Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

L W de Boo; K Józwiak; N D Ter Hoeve; P J van Diest; M Opdam; Y Wang; M K Schmidt; V de Jong; S Kleiterp; S Cornelissen; D Baars; R H T Koornstra; E D Kerver; T van Dalen; A D Bins; A Beeker; S M van den Heiligenberg; P C de Jong; S D Bakker; R C Rietbroek; I R Konings; R Blankenburgh; R M Bijlsma; A L T Imholz; N Stathonikos; W Vreuls; J Sanders; E H Rosenberg; E A Koop; Z Varga; C H M van Deurzen; A L Mooyaart; A Córdoba; E Groen; J Bart; S M Willems; V Zolota; J Wesseling; A Sapino; E Chmielik; A Ryska; A Broeks; A C Voogd; E van der Wall; S Siesling; R Salgado; G M H E Dackus; M Hauptmann; M Kok; S C Linn

doi:10.1016/j.esmoop.2024.102923

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

L W de Boo, K Józwiak, N D Ter Hoeve, P J van Diest, M Opdam, Y Wang, M K Schmidt, V de Jong, S Kleiterp, S Cornelissen, D Baars, R H T Koornstra, E D Kerver, T van Dalen, A D Bins, A Beeker, S M van den Heiligenberg, P C de Jong, S D Bakker, R C RietbroekI R Konings, R Blankenburgh, R M Bijlsma, A L T Imholz, N Stathonikos, W Vreuls, J Sanders, E H Rosenberg, E A Koop, Z Varga, C H M van Deurzen, A L Mooyaart, A Córdoba, E Groen, J Bart, S M Willems, V Zolota, J Wesseling, A Sapino, E Chmielik, A Ryska, A Broeks, A C Voogd, E van der Wall, S Siesling, R Salgado, G M H E Dackus, M Hauptmann, M Kok, S C Linn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the =75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

Original language	English
Article number	102923
Number of pages	11
Journal	ESMO Open
Volume	9
Issue number	3
DOIs	https://doi.org/10.1016/j.esmoop.2024.102923
Publication status	Published - 6 Mar 2024

Keywords

fibrotic focus
lymphovascular invasion
prognostic biomarkers
stromal tumor-infiltrating lymphocytes
triple-negative breast cancer

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10.1016/j.esmoop.2024.102923Licence: CC BY-NC-ND

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de Boo, L. W., Józwiak, K., Ter Hoeve, N. D., van Diest, P. J., Opdam, M., Wang, Y., Schmidt, M. K., de Jong, V., Kleiterp, S., Cornelissen, S., Baars, D., Koornstra, R. H. T., Kerver, E. D., van Dalen, T., Bins, A. D., Beeker, A., van den Heiligenberg, S. M., de Jong, P. C., Bakker, S. D., ... Linn, S. C. (2024). Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer. ESMO Open, 9(3), Article 102923. https://doi.org/10.1016/j.esmoop.2024.102923

@article{036336e6ff4549c0a86bada8e1110b85,

title = "Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-na{\"i}ve patients with triple-negative breast cancer",

abstract = "BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-na{\"i}ve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the =75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.",

keywords = "fibrotic focus, lymphovascular invasion, prognostic biomarkers, stromal tumor-infiltrating lymphocytes, triple-negative breast cancer",

author = "{de Boo}, {L W} and K J{\'o}zwiak and {Ter Hoeve}, {N D} and {van Diest}, {P J} and M Opdam and Y Wang and Schmidt, {M K} and {de Jong}, V and S Kleiterp and S Cornelissen and D Baars and Koornstra, {R H T} and Kerver, {E D} and {van Dalen}, T and Bins, {A D} and A Beeker and {van den Heiligenberg}, {S M} and {de Jong}, {P C} and Bakker, {S D} and Rietbroek, {R C} and Konings, {I R} and R Blankenburgh and Bijlsma, {R M} and Imholz, {A L T} and N Stathonikos and W Vreuls and J Sanders and Rosenberg, {E H} and Koop, {E A} and Z Varga and {van Deurzen}, {C H M} and Mooyaart, {A L} and A C{\'o}rdoba and E Groen and J Bart and Willems, {S M} and V Zolota and J Wesseling and A Sapino and E Chmielik and A Ryska and A Broeks and Voogd, {A C} and {van der Wall}, E and S Siesling and R Salgado and Dackus, {G M H E} and M Hauptmann and M Kok and Linn, {S C}",

year = "2024",

month = mar,

day = "6",

doi = "10.1016/j.esmoop.2024.102923",

language = "English",

volume = "9",

journal = "ESMO Open",

issn = "2059-7029",

publisher = "BMJ Publishing Group",

number = "3",

}

de Boo, LW, Józwiak, K, Ter Hoeve, ND, van Diest, PJ, Opdam, M, Wang, Y, Schmidt, MK, de Jong, V, Kleiterp, S, Cornelissen, S, Baars, D, Koornstra, RHT, Kerver, ED, van Dalen, T, Bins, AD, Beeker, A, van den Heiligenberg, SM, de Jong, PC, Bakker, SD, Rietbroek, RC, Konings, IR, Blankenburgh, R, Bijlsma, RM, Imholz, ALT, Stathonikos, N, Vreuls, W, Sanders, J, Rosenberg, EH, Koop, EA, Varga, Z, van Deurzen, CHM, Mooyaart, AL, Córdoba, A, Groen, E, Bart, J, Willems, SM, Zolota, V, Wesseling, J, Sapino, A, Chmielik, E, Ryska, A, Broeks, A, Voogd, AC, van der Wall, E, Siesling, S, Salgado, R, Dackus, GMHE, Hauptmann, M, Kok, M & Linn, SC 2024, 'Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer', ESMO Open, vol. 9, no. 3, 102923. https://doi.org/10.1016/j.esmoop.2024.102923

TY - JOUR

T1 - Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

AU - de Boo, L W

AU - Józwiak, K

AU - Ter Hoeve, N D

AU - van Diest, P J

AU - Opdam, M

AU - Wang, Y

AU - Schmidt, M K

AU - de Jong, V

AU - Kleiterp, S

AU - Cornelissen, S

AU - Baars, D

AU - Koornstra, R H T

AU - Kerver, E D

AU - van Dalen, T

AU - Bins, A D

AU - Beeker, A

AU - van den Heiligenberg, S M

AU - de Jong, P C

AU - Bakker, S D

AU - Rietbroek, R C

AU - Konings, I R

AU - Blankenburgh, R

AU - Bijlsma, R M

AU - Imholz, A L T

AU - Stathonikos, N

AU - Vreuls, W

AU - Sanders, J

AU - Rosenberg, E H

AU - Koop, E A

AU - Varga, Z

AU - van Deurzen, C H M

AU - Mooyaart, A L

AU - Córdoba, A

AU - Groen, E

AU - Bart, J

AU - Willems, S M

AU - Zolota, V

AU - Wesseling, J

AU - Sapino, A

AU - Chmielik, E

AU - Ryska, A

AU - Broeks, A

AU - Voogd, A C

AU - van der Wall, E

AU - Siesling, S

AU - Salgado, R

AU - Dackus, G M H E

AU - Hauptmann, M

AU - Kok, M

AU - Linn, S C

PY - 2024/3/6

Y1 - 2024/3/6

N2 - BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the =75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

AB - BACKGROUND: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. MATERIALS AND METHODS: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged <40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. RESULTS: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs <30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the =75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. CONCLUSIONS: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.

KW - fibrotic focus

KW - lymphovascular invasion

KW - prognostic biomarkers

KW - stromal tumor-infiltrating lymphocytes

KW - triple-negative breast cancer

U2 - 10.1016/j.esmoop.2024.102923

DO - 10.1016/j.esmoop.2024.102923

M3 - Article

SN - 2059-7029

VL - 9

JO - ESMO Open

JF - ESMO Open

IS - 3

M1 - 102923

ER -

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

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Keywords

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