Mabel Mardones, MD

@ErikaHamilton9 I have been curious

Kinda fun to try something new for spring 🐣 🌺....not bad!

WATCH: @mabelonc explains how TROP2-directed ADCs such as Dato-DXd and sacituzumab govitecan are poised to reshape the frontline treatment paradigm in metastatic TNBC #bcsm #oncology onclive.com/view/dr-mardon…

Good news to start the year. In a RW cohort of 67 patients receiving concomitant T-DXd and RT (within 10 days - 55% brain), the risk of AEs or discontinuation was comparable to patients not receiving RT. Only one case of symptomatic radionecrosis (1.5%). thebreastonline.com/article/S0960-…

#sabcs2025 Terry Mamounas presents SET index analysis of extended ET in NSABP B-42. High SET ER/PR predicted dramatic benefit in BCFI. Most impressive data predicting benefit from ext ET. Benefit incr with incr risk. @OncoAlert

🩺 How Aspirin Prevents Cancer Metastasis—Finally Explained For over 50 years, aspirin has been linked to reduced cancer metastasis—but why remained unclear. New mechanistic work now provides a clear immunologic explanation. 🔬 Key Discovery Yang et al. identify a platelet-driven immunosuppressive pathway that prevents T cells from eliminating metastatic cancer cells. Central to this mechanism is ARHGEF1, a protein in T cells activated by thromboxane A₂ (TXA₂)—a platelet metabolite generated via COX-1, the very pathway inhibited by low-dose aspirin. 🧠 What the data show • TXA₂ signaling suppresses T-cell–mediated clearance of metastases • Genetic deletion of ARHGEF1 in T cells reduces metastatic burden • Low-dose aspirin blocks this pathway by irreversibly inhibiting platelet COX-1 • Aspirin’s antimetastatic effect disappears when ARHGEF1 is absent in T cells 🩸 Why low-dose aspirin works Once-daily 75–100 mg aspirin permanently suppresses TXA₂ production in platelets (which cannot resynthesize COX-1), explaining its long-recognized anticancer effects—distinct from its higher-dose anti-inflammatory actions. 💡 Clinical implications • Platelets actively promote metastasis and immune evasion • Immunogenic tumors may benefit most from aspirin • Supports clinical data in Lynch syndrome and PIK3CA-mutant colorectal cancer • Identifies immune biomarkers that may predict aspirin benefit 🔍 Bottom Line Aspirin’s anticancer effect is not nonspecific—it is immune-mediated, platelet-dependent, and mechanistically defined. This work revives interest in repurposing a low-cost, globally accessible drug to prevent cancer progression. nejm.org/doi/full/10.10… #CancerMetastasis #Immunology #Platelets #Aspirin #CancerPrevention #Oncology #TumorImmunology #DrugRepurposing

Great news for patients. Now we have to decide how to optimally use this combo! FDA Approves T-DXd Plus Pertuzumab for HER2-Positive Breast Cancer! Maintenance and added value of P are key issues. ⁦@OncoAlert⁩ targetedonc.com/view/fda-appro…

A great, practical guide.

Our meta-analysis and cost-effectiveness analysis show a low incidence of LVEF drop, esp w/ADCs. Routine echocardiograms every 3 months are not cost-effective for most patients with standard cardiovascular risk. Is it time to change practice? @stolaney1 @AnaBaracCardio #sabcs25

Amazing news for our patients! This sets a new standard for our first line HER2 positive mBC patient, the first since Cleopatra 2015

🚨 #SABCS25 Highlight — New Treatment Algorithm for mTNBC from @stolaney1 @DFCI_BreastOnc One of the updates from SABCS25 is this proposed new therapeutic algorithm for metastatic triple-negative breast cancer (mTNBC) — integrating recent advances across antibody–drug conjugates, immunotherapy, and targeted therapy. 🔹 PD-L1–positive (1L) • Sacituzumab govitecan + pembrolizumab emerges as a frontline option. 🔹 PD-L1–negative (1L) • Datopotamab deruxtecan, reshaping expectations for ADCs in early lines. • Sacituzumab govitecan or PARP inhibitors (olaparib/talazoparib) for BRCA-mutated disease. • Reinforces the importance of germline testing early. 🔹 2L and beyond • Movement toward sequencing ADCs: SG → T-DXd (if HER2-low). • Continued role of PARP inhibitors in BRCA mutation carriers. • Chemotherapy reserved for later lines or biomarker-directed choices (MSI-H, TMB-H, NTRK/RET fusions). 💥 Why this matters This evolving landscape highlights: ✔ The shift toward ADC-first strategies in mTNBC ✔ The growing relevance of HER2-low classification even in TNBC ✔ The need for comprehensive biomarker testing at diagnosis ✔ A clearer, more personalized roadmap for sequencing therapies mTNBC is rapidly changing — these updates may redefine frontline and subsequent treatment decisions globally. @PTarantinoMD @OncoAlert @weoncologists

Important work that helps validate patient experience. We need better preventative and treatment strategies for treatment associated CI

Fantastic @IDEOlogyHealth social media poll event tonight with a fantastic group of friends. I know they helped me clarify my thoughts on a lot of complicated very new data and how to integrate it all into my clinical practice. #SABCS25

HR+ Metastatic Breast Cancer: Progress, Regulatory Approvals, and the Trials Ahead— @LalehAmiri-Kordestani & @AngieDemichele moderated this special @FDAOncology session, which featured Melanie Royce, Maria Garcia-Jimenez, Christy Osgood, & @StephWalkerMD. #SABCS25 @mariagjMD

@PTarantinoMD Haha

Global warming 🌎 🔥 — #SABCS21 vs #SABCS25 #AleixPrat

50yo patient with de-novo ER+/HER2+ MBC with multiple liver metastases; normal liver function. What 1L would you choose, assuming all available?

“Most important trial in SABCS25” commented by Eric P. Winer. WISDOM trial: Risk-based breast cancer screening was non-inferior for safety, with no increase in stage ≥2B cancers, while reducing biopsies and mammograms. Cancer incidence was similar, but shifted toward earlier stages. Population-based germline testing proved feasible. #SABCS25 @OncoAlert jamanetwork.com/journals/jama/…

So proud of our amazing leader Dr Sara Tolaney ⁦@stolaney1⁩ from ⁦@DFCI_BreastOnc⁩ receiving the 2025 ⁦@AACR⁩ Outstanding Investigator Award; teaching us all important core lessons for success!

IDEO Xchange: SERENA-6: Switching to camizestrant + CDK4/6i atESR1m detection delayed QoL decline (23.0 vs 6.4 mo vs AI). How impactful are these PRO findings on your treatment decisions?

IDEO Xchange: TROPION-Breast02: Dato-DXd in 1L mTNBC showed strong efficacy (PFS, OS, response rates). How practice-changing are these results?

IDEO Xchange: Which trial shows greater clinical impact?​ 🔹 DESTINY-Breast11: T-DXd ± THP improved pCR vs ddAC-THP​ 🔹 DESTINY-Breast05: T-DXd cut IDFS risk by 53% vs T-DM1