Abstract 68P
Background
Luminal A (ER+/ HER2-low) is the most common breast cancer subtype and hormonal therapy is the preferred first-line treatment. However, most patients (>50%) develop resistance, leading to disease recurrence and limited clinical benefit, even with the addition of a combination regimen. Therefore, treatment optimization is required urgently. Furthermore, studies have indicated that the tumours with low HER2 and ER levels evade ER blockade via the upregulation of EGFR/HER2 signalling. Therefore, this study will aim to assess the effects of anti-HER2 in combination with hormone treatment in ER+/HER2-low breast cancer.
Methods
A panel of patient-derived organoids ( n=31) was successfully established and characterized using immunohistochemical and confocal imaging. Through the drug sensitivity test, the drug combination efficacy of the anti-HER2 drug (neratinib), hormone treatment (fulvestrant), and CDK4/6 inhibitor (palbociclib) was tested in HER2-low breast cancer patient-derived organoids. The underlying molecular mechanisms were investigated using immunofluorescence, western blot analysis, immunohistochemical staining, and cell cycle analysis.
Results
We found that neratinib combined with palbociclib and or fulvestrant showed better efficacy than palbociclib and fulvestrant combination in HER2-low breast cancer, resulting in the deactivation of HER2-EGFR signalling pathway, decreased transcriptional activation of ER and cycle proteins. Furthermore, the dual or triple combination of neratinib, palbociclib, and fulvestrant could decrease the nuclear translocation of ER. This may be the underlying mechanism by which the addition of palbociclib and/or fulvestrant to neratinib was more beneficial than the combination of palbociclib plus fulvestrant.
Conclusions
Our study provides the rationale for combining neratinib with fulvestrant and or palbociclib for the treatment of ER+/HER2-low breast cancer and indicates that the dual or triple combination treatment may be a better strategy to overcome resistance to hormone treatment. Moreover, future translational research will investigate the potential biomarkers indicating the responsiveness to the treatment.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Puma biotechnology.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
341P - NUP214 gene rearrangements in leukemia patients: Case series from a single institution
Presenter: Yu Jeong Choi
Session: Poster Display
Resources:
Abstract
344P - Venetoclax and azacitidine compared with azacitidine monotherapy for acute myeloid leukemia patients: A systematic review and meta-analysis
Presenter: Azzahra Noersamsjah
Session: Poster Display
Resources:
Abstract
345P - Safety and efficacy of platinum substitution in induction chemotherapy for mantle cell lymphoma
Presenter: Omali Pitiyarachchi
Session: Poster Display
Resources:
Abstract
346P - An assessment of marrow-infiltrating T cells in early relapsed hematologic cancer patients after allogeneic hematopoietic stem cell transplantation
Presenter: Ik-Chan Song
Session: Poster Display
Resources:
Abstract
347P - New targets for adult T cell leukemia/lymphoma (ATLL): A map for ATLL immunotherapy
Presenter: Zahra Rezaei Borojerdi
Session: Poster Display
Resources:
Abstract
348P - In-depth molecular analysis in the diagnosis of lymphomas with lymphoplasmacytic differentiation may provide a more precise diagnosis and rational treatment allocation
Presenter: Ella Willenbacher
Session: Poster Display
Resources:
Abstract
349P - Overall survival and progression-free survival comparison of lenalidomide + standard therapy versus standard therapy only in indolent lymphoma: A meta-analysis
Presenter: Kevin Winston
Session: Poster Display
Resources:
Abstract
350P - Intratumoural CD66b+ to predict treatment response in diffuse large B cell lymphoma (DLBCL)
Presenter: Mita Adriani
Session: Poster Display
Resources:
Abstract
351P - Clinical features and treatment outcomes of Waldenstrom macroglobulinemia patients: A single center study
Presenter: Devi Amelia
Session: Poster Display
Resources:
Abstract
352TiP - Randomized phase III study of daratumumab (D) versus bortezomib plus D as a maintenance therapy after D-MPB for elderly or non-elderly patients refusing transplant with untreated multiple myeloma (JCOG1911, B-DASH study)
Presenter: Tomotaka Suzuki
Session: Poster Display
Resources:
Abstract