Cyclin A Is a Proliferative Marker with Good Prognostic Value in Node-Negative Breast Cancer

Abstract

Background: Proliferative markers are not recommended as prognostic factors for clinical use in breast cancer due to lack of standardization in methodology. However, proliferation is driving several gene expression signatures emphasizing the need for a reliable proliferative marker for clinical use. Studies suggest that cyclin A is a prognostic marker with satisfying reproducibility. We investigated cyclin A as a prognostic marker in node-negative breast cancer using previously defined cutoff values. Patients and Methods: In a case-control study, we defined 190 women who died from breast cancer as cases and 190 women alive at the time for the corresponding case's death as controls. Inclusion criteria were tumor size ≤50 mm, no lymph node metastases and no adjuvant chemotherapy. Tumor tissues were immunostained for cyclin A using commercially available antibodies.

Characterization of Tumor-Suppressive Function of SOX6 in Human Esophageal Squamous Cell Carcinoma

“…Expression of cyclin A has been strongly implicated in the control of cell proliferation and prognoses in human cancers (31)(32)(33). These findings are complementary to ours and suggest that downregulation of SOX6 would favor tumor progression.…”

High proliferation is associated with inferior outcome in male breast cancer patients

“…In addition, we could demonstrate that a high mitotic count was associated with an increased risk of breast cancer death, which further strengthens the conclusion that proliferation is of prognostic importance in male breast cancer. Ki-67 did not demonstrate any prognostic value in this cohort, but some studies in female breast cancer have shown that Ki-67 may be a weaker prognostic factor compared with cyclins A and B 12,15 and, hence, a larger cohort may be needed to be able to establish its prognostic impact in male breast cancer. Another issue with potential influence on our results is that a subset of our patients had received adjuvant and/or palliative chemotherapy treatment, which is known to diminish the prognostic impact of proliferation markers as proliferation is predictive of chemotherapy response.…”

“…10 Several studies in female breast cancer have demonstrated that overexpression of Ki-67, cyclin A and cyclin B is associated with inferior outcome. [11][12][13][14][15] Furthermore, results indicate that cyclins A and B could have an increased prognostic impact when compared with Ki-67. 12,15 The prognostic role of cyclin D1 in female breast cancer is unclear but some studies indicate that cyclin D1 may have a predictive role, with overexpression linked to tamoxifen resistance.…”

“…[11][12][13][14][15] Furthermore, results indicate that cyclins A and B could have an increased prognostic impact when compared with Ki-67. 12,15 The prognostic role of cyclin D1 in female breast cancer is unclear but some studies indicate that cyclin D1 may have a predictive role, with overexpression linked to tamoxifen resistance. 16,17 Cyclin D1 has been evaluated in a few smaller studies of male breast cancer and overexpression seems to be associated with a better outcome.…”

Combination of the proliferation marker cyclin A, histological grade, and estrogen receptor status in a new variable with high prognostic impact in breast cancer

“…Ki67 and mitotic activity have recently been included in the St Gallen guidelines [8], but the role of other proliferation markers, such as cyclin A, is still debated. Cyclin A has been associated with a worse outcome in breast cancer patients in some studies [1,[9][10][11] but others were unable to confirm this finding [2,12,13]. Reasons for discrepant results include small numbers of patients (only two studies included more than 200 patients) and differences in lymph node status, cut-points, end-points and follow-up times, and adjuvant systemic treatment.…”