-analysis): pooled improvements vs placebo: PFS HR 0.398, OS HR 0.677, with increased toxicities (any-grade TEAEs RR 1.046; grade ≥3 RR 2.931). (sun2024efficacyandsafety pages 1-2)
HRD/BRCA1/2 deficiency predicts increased sensitivity to platinum agents across tumor types. (elze2024genomicinstabilityin pages 1-2)
Interventional studies retrieved include: * NCT03344965 (Olaparib in metastatic breast cancer) (arun2024brcamutatedbreastcancer pages 6-7) * NCT03150576 (PARTNER; neoadjuvant olaparib + chemotherapy in TNBC; gBRCA wild-type population) (abraham2024thepartnertrial pages 1-4) * Risk-management/education/decision-support trials include NCT04683068, NCT06914726, NCT00673335 (beamer2019hereditarybreastand pages 1-3)
Key prevention approaches are summarized in artifact-01 and include: * RRSO: mortality and ovarian cancer risk reduction with variable uptake (liu2023prophylacticinterventionsfor pages 1-2, assad2024uptakeofscreening pages 1-3, inzoli2024uptakeofrisk‐reducing pages 1-2) * Risk-reducing mastectomy: large breast cancer risk reduction; uptake variable (bertozzi2023riskreducingbreastand pages 6-7, assad2024uptakeofscreening pages 1-3) * Intensified surveillance: annual MRI with supplemental imaging per programmatic models (speiser2023primarypreventionand pages 2-3, assad2024uptakeofscreening pages 1-3)
No naturally occurring non-human HBOC syndrome evidence was retrieved; however, the genes and pathways are evolutionarily conserved and modeled in mice and organoids (see Model Organisms).
The HGSOC GEMM highlights limitations such as differences in mouse anatomy (ovarian bursa) and challenges modeling metastasis. (blackman2024mycissufficient pages 20-21)
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