DNA aneuploidy and breast cancer: a meta-analysis of 141,163 cases

Abstract

Background & AimsDNA ploidy, a DNA flow cytometry parameter, reflects tumor cell cycle. In breast cancer (BC), ploidy status characterizes genotypic stability and potential metastatic capacity. It is suggested that aneuploidy is an independent prognosticator for BC patients and could aid for individualized medicine. There are extensive studies concerning the prognostic significance of DNA aneuploidy, however, its clinical utility remains controversial. Herein we conducted a meta-analysis to determine the correlation between DNA ploidy status and BC characteristics and survival.MethodsThe electronic databases PubMed, EMBASE, and Web of Science were searched for relevant studies. The major investigated parameters were the BC aneuploidy rates in relation to tumor stage, size, lymph node metastasis, grading, estrogen receptor (ER) status, disease-free survival (DFS), and overall survival (OS). Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for DFS and OS were extracted from each study before meta-analyzed. Risk ratios (RRs) were computed using the fixed-effect or random-effects model according to data heterogeneity, and the Mantel-Haenszel or the inverse-variance method was adopted where appropriate to obtain pooled estimates using RevMan 5.3. The Egger's test was conducted with Stata 11.ResultsPooled analyses of data from 29 studies involving a total of 141,163 cases showed that BC patients with more advanced tumors (stage I vs. stages II-IV, RR=0.84; 95% CI, 0.74 to 0.96; P=0.01), larger tumors (≤2 cm vs. >2 cm: RR=0.82; 95% CI, 0.77 to 0.87; P<0.00001), lymph node metastasis (pN0 vs. pN1-3: RR=0.85; 95% CI, 0.83 to 0.87, P<0.00001), poorer tumor proliferation (G2 vs. G1: RR=1.58; 95% CI, 1.40 to 1.79; P<0.00001; G3 vs. G1: RR=2.17; 95% CI, 1.77 to 2.67; P<0.00001; G3 vs. G2: RR=1.41; 95% CI, 1.25 to 1.60; P<0.00001), and ER− status (ER− vs. ER+: RR=1.32; 95% CI, 1.22 to 1.43; P<0.00001) were significantly more frequently aneuploid. BC patients with diploid tumors had better clinical outcomes than those with aneuploid cancers. The pooled HR estimates were0.73 (P<0.0001) for DFS and 0.72 (P=0.0001) for OS, respectively.ConclusionThis meta-analysis implies that DNA aneuploidy is a significant predictor for BC progression and survival, and should be focused on in the therapeutic planning.

Comprehensive multi-omics analysis identifies an immune related predicting model in early stage breast cancer

“…DNA aneuploidy, as reported were related to cell proliferation and poor tumor differentiation [43]. In our study, the high risk group patients had higher Aneuploidy score, proliferation and worse prognosis which consistent with the results from a large meta-analysis that aneuploid breast cancer patients had poor DFS and OS [44]. The immunotherapy is an attempt in breast cancer patients when there is no other way out and the current immunotherapy response were relatively poor [3].…”

Altering microtubule dynamics is synergistically toxic with spindle assembly checkpoint inhibition

“…As three of four cancers are aneuploid (Weaver & Cleveland, 2006;Foijer et al, 2008;Duijf et al, 2013), CIN is considered an important contributor to tumorigenesis. Indeed, CIN has been associated with metastasis (Bloomfield & Duesberg, 2016;Xu et al, 2016), increased probability of drug resistance (Lee et al, 2011;Sansregret & Swanton, 2017) and generally, a lowered patient survival (Carter et al, 2006;Walther et al, 2008;McGranahan et al, 2012). While the frequent occurrence of CIN and resulting aneuploidy in cancer is generally attributed to the acquired ability of cancer cells to adapt their palette of oncogenic features as the tumor evolves, ongoing chromosome missegregation also has negative effects on cancer cells.…”

Does DNA ploidy and synthesis phase dynamic accentuate the predictive power of oestrogen and progesterone receptors in breast cancer progression and prognosis?

“…Notwithstanding the dissensions concerning the relationship of growth factor and steroid receptors to genomic instability, aneuploidy is considered to be significantly predictive of breast cancer prognosis (Xu et al 2016). Aneuploid tumours showed high SPF and this correlated with advanced stage disease (Pinto et al 2013, Bianco et al 2013.…”