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Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy

Ács, Balåzs

Zambo, Veronika

VĂ­zkeleti, Laura

SzĂĄsz, Attila Marcell

Madaras, Lilla

SzentmĂĄrtoni, GyĂśngyvĂŠr

Tőkés, Tímea

Molnår, BÊla Ákos

MolnĂĄr, IstvĂĄn Arthur

VĂĄri-Kakas, StefĂĄn

Kulka, Janina

Tőkés, Anna-Mária

BioMed Central

2017-02-21

R1 Medicine (General) / orvostudomĂĄny ĂĄltalĂĄban

RB Pathology / patolĂłgia, kĂłrtan

Studies have partly demonstrated the clinical validity of Ki-67 as a predictive marker in the neoadjuvant setting, but the question of the best cut-off points as well as the importance of this marker as a prognostic factor in partial responder/non-responder groups remains uncertain.
METHODS:
One hundred twenty patients diagnosed with invasive breast cancer and treated with neoadjuvant chemotherapy (NAC) between 2002 and 2013 were retrospectively recruited to this study. The optimal cut-off value for Ki-67 labeling index (LI) to discriminate response to treatment was assessed by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier curve estimation, log-rank test and cox regression analysis were carried out to reveal the association between Ki-67 categories and survival (DMFS = Distant metastases-free survival, OS = Overall survival).
RESULTS:
Twenty three out of 120 patients (19.2%) achieved pathologic complete remission (pCR), whereas partial remission (pPR) and no response (pNR) to neoadjuvant chemotherapy (NAC) was detected in 60.8% and 20.0%, respectively. The distribution of subtypes showed a significant difference in pathological response groups (p < 0.001). Most of the TNBC cases were represented in pCR group. The most relevant cut-off value for the Ki-67 distinguishing pCR from pNR cases was 20% (p = 0.002). No significant threshold for Ki-67 was found regarding DMFS (p = 0.208). Considering OS, the optimal cut-off point occurred at 15% Ki-67 (p = 0.006). The pPR group represented a significant Ki-67 threshold at 30% regarding OS (p = 0.001). Ki-67 and pPR subgroups were not significantly associated (p = 0.653). For prognosis prediction, Ki-67 at 30% cut-off value (p = 0.040) furthermore subtype (p = 0.037) as well as pathological response (p = 0.044) were suitable to separate patients into good and unfavorable prognosis cohorts regarding OS. However, in multivariate analyses, only Ki-67 at 30% threshold (p = 0.029), and subtype (p = 0.008) were independently linked to OS.
CONCLUSIONS:
NAC is more efficient in tumors with at least 20% Ki-67 LI. Both Ki-67 LI and subtype showed a significant association with pathological response. Ki-67 LI represented independent prognostic potential to OS in our neoadjuvant patient cohort, while pathological response did not. Additionally, our data also suggest that if a tumor is non-responder to NAC, increased Ki-67 is a poor prognostic marker.

angol

Article

PeerReviewed

info:eu-repo/semantics/article

text

http://real.mtak.hu/64122/1/Ki-67%20as%20a%20controversial%...

Ács, Balázs and Zambo, Veronika and Vízkeleti, Laura and Szász, Attila Marcell and Madaras, Lilla and Szentmártoni, Gyöngyvér and Tőkés, Tímea and Molnár, Béla Ákos and Molnár, István Arthur and Vári-Kakas, Stefán and Kulka, Janina and Tőkés, Anna-Mária (2017) Ki-67 as a controversial predictive and prognostic marker in breast cancer patients treated with neoadjuvant chemotherapy. Diagnostic pathology, 12 (20). pp. 1-12. ISSN 1746-1596, ESSN: 1746-1596

http://real.mtak.hu/64122/

https://doi.org/10.1186/s13000-017-0608-5