Predictive and prognostic role of tumor-infiltrating lymphocytes for early breast cancer according to disease subtypes: Sensitivity analysis of randomized trials in adjuvant and neoadjuvant setting

Luisa Carbognin, Sara Pilotto, Rolando Nortilli, Matteo Brunelli, Alessia Nottegar, Isabella Sperduti, Diana Giannarelli, Emilio Bria, Giampaolo Tortora

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background. The role of tumor-infiltrating lymphocytes (TILs) in breastcancer (BC) is still an issue for clinical research.Toward this end, a sensitivity analysis of neoadjuvant and adjuvant randomized clinical trials was performed according to disease subtypes. Methods. Pathological complete responses (pCRs) after neoadjuvant treatment according to the presence or absence of lymphocyte-predominant BC (LPBC) were extracted and cumulated as odds ratios (ORs) by adopting a random-effects model by subtype. Overall survival hazard ratios as a function of 10% incremental values of stromal TILs (sTILs) in adjuvant trials were extracted. The interaction test was adopted to determine the differential effect according to the subtype. Results. Eight trials (5,514 patients) were identified. With regard to neoadjuvant setting (4 studies), a significant interaction (p <.0001) according to LPBC was found. The presence of LPBC was associated with a 29.5% increase in pCR rate compared with non-LPBC (p <.0001). The pCR rate was significantly higher in patients with LPBC in triple-negative BC (TNBC) and HER2-positive BC settings, with an absolute difference of 15.7% (95% confidence interval [CI], 4.9%–26.2%) and 33.3% (95% CI, 23.6%–42.7%), respectively. With respect to the adjuvant setting (4 studies), a significant interaction (p,.0001) according to sTILs was found. A survival benefit was more likely to be determined for HER2-positive BC (p = .025) and TNBC (p <.0001), with no statistically significant difference for estrogen receptor-positive/HER2- negative disease. Conclusion. Despite the retrospective nature of this analysis, the presence of TILs may represent a robust predictive and prognostic marker for BC, particularly for TNBC and HER2- positive disease.

Original languageEnglish
Pages (from-to)283-291
Number of pages9
JournalThe oncologist
Volume21
Issue number3
DOIs
Publication statusPublished - Feb 10 2016

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Tumor-Infiltrating Lymphocytes
Lymphocytes
Breast Neoplasms
Confidence Intervals
Neoadjuvant Therapy
Survival
Estrogen Receptors
Randomized Controlled Trials
Odds Ratio
Research

Keywords

  • Adjuvant
  • Breast cancer
  • Neoadjuvant
  • Prognosis
  • Sensitivity analysis
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Predictive and prognostic role of tumor-infiltrating lymphocytes for early breast cancer according to disease subtypes : Sensitivity analysis of randomized trials in adjuvant and neoadjuvant setting. / Carbognin, Luisa; Pilotto, Sara; Nortilli, Rolando; Brunelli, Matteo; Nottegar, Alessia; Sperduti, Isabella; Giannarelli, Diana; Bria, Emilio; Tortora, Giampaolo.

In: The oncologist, Vol. 21, No. 3, 10.02.2016, p. 283-291.

Research output: Contribution to journalArticle

Carbognin, Luisa ; Pilotto, Sara ; Nortilli, Rolando ; Brunelli, Matteo ; Nottegar, Alessia ; Sperduti, Isabella ; Giannarelli, Diana ; Bria, Emilio ; Tortora, Giampaolo. / Predictive and prognostic role of tumor-infiltrating lymphocytes for early breast cancer according to disease subtypes : Sensitivity analysis of randomized trials in adjuvant and neoadjuvant setting. In: The oncologist. 2016 ; Vol. 21, No. 3. pp. 283-291.
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abstract = "Background. The role of tumor-infiltrating lymphocytes (TILs) in breastcancer (BC) is still an issue for clinical research.Toward this end, a sensitivity analysis of neoadjuvant and adjuvant randomized clinical trials was performed according to disease subtypes. Methods. Pathological complete responses (pCRs) after neoadjuvant treatment according to the presence or absence of lymphocyte-predominant BC (LPBC) were extracted and cumulated as odds ratios (ORs) by adopting a random-effects model by subtype. Overall survival hazard ratios as a function of 10{\%} incremental values of stromal TILs (sTILs) in adjuvant trials were extracted. The interaction test was adopted to determine the differential effect according to the subtype. Results. Eight trials (5,514 patients) were identified. With regard to neoadjuvant setting (4 studies), a significant interaction (p <.0001) according to LPBC was found. The presence of LPBC was associated with a 29.5{\%} increase in pCR rate compared with non-LPBC (p <.0001). The pCR rate was significantly higher in patients with LPBC in triple-negative BC (TNBC) and HER2-positive BC settings, with an absolute difference of 15.7{\%} (95{\%} confidence interval [CI], 4.9{\%}–26.2{\%}) and 33.3{\%} (95{\%} CI, 23.6{\%}–42.7{\%}), respectively. With respect to the adjuvant setting (4 studies), a significant interaction (p,.0001) according to sTILs was found. A survival benefit was more likely to be determined for HER2-positive BC (p = .025) and TNBC (p <.0001), with no statistically significant difference for estrogen receptor-positive/HER2- negative disease. Conclusion. Despite the retrospective nature of this analysis, the presence of TILs may represent a robust predictive and prognostic marker for BC, particularly for TNBC and HER2- positive disease.",
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T2 - Sensitivity analysis of randomized trials in adjuvant and neoadjuvant setting

AU - Carbognin, Luisa

AU - Pilotto, Sara

AU - Nortilli, Rolando

AU - Brunelli, Matteo

AU - Nottegar, Alessia

AU - Sperduti, Isabella

AU - Giannarelli, Diana

AU - Bria, Emilio

AU - Tortora, Giampaolo

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N2 - Background. The role of tumor-infiltrating lymphocytes (TILs) in breastcancer (BC) is still an issue for clinical research.Toward this end, a sensitivity analysis of neoadjuvant and adjuvant randomized clinical trials was performed according to disease subtypes. Methods. Pathological complete responses (pCRs) after neoadjuvant treatment according to the presence or absence of lymphocyte-predominant BC (LPBC) were extracted and cumulated as odds ratios (ORs) by adopting a random-effects model by subtype. Overall survival hazard ratios as a function of 10% incremental values of stromal TILs (sTILs) in adjuvant trials were extracted. The interaction test was adopted to determine the differential effect according to the subtype. Results. Eight trials (5,514 patients) were identified. With regard to neoadjuvant setting (4 studies), a significant interaction (p <.0001) according to LPBC was found. The presence of LPBC was associated with a 29.5% increase in pCR rate compared with non-LPBC (p <.0001). The pCR rate was significantly higher in patients with LPBC in triple-negative BC (TNBC) and HER2-positive BC settings, with an absolute difference of 15.7% (95% confidence interval [CI], 4.9%–26.2%) and 33.3% (95% CI, 23.6%–42.7%), respectively. With respect to the adjuvant setting (4 studies), a significant interaction (p,.0001) according to sTILs was found. A survival benefit was more likely to be determined for HER2-positive BC (p = .025) and TNBC (p <.0001), with no statistically significant difference for estrogen receptor-positive/HER2- negative disease. Conclusion. Despite the retrospective nature of this analysis, the presence of TILs may represent a robust predictive and prognostic marker for BC, particularly for TNBC and HER2- positive disease.

AB - Background. The role of tumor-infiltrating lymphocytes (TILs) in breastcancer (BC) is still an issue for clinical research.Toward this end, a sensitivity analysis of neoadjuvant and adjuvant randomized clinical trials was performed according to disease subtypes. Methods. Pathological complete responses (pCRs) after neoadjuvant treatment according to the presence or absence of lymphocyte-predominant BC (LPBC) were extracted and cumulated as odds ratios (ORs) by adopting a random-effects model by subtype. Overall survival hazard ratios as a function of 10% incremental values of stromal TILs (sTILs) in adjuvant trials were extracted. The interaction test was adopted to determine the differential effect according to the subtype. Results. Eight trials (5,514 patients) were identified. With regard to neoadjuvant setting (4 studies), a significant interaction (p <.0001) according to LPBC was found. The presence of LPBC was associated with a 29.5% increase in pCR rate compared with non-LPBC (p <.0001). The pCR rate was significantly higher in patients with LPBC in triple-negative BC (TNBC) and HER2-positive BC settings, with an absolute difference of 15.7% (95% confidence interval [CI], 4.9%–26.2%) and 33.3% (95% CI, 23.6%–42.7%), respectively. With respect to the adjuvant setting (4 studies), a significant interaction (p,.0001) according to sTILs was found. A survival benefit was more likely to be determined for HER2-positive BC (p = .025) and TNBC (p <.0001), with no statistically significant difference for estrogen receptor-positive/HER2- negative disease. Conclusion. Despite the retrospective nature of this analysis, the presence of TILs may represent a robust predictive and prognostic marker for BC, particularly for TNBC and HER2- positive disease.

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KW - Prognosis

KW - Sensitivity analysis

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