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 P.
N1 - Funding Information:
Funding This work was supported by the Mayo Clinic Center for Individualized Medicine; the Mayo Clinic Cancer Center (Grant Number CA15083-40A2 to MPG, JNI); George M. Eisenberg Foundation for Charities; the Mayo Clinic Breast SPORE (Grant Number P50CA 116201-9 to MPG, FJC, JNI, DWV, MP, KRK); and NIH Grant R01CA192393.
Publisher Copyright:
© 2017, Springer Science+Business Media, LLC.
PY - 2018/1/1
Y1 - 2018/1/1
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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U2 - 10.1007/s10549-017-4499-7
DO - 10.1007/s10549-017-4499-7
M3 - Article
C2 - 28913760
AN - SCOPUS:85029492496
SN - 0167-6806
VL - 167
SP - 89
EP - 99
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -