Impact of histopathology, tumor-infiltrating lymphocytes, and adjuvant chemotherapy on prognosis of triple-negative breast cancer

Roberto A. Leon-Ferre, Mei-Yin Polley, Heshan Liu, Judith A. Gilbert, Victoria Cafourek, David W. Hillman, Ahmed Elkhanany, Margaret Akinhanmi, Jenna Lilyquist, Abigail Thomas, Vivian Negron, Judy C Boughey, Minetta C Liu, James N. Ingle, Krishna R Kalari, Fergus J Couch, Daniel W Visscher, Matthew Philip Goetz

Research output: Contribution to journalArticle

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Abstract

Background: Given its high recurrence risk, guidelines recommend systemic therapy for most patients with early-stage triple-negative breast cancer (TNBC). While some clinicopathologic factors and tumor-infiltrating lymphocytes (TILs) are known to be prognostic in patients receiving chemotherapy, their prognostic implications in systemically untreated patients remain unknown. Methods: From a cohort of 9982 women with surgically treated non-metastatic breast cancer, all patients with clinically reported ER-negative/borderline (≤10%) disease were selected for central assessment of ER/PR/HER2, histopathology, Ki-67, and TILs. The impact of these parameters on invasive disease-free survival (IDFS) and overall survival (OS) was assessed using Cox proportional hazards models. Results: Six hundred five patients met the criteria for TNBC (ER/PR < 1% and HER2 negative). Most were T1–2 (95%), N0–1 (86%), grade 3 (88%), and had a Ki-67 >15% (75%). Histologically, 70% were invasive carcinoma of no special type, 16% medullary, 8% metaplastic, and 6% apocrine. The median stromal TIL content was 20%. Four hundred twenty-three (70%) patients received adjuvant chemotherapy. Median OS follow-up was 10.6 years. On multivariate analysis, only higher nodal stage, lower TILs, and the absence of adjuvant chemotherapy were associated with worse IDFS and OS. Among systemically untreated patients (n = 182), the 5-year IDFS was 69.9% (95% CI 60.7–80.5) [T1a: 82.5% (95% CI 62.8–100), T1b: 67.5% (95% CI 51.9–87.8) and T1c: 67.3% (95% CI 54.9–82.6)], compared to 77.8% (95% CI 68.3–83.6) for systemically treated T1N0. Nodal stage and TILs remained strongly associated with outcomes. Conclusions: In early-stage TNBC, nodal involvement, TILs, and receipt of adjuvant chemotherapy were independently associated with IDFS and OS. In systemically untreated TNBC, TILs remained prognostic and the risk of recurrence or death was substantial, even for T1N0 disease.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalBreast Cancer Research and Treatment
DOIs
StateAccepted/In press - Sep 14 2017

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Triple Negative Breast Neoplasms
Tumor-Infiltrating Lymphocytes
Adjuvant Chemotherapy
Disease-Free Survival
Survival
Recurrence
Proportional Hazards Models
Multivariate Analysis
Guidelines
Breast Neoplasms
Carcinoma
Drug Therapy

Keywords

  • Adjuvant chemotherapy
  • Histology
  • Prognosis
  • Triple-negative breast cancer
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Impact of histopathology, tumor-infiltrating lymphocytes, and adjuvant chemotherapy on prognosis of triple-negative breast cancer. / Leon-Ferre, Roberto A.; Polley, Mei-Yin; Liu, Heshan; Gilbert, Judith A.; Cafourek, Victoria; Hillman, David W.; Elkhanany, Ahmed; Akinhanmi, Margaret; Lilyquist, Jenna; Thomas, Abigail; Negron, Vivian; Boughey, Judy C; Liu, Minetta C; Ingle, James N.; Kalari, Krishna R; Couch, Fergus J; Visscher, Daniel W; Goetz, Matthew Philip.

In: Breast Cancer Research and Treatment, 14.09.2017, p. 1-11.

Research output: Contribution to journalArticle

Leon-Ferre, Roberto A. ; Polley, Mei-Yin ; Liu, Heshan ; Gilbert, Judith A. ; Cafourek, Victoria ; Hillman, David W. ; Elkhanany, Ahmed ; Akinhanmi, Margaret ; Lilyquist, Jenna ; Thomas, Abigail ; Negron, Vivian ; Boughey, Judy C ; Liu, Minetta C ; Ingle, James N. ; Kalari, Krishna R ; Couch, Fergus J ; Visscher, Daniel W ; Goetz, Matthew Philip. / Impact of histopathology, tumor-infiltrating lymphocytes, and adjuvant chemotherapy on prognosis of triple-negative breast cancer. In: Breast Cancer Research and Treatment. 2017 ; pp. 1-11.
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title = "Impact of histopathology, tumor-infiltrating lymphocytes, and adjuvant chemotherapy on prognosis of triple-negative breast cancer",
abstract = "Background: Given its high recurrence risk, guidelines recommend systemic therapy for most patients with early-stage triple-negative breast cancer (TNBC). While some clinicopathologic factors and tumor-infiltrating lymphocytes (TILs) are known to be prognostic in patients receiving chemotherapy, their prognostic implications in systemically untreated patients remain unknown. Methods: From a cohort of 9982 women with surgically treated non-metastatic breast cancer, all patients with clinically reported ER-negative/borderline (≤10{\%}) disease were selected for central assessment of ER/PR/HER2, histopathology, Ki-67, and TILs. The impact of these parameters on invasive disease-free survival (IDFS) and overall survival (OS) was assessed using Cox proportional hazards models. Results: Six hundred five patients met the criteria for TNBC (ER/PR < 1{\%} and HER2 negative). Most were T1–2 (95{\%}), N0–1 (86{\%}), grade 3 (88{\%}), and had a Ki-67 >15{\%} (75{\%}). Histologically, 70{\%} were invasive carcinoma of no special type, 16{\%} medullary, 8{\%} metaplastic, and 6{\%} apocrine. The median stromal TIL content was 20{\%}. Four hundred twenty-three (70{\%}) patients received adjuvant chemotherapy. Median OS follow-up was 10.6 years. On multivariate analysis, only higher nodal stage, lower TILs, and the absence of adjuvant chemotherapy were associated with worse IDFS and OS. Among systemically untreated patients (n = 182), the 5-year IDFS was 69.9{\%} (95{\%} CI 60.7–80.5) [T1a: 82.5{\%} (95{\%} CI 62.8–100), T1b: 67.5{\%} (95{\%} CI 51.9–87.8) and T1c: 67.3{\%} (95{\%} CI 54.9–82.6)], compared to 77.8{\%} (95{\%} CI 68.3–83.6) for systemically treated T1N0. Nodal stage and TILs remained strongly associated with outcomes. Conclusions: In early-stage TNBC, nodal involvement, TILs, and receipt of adjuvant chemotherapy were independently associated with IDFS and OS. In systemically untreated TNBC, TILs remained prognostic and the risk of recurrence or death was substantial, even for T1N0 disease.",
keywords = "Adjuvant chemotherapy, Histology, Prognosis, Triple-negative breast cancer, Tumor-infiltrating lymphocytes",
author = "Leon-Ferre, {Roberto A.} and Mei-Yin Polley and Heshan Liu and Gilbert, {Judith A.} and Victoria Cafourek and Hillman, {David W.} and Ahmed Elkhanany and Margaret Akinhanmi and Jenna Lilyquist and Abigail Thomas and Vivian Negron and Boughey, {Judy C} and Liu, {Minetta C} and Ingle, {James N.} and Kalari, {Krishna R} and Couch, {Fergus J} and Visscher, {Daniel W} and Goetz, {Matthew Philip}",
year = "2017",
month = "9",
day = "14",
doi = "10.1007/s10549-017-4499-7",
language = "English (US)",
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TY - JOUR

T1 - Impact of histopathology, tumor-infiltrating lymphocytes, and adjuvant chemotherapy on prognosis of triple-negative breast cancer

AU - Leon-Ferre, Roberto A.

AU - Polley, Mei-Yin

AU - Liu, Heshan

AU - Gilbert, Judith A.

AU - Cafourek, Victoria

AU - Hillman, David W.

AU - Elkhanany, Ahmed

AU - Akinhanmi, Margaret

AU - Lilyquist, Jenna

AU - Thomas, Abigail

AU - Negron, Vivian

AU - Boughey, Judy C

AU - Liu, Minetta C

AU - Ingle, James N.

AU - Kalari, Krishna R

AU - Couch, Fergus J

AU - Visscher, Daniel W

AU - Goetz, Matthew Philip

PY - 2017/9/14

Y1 - 2017/9/14

N2 - Background: Given its high recurrence risk, guidelines recommend systemic therapy for most patients with early-stage triple-negative breast cancer (TNBC). While some clinicopathologic factors and tumor-infiltrating lymphocytes (TILs) are known to be prognostic in patients receiving chemotherapy, their prognostic implications in systemically untreated patients remain unknown. Methods: From a cohort of 9982 women with surgically treated non-metastatic breast cancer, all patients with clinically reported ER-negative/borderline (≤10%) disease were selected for central assessment of ER/PR/HER2, histopathology, Ki-67, and TILs. The impact of these parameters on invasive disease-free survival (IDFS) and overall survival (OS) was assessed using Cox proportional hazards models. Results: Six hundred five patients met the criteria for TNBC (ER/PR < 1% and HER2 negative). Most were T1–2 (95%), N0–1 (86%), grade 3 (88%), and had a Ki-67 >15% (75%). Histologically, 70% were invasive carcinoma of no special type, 16% medullary, 8% metaplastic, and 6% apocrine. The median stromal TIL content was 20%. Four hundred twenty-three (70%) patients received adjuvant chemotherapy. Median OS follow-up was 10.6 years. On multivariate analysis, only higher nodal stage, lower TILs, and the absence of adjuvant chemotherapy were associated with worse IDFS and OS. Among systemically untreated patients (n = 182), the 5-year IDFS was 69.9% (95% CI 60.7–80.5) [T1a: 82.5% (95% CI 62.8–100), T1b: 67.5% (95% CI 51.9–87.8) and T1c: 67.3% (95% CI 54.9–82.6)], compared to 77.8% (95% CI 68.3–83.6) for systemically treated T1N0. Nodal stage and TILs remained strongly associated with outcomes. Conclusions: In early-stage TNBC, nodal involvement, TILs, and receipt of adjuvant chemotherapy were independently associated with IDFS and OS. In systemically untreated TNBC, TILs remained prognostic and the risk of recurrence or death was substantial, even for T1N0 disease.

AB - Background: Given its high recurrence risk, guidelines recommend systemic therapy for most patients with early-stage triple-negative breast cancer (TNBC). While some clinicopathologic factors and tumor-infiltrating lymphocytes (TILs) are known to be prognostic in patients receiving chemotherapy, their prognostic implications in systemically untreated patients remain unknown. Methods: From a cohort of 9982 women with surgically treated non-metastatic breast cancer, all patients with clinically reported ER-negative/borderline (≤10%) disease were selected for central assessment of ER/PR/HER2, histopathology, Ki-67, and TILs. The impact of these parameters on invasive disease-free survival (IDFS) and overall survival (OS) was assessed using Cox proportional hazards models. Results: Six hundred five patients met the criteria for TNBC (ER/PR < 1% and HER2 negative). Most were T1–2 (95%), N0–1 (86%), grade 3 (88%), and had a Ki-67 >15% (75%). Histologically, 70% were invasive carcinoma of no special type, 16% medullary, 8% metaplastic, and 6% apocrine. The median stromal TIL content was 20%. Four hundred twenty-three (70%) patients received adjuvant chemotherapy. Median OS follow-up was 10.6 years. On multivariate analysis, only higher nodal stage, lower TILs, and the absence of adjuvant chemotherapy were associated with worse IDFS and OS. Among systemically untreated patients (n = 182), the 5-year IDFS was 69.9% (95% CI 60.7–80.5) [T1a: 82.5% (95% CI 62.8–100), T1b: 67.5% (95% CI 51.9–87.8) and T1c: 67.3% (95% CI 54.9–82.6)], compared to 77.8% (95% CI 68.3–83.6) for systemically treated T1N0. Nodal stage and TILs remained strongly associated with outcomes. Conclusions: In early-stage TNBC, nodal involvement, TILs, and receipt of adjuvant chemotherapy were independently associated with IDFS and OS. In systemically untreated TNBC, TILs remained prognostic and the risk of recurrence or death was substantial, even for T1N0 disease.

KW - Adjuvant chemotherapy

KW - Histology

KW - Prognosis

KW - Triple-negative breast cancer

KW - Tumor-infiltrating lymphocytes

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DO - 10.1007/s10549-017-4499-7

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JO - Breast Cancer Research and Treatment

JF - Breast Cancer Research and Treatment

SN - 0167-6806

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