HER2+ cancer du sein métastatique : raisonnement de première ligne

Objectifs d'apprentissage

1. Identify the HER2-IHC/FISH workup, organ-function baseline, and ER/PR co-status needed before HER2+ metastatic first-line treatment selection.
2. Explain why docetaxel + trastuzumab + pertuzumab (THP) remains the standard first-line backbone in the OpenOnco model and where T-DXd, T-DM1, and tucatinib fit downstream.
3. Recognize parallel obligations — baseline LVEF, brain MRI when CNS symptoms are present, and germline BRCA testing — that do not change the first-line regimen but change the safety plan.

En un coup d'oeil

• L'amplification HER2 confirmée par IHC 3+ ou ISH-positif est nécessaire avant le plan de première ligne; la bande HER2, faible, appartient toujours au chapitre HR+.
• Docetaxel + trastuzumab + pertuzumab (THP) is the standard first-line backbone; trastuzumab + pertuzumab maintenance continues after chemotherapy completion.
• Le Trastuzumab deruxtecan (T-DXd) est modélisé comme l'option canonique 2L après la progression du THP (DESTINY-Breast03).
• Active CNS metastases and germline BRCA status are parallel obligations that do not shift the 1L backbone but bring tucatinib- and PARP-inhibitor reasoning into the longer arc.
• This chapter is an OpenOnco-authored learning aid, not official ESMO content or a CME-credit activity.

Minimum de diagnostic

HER2-positive metastatic breast cancer is defined by IHC 3+ or in-situ hybridization-positive HER2 amplification on the metastatic lesion or, when not feasible, on the primary tumor with a clear discussion of discordance risk. Before the first-line plan the chapter expects confirmed HER2 amplification, ER/PR co-status (because endocrine therapy joins the conversation after THP completion), baseline LVEF and ECG before any HER2-directed antibody, germline BRCA1/2 testing, and brain imaging when CNS symptoms are present even though the regimen does not change for asymptomatic CNS disease.

Entités liées

Sources des sections

• SRC-NCCN-BREAST-2025 NCCN Guides de pratique clinique — Cancer du sein
• SRC-ESMO-BREAST-METASTATIC-2024 ESMO Ligne directrice sur la pratique clinique du cancer du sein métastatique

Logique de décision de première ligne

OpenOnco models the first-line decision as docetaxel + trastuzumab + pertuzumab (THP) for HER2-amplified metastatic disease, with trastuzumab + pertuzumab maintenance continuing after taxane completion (CLEOPATRA). HR co-positive disease adds endocrine therapy to the maintenance phase rather than replacing the HER2-directed backbone. Frailty, organ dysfunction, or cardiac contraindications are evaluated against THP before any de-intensification choice, and active visceral crisis remains a separate emergency pathway.

Entités liées

Sources des sections

• SRC-CLEOPATRA-SWAIN-2015 Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study
• SRC-NCCN-BREAST-2025 NCCN Guides de pratique clinique — Cancer du sein

Séquençage de deuxième ligne et de la connaissance du SNC

After progression on THP the canonical 2L option in the OpenOnco model is trastuzumab deruxtecan (DESTINY-Breast03). Patients with active CNS metastases — particularly progression after IO/HER2-directed therapy — pull tucatinib + trastuzumab + capecitabine into the conversation because the HER2CLIMB trial demonstrated CNS activity. Germline BRCA1/2 status brings PARP-inhibitor reasoning into the longer sequencing arc but does not displace the HER2-directed backbone at any line.

Entités liées

Sources des sections

• SRC-DESTINY-BREAST03-CORTES-2022 Trastuzumab Deruxtecan versus Trastuzaumab Emtansine pour le cancer du sein
• SRC-HER2CLIMB-MURTHY-2019 Tucatinib, Trastuzumab et Capecitabine pour le cancer métastatique du sein Positif HER2
• SRC-OLYMPIAD-ROBSON-2017 Olaparib pour le cancer du sein métastatique chez les patients atteints d'une mutation de la germline BRCA

Trappes communes

Do not treat regimen selection as the whole task. LVEF surveillance is required throughout HER2-directed therapy, not only at baseline; pregnancy and contraception planning are required for premenopausal patients because anti-HER2 antibodies are teratogenic; CNS imaging on symptom rather than schedule remains the OpenOnco default unless a HER2CLIMB-driven question changes the cadence; and HER2 status should be re-biopsied at progression because discordance between primary and metastatic samples is well-described. None of these change the 1L THP call by themselves, but missing them changes the safety plan.

Entités liées

Sources des sections

• SRC-NCCN-BREAST-2025 NCCN Guides de pratique clinique — Cancer du sein
• SRC-ESMO-BREAST-METASTATIC-2024 ESMO Ligne directrice sur la pratique clinique du cancer du sein métastatique

Cas synthétiques travaillés

• patient_breast_her2_pos_met_1l_thp HER2+ 1L on docetaxel + trastuzumab + pertuzumab - raisonnement standard, FEVE et ECG de référence examples/patient_breast_her2_pos_met_1l_thp.json
• patient_breast_her2_pos_met_2l_tdxd HER2+ après THP: T-DXd à 2L - DESTINY-Breast03 sequencing examples/patient_breast_her2_pos_met_2l_tdxd.json
• patient_breast_her2_pos_2l_brain_mets_tucatinib HER2+ avec des mets cérébraux actifs: triplet de tucatinib - Séquençage consciencieux du SNC, contexte HER2CLIMB examples/patient_breast_her2_pos_2l_brain_mets_tucatinib.json