Patricia Ibeas

El miércoles 25_03_2026, nuevo episodio del @GuAnalisis: mantenimiento con Palbociclib en cáncer de mama metastásico RRHH+, con Begoña Bermejo y @nacho_pelaez. Entra aquí para inscribirte: oncologia.alebateducation.com/gu/ o clubdeanalisisgu@gmail.com @jarranza @GEICAM

In mBC, not all imaging changes mean your therapy has stopped working and switching too early is a real risk. 1/ RECIST 1.1 sets a clear bar for progression: ≥20% increase in the sum of target lesion diameters (with ≥5mm absolute increase), unequivocal progression of non-target lesions, or new lesions. Not every change on imaging meets this threshold. 2/ Three scenarios commonly and incorrectly flagged as progression: new asymptomatic sclerotic bone lesions, small mm asymptomatic changes in known lesions, and increased SUV on PET without corresponding size change. None of these, in isolation, trigger a therapy switch for me. 3/ Sclerotic bone lesions deserve particular attention. When effective therapy kills tumor cells in bone, the body lays down new bone matrix appearing dense and white on CT. This is a healing response, not new disease. 4/ The consequences of switching too early are real: loss of disease control from a working regimen, premature exhaustion of sequencing options. 5/ My approach: I integrate clinical symptoms, tumor markers, and serial scans together before making any decision to change therapy. 6/ Bottom line: confirm true progression before changing course. When in doubt, a short interval rescan is almost always preferable to an unnecessary switch. #BreastCancer #MedOnc

Puntos clave – Cáncer de ovario (Nature Reviews Disease Primers 2026) 1.El cáncer epitelial de ovario no es una sola enfermedad. Incluye subtipos con biología, origen, pronóstico y tratamiento distintos. 2.El HGSOC suele originarse en la trompa de Falopio, no en el ovario. Hoy se reconoce el extremo fimbrial como origen frecuente, con diseminación peritoneal temprana. 3.El gran problema sigue siendo el diagnóstico tardío. La mayoría debuta en fases avanzadas, lo que explica gran parte de su mortalidad. 4.No hay un screening eficaz para población general. Ni CA125 ni ecografía transvaginal han demostrado beneficio en mortalidad en los grandes ensayos. 5.BRCA1/2 y HRD cambiaron el enfoque clínico. No solo aumentan el riesgo: también predicen sensibilidad a platinos y a inhibidores PARP. 6.TP53 está alterado en casi todos los HGSOC. Es un evento molecular precoz y central en la oncogénesis de este subtipo. 7.El estándar sigue siendo cirugía + carboplatino/paclitaxel. La meta quirúrgica ideal continúa siendo citorreducción completa a enfermedad macroscópica cero. 8.La neoadyuvancia no reemplaza a la buena cirugía primaria, pero sí tiene un lugar. Se prefiere cuando R0 no es factible o la paciente no toleraría una cirugía agresiva inicial. 9.Los PARP inhibitors marcaron un antes y un después en mantenimiento. El beneficio es más claro en tumores con BRCA mutado o firma HRD. 10.No todos los subtipos se comportan igual. LGSOC se relaciona con vía MAPK; clear cell y endometrioide con endometriosis; el mucinoso obliga a descartar origen GI/apendicular. 11.Bevacizumab sigue teniendo espacio en enfermedad avanzada seleccionada. Especialmente en pacientes con ascitis, enfermedad bulky o compromiso parenquimatoso. 12.La biología molecular ya no es “extra”, es parte del tratamiento. Hoy entender BRCA, HRD y subtipo histológico cambia decisiones reales.

gBRCA-Mutant Luminal Breast Cancer: CDK4/6 or PARP Inhibition? CDK4/6 inhibitors combined with ET have become the central therapeutic backbone of HR+/HER2− BC. This paradigm has proven remarkably durable across both aBC and high-risk eBC. Yet gBRCA1/2 mutations introduce a biological context that may challenge the assumption that all luminal tumors behave similarly under CDK4/6 inhibition. A recent clinicogenomic analysis published in Nature provides an important piece of this puzzle. In a cohort of more than 5,800 patients, gBRCA2 mutations were strongly associated with HR+/HER2− disease and with a genomic landscape enriched for alterations linked to CDK4/6 resistance, including RB1 loss-of-function, MYC amplification, and AURKA amplification. This constellation suggests that BRCA2-mutant luminal tumors may harbor a baseline vulnerability that facilitates escape from CDK4/6 inhibition. In clinical cohorts from the same study, pts with gBRCA2 mutations experienced significantly shorter PFS under CDK4/6i + ET compared with BRCA-wild-type patients. This biological signal aligns with the clinical observation I reported in my recent meta-analysis presented at ESMO 2025. Across 5,002 evaluable patients with HR+/HER2− mBC receiving CDK4/6i + ET, gBRCA1/2 mutations were associated with significantly worse PFS and OS compared with wild-type tumors. Importantly, the adverse effect was most pronounced in the gBRCA2 subgroup, suggesting that this genotype may identify a population in which CDK4/6-based strategies are less durable. Taken together, these data do not support abandoning CDK4/6i in BRCA-mutated BC. Rather, they suggest that gBRCA2-mutant HR+/HER2− BC may represent a biologically distinct luminal subtype in which resistance pathways are primed early. In practical terms, this distinction matters most when considering treatment sequencing. In the metastatic setting, CDK4/6i + ET remain a reasonable first-line option in patients with endocrine-sensitive disease, long DFI, and low tumor burden. However, aggressive clinical features—short DFI, primary endocrine resistance, or high tumor burden—earlier use of PARPis may be biologically justified. The Nature analysis notably showed that PARP inhibition often produced longer disease control even when administered after CDK4/6 therapy, reinforcing the concept that HRD remains a therapeutically exploitable vulnerability. The implications extend to early disease as well. Adjuvant olaparib has demonstrated a clear survival benefit in high-risk HER2-negative gBRCA-mutated BC, establishing PARP inhibition as a biologically targeted strategy in this population. At the same time, adjuvant CDK4/6is have shown meaningful benefit in high-risk HR+/HER2− eBC. Abemaciclib now has OS support in long-term F/U of the monarchE study, and ribociclib has demonstrated durable iDFS improvement in the NATALEE trial. These advances raise a practical question in patients who meet criteria for both approaches—particularly those with gBRCA-mutant, node-positive HR+/HER2− early BC with substantial residual risk. In such cases, it may be overly simplistic to frame treatment as a choice between PARPi and CDK4/6i. Instead, these therapies target distinct biological layers: PARP inhibitors exploit HRD, whereas CDK4/6is suppress residual luminal proliferative signaling. From this perspective, a sequential strategy—such as one year of adjuvant olaparib followed by CDK4/6i in selected very high-risk pts—can be considered a biologically rational approach, even though prospective evidence for this sequence is currently lacking. For patients with substantial nodal burden or RD after neoadjuvant treatment, integrating both mechanisms may be a reasonable risk-adapted strategy. #X comment

Tremendous, fun, informative symposium on ADCs across breast cancer types and stages. Such a pleasure to join this along @curijoey and #AlastairThompson — moderated by @hoperugo

Bad Bunny's Full Super Bowl Halftime show #SuperBowl