Synthetic educational example. Do not self-treat: a qualified treating physician must verify the sources, patient data, contraindications, and final plan.
Patient
BREAST-TNBC-EARLY-001 · Algorithm: ALGO-BREAST-1L
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 |
|---|
| No clinically actionable variants matched in this profile. |
| Biomarker | Status |
|---|
| BIO-ER | Excluded (negative) |
| BIO-PR | Excluded (negative) |
| BIO-HER2-SOLID | Excluded (negative) |
| BIO-PDL1-CPS | BIO definition in KB; no ESCAT BMA entry — verify with clinician |
Primary current-line option
- Indication
- IND-BREAST-TNBC-EARLY-NEOADJUVANT
- Regimen
- Pembrolizumab + chemo (TNBC neoadjuvant)
- Drugs + NSZU
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV q3 weeks · Days 1 of cycles 1-8 (4 cycles each phase) · IV ⚠ NSZU — not for this indication
- Paclitaxel (DRUG-PACLITAXEL) 80 mg/m² IV weekly · Cycles 1-4 (12 weekly doses) · IV ✓ NSZU covered
- Carboplatin (DRUG-CARBOPLATIN) AUC 5 IV · Cycles 1-4 q3 weeks (or weekly AUC 1.5) · IV ⚠ NSZU — not for this indication
- Doxorubicin (DRUG-DOXORUBICIN) 60 mg/m² IV · Cycles 5-8 q3 weeks · IV ✓ NSZU covered
- Cyclophosphamide (DRUG-CYCLOPHOSPHAMIDE) 600 mg/m² IV · Cycles 5-8 q3 weeks · IV ✓ NSZU covered
- Supportive care
- SUP-G-CSF-PRIMARY-PROPHYLAXIS-PROSTATE, SUP-BONE-HEALTH-PROSTATE
- Reason
- Primary current-line option selected by ALGO-BREAST-1L at step 4.
Other current-line alternatives (8 tracks)
Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.
- Indication
- IND-BREAST-HR-POS-MET-1L-CDKI
- Regimen
- AI + ribociclib (HR+/HER2- metastatic 1L; OS-validated)
- Drugs + NSZU
- Letrozole (DRUG-LETROZOLE) 2.5 mg PO daily · Continuous · PO ✓ NSZU covered
- Ribociclib (DRUG-RIBOCICLIB) 600 mg PO daily, days 1-21 of 28-day cycle · 21 days on, 7 days off · PO ⚠ NSZU — not for this indication
- Supportive care
- SUP-BONE-HEALTH-PROSTATE
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-BREAST-HR-POS-EARLY-ADJ-CDK46I
- Regimen
- Abemaciclib adjuvant (HR+/HER2- early high-risk breast cancer)
- Drugs + NSZU
- Abemaciclib (DRUG-ABEMACICLIB) 150 mg PO BID · Continuous BID x 2 years (fixed duration) · PO ⚠ NSZU — not for this indication
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB
- Regimen
- Ribociclib adjuvant + AI (HR+/HER2- early breast cancer; NATALEE)
- Drugs + NSZU
- Ribociclib (DRUG-RIBOCICLIB) 400 mg PO QD · Days 1-21 of each 28-day cycle (3 weeks on, 1 week off) · PO ⚠ NSZU — not for this indication
- Letrozole (DRUG-LETROZOLE) 2.5 mg PO QD · Continuous (or anastrozole 1 mg QD or exemestane 25 mg QD as alternatives) · PO ✓ NSZU covered
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-BREAST-HER2-POS-EARLY-NEOADJUVANT
- Regimen
- TCHP — docetaxel + carboplatin + trastuzumab + pertuzumab (HER2+ neoadjuvant)
- Drugs + NSZU
- Docetaxel (DRUG-DOCETAXEL) 75 mg/m² IV · Day 1 of 21-day cycle x 6 cycles · IV ✓ NSZU covered
- Carboplatin (DRUG-CARBOPLATIN) AUC 6 IV · Day 1 of 21-day cycle x 6 cycles · IV ⚠ NSZU — not for this indication
- Trastuzumab (DRUG-TRASTUZUMAB) 8 mg/kg IV loading, 6 mg/kg IV maintenance · Day 1 of 21-day cycle · IV ✓ NSZU covered
- Pertuzumab (DRUG-PERTUZUMAB) 840 mg IV loading, 420 mg IV maintenance · Day 1 of 21-day cycle · IV ✓ NSZU covered
- Supportive care
- SUP-BONE-HEALTH-PROSTATE, SUP-G-CSF-PRIMARY-PROPHYLAXIS-PROSTATE
- Reason
- Current-line alternative presented for HCP consideration
- Indication
- IND-BREAST-HER2-POS-MET-1L-THP
- Regimen
- THP — docetaxel + trastuzumab + pertuzumab (HER2+ metastatic 1L)
- Drugs + NSZU
- Docetaxel (DRUG-DOCETAXEL) 75-100 mg/m² IV · Day 1 of 21-day cycle x 6-8 cycles, then HP maintenance · IV ✓ NSZU covered
- Trastuzumab (DRUG-TRASTUZUMAB) 8 mg/kg loading, 6 mg/kg maintenance IV · Day 1 of 21-day cycle, continuous until progression · IV ✓ NSZU covered
- Pertuzumab (DRUG-PERTUZUMAB) 840 mg loading, 420 mg maintenance 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-HER2-POS-MET-2L-TDXD
- 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-BRCA-POS-MET-PARPI
- 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-METASTATIC-1L-PEMBRO-CHEMO
- Regimen
- Pembrolizumab + chemotherapy (TNBC, metastatic PD-L1+)
- Drugs + NSZU
- Pembrolizumab (DRUG-PEMBROLIZUMAB) 200 mg IV over 30 min · Day 1 q21d (when combined with paclitaxel or gem-carbo); or Day 1 q28d (when combined with nab-paclitaxel) · IV ⚠ NSZU — not for this indication
- 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 3 → branch 4
- RF-BREAST-TNBC ★ winner: Triple-negative breast cancer (TNBC): estrogen receptor (ER) <1% nuclear staining on IHC AND progesterone receptor (PR) <1% nuclear staining on IHC AND HER2-negative (IHC 0 or 1+, OR IHC 2+ with ISH non-amplified). TNBC represents ~15-20% of all invasive breast cancers and is defined by the absence of all three hormone/growth-factor receptor targets.
Clinical significance: TNBC lacks ER, PR, and HER2 targets, precluding endocrine therapy (tamoxifen, aromatase inhibitors) and HER2-directed therapy. Treatment is chemotherapy-based: - Early TNBC: pembrolizumab + neoadjuvant chemotherapy (KEYNOTE-522;
Schmid NEJM 2022) — pCR rate 64.8% vs 51.2% with chemo alone, regardless
of PD-L1 status. KEYNOTE-522 is the standard-of-care regimen.
- Metastatic TNBC (BRCA-WT): pembrolizumab + chemotherapy (KEYNOTE-355)
for CPS ≥10; chemotherapy alone (nab-paclitaxel, paclitaxel, or
gemcitabine+carboplatin) for CPS <10.
- Metastatic TNBC + germline BRCA1/2 mutation: olaparib or talazoparib
preferred 1L over chemotherapy (OlympiAD; exploits HRD).
Fires to route ALGO-BREAST-1L step 3 toward the TNBC track (step 4 stage gate → PARPi or pembro+chemo routing) instead of the HR+/HER2- track (CDK4/6i+AI, step 5).
The engine sequential check (step 1: HER2+ gate via RF-BREAST-HER2-AMP- ACTIONABLE; step 3: TNBC gate via this RF) means HER2-positive patients are already routed away before step 3 fires. The HER2-negative component of the TNBC definition is therefore confirmed by the prior sequential filtering, but is included in the trigger for completeness and for use in non-sequential contexts.
SRC-NCCN-BREAST-2025SRC-KEYNOTE-522-SCHMID-2022SRC-KEYNOTE-355-CORTES-2020
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CECT-CAP | CECT chest/abdomen/pelvis | Critical | imaging | — | standard |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | all tracks |
| TEST-ER-PR-IHC | ER + PR immunohistochemistry on tumor | Critical | — | CSD Lab ✓ (code TBC) | standard |
| TEST-HER2-IHC-FISH | HER2 IHC + reflex FISH on tumor | Critical | — | CSD Lab ✓ (code TBC) | standard |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-BONE-SCAN | Whole-body Tc-99m MDP bone scintigraphy | Standard | — | — | standard |
| TEST-CT-CAP | CT chest/abdomen/pelvis | Standard | imaging | — | standard |
| TEST-ECG | Electrocardiogram | Standard | clinical_assessment | — | aggressive |
| TEST-ECHO | Echocardiography | Standard | imaging | — | all tracks |
| TEST-GERMLINE-BRCA-PANEL | Germline BRCA1/2 + HRR panel sequencing | Standard | — | CSD Lab: M089 | standard |
| TEST-PIK3CA-NGS | PIK3CA mutation testing (tumor or ctDNA) | Standard | — | CSD Lab: M065 | desired (standard) |
| TEST-TSH | Thyroid-stimulating hormone | Standard | lab | — | standard |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- ESR1 ligand-binding-domain hotspot Y537S or D538G — the two dominant hotspots (~70% of all ESR1-LBD mutations) acquired in HR+/HER2- metastatic breast progressing on aromatase inhibitor. EMERALD (Bidard 2022) randomized post-AI ± CDK4/6i HR+ MBC to elacestrant vs endocrine standard-of-care; PFS benefit was concentrated in the ESR1-mutant subgroup (mPFS 3.8 vs 1.9 mo, HR 0.55). Y537S is associated with more aggressive biology than D538G in some series. Candidate RF refines RF-BREAST-ESR1-MUT-ACTIONABLE for the predominant hotspots specifically targeted by elacestrant data.
Hotspot-specific narrowing of RF-BREAST-ESR1-MUT-ACTIONABLE. Y537S + D538G together account for ~70% of LBD mutations and are the hotspots most consistently represented in EMERALD subgroup analyses. Test on ctDNA at progression on AI ±…
RF-BREAST-ESR1-Y537S-D538G-CANDIDATESRC-NCCN-BREAST-2025SRC-ESMO-BREAST-METASTATIC-2024SRC-EMERALD-BIDARD-2022 - Age ≥75 + ECOG ≥2 + significant comorbidity — anthracycline + dose-dense regimens poorly tolerated; consider TC, weekly paclitaxel, single-agent endocrine, or trastuzumab + chemo of reduced intensity.
Geriatric assessment (G8 / CGA) recommended pre-treatment for ≥70. HR+ disease in frail elderly may be managed with endocrine therapy alone (favorable risk-benefit). HER2+: trastuzumab + paclitaxel weekly or T-DM1 monotherapy…
RF-BREAST-FRAILTY-AGESRC-NCCN-BREAST-2025SRC-ESMO-BREAST-EARLY-2024 - HBV/HCV/HIV serology + dental evaluation pre-bisphosphonate/denosumab + DPYD genotyping for capecitabine-containing regimens (EU practice).
Cross-disease HBV reactivation handled by RF-UNIVERSAL-HBV-REACTIVATION- RISK. DPYD deficiency screening unique to fluoropyrimidine-containing regimens; severe / fatal toxicity in homozygous deficient patients — EU/EMA-recommended pre-test.
RF-BREAST-INFECTION-SCREENINGSRC-NCCN-BREAST-2025SRC-ESMO-BREAST-EARLY-2024 - Cardiac dysfunction (LVEF <50%) — anthracycline + trastuzumab/pertuzumab + T-DM1/T-DXd all carry cardiotoxicity risk; baseline echo + serial monitoring required.
Anthracycline + trastuzumab cumulative cardiotoxicity well-established. Modern strategies: cardio-oncology consult; substitute non-anthracycline regimen (TC for HER2-) or modified HER2-backbone if anthracycline contraindicated. T-DXd…
RF-BREAST-ORGAN-DYSFUNCTIONSRC-NCCN-BREAST-2025SRC-ESMO-BREAST-EARLY-2024 - Somatic (tumor-only) BRCA1 or BRCA2 pathogenic variant identified on tumor NGS — pan-tumor PARPi-candidate signal. Disease applicability varies: ovarian (PAOLA-1, SOLO-1 — somatic BRCA pooled with germline in HRD-positive maintenance indication), mCRPC (PROfound cohort-A — olaparib mPFS 7.4 vs 3.6 mo, HR 0.34, somatic + germline pooled), pancreatic PDAC (POLO label is germline-only — somatic BRCA falls to off-label / NCCN "consider" tier), breast (OlympiAD / EMBRACA / OlympiA labels are germline-only — somatic BRCA breast remains investigational). Confirm somatic vs germline status via paired germline NGS before cascade-testing decisions (~40% of tumor-only "BRCA" calls are in fact germline per ASCO/CAP guidance).
Distinct trigger keys from RF-OVARIAN-BRCA-MUT-ACTIONABLE and RF-PROSTATE-HIGH-RISK-BIOLOGY to avoid double-firing on germline cases — this RF keys specifically on "*_somatic" / "tumor_*" findings. Breast included as informational (no…
RF-PAN-BRCA-SOMATIC-PARPI-CANDIDATESRC-PROFOUND-DEBONO-2020SRC-NCCN-OVARIAN-2025SRC-NCCN-PROSTATE-2025
CONTRA-AGGRESSIVE
Hard contraindications to escalation
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Standard plan (IND-BREAST-HR-POS-EARLY-ADJ-CDK46I)
- Do NOT use in pregnancy — CDK4/6i are teratogenic.
- Do NOT start until full surgical wound healing.
- Do NOT combine with strong CYP3A4 inhibitors — significant abemaciclib concentration increase.
- Do NOT skip CBC monitoring q2w first 2 months — severe neutropenia risk.
Aggressive plan (IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB)
- Do NOT use in pregnancy — CDK4/6i are teratogenic.
- Do NOT start if baseline QTcF >450 ms — ribociclib prolongs QT interval (boxed warning; fatal arrhythmia risk).
- Do NOT combine with strong CYP3A4 inhibitors (azole antifungals, clarithromycin, etc.) — significant ribociclib exposure increase.
- Do NOT skip ECG/QTc monitoring (baseline, Day 14 Cycle 1, periodic thereafter) — fatal arrhythmia risk.
- Do NOT use 600 mg dose adjuvantly — NATALEE protocol uses 400 mg; 600 mg is metastatic dosing only.
Standard plan (IND-BREAST-TNBC-METASTATIC-1L-PEMBRO-CHEMO)
- НІКОЛИ не призначати пембролізумаб при CPS <10 — відсутня OS перевага; тільки токсичnoсть
- Не призначати без тестування BRCA1/2 — BRCA-мутоваno пацієнти мають кращу відповідь на PARPi
- Не використовувати атезолізумаб при TNBC — FDA відкликала реєстрацію у серпno 2021
- Не застосовувати схему при стадії I-III (неоад'ювантnoй) — використовувати KEYNOTE-522 протокол
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Standard plan
Induction · Pembrolizumab + chemo (TNBC neoadjuvant)
21-day cycles × 8 (paclitaxel/carbo+pembro phase 1-4, then AC+pembro phase 5-8)
Standard plan
Induction · AI + ribociclib (HR+/HER2- metastatic 1L; OS-validated)
28-day cycles × Continuous until progression
Standard plan
Induction · Abemaciclib adjuvant (HR+/HER2- early high-risk breast cancer)
28-day cycles × 26 cycles (2 years fixed duration)
Aggressive plan
Induction · Ribociclib adjuvant + AI (HR+/HER2- early breast cancer; NATALEE)
28-day cycles × 36 cycles (3 years) for ribociclib; AI continues to 5 years
Standard plan
Induction · TCHP — docetaxel + carboplatin + trastuzumab + pertuzumab (HER2+ neoadjuvant)
21-day cycles × 6 (then surgery → adjuvant trastuzumab + pertuzumab to complete 1 year HER2-targeted therapy; T-DM1 if residual disease)
Standard plan
Induction · THP — docetaxel + trastuzumab + pertuzumab (HER2+ metastatic 1L)
21-day cycles × Docetaxel × 6-8; HP continues 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 · Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early)
28-day cycles × Adjuvant: 12; Metastatic: continuous until progression
Standard plan
Induction · Pembrolizumab + chemotherapy (TNBC, metastatic PD-L1+)
28-day cycles × Pembrolizumab: up to 35 cycles (2 years) total or until progression/toxicity; chemo: typically 6-8 cycles then pembrolizumab maintenance
MDT brief
Discussion questions (4, 1 blocking)
OQ-LDH-CURRENT
What is the current LDH? Marker of tumor burden and transformation.
LDH is part of the prognostic indices of indolent lymphomas.
→ hematologist
BLOCKING OQ-BIOMARKER-ESTROGEN-RECEPTOR
What is the status of Estrogen receptor (ER) (BIO-ESTROGEN-RECEPTOR)? It is required by track(s): IND-BREAST-TNBC-EARLY-NEOADJUVANT, IND-BREAST-HR-POS-MET-1L-CDKI, IND-BREAST-HR-POS-EARLY-ADJ-CDK46I, IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB. Expected value: negative.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ pathologist
OQ-BIOMARKER-BRCA-GERMLINE
What is the status of Germline BRCA1/2 mutation status (BIO-BRCA-GERMLINE)? It is required by track(s): IND-BREAST-BRCA-POS-MET-PARPI. Expected value: positive.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ molecular_geneticist
OQ-BIOMARKER-PROGESTERONE-RECEPTOR
What is the status of Progesterone receptor (PR) (BIO-PROGESTERONE-RECEPTOR)? It is required by track(s): IND-BREAST-HR-POS-MET-1L-CDKI. Expected value: positive.
A treatment-track biomarker requirement is missing from the patient profile; the MDT should verify the test result, method, specimen, and date before relying on this option.
→ pathologist
MDT talk tree (5 steps)
| # | Owner | Topic | Action |
|---|
| 1 | pathologist | Biomarker status BLOCKING | What is the status of Estrogen receptor (ER) (BIO-ESTROGEN-RECEPTOR)? It is required by track(s): IND-BREAST-TNBC-EARLY-NEOADJUVANT, IND-BREAST-HR-POS-MET-1L-CDKI, IND-BREAST-HR-POS-EARLY-ADJ-CDK46I, IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB. Expected value: negative. |
| 2 | hematologist | Staging / disease burden | What is the current LDH? Marker of tumor burden and transformation. |
| 3 | molecular_geneticist | Biomarker status | What is the status of Germline BRCA1/2 mutation status (BIO-BRCA-GERMLINE)? It is required by track(s): IND-BREAST-BRCA-POS-MET-PARPI. Expected value: positive. |
| 4 | pathologist | Biomarker status | What is the status of Progesterone receptor (PR) (BIO-PROGESTERONE-RECEPTOR)? It is required by track(s): IND-BREAST-HR-POS-MET-1L-CDKI. Expected value: positive. |
| 5 | clinical_pharmacist | Specialist review | Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication. |
Skills (recommended) — for consideration (3)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
- Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Owns: OQ-BIOMARKER-BRCA-GERMLINE
- Pathologist (general) recommended
Confirm lymphoma histology + assess transformation risk (DLBCL/Richter).
Owns: OQ-BIOMARKER-ESTROGEN-RECEPTOR, OQ-BIOMARKER-PROGESTERONE-RECEPTOR
Data quality
Incomplete for default-track review. Default-track review is incomplete until required biomarker gaps are resolved.
- Biomarker coverage: 2/5 known (40%), 3 missing, 1 default-track gaps
- Unevaluated RedFlags: RF-ACTIVE-AUTOIMMUNE-DISEASE-ICI-RISK, RF-ATM-CONFIRMED-CARRIER, RF-ATM-FAMILY-HISTORY-SUSPICION, RF-BARD1-CONFIRMED-CARRIER, RF-BARD1-FAMILY-HISTORY-SUSPICION, RF-BLM-CONFIRMED-CARRIER, RF-BRCA-CONFIRMED-CARRIER, RF-BRCA-HBOC-FAMILY-HISTORY-SUSPICION, 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-CASCADE-BRCA-FDR-POSITIVE, RF-CASCADE-LFS-FDR-POSITIVE, RF-CHEK2-CONFIRMED-CARRIER, RF-CHEK2-FAMILY-HISTORY-SUSPICION, RF-CHRONIC-SEVERE-OBESITY-BMI40-PREVENTION, RF-CHRONIC-T2DM-CANCER-RISK-PREVENTION, RF-COWDEN-CONFIRMED-CARRIER, RF-COWDEN-FAMILY-HISTORY-SUSPICION, RF-HDGC-CDH1-CONFIRMED-CARRIER, RF-IATROGENIC-COMBINED-HRT-PREVENTION, RF-IATROGENIC-IODINE131-SECONDARY-PREVENTION, RF-IATROGENIC-LONG-TERM-HRMNL-CONTRACEPTION-PREVENTION, RF-IATROGENIC-PRIOR-RADIATION-PREVENTION, RF-LI-FRAUMENI-CONFIRMED-CARRIER, RF-LI-FRAUMENI-FAMILY-HISTORY-SUSPICION, RF-LIFESTYLE-ALCOHOL-CANCER-PREVENTION, RF-LIFESTYLE-OBESITY-CANCER-PREVENTION, RF-LIFESTYLE-SEDENTARY-PREVENTION, RF-LIFESTYLE-SUGARY-BEVERAGES-PREVENTION, RF-NBN-CONFIRMED-CARRIER, RF-NF1-CONFIRMED-CARRIER, RF-NF1-FAMILY-HISTORY-SUSPICION, RF-OCC-IONIZING-RADIATION-PREVENTION, RF-OCC-SHIFTWORK-CIRCADIAN-PREVENTION, RF-PALB2-CONFIRMED-CARRIER, RF-PALB2-FAMILY-HISTORY-SUSPICION, RF-PAN-ATM-CHEK2-CDK12-PARPI-CANDIDATE, RF-PAN-BRCA-SOMATIC-PARPI-CANDIDATE, RF-PAN-PALB2-PARPI-CANDIDATE, RF-PEUTZ-JEGHERS-CONFIRMED-CARRIER, RF-PEUTZ-JEGHERS-FAMILY-HISTORY-SUSPICION, RF-RAD51C-D-CONFIRMED-CARRIER, RF-RAD51C-D-FAMILY-HISTORY-SUSPICION, RF-REPRODUCTIVE-BREAST-ENDOMETRIAL-PREVENTION, RF-REPRODUCTIVE-DES-IN-UTERO-EXPOSURE-PREVENTION, RF-REPRODUCTIVE-LATE-FIRST-PREGNANCY-PREVENTION, RF-REPRODUCTIVE-OCP-LONG-TERM
| Missing biomarker | Label | MDT owner | Default track | Required by | Next action |
|---|
BIO-ESTROGEN-RECEPTOR | Estrogen receptor (ER) | pathologist | yes | IND-BREAST-TNBC-EARLY-NEOADJUVANT, IND-BREAST-HR-POS-MET-1L-CDKI, IND-BREAST-HR-POS-EARLY-ADJ-CDK46I, IND-BREAST-HR-POS-EARLY-ADJ-RIBOCICLIB | Verify result, method, specimen, and report date before sign-off. Expected/constraint: negative |
BIO-BRCA-GERMLINE | Germline BRCA1/2 mutation status | molecular_geneticist | no | IND-BREAST-BRCA-POS-MET-PARPI | Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive |
BIO-PROGESTERONE-RECEPTOR | Progesterone receptor (PR) | pathologist | no | IND-BREAST-HR-POS-MET-1L-CDKI | Verify result, method, specimen, and report date before sign-off. Expected/constraint: positive |
Technical MDT skill metadata (3/16 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-DESTINY-BREAST03-CORTES-2022: Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer (2022)
- SRC-ESMO-BREAST-EARLY-2024: ESMO Clinical Practice Guideline on Early Breast Cancer (2024)
- SRC-ESMO-BREAST-METASTATIC-2024: ESMO Clinical Practice Guideline on Metastatic Breast Cancer (2024)
- SRC-HER2CLIMB-MURTHY-2019: Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer (2019)
- SRC-KEYNOTE-355-CORTES-2020: Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355) (2020)
- SRC-KEYNOTE-522-SCHMID-2022: Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer (2022)
- SRC-MONALEESA-2-HORTOBAGYI-2016: Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer (2016)
- SRC-MONALEESA-3-SLAMON-2018: Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer (MONALEESA-3) (2018)
- SRC-MONALEESA-7-TRIPATHY-2018: Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7) (2018)
- SRC-MONARCHE-JOHNSTON-2023: Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial (2023)
- SRC-NATALEE-SLAMON-2024: Ribociclib plus Endocrine Therapy in Early Breast Cancer (2024)
- SRC-NCCN-BREAST-2025: NCCN Clinical Practice Guidelines — Breast Cancer (2025.v4)
Experimental options (clinical trials)
Third plan track — open-enrollment trials from ClinicalTrials.gov. Render-time metadata; engine selection is not affected by this block (CHARTER §8.3). Last synced: 2026-08-17.
| NCT | Title | Phase | Status | Sponsor | UA | Signals | Eligibility (excerpt) |
|---|
| NCT07102381 | A Phase 2 Neoadjuvant Study of Zanidatamab in Combination With Chemotherapy in Participants With HER2-positive Breast Cancer | PHASE2 | RECRUITING | — | — | |
| NCT06995118 | The Application of "HUAXI Hole 1" in Reverse-sequence Endoscopic Nipple-sparing Mastectomy With Direct-to-implant Breast Reconstruction | NA | RECRUITING | — | Single country | |
| NCT05196087 | Non-Invasive Artificial Intelligence-Based Platform MonIToring Program (NIP IT!) | N/A | RECRUITING | — | Single country | |
| NCT06268665 | Tart Cherry Juice as a Dietary Supplement for the Prevention of Paclitaxel-Induced Neuropathy | PHASE2 | RECRUITING | — | Single country | |
| NCT05919108 | Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers | PHASE2 | RECRUITING | — | Small N (<50) Single country | |
| NCT07483307 | A Study of the Impact of Endocrine Therapy on Surgical Outcomes in People With Lobular Breast Cancer | PHASE2 | RECRUITING | — | Single country | |
| NCT00477100 | Biospecimen and Medical Data Collection and Tumor Biopsy in Creating Research Tissue Registry in Patients With Inflammatory or Invasive Breast Cancer | N/A | RECRUITING | — | Single country | |
| NCT05059444 | ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation | N/A | RECRUITING | — | — | |
| NCT06518837 | Tirzepatide for Weight Loss Intervention in Early-Stage Hormone Receptor Positive/HER2 Negative Breast Cancer | PHASE2 | RECRUITING | — | Small N (<50) Single country | |
| NCT07067437 | Single-Fraction Very Accelerated Partial Breast Irradiation (sfVAPBI) | NA | RECRUITING | — | — | |
Verify recruitment status directly with the trial site. ctgov data can lag behind current UA-site status.
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 Pembrolizumab + chemo (TNBC neoadjuvant) (REG-PEMBRO-CHEMO-TNBC-NEOADJUVANT) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan AI + ribociclib (HR+/HER2- metastatic 1L; OS-validated) (REG-AI-RIBOCICLIB) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Abemaciclib adjuvant (HR+/HER2- early high-risk breast cancer) (REG-ABEMACICLIB-ADJUVANT) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan Ribociclib adjuvant + AI (HR+/HER2- early breast cancer; NATALEE) (REG-RIBOCICLIB-AI-ADJUVANT) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan TCHP — docetaxel + carboplatin + trastuzumab + pertuzumab (HER2+ neoadjuvant) (REG-TCHP-NEOADJUVANT) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan THP — docetaxel + trastuzumab + pertuzumab (HER2+ metastatic 1L) (REG-THP-METASTATIC) | ✓ 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 Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early) (REG-OLAPARIB-BREAST) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Pembrolizumab + chemotherapy (TNBC, metastatic PD-L1+) (REG-PEMBRO-CHEMO-TNBC-MET) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Trial · NCT07102381 A Phase 2 Neoadjuvant Study of Zanidatamab in Combination With Chemotherapy in Participants With HER2-positive Breast Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06995118 The Application of "HUAXI Hole 1" in Reverse-sequence Endoscopic Nipple-sparing Mastectomy With Direct-to-implant Breast Reconstruction No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05196087 Non-Invasive Artificial Intelligence-Based Platform MonIToring Program (NIP IT!) No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06268665 Tart Cherry Juice as a Dietary Supplement for the Prevention of Paclitaxel-Induced Neuropathy No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05919108 Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07483307 A Study of the Impact of Endocrine Therapy on Surgical Outcomes in People With Lobular Breast Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT00477100 Biospecimen and Medical Data Collection and Tumor Biopsy in Creating Research Tissue Registry in Patients With Inflammatory or Invasive Breast Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT05059444 ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT06518837 Tirzepatide for Weight Loss Intervention in Early-Stage Hormone Receptor Positive/HER2 Negative Breast Cancer No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
| Trial · NCT07067437 Single-Fraction Very Accelerated Partial Breast Irradiation (sfVAPBI) No UA site listed — international referral required | — unknown | — unknown | self-pay: ₴0/course | Trial sponsor |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-08-17.