OpenOnco · Treatment Plan

Treatment plan — Invasive breast cancer

PLAN-BREAST-TNBC-2L-HER2LOW-001-V1 · v1 · 2026-05-13

Patient

BREAST-TNBC-2L-HER2LOW-001 · Algorithm: ALGO-BREAST-TNBC-2L

DiagnosisInvasive breast cancer

MOH / ICD-10C50

ICD-O-38500/3; C50.9

StageIV

Histologyinvasive_ductal_carcinoma_NST

Clinical significance of mutations (ESCAT)

Tumor-board context — the engine does not use these tiers to rank tracks

✅ Covered biomarkers (matched in KB)

Biomarker	Variant	ESCAT	Evidence	Clinical significance	Drugs	Sources
BIO-HER2-LOW	IHC 1+ OR IHC 2+/ISH-negative (HER2-low by ASCO/CAP 2023 criteria)	IA	Standard care SRC-DESTINY-BREAST04-MODI-2022: Level A (Supports, Sensitivity/Response) SRC-NCCN-BREAST-2025: Level Category 1 (Supports, Sensitivity/Response) SRC-ESMO-BREAST-METASTATIC-2024: Level A (Supports, Sensitivity/Response)	Trastuzumab deruxtecan (T-DXd, DS-8201) is FDA-approved (Aug 2022) for unresectable or metastatic HER2-low (IHC 1+ or 2+/ISH-) breast cancer following prior chemotherapy. DESTINY-Breast04 (Modi et al. NEJM 2022): HR+/HER2-low — mPFS 10.1 vs 5.4 mo (HR 0.49, p<0.001); mOS 23.9 vs 17.5 mo (HR 0.64, p=0.003). HR-/HER2-low (TNBC subgroup) — mOS 18.2 vs 8.3 mo. DESTINY-Breast06 (Curigliano et al. NEJM 2024) extended indication to HER2-low and HER2-ultralow (IHC 0 with incomplete staining) HR+/HER2- endocrine-pretreated patients — mPFS 13.2 vs 8.1 mo (HR 0.62, p<0.001). T-DXd dose: 5.4 mg/kg IV q3w. Key safety: interstitial lung disease (ILD) / pneumonitis ~12% (grade ≥3 ~3%) — mandatory baseline CT and monitoring per NCCN/ESMO. HER2-low reclassification affects ~60% of previously HER2-negative metastatic breast cancer patients — large population impact.	trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV q3w monotherapy (post-chemotherapy; DESTINY-Breast04) trastuzumab deruxtecan (T-DXd) 5.4 mg/kg IV q3w monotherapy (post-endocrine HR+ disease; DESTINY-Breast06)	SRC-NCCN-BREAST-2025 SRC-ESMO-BREAST-METASTATIC-2024 SRC-DESTINY-BREAST04-MODI-2022

⚠️ Not included in plan

Biomarker	Status
BIO-ER	Excluded (negative)
BIO-PR	Excluded (negative)

Primary current-line option

Standard plan

★ DEFAULT

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

Primary current-line option selected by ALGO-BREAST-TNBC-2L at step 3.

Other current-line alternatives (3 tracks)

Same treatment line; review when biomarker, access, contraindication, or patient-context assumptions change.

Standard plan

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

Current-line alternative presented for HCP consideration

Standard plan

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

Standard plan

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 2 → branch 3

RF-BREAST-HER2-LOW-ACTIONABLE ★ winner: HER2-low breast cancer (IHC 1+ OR IHC 2+ with non-amplified ISH) — ~50-55% of HER2-non-positive breast cancers. T-DXd 2L+ approved in HR+ and TNBC HER2-low post-chemo (DESTINY-Breast04 — mPFS 9.9 vs 5.1 mo, OS 23.4 vs 16.8 mo). SRC-NCCN-BREAST-2025SRC-ESMO-BREAST-METASTATIC-2024SRC-DESTINY-BREAST04-MODI-2022

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 · 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 · Sacituzumab govitecan monotherapy (TNBC ≥2L; HR+/HER2- ≥3L)

21-day cycles × Continuous until progression

MDT brief

Discussion questions (1, 0 blocking)

OQ-BIOMARKER-BRCA1-BRCA2-GERMLINE
What is the status of BRCA1/BRCA2 germline pathogenic variant (BIO-BRCA1-BRCA2-GERMLINE)? It is required by track(s): IND-BREAST-TNBC-2L-BRCA-OLAPARIB, IND-BREAST-TNBC-2L-BRCA-TALAZOPARIB. Expected value: pathogenic OR likely-pathogenic germline variant.
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

MDT talk tree (1 steps)

#	Owner	Topic	Action
1	molecular_geneticist	Biomarker status	What is the status of BRCA1/BRCA2 germline pathogenic variant (BIO-BRCA1-BRCA2-GERMLINE)? It is required by track(s): IND-BREAST-TNBC-2L-BRCA-OLAPARIB, IND-BREAST-TNBC-2L-BRCA-TALAZOPARIB. Expected value: pathogenic OR likely-pathogenic germline variant.

Skills (recommended) — for consideration (1)

Molecular geneticist / molecular oncologist recommended
Indication references an actionable genomic biomarker — mutation / target / actionability interpretation needed.
Owns: OQ-BIOMARKER-BRCA1-BRCA2-GERMLINE

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: 1/2 known (50%), 1 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

Missing biomarker	Label	MDT owner	Default track	Required by	Next action
`BIO-BRCA1-BRCA2-GERMLINE`	BRCA1/BRCA2 germline pathogenic variant	molecular_geneticist	no	IND-BREAST-TNBC-2L-BRCA-OLAPARIB, IND-BREAST-TNBC-2L-BRCA-TALAZOPARIB	Verify result, method, specimen, and report date before sign-off. Expected/constraint: pathogenic OR likely-pathogenic germline variant

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	Domain
Cellular therapy specialist (CAR-T)	`cellular_therapy_specialist`	v0.1.0	2026-04-25	cellular_therapy
Clinical pharmacist	`clinical_pharmacist`	v0.1.0	2026-04-25	clinical_pharmacy
Hematologist / oncohematologist	`hematologist`	v0.1.0	2026-04-25	hematology_oncology
Hematopathologist (lymphoma / leukemia / myeloma)	`hematopathologist`	v0.1.0	2026-04-25	hematopathology
Infectious disease / hepatology	`infectious_disease_hepatology`	v0.1.0	2026-04-25	infectious_diseases
Medical oncologist (solid-tumor chemotherapist)	`medical_oncologist`	v0.1.0	2026-04-25	solid_oncology
Molecular geneticist / molecular oncologist	`molecular_geneticist`	v0.1.0	2026-04-25	molecular_oncology
Palliative care	`palliative_care`	v0.1.0	2026-04-25	palliative_care
Pathologist (general)	`pathologist`	v0.1.0	2026-04-25	pathology
Primary care / family physician	`primary_care`	v0.1.0	2026-04-25	primary_care
Psycho-oncologist	`psychologist`	v0.1.0	2026-04-25	psychosocial
Radiation oncologist	`radiation_oncologist`	v0.1.0	2026-04-25	radiation_oncology
Radiologist	`radiologist`	v0.1.0	2026-04-25	diagnostic_imaging
Social worker / case manager	`social_worker_case_manager`	v0.1.0	2026-04-25	psychosocial
Surgical oncologist	`surgical_oncologist`	v0.1.0	2026-04-25	surgical_oncology
Transplant specialist (BMT)	`transplant_specialist`	v0.1.0	2026-04-25	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)

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: 2026-05-13.

NCT	Title	Phase	Status	Sponsor	UA	Signals
NCT07318051	Sample Collection for Ongoing Research and Product Evaluation Study	N/A	RECRUITING	Natera, Inc.	—	Single country
NCT07137416	Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer	PHASE1	RECRUITING	National Cancer Institute (NCI)	—	Phase 1 only Small N (<50) Single country
NCT05607004	(Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer	PHASE2	RECRUITING	Atossa Therapeutics, Inc.	—	Surrogate endpoint only Single country
NCT07122713	Definitive Radiation Therapy for Inoperable Breast Cancer	NA	RECRUITING	Alexander Stessin	—	Small N (<50) Single country
NCT05877859	Evaluating and Monitoring Immune and Clinical Responses in Early-Stage Triple Negative Breast Cancer Undergoing Neoadjuvant Chemo-immunotherapy With Pembrolizumab	N/A	RECRUITING	Emory University	—	Small N (<50) 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	M.D. Anderson Cancer Center	—	Single country
NCT04959474	Pre-operative SABR With and Without Caloric Restriction for Early Stage Breast Cancer	NA	RECRUITING	Thomas Jefferson University	—	Single country
NCT06067503	Biomarkers to Detect Endocrine Therapy Resistance	PHASE2	RECRUITING	University of Wisconsin, Madison	—	Small N (<50) Single country
NCT05412225	A Study of an Alternative Treatment Approach (Preoperative Radiotherapy, Then Mastectomy, Then Immediate Reconstruction Surgery) in People With T4 Breast Cancer	PHASE1	RECRUITING	Memorial Sloan Kettering Cancer Center	—	Phase 1 only Single country
NCT04084730	Study of 3-Day Partial Breast Radiation Therapy in Women With Breast Cancer	PHASE2	RECRUITING	Memorial Sloan Kettering Cancer Center	—	Single country

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 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 Olaparib monotherapy (BRCA-mutant HER2- breast: metastatic OR adjuvant high-risk early) (REG-OLAPARIB-BREAST)	✓ 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
Trial · NCT07318051 Sample Collection for Ongoing Research and Product Evaluation Study No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07137416 Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05607004 (Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT07122713 Definitive Radiation Therapy for Inoperable Breast Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05877859 Evaluating and Monitoring Immune and Clinical Responses in Early-Stage Triple Negative Breast Cancer Undergoing Neoadjuvant Chemo-immunotherapy With Pembrolizumab 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 · NCT04959474 Pre-operative SABR With and Without Caloric Restriction for Early Stage Breast Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT06067503 Biomarkers to Detect Endocrine Therapy Resistance No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT05412225 A Study of an Alternative Treatment Approach (Preoperative Radiotherapy, Then Mastectomy, Then Immediate Reconstruction Surgery) in People With T4 Breast Cancer No UA site listed — international referral required	— unknown	— unknown	self-pay: ₴0/course	Trial sponsor
Trial · NCT04084730 Study of 3-Day Partial Breast Radiation Therapy in Women With Breast Cancer 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: 2026-05-13.

plan_id: PLAN-BREAST-TNBC-2L-HER2LOW-001-V1 | version: 1 | generated: 2026-05-13T10:01:52.951729+00:00

Per FDA non-device CDS positioning (CHARTER §15): Outpatient oncology treatment planning to support tumor-board discussion. Not a medical device; not for autonomous clinical decision-making.

Per FDA non-device CDS positioning (CHARTER §15): Both treatment options below are presented for review. The engine's selection of a 'recommended' default does not constitute a clinical decision. Final treatment selection requires HCP judgment incorporating information not available to the system.

This document is an informational resource supporting tumor-board discussion (per CHARTER §11). It is not a system that makes clinical decisions. Every recommendation must be verified by the treating physician.