6533b7d8fe1ef96bd126a538
RESEARCH PRODUCT
Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study
Alessandro GulinoBiagio PaoliniAnna MorettiGianfranco ScaperrottaSerena Di CosimoLuigi MarianiMario P. ColomboMarina Elena CazzanigaGiulia BianchiGiovanni ApoloneMassimo Di NicolaFlavio CrippaClaudio TripodoValter TorriFilippo De BraudMaria De SantisNicla La VerdeS. FolliDaniele Generalisubject
0301 basic medicineOncologyCancer TreatmentTriple Negative Breast NeoplasmsImmunostainingToxicologyPathology and Laboratory MedicineBiochemistryMetastasis0302 clinical medicineBreast TumorsClinical endpointMedicine and Health Sciencesmetastatic breast cancer Eribulin mesylate epithelial–mesenchymal transition.AnthracyclinesTriple-negative breast cancerStainingMultidisciplinaryPharmaceuticsQRKetonesMetastatic breast cancerNeoadjuvant TherapyTreatment OutcomeSurgical OncologyOncology030220 oncology & carcinogenesisMedicineFemaleTaxoidsResearch ArticleAdultBridged-Ring CompoundsClinical Oncologymedicine.medical_specialtyAnthracyclineScienceSurgical and Invasive Medical ProceduresNeutropeniaResearch and Analysis Methods03 medical and health sciencesCancer ChemotherapyBreast cancerbreast cancerDrug TherapyInternal medicinemedicineHumansChemotherapyFuransTaxaneToxicitybusiness.industryCancers and NeoplasmsBiology and Life Sciencesmedicine.disease030104 developmental biologySpecimen Preparation and TreatmentMED/06 - ONCOLOGIA MEDICAClinical MedicinebusinessBiomarkersdescription
BackgroundEribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy.MethodsPatients with primary triple negative breast cancer ≥2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study.ResultsIn stage I of the study 13 women were enrolled, median age 43 years, tumor size 2-5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR.ConclusionsDespite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial-mesenchymal transition, claims for further investigation.Trial registrationEU Clinical Trial Register, EudraCT number 2012-004956-12.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-01-01 |