If HER2-low breast cancer (BC) as a new separate clinical entity is a matter of debate, little is known on the incidence and the prognostic impact of brain or leptomeningeal metastases (BLMM) in this subgroup of patients (pts). Our objectives were to compare the cumulative incidence of BLMM and associated outcomes among pts with HER2-low, HER2-negative (HER2-) and HER2-positive (HER2+) metastatic BC (mBC).
This cohort study was conducted from the Epidemiological Strategy and Medical Economics (ESME) mBC platform and included pts with mBC treated between 2012 and 2020 in 18 French comprehensive cancer centers. Cumulative incidence of BLMM was estimated using a competing risk methodology with death defined as competing event.
19585 pts were included with 6118 (31.2%), 9943 (50.8%), 3524 (18.0%), having HER2-low, HER2- and HER2+ mBC respectively. BLMM were present at first diagnosis of mBC in 4.5%, 5.4% and 10.6% of pts with HER2-low, HER2- and HER2+ disease respectively. BLMM were the unique metastatic site at first diagnosis of mBC in 1.4%, 1.9% and 5.3% of pts with HER2-low, HER2- and HER2+ respectively. During the course of the disease, cumulative incidence of BLMM at 5 years was 18.9% [95%CI 17.8;20.1], 21.0% [20.0;21.9] and 33.7% [31.7;35.7] in HER2-low, HER2- and HER2+ pts. In HER2-low subgroup, cumulative incidence at 5 years was 17.6% [16.3;18.8] and 27.6% [95%CI 24.2;31.0] in HR+ and HR- mBC. The median overall survival (mOS) after BLMM diagnosis was 5.3 months [95%CI 4.2;6.8], 4.4 months [3.9;5.3] and 22.6 months [19.4;27.1] in HR-/HER2-low, HR-/HER2- and HR-/HER2+ pts. The mOS after BLMM was 7.0 months [95%CI 5.9;7.9], 6.2 months [5.5;6.9] and 25.2 months [21.8;27.8] HR+/HER2-low, HR+/HER2- HR+/HER2+ pts.
The prognosis of pts with HER2-low mBC with BLMM appears close to that of HER2- pts, and significantly worse than that of HER2+ pts. Development of new treatment strategies, such as antibody drug conjugates, with higher activity on central nervous system is eagerly awaited for pts with HER2-low or HER2- mBC.
The authors.
Has not received any funding.
W. Jacot: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, Novartis, Roche, Pfizer, Eli Lilly, MSD, BMS, Chugai, Seagen, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca, Daiichi Sankyo; Financial Interests, Invited Speaker: Roche, Novartis, Daiichi Sankyo, Daiichi Sankyo. T. Bachelot: Financial Interests, Personal, Advisory Board: Roche, Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, Seagen, Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca. V.C. Dieras: Financial Interests, Personal, Advisory Board, National advisory board: Pierre Fabre Oncologie; Financial Interests, Personal, Advisory Board, Steering Committee, consultant, Symposium, travel expenses: Roche Genentech; Financial Interests, Personal, Advisory Board, + Symposia and travel expenses: Novartis; Financial Interests, Personal, Advisory Board, Advisory boards, symposia, travel expenses: Pfizer; Financial Interests, Personal, Advisory Board, Symposia, travel expenses: Lilly, AstraZeneca, MSD; Financial Interests, Personal, Advisory Board, Symposia, travel expenses: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, symposia, travel expenses: Seagen, Gilead; Financial Interests, Personal, Advisory Board, Steering Committee: AbbVie; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Other, IDMC: Sanofi; Financial Interests, Personal and Institutional, Other, IDMC: Sanofi; Financial Interests, Institutional, Invited Speaker: Roche Genentech, AstraZeneca; Financial Interests, Institutional, Invited Speaker, Steering Committee: Lilly; Financial Interests, Institutional, Invited Speaker, + IDMC: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, PI: Seagen. E.G.C. Brain: Financial Interests, Personal, Invited Speaker, Webinars, optimized endocrine therapy for older breast cancer patients: Eli Lilly; Financial Interests, Personal, Advisory Board, Palbociclib and older breast cancer patients: Pfizer; Financial Interests, Personal, Invited Speaker, Symposium HER2+ MAO conference 03/21: Seagen; Financial Interests, Personal, Invited Speaker, ELEVATE 10/2021 and ABC 11/2021 meeetings: Pfizer; Financial Interests, Personal, Other, IDMC DESTINY 05: Daiichi; Financial Interests, Personal, Advisory Board, GCSF and FN in older patients: Sandoz; Financial Interests, Institutional, Invited Speaker, APPALACHES study EORTC 1745: Pfizer; Financial Interests, Institutional, Invited Speaker, TOUCH study (IBCSG 55/GERICO study): Pfizer; Financial Interests, Institutional, Invited Speaker, DEESTINY 09: Daiichi; Financial Interests, Institutional, Invited Speaker, DESTINY 06: Daiichi; Financial Interests, Institutional, Invited Speaker, SERENA 06: AstraZeneca; Financial Interests, Institutional, Invited Speaker, AMEERA 6: Sanofi. J. Ferrero: Financial Interests, Personal, Advisory Board: Pfizer, Exact sciences, Novartis; Financial Interests, Personal, Invited Speaker: Lilly. T. Filleron: Other, Consulting (compensated to my institution): Cellectis. L. Bosquet: Financial Interests, Institutional, Full or part-time Employment, In charge of scientific projects at Unicancer, Health Data and Partnership Department: Unicancer. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis, AstraZeneca, Gilead, Seagen, MSD, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Project Lead: Unicancer. J. Frenel: Financial Interests, Personal, Advisory Board: Pfizer, Novocure, Pierre Fabre, Eisai, Seagen, Gilead; Financial Interests, Personal, Invited Speaker: GSK, Amgen; Financial Interests, Institutional, Advisory Board: Exactscience, Lilly, Daiichi Sankyo, AstraZeneca, Clovis Oncology; Financial Interests, Institutional, Invited Speaker: Novartis, MSD; Financial Interests, Invited Speaker: AstraZeneca, Seagen, MSD, Daiichi; Non-Financial Interests, Principal Investigator: Novartis, Lilly, AstraZeneca, Pfizer, Daiichi, MSD. All other authors have declared no conflicts of interest.