Perifere circulerende tumorlymfocyten (pCTL) in bloed blijken alleen voorspellend te zijn voor HER2-positieve ziekte bij borstkankerpatiënten die werden behandeld met anti-HER2 medicijnen.

15 december 2020: Bron: Thebreast online

Uit een prospectieve observatie studie blijkt dat de voorspellende waarde van perifere bloedlymfocyten voor met name progressievrije overleving (PFS) bij patiënten met gevorderde borstkanker alleen statistisch significant was voor borstkankerpatiënten met een HER2-positieve ziekte en die daarvoor ook werden behandeld met anti-HER2 medicijnen (bv Herceptin - trastuzumab). Hoewel bij alle deelnemende borstkankerpatiënten meerdere subtypen van perifere bloedlymfocyten werden getest, bleken dus alleen perifere circulerende tumorlymfocyten (pCTL) voorspellend te zijn voor de progressievrije ziektetijd (PFS) bij de Her2 positieve borstkankerpatiënten.

Perifere bloedlymfocyten (PBL) zijn volgroeide lymfocyten die circuleren in het bloed , in plaats lokaliseren organen (zoals de milt of lymfeknopen ). Ze bestaan uit T-cellen , NK-cellen en B-cellen.

Een hoger pCTL-niveau werd geassocieerd met een kortere ziekteprogressievrije tijd (PFS) en meer FGFR1-mutaties bij HER2 + ABC-patiënten.

Fig. 2

Fig. 2 Predictive value of pCTL in different IHC subgroups. (A) Kaplan-Meier plot of PFS according to baseline pCTL in HR-positive subgroup. (B) Kaplan-Meier plot of PFS according to baseline pCTL in TNBC subgroup. (C) Kaplan-Meier plot of PFS according to baseline pCTL in HER2-positive subgroup. (D) Cox-regression plot of PFS according to baseline pCTL in HER2-positive subgroup. DFS: disease free survival; Grade: tumor grade at primary diagnosis; pCTL: peripheral cytotoxic lymphocyte.

Kernpunten uit de studie:

Een hoog pCTL-niveau voorspelt een kortere eerstelijns PFS bij HER2 + -patiënten die anti-HER2-gebaseerde regimes krijgen.
De voorspellende rol van het pCTL-niveau gevonden bij HER2 + -patiënten was niet van toepassing op HR +- en TNBC-patiënten.
Een hoog pCTL-niveau was geassocieerd met immunosuppressieve status en FGFR1-mutaties bij HER2 + -borstkankerpatiënten.

Hier het gratis in te kijken studierapport: Peripheral cytotoxic T lymphocyte predicts first-line progression free survival in HER2-positive advanced breast cancer

Open AccessPublished:November 11, 2020DOI:https://doi.org/10.1016/j.breast.2020.11.006

Highlights

•
High pCTL level predicts shorter first-line PFS in HER2+ patients receiving anti-HER2 based regimens.
•
The predictive role of pCTL level found in HER2+ patients was not applicable in HR+ and TNBC patients.
•
High level of pCTL was associated with immunosuppressive status and FGFR1 mutations in HER2+ breast cancer patients.

Abstract

Background

The role of peripheral blood lymphocyte (pBL) in breast cancer has long been studied. However, the predictive role of pBL in advanced breast cancer (ABC) is poorly understood.

Methods

A total of 303 patients with ABC were consecutively recruited at our center between January 2015 and September 2019. At baseline, pBL subtypes were detected in all patients with 229 blood samples available for circulating tumor DNA (ctDNA) detection. pBL was analyzed through flow cytometry. ctDNA-based gene mutations were detected using next generation sequencing. The cutoff value of pCTL was estimated by X-tile software. Progression free survival (PFS) was estimated by Kaplan-Meier curve and Cox hazard proportion regression model, with difference detection by log-rank test.

Results

Median follow-up time of the study was 21.0 months. The median age of diagnosis was 52.0 years. Among the pBL subtypes, only pCTL level was found predictive for PFS in the HER2+ patients whom received anti-HER2 therapy (13.1 vs. 5.6 months, P = 0.001). However, the predictive role of pCTL was not found in HR-positive (P = 0.716) and TNBC (P = 0.202). pCTL high associated with suppressive immune indictors including lower CD4/CD8 ratio (P = 0.004) and high level of Treg cell (P = 0.004). High occurrence of FGFR1 amplification which has been reported as immune suppressor was also found in HER2+ patients with pCTL high (22.2% vs. 4.3%, P = 0.048).

Conclusions

Higher pCTLs level associated with shorter PFS and FGFR1 mutation in HER2+ ABC patients.

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Article Info

Publication History

Published online: November 11, 2020

Accepted: November 9, 2020

Received in revised form: November 6, 2020

Received: July 5, 2020

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DOI: https://doi.org/10.1016/j.breast.2020.11.006

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Figures

Fig. 1Univariate and multivariate survival analysis regarding baseline CTL. (A) Kaplan-Meier plot of PFS according to baseline pCTL. (B) Cox-regression plot of PFS according to baseline pCTL. (C) Gates and thresholds for pCTL selection. DFS: Disease free survival; IHC: Immunohistochemistry of primary tumor; Grade: tumor grade at primary diagnosis; pCTL: Peripheral cytotoxic lymphocyte.
Fig. 2Predictive value of pCTL in different IHC subgroups. (A) Kaplan-Meier plot of PFS according to baseline pCTL in HR-positive subgroup. (B) Kaplan-Meier plot of PFS according to baseline pCTL in TNBC subgroup. (C) Kaplan-Meier plot of PFS according to baseline pCTL in HER2-positive subgroup. (D) Cox-regression plot of PFS according to baseline pCTL in HER2-positive subgroup. DFS: disease free survival; Grade: tumor grade at primary diagnosis; pCTL: peripheral cytotoxic lymphocyte.
Fig. 3Immunohistochemistry of ErbB2 in HER2-positive patients with different pCTL level. (A) HER2-positive patient with low level of pCTL. (B) HER2-positive patient with high level of pCTL. Magnification times: 200.
Fig. 4Mutational landscape of 158 tumor related genes in HER2-positive patients. (A) Mutational distribution of SNVs and CNVs according to pCTL level. (B) Mutational distribution of FGFR1 pathway genes according to pCTL level. SNV: single nucleotide variant; CNVs: copy number variation; pCTL low: ≤14.0%; pCTL high:＞14.0%.