Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years

Jan P A Baak, Paul J. van Diest, Feja J. Voorhorst, Elsken van der Wall, Louk V A M Beex, Jan B. Vermorken, Emiel A M Janssen

Research output: Contribution to journalArticle

Abstract

Purpose: To validate the independent strong prognostic value of mitotic activity index (MAI) in lymph node (LN)-negative invasive breast cancer patients younger than 55 years in a nationwide multicenter prospective study. Patients and Methods: Analysis of routinely assessed MAI and other prognosticators in 516 patients (median follow-up, 118 months; range, 8 to 185 months), without systemic adjuvant therapy or previous malignancies. Results: Distant metastases occurred in 127 patients (24.6%); 90 (17.4%) died as a result of metastases. MAI (<10, ≥ 10) showed strong association with recurrence (hazard ratio [HR], 3.12; 95% CI, 2.17 to 4.50; P ≤ .0001) and mortality (HR, 4.42; 95% CI, 2.79 to 7.01; P <.0001). The absolute difference in 10-year Kaplan-Meier estimates of time to distant recurrence as well as survival was 22% between MAI less than 10 versus ≥ 10. This effect was independent of age, estrogen receptor (ER) status, and tumor diameter (which were significant prognosticators). In multivariate analysis with regard to patient age, tumor diameter, grade, ER status, and the St Gallen criterion, MAI proved to be an independent and the strongest prognosticator. Tubular formation (TF) and nuclear atypia (NA), as constituents of (expert revised) grade, had no (for TF) or limited (for NA, P = .048) additional prognostic value to the MAI. In the group with MAI less than 10, MAI less than 3 versus more than 3 had additional value but the classical threshold of 0 to 5 v 6 to 10 did not. With this additional subdivision of MAl as less than 3, 3 to 9, and more than 9, NA lost its additive prognostic value. Conclusion: The MAI is the strongest, most widely available, easily assessable, inexpensive, well-reproducible prognosticator and is well suited to routinely differentiate between high- and low-risk LN-negative breast cancer patients younger than 55 years.

Original languageEnglish (US)
Pages (from-to)5993-6001
Number of pages9
JournalJournal of Clinical Oncology
Volume23
Issue number25
DOIs
StatePublished - 2005
Externally publishedYes

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Mitotic Index
Lymph Nodes
Breast Neoplasms
Estrogen Receptors
Neoplasm Metastasis
Recurrence
Neoplasms
Kaplan-Meier Estimate
Multicenter Studies
Multivariate Analysis
Prospective Studies
Survival
Mortality

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Baak, J. P. A., van Diest, P. J., Voorhorst, F. J., van der Wall, E., Beex, L. V. A. M., Vermorken, J. B., & Janssen, E. A. M. (2005). Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years. Journal of Clinical Oncology, 23(25), 5993-6001. https://doi.org/10.1200/JCO.2005.05.511

Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years. / Baak, Jan P A; van Diest, Paul J.; Voorhorst, Feja J.; van der Wall, Elsken; Beex, Louk V A M; Vermorken, Jan B.; Janssen, Emiel A M.

In: Journal of Clinical Oncology, Vol. 23, No. 25, 2005, p. 5993-6001.

Research output: Contribution to journalArticle

Baak, Jan P A ; van Diest, Paul J. ; Voorhorst, Feja J. ; van der Wall, Elsken ; Beex, Louk V A M ; Vermorken, Jan B. ; Janssen, Emiel A M. / Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years. In: Journal of Clinical Oncology. 2005 ; Vol. 23, No. 25. pp. 5993-6001.
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abstract = "Purpose: To validate the independent strong prognostic value of mitotic activity index (MAI) in lymph node (LN)-negative invasive breast cancer patients younger than 55 years in a nationwide multicenter prospective study. Patients and Methods: Analysis of routinely assessed MAI and other prognosticators in 516 patients (median follow-up, 118 months; range, 8 to 185 months), without systemic adjuvant therapy or previous malignancies. Results: Distant metastases occurred in 127 patients (24.6{\%}); 90 (17.4{\%}) died as a result of metastases. MAI (<10, ≥ 10) showed strong association with recurrence (hazard ratio [HR], 3.12; 95{\%} CI, 2.17 to 4.50; P ≤ .0001) and mortality (HR, 4.42; 95{\%} CI, 2.79 to 7.01; P <.0001). The absolute difference in 10-year Kaplan-Meier estimates of time to distant recurrence as well as survival was 22{\%} between MAI less than 10 versus ≥ 10. This effect was independent of age, estrogen receptor (ER) status, and tumor diameter (which were significant prognosticators). In multivariate analysis with regard to patient age, tumor diameter, grade, ER status, and the St Gallen criterion, MAI proved to be an independent and the strongest prognosticator. Tubular formation (TF) and nuclear atypia (NA), as constituents of (expert revised) grade, had no (for TF) or limited (for NA, P = .048) additional prognostic value to the MAI. In the group with MAI less than 10, MAI less than 3 versus more than 3 had additional value but the classical threshold of 0 to 5 v 6 to 10 did not. With this additional subdivision of MAl as less than 3, 3 to 9, and more than 9, NA lost its additive prognostic value. Conclusion: The MAI is the strongest, most widely available, easily assessable, inexpensive, well-reproducible prognosticator and is well suited to routinely differentiate between high- and low-risk LN-negative breast cancer patients younger than 55 years.",
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T1 - Prospective multicenter validation of the independent prognostic value of the mitotic activity index in lymph node-negative breast cancer patients younger than 55 years

AU - Baak, Jan P A

AU - van Diest, Paul J.

AU - Voorhorst, Feja J.

AU - van der Wall, Elsken

AU - Beex, Louk V A M

AU - Vermorken, Jan B.

AU - Janssen, Emiel A M

PY - 2005

Y1 - 2005

N2 - Purpose: To validate the independent strong prognostic value of mitotic activity index (MAI) in lymph node (LN)-negative invasive breast cancer patients younger than 55 years in a nationwide multicenter prospective study. Patients and Methods: Analysis of routinely assessed MAI and other prognosticators in 516 patients (median follow-up, 118 months; range, 8 to 185 months), without systemic adjuvant therapy or previous malignancies. Results: Distant metastases occurred in 127 patients (24.6%); 90 (17.4%) died as a result of metastases. MAI (<10, ≥ 10) showed strong association with recurrence (hazard ratio [HR], 3.12; 95% CI, 2.17 to 4.50; P ≤ .0001) and mortality (HR, 4.42; 95% CI, 2.79 to 7.01; P <.0001). The absolute difference in 10-year Kaplan-Meier estimates of time to distant recurrence as well as survival was 22% between MAI less than 10 versus ≥ 10. This effect was independent of age, estrogen receptor (ER) status, and tumor diameter (which were significant prognosticators). In multivariate analysis with regard to patient age, tumor diameter, grade, ER status, and the St Gallen criterion, MAI proved to be an independent and the strongest prognosticator. Tubular formation (TF) and nuclear atypia (NA), as constituents of (expert revised) grade, had no (for TF) or limited (for NA, P = .048) additional prognostic value to the MAI. In the group with MAI less than 10, MAI less than 3 versus more than 3 had additional value but the classical threshold of 0 to 5 v 6 to 10 did not. With this additional subdivision of MAl as less than 3, 3 to 9, and more than 9, NA lost its additive prognostic value. Conclusion: The MAI is the strongest, most widely available, easily assessable, inexpensive, well-reproducible prognosticator and is well suited to routinely differentiate between high- and low-risk LN-negative breast cancer patients younger than 55 years.

AB - Purpose: To validate the independent strong prognostic value of mitotic activity index (MAI) in lymph node (LN)-negative invasive breast cancer patients younger than 55 years in a nationwide multicenter prospective study. Patients and Methods: Analysis of routinely assessed MAI and other prognosticators in 516 patients (median follow-up, 118 months; range, 8 to 185 months), without systemic adjuvant therapy or previous malignancies. Results: Distant metastases occurred in 127 patients (24.6%); 90 (17.4%) died as a result of metastases. MAI (<10, ≥ 10) showed strong association with recurrence (hazard ratio [HR], 3.12; 95% CI, 2.17 to 4.50; P ≤ .0001) and mortality (HR, 4.42; 95% CI, 2.79 to 7.01; P <.0001). The absolute difference in 10-year Kaplan-Meier estimates of time to distant recurrence as well as survival was 22% between MAI less than 10 versus ≥ 10. This effect was independent of age, estrogen receptor (ER) status, and tumor diameter (which were significant prognosticators). In multivariate analysis with regard to patient age, tumor diameter, grade, ER status, and the St Gallen criterion, MAI proved to be an independent and the strongest prognosticator. Tubular formation (TF) and nuclear atypia (NA), as constituents of (expert revised) grade, had no (for TF) or limited (for NA, P = .048) additional prognostic value to the MAI. In the group with MAI less than 10, MAI less than 3 versus more than 3 had additional value but the classical threshold of 0 to 5 v 6 to 10 did not. With this additional subdivision of MAl as less than 3, 3 to 9, and more than 9, NA lost its additive prognostic value. Conclusion: The MAI is the strongest, most widely available, easily assessable, inexpensive, well-reproducible prognosticator and is well suited to routinely differentiate between high- and low-risk LN-negative breast cancer patients younger than 55 years.

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