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Annals of Oncology Advance Access originally published online on November 27, 2007
Annals of Oncology 2008 19(4):649-654; doi:10.1093/annonc/mdm535
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© The Author 2007. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

breast cancer

Proliferation accurately identifies the high-risk patients among small, low-grade, lymph node-negative invasive breast cancers

J. P. A. Baak1,3,4,*, P. J. van Diest1,{dagger}, E. A. M. Janssen3, E. Gudlaugsson3, F. J. Voorhorst1,2, E. van der Wall5,{dagger}, J. B. Vermorken6 and other collaborators of the Multicenter Morphometric Mammary Carcinoma Project (MMMCP)

1 Departments of Pathology
2 Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
3 Department of Pathology, Stavanger University Hospital, Stavanger
4 The Gade Institute, University of Bergen, Bergen, Norway
5 Department of Medical Oncology, VU Medical Center, Amsterdam, The Netherlands
6 Department of Medical Oncology, University Hospital, Antwerpen, Belgium

* Correspondence to: (at his current address) Prof. J. P. A. Baak, Department of Pathology, Stavanger University Hospital, PO Box 8100, 4068 Stavanger, Norway. Tel: +47-51-519534; Fax: +47-51-519920; E-mail: baja{at}sus.no

Background: The proliferation factor mitotic activity index (MAI) is the strongest prognosticator in lymph node-negative invasive breast cancer patients under age 71. The question remains, whether this also holds for ‘favourable prognosis’ subgroups.

Patients and methods: The study was a multicentre prospective analysis of the MAI for recurrence-free survival and overall cancer-related survival of grade, MAI, and other prognosticators in 853 long-term follow-up, T1–3N0M0 breast cancer patients under 71 years.

Results: In all tumours together (N = 853), in grade 3 (n = 269), in tumours <1 cm all grades (n = 84), 1–2 cm, grades 1 + 2 (n = 300), and 2–3 cm, grades 1 + 2 (n = 124), the MAI is prognostically superior. Other features [grade, estrogen receptor (ER), diameter, and age] did not enhance its prognostic value except in grades 1 + 2 tumours 2–3 cm diameter with MAI <10, where ER has an additional prognostic value.

Conclusions: In women <71 years with T1–3N0M0 small or low-grade invasive breast cancer usually not receiving systemic treatment, MAI ≥10 accurately identifies those at high risk. These high-risk patients should be considered for adjuvant systemic therapy.

Key words: breast cancer, mitotic index, prognosis, proliferation, small tumours, well-differentiated cancers

{dagger} Present address: Department of Pathology, University Medical Center, Utrecht, The Netherlands

Received for publication July 3, 2007. Accepted for publication October 22, 2007.


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