Cyclin E confers a prognostic value in premenopausal breast cancer patients with tumours exhibiting an infiltrative growth pattern

Abstract

Cyclin E confers a prognostic value in premenopausal breast cancer patients with tumours exhibiting an infiltrative growth pattern.Berglund, Pontus; Stighall, Maria; Jirström, Karin; Rydén, Lisa; Fernö, Mårten; Nordenskjold, Bo; Landberg, Göran Link to publication Citation for published version (APA): Berglund, P., Stighall, M., Jirström, K., Rydén, L., Fernö, M., Nordenskjold, B., & Landberg, G. (2008). Cyclin E confers a prognostic value in premenopausal breast cancer patients with tumours exhibiting an infiltrative growth pattern. Journal of Clinical Pathology, 61, 184-191. DOI: 10.1136/jcp.2007 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal AbstractAim: This study investigates the prognostic value of cyclin E in relation to tumour growth pattern by analysing stage II primary breast cancers from premenopausal women not subjected to any further adjuvant treatment. In addition, the value of cyclin E as a predictor of tamoxifen response was analysed, by comparing untreated and treated patients with oestrogen receptor positive tumours. Methods: Breast cancer samples, assembled in tissue microarrays, were immunohistochemically stained for cyclin E and evaluated regarding the presence of nuclear staining. The overall growth characteristics of each tumour were assessed using whole tissue sections. Results: Tumours displaying a pushing margin phenotype were strongly associated with high cyclin E levels, lymph node negative disease, a high histological grade, ER negativity, and exhibited a better prognosis compared to tumours with an infiltrative growth pattern. In the total cohort of non-treated patients (N=187), cyclin E was not associated with recurrence free survival (RFS). However, when analysing the subgroup of tumours lacking a pushing growth pattern (N=141), cyclin E was significantly associated with RFS, independent of histological grade and node status. There was no significant difference in tamoxifen response with regard to different cyclin E levels. Conclusion:The prognostic value of cyclin E in premenopausal breast cancer is limited to patients with breast carcinomas exhibiting an exclusively infiltrative growth pattern. This limitation could be explained by the presence of a small but distinct subgroup of cyclin E-high breast cancers with a pushing margin phenotype and a more favourable outcome.

Cyclin E amplification/overexpression is a mechanism of trastuzumab resistance in HER2 + breast cancer patients

“…S1). Our cutoff values are similar to those previously adopted by other groups (30,31). The levels of cyclin E amplification and overexpression in breast tumors are lower than those described for HER2 (breast cancer) or MET (lung cancer) genes.…”

Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer

“…Most studies evaluating the association of cyclin E with histopathological markers have found correlation with aggressive features such as high grade and negative hormone receptor status [17,19,27], and some studies furthermore a correlation with high Ki67 expression, younger age at diagnosis and large tumour size [22,23,43]. The associations in our study were similar; high cyclin E correlated with high grade, high Ki67 expression and cyclin A expression, ER and PR negativity, large tumour size and younger age at disease onset.…”

Cyclin E1 and cyclin E2 in ER+ breast cancer: prospects as biomarkers and therapeutic targets

“…Printed in Great Britain Endocrine-Related Cancer poorer overall survival or disease-free survival in ER+ or ER-patients, using a nuclear staining cyclin E antibody (Porter et al 2006). Using a nuclear/cytoplasmic staining antibody (raised against the HE12 epitope), Cyclin E1 did not predict for poor outcome in a cohort of 51 ER+ patients (Agarwal et al 2009), nor did it predict tamoxifen response (Berglund et al 2008).…”