HR+/HER2- cáncer de mama metastásico: razonamiento de primera línea

Objetivos didácticos

1. Prioritize ER/PR, HER2 (including HER2-low), germline BRCA, PIK3CA, ESR1, and AKT1 status before first-line HR+/HER2- metastatic breast cancer treatment selection.
2. Explicar por qué un inhibidor de la aromatasa más un inhibitor de CDK4/6 es la columna vertebral estándar de primera línea, y reconocer dónde la exposición previa a CDK4/6i o crisis visceral cambia la conversación.
3. Reconocer las banderas rojas que no cambian el régimen de primera línea, sino que cambian las obligaciones paralelas (base basal de la cardiopatía, anticoncepción, análisis de los niveles de SNC, cuidados de apoyo).

De un vistazo

• Histology + ER/PR + HER2 (with HER2-low captured) + germline BRCA testing are required before first-line treatment planning.
• El inhibidor de la aromatasa + inhibidor de CDK4/6 es la columna vertebral estándar de primera línea para la enfermedad sensible a la endocrina en el modelo de primera línea de OpenOnco.
• Inavolisib + palbociclib + fulvestrant se modela como la vía intensificada cuando la coalteración PIK3CA está presente y permite el acceso.
• Visceral crisis, leptomeningeal disease, and active CNS mets are parallel obligations — they shape supportive care and MDT discussion even when the systemic regimen is unchanged.
• This chapter is an OpenOnco-authored learning aid, not official ESMO content or a CME-credit activity.

Mínimo diagnóstico

The learning path starts after histology confirms invasive breast carcinoma with metastatic disease. Before any first-line plan is drafted the chapter expects a complete ER/PR result, a HER2 result that captures the HER2-low band (IHC 1+ or 2+ ISH-negative) for later 2L options, germline BRCA1/2 testing, an ECOG/fitness summary, baseline LVEF and ECG before any drug with cardiac risk, and brain imaging when CNS symptoms are present. Comprehensive NGS (PIK3CA, ESR1, AKT1, ERBB2 activating mutations) becomes treatment-defining at progression and may be ordered up-front when access permits.

Entidades vinculadas

Fuentes de las secciones

• SRC-NCCN-BREAST-2025 NCCN Directrices de Práctica Clínica - Cáncer de Seno
• SRC-ESMO-BREAST-METASTATIC-2024 ESMO Guía de Práctica Clínica sobre Cáncer de Seno Metástico

Lógica de decisión de primera línea

OpenOnco models the first-line decision as an aromatase inhibitor plus a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) for endocrine-sensitive metastatic disease. The intensified track is inavolisib + palbociclib + fulvestrant when the patient has a PIK3CA co-alteration in the inavolisib-eligible setting and access conditions are addressed. Germline BRCA1/2 mutation pulls a parallel option (talazoparib monotherapy or olaparib post-endocrine progression) into the discussion. Visceral crisis or imminent organ failure is an explicit gate that may push the learner toward chemotherapy even in endocrine-sensitive disease.

Entidades vinculadas

Fuentes de las secciones

• SRC-NCCN-BREAST-2025 NCCN Directrices de Práctica Clínica - Cáncer de Seno
• SRC-ESMO-BREAST-METASTATIC-2024 ESMO Guía de Práctica Clínica sobre Cáncer de Seno Metástico
• SRC-MONALEESA-2-HORTOBAGYI-2016 Ribociclib como terapia de primera línea para el cáncer de mama avanzado y positivo en la FC
• SRC-PALOMA-2-FINN-2016 Palbociclib and Letrozole in Advanced Breast Cancer (PALOMA-2)

Triaje de biomarcadores post-CDK4/6i

When the patient has already progressed on a CDK4/6 inhibitor, the chapter expects the learner to test for PIK3CA (alpelisib + fulvestrant), AKT1 E17K (capivasertib + fulvestrant), ESR1 (elacestrant), and HER2-low (T-DXd as a 2L option) before defaulting to fulvestrant ± everolimus. The order of these biomarker checks matters because access, toxicity profile, and overlap with prior endocrine exposure differ. The chapter explicitly maps each biomarker to its OpenOnco indication so the learner sees the same routing the engine uses at progression.

Entidades vinculadas

Fuentes de las secciones

• SRC-SOLAR1-ANDRE-2019 Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer
• SRC-CAPITELLO291-TURNER-2023 Capivasertib in Hormone Receptor-Positive Advanced Breast Cancer
• SRC-EMERALD-BIDARD-2022 Elacestrant (Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer: Results from the Randomized Phase III EMERALD Trial
• SRC-OLYMPIAD-ROBSON-2017 Olaparib para el cáncer de mama metastásico en pacientes con mutación de la BRCA Germlina

Encuadernaciones comunes

Do not treat regimen selection as the whole task. Baseline LVEF and ECG must precede CDK4/6i exposure when cardiac risk is unclear; contraception and pregnancy planning are required for premenopausal patients on endocrine therapy; CNS metastases or leptomeningeal disease change supportive care and surveillance even when the systemic regimen is unchanged; and HER2-low must be re-checked at progression because results can shift between primary and metastatic samples. None of these change the first-line CDK4/6i call by themselves, but missing them changes the safety plan.

Entidades vinculadas

Fuentes de las secciones

• SRC-NCCN-BREAST-2025 NCCN Directrices de Práctica Clínica - Cáncer de Seno
• SRC-ESMO-BREAST-METASTATIC-2024 ESMO Guía de Práctica Clínica sobre Cáncer de Seno Metástico

Casos sintéticos trabajados

• patient_breast_hr_pos_her2_neg_met_1l_cdk46i HR+/HER2- 1L sobre inhibidor de aromatasa + CDK4/6i - razonamiento estándar, análisis cardíaco y endocrino basal examples/patient_breast_hr_pos_her2_neg_met_1l_cdk46i.json
• patient_breast_hr_pos_post_cdk46i_pik3ca_alpelisib Post-CDK4/6i PIK3CA-mut: alpelisib + fulvestrant - triaje de biomarcadores post-progreso, intensificación definida por PIK3CA examples/patient_breast_hr_pos_post_cdk46i_pik3ca_alpelisib.json
• patient_breast_brca_germline_met_olaparib Germline BRCA: Razonamiento de los inhibidores del PARP - Track alternativo basado en la gérmena examples/patient_breast_brca_germline_met_olaparib.json