Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study

Dieci, Maria Vittoria; Criscitiello, Carmen; Goubar, Aïcha; Viale, Giuseppe; Conte, Pierfranco; Guarneri, Valentina; Ficarra, Guido; Mathieu, Marie Christine; Delaloge, Suzette; Curigliano, Giuseppe; Varga, Andrea

doi:10.1093/annonc/mdt556

Cited by 374 publications

(215 citation statements)

References 10 publications

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“…19 out of 27 patients with high-TIL residual disease were evaluated for TILs on the diagnostic biopsy. With only 1 exception, the TIL percentage in post-chemotherapy surgical specimens was higher compared to that in pre-chemotherapy specimens, suggesting that the inflammatory process plays a part in the efficacy of antitumor drug therapy [10]. An analysis of 368 patients consisting of 2 cohorts of ER-negative patients treated with anthracylcine-containing neoadjuvant chemotherapy for BC showed that, for the HER2-positive and triple-negative patients, a high level of TILs was significantly correlated with achieving pathologic complete response [11].…”

Section: Discussionmentioning

confidence: 99%

The Preoperative Neutrophil/Lymphocyte Ratio Does not Correlate with the 21-Gene Recurrence Score in Estrogen Receptor-Positive Breast Cancer Patients

Grenader¹,

Plotkin²,

Geffen³

2015

Oncol Res Treat

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Aims: The aim of this study was to examine the correlation, if any, between the preoperative neutrophil/lymphocyte ratio (NLR) and the OncotypeDX™ 21-gene recurrence score (RS) in patients with early-stage estrogen receptor (ER)-positive breast cancer (BC). Materials and Methods: We retrospectively reviewed the medical records of patients diagnosed with primary ER-positive BC who were referred for the RS assay. The correlation between the preoperative NLR and the RS was analyzed. Results: For the 242 patients with sufficient data for analysis, the median age at diagnosis was 59.5 years. The tumor size ranged from 0.50 to 5.50 cm, with a mean size of 1.8 cm; 73.2% of the tumors were < 2 cm in size. Most of the tumors (66.3%) were of grade 2; the rest was nearly equally divided between grades 1 and 3. The test results for the progesterone receptor (PR) were positive in 86.6% of the cases. Lymph node metastases were present in 22.3% of the patients. The median RS was 18 (range 0-60) and the mean NLR value was 2.11 (range 0.49-7.49). We found no significant correlation between the NLR and the RS. Conclusion: Our data suggest that the preoperative NLR does not predict the 21-gene RS in patients with early-stage hormone-sensitive BC.

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Section: Discussionmentioning

confidence: 99%

The Preoperative Neutrophil/Lymphocyte Ratio Does not Correlate with the 21-Gene Recurrence Score in Estrogen Receptor-Positive Breast Cancer Patients

Grenader¹,

Plotkin²,

Geffen³

2015

Oncol Res Treat

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“…Tumor infiltrating lymphocytes (TILs) in pretreatment tumor samples are associated with improved response to neoadjuvant chemotherapy in TNBC and survival among those patients with residual disease after neoadjuvant chemotherapy [46][47][48][49]. Lymphocytes can intercalate between tumor cells (intratumoral TILs) or infiltrate the surrounding stromal tissue (stromal TILs).…”

Section: Host Anti-tumor Immunity In Tnbcmentioning

confidence: 99%

Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer

Telli

Stover

Loi

et al. 2018

Breast Cancer Res Treat

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Purpose Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit. Methods We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection. Results Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise. Conclusions HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of 'immune cold' TNBCs.

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“…7 Confusingly, an analysis of 3771 samples from patients enrolled in six randomized trials demonstrated that higher TIL counts were associated with decreased overall survival (OS) in HR positive BC, although TILs were associated with a higher probability for pCR in the same patients 6 Moreover, few studies have reported on TIL kinetics under NACT, with the vast majority of those comparing pre-chemotherapy samples with surgical specimens, after the completion of the entire schedule of NACT. Again, the published results are inconsistent, with studies suggesting both improved 8, 9 and worse patient outcomes 10 , 11 associated with high TIL counts after NACT. In addition, the prognostic value of Forkhead Box P3 (FOXP3+) T-lymphocytes in BC has been controversial; however, a recent meta-analysis suggests that high FOXP3+ cells are associated with poor recurrence-free survival.…”

Section: Introductionmentioning

confidence: 99%

Dynamic evaluation of the immune infiltrate and immune function genes as predictive markers for neoadjuvant chemotherapy in hormone receptor positive, HER2 negative breast cancer

et al. 2018

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Gene expression (GE) signatures and Tumor Infiltrating Lymphocytes (TIL) enumeration are predictive for response to neoadjuvant chemotherapy in HR- and in HER2+ breast cancer, but data are conflicting in HR+/HER2- disease. This study aimed to explore their predictive value in this subset, measured both at baseline and after short exposure to chemotherapy. Specifically, the PROMIX phase 2 trial enrolled patients with locally advanced HER2- BC to receive six cycles of epirubicin and docetaxel, plus bevacizumab during cycles 3–6. Patients underwent tumor biopsies at baseline and after cycle 2 for GE profiling and enumeration of TIL, FOXP3+ T-cells and CD163+ macrophages. An immune related gene module and the quantification of the immune infiltrate were analyzed for association with pathologic complete response (pCR), decrease in tumor size and disease-free survival (DFS). Of the 150 patients enrolled in PROMIX, 113 were HR+/HER2-. Baseline GE and immune cell enumeration data were available from 71 patients, while data after 2 cycles of chemotherapy were available from 41. At baseline, only GE was statistically significantly associated with higher pCR rates (OR 2.29, 95% CI 1.05 – 5.38, p = 0.037) and decrease in tumor size (r = 0.25, p = 0.047). In contrast, longitudinal data indicate that both GE (r = 0.54, p<0.001) and TIL abundance (p = 0.009) are stronger predictors for the reduction of tumor size, while low FOXP3+ was statistically significantly associated with an improved DFS (p = 0.027). In conclusion, GE analysis, TIL and FOXP3+ enumeration after short-term exposure to chemotherapy carry important predictive information in HR+/HER2- breast cancer at the neoadjuvant setting.

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Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study

Cited by 374 publications

References 10 publications

The Preoperative Neutrophil/Lymphocyte Ratio Does not Correlate with the 21-Gene Recurrence Score in Estrogen Receptor-Positive Breast Cancer Patients

The Preoperative Neutrophil/Lymphocyte Ratio Does not Correlate with the 21-Gene Recurrence Score in Estrogen Receptor-Positive Breast Cancer Patients

Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer

Dynamic evaluation of the immune infiltrate and immune function genes as predictive markers for neoadjuvant chemotherapy in hormone receptor positive, HER2 negative breast cancer

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