PO.CL12.02 · 临床研究
Genomic, immune, and clinical characterization of estrogen receptor-positive, HER2-low breast cancer: The NextGIM trial latest updates
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摘要 Abstract
Background: Approximately 47-65% of estrogen receptor-positive (ER+)/HER2-negative breast cancers (BC), although classified as HER2-negative due to the absence of HER2 gene amplification, exhibit low levels of HER2 expression (referred to as HER2-low BC) with immunohistochemistry (IHC) 1+ or 2+ without amplification scores. More recently, an additional subclass-HER2-ultralow-has been proposed for tumors with HER2 IHC-0 and <10% tumor cell staining. Emerging evidence indicates that HER2-low and HER2-ultralow BC may represent biologically distinct entities compared with HER2-null BC. Here, the latest updates of the NextGIM trail, a retrospective, multicenter translational study designed to comprehensively characterize ER+/HER2-low BC, are presented.
Methods: Primary tumor samples from patients enrolled in three randomized clinical trials (GIM2, GIM4, and GIM10) of the GIM (Gruppo Italiano Mammella) Investigator Group, underwent re-assessment of HER2 expression and tumor-infiltrating lymphocytes (TILs) in accordance with ASCO/CAP and TILs Working Group guidelines. In parallel, gene expression profiling was performed using the nCounter Breast Cancer 360 Panel on the NanoString platform. Clinical and survival data will be updated and integrated to evaluate potential prognostic markers and to investigate mechanisms of treatment resistance.
Results: To date, from a total of 283 patients selected at participating centres, 208 samples were deemed suitable for molecular analyses after pathological and RNA quality/quantity assessment. HER2 expression has been re-evaluated in 179 samples. At diagnosis, HER2 classification was: 45.8% HER2-negative (IHC not specified), 26.8% HER2-0, 19.6% HER2-1+, and 7.8% HER2-2+. After pathological reassessment, the distribution shifted to 58.7% HER2-null, 20.7% HER2-ultralow, 15.1% HER2 1+, 5.0% HER2 2+, and 0.6% HER2 3+. Notably, HER2-null BC resulted more prevalent in older archival samples (before 2011). TILs levels ≤1% were more frequently observed in HER2-null and HER2-ultralow tumors compared with HER2-1+ and HER2-2+ (59.1% & 67.6% vs. 25.9% & 55.6%).. Genomic profiling has been completed for 208 cases and data analyses are ongoing. An integrated analysis of molecular, pathological and clinical data will be conducted upon completion of the dataset.
Conclusion: The results obtained so far from HER2 re-evaluation has indicated that the interval between sample collection and reassessment can affect tissue antigenicity and immunohistochemistry results, and should be considered when re-evaluating HER2 status for therapeutic purposes. Overall, the study is expected, integrating genomic, immunological, and clinical information, to validate HER2-low and -ultralow expression as prognostic/predictive biomarkers to support personalized treatment.
利益披露 Disclosure
B. Cardinali,
Menarini Silicon Biosystem ), Travel.
A. Stella, None.
C. Molinelli,
Daiichi Sankyo Other, Consulting Fee
.
Seagen Other, Medical Writing fees
.
Astrazeneca Travel, support for attending medical conferences.
Menarini Travel, support for attending medical conferences.
Accademia Nazionale di Medicina Other, Speaker honoraria
.
M. Bruzzone, None.
Y. Castillo,
Daichii Sanchyo Other, Advisory Board.
F. Pitto,
Daichii Sanchyo Other, Advisory Board.
B. Massa,
Genomic Health Other, Advisory Board.
S. Pigozzi, None..
A. Sciutto, None..
G. Anselmi, None..
M. Dono, None..
V. Maltoni, None.
B. Conte,
Pfizer Travel.
Roche Travel.
Novartis Travel.
Gilead ).
AstraZeneca Other, Speaker Fee.
Menarini Other, Speaker Fee.
Varacyte Other, Speaker Fee.
G. Buzzatti,
Novartis Travel.
Menarini Travel.
AstraZeneca Other, Speaker Honoraria.
Gentili Other, Speaker Honoraria.
Daiichi Sanchyo Other, Speaker Honoraria.
Novartis Other, Speaker Honoraria.
D. Soldato,
AstraZeneca Other, Honoraria.
Novartis Travel.
Merck Travel.
Daiichi-Sankyo Travel.
G. Griguolo,
Gilead Travel, Other, advisory role.
Seagen Other, advisory role.
Menarini Other, advisory role.
Eli Lilly Travel, Other, personal fees as an invited speaker.
Novartis Travel, personal fees as an invited speaker.
MSD Other, personal fees as an invited speaker.
AstraZeneca Travel.
Daiichi Sankyo Travel.
Pfizer Travel.
V. Guarneri,
AstraZeneca Other, advisory board membership
Personal fees as an invited speaker.
Daiichi Sankyo Other, advisory board membership
Personal fees as an invited speaker.
Eli Lilly Other, advisory board membership
Personal fees as an invited speaker.
Exact Sciences Other, advisory board membership
Personal fees as an invited speaker.
Menarini Stemline Other, advisory board membership
Personal fees as an invited speaker.
MSD Other, advisory board membership.
Novartis Other, advisory board membership
Personal fees as an invited speaker.
Pfizer Other, advisory board membership
Personal fees as an invited speaker.
Roche Other, advisory board membership
Personal fees as an invited speaker.
Gilead advisory board membership
Personal fees as an invited speaker.
Abbvie Other, Personal fees as an invited speake.
M. Giuliano,
AstraZeneca Travel, Other, Consulting/Advisor
Honoraria.
Daichii Sankyo Other, Consulting/Advisor
Honoraria.
Eisai Other, Consulting/Advisor
.
Exact Sciences Other, Consulting/Advisor
Honoraria.
Gilead Travel, Other, Consulting/Advisor.
Gentili Other, Consulting/Advisor.
Lilly Travel, Other, Consulting/Advisor
Honoraria.
Menarini Stemline Other, Consulting/Advisor.
MSD Other, Consulting/Advisor
Honoraria.
Novartis Travel, Consulting/Advisor
Honoraria.
Pfizer Travel, Other, Consulting/Advisor
Honoraria.
Roche Other, Consulting/Advisor.
Seagen Other, Consulting/Advisor.
C. Marchiò,
Menarini Other, Advisory Board.
Roche Other, Advisory Board.
Illumina Other, Advisory Board.
F. Puglisi,
Amgen ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants.
Astrazeneca ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants
Honoraria for advisory boards, activities as a speaker, travel grants, research grants
Research funding.
Bayer ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants.
Daiichi Sankyo ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants.
Celgene ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants.
Eisai ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants
Research funding.
Eli Lilly ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants.
Exact Sciences ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants.
Gilead ), Travel, Other, Honoraria for advisory boards, activities as a speaker, travel grants, research grants.
Ipsen ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants.
Italfarmaco ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants.
Menarini ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants.
MSD ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants.
Novartis ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants.
Pierre Fabre ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants.
Pfizer ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants.
Roche ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants;
Research Fundings.
Seagen ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants.
Takeda ), Travel, Other, Honoraria for advisory boards, activities as a speaker, research grants.
L. Gerratana,
AstraZeneca Consulting or Advisory Role.
Daiichi Sanckyo Other, Consulting or Advisory Role.
Eli Lilly Other, Consulting or Advisory Role.
GlaxoSmithKline Other, Consulting or Advisory Role.
Incyte Other, Consulting or Advisory Role.
Novartis Travel, Other, Consulting or Advisory Role.
Pfizer Other, Consulting or Advisory Role.
Merck Sharp & Dohme Other, Consulting or Advisory Role.
Menarini Stemline Travel, Consulting or Advisory Role.
Abbvie Consulting or Advisory Role.
Gilead ), Travel, Consulting or Advisory Role.
F. Poggio,
Pfizer Other, Speaker Fee
Advisory board.
Eli Lilly Other, Speaker Fee.
Novartis Travel, Other, Speaker Fee.
Daiichi Sanckyo Other, Speaker Honoraria.
Menarini Other, Speaker Fee.
Gilead Travel.
Roche Travel, Other, Advisory board.
AstraZeneca Other, Advisory board.
L. Del Mastro,
Eli Lilly ), Other, consulting fees
Speaker Honoraria
Advisory Board.
Novartis ), Other, Speaker Honoraria,
Advisory Board.
Roche ), Travel, Speaker Honoraria,
Advisory Board.
Daiichi Sankyo ), Travel, Other, consulting fees,
Advisory Board.
Seagen ), Other, Speaker Honoraria,
Advisory Board.
AstraZeneca ), Travel, Other, Speaker Honoraria,
Advisory Board.
Gilead ), Other, consulting fees,
Speaker Honoraria,
Advisory Board.
Pierre Fabre ), Other, Speaker Honoraria,
Advisory Board.
Pfizer Travel, Other, Speaker Honoraria,
Advisory Board.
MSD Other, Speaker Honoraria.
Eisai Travel, Other, Speaker Honoraria,
Advisory Board.
Exact Sciences Other, Speaker Honoraria,
Advisory Board.
Ibsen Other, Speaker Honoraria.
GSK Other, Speaker Honoraria,
Advisory Board.
Agendia_Stemline Other, Speaker Honoraria,
Advisory Board.