Association of molecular subtypes with Ki-67 changes in untreated breast cancer patients undergoing pre-surgical trials

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Abstract

Background: Ki-67 is increasingly being used as a response biomarker in window of opportunity, pre-surgical trials for breast cancer patients. Since Ki-67 is often higher at surgery than at baseline core biopsy in subjects allocated to placebo, we investigated which factors affected this change. Patients and methods: We retrieved data from 274 patients who received no active treatment in three consecutive pre-surgical trials from a single institution. We assessed the association between changes in Ki-67 from diagnostic biopsy to surgical specimen and the following factors: age, body mass index, tumor prognostic and predictive factors, including immunohistochemical molecular subtype, number and size of biopsy specimens, time from biopsy to surgery, circulating insulin-like growth factor-I, sex hormone-binding globulin and hsCRP. Results: A total of 269 patients with paired measures of Ki-67 at biopsy and surgery were analyzed. Overall, the mean (±SD) change was 2.2 ± 9.2% after a median interval of 41 days (inter-quartile range 33-48). Molecular subtype was the only factor associated with a significant change of Ki-67 (P = 0.004), with a mean absolute increase of 5.3% [95% confidence interval (CI): 2.3-8.3, P = 0.0005] in estrogen receptor-negative HER2-positive tumors (n = 36) and 5.4% (95% CI: 2.9-7.9, P <0.0001) in triple-negative tumors (n = 78). No significant change in luminal-A (n = 46), luminal-B (n = 85) and luminal-B HER2-positive (n = 24) tumors was observed. Conclusions: A significant increase in Ki-67 from baseline biopsy to end point surgery in untreated subjects was ascertained in HER2-positive and triple-negative tumors. This biological association suggests a real increase in cancer proliferation, possibly as a result of a biopsy-driven wound healing effect, and should be considered in the design and interpretation of pre-surgical studies.

Original languageEnglish
Article numbermdt528
Pages (from-to)618-623
Number of pages6
JournalAnnals of Oncology
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 2014

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Breast Neoplasms
Biopsy
Neoplasms
Confidence Intervals
Sex Hormone-Binding Globulin
Age Factors
Insulin-Like Growth Factor I
Estrogen Receptors
Wound Healing
Body Mass Index
Biomarkers
Placebos
Therapeutics

Keywords

  • Ki 67 antigen
  • Molecular subtype breast cancer
  • Neoadjuvant treatment breast cancer
  • Triple-negative breast cancer
  • Window of opportunity

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

@article{4f601bbab2c641f2ad5a60c3e60a09c2,
title = "Association of molecular subtypes with Ki-67 changes in untreated breast cancer patients undergoing pre-surgical trials",
abstract = "Background: Ki-67 is increasingly being used as a response biomarker in window of opportunity, pre-surgical trials for breast cancer patients. Since Ki-67 is often higher at surgery than at baseline core biopsy in subjects allocated to placebo, we investigated which factors affected this change. Patients and methods: We retrieved data from 274 patients who received no active treatment in three consecutive pre-surgical trials from a single institution. We assessed the association between changes in Ki-67 from diagnostic biopsy to surgical specimen and the following factors: age, body mass index, tumor prognostic and predictive factors, including immunohistochemical molecular subtype, number and size of biopsy specimens, time from biopsy to surgery, circulating insulin-like growth factor-I, sex hormone-binding globulin and hsCRP. Results: A total of 269 patients with paired measures of Ki-67 at biopsy and surgery were analyzed. Overall, the mean (±SD) change was 2.2 ± 9.2{\%} after a median interval of 41 days (inter-quartile range 33-48). Molecular subtype was the only factor associated with a significant change of Ki-67 (P = 0.004), with a mean absolute increase of 5.3{\%} [95{\%} confidence interval (CI): 2.3-8.3, P = 0.0005] in estrogen receptor-negative HER2-positive tumors (n = 36) and 5.4{\%} (95{\%} CI: 2.9-7.9, P <0.0001) in triple-negative tumors (n = 78). No significant change in luminal-A (n = 46), luminal-B (n = 85) and luminal-B HER2-positive (n = 24) tumors was observed. Conclusions: A significant increase in Ki-67 from baseline biopsy to end point surgery in untreated subjects was ascertained in HER2-positive and triple-negative tumors. This biological association suggests a real increase in cancer proliferation, possibly as a result of a biopsy-driven wound healing effect, and should be considered in the design and interpretation of pre-surgical studies.",
keywords = "Ki 67 antigen, Molecular subtype breast cancer, Neoadjuvant treatment breast cancer, Triple-negative breast cancer, Window of opportunity",
author = "S. Gandini and A. Guerrieri-Gonzaga and G. Pruneri and D. Serrano and M. Cazzaniga and M. Lazzeroni and P. Veronesi and H. Johansson and B. Bonanni and G. Viale and A. Decensi",
year = "2014",
month = "3",
doi = "10.1093/annonc/mdt528",
language = "English",
volume = "25",
pages = "618--623",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "NLM (Medline)",
number = "3",

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TY - JOUR

T1 - Association of molecular subtypes with Ki-67 changes in untreated breast cancer patients undergoing pre-surgical trials

AU - Gandini, S.

AU - Guerrieri-Gonzaga, A.

AU - Pruneri, G.

AU - Serrano, D.

AU - Cazzaniga, M.

AU - Lazzeroni, M.

AU - Veronesi, P.

AU - Johansson, H.

AU - Bonanni, B.

AU - Viale, G.

AU - Decensi, A.

PY - 2014/3

Y1 - 2014/3

N2 - Background: Ki-67 is increasingly being used as a response biomarker in window of opportunity, pre-surgical trials for breast cancer patients. Since Ki-67 is often higher at surgery than at baseline core biopsy in subjects allocated to placebo, we investigated which factors affected this change. Patients and methods: We retrieved data from 274 patients who received no active treatment in three consecutive pre-surgical trials from a single institution. We assessed the association between changes in Ki-67 from diagnostic biopsy to surgical specimen and the following factors: age, body mass index, tumor prognostic and predictive factors, including immunohistochemical molecular subtype, number and size of biopsy specimens, time from biopsy to surgery, circulating insulin-like growth factor-I, sex hormone-binding globulin and hsCRP. Results: A total of 269 patients with paired measures of Ki-67 at biopsy and surgery were analyzed. Overall, the mean (±SD) change was 2.2 ± 9.2% after a median interval of 41 days (inter-quartile range 33-48). Molecular subtype was the only factor associated with a significant change of Ki-67 (P = 0.004), with a mean absolute increase of 5.3% [95% confidence interval (CI): 2.3-8.3, P = 0.0005] in estrogen receptor-negative HER2-positive tumors (n = 36) and 5.4% (95% CI: 2.9-7.9, P <0.0001) in triple-negative tumors (n = 78). No significant change in luminal-A (n = 46), luminal-B (n = 85) and luminal-B HER2-positive (n = 24) tumors was observed. Conclusions: A significant increase in Ki-67 from baseline biopsy to end point surgery in untreated subjects was ascertained in HER2-positive and triple-negative tumors. This biological association suggests a real increase in cancer proliferation, possibly as a result of a biopsy-driven wound healing effect, and should be considered in the design and interpretation of pre-surgical studies.

AB - Background: Ki-67 is increasingly being used as a response biomarker in window of opportunity, pre-surgical trials for breast cancer patients. Since Ki-67 is often higher at surgery than at baseline core biopsy in subjects allocated to placebo, we investigated which factors affected this change. Patients and methods: We retrieved data from 274 patients who received no active treatment in three consecutive pre-surgical trials from a single institution. We assessed the association between changes in Ki-67 from diagnostic biopsy to surgical specimen and the following factors: age, body mass index, tumor prognostic and predictive factors, including immunohistochemical molecular subtype, number and size of biopsy specimens, time from biopsy to surgery, circulating insulin-like growth factor-I, sex hormone-binding globulin and hsCRP. Results: A total of 269 patients with paired measures of Ki-67 at biopsy and surgery were analyzed. Overall, the mean (±SD) change was 2.2 ± 9.2% after a median interval of 41 days (inter-quartile range 33-48). Molecular subtype was the only factor associated with a significant change of Ki-67 (P = 0.004), with a mean absolute increase of 5.3% [95% confidence interval (CI): 2.3-8.3, P = 0.0005] in estrogen receptor-negative HER2-positive tumors (n = 36) and 5.4% (95% CI: 2.9-7.9, P <0.0001) in triple-negative tumors (n = 78). No significant change in luminal-A (n = 46), luminal-B (n = 85) and luminal-B HER2-positive (n = 24) tumors was observed. Conclusions: A significant increase in Ki-67 from baseline biopsy to end point surgery in untreated subjects was ascertained in HER2-positive and triple-negative tumors. This biological association suggests a real increase in cancer proliferation, possibly as a result of a biopsy-driven wound healing effect, and should be considered in the design and interpretation of pre-surgical studies.

KW - Ki 67 antigen

KW - Molecular subtype breast cancer

KW - Neoadjuvant treatment breast cancer

KW - Triple-negative breast cancer

KW - Window of opportunity

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DO - 10.1093/annonc/mdt528

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JF - Annals of Oncology

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