Patient
BREAST-TNBC-2L-TALAZO-001 · Algorithm: ALGO-BREAST-TNBC-2L
Clinical significance of mutations (ESCAT)
Tumor-board context — the engine does not use these tiers to rank tracks
| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|
| BIO-BRCA1-BRCA2-GERMLINE | BRCA1 germline pathogenic | IA | Molecular evidence option - SRC-CIVIC: Level A (Supports, Sensitivity/Response)
- SRC-CIVIC: Level B (Supports, Better Outcome)
Resistance or avoidance signal | BRCA1 germline pathogenic in HER2-negative metastatic breast (HR+ or TNBC): olaparib (OlympiAD, Robson 2017) and talazoparib (EMBRACA, Litton 2018) improve PFS vs physician-choice chemotherapy. In early-stage high-risk HER2-negative: 1y adjuvant olaparib improves iDFS and OS (OlympiA, Tutt 2021). ESCAT IA / OncoKB Level 1. | olaparib monotherapy
talazoparib monotherapy
olaparib adjuvant 1y (high-risk early) | - SRC-NCCN-BREAST-2025
- SRC-ESMO-BREAST-METASTATIC-2024
- SRC-ESMO-BREAST-EARLY-2024
|
| BIO-BRCA1-BRCA2-GERMLINE | BRCA2 germline pathogenic | IA | Molecular evidence option - SRC-CIVIC: Level A (Supports, Sensitivity/Response)
- SRC-CIVIC: Level B (Supports, Better Outcome)
Resistance or avoidance signal Trial or research option - SRC-CIVIC: Level C (Supports, Sensitivity/Response)
| BRCA2 germline pathogenic in HER2-negative metastatic breast: olaparib (OlympiAD) and talazoparib (EMBRACA) improve PFS; in early-stage high-risk HER2-negative, 1y adjuvant olaparib improves iDFS and OS (OlympiA). ESCAT IA / OncoKB Level 1. | olaparib monotherapy
talazoparib monotherapy
olaparib adjuvant 1y
platinum-based chemo (TNBC) | - SRC-NCCN-BREAST-2025
- SRC-ESMO-BREAST-METASTATIC-2024
- SRC-ESMO-BREAST-EARLY-2024
|
| Biomarker | Status |
|---|
| BIO-ER | Excluded (negative) |
| BIO-PR | Excluded (negative) |
| BIO-HER2-SOLID | Excluded (negative) |
Primary current-line option
- Indication
- IND-BREAST-TNBC-2L-BRCA-OLAPARIB
- Regimen
- Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early)
- Drugs + NSZU
- Olaparib (DRUG-OLAPARIB) 300 mg PO BID continuous · Until progression (metastatic) or 1 year (OlympiA adjuvant) · PO ⚠ NSZU — not for this indication
- Supportive care
- SUP-BONE-HEALTH-PROSTATE
- Reason
- Primary current-line option selected by ALGO-BREAST-TNBC-2L at step 1; branch-driving red flag: RF-BREAST-BRCA-GERMLINE-ACTIONABLE.
Other current-line alternatives (3 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-BREAST-TNBC-2L-BRCA-TALAZOPARIB
- Regimen
- Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early)
- Drugs + NSZU
- Olaparib (DRUG-OLAPARIB) 300 mg PO BID continuous · Until progression (metastatic) or 1 year (OlympiA adjuvant) · PO ⚠ NSZU — not for this indication
- Supportive care
- SUP-BONE-HEALTH-PROSTATE
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-BREAST-TNBC-2L-T-DXD-HER2-LOW
- Regimen
- T-DXd monotherapy (HER2+ metastatic 2L+, also HER2-low metastatic)
- Drugs + NSZU
- Trastuzumab deruxtecan (T-DXd) (DRUG-TRASTUZUMAB-DERUXTECAN) 5.4 mg/kg IV · Day 1 of 21-day cycle, continuous until progression · IV ✓ NSZU covered
- Supportive care
- SUP-BONE-HEALTH-PROSTATE
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-BREAST-TNBC-2L-SACITUZUMAB
- Regimen
- Sacituzumab govitecan monotherapy (TNBC ≥2L; HR+/HER2- ≥3L)
- Drugs + NSZU
- Sacituzumab govitecan (DRUG-SACITUZUMAB-GOVITECAN) 10 mg/kg IV · Days 1, 8 of 21-day cycle, until progression · IV ✗ Not registered in UA
- Supportive care
- SUP-G-CSF-PRIMARY-PROPHYLAXIS-PROSTATE, SUP-BONE-HEALTH-PROSTATE
- Reason
- Current-line alternative presented for HCP consideration
Why this branch was chosen
Triggers from the patient profile that fired and drove the chosen branch.
Step 1 → branch IND-BREAST-TNBC-2L-BRCA-OLAPARIB
- RF-BREAST-BRCA-GERMLINE-ACTIONABLE ★ winner: Germline BRCA1 or BRCA2 pathogenic variant in HER2-negative breast cancer (HR+ or TNBC). Olaparib (OlympiAD — mPFS 7.0 vs 4.2 mo vs chemo) and talazoparib (EMBRACA — mPFS 8.6 vs 5.6 mo) are FDA-approved for metastatic gBRCA HER2-negative breast. Adjuvant olaparib (OlympiA) for high-risk HER2-negative gBRCA early breast.
SRC-NCCN-BREAST-2025SRC-ESMO-BREAST-METASTATIC-2024SRC-OLYMPIAD-ROBSON-2017SRC-EMBRACA-LITTON-2018
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-CECT-CAP | CECT chest/abdomen/pelvis | Critical | imaging | — | all tracks |
| TEST-ER-PR-IHC | ER + PR immunohistochemistry on tumor | Critical | — | CSD Lab ✓ (code TBC) | all tracks |
| TEST-HER2-IHC-FISH | HER2 IHC + reflex FISH on tumor | Critical | — | CSD Lab ✓ (code TBC) | all tracks |
| TEST-GERMLINE-BRCA-PANEL | Germline BRCA1/2 + HRR panel sequencing | Standard | — | CSD Lab: M089 | all tracks |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- HER2-ultralow breast cancer (IHC > 0 < 1+; faint/incomplete membrane staining ≤10% of tumor cells) — a sub-tier between IHC 0 and IHC 1+ not part of standard ASCO/CAP scoring. DESTINY-Breast06 (Bardia 2024 ASCO plenary) extended T-DXd benefit beyond HER2-low to HER2-ultralow HR+ metastatic breast post-endocrine + CDK4/6i, chemo-naive in the metastatic setting (HER2-low cohort mPFS 13.2 vs 8.1 mo, HR 0.62; HER2-ultralow exploratory n=153 mPFS 13.2 vs 8.3 mo, HR 0.78). FDA label expansion anticipated 2026 — candidate RF until pivotal-trial Source SRC-DESTINY-BREAST06-BARDIA-2024 ingested.
RF-BREAST-HER2-ULTRALOW-CANDIDATE
- HBV/HCV/HIV serology + dental evaluation pre-bisphosphonate/denosumab + DPYD genotyping for capecitabine-containing regimens (EU practice).RF-BREAST-INFECTION-SCREENING
CONTRA-AGGRESSIVE
Hard contraindications to escalation
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early)
28-day cycles × Adjuvant: 12; Metastatic: continuous until progression
Standard plan
Induction · T-DXd monotherapy (HER2+ metastatic 2L+, also HER2-low metastatic)
21-day cycles × Continuous until progression or unacceptable toxicity
Standard plan
Induction · Sacituzumab govitecan monotherapy (TNBC ≥2L; HR+/HER2- ≥3L)
21-day cycles × Continuous until progression
MDT brief
MDT talk tree (1 steps)
| # | Owner | Topic | Action |
|---|
| 1 | molecular_geneticist | Specialist review | Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed. |
Skills (recommended) — for consideration (1)
Data quality
Usable with caveats. No critical default-track gap was found, but the MDT should review the listed caveats before final sign-off.
- Biomarker coverage: 2/2 known (100%), 0 missing, 0 default-track gaps
- Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-BREAST-AKT1-E17K-ACTIONABLE, RF-BREAST-AKT1-E17K-CAPIVASERTIB-CANDIDATE, RF-BREAST-BRCA-GERMLINE-ACTIONABLE, RF-BREAST-CDH1-LOBULAR-CANDIDATE, RF-BREAST-EARLY-STAGE, RF-BREAST-ESR1-MUT-ACTIONABLE, RF-BREAST-ESR1-Y537S-D538G-CANDIDATE, RF-BREAST-FRAILTY-AGE, RF-BREAST-HER2-AMP-ACTIONABLE, RF-BREAST-HER2-LOW-ACTIONABLE, RF-BREAST-HER2-ULTRALOW-CANDIDATE, RF-BREAST-HIGH-RISK-BIOLOGY, RF-BREAST-INFECTION-SCREENING, RF-BREAST-ORGAN-DYSFUNCTION, RF-BREAST-OVARIAN-HRD-ASSAY-DISTINCTION, RF-BREAST-PIK3CA-COALT-INAVOLISIB-CANDIDATE, RF-BREAST-PIK3CA-MUT-ACTIONABLE, RF-BREAST-STAGE-IV-METASTATIC, RF-BREAST-TNBC, RF-BREAST-TRANSFORMATION-PROGRESSION, RF-PAN-ATM-CHEK2-CDK12-PARPI-CANDIDATE, RF-PAN-BRCA-SOMATIC-PARPI-CANDIDATE, RF-PAN-PALB2-PARPI-CANDIDATE
Technical MDT skill metadata (1/16 activated in this plan)
All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
| Specialist | skill_id | Version | Last reviewed | Sign-offs | Domain |
|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
Sources cited
- SRC-ASCENT-BARDIA-2021: Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer (2021)
- SRC-DESTINY-BREAST04-MODI-2022: Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer (2022)
- SRC-EMBRACA-LITTON-2018: Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation (2018)
- SRC-ESMO-BREAST-METASTATIC-2024: ESMO Clinical Practice Guideline on Metastatic Breast Cancer (2024)
- SRC-NCCN-BREAST-2025: NCCN Clinical Practice Guidelines — Breast Cancer (2025.v4)
- SRC-OLYMPIAD-ROBSON-2017: Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation (2017)
Experimental options (clinical trials)
Last synced: 2026-05-12 · ctgov.
No active trials matched this scenario in ctgov.
Option availability in Ukraine
Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|
| Standard plan Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early) (REG-OLAPARIB-BREAST) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early) (REG-OLAPARIB-BREAST) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan T-DXd monotherapy (HER2+ metastatic 2L+, also HER2-low metastatic) (REG-TDXD-METASTATIC) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Sacituzumab govitecan monotherapy (TNBC ≥2L; HR+/HER2- ≥3L) (REG-SACITUZUMAB) 1/1 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-12.