Background

Ki67 index, a prognostic biomarker in early breast cancer (eBC), is being used as an endpoint in neoadjuvant endocrine therapy (NET) clinical trials. We aim to describe baseline characteristics associated with Ki67 drop (Ki67d) after NET in patients (pts) with HR+/HER2- eBC.

Methods

We did a systematic search of PubMed, Embase, CENTRAL, and conference proceedings (ASCO, ESMO, ESMO Breast, and SABCS) up to 28 June 2022, to identify studies reporting Ki67d after NET in pts with HR+/HER2- eBC (PROSPERO ID: CRD42022333735). Here we report data from studies assessing the association of baseline characteristics with Ki67d after NET.

Results

56 studies tested the association of 45 different baseline characteristics with Ki67d after NET (Table). For clinical variables, most studies reported higher Ki67d after NET in postmenopausal pts. Conversely, one study using telapristone acetate showed Ki67d only in premenopausal pts. Higher body mass index (BMI) was reported to be associated with Ki67d, in one of the studies together with metformin. For pathological factors, Ki67d was associated with higher baseline estrogen receptor (ER) and progesterone receptor (PR) expression. Regarding genomic determinants, we mostly found higher Ki67d in pts with favorable intrinsic subtypes (luminal A vs luminal B, or luminal vs non-luminal). Two studies showed more pronounced Ki67d in pts with luminal B tumors (vs luminal A). Higher Ki67d was reported when pictilisib or enzalutamide were added to NET in luminal B or luminal A tumors, respectively. PIK3CA exon 9 mutation was associated with lower Ki67d. The effect of this mutation was reverted in these studies by the addition of targeted therapy to NET (pictilisib, everolimus, or lapatinib). Table: 64P

Summary of the six most assessed baseline characteristics, two per category

Conclusions

We summarize baseline characteristics associated with Ki67d after NET in pts with eBC. These characteristics are important to inform clinical trial design and pts selection in clinical practice.

Legal entity responsible for the study

Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Academic Trials Promoting Team (ATPT), Brussels, Belgium.

Funding

Research Grant - Fonds de Barsy-Laffut from Université Libre de Bruxelles (ULB).

Disclosure

D. Martins Branco: Financial Interests, Personal, Advisory Board: Angelini, AstraZeneca, Janssen, Merck Sharp & Dohme, Novartis, Pfizer; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Merck Sharp & Dohme, Novartis; Financial Interests, Personal, Other, meeting/travel grant: Gilead Sciences, Ipsen, Janssen, LEO Farmacêuticos, Laboratórios Vitória, Pfizer, Roche; Financial Interests, Personal, Other, Meeting/travel grant.: Merck Sharp & Dohme, Novartis; Financial Interests, Institutional, Research Grant, Institutional funding for an observational research project.: Novartis; Financial Interests, Institutional, Research Grant, Institutional funding for an investigator-initiated clinical trial.: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Invited Speaker: Associação de Investigação e Cuidados de Suporte em Oncologia - Portuguese MASCC affiliate; Non-Financial Interests, Leadership Role, Portuguese Young Oncologists Committee Chair: November 2020 - May 2022: Sociedade Portuguesa de Oncologia; Non-Financial Interests, Leadership Role, Oncology Committee Chair: January 2020 - January 2021: Health Parliament Portugal. C. Molinelli: Financial Interests, Personal, Invited Speaker: Novartis, Lilly; Financial Interests, Personal, Other, travel grant: Novartis, Gilead. G. Nader Marta: Financial Interests, Personal, Other, meeting/travel grant: Roche, Bayer. R.F. Salgado: Financial Interests, Personal, Advisory Board: Roche, BMS, Exact Sciences; Financial Interests, Personal, Funding, Roche funded personally the assessment of immune-markers in a research study. This was in 2019.: Roche; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Funding: Puma Biotechnology. P.G. Aftimos: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius, Deloitte, Menarini, Gilead, Novartis, Eisai, Lilly; Financial Interests, Personal, Invited Speaker: Synthon, Amgen; Financial Interests, Institutional, Research Grant: Roche. E. de Azambuja: Financial Interests, Personal, Advisory Board: Roche/GNE, Novartis, Seagen; Financial Interests, Personal, Invited Speaker: Zodiac, Libbs, Pierre Fabre, Lilly, Astra-Zeneca; Financial Interests, Institutional, Research Grant: Roche/GNE, AstraZeneca, GSK/Novartis, Servier; Financial Interests, Institutional, Other, Travel Grant: Roche/GNE; Financial Interests, Institutional, Invited Speaker: MSD, ABCSG, Nektar, Gilead, Immunomedics, Synthon, Odonate Therapeutics; Financial Interests, Invited Speaker, Chair of the Gilead Sciences Research Scholars Program in Solid Tumours: Gilead; Financial Interests, Invited Speaker, Aphinity, Lorelei, Impassion03: Roche; Financial Interests, Invited Speaker, AURORA: Breast International Group; Financial Interests, Invited Speaker, Olympia: Astra-Zeneca; Financial Interests, Personal, Other, Travel grant: Astra-Zeneca; Non-Financial Interests, Advisory Role, Member of the cardio-oncology council: European Society for Cardiology (ESC); Non-Financial Interests, Advisory Role, Belgium governmental institution for cancer: KCE; Non-Financial Interests, Other, Editorial board member: ESMO Open; Non-Financial Interests, Advisory Role: Anticancer Fund. All other authors have declared no conflicts of interest.