Combination of the proliferation marker cyclin A, histological grade, and estrogen receptor status in a new variable with high prognostic impact in breast cancer
2012 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 131, no 1, 33-40 p.Article in journal (Refereed) Published
Global gene expression profiles, consisting mainly of genes associated with proliferation, have been shown to subdivide histological grade 2 breast cancers into groups with different prognosis. We raised the question whether this subdivision could be done using a single proliferation marker, cyclin A. Furthermore, we combined cyclin A (CA), histological grade (G), and estrogen receptor-ER (E) into a new variable, CAGE. Our aim was to investigate not only the prognostic importance of cyclin A alone but also the value of the combination variable CAGE. In 219 premenopausal node-negative patients, cyclin A was assessed using immunohistochemistry on tissue microarrays. High cyclin A was defined as above the seventh decile of positive cells. Only 13% of the patients received adjuvant systemic therapy. Cox proportional hazards regression was used to model the impact of the factors on distant disease-free survival (DDFS). Cyclin A divided histological grade 2 tumors into two groups with significantly different DDFS (hazard ratio [HR]: 15, P < 0.001). When stratifying for ER status, cyclin A was a prognostic factor only in the ER positive subgroup. We found that CAGE was an independent prognostic factor for DDFS in multivariate analysis (HR: 4.1, P = 0.002), together with HER2. CAGE and HER2 identified 53% as low-risk patients with a 5-year DDFS of 95%. A new prognostic variable was created by combining cyclin A, histological grade, and ER (CAGE). CAGE together with HER2 identified a large low-risk group for whom adjuvant chemotherapy will have limited efficacy and may be avoided.
Place, publisher, year, edition, pages
2012. Vol. 131, no 1, 33-40 p.
Breast cancer, Prognosis, Histological grade, ER status, Proliferation, Cyclin A
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-168117DOI: 10.1007/s10549-011-1386-5ISI: 000298006300004OAI: oai:DiVA.org:uu-168117DiVA: diva2:491761