Success predictors of adjuvant chemotherapy in node-negative breast cancer patients under 55 years

Article type: Research Article

Authors: Janssen, Emiel A.M. | van Diest, Paul J. | Søiland, Håvard | Gudlaugson, Einar | Nysted, Arne | Voorhorst, Feja J. | Vermorken, Jan B. | Søreide, Jon-Arne^; | Baak, Jan P.A.^{; ; ;}

Affiliations: Department of Pathology, Stavanger University Hospital, Stavanger, Norway | Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands | Department of Surgery, Stavanger University Hospital, Stavanger, Norway | Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands | Department of Medical Oncology, University Hospital, Antwerpen, Belgium | Institute of Surgical Sciences, University of Bergen, Norway | Department of Pathology, The Gade Institute, University of Bergen, Norway

Note: [] Corresponding author: Prof. dr. J.P.A. Baak, Department of Pathology, Stavanger University Hospital, Box 8100, 4068 Stavanger, Norway. Tel.: +47 51 519534; Fax: +47 51 519920; E-mail: [email protected].

Abstract: Background: Adjuvant systemic chemotherapy (ASCT) in lymph node-negative breast (LN−) cancers improves survival. The majority of (LN−) patients receive ASCT when the St. Gallen criteria or its modifications are used, as accurate identifiers which patients benefit from ASCT are lacking. This may imply over-treatment in many patients. Aim: To evaluate which patients or primary tumor factors predict ASCT success. Material and method: Retrospective analysis by single and multivariate survival analysis of clinical and tumor characteristics in (LN−) breast cancers <55 years, related to ASCT (n=125) or-not (n=516). Results: The two patient groups did not differ in age, tumor diameter, grade, type, number of mitoses and other factors. Fourteen-year survival for the ASCT and non-ASCT patients was 83% and 74% (Hazard Ratio = HR = 0.33; p<0.0001, 9% absolute = 12% relative difference). Subgroup analysis showed that the recurrence-free survival = RFS of ASCT treated vs. non-treated patients differed in patients with grade 1 cancers (p=0.008), grade 2 cancers (p=0.004), grades 3 (p=0.02), tumors under and ≥2 cm (p=0.001 and 0.0002), oestrogen receptor-positive or -negative tumors (p=0.003,0.04), MAI < 10 and ≥10 (p=0.005,0.003) and fibrotic focus absent (p=0.002). With multivariate analysis the most important predictor of ASCT effect was the MAI. In patients with slowly proliferating tumors (MAI <3) no advantage was found between patients treated-or-not with adjuvant chemotherapy (RFS = 92% and 91%, p=0.13, p=0.63 for overall survival), contrasting those with MAI ≥3 (p=0.0001; HR = 0.32, 95% CI 0.18–0.58). Conclusion: MAI is the strongest predictor of adjuvant systemic chemotherapy success. In patients with MAI < 3 (31% of all patients), ASCT does not improve survival.

Keywords: Breast cancer, proliferation, Mitotic Activity Index, prognosis, therapy

Journal: Analytical Cellular Pathology, vol. 28, no. 5-6, pp. 295-303, 2006