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. 2021 Apr 16;7(1):41.
doi: 10.1038/s41523-021-00252-6.

Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

Thomas Grinda #  1 , Natacha Joyon #  1 , Amélie Lusque  2 , Sarah Lefèvre  1 , Laurent Arnould  3 , Frédérique Penault-Llorca  4 , Gaëtan Macgrogan  5 , Isabelle Treilleux  6 , Anne Vincent-Salomon  7 , Juliette Haudebourg  8 , Aurélie Maran-Gonzalez  9 , Emmanuelle Charafe-Jauffret  10 , Coralie Courtinard  11 , Camille Franchet  2 , Véronique Verriele  12 , Etienne Brain  13 , Patrick Tas  14 , Cécile Blanc-Fournier  15 , Agnès Leroux  16 , Delphine Loussouarn  17 , Anca Berghian  18 , Eva Brabencova  19 , Jean Pierre Ghnassia  20 , Jean-Yves Scoazec  1 , Suzette Delaloge  1 , Thomas Filleron  2 , Magali Lacroix-Triki  21
Affiliations

Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

Thomas Grinda et al. NPJ Breast Cancer. .

Abstract

Expression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

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Conflict of interest statement

S.D. reports grants and non-financial support from Pfizer, grants from Novartis, grants and non-financial support from AstraZeneca, grants and non-financial support from Roche Genentech, grants from Lilly, grants from Puma, grants from Myriad, grants from Orion, grants from Amgen, grants from Sanofi, grants from Genomic Health, grants from GE, grants from Servier, grants from MSD, grants from BMS, grants from Pierre Fabre, outside the submitted work. G.M. reports personal fees from ROCHE, personal fees from ASTRA ZENECA, personal fees from DAIICHI SANKYO, personal fees from MSD, personal fees from BMS, outside the submitted work. F.P.-L. reports personal fees from astrazeneca, grants from astrazeneca, grants from roche, personal fees from roche, personal fees from pfizer, personal fees from lilly, personal fees from novartis, grants from msd, personal fees from bms, grants from bms, personal fees from genomic health, grants from nanostring, grants from nanostring, personal fees from myriad, grants from myriad, grants from agendia, outside the submitted work. E.B. reports personal fees and other from Pfizer, personal fees and other from Roche, other from Pierre Fabre, grants, personal fees and other from BMS, personal fees from Samsung, other from Novartis, other from AstraZeneca, personal fees from TLC PharmaChem, personal fees from Clinigen, personal fees from Mylan, personal fees from G1 Therapeutics, personal fees from Lilly, outside the submitted work. T.G., N.J., A.L., S.L., L.A., I.T., A.V.-S., J.H., A.M.-G., E.C.-J., C.C., C.F., V.V. P.T., C.B.-F., A.L., D.L., E.B., A.B., J.P.G., T.F., M.L.-T. declare no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart.
Fig. 2
Fig. 2. Modification of ER, PR and HER2 status between primary tumour and metastasis.
a Hormone receptor status on primary tumour and metastasis (n = 1566), b HER2 status on primary tumour and metastasis (n = 1076), c Estrogen receptor status on primary tumour and metastasis (n = 1557), d Progesterone receptor status on primary tumour and metastasis (n = 1461). HR Hormone receptor expression, HER2 human epidermal growth factor receptor 2, ER Estrogen receptor expression, PR Progesterone receptor expression.
Fig. 3
Fig. 3. Breast cancer subtypes on primary tumour and metastatic disease.
Primary HR+ HER2− (n = 641), Primary TNBC (n = 181), Primary HR−/HER2+ (n = 58), Primary HR+/HER2+ (n = 92). HR Hormone receptor expression, HER2 human epidermal growth factor receptor 2 status, TNBC Triple negative breast cancer.
Fig. 4
Fig. 4. Phenotypic discordance by metastatic site.
CNS central nervous system, CSF cerebro-spinal fluid, ER Estrogen receptor expression change, HER2 human epidermal growth factor receptor 2 expression change.
Fig. 5
Fig. 5
Overall survival according to HR modification status.
See this image and copyright information in PMC

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