The immune response to cancer serves an important role in disease progression and patient prognosis. For triple-negative breast cancer showing aggressive behavior, immunotherapy has a good efficacy because of the potent immunogenicity of this type of cancer. However, the dominant subtype, luminal human epidermal growth factor receptor-2 (HER2)-negative breast cancer, is less immunogenic. To determine whether luminal HER2-negative cancer reacts to the anticancer immune response, the present study analyzed the status and prognostic value of the principal immunological biomarkers of breast cancer, including tumor-infiltrating lymphocytes (TILs), CD8+ T lymphocytes, the major histocompatibility complex and programmed cell death ligand-1 (PD-L1). The biomarkers were compared between patients with luminal HER2-negative breast cancer and those with immunogenic subtypes including triple-negative and HER2-overexpressed breast cancer. A total of 71 patients with primary breast cancer were classified into the immunogenic non-luminal (n=23) and less immunogenic luminal HER2-negative groups (n=48) based on immunogenicity. In the luminal HER2-negative group, compared with patients with low TIL levels, those with high TIL levels were at an advanced stage of cancer (P=0.024) and showed worse relapse-free survival (P=0.057); however, the remaining biomarkers exhibited no association with cancer progression or prognosis. In the non-luminal group, patients with high TIL levels showed significantly better RFS than those with low TIL levels (P=0.014). Compared with non-luminal patients negative for PD-L1, those positive for PD-L1 exhibited better overall survival (P=0.064). Notably, TIL status was found to exhibit contrasting prognostic predictions based on immunogenicity. In conclusion, TILs are a strong candidate for prognostic prediction in breast cancer, regardless of the subtype. PD-L1 is a potential candidate for prognostic prediction in immunogenic breast cancers, but not in the luminal HER2-negative subtype.
Several biomarkers predict cancer progression, patient prognosis, and therapeutic efficacy in cancer. Some of the most useful biomarkers are involved in the growth or metastasis of cancers (
Clinical trials of the therapeutic potential of immune checkpoint inhibitors, such as atezolizumab and pembrolizumab, in the treatment of advanced TN breast cancer have achieved an objective treatment response rate of 53.2-56.0%, with a significantly longer progression-free survival compared with that of placebo group patients (
As described above, antitumor immune responses can affect cancer progression and patient prognosis in immunogenic subtypes such as TN and HER2-overexpressed breast cancer; however, antitumor immunity is unlikely to affect luminal HER2-negative breast cancer, a dominant subtype, because of its lower immunogenicity. Indeed, compared with other cancer types, breast cancer including luminal HER2-negative breast cancer, which occurs in a majority of the population, exhibits fewer mismatch repair deficiencies and microsatellite instabilities; this is partly because breast cancer is a well-differentiated and slow-growing cancer (
In this study, we retrospectively evaluated the status and prognostic value of the immunological breast cancer biomarkers, TILs, CD8+ T lymphocyte infiltrates, MHC molecules, and PD-L1. We compared these biomarkers between patients with less immunogenic luminal HER2-negative breast cancer and those with immunogenic non-luminal breast cancer including TN and non-luminal HER2-overexpressed breast cancers.
Seventy-one female patients with primary breast cancer who had undergone surgery such as mastectomy or partial resection for primary lesions with either axillary dissection or sentinel node biopsy from January 2010 to December 2021 at Kagawa University Hospital were included in this study. The exclusion criteria were as follows: previous invasive breast cancer or non-breast cancer within 5 years before surgery for primary breast cancer; any previous chemotherapy or endocrine therapy for cancer; any previous anti-HER2 therapy or other previous anticancer biologic therapy or immunotherapy; and concurrent serious diseases interfering with adjuvant therapy for breast cancer. The median patient age was 59 (
TIL levels in patient tissue samples were evaluated. After the samples were fixed in formalin and embedded in paraffin, they were sectioned into 4-µm-thick slices and stained in hematoxylin-eosin solution, as previously described (
Serial sections (4-µm-thick) of formalin-fixed paraffin-embedded tissue specimens were stained via standard indirect immunoperoxidase procedures for PD-L1, CD8, and MHC class I molecules, according to the staining kit manufacturer's instructions. Briefly, each tissue section was deparaffinized in xylene and rehydrated in ethanol and distilled water. Antigen retrieval was performed via 10 min of microwave treatment in 10 mM sodium citrate buffer (pH 6.0) for PD-L1 or 10 mM Tris/1 mM ethylenediaminetetraacetic acid (pH 9.0) for MHC class I molecules. Endogenous peroxidase activity was blocked by treatment with 3% H2O2 for 10 min. After blocking in Tris-buffered saline with Tween-20 and 5% normal goat serum for 1 h at room temperature, the sections were incubated at 4°C overnight with antihuman PD-L1 monoclonal antibodies (clone: E1L3N, diluted 1:200, Cell Signaling Technology, Danvers, MA, USA; SP263, diluted 1:100, Ventana Medical Systems, Tucson, AZ, USA), which were produced by immunizing rabbits with peptides derived from the C-terminus of PD-L1 protein, anti-CD8 monoclonal antibody (clone: SP57, diluted 1:100, Ventana Medical Systems), or an anti-HLA class I monoclonal antibody (clone: EMR8-5, diluted 1:500, Hokudo Co., Ltd., Sapporo, Japan). The sections were then incubated with SignalStain boost IHC detection reagent (Cell Signaling Technology) for PD-L1 or Envision Dako ChemMate (Dako Ltd., Kyoto, Japan) for CD8 and MHC class I molecules. They were visualized using a SignalStain DAB (3,3′-diaminobenzidine) substrate kit (Cell Signaling Technology) for PD-L1 or Envision Dako ChemMate/horseradish peroxidase (HRP) DAB for CD8 and MHC class I molecules for 1 min. This was followed by counterstaining with hematoxylin. Isotype-matched control antibodies were used for immunohistochemistry. These were rabbit immunoglobulin G (IgG) monoclonal antibody (Cell Signaling Technology) for PD-L1, and mouse IgG monoclonal antibody (Dako) for CD8 and MHC class I molecules.
Serial sections of stained tumor tissues were independently examined by two researchers, including a pathologist. To compare the cellular staining intensities of PD-L1, CD8, and MHC class I molecules, cells from the serial sections were evaluated microscopically (magnification: ×200). Three representative fields of view were selected and any expression of PD-L1 and MHC class I molecules was identified in 100 tumor cells per field. Cases in which the proportion of tumor cells positive for PD-L1 was ≥1% were considered PD-L1+ tumor cell-dominant. Cases in which the proportion of tumor cells positive for MHC class I molecules was ≥80% were considered MHC class I+ tumor cell-dominant, as previously reported (
All statistical analyses were performed using SPSS Statistics for Windows (IBM Corp., Armonk, NY, USA) software. For comparisons between two groups, we used the Mann-Whitney U test or the χ2 test. The effects of clinical and demographic variables, clinical responses, and prognostic parameters on the duration of survival and risk of progression were assessed using Kaplan-Meier survival analyses and log-rank tests. A 95% confidence interval for the median of each variable was calculated using the Brookmeyer and Crowley method (
The patient cohort included 48 (67.6%) patients with luminal HER2-negative, 21 (29.6%) with TN, and two (2.8%) with non-luminal HER2-overexpressed breast cancer. At the time of the study, 30 patients experienced relapsed lesions. The relapse-free survival (RFS) and overall survival (OS) rates 10 years after the primary operation were 60.3 and 78.1%, respectively (
The non-luminal group included 21 patients with TN and 2 with non-luminal HER2-overexpressed breast cancer. The proportion of patients positive for PD-L1 expression was significantly higher in patients positive for MHC expression than that in patients negative for MHC expression (P=0.048 for E1L3N and P=0.019 for SP263,
In patients with luminal HER2-negative cancer, the proportion of patients positive for MHC expression and median number of CD8+ T lymphocyte infiltrates per patient were significantly higher in patients with high TIL levels than those in patients with low TIL levels (MHC-positive patients: low TIL and high TIL levels, 50.0 and 83.3%, respectively, P=0.016; median CD8+ T lymphocyte counts: low TIL and high TIL levels, 39.8 and 62.3, respectively, P<0.001,
In patients with cancer, the antitumor immune response is crucial to the regulation of cancer progression and improvement of prognosis. However, cancer cells possess a wide range of mechanisms for evading host immune responses including the modification of cancer phenotypes, reduction or deletion of the expression of antigenic proteins and MHC molecules, and production of cytokines and factors that inhibit anticancer immune response activation (
We evaluated the status of immunological biomarkers, including TIL levels, CD8+ T lymphocyte infiltrate count, MHC expression, and PD-L1 expression, in the tumors of 71 patients with primary breast cancer to determine their utility as predictors of cancer progression and prognosis. To date, only B cells and macrophages in TILs have been found to predict survival rates in luminal HER2-negative breast cancer (
We observed that PD-L1 expression (reactive with both E1L3N and SP263) was generally associated with MHC expression in tumor cells and with stromal TIL levels (
The present study results suggested that MHC and TIL status were strongly associated with cancer progression and that PD-L1 status (in terms of its reactivity with E1L3N) exhibited possible prognostic value for all breast cancer subtypes. To determine whether the status of these biomarkers differed between cancer subtypes and whether they interacted with cancer progression or prognosis in each subtype, the patients were classified into two cancer subtype groups according to immunogenicity: patients with less immunogenic luminal HER2-negative cancer and those with immunogenic non-luminal breast cancers. In the immunogenic group, no association was observed between TIL levels and MHC expression; however, TIL levels and MHC expression were closely associated with PD-L1 expression (
In the less immunogenic luminal HER2-negative breast cancer group, high TIL levels were strongly associated with cancer progression and associated with poor prognoses (
One of the limitations of our study is the small sample size (n=71); we thus could not classify a sufficient number of patients into groups to perform more convincing comparative analyses. Furthermore, we did not analyze systemic immunological responses, such as leukocyte profiles in peripheral blood, immunoglobulin and complement levels, or cytokine production in the studied patients. By including analysis of systemic immunological responses in patients with breast cancer in a future study, we will be able to understand the role of antitumor immunity more comprehensively in breast cancer. In this study, we used two anti-PD-L1 monoclonal antibodies, which were produced by immunizing rabbits with synthetic peptides derived from residues near the C-terminus of PD-L1 protein. The sensitivity of SP263 in detecting PD-L1 expression was generally higher than that of E1L3N. Although the precise epitopes of both monoclonal antibodies has not been reported, these may be different but located nearby. As these antibodies recognize their antigenic determinants on the three-dimensional components of the target protein in immunological assays, the sensitivity of each monoclonal antibody is expected to differ. Regarding the prognostic value of the PD-L1 status in luminal HER2-negative breast cancer, Zhang
In conclusion, the immunological biomarkers MHC, TIL, and PD-L1 exhibited different patterns of expression depending on the breast cancer subtype of the patient. However, CD8+ T lymphocyte infiltrate counts were closely associated with TIL levels and MHC and PD-L1 expression regardless of the breast cancer subtype. Of these biomarkers, only TIL levels are expected to be associated with cancer progression and patient prognosis, regardless of the breast cancer subtype. Although the PD-L1 protein reactive to SP263 is a potential prognostic biomarker in immunogenic cancers, it is unrelated to either cancer progression or patient prognosis in luminal HER2-negative breast cancer.
The authors would like to thank Ms. Hiromi Kita and Ms. Miho Takigawa (Department of Thoracic, Breast and Endocrine Surgery, Kagawa University Faculty of Medicine, Kagawa, Japan) for their editorial assistance with an earlier version of this manuscript.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
CM, KeK and KT conceived and designed the present study. KaK, SN, SH, MM and TM contributed to data acquisition and analysis. KeK, CM, TY and RH were major contributors in writing the manuscript. TY RH and NH were involved in data interpretation and discussion. NA and MI performed the statistical analysis. NH, NA and MI confirm the authenticity of all the raw data. All authors read and approved the final manuscript.
The research protocol for this study complied with the guidelines of the Ethics Committee at Kagawa University Hospital and was approved by the ethical review board of Kagawa University (approval no. HEISEI23-085); it conformed to the provisions in the Declaration of Helsinki in 1995. Written informed consent to participate was obtained from all study participants.
When patients were given written information about the present study, written patient consent for publication was also obtained.
The authors declare that they have no competing interests.
cluster of differentiation
cytotoxic T lymphocyte
3,3′-diaminobenzidine
human epidermal growth factor receptor-2
major histocompatibility complex
overall survival
phosphate-buffered saline
programmed cell death 1
programmed cell death-ligand-1
relapse-free survival
tumor-infiltrating lymphocyte
triple-negative
Stromal lymphocytic infiltrates and MHC expression in tumor cells in breast cancer tissues. (A) Low levels of TILs (<10%); (B) high levels of TILs (≥10%); (C) low MHC expression in tumor cells; (D) high MHC expression in tumor cells (magnification, ×200). Arrows indicate TILs in the tumor stroma. MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes.
PD-L1 expression in breast cancer tissues. (A) None of the tumor cells showing reactivity with E1L3N; (B) many tumor cells showing reactivity with E1L3N; (C) none of the tumor cells showing reactivity with SP263; (D) many tumor cells showing reactivity with SP263 (magnification, ×200). PD-L1, programed cell death-ligand-1.
Comparison of relapse-free survival of two breast cancer patient groups with different biomarker statuses. (A) MHC expression; (B) TIL levels; (C) reactivity with E1L3N; (D) reactivity with SP263. MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes.
Comparison of overall survival of two breast cancer patient groups with different biomarker statuses. (A) MHC expression; (B) TIL levels; (C) reactivity with E1L3N; (D) reactivity with SP263. MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes.
CD8 expression in TILs. (A) Very few CD8+ T lymphocytes infiltrate in the stroma; (B) many CD8+ T lymphocytes infiltrate in the stroma (magnification, ×200). CD, cluster of differentiation; TILs, tumor-infiltrating lymphocytes.
Comparison of relapse-free survival of two groups of patients with non-luminal immunogenic breast cancer with different biomarker statuses. (A) MHC expression; (B) TIL levels; (C) reactivity with E1L3N; (D) reactivity with SP263. MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes.
Comparison of overall survival of two groups of patients with non-luminal breast cancer with different biomarker statuses. (A) MHC expression; (B) TIL levels; (C) reactivity with E1L3N; (D) reactivity with SP263. MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes.
Comparison of relapse-free survival of two groups of patients with luminal HER2-negative breast cancer with different biomarker statuses. (A) MHC expression; (B) TIL levels; (C) reactivity with E1L3N; (D) reactivity with SP263. HER2, human epidermal growth factor receptor-2; MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes.
Comparison of overall survival of two groups of patients with luminal HER2-negative breast cancer with different biomarker statuses. (A) MHC expression; (B) TIL levels; (C) reactivity with E1L3N; (D) reactivity with SP263. HER2, human epidermal growth factor receptor-2; MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes.
Clinical features and prognoses of the primary breast cancer patient cohort in this study.
Variable | All (n=71) | Non-luminal (n=23) | Luminal HER2 (−) (n=48) | P-value |
---|---|---|---|---|
Median age, years | 59 ( |
58 ( |
60 ( |
0.681 |
Median tumor size, cm | 2 (0.5-8.5) | 2.1 (0.5-6.5) | 1.7 (0.7-8.0) | 0.269 |
N-positive, % | 43.6% | 60.9% | 31.3% | 0.018 |
Stage | ||||
1 | 27 | 4 | 23 | 0.014 |
2 | 42 | 19 | 23 | 0.006 |
3 | 2 | 0 | 2 | 0.324 |
MHC-positive, % | 70.4% | 78.3% | 66.7% | 0.319 |
High TILs, % | 60.6% | 82.7% | 50.0% | 0.009 |
Median no. CD8+ T, % | 66.0 (1.0-176.3) | 88.0 (17.3-176.3) | 55.7 (1.0-130.0) | 0.001 |
PDL1-E1L3N (+), % | 19.7% | 39.1% | 10.4% | 0.005 |
PDL1-SP263 (+), % | 54.9% | 60.9% | 47.9% | 0.174 |
RFS at 10 years | 60.3% | 52.1% | 66.7% | 0.059 |
OS at 10 years | 78.1% | 60.9% | 87.5% | 0.038 |
P<0.05. RFS, relapse-free survival; OS, overall survival; MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes Median age and tumor size, and the number of CD8+ T lymphocytes were compared between two groups using Mann-Whitney-U test. Positive rates of MHC and PD-L1 expression, the proportion of patients with N-positive cancer and that of patients with each clinical stage, and high TIL rates were compared between two groups using χ2 test or Fisher's exact test. The duration of RFS and OS was assessed using Kaplan-Meier survival analyses and log-rank tests.
Relationships between MHC and TILs status of breast cancer and cancer progression and prognosis as determined by the clinicopathological feature of the patient cohort.
Variable | MHC(−) (n=21) | MHC(+) (n=50) | P-value | Low TIL (n=28) | High TIL (n=43) | P-value |
---|---|---|---|---|---|---|
Median age, years | 61 ( |
57 ( |
0.286 | 60 ( |
58 ( |
0.861 |
Median tumor size, cm | 1.7 (0.5–3.5) | 2.1 (0.7–6.6) | 0.017 |
1.5 (0.7–3.5) | 2.1 (0.5–8.0) | 0.021 |
N-positive, % | 27.2% | 45.1% | 0.229 | 21.4% | 55.6% | 0.005 |
Median stage | 1 ( |
2 ( |
0.046 |
1 ( |
2 ( |
0.006 |
MHC-positive, % | - | - | - | 50.0% | 83.7% | 0.004 |
High TILs, % | 31.8% | 70.6% | 0.004 |
- | - | - |
Median no. CD8+ T | 39.7 (1.0–109.7) | 74.3 (27.0–176.3) | 0.001 |
33.7 (1.0–74.3) | 83.3 (31.0–176.3) | <0.001 |
PDL1-E1L3N (+), % | 0% | 27.5% | 0.007 |
3.6% | 30.2% | 0.008 |
PDL1-SP263 (+), % | 31.8% | 60.8% | 0.016 |
32.1% | 65.1% | 0.018 |
P<0.05. MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes. Median age, stage and tumor size, and the number of CD8+ T lymphocytes were compared between two groups using Mann-Whitney-U test. Positive rates of MHC and PD-L1 expression, the proportion of patients with N-positive cancer, and high TIL rates were compared between two groups using χ2 test or Fisher's exact test.
Relationships between PD-L1 status of breast cancer and cancer progression and prognosis as determined by the clinicopathological feature of the patient cohort.
Variable | E1L3N(−) (n=57) | E1L3N(+) (n=14) | P-value | SP263(−) (n=32) | SP263(+) (n=39) | P-value |
---|---|---|---|---|---|---|
Median age, years | 60 ( |
57 ( |
0.714 | 62 ( |
58 ( |
0.328 |
Median tumor size, cm | 2.0 (0.5–8.0) | 2.0 (1.3–6.5) | 0.624 | 1.9 (0.5–8.0) | 2.0 (0.7–6.5) | 0.766 |
N-positive, % | 39.0% | 57.1% | 0.219 | 41.2% | 41.0% | 0.791 |
Median stage | 2 ( |
2 ( |
0.553 | 2 ( |
2 ( |
0.705 |
MHC-positive, % | 63.2% | 100% | 0.007 |
57.6% | 81.6% | 0.016 |
High TILs, % | 52.6% | 92.9 | 0.008 |
45.5% | 73.7% | 0.018 |
Median no. CD8+ T | 58.3 (1.0–125.7) | 100.3 (54.0–176.3) | <0.001 |
43.3 (12.0–109.7) | 79.0 (1.0–176.3) | <0.001 |
PDL1-E1L3N (+), % | - | - | - | 0% | 36.8% | <0.001 |
PDL1-SP263 (+), % | 42.1% | 100% | <0.001 |
- | - | - |
P<0.05. MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes. Median age, stage and tumor size and the number of CD8+ T lymphocytes were compared between two groups using Mann-Whitney-U test. Positive rates of MHC and PD-L1 expression, the proportion of patients with N-positive cancer, and high TIL rates were compared between two groups using χ2 test or Fisher's exact test.
Relationships between MHC and TILs status of breast cancer and cancer progression and prognosis as determined by the clinicopathological feature of patients with non-luminal breast cancer.
Variable | MHC(−) (n=5) | MHC(+) (n=18) | P-value | Low TIL (n=4) | High TIL (n=19) | P-value |
---|---|---|---|---|---|---|
Median age, years | 66 ( |
57 ( |
0.141 | 47 ( |
61 ( |
0.109 |
Median tumor size, cm | 1.8 (0.5–3.5) | 2.2 (1.2–6.5) | 0.359 | 3.3 (1.0–4.0) | 2.0 (0.5–6.5) | 0.545 |
N-positive, % | 60.0% | 61.1% | 0.965 | 75.0% | 57.9% | 0.533 |
Median stage | 2 ( |
2 ( |
0.310 | 1 ( |
2 ( |
0.750 |
MHC-positive, % | - | - | - | 50.0% | 84.2% | 0.140 |
High TILs, % | 60.0% | 88.9% | 0.140 | - | - | - |
Median no. CD8+ T | 31.0 (17.3–109.7) | 97.8 (32.7–176.3) | 0.052 | 28.7 (17.3–74.3) | 99.7 (51.7–176.3) | 0.007 |
PDL1-E1L3N (+), % | 0% | 50.0% | 0.048 |
0% | 47.3% | 0.084 |
PDL1-SP263 (+), % | 20.0% | 77.8% | 0.019 |
25.0% | 73.7% | 0.069 |
P<0.05. MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes. Median age, stage and tumor size, and the number of CD8+ T lymphocytes were compared between two groups using Mann-Whitney-U test. Positive rates of MHC and PD-L1 expression, the proportion of patients with N-positive cancer, and high TIL rates were compared between two groups using χ2 test or Fisher's exact test.
Relationships between PD-L1 status of breast cancer and cancer progression and prognosis as determined by the clinicopathological feature of patients with non-luminal breast cancer.
Variable | E1L3N(−) (n=14) | E1L3N(+) (n=9) | P-value | SP263(−) (n=8) | SP263(+) (n=15) | P-value |
---|---|---|---|---|---|---|
Median age, years | 61 ( |
53 ( |
0.250 | 64 ( |
56 ( |
0.125 |
Median tumor size, cm | 2.4 (0.5–3.5) | 2.0 (1.2–6.5) | 0.785 | 2.6 (0.5–3.5) | 2.1 (1.2–6.5) | 0.716 |
N-positive, % | 57.1% | 66.7% | 0.655 | 62.5% | 60.0% | 0.909 |
Median stage | 2 ( |
2 ( |
0.520 | 2 ( |
2 ( |
0.150 |
MHC-positive, % | 64.3% | 100% | 0.048 |
50.0% | 93.3% | 0.019 |
High TILs, % | 71.4% | 100% | 0.084 | 62.5% | 93.3% | 0.069 |
Median no. CD8+ T | 75.3 (17.3–125.7) | 101.0 (71.7–176.3) | 0.012 |
42.2 (17.3–109.7) | 101.0 (71.7–176.3) | 0.004 |
PDL1-E1L3N (+), % | - | - | - | 0% | 60.0% | 0.006 |
PDL1-SP263 (+), % | 42.9% | 100% | 0.006 |
- | - | - |
P<0.05. MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes. Median age, stage tumor size, and the number of CD8+ T lymphocytes were compared between two groups using Mann-Whitney-U test. Positive rates of MHC and PD-L1 expression, the proportion of patients with N-positive cancer, and high TIL rates were compared between two groups using χ2 test or Fisher's exact test.
Relationships between MHC and TILs status of breast cancer and cancer progression and prognosis as determined by the clinicopathological feature of patients with luminal HER2-negative breast cancer.
Variable | MHC(−) (n=16) | MHC(+) (n=32) | P-value | Low TIL (n=24) | High TIL (n=24) | P-value |
---|---|---|---|---|---|---|
Median age, years | 61 ( |
58 ( |
0.641 | 61 ( |
58 ( |
0.411 |
Median tumor size, cm | 1.7 (0.7–3.1) | 1.9 (0.7–8.0) | 0.063 | 1.5 (0.7–3.1) | 2.4 (0.8–8.0) | 0.009 |
N-positive, % | 18.8% | 31.3% | 0.191 | 12.5% | 50.0% | 0.006 |
Median stage | 1 ( |
2 ( |
0.270 | 1 ( |
2 ( |
0.024 |
MHC-positive, % | - | - | - | 50.0% | 83.3% | 0.016 |
High TILs, % | 25.0% | 62.5% | 0.016 |
- | - | - |
Median no. CD8+ T | 39.7 (1.0–75.3) | 62.3 (24.7–137.0) | 0.002 |
39.8 (1.0–66.7) | 62.3 (24.7–137.0) | <0.001 |
PDL1-E1L3N (+), % | 0% | 12.5% | 0.099 | 4.2% | 16.7% | 0.161 |
PDL1-SP263 (+), % | 37.5% | 53.1% | 0.313 | 37.5% | 58.3% | 0.153 |
P<0.05. MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes. Median age, stage and tumor size, and the number of CD8+ T lymphocytes were compared between two groups using Mann-Whitney-U test. Positive rates of MHC and PD-L1 expression, the proportion of patients with N-positive cancer, and high TIL rates were compared between two groups using χ2 test or Fisher's exact test.
Relationships between PD-L1 status of breast cancer and cancer progression and prognosis as determined by the clinicopathological feature of patients with luminal HER2-negative breast cancer.
Variable | E1L3N(−) (n=43) | E1L3N(+) (n=5) | P-value | SP263(−) (n=25) | SP263(+) (n=23) | P-value |
---|---|---|---|---|---|---|
Median age, years | 59 ( |
63 ( |
0.354 | 62 ( |
59 ( |
0.904 |
Median tumor size, cm | 1.7 (0.5–3.5) | 1.5 (1.3–4.0) | 0.907 | 1.7 (0.7–8.0) | 1.5 (0.7–4.0) | 0.329 |
N-positive, % | 27.9% | 40.0% | 0.659 | 36.0% | 26.1% | 0.464 |
Median stage | 2 ( |
1 ( |
0.517 | 2 ( |
1 ( |
0.336 |
MHC-positive, % | 62.8% | 100% | 0.098 | 60.0% | 73.9% | 0.312 |
%High TILs, % | 46.5% | 80.0% | 0.161 | 40.0% | 60.8% | 0.153 |
Median no. CD8+ T | 53.3 (1.0–108.0) | 80.0 (54.0–130.0) | 0.097 | 42.0 (12.0–120.3) | 66.0 (1.0–130.0) | 0.021 |
PDL1-E1L3N (+), % | - | - | - | 0% | 21.7% | 0.015 |
PDL1-SP263 (+), % | 41.9% | 100% | 0.015 |
- | - | - |
P<0.05. MHC, major histocompatibility complex; TILs, tumor-infiltrating lymphocytes. Median age, stage and tumor size, and the number of CD8+ T lymphocytes were compared between two groups using Mann-Whitney-U test. Positive rates of MHC and PD-L1 expression, the proportion of patients with N-positive cancer, and high TIL rates were compared between two groups using χ2 test or Fisher's exact test.