Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Nov;178(2):451-458.
doi: 10.1007/s10549-019-05402-w. Epub 2019 Aug 17.

Ki-67 (30-9) scoring and differentiation of Luminal A- and Luminal B-like breast cancer subtypes

Giuseppe Viale  1   2 , Amy E Hanlon Newell  3 , Espen Walker  3 , Greg Harlow  4 , Isaac Bai  3 , Leila Russo  1 , Patrizia Dell'Orto  1 , Patrick Maisonneuve  5
Affiliations

Ki-67 (30-9) scoring and differentiation of Luminal A- and Luminal B-like breast cancer subtypes

Giuseppe Viale et al. Breast Cancer Res Treat. 2019 Nov.

Abstract

Introduction: Ki-67 labeling index assessed by immunohistochemical assays has been shown useful in assessing the risk of recurrence for estrogen receptor (ER)-positive HER2-negative breast cancers (BC) and distinguishing Luminal A-like from Luminal B-like tumors. We aimed to assess the performance of the Ventana CONFIRM anti-Ki-67 (30-9) Rabbit Monoclonal Primary Antibody.

Methods: We constructed a case-cohort design based on a random sample (n = 679) of all patients operated on for a first primary, non-metastatic, ER-positive, HER2-negative BC at the European Institute of Oncology (IEO) Milan, Italy during 1998-2002 and all additional patients (n = 303) operated during the same period, who developed an event (metastasis in distant organs or death due to BC as primary event) and were not included in the previous subset. Multivariable Cox proportional hazards regression with inverse subcohort sampling probability weighting was used to evaluate the risk of event according to Ki-67 (30-9) and derived intrinsic molecular subtype, using previously defined cutoff values, i.e., respectively 14% and 20%.

Results: Ki-67 was < 14% in 318 patients (32.4%), comprised between 14 and 19% in 245 patients (24.9%) and ≥ 20 in 419 patients (42.7%). At multivariable analysis, the risk of developing distant disease was 1.88 (95% CI 1.20-2.93; P = 0.006) for those with Ki-67 comprised between 14 and 19%, and 3.06 (95% CI 1.93-4.84; P < 0.0001) for those with Ki-67 ≥ 20% compared to those with Ki-67 < 14%. Patients with Luminal B-like BC had an approximate twofold risk of developing distant disease (HR = 1.91; 95% CI 1.35-2.71; P = 0.0003) than patients with Luminal A-like BC defined using Ki-67 (30-9).

Conclusions: Ki-67 evaluation using the 30-9 rabbit monoclonal primary antibody was able to stratify patients with ER-positive HER2-negative BC into prognostically distinct groups. Ki-67 assessment, with strict adherence to the international recommendations, should be included among the clinically useful biological parameters for the best treatment of patients with BC.

Keywords: Biomarker; Differentiation; Ki-67; Luminal A; Luminal B.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Cumulative incidence of events in the subcohort (N = 679) and corresponding Hazards Ratios in the case–cohort (N = 982) according to Ki-67 (30-9) and derived intrinsic molecular subtype
Fig. 2
Fig. 2
Event rate* in the subcohort and Hazard Ratio** for distant disease-free survival according to Ki-67 (HR set to 1.00 for Ki-67 = 14%) in the case–cohort
See this image and copyright information in PMC

References

    1. Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. J Cell Physiol. 2000;182:311–322. doi: 10.1002/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9. - DOI - PubMed
    1. Arima N, Nishimura R, Osako T, Okumura Y, Nakano M, Fujisue M, Nishiyama Y, Toyozumi Y. Ki-67 index value and progesterone receptor status can predict prognosis and suitable treatment in node-negative breast cancer patients with estrogen receptor-positive and HER2-negative tumors. Oncol Lett. 2019;17:616–622. - PMC - PubMed
    1. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, Senn HJ, Panel members Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol. 2013;24:2206–2223. doi: 10.1093/annonc/mdt303. - DOI - PMC - PubMed
    1. Duffy MJ, Harbeck N, Nap M, Molina R, Nicolini A, Senkus E, Cardoso F. Clinical use of biomarkers in breast cancer: updated guidelines from the European group on tumor markers (EGTM) Eur J Cancer. 2017;75:284–298. doi: 10.1016/j.ejca.2017.01.017. - DOI - PubMed
    1. Petrelli F, Viale G, Cabiddu M, Barni S. Prognostic value of different cut-off levels of Ki-67 in breast cancer: a systematic review and meta-analysis of 64,196 patients. Breast Cancer Res Treat. 2015;153:477e91. doi: 10.1007/s10549-015-3559-0. - DOI - PubMed

LinkOut - more resources