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

Arima,Nobuyuki; Nishimura,Reiki; Osako,Tomofumi; Okumura,Yasuhiro; Nakano,Masahiro; Fujisue,Mamiko; Nishiyama,Yasuyuki; Toyozumi,Yasuo

doi:10.3892/ol.2018.9633

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

Authors:
- Nobuyuki Arima
- Reiki Nishimura
- Tomofumi Osako
- Yasuhiro Okumura
- Masahiro Nakano
- Mamiko Fujisue
- Yasuyuki Nishiyama
- Yasuo Toyozumi
View Affiliations

Affiliations: Department of Pathology, Kumamoto Shinto General Hospital, Kumamoto 862‑8655, Japan, Department of Breast Oncology, Kumamoto Shinto General Hospital, Kumamoto 862‑8655, Japan, Department of Breast Surgery, Fukuoka Wajiro Hospital, Fukuoka 811‑0213, Japan, Department of Pathology, Kumamoto City Hospital, Kumamoto 862‑8505, Japan
Published online on: October 29, 2018 https://doi.org/10.3892/ol.2018.9633
Pages: 616-622

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Gene profiling has identified at least 4 breast cancer subtypes, including Luminal A, Luminal B, HER2‑enriched and basal‑like, and immunohistochemistry is used as a guide to determine these subtypes. In the present study, patients with ER‑positive, HER2‑negative and negative nodes were classified into 4 groups according to the PgR and the Ki‑67 status and were retrospectively examined. The analysis was based on the clinicopathological findings, and includes the recurrence score (RS) and disease‑free survival (DFS) rates. Patients with invasive breast cancer (n=1866) were classified as LA (high PgR/low Ki‑67), LB‑1 (high PgR/high Ki‑67), LB‑2 (low PgR/high Ki‑67), and LB‑3 (low PgR/low Ki‑67). In addition, 41 of the cases underwent a 21‑gene expression assay. The data revealed that T1 tumors were more prevalent in the LA group and rare in the LB‑2 group. Furthermore, nuclear grade 3 and p53 overexpression was revealed to be significantly correlated with LB‑2. In terms of prognosis, LA had a significantly more favorable DFS; however, no differences were observed in the LB‑3 group. LB‑2 had a significantly worse DFS in all cases, and in the cases administered with endocrine therapy alone. Chemotherapy in combination with endocrine therapy was administered to cases with a higher risk of recurrence. In the LB‑2 group, there was no difference in the DFS rates between the cases with endocrine therapy and chemo‑endocrine therapy. These findings suggest that chemotherapy could improve the DFS in the LB‑2 group. In addition, the majority of cases with LA, LB‑3 and LB‑1 had a RS of ≤25 and the majority of the LB‑2 cases had a RS of >25. The patients with LA and LB‑3 had a favorable DFS even in the group that received endocrine therapy alone. LB‑2 was significantly correlated with a higher degree of malignancy and benefited from chemotherapy. These data suggest that the PgR and the Ki‑67 status are effective in predicting prognosis, and for deciding on the most effective treatment strategy in patients with breast cancer.

View Figures

View References

1	Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B and 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. 24:2206–2223. 2013. View Article : Google Scholar : PubMed/NCBI
2	Arima N, Nishimura R, Osako T, Nishiyama Y, Fujisue M, Okumura Y, Nakano M, Tashima R and Toyozumi Y: A Comparison of the hot Spot and the average cancer cell counting methods and the optimal cutoff point of the Ki-67 index for luminal type breast cancer. Oncology. 90:43–50. 2016. View Article : Google Scholar : PubMed/NCBI
3	Tashima R, Nishimura R, Osako T, Nishiyama Y, Okumura Y, Nakano M, Fujisue M, Toyozumi Y and Arima N: Evaluation of an optimal cut-off point for the Ki-67 index as a prognostic factor in primary breast cancer: A retrospective study. PLoS One. 10:e01195652015. View Article : Google Scholar : PubMed/NCBI
4	Bustreo S, Osella-Abate S, Cassoni P, Donadio M, Airoldi M, Pedani F, Papotti M, Sapino A and Castellano I: Optimal Ki67 cut-off for luminal breast cancer prognostic evaluation: A large case series study with a long-term follow-up. Breast Cancer Res Treat. 157:363–371. 2016. View Article : Google Scholar : PubMed/NCBI
5	Prat A, Cheang MC, Martín M, Parker JS, Carrasco E, Caballero R, Tyldesley S, Gelmon K, Bemard PS, Nielsen TO and Perou CM: Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer. J Clin Oncol. 31:203–209. 2013. View Article : Google Scholar : PubMed/NCBI
6	Tashima R, Nishimura Y, Arima N, Fujisue M, Nakano M, Okumura Y, Osako T and Toyozumi Y: P260 Evaluation of PgR expression as a prognostic factor in luminal HER2-negative breast cancer. The Breast. 24 Suppl 1:S1162015. View Article : Google Scholar
7	O'Brien KM, Cole SR, Tse CK, Perou CM, Carey LA, Foulkes WD, Dressler LG, Geradts J and Millikan RC: Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina breast cancer study. Clin Cancer Res. 16:6100–6110. 2010. View Article : Google Scholar : PubMed/NCBI
8	Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, Deng S, Johnsen H, Pesich R, Geisler S, et al: Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 100:8418–8423. 2003. View Article : Google Scholar : PubMed/NCBI
9	Brenton JD, Carey LA, Ahmed AA and Caldas C: Molecular classification and molecular forecasting of breast cancer: Ready for clinical application? J Clin Oncol. 23:7350–7360. 2005. View Article : Google Scholar : PubMed/NCBI
10	Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, Baehner FL, Walker MG, Watson D, Park T, et al: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 351:2817–2826. 2004. View Article : Google Scholar : PubMed/NCBI
11	Gianni L, Zambetti M, Clark K, Baker J, Cronin M, Wu J, Mariani G, Rodriguez J, Carcangiu M, Watson D, et al: Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol. 23:7265–7277. 2005. View Article : Google Scholar : PubMed/NCBI
12	Barcenas CH, Raghavendra A, Sinha AK, Syed MP, Hsu L, Patangan MG Jr, Chavez-MacGregor M, Shen Y, Hortobagyi GH, Valero V, et al: Outcomes in patients with early-stage breast cancer who underwent a 21-gene expression assay. Cancer. 123:2422–2431. 2017. View Article : Google Scholar : PubMed/NCBI
13	Kai K, Nishimura R, Arima N, Miyayama H and Iwase H: p53 expression status is a significant molecular marker in predicting the time to endocrine therapy failure in recurrent breast cancer: A cohort study. Int J Clin Oncol. 11:426–433. 2006. View Article : Google Scholar : PubMed/NCBI
14	Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO and Kennecke H: Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 28:1684–1691. 2010. View Article : Google Scholar : PubMed/NCBI
15	Arvold ND, Taghian AG, Niemierko A, Abi Raad RF, Sreedhara M, Nguyen PL, Bellon JR, Wong JS, Smith BL and Harris JR: Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. J Clin Oncol. 29:3885–3891. 2011. View Article : Google Scholar : PubMed/NCBI
16	Metzger-Filho O, Sun Z, Viale G, Price KN, Crivellari D, Snyder RD, Gelber RD, Castiglione-Gertsch M, Coates AS, Goldhirsch A and Cardoso F: Patterns of recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: Results from international breast cancer study group trials VIII and IX. J Clin Oncol. 31:3083–3090. 2013. View Article : Google Scholar : PubMed/NCBI
17	McGuire A, Lowery AJ, Kell MR, Kerin MJ and Sweeney KJ: Locoregional recurrence following breast cancer surgery in the trastuzumab era: A systematic review by subtype. Ann Surg Oncol. 24:3124–3132. 2017. View Article : Google Scholar : PubMed/NCBI
18	Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF and Bast RC Jr; American Society of Clinical Oncology, . American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 25:5287–5312. 2007. View Article : Google Scholar : PubMed/NCBI
19	National Comprehensive Cancer Network (NCCN) guidelines, Breast Cancer Version 2.2011. http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
20	Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, Cronin M, Baehner FL, Watson D, Bryant J, et al: Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 24:3726–3734. 2006. View Article : Google Scholar : PubMed/NCBI
21	Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, Ravdin P, Bugarini R, Baehner FL, Davidson NE, et al: Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: A retrospective analysis of a randomised trial. Lancet Oncol. 11:55–65. 2010. View Article : Google Scholar : PubMed/NCBI
22	Nishimura R, Osako T, Okumura Y, Hayashi M, Toyozumi Y and Arima N: Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer. Exp Ther Med. 1:747–754. 2010. View Article : Google Scholar : PubMed/NCBI
23	Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M and Ortmann O: Ki-67 is a prognostic parameter in breast cancer patients: Results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat. 139:539–552. 2013. View Article : Google Scholar : PubMed/NCBI
24	Fasching PA, Heusinger K, Haeberle L, Niklos M, Hein A, Bayer CM, Rauh C, Schulz-Wendtland R, Bani MR, Schrauder M, et al: Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer. 11:4862011. View Article : Google Scholar : PubMed/NCBI
25	Bae SY, Kim S, Lee JH, Lee HC, Lee SK, Kil WH, Kim SW, Lee JE and Nam SJ: Poor prognosis of single hormone receptor-positive breast cancer: Similar outcome as triple-negative breast cancer. BMC Cancer. 15:1382015. View Article : Google Scholar : PubMed/NCBI
26	Viale G, Regan MM, Maiorano E, Mastropasqua MG, Golouh R, Penin T, Brown RW, Kovács A, Pillay K, Ohlschlegel C, et al: Chemoendocrine compared with endocrine adjuvant therapies for node-negative breast cancer: Predictive value of centrally reviewed expression of estrogen and progesterone receptors-An International Breast Cancer Study Group. J Clin Oncol. 26:1404–1410. 2008. View Article : Google Scholar : PubMed/NCBI