Back to Basics: Traditional Nottingham Grade Mitotic Counts Alone are Significant in Predicting Survival in Invasive Breast Carcinoma

James M. Chang, Ann E. McCullough, Amylou Dueck, Heidi E. Kosiorek, Idris T. Ocal, Thomas K. Lidner, Richard J. Gray, Nabil Wasif, Donald W Northfelt, Karen S. Anderson, Barbara A Pockaj

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Abstract

Background: Newer multigene molecular profiling assays for breast carcinoma rely heavily on the quantification of genes of proliferation, whereas traditional histological grading reports the mitotic count. The mitotic activity of invasive breast carcinomas may be undervalued; therefore, an evaluation of the prognostic significance of mitotic score in predicting prognosis was performed. Methods: Retrospective analysis of a single institutional cohort of newly diagnosed estrogen receptor positive (ER+), HER2 negative (HER2−) unilateral invasive breast carcinomas was performed. Mitotic scores from the 3-part Nottingham combined histological grade were compared with clinical parameters. Mitoses were counted on Olympus BX50 microscopes and assigned scores of 1–3 based on observed mitoses. Results: A total of 1292 ER+, HER2− invasive breast carcinoma patients were identified, with a median follow-up time of 2.6 years (range 0–14 years). Higher mitotic score was significantly associated with younger age, larger tumor size, angiolymphatic invasion, node-positive disease, higher stage, and the use of hormonal and cytotoxic chemotherapy. Mitotic score was significant in modeling time to local/regional recurrence (p = 0.02), recurrence-free survival/RFS (p < 0.001), and overall survival/OS (p = 0.01) with higher mitotic scores associated with worse outcomes. Higher mitotic score correlated significantly with intermediate/high risk Oncotype Dx recurrence scores (p = 0.009). Conclusions: First-generation molecular profiling assays for estrogen receptor positive invasive breast carcinomas derive much of their predictive power from quantifying genes of proliferation into a single score. Sometimes overlooked in the profusion of molecular data, the time-tested, mitotic count in the Nottingham combined histological grade is a good single-parameter predictor of survival.

Original languageEnglish (US)
JournalAnnals of Surgical Oncology
DOIs
StateAccepted/In press - May 22 2015

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Breast Neoplasms
Survival
Mitosis
Recurrence
Estrogen Receptors
Genes
Drug Therapy
Neoplasms

ASJC Scopus subject areas

  • Surgery
  • Oncology

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Back to Basics : Traditional Nottingham Grade Mitotic Counts Alone are Significant in Predicting Survival in Invasive Breast Carcinoma. / Chang, James M.; McCullough, Ann E.; Dueck, Amylou; Kosiorek, Heidi E.; Ocal, Idris T.; Lidner, Thomas K.; Gray, Richard J.; Wasif, Nabil; Northfelt, Donald W; Anderson, Karen S.; Pockaj, Barbara A.

In: Annals of Surgical Oncology, 22.05.2015.

Research output: Contribution to journalArticle

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title = "Back to Basics: Traditional Nottingham Grade Mitotic Counts Alone are Significant in Predicting Survival in Invasive Breast Carcinoma",
abstract = "Background: Newer multigene molecular profiling assays for breast carcinoma rely heavily on the quantification of genes of proliferation, whereas traditional histological grading reports the mitotic count. The mitotic activity of invasive breast carcinomas may be undervalued; therefore, an evaluation of the prognostic significance of mitotic score in predicting prognosis was performed. Methods: Retrospective analysis of a single institutional cohort of newly diagnosed estrogen receptor positive (ER+), HER2 negative (HER2−) unilateral invasive breast carcinomas was performed. Mitotic scores from the 3-part Nottingham combined histological grade were compared with clinical parameters. Mitoses were counted on Olympus BX50 microscopes and assigned scores of 1–3 based on observed mitoses. Results: A total of 1292 ER+, HER2− invasive breast carcinoma patients were identified, with a median follow-up time of 2.6 years (range 0–14 years). Higher mitotic score was significantly associated with younger age, larger tumor size, angiolymphatic invasion, node-positive disease, higher stage, and the use of hormonal and cytotoxic chemotherapy. Mitotic score was significant in modeling time to local/regional recurrence (p = 0.02), recurrence-free survival/RFS (p < 0.001), and overall survival/OS (p = 0.01) with higher mitotic scores associated with worse outcomes. Higher mitotic score correlated significantly with intermediate/high risk Oncotype Dx recurrence scores (p = 0.009). Conclusions: First-generation molecular profiling assays for estrogen receptor positive invasive breast carcinomas derive much of their predictive power from quantifying genes of proliferation into a single score. Sometimes overlooked in the profusion of molecular data, the time-tested, mitotic count in the Nottingham combined histological grade is a good single-parameter predictor of survival.",
author = "Chang, {James M.} and McCullough, {Ann E.} and Amylou Dueck and Kosiorek, {Heidi E.} and Ocal, {Idris T.} and Lidner, {Thomas K.} and Gray, {Richard J.} and Nabil Wasif and Northfelt, {Donald W} and Anderson, {Karen S.} and Pockaj, {Barbara A}",
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T2 - Traditional Nottingham Grade Mitotic Counts Alone are Significant in Predicting Survival in Invasive Breast Carcinoma

AU - Chang, James M.

AU - McCullough, Ann E.

AU - Dueck, Amylou

AU - Kosiorek, Heidi E.

AU - Ocal, Idris T.

AU - Lidner, Thomas K.

AU - Gray, Richard J.

AU - Wasif, Nabil

AU - Northfelt, Donald W

AU - Anderson, Karen S.

AU - Pockaj, Barbara A

PY - 2015/5/22

Y1 - 2015/5/22

N2 - Background: Newer multigene molecular profiling assays for breast carcinoma rely heavily on the quantification of genes of proliferation, whereas traditional histological grading reports the mitotic count. The mitotic activity of invasive breast carcinomas may be undervalued; therefore, an evaluation of the prognostic significance of mitotic score in predicting prognosis was performed. Methods: Retrospective analysis of a single institutional cohort of newly diagnosed estrogen receptor positive (ER+), HER2 negative (HER2−) unilateral invasive breast carcinomas was performed. Mitotic scores from the 3-part Nottingham combined histological grade were compared with clinical parameters. Mitoses were counted on Olympus BX50 microscopes and assigned scores of 1–3 based on observed mitoses. Results: A total of 1292 ER+, HER2− invasive breast carcinoma patients were identified, with a median follow-up time of 2.6 years (range 0–14 years). Higher mitotic score was significantly associated with younger age, larger tumor size, angiolymphatic invasion, node-positive disease, higher stage, and the use of hormonal and cytotoxic chemotherapy. Mitotic score was significant in modeling time to local/regional recurrence (p = 0.02), recurrence-free survival/RFS (p < 0.001), and overall survival/OS (p = 0.01) with higher mitotic scores associated with worse outcomes. Higher mitotic score correlated significantly with intermediate/high risk Oncotype Dx recurrence scores (p = 0.009). Conclusions: First-generation molecular profiling assays for estrogen receptor positive invasive breast carcinomas derive much of their predictive power from quantifying genes of proliferation into a single score. Sometimes overlooked in the profusion of molecular data, the time-tested, mitotic count in the Nottingham combined histological grade is a good single-parameter predictor of survival.

AB - Background: Newer multigene molecular profiling assays for breast carcinoma rely heavily on the quantification of genes of proliferation, whereas traditional histological grading reports the mitotic count. The mitotic activity of invasive breast carcinomas may be undervalued; therefore, an evaluation of the prognostic significance of mitotic score in predicting prognosis was performed. Methods: Retrospective analysis of a single institutional cohort of newly diagnosed estrogen receptor positive (ER+), HER2 negative (HER2−) unilateral invasive breast carcinomas was performed. Mitotic scores from the 3-part Nottingham combined histological grade were compared with clinical parameters. Mitoses were counted on Olympus BX50 microscopes and assigned scores of 1–3 based on observed mitoses. Results: A total of 1292 ER+, HER2− invasive breast carcinoma patients were identified, with a median follow-up time of 2.6 years (range 0–14 years). Higher mitotic score was significantly associated with younger age, larger tumor size, angiolymphatic invasion, node-positive disease, higher stage, and the use of hormonal and cytotoxic chemotherapy. Mitotic score was significant in modeling time to local/regional recurrence (p = 0.02), recurrence-free survival/RFS (p < 0.001), and overall survival/OS (p = 0.01) with higher mitotic scores associated with worse outcomes. Higher mitotic score correlated significantly with intermediate/high risk Oncotype Dx recurrence scores (p = 0.009). Conclusions: First-generation molecular profiling assays for estrogen receptor positive invasive breast carcinomas derive much of their predictive power from quantifying genes of proliferation into a single score. Sometimes overlooked in the profusion of molecular data, the time-tested, mitotic count in the Nottingham combined histological grade is a good single-parameter predictor of survival.

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JO - Annals of Surgical Oncology

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