Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Sep:213:104793.
doi: 10.1016/j.critrevonc.2025.104793. Epub 2025 Jun 6.

The evolving landscape of hormone receptor-positive/HER2-negative metastatic breast cancer (EVOLVE): An Italian Delphi consensus report

Federica Miglietta  1 , Maria Grazia Razeti  2 , Aldo Caltavituro  3 , Arianna Dri  4 , Carmine Valenza  5 , Giampaolo Bianchini  6 , Laura Biganzoli  7 , Andrea Botticelli  8 , Michele Caruso  9 , Saverio Cinieri  10 , Carmen Criscitiello  11 , Carmine De Angelis  12 , Michelino De Laurentis  13 , Lucia Del Mastro  14 , Sabino De Placido  15 , Marzia Del Re  16 , Maria Vittoria Dieci  17 , Alessandra Fabi  18 , Daniele Generali  19 , Alessandra Gennari  20 , Lorenzo Gerratana  4 , Mario Giuliano  15 , Matteo Lambertini  14 , Umberto Malapelle  21 , Luca Malorni  7 , Icro Meattini  22 , Ida Paris  23 , Giancarlo Pruneri  24 , Claudio Zamagni  25 , Alberto Zambelli  26 , Francois Clement Bidard  27 , Valentina Guarneri  17 , Fabio Puglisi  4 , Giuseppe Curigliano  5 , Grazia Arpino  15
Affiliations
Free article
Review

The evolving landscape of hormone receptor-positive/HER2-negative metastatic breast cancer (EVOLVE): An Italian Delphi consensus report

Federica Miglietta et al. Crit Rev Oncol Hematol. 2025 Sep.
Free article

Abstract

Background: The expanding treatment landscape for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC) has led to the emergence of new "grey areas" not covered by international guidelines, where treatment decision making is particularly challenging.

Methods: Sixteen relevant statements regarding the management of HR+ /HER2- mBC were formulated by an Executive Board and validated by a Scientific Board, composed by internationally recognized experts in the field of BC. Subsequently, 50 Italian oncologists were surveyed between May 2024 and June 2024 through the modified Delphi method, in order to capture their rate of agreement and disagreement on the proposed statements.

Results: The consensus was reached for all 16 statements: 4 were related to resistance and sensitivity to CDK4/6 inhibitors and endocrine therapy, 6 to biomarkers for HR+ /HER2- mBC, and 6 to treatment algorithm of HR+ /HER2- mBC. The Panel critically and comprehensively discussed the most relevant results, especially regarding the statements with lower level of agreement (which ranged from 85.4 % to 100 %).

Conclusions: The treatment of HR+ /HER2- mBC is currently being reshaped due to the expansion of its pharmacopoeia, the better understanding of its molecular determinants and the validation of biomarkers for patient selection. This consensus addressed the most controversial questions related to treatment decision and reached the agreement in all statements.

Keywords: Endocrine therapy; Hormone receptor-positive breast cancer; Luminal-like breast cancer; Metastatic breast cancer.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest F Miglietta reports financial interests with Astrazeneca, Pfizer/Seagen, Roche, Daiichi Sankyo, Novartis, MSD. G Bianchini reports Personal fee for consultancy/honorarium/advisory role: Lilly, Novartis, Pfizer, Roche, AstraZeneca, Amgen, MSD, Chugai, Sanofi, Daiichi Sankyo, EISAI, Gilead, Menarini/stemline, Exact Science, Seagen, Agendia. L Biganzoli reports personal financial interests (Honoraria, consultancy or advisory role): Amgen, AstraZeneca, Boehringer-Ingelheim, Daiichi-Sankyo, Eisai, Exact Sciences, Gilead, Lilly, Menarini, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, SeaGen; institutional financial interests: Celgene, Genomic Health, Novartis; travel grant: AstraZeneca, Daiichi-Sankyo. A Botticelli reports personal fees for advisory/consultancy role from: Eli Lilly, Pfizer, Novartis, Roche, BMS, AstraZeneca, MSd, Daiichi Sankyo, Gilead, Seagen. M Caruso reports personal fees for dvisory board: Novartis, Astra Zeneca, Gentili, Daiichi Sankio, Roche, MSD; S Cinieri reports the following: past Presidente AIOM e Presidente Fondazione AIOM; C Criscitiello reports advisory or consultancy roles and speakers’ bureau engagements for Eli Lilly, Pfizer, Novartis, Roche, AstraZeneca, MSD, Daiichi Sankyo, Gilead, and Seagen. M De Laurentiis reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Eli Lilly, Novartis, Seagen, Takeda, Roche, Daiichi Sankyo, Tomalab, Gilead, Genetic, Menarini, Sophos, Istituto Gentili; support for attending meetings and/or travel: Gilead, Novartis, Roche, Astra Zeneca, Menarini; Participation on a Data Safety Monitoring Board or Advisory Board: Pfizer, Astra Zeneca, Sanofi, Seagen, Novartis, Ipsen, Roche, Pierre-Fabre, Daiichi-Sankyo, GSK, MSD, Menarini. C De Angelis reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Daiichi-Sankyo, Gilead, and GSK and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Seagen, GSK, GILEAD, and Daiichi-Sankyo. Travel Grants from Gilead and research support (to the Institution) from Novartis, GILEAD, and Daiichi-Sankyo outside the submitted work. L Del Mastro reports consulting fees from: Eli lilly, Gilead, Daiichi Sankyio, Menarini Stemline, Novartis, Olema, Astrazeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Roche, Novartis, Pfizer, Eli Lilly, Astrazeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, Ipsen, GSK, Agendia, Menarini Stemline; support for attending meetings and/or travel: Roche, Pfizer, Eisai, Daiichi Sankyo, Astrazeneca, Gilead, Menarini Stemline; Participation on a Data Safety Monitoring Board or Advisory Board: Novartis, Roche, Eli Lilly, Pfizer, Daiichi Sakyo, Exact Science, Gilead, Pierre Fabre, Eisai, Astrazeneca, Agendia, GSK, Seagen; M Del Re reports speaker at national and international congresses: Roche, AstraZeneca, Novartis, Menarini, Pfizer, BMS, Astellas, Amgen, Daiichi Sankyo, Qiagen, GSK, Regeneron, Lilly; consultancy or advisory role: Roche, AstraZeneca, Daiichi Sankyo, Amgen, Recordati; rResearch fundings: AstraZeneca. MV Dieci reports Personal fees for consultancy/advisory role from: Eli Lilly, Pfizer/Seagen, Bristol Myers Squibb, Novartis, Roche, Gilead, Daiichi Sankyo, Exact Sciences, MSD, AstraZeneca; Research grant from Roche (Institution). A Fabi reports Consultant or Advisor: Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Menarini Stemline, Dompè Biotech Speaker Honoraria: Astra Zeneca, Roche, Lilly, Novartis, Gilead, Pfizer, Daiichi Sankyo Exact Sciences Research Support (to the Institution): Astra Zeneca, Roche; Member of the national council of the Italian Society of Medical Oncology (AIOM); D Generali reports Advisory role for Roche, Novartis, Pfizer; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Menarini, AstraZeneca, Gilead; travel Grants from Roche; research funding (to the Uni) from Novartis. L Gerratana reports Consulting or Advisory Role: AstraZeneca, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Incyte, Novartis, Pfizer, Merck Sharp & Dohme, Menarini Stemline, Abbvie Travel Expenses: Menarini Stemline, Novartis, Gilead. M Giuliano reports financial interests with AstraZeneca, Daichii Sankyo, Eisai, Exact Sciences, Gilead, Gentili, Lilly, MSD, Novartis, Pfizer, Roche. M Lambertini reports Advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre, Menarini; speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Menarini, AstraZeneca; travel Grants from Gilead, Daiichi Sankyo, Roche; research funding (to the Institution) from Gilead. A Gennari reports Research grants: Pharmanutra, AAA; advisory boards, activities as a speaker, travel grants, consultancy: Roche, Novartis, Pfizer, Eli Lilly, Daiichi Sankyo, AstraZeneca, MSD, Seagen, Gilead, Pierre Fabre, Eisai, Exact Sciences, Stemline. L Malorni reports advisory role for: AstraZeneca, Pfizer, Lilly, Novartis, Seagen, Roche, Menarini; research support from Pfizer, Novartis; travel grants from Pfizer, Gilead. I Meattini reports honoraria from Menarini StemLine, Eli Lilly, AstraZeneca, Daiichi Sankyo, Novartis, Pfizer, Gilead. I Paris Speaker/Advisory: Novartis, Lilly, Pfizer, Daiichi Sankyo, Genetic, Astra Zeneca, Gentili, Gilead. U Malapelle reports personal fees (as speaker bureau or advisor) from Amgen Inc., AstraZeneca, Boehringer Ingelheim, Diatech, Eli Lilly & Company, GlaxoSmithKline, Hedera, Janssen, Merck Sharpe & Dohme Corporation, Novartis, Qiagen, Roche Health Solutions Inc., Thermo Fisher Scientific. Leadership Role: International Society of Liquid Biopsy and The Journal of Liquid Biopsy - Elsevier. C Zamagni reports Receipt of grants/research supports: Roche, AstraZeneca, Daiichi Sankyo, Gilead, MSD, GSK, Eisai, Pfizer, Lilly, Novartis, Exact Sciences, Menarini, Stemline; receipt of honoraria or consultation fees: Roche, AstraZeneca, Daiichi Sankyo, Gilead, MSD, GSK, Eisai, Pfizer, Lilly, Novartis, ExactSciences, Menarini, Stemline. A Zambelli reports Honoraria for advisory board: Roche, Pfizer, Novartis, Lilly, AstraZeneca, Daiichi-Sankyo, Gilead, Menarini-Stemline, MSD, Exact-Sceince. V Guarneri reports financial interests for advisory board membership for AstraZeneca, Daiichi Sankyo, Eisai, Eli Lilly, Exact Sciences, Gilead, Merck Serono, MSD, Novartis, Pfizer, Olema Oncology, Pierre Fabre; personal fees as an invited speaker for AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, Gilead, GSK, Novartis, Roche and Zentiva; personal fees for expert testimony for Eli Lilly. G Curigliano reports financial interests with AstraZeneca, Celcuity, Daiichi Sankyo, Exact Sciences, Lilly, Merck, Novartis, Pfizer, Roche, Veracyte, Ellipsis, Astellas, Blueprint Medicine, BMS, Kymab, Merck, Novartis, Philogen, Relay Therapeutics, Sanofi; and non-financial interests with the Italian National Health Council as Advisor for Ministry of Health ESMO, ESMO as Clinical Practice Guidelines Chair, Europa Donna as Member of the Scientific Council, EUSOMA as member of the Advisory Council, Fondazione Beretta, Lega Italiana Lotta ai Tumori as member of Board of Directors.