Cyclin A is a prognostic indicator in early stage breast cancer with and without tamoxifen treatment

Abstract

Overexpression of G1-S regulators cyclin D1 or cyclin A is frequently observed in breast cancer and is also to result in ligandindependent activation of oestrogen receptor in vitro. This might therefore, provide a mechanism for failure of tamoxifen treatment. We examined by immunohistochemical staining the effect of deregulation of these, and other cell cycle regulators on tamoxifen treatment in a group of 394 patients with early stage breast cancer. In univariate analysis, expression of cyclin A, Neu, Ki-67 index, and lack of OR expression were significantly associated with worse prognosis. When adjusted by the clinical model (for lymph node status, age, performance status, T-classification, grade, prior surgery, oestrogen receptor status and tamoxifen use), only overexpression of cyclin A and Neu were significantly associated with worse prognosis with hazard ratios of, respectively, 1.709 (P=0.0195) and 1.884 (P=0.0151). Overexpression of cyclin A was found in 86 out of the 201 ORpositive cases treated with tamoxifen, and was the only independent marker associated with worse prognosis (hazard ratio 2.024, P=0.0462). In conclusion, cyclin A is an independent predictor of recurrence of early stage breast cancer and is as such a marker for response in patients treated with tamoxifen.

Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer

“…We found a strong correlation between cyclin A, mitotic count, tumour grade and Ki-67, which is in line with previous studies in breast cancer (Michalides et al, 2002;Michels et al, 2002). Cyclin A was the only marker that showed a statistically significant correlation to both TFR and OS; therefore, it seems to be the most useful marker of proliferation.…”

“…We used a cutoff value of 10.5% for the high and low cyclin A positivity groups. This is in line with three other studies, where median values varying between 8 and 11% have been used (Michalides et al, 2002;Michels et al, 2002;Kuhling et al, 2003;Rudolph et al, 2003). In the fourth study, four different categories were used for cyclin A positivity and the median category was between 15 and 30% (Bukholm et al, 2001).…”

“…An association between a high cyclin A expression and poor prognosis has previously been described in three studies, all executed after primary therapy for breast cancer (Bukholm et al, 2001;Michalides et al, 2002;Michels et al, 2002). A fourth study, however, in node-negative patients showed no correlation between cyclin A and prognosis Rudolph et al, 2003).…”

“…Cyclin A is essential in the S phase for DNA replication, it is also involved in G2 -M-phase transition (Zindy et al, 1992;Fan and Bertino, 1997), and is therefore one of the most useful markers signifying proliferating cells. Overexpression of cyclin A has been associated with worse prognosis for breast cancer in several studies (Bukholm et al, 2001;Michalides et al, 2002;Michels et al, 2002), but the results have not been consistent Rudolph et al, 2003). Since the lack of prognostic significance of cyclin A is mainly seen in patients with lymph node-negative breast cancer, it is possible that cyclin A plays a more important role in aggressive tumours and metastatic disease .…”

Patterns of cyclin A and B1 immunostaining in papillary thyroid carcinoma

“…In some of them, the expression of these proteins is considered to be a prognostic factor with proven clinical utility. Breast cancer seems to be the best example, as the intense expression of cyclin A in primary tumour cells is proven to be associated with an increased risk of relapse, and poor response to treatment with tamoxifen [15]. Baldini et al [16] suggest using the expression of cyclin A as an additional factor to proceed in some patients into a group with high risk of relapse.…”