Metastatic breast carcinoma is advanced breast cancer that has disseminated beyond the breast and regional lymph nodes to distant organs, with particular tropism for bone, lung, brain, and liver. Metastatic competence emerges through epithelial to mesenchymal transition, collective and single-cell invasion, angiogenesis, immune evasion, and adaptation to organ-specific microenvironments. During dissemination, endocrine and HER2 pathway dependence may be retained, lost, or reconfigured through clonal selection and receptor discordance, creating clinically important differences between primary and metastatic lesions.
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name: Metastatic Breast Carcinoma
creation_date: '2026-03-28T21:00:00Z'
updated_date: '2026-05-09T19:42:12Z'
description: >-
Metastatic breast carcinoma is advanced breast cancer that has disseminated beyond
the breast and regional lymph nodes to distant organs, with particular tropism for
bone, lung, brain, and liver. Metastatic competence emerges through epithelial to
mesenchymal transition, collective and single-cell invasion, angiogenesis, immune
evasion, and adaptation to organ-specific microenvironments. During dissemination,
endocrine and HER2 pathway dependence may be retained, lost, or reconfigured through
clonal selection and receptor discordance, creating clinically important differences
between primary and metastatic lesions.
categories:
- Breast Cancer
- Metastatic Cancer
- Solid Tumor
parents:
- breast carcinoma
disease_term:
preferred_term: metastatic breast carcinoma
term:
id: MONDO:0004989
label: breast carcinoma
mappings:
mondo_mappings:
- term:
id: MONDO:0004989
label: breast carcinoma
mapping_predicate: skos:closeMatch
mapping_source: MONDO
mapping_justification: Closest MONDO parent term available for metastatic breast carcinoma.
prevalence:
- population: Advanced breast cancer cohorts with brain metastasis
percentage: 30
notes: Brain metastases occur in up to 30% of advanced breast cancer cases.
evidence:
- reference: PMID:37386445
reference_title: "Breast cancer brain metastasis: from etiology to state-of-the-art modeling."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Brain metastases occur in as many as 30% of patients with advanced breast cancer, and the 1-year survival rate of these patients is around 20%.
explanation: This review summarizes the high burden of brain dissemination in advanced breast cancer.
- population: Swedish metastatic breast cancer cohort
percentage: 46
notes: The best 5-year survival in the cohort was observed in HER2-positive luminal disease.
evidence:
- reference: PMID:36138404
reference_title: "Long-term treatment patterns and survival in metastatic breast cancer by intrinsic subtypes - an observational cohort study in Sweden."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The 5-year survival rate was highest for HER2+/Luminal (46%) patients, followed by Luminal B (29%), Luminal A (28%), HER2+/ER- (21%), and TNBC (7%).
explanation: This provides subtype-stratified long-term survival data for metastatic breast cancer.
pathophysiology:
- name: EMT-Driven Dissemination
description: >-
Metastatic breast carcinoma acquires motile and invasive phenotypes through epithelial
to mesenchymal transition and related plasticity programs. EMT reduces epithelial
adhesion, increases migratory behavior, and facilitates escape from the primary
tumor,
intravasation, and colonization of distant tissue niches.
evidence:
- reference: PMID:37386445
reference_title: "Breast cancer brain metastasis: from etiology to state-of-the-art modeling."
supports: PARTIAL
evidence_source: HUMAN_CLINICAL
snippet: The metastasis of cancer cells from the primary tumor site to other organs in the body, notably the lungs, bones, brain, and liver, is what causes breast cancer to ultimately be fatal.
explanation: This supports the central role of distant dissemination and organotropism in lethal breast cancer.
biological_processes:
- preferred_term: epithelial to mesenchymal transition
modifier: INCREASED
term:
id: GO:0001837
label: epithelial to mesenchymal transition
- preferred_term: cell migration
modifier: INCREASED
term:
id: GO:0016477
label: cell migration
- preferred_term: positive regulation of cell migration
modifier: INCREASED
term:
id: GO:0030335
label: positive regulation of cell migration
- name: Organ-Specific Tropism
description: >-
Breast cancer metastases display seed-and-soil behavior, with preferential colonization
of bone, lung, brain, and liver. This reflects both intrinsic tumor programs and
permissive microenvironments, including osteotropic signaling in bone, vascular
adaptation in lung, and blood-brain barrier traversal in brain metastasis.
evidence:
- reference: PMID:37386445
reference_title: "Breast cancer brain metastasis: from etiology to state-of-the-art modeling."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The metastasis of cancer cells from the primary tumor site to other organs in the body, notably the lungs, bones, brain, and liver, is what causes breast cancer to ultimately be fatal.
explanation: This directly supports the dominant distant sites highlighted in metastatic breast cancer.
biological_processes:
- preferred_term: cell migration
modifier: INCREASED
term:
id: GO:0016477
label: cell migration
- name: ER and HER2 Receptor Heterogeneity
description: >-
Intratumoral spatial heterogeneity in estrogen receptor (ER), progesterone receptor
(PR),
and HER2 expression occurs in a meaningful subset of breast tumors, with biomarker
status
differing between sampled regions of the same tumor. This heterogeneity affects
breast
cancer classification accuracy from biopsy sampling and has clinical implications
for
selecting endocrine and HER2-targeted therapy.
evidence:
- reference: PMID:27349894
reference_title: "Intratumoral heterogeneity as a source of discordance in breast cancer biomarker classification."
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Intratumoral biomarker heterogeneity may impact breast cancer classification accuracy, with implications for clinical management.
explanation: This supports clinically meaningful intratumoral ER/PR/HER2 heterogeneity within primary breast cancers, affecting biomarker-based classification and treatment selection.
biological_processes:
- preferred_term: estrogen receptor signaling pathway
modifier: ABNORMAL
term:
id: GO:0030520
label: estrogen receptor signaling pathway
- preferred_term: cell surface receptor protein tyrosine kinase signaling pathway
modifier: ABNORMAL
term:
id: GO:0007169
label: cell surface receptor protein tyrosine kinase signaling pathway
- name: Angiogenic Outgrowth
description: >-
Successful metastatic colonization requires neovascular support both at the primary
site and in distant lesions. Angiogenesis promotes survival of micrometastatic
foci,
sustains growth in bone and lung deposits, and supports blood-brain barrier adaptation
in brain metastases.
biological_processes:
- preferred_term: angiogenesis
modifier: INCREASED
term:
id: GO:0001525
label: angiogenesis
- name: Immune Evasion in Metastatic Niches
description: >-
Disseminated breast cancer cells evade immune elimination by remodeling cytokine
gradients, recruiting suppressive myeloid and lymphoid populations, and adapting
to
organ-specific immune milieus. These programs help metastatic clones persist despite
host antitumor surveillance and systemic therapy.
biological_processes:
- preferred_term: negative regulation of immune response
modifier: INCREASED
term:
id: GO:0050777
label: negative regulation of immune response
phenotypes:
- category: Neurologic
name: Headache
frequency: FREQUENT
description: Brain metastases often present with headache from edema or mass effect.
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
- category: Respiratory
name: Dyspnea
frequency: FREQUENT
description: Dyspnea can reflect pulmonary metastases, pleural involvement, or treatment-related cardiopulmonary compromise.
phenotype_term:
preferred_term: Dyspnea
term:
id: HP:0002094
label: Dyspnea
- category: Musculoskeletal
name: Bone pain
frequency: VERY_FREQUENT
description: Bone-tropic metastases commonly produce pain, impending fracture risk, and spinal instability.
phenotype_term:
preferred_term: Bone pain
term:
id: HP:0002653
label: Bone pain
- category: Constitutional
name: Fatigue
frequency: VERY_FREQUENT
description: Fatigue reflects systemic inflammatory burden, anemia, treatment toxicity, and advanced metastatic disease.
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
- category: Constitutional
name: Weight loss
frequency: FREQUENT
description: Progressive metastatic disease often causes anorexia, catabolism, and cancer-associated weight loss.
phenotype_term:
preferred_term: Weight loss
term:
id: HP:0001824
label: Weight loss
treatments:
- name: CDK4/6 Inhibitor Plus Endocrine Therapy
description: >-
HR-positive, HER2-negative metastatic breast carcinoma is commonly treated
with endocrine therapy combined with a CDK4/6 inhibitor, using aromatase
inhibitor or fulvestrant backbones selected by treatment history and
resistance profile.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: palbociclib
term:
id: CHEBI:85993
label: palbociclib
- preferred_term: fulvestrant
term:
id: CHEBI:31638
label: fulvestrant
evidence:
- reference: DOI:10.1007/s10549-024-07376-w
reference_title: 'Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(−) metastatic breast cancer: prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Patients receiving 1st-line aromatase inhibitor + CDK4/6 inhibitor (n = 573) with ESR1mut had less favorable rwPFS and rwOS versus ESR1 wild-type; no differences were observed for fulvestrant + CDK4/6 inhibitor (n = 348).
explanation: >-
Real-world metastatic HR+/HER2- cohorts document aromatase-inhibitor and
fulvestrant backbones paired with CDK4/6 inhibitors in first-line therapy.
- name: Elacestrant Oral SERD for ESR1-Mutated Disease
description: >-
Elacestrant is an oral selective estrogen receptor degrader used after prior
endocrine therapy for ER-positive, HER2-negative metastatic breast carcinoma
with ESR1 mutations.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: elacestrant
term:
id: CHEBI:229213
label: elacestrant
evidence:
- reference: DOI:10.1200/jco.23.02112
reference_title: 'US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative, <i>ESR1</i>-Mutated Advanced or Metastatic Breast Cancer'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The US Food and Drug Administration (FDA) approved elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2–), estrogen receptor 1 ( ESR1)–mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy (ET).
explanation: FDA approval summary supports elacestrant for ESR1-mutated ER+/HER2- advanced or metastatic breast cancer after endocrine therapy.
- name: Capivasertib Plus Fulvestrant for PI3K/AKT/PTEN-Altered Disease
description: >-
Capivasertib plus fulvestrant targets AKT-pathway dependence in HR-positive,
HER2-negative metastatic breast carcinoma with PIK3CA, AKT1, or PTEN
alterations after progression on endocrine therapy.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: capivasertib
term:
id: CHEBI:229222
label: capivasertib
- preferred_term: fulvestrant
term:
id: CHEBI:31638
label: fulvestrant
evidence:
- reference: clinicaltrials:NCT04305496
reference_title: "A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Fulvestrant Versus Placebo + Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Breast Cancer Following Recurrence or Progression On or After Treatment With an Aromatase Inhibitor"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Phase III, double-blind, randomised study assessing the efficacy of capivasertib + fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer following recurrence or progression on or after AI therapy.
explanation: CAPItello-291 directly evaluates capivasertib plus fulvestrant in locally advanced or metastatic HR+/HER2- breast cancer after aromatase-inhibitor progression.
- name: PARP Inhibitors for Germline BRCA-Mutated Disease
description: >-
PARP inhibitors exploit homologous recombination deficiency in metastatic
breast carcinoma with germline BRCA1 or BRCA2 pathogenic variants.
treatment_term:
preferred_term: targeted therapy
term:
id: NCIT:C93352
label: Targeted Therapy
therapeutic_agent:
- preferred_term: olaparib
term:
id: CHEBI:83766
label: olaparib
- preferred_term: talazoparib
term:
id: CHEBI:231344
label: talazoparib
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: BC resulting from a germline BRCAm (gBRCAm) has distinct clinical characteristics along with increased sensitivity to DNA-damaging agents such as poly(ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapies, and potentially decreased sensitivity to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors.
explanation: Review-level evidence supports PARP inhibitor sensitivity in germline BRCA-mutated breast cancer, including advanced-disease treatment planning.
- name: Trastuzumab Deruxtecan for HER2-Positive or HER2-Low Disease
description: >-
Trastuzumab deruxtecan is an antibody-drug conjugate used for metastatic
breast carcinoma with HER2-positive or HER2-low expression after appropriate
prior therapy.
treatment_term:
preferred_term: immunotherapy
term:
id: NCIT:C15262
label: Immunotherapy
therapeutic_agent:
- preferred_term: trastuzumab deruxtecan
term:
id: NCIT:C128799
label: Trastuzumab Deruxtecan
evidence:
- reference: DOI:10.3390/cancers17213505
reference_title: 'Trastuzumab–Deruxtecan for the Treatment of Metastatic Breast Cancer Patients: Data from Real World Studies'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Trastuzumab–deruxtecan (T-DXd), a new-generation antibody drug conjugate, has greatly improved the survival and clinical benefit rates of patients affected by advanced HER2-positive/HER2-low breast cancer according to the results of controlled clinical trials with a manageable safety profile.
explanation: This review summarizes T-DXd benefit for advanced HER2-positive and HER2-low metastatic breast cancer.
- name: Sacituzumab Govitecan Antibody-Drug Conjugate
description: >-
Sacituzumab govitecan is a Trop-2-directed antibody-drug conjugate used for
metastatic breast carcinoma after prior systemic therapy, including
HR-positive/HER2-negative disease after multiple chemotherapy regimens.
treatment_term:
preferred_term: Pharmacotherapy
term:
id: NCIT:C15986
label: Pharmacotherapy
therapeutic_agent:
- preferred_term: sacituzumab govitecan
term:
id: NCIT:C102783
label: Sacituzumab Govitecan
evidence:
- reference: clinicaltrials:NCT04639986
reference_title: "A Phase 3 Asian Study of Sacituzumab Govitecan (IMMU-132) Versus Treatment of Physician's Choice (TPC) in Subjects With Hormonal Receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (MBC) Who Have Failed at Least 2 Prior Chemotherapy Regimens"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The goal of this study is to compare the study drug, sacituzumab govitecan-hziy, versus doctors' treatment of choice in participants with HR+/HER2- metastatic breast cancer (MBC) who have failed at least 2 prior chemotherapy regimens.
explanation: The phase 3 record supports sacituzumab govitecan evaluation in heavily pretreated HR+/HER2- metastatic breast cancer.
clinical_trials:
- name: CAPItello-291
phase: PHASE_III
status: ACTIVE_NOT_RECRUITING
description: >-
Phase 3 randomized study of capivasertib plus fulvestrant versus placebo plus
fulvestrant in locally advanced or metastatic HR+/HER2- breast cancer after
recurrence or progression on aromatase-inhibitor therapy.
evidence:
- reference: clinicaltrials:NCT04305496
reference_title: "A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Fulvestrant Versus Placebo + Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Breast Cancer Following Recurrence or Progression On or After Treatment With an Aromatase Inhibitor"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Phase III, double-blind, randomised study assessing the efficacy of capivasertib + fulvestrant vs placebo + fulvestrant for the treatment of patients with locally advanced (inoperable) or metastatic HR+/HER2- breast cancer following recurrence or progression on or after AI therapy.
explanation: ClinicalTrials.gov summary establishes the CAPItello-291 regimen and metastatic HR+/HER2- population.
- name: EMERALD
phase: PHASE_III
status: COMPLETED
description: >-
Phase 3 randomized trial of elacestrant monotherapy versus standard endocrine
therapy options after progression on endocrine therapy plus a CDK4/6
inhibitor.
evidence:
- reference: clinicaltrials:NCT03778931
reference_title: "Elacestrant Monotherapy vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer Following CDK4/6 Inhibitor Therapy: A Phase 3 Randomized, Open-label, Active-controlled, Multicenter Trial"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: This Phase 3 clinical study compares the efficacy and safety of elacestrant to the standard of care (SoC) options of fulvestrant or an aromatase inhibitor (AI) in women and men with breast cancer whose disease has advanced on at least one endocrine therapy including a CDK4/6 inhibitor in combination with fulvestrant or an aromatase inhibitor (AI).
explanation: ClinicalTrials.gov summary establishes the EMERALD comparator design after CDK4/6 inhibitor and endocrine therapy exposure.
- name: Sacituzumab Govitecan Versus Treatment of Physician's Choice
phase: PHASE_III
status: ACTIVE_NOT_RECRUITING
description: >-
Phase 3 trial comparing sacituzumab govitecan-hziy with physician's choice
chemotherapy in HR+/HER2- metastatic breast cancer after at least two prior
chemotherapy regimens.
evidence:
- reference: clinicaltrials:NCT04639986
reference_title: "A Phase 3 Asian Study of Sacituzumab Govitecan (IMMU-132) Versus Treatment of Physician's Choice (TPC) in Subjects With Hormonal Receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (MBC) Who Have Failed at Least 2 Prior Chemotherapy Regimens"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The goal of this study is to compare the study drug, sacituzumab govitecan-hziy, versus doctors' treatment of choice in participants with HR+/HER2- metastatic breast cancer (MBC) who have failed at least 2 prior chemotherapy regimens.
explanation: ClinicalTrials.gov summary establishes the ADC comparator trial in heavily pretreated HR+/HER2- metastatic breast cancer.
genetic:
- name: ESR1
association: Acquired endocrine resistance mutation
notes: >-
ESR1 ligand-binding domain mutations emerge during metastatic endocrine therapy
and
permit ligand-independent ER signaling.
- name: ERBB2 (HER2)
association: Amplification or overexpression
notes: >-
HER2 amplification supports aggressive dissemination and remains a major therapeutic
dependency in a subset of metastatic lesions.
- name: PIK3CA
association: Somatic activating mutation
notes: >-
PIK3CA hotspot mutations promote survival signaling, metastatic fitness, and partial
resistance to endocrine and HER2-directed therapies.
- name: TP53
association: Somatic loss of function
notes: >-
TP53 disruption facilitates genomic instability and metastatic clonal evolution,
especially
in aggressive HER2-positive and triple-negative disease.
environmental:
- name: Obesity
notes: Obesity increases inflammatory and endocrine signals that can promote recurrence and metastatic progression.
- name: Alcohol exposure
notes: Alcohol contributes to breast cancer risk and may amplify metastatic recurrence risk through endocrine and inflammatory effects.
notes: >-
Requested NCIT cross-reference: NCIT:C153238. This entry uses MONDO:0004989
(breast carcinoma) as the structured disease term because the current schema
only provides explicit MONDO mapping slots. The dominant metastatic biology is
driven by EMT, receptor plasticity, angiogenesis, immune evasion, and organotropism
to bone, lung, brain, and liver.
references:
- reference: clinicaltrials:NCT04305496
title: A Phase III Double-blind Randomised Study Assessing the Efficacy and Safety of Capivasertib + Fulvestrant Versus Placebo + Fulvestrant as Treatment for Locally Advanced (Inoperable) or Metastatic Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative (HR+/HER2-) Breast Cancer Following Recurrence or Progression On or After Treatment With an Aromatase Inhibitor
findings: []
- reference: clinicaltrials:NCT03778931
title: 'Elacestrant Monotherapy vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer Following CDK4/6 Inhibitor Therapy: A Phase 3 Randomized, Open-label, Active-controlled, Multicenter Trial'
findings: []
- reference: clinicaltrials:NCT04639986
title: A Phase 3 Asian Study of Sacituzumab Govitecan (IMMU-132) Versus Treatment of Physician's Choice (TPC) in Subjects With Hormonal Receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer (MBC) Who Have Failed at Least 2 Prior Chemotherapy Regimens
findings: []
- reference: DOI:10.1007/s10549-024-07376-w
title: 'Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(−) metastatic breast cancer: prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice'
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: The treatment landscape for HR(+)HER2(−) metastatic breast cancer (MBC) is evolving for patients with ESR1 mutations (mut) and PI3K/AKT pathway genomic alterations (GA).
supporting_text: The treatment landscape for HR(+)HER2(−) metastatic breast cancer (MBC) is evolving for patients with ESR1 mutations (mut) and PI3K/AKT pathway genomic alterations (GA).
evidence:
- reference: DOI:10.1007/s10549-024-07376-w
reference_title: 'Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(−) metastatic breast cancer: prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The treatment landscape for HR(+)HER2(−) metastatic breast cancer (MBC) is evolving for patients with ESR1 mutations (mut) and PI3K/AKT pathway genomic alterations (GA).
explanation: Deep research cited this publication as relevant literature for Metastatic Breast Carcinoma.
- reference: DOI:10.1007/s10549-024-07469-6
title: 'Trends in HR+ metastatic breast cancer survival before and after CDK4/6 inhibitor introduction in the United States: a SEER registry analysis of patients with HER2− and HER2+ metastatic breast cancer'
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: 'Trends in HR+ metastatic breast cancer survival before and after CDK4/6 inhibitor introduction in the United States: a SEER registry analysis of patients with HER2− and HER2+ metastatic breast cancer'
supporting_text: 'Trends in HR+ metastatic breast cancer survival before and after CDK4/6 inhibitor introduction in the United States: a SEER registry analysis of patients with HER2− and HER2+ metastatic breast cancer'
- reference: DOI:10.1016/j.esmoop.2024.104083
title: 'Use and outcomes of trastuzumab deruxtecan in HER2-positive and HER2-low metastatic breast cancer in a real-world setting: a nationwide cohort study'
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: 'Use and outcomes of trastuzumab deruxtecan in HER2-positive and HER2-low metastatic breast cancer in a real-world setting: a nationwide cohort study'
supporting_text: 'Use and outcomes of trastuzumab deruxtecan in HER2-positive and HER2-low metastatic breast cancer in a real-world setting: a nationwide cohort study'
- reference: DOI:10.1038/s41591-024-03269-z
title: 'Sacituzumab govitecan in HR+HER2− metastatic breast cancer: the randomized phase 3 EVER-132-002 trial'
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: 'Sacituzumab govitecan in HR+HER2− metastatic breast cancer: the randomized phase 3 EVER-132-002 trial'
supporting_text: 'Sacituzumab govitecan in HR+HER2− metastatic breast cancer: the randomized phase 3 EVER-132-002 trial'
- reference: DOI:10.1038/s41598-025-12883-x
title: Patterns and prognostic implications of distant metastasis in breast Cancer based on SEER population data
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: Distant metastasis remains the leading cause of mortality in breast cancer, yet comprehensive population-based evaluations of metastatic site combinations and their survival implications are limited.
supporting_text: Distant metastasis remains the leading cause of mortality in breast cancer, yet comprehensive population-based evaluations of metastatic site combinations and their survival implications are limited.
evidence:
- reference: DOI:10.1038/s41598-025-12883-x
reference_title: Patterns and prognostic implications of distant metastasis in breast Cancer based on SEER population data
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Distant metastasis remains the leading cause of mortality in breast cancer, yet comprehensive population-based evaluations of metastatic site combinations and their survival implications are limited.
explanation: Deep research cited this publication as relevant literature for Metastatic Breast Carcinoma.
- reference: DOI:10.1056/nejmoa2214131
title: Capivasertib in Hormone Receptor–Positive Advanced Breast Cancer
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: Capivasertib in Hormone Receptor–Positive Advanced Breast Cancer
supporting_text: Capivasertib in Hormone Receptor–Positive Advanced Breast Cancer
- reference: DOI:10.1186/s12885-025-14786-6
title: Epidemiology and outcomes associated with brain metastases among patients with metastatic breast cancer – a cohort study in US electronic health record data
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: Epidemiology and outcomes associated with brain metastases among patients with metastatic breast cancer – a cohort study in US electronic health record data
supporting_text: There are limited real-world data on the prevalence of brain metastases (BM) in metastatic breast cancer (mBC) across the treatment pathway, especially when stratified by human epidermal growth factor receptor 2–positive (HER2+) or HER2–negative (HER2−) status.
evidence:
- reference: DOI:10.1186/s12885-025-14786-6
reference_title: Epidemiology and outcomes associated with brain metastases among patients with metastatic breast cancer – a cohort study in US electronic health record data
supports: SUPPORT
evidence_source: OTHER
snippet: There are limited real-world data on the prevalence of brain metastases (BM) in metastatic breast cancer (mBC) across the treatment pathway, especially when stratified by human epidermal growth factor receptor 2–positive (HER2+) or HER2–negative (HER2−) status.
explanation: Deep research cited this publication as relevant literature for Metastatic Breast Carcinoma.
- reference: DOI:10.1200/jco.23.02112
title: 'US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative, <i>ESR1</i>-Mutated Advanced or Metastatic Breast Cancer'
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: 'US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative, <i>ESR1</i>-Mutated Advanced or Metastatic Breast Cancer'
supporting_text: The US Food and Drug Administration (FDA) approved elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2–), estrogen receptor 1 ( ESR1)–mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy (ET).
evidence:
- reference: DOI:10.1200/jco.23.02112
reference_title: 'US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative, <i>ESR1</i>-Mutated Advanced or Metastatic Breast Cancer'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The US Food and Drug Administration (FDA) approved elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2–), estrogen receptor 1 ( ESR1)–mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy (ET).
explanation: Deep research cited this publication as relevant literature for Metastatic Breast Carcinoma.
- reference: DOI:10.33590/oncolamj/ctrc4560
title: 'Updates in Advanced Hormone Receptor-Positive Breast Cancer: From Circulating Tumor DNA-Guided Therapy to Precision Medicine'
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: The therapeutic landscape for hormone receptor-positive (HR+) advanced breast cancer (BC) is moving from generalized endocrine therapies to highly targeted, biomarker-driven strategies.
supporting_text: The therapeutic landscape for hormone receptor-positive (HR+) advanced breast cancer (BC) is moving from generalized endocrine therapies to highly targeted, biomarker-driven strategies.
evidence:
- reference: DOI:10.33590/oncolamj/ctrc4560
reference_title: 'Updates in Advanced Hormone Receptor-Positive Breast Cancer: From Circulating Tumor DNA-Guided Therapy to Precision Medicine'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The therapeutic landscape for hormone receptor-positive (HR+) advanced breast cancer (BC) is moving from generalized endocrine therapies to highly targeted, biomarker-driven strategies.
explanation: Deep research cited this publication as relevant literature for Metastatic Breast Carcinoma.
- reference: DOI:10.3389/fendo.2023.1184895
title: 'Patterns of de novo metastasis and survival outcomes by age in breast cancer patients: a SEER population-based study'
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: The role of age in metastatic disease, including breast cancer, remains obscure.
supporting_text: The role of age in metastatic disease, including breast cancer, remains obscure.
evidence:
- reference: DOI:10.3389/fendo.2023.1184895
reference_title: 'Patterns of de novo metastasis and survival outcomes by age in breast cancer patients: a SEER population-based study'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: The role of age in metastatic disease, including breast cancer, remains obscure.
explanation: Deep research cited this publication as relevant literature for Metastatic Breast Carcinoma.
- reference: DOI:10.3390/cancers17213505
title: 'Trastuzumab–Deruxtecan for the Treatment of Metastatic Breast Cancer Patients: Data from Real World Studies'
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: 'Trastuzumab–Deruxtecan for the Treatment of Metastatic Breast Cancer Patients: Data from Real World Studies'
supporting_text: Trastuzumab–deruxtecan (T-DXd), a new-generation antibody drug conjugate, has greatly improved the survival and clinical benefit rates of patients affected by advanced HER2-positive/HER2-low breast cancer according to the results of controlled clinical trials with a manageable safety profile.
evidence:
- reference: DOI:10.3390/cancers17213505
reference_title: 'Trastuzumab–Deruxtecan for the Treatment of Metastatic Breast Cancer Patients: Data from Real World Studies'
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Trastuzumab–deruxtecan (T-DXd), a new-generation antibody drug conjugate, has greatly improved the survival and clinical benefit rates of patients affected by advanced HER2-positive/HER2-low breast cancer according to the results of controlled clinical trials with a manageable safety profile.
explanation: Deep research cited this publication as relevant literature for Metastatic Breast Carcinoma.
- reference: DOI:10.3390/curroncol32010001
title: The Real-World Clinical Outcomes of Heavily Pretreated HER2+ and HER2-Low Metastatic Breast Cancer Patients Treated with Trastuzumab Deruxtecan at a Single Centre
found_in:
- Metastatic_Breast_Carcinoma-deep-research-falcon.md
findings:
- statement: Trastuzumab deruxtecan (TDXd) is an antibody–drug conjugate that has demonstrated impressive activity in randomized controlled clinical trials in the context of patients with HER2-amplified and HER2-low metastatic breast cancer.
supporting_text: Trastuzumab deruxtecan (TDXd) is an antibody–drug conjugate that has demonstrated impressive activity in randomized controlled clinical trials in the context of patients with HER2-amplified and HER2-low metastatic breast cancer.
evidence:
- reference: DOI:10.3390/curroncol32010001
reference_title: The Real-World Clinical Outcomes of Heavily Pretreated HER2+ and HER2-Low Metastatic Breast Cancer Patients Treated with Trastuzumab Deruxtecan at a Single Centre
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: Trastuzumab deruxtecan (TDXd) is an antibody–drug conjugate that has demonstrated impressive activity in randomized controlled clinical trials in the context of patients with HER2-amplified and HER2-low metastatic breast cancer.
explanation: Deep research cited this publication as relevant literature for Metastatic Breast Carcinoma.
Scope and evidence note: This report is limited to sources successfully retrieved in the tool run. Several requested ontology identifiers (e.g., specific MONDO term for metastatic breast carcinoma, ICD-10/ICD-11 codes, MeSH tree numbers) were not directly retrievable from the available corpus; where absent, this is stated explicitly.
Metastatic breast carcinoma refers to breast carcinoma that has spread beyond the breast and regional lymph nodes to distant organs (distant metastasis). It is clinically aligned with stage IV breast cancer, including both de novo metastatic disease (metastatic at first diagnosis) and recurrent metastatic disease (metastasis after earlier-stage treatment). Population-based analyses use SEER “distant metastasis” indicators and commonly track organ sites including bone, lung, liver, and brain (zhang2025patternsandprognostic pages 1-2, zhang2025patternsandprognostic pages 2-4).
Commonly used synonyms in the retrieved literature include: - metastatic breast cancer (mBC) - de novo metastatic breast cancer - stage IV breast cancer - advanced breast cancer (often includes locally advanced + metastatic; context dependent) (OpenTargets Search: metastatic breast carcinoma, varghese2025epidemiologyandoutcomes pages 1-2)
Metastatic breast carcinoma represents progression of breast carcinoma via biological programs enabling invasion, dissemination, and colonization of distant sites. In the retrieved corpus, etiology is most directly addressed through genomic correlates of endocrine resistance and treatment-driven selection.
A central mechanistic theme in HR+/HER2− metastatic disease is endocrine therapy resistance associated with acquired ESR1 mutations (shah2024usfoodand pages 1-2, bhave2024comprehensivegenomicprofiling pages 1-2).
Not directly retrievable from the available sources.
Not directly retrievable from the available sources.
SEER-based patterning (2014–2023) reports that among metastatic cases, bone was most common (21.3%), followed by lung (16.1%), liver (9.2%), and brain (2.9%) (zhang2025patternsandprognostic pages 1-2). In the same dataset, specific metastatic patterns had reported median OS values, e.g., bone-only 16.0 months, lung-only 14.0, liver-only 12.0, brain-only 5.0 (zhang2025patternsandprognostic pages 6-8).
Brain metastases are a clinically important complication: an EHR-derived cohort study emphasizes prevalence and survival penalties associated with brain metastases, including lower median OS among patients with brain metastases versus those without (varghese2025epidemiologyandoutcomes pages 1-2).
Direct patient-reported outcome instruments (e.g., EQ-5D, SF-36) were not retrievable in the available sources. However, brain metastases are noted to be associated with worse outcomes and limited uptake of guideline-recommended systemic therapies in practice, suggesting substantial morbidity and care gaps (varghese2025epidemiologyandoutcomes pages 1-2).
Because HPO mappings were not present explicitly in retrieved sources, the following are suggested mappings consistent with metastatic patterns and clinical manifestations: - Metastatic lesion / distant metastasis: Metastatic neoplasm (HP:0003002; candidate) - Bone metastasis-related: bone pain (HP:0002653; candidate), pathological fracture (HP:0002756; candidate) - Lung metastasis-related: dyspnea (HP:0002094; candidate) - Liver metastasis-related: hepatomegaly (HP:0002240; candidate), abnormal liver function tests (HP:0002910; candidate) - Brain metastasis-related: headache (HP:0002315; candidate), seizures (HP:0001250; candidate), focal neurologic deficits (broad)
(These are ontology suggestions; frequencies for each symptom were not available in the retrieved literature.)
In HR+/HER2− metastatic breast cancer: - ESR1 mutations in 1st line: 8.1% (tissue biopsy), 17.5% (liquid biopsy, ctDNA tumor fraction ≥1%), 4.9% (liquid biopsy, tumor fraction <1%), rising to 59% in 3rd line (liquid biopsy, tumor fraction ≥1%) (bhave2024comprehensivegenomicprofiling pages 1-2).
The retrieved evidence emphasizes somatic acquired ESR1 mutations (endocrine resistance) (shah2024usfoodand pages 1-2, bhave2024comprehensivegenomicprofiling pages 1-2). Germline predisposition genes (e.g., BRCA1/2, PALB2) were not characterized in detail within the evidence snippets obtained here.
Not directly retrievable from the available sources.
Not directly retrievable from the available sources.
(Specific single-cell/spatial transcriptomic findings were not retrievable in this run.)
Common distant sites include: - Bone (most common) (zhang2025patternsandprognostic pages 1-2) - Lung (zhang2025patternsandprognostic pages 1-2) - Liver (zhang2025patternsandprognostic pages 1-2) - Brain (less frequent, but high impact) (zhang2025patternsandprognostic pages 1-2, varghese2025epidemiologyandoutcomes pages 1-2)
In the SEER metastatic-pattern analysis, increasing metastatic burden correlated with worse median OS, e.g., single-site median OS 15.0 months, double-site 12.0 months, and specific multi-organ combinations including brain reaching median OS 4.0 months (zhang2025patternsandprognostic pages 6-8).
Hereditary breast cancer genetics (inheritance patterns, penetrance, founder effects) were not directly retrievable in this run.
A T-DXd synthesis reports HER2-low definition consistent with modern practice: IHC 1+ or IHC 2+ with negative ISH (quaquarini2025trastuzumab–deruxtecanforthe pages 3-4).
Specific imaging performance metrics were not retrievable in this run; however, registry/EHR studies operationalize metastatic site assignment using structured metastasis variables (SEER) and EHR documentation by line-of-therapy (varghese2025epidemiologyandoutcomes pages 1-2, zhang2025patternsandprognostic pages 1-2).
In a SEER-based metastatic pattern study, median OS differed by site and combinations: - Bone-only 16.0 months; lung-only 14.0; liver-only 12.0; brain-only 5.0 (zhang2025patternsandprognostic pages 6-8). - Liver+lung+brain had the shortest median OS 4.0 months (zhang2025patternsandprognostic pages 1-2, zhang2025patternsandprognostic pages 6-8).
A SEER registry analysis comparing pre-2015 vs post-2015 guideline era in HR+/HER2− de novo metastatic breast cancer found an adjusted ~10% reduction in risk of breast cancer-specific death post-2015 (HR 0.895; p<0.0001) (OpenTargets Search: metastatic breast carcinoma).
A summary table is provided for rapid reference.
| Intervention/Study | Population | Key biomarker/setting | Primary endpoint result (median PFS, HR, p) | OS result | Notable safety | Publication (journal, month/year), PMID/DOI, URL |
|---|---|---|---|---|---|---|
| Capivasertib + fulvestrant; CAPItello-291 | HR+/HER2− advanced breast cancer after relapse/progression on aromatase inhibitor; 708 randomized; 40.8% AKT-pathway altered; 69.1% prior CDK4/6i | PIK3CA/AKT1/PTEN-altered and overall populations | Overall: median PFS 7.2 vs 3.6 mo; HR 0.60 (95% CI 0.51–0.71); P<0.001. AKT-pathway altered: median PFS 7.3 vs 3.1 mo; HR 0.50 (95% CI 0.38–0.65); P<0.001 (turner2023capivasertibinhormone media c3df1a43, turner2023capivasertibinhormone media 7aa4aaf1) | Not reported in gathered evidence | Grade ≥3 rash 12.1% vs 0.3%; grade ≥3 diarrhea 9.3% vs 0.3%; discontinuation 13.0% vs 2.3% (turner2023capivasertibinhormone media c3df1a43, turner2023capivasertibinhormone media 7aa4aaf1) | N Engl J Med, Jun 2023; DOI: 10.1056/NEJMoa2214131; https://doi.org/10.1056/NEJMoa2214131 (turner2023capivasertibinhormone media c3df1a43, turner2023capivasertibinhormone media 7aa4aaf1) |
| Sacituzumab govitecan; EVER-132-002 | Asian patients with HR+/HER2− metastatic breast cancer; SG n=166 vs chemotherapy n=165 | Post-chemotherapy HR+/HER2− mBC | Median PFS 4.3 vs 4.2 mo; HR 0.67 (95% CI 0.52–0.87); P=0.0028 (evangelou2025updatesinadvanced pages 3-4) | Median OS 21.0 vs 15.3 mo; HR 0.64 (95% CI 0.47–0.88); P=0.0061 (evangelou2025updatesinadvanced pages 3-4) | Most common grade ≥3 TEAEs: neutropenia, leukopenia, anemia (evangelou2025updatesinadvanced pages 3-4) | Nature Medicine, Oct 2024; DOI: 10.1038/s41591-024-03269-z; https://doi.org/10.1038/s41591-024-03269-z (evangelou2025updatesinadvanced pages 3-4) |
| Elacestrant; FDA approval summary based on EMERALD | ER+/HER2− advanced/metastatic breast cancer; 478 randomized, including 228 ESR1-mutant patients | ESR1-mutated disease after ≥1 prior endocrine therapy; first approved oral ER antagonist for ESR1-mutant setting | ESR1-mutant subgroup: PFS HR 0.55 (95% CI 0.39–0.77); P=.0005. ITT: PFS HR 0.70 (95% CI 0.55–0.88); P=.0018. Median PFS not reported in gathered evidence from this source (shah2024usfoodand pages 1-2) | ESR1-mut subgroup OS HR 0.90 (95% CI 0.63–1.30); OS endpoint not met (shah2024usfoodand pages 1-2) | More nausea, vomiting, dyslipidemia with elacestrant (shah2024usfoodand pages 1-2) | J Clin Oncol, Apr 2024; DOI: 10.1200/JCO.23.02112; https://doi.org/10.1200/JCO.23.02112 (shah2024usfoodand pages 1-2) |
| Trastuzumab deruxtecan; French nationwide real-world cohort | 5,890 mBC patients initiating T-DXd in France (2010 HER2+ third-line; 1260 HER2+ second-line; 2620 HER2-low second-line) | HER2+ 2L/3L and HER2-low 2L routine care | Non-randomized real-world outcomes study; PFS not reported in gathered evidence | Median OS 30.2 mo (95% CI 28.1–33.5) for HER2+ 3L; not reached for HER2+ 2L; 16.8 mo (95% CI 14.5–NR) for HER2-low 2L (jourdain2024useandoutcomes pages 1-2) | Interstitial lung disease/pneumonitis can be severe; HER2-low patients had higher hospitalization incidence rates for cardiac/respiratory/digestive/hematologic disorders than HER2+ cohorts (jourdain2024useandoutcomes pages 1-2) | ESMO Open, Dec 2024; DOI: 10.1016/j.esmoop.2024.104083; https://doi.org/10.1016/j.esmoop.2024.104083 (jourdain2024useandoutcomes pages 1-2) |
| Trastuzumab deruxtecan; single-centre retrospective series | 38 heavily pretreated mBC patients (15 HER2+, 23 HER2-low); included active CNS metastases | Heavily pretreated HER2+ and HER2-low mBC in routine practice | Non-randomized real-world response study; among 33 evaluable patients, ORR 63%, including 9% complete responses (lazaratos2024therealworldclinical pages 1-2) | OS not reported in gathered evidence | No grade 4–5 toxicities; pneumonitis in 4/38 (10.5%): grade 3 in 2, grade 2 in 1, grade 1 in 1; discontinuation in 3 cases (lazaratos2024therealworldclinical pages 1-2) | Current Oncology, Dec 2024; DOI: 10.3390/curroncol32010001; https://doi.org/10.3390/curroncol32010001 (lazaratos2024therealworldclinical pages 1-2) |
| SEER registry survival trend after CDK4/6i introduction | 11,467 women with HR+/HER2− de novo mBC; comparison pre-2015 vs post-2015 guideline era | Population-level HR+/HER2− de novo mBC; epidemiology/outcomes, not a treatment trial | Not a PFS trial; adjusted post-2015 vs pre-2015 breast cancer–specific death HR 0.895; P<0.0001 (OpenTargets Search: metastatic breast carcinoma) | Indicates ~10% reduction in risk of breast cancer–specific death post-2015; no significant BCSS change in HR+/HER2+ comparator population (OpenTargets Search: metastatic breast carcinoma) | Not reported in gathered evidence | Breast Cancer Research and Treatment, Aug 2024; DOI: 10.1007/s10549-024-07469-6; https://doi.org/10.1007/s10549-024-07469-6 (OpenTargets Search: metastatic breast carcinoma) |
| De novo metastatic breast cancer by age; SEER | 24,155 de novo metastatic breast cancer patients (2010–2019) | Epidemiology/outcomes by age group, not a trial | Not applicable | 5-year OS: young ≤40 y 42.1%; 41–60 y 34.8%; 61–80 y 28.3%; >80 y 11.8%. Mortality worse vs young: middle-aged aHR 1.18, older 1.42, oldest old 2.15 (OpenTargets Search: metastatic breast carcinoma) | Not reported in gathered evidence | Frontiers in Endocrinology, Nov 2023; DOI: 10.3389/fendo.2023.1184895; https://doi.org/10.3389/fendo.2023.1184895 (OpenTargets Search: metastatic breast carcinoma) |
| Brain metastases in mBC; US EHR cohort | 12,644 patients with mBC in US oncology EHR data; HER2+ and HER2− cohorts | Epidemiology/outcomes for brain metastases, not a trial | Not applicable | Median OS from mBC diagnosis with vs without BM: HER2+ 24 vs 37 mo; HER2− 12 vs 27 mo. BM prevalence at mBC diagnosis: HER2+ 12.5%, HER2− 1.7% (varghese2025epidemiologyandoutcomes pages 1-2) | Most patients with BM were not receiving NCCN-recommended systemic therapies; first-line uptake 25.0% in HER2+ BM vs 12.8% in HER2− BM (varghese2025epidemiologyandoutcomes pages 1-2) | BMC Cancer, Oct 2025; DOI: 10.1186/s12885-025-14786-6; https://doi.org/10.1186/s12885-025-14786-6 (varghese2025epidemiologyandoutcomes pages 1-2) |
Table: This table summarizes pivotal 2023–2024 trials and selected registry/real-world studies relevant to metastatic breast carcinoma, emphasizing efficacy, survival, and safety outcomes. It is useful for quickly comparing biomarker-defined treatment evidence with real-world epidemiology and outcome data.
CAPItello-291 (NCT04305496) showed statistically significant PFS improvements: - Overall: median PFS 7.2 vs 3.6 months; HR 0.60 (95% CI 0.51–0.71); P<0.001 (turner2023capivasertibinhormone media c3df1a43). - AKT pathway–altered: median PFS 7.3 vs 3.1 months; HR 0.50 (95% CI 0.38–0.65); P<0.001 (turner2023capivasertibinhormone media 7aa4aaf1). Notable grade ≥3 AEs included rash and diarrhea; discontinuations were higher in the capivasertib arm (turner2023capivasertibinhormone media c3df1a43).
EVER-132-002 (NCT04639986) reported: - PFS HR 0.67 with median 4.3 vs 4.2 months (P=0.0028) - OS HR 0.64 with median 21.0 vs 15.3 months (P=0.0061) with common grade ≥3 hematologic toxicities (evangelou2025updatesinadvanced pages 3-4).
From the FDA approval summary: - ESR1-mutant subgroup PFS benefit: HR 0.55 (95% CI 0.39–0.77); P=.0005 - OS endpoint not met; no OS detriment signal: HR 0.90 (95% CI 0.63–1.30) - More nausea, vomiting, dyslipidemia with elacestrant (shah2024usfoodand pages 1-2).
(Exact MAXO identifiers were not retrievable in this run; these are semantic suggestions.)
Not directly retrievable from the available sources.
Not directly retrievable from the available sources.
Not directly retrievable from the available sources.
In a large EHR cohort, “most [patients with brain metastases] were not receiving NCCN Guideline®-recommended systemic therapies,” with poorer OS in those with brain metastases (varghese2025epidemiologyandoutcomes pages 1-2).
URLs and dates are provided inline in each cited publication row and in the trial table artifact. Key examples include: - Turner et al., N Engl J Med, Jun 2023, CAPItello-291. https://doi.org/10.1056/NEJMoa2214131 (turner2023capivasertibinhormone media c3df1a43, turner2023capivasertibinhormone media 7aa4aaf1) - Xu et al., Nature Medicine, Oct 2024, EVER-132-002. https://doi.org/10.1038/s41591-024-03269-z (evangelou2025updatesinadvanced pages 3-4) - Shah et al., J Clin Oncol, Apr 2024, FDA summary for elacestrant. https://doi.org/10.1200/jco.23.02112 (shah2024usfoodand pages 1-2) - Jourdain et al., ESMO Open, Dec 2024, French nationwide T-DXd cohort. https://doi.org/10.1016/j.esmoop.2024.104083 (jourdain2024useandoutcomes pages 1-2) - Lazaratos et al., Current Oncology, Dec 2024, single-center T-DXd series. https://doi.org/10.3390/curroncol32010001 (lazaratos2024therealworldclinical pages 1-2)
References
(OpenTargets Search: metastatic breast carcinoma): Open Targets Query (metastatic breast carcinoma, 50 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(zhang2025patternsandprognostic pages 1-2): Maoquan zhang, Hanqing Deng, Rihua Hu, Fuwei Chen, Shiwen Dong, Shiyi Zhang, Wenyan Guo, Wen Yang, and Wenxin Chen. Patterns and prognostic implications of distant metastasis in breast cancer based on seer population data. Scientific Reports, Jul 2025. URL: https://doi.org/10.1038/s41598-025-12883-x, doi:10.1038/s41598-025-12883-x. This article has 34 citations and is from a peer-reviewed journal.
(zhang2025patternsandprognostic pages 2-4): Maoquan zhang, Hanqing Deng, Rihua Hu, Fuwei Chen, Shiwen Dong, Shiyi Zhang, Wenyan Guo, Wen Yang, and Wenxin Chen. Patterns and prognostic implications of distant metastasis in breast cancer based on seer population data. Scientific Reports, Jul 2025. URL: https://doi.org/10.1038/s41598-025-12883-x, doi:10.1038/s41598-025-12883-x. This article has 34 citations and is from a peer-reviewed journal.
(varghese2025epidemiologyandoutcomes pages 1-2): Della Varghese, Jenna Collins, Beth Nordstrom, Miguel Miranda, Brian Murphy, and David Harland. Epidemiology and outcomes associated with brain metastases among patients with metastatic breast cancer – a cohort study in us electronic health record data. BMC Cancer, Oct 2025. URL: https://doi.org/10.1186/s12885-025-14786-6, doi:10.1186/s12885-025-14786-6. This article has 1 citations and is from a peer-reviewed journal.
(zhang2025patternsandprognostic pages 8-10): Maoquan zhang, Hanqing Deng, Rihua Hu, Fuwei Chen, Shiwen Dong, Shiyi Zhang, Wenyan Guo, Wen Yang, and Wenxin Chen. Patterns and prognostic implications of distant metastasis in breast cancer based on seer population data. Scientific Reports, Jul 2025. URL: https://doi.org/10.1038/s41598-025-12883-x, doi:10.1038/s41598-025-12883-x. This article has 34 citations and is from a peer-reviewed journal.
(turner2023capivasertibinhormone media c3df1a43): Nicholas C. Turner, Mafalda Oliveira, Sacha J. Howell, Florence Dalenc, Javier Cortes, Henry L. Gomez Moreno, Xichun Hu, Komal Jhaveri, Petr Krivorotko, Sibylle Loibl, Serafin Morales Murillo, Meena Okera, Yeon Hee Park, Joohyuk Sohn, Masakazu Toi, Eriko Tokunaga, Samih Yousef, Lyudmila Zhukova, Elza C. de Bruin, Lynda Grinsted, Gaia Schiavon, Andrew Foxley, and Hope S. Rugo. Capivasertib in hormone receptor-positive advanced breast cancer. The New England journal of medicine, 388 22:2058-2070, Jun 2023. URL: https://doi.org/10.1056/nejmoa2214131, doi:10.1056/nejmoa2214131. This article has 832 citations and is from a highest quality peer-reviewed journal.
(turner2023capivasertibinhormone media 7aa4aaf1): Nicholas C. Turner, Mafalda Oliveira, Sacha J. Howell, Florence Dalenc, Javier Cortes, Henry L. Gomez Moreno, Xichun Hu, Komal Jhaveri, Petr Krivorotko, Sibylle Loibl, Serafin Morales Murillo, Meena Okera, Yeon Hee Park, Joohyuk Sohn, Masakazu Toi, Eriko Tokunaga, Samih Yousef, Lyudmila Zhukova, Elza C. de Bruin, Lynda Grinsted, Gaia Schiavon, Andrew Foxley, and Hope S. Rugo. Capivasertib in hormone receptor-positive advanced breast cancer. The New England journal of medicine, 388 22:2058-2070, Jun 2023. URL: https://doi.org/10.1056/nejmoa2214131, doi:10.1056/nejmoa2214131. This article has 832 citations and is from a highest quality peer-reviewed journal.
(evangelou2025updatesinadvanced pages 3-4): Christos Evangelou. Updates in advanced hormone receptor-positive breast cancer: from circulating tumor dna-guided therapy to precision medicine. American Medical Journal Oncology, pages 40-49, Jul 2025. URL: https://doi.org/10.33590/oncolamj/ctrc4560, doi:10.33590/oncolamj/ctrc4560. This article has 1 citations.
(shah2024usfoodand pages 1-2): Mirat Shah, Hima Lingam, Xin Gao, Haley Gittleman, Mallorie H. Fiero, Danielle Krol, Nikolett Biel, Tiffany K. Ricks, Wentao Fu, Salaheldin Hamed, Fang Li, Jillian (Jielin) Sun, Jianghong Fan, Robert Schuck, Manuela Grimstein, Liuya Tang, Shyam Kalavar, Abdelrahmman Abukhdeir, Anand Pathak, Soma Ghosh, Ilynn Bulatao, Amy Tilley, William F. Pierce, Bronwyn D. Mixter, Shenghui Tang, Richard Pazdur, Paul Kluetz, and Laleh Amiri-Kordestani. Us food and drug administration approval summary: elacestrant for estrogen receptor–positive, human epidermal growth factor receptor 2–negative, esr1-mutated advanced or metastatic breast cancer. Journal of Clinical Oncology, 42:1193-1201, Apr 2024. URL: https://doi.org/10.1200/jco.23.02112, doi:10.1200/jco.23.02112. This article has 39 citations and is from a highest quality peer-reviewed journal.
(jourdain2024useandoutcomes pages 1-2): H. Jourdain, A. Di Meglio, I. Mansouri, D. Desplas, M. Zureik, and N. Haddy. Use and outcomes of trastuzumab deruxtecan in her2-positive and her2-low metastatic breast cancer in a real-world setting: a nationwide cohort study. ESMO Open, 9:104083, Dec 2024. URL: https://doi.org/10.1016/j.esmoop.2024.104083, doi:10.1016/j.esmoop.2024.104083. This article has 15 citations and is from a domain leading peer-reviewed journal.
(lazaratos2024therealworldclinical pages 1-2): Anna-Maria Lazaratos, Matthew Dankner, Aalya Hamouda, Soumaya Labidi, Victor Cohen, Lawrence Panasci, Jennifer E. Friedmann, François Patenaude, Cristiano Ferrario, Mark Basik, April A. N. Rose, and Parvaneh Fallah. The real-world clinical outcomes of heavily pretreated her2+ and her2-low metastatic breast cancer patients treated with trastuzumab deruxtecan at a single centre. Current Oncology, 32:1, Dec 2024. URL: https://doi.org/10.3390/curroncol32010001, doi:10.3390/curroncol32010001. This article has 9 citations.
(bhave2024comprehensivegenomicprofiling pages 1-2): Manali A. Bhave, Julia C. F. Quintanilha, Hanna Tukachinsky, Gerald Li, Takara Scott, Jeffrey S. Ross, Lincoln Pasquina, Richard S. P. Huang, Heather McArthur, Mia A. Levy, Ryon P. Graf, and Kevin Kalinsky. Comprehensive genomic profiling of esr1, pik3ca, akt1, and pten in hr(+)her2(−) metastatic breast cancer: prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice. Breast Cancer Research and Treatment, 207:599-609, Jun 2024. URL: https://doi.org/10.1007/s10549-024-07376-w, doi:10.1007/s10549-024-07376-w. This article has 50 citations and is from a peer-reviewed journal.
(zhang2025patternsandprognostic pages 6-8): Maoquan zhang, Hanqing Deng, Rihua Hu, Fuwei Chen, Shiwen Dong, Shiyi Zhang, Wenyan Guo, Wen Yang, and Wenxin Chen. Patterns and prognostic implications of distant metastasis in breast cancer based on seer population data. Scientific Reports, Jul 2025. URL: https://doi.org/10.1038/s41598-025-12883-x, doi:10.1038/s41598-025-12883-x. This article has 34 citations and is from a peer-reviewed journal.
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