Skip to main content

Advertisement

SpringerLink
Log in

Prognostic Factors Affecting Disease-Free Survival in Triple-Negative Breast Cancer and Impact of Ki-67

  • Original Article
  • Published:
Indian Journal of Surgery Aims and scope Submit manuscript

Abstract

We aimed to investigate the prognostic factors affecting disease-free survival in patients with triple-negative breast cancer (TNBC), especially to reveal the prognostic value of Ki-67 and which cutoff value should be used. The medical records of the 180 patients who underwent surgery for invasive breast cancer were retrospectively reviewed. Potential prognostic factors that could affect the disease-free survival (DFS) in TNBC such as age (< 40, ≥ 40), grade (1, 2, 3), lymphovascular invasion (LVI) (positive, negative), perineural invasion (PNI) (positive, negative), histopathological type of tumor (invasive ductal, invasive lobular), axillary lymph node metastasis (positive, negative), number of axillary-positive lymph nodes (1–3, ≥ 4), pathological tumor size (< 2 cm, ≥ 2 cm), and Ki-67 cutoff (14%, 25%) were investigated. Univariate analysis for DFS was made by Kaplan–Meier method and comparisons were performed using log-rank test. Independent risk factors for DFS were determined by Cox proportional hazard method. The median follow-up interval was 69 months (range, 2–172). The 5-year DFS rate was 74.1%. Pathological tumor size ≥ 2 cm (HR: 7.82, 95% CI 0.14–0.34, P = 0.001), presence of axillary lymph node metastasis (HR: 8.93, 95% CI 0.15–0.66, P = 0.003), and Ki-67 cutoff of 25% (HR: 1.73, 95% CI 0.21–0.96, P = 0.040) were found to be independent prognostic factors that negatively affect DFS in TNBC. Tumor size ≥ 2 cm, axillary lymph node involvement, and Ki-67 ≥ 25% are prognostic factors that negatively affect DFS in TNBC. Post-treatment control examinations and tests should be performed at shorter intervals in TNBC patients with these characteristics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, Senn HJ, Panel members (2013) 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(9):2206–23. https://doi.org/10.1093/annonc/mdt303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Morris GJ, Naidu S, Topham AK, Guiles F, Xu Y, McCue P, Schwartz GF, Park PK, Rosenberg AL, Brill K, Mitchell EP (2007) Differences in breast carcinoma characteristics in newly diagnosed African-American and Caucasian patients: a single-institution compilation compared with the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. Cancer 110(4):876–884

    Article  PubMed  Google Scholar 

  3. Yin L, Duan JJ, Bian XW, Yu SC (2020) Triple-negative breast cancer molecular subtyping and treatment progress. Breast Cancer Res 22(1):61. https://doi.org/10.1186/s13058-020-01296-5

    Article  PubMed  PubMed Central  Google Scholar 

  4. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, Lickley LA, Rawlinson E, Sun P, Narod SA (2007) Triple-negative breast cancer: clinical features and patterns of recurrence. Clin CancerRes 13(15 Pt 1):4429–4434. https://doi.org/10.1158/1078-0432

    Article  Google Scholar 

  5. Daidone MG, Silvestrini R (2001) Prognostic and predictive role of proliferation indices in adjuvant therapy of breast cancer. J NatlCancerInstMonogr 30:27–35. https://doi.org/10.1093/oxfordjournals.jncimonographs.a003457

    Article  Google Scholar 

  6. Zhu X, Chen L, Huang B, Wang Y, Ji L, Wu J, Di G, Liu G, Yu K, Shao Z, Wang Z (2020) The prognostic and predictive potential of Ki-67 in triple-negative breast cancer. SciRep 10(1):225. https://doi.org/10.1038/s41598-019-57094-3

    Article  CAS  Google Scholar 

  7. Brown JR, DiGiovanna MP, Killelea B, Lannin DR, Rimm DL (2014) Quantitative assessment Ki-67 score for prediction of response to neoadjuvant chemotherapy in breast cancer. LabInvest 94(1):98–106. https://doi.org/10.1038/labinvest.2013.128

    Article  CAS  Google Scholar 

  8. Matsubara N, Mukai H, Masumoto M, Sasaki M, Naito Y, Fujii S, Wada N (2014) Survival outcome and reduction rate of Ki-67 between pre- and post-neoadjuvant chemotherapy in breast cancer patients with non-pCR. Breast CancerResTreat 147(1):95–102. https://doi.org/10.1007/s10549-014-3084-6

    Article  Google Scholar 

  9. Alcantara VS, Lim GH, Lim SH, Sultana R, Lee JA (2017) Incidence and prognosis of non-metastatic triple negative breast cancer (TNBC) among different races in Southeast Asia. J SurgOncol 115(5):523–537. https://doi.org/10.1002/jso.24559 (Epub 2017 Feb 7 PMID: 28168712)

    Article  Google Scholar 

  10. Chandra D, Suresh P, Sinha R, Azam S, Batra U, Talwar V, Kumar K, Mehta A (2016) Eight year survival analysis of patients with triple negative breast cancer in India. AsianPac J CancerPrev 17(6):2995–2999

    Google Scholar 

  11. De-la-Cruz-Ku G, Luyo M, Morante Z, Enriquez D, Möller MG, Chambergo-Michilot D, Flores L, Luque R, Saavedra A, Eyzaguirre-Sandoval ME, Luján-Peche MG, Noel N, Calderon H, Razuri C, Fuentes HA, Cotrina JM, Neciosup SP, Araujo J, Lema A, Pinto J, Gomez HL, Valcarcel B (2020) Triple-negative breast cancer in Peru: 2000 patients and 15 years of experience. PLoSOne 15(8):e0237811. https://doi.org/10.1371/journal.pone.0237811

    Article  CAS  Google Scholar 

  12. Budakoglu B, Altundag K, Aksoy S, Kaplan MA, Ozdemir NY, Berk V, Ozkan M, Algin E, Kandemir N, Dogu GG, Harputluoglu H, Arslan UY, Coskun U, Isikdogan A, Oksuzoglu B (2014) Outcome of 561 non-metastatic triple negative breast cancer patients: multi-center experience from Turkey. J BUON 19(4):872–8

    PubMed  Google Scholar 

  13. Pan Y, Yuan Y, Liu G, Wei Y (2017) P53 and Ki-67 as prognostic markers in triple-negative breast cancer patients. PLoS ONE 12(2):e0172324. https://doi.org/10.1371/journal.pone.0172324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Badowska-Kozakiewicz AM, Budzik MP, Liszcz A, Sobieraj MT, Czerw AI, Sobol M, Patera J, Deptała A (2019) Clinicopathological factors associated with novel prognostic markers for patients with triple negative breast cancer. Arch Med Sci 15(6):1433–1442. https://doi.org/10.5114/aoms.2018.79568

    Article  CAS  PubMed  Google Scholar 

  15. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, Panel Members (2011) Strategies for subtypes – dealing with the diversity of breast cancer: Highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22:1736–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gnant M, Thomssen C, Harbeck NS, Gallen V (2015) A brief summary of the consensus discussion. BreastCare (Basel) 2015(10):124–130

    Article  Google Scholar 

  17. Hashmi AA, Hashmi KA, Irfan M, Khan SM, Edhi MM, Ali JP, Hashmi SK, Asif H, Faridi N, Khan A (2019) Ki67 index in intrinsic breast cancer subtypes and its association with prognostic parameters. BMC ResNotes 12(1):605. https://doi.org/10.1186/s13104-019-4653-x

    Article  CAS  Google Scholar 

  18. Soliman NA, Yussif SM (2016) Ki-67 as a prognostic marker according to breast cancer molecular subtype. Cancer Biol Med 13(4):496–504. https://doi.org/10.20892/j.issn.2095-3941.2016.0066

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ricciardi GR, Adamo B, Ieni A, Licata L, Cardia R, Ferraro G et al (2015) Androgen receptor (AR), E-cadherin, and Ki-67 as emerging targets and novel prognostic markers in triple-negative breast cancer (TNBC) patients. PLoSOne 10:e0128368

    Article  Google Scholar 

  20. Fulawka L, Halon A (2017) Ki-67 evaluation in breast cancer: the daily diagnostic practice. Indian J Pathol Microbiol. 60(2):177–184. https://doi.org/10.4103/IJPM.IJPM_732_15

    Article  PubMed  Google Scholar 

  21. deAzambuja E, Cardoso F, de Castro G et al (2007) Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer 96:1504. https://doi.org/10.1038/sj.bjc.6603756

    Article  CAS  Google Scholar 

  22. Trihia H, Murray S, Price K et al (2003) Ki-67 expression in breast carcinoma: its association with grading systems, clinical parameters, and other prognostic factors—a surrogate marker? Cancer 97:1321. https://doi.org/10.1002/cncr.11188

    Article  CAS  PubMed  Google Scholar 

  23. Nishimura R, Osako T, Okumura Y, Hayashi M, Toyozumi Y, Arima N (2010) Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer. ExpTherMed 1:747–754

    Google Scholar 

  24. Petrelli F, Viale G, Cabiddu M, Barni S (2015) Prognostic value of different cut-of levels of ki67 in breast cancer: a systematic review and meta-analysis of 64196 patients. Breast Cancer ResTreat. 153:477–91. https://doi.org/10.1007/s10549-015-3559-0

    Article  Google Scholar 

  25. Keam B, Im SA, Lee KH, Han SW, Oh DY, Kim JH, Lee SH, Han W, Kim DW, Kim TY, Park IA, Noh DY, Heo DS, Bang YJ (2011) Ki-67 can be used for further classification of triple negative breast cancer into two subtypes with different response and prognosis. Breast Cancer Res 13(2):R22. https://doi.org/10.1186/bcr2834

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wu Q, Ma G, Deng Y, Luo W, Zhao Y, Li W, Zhou Q (2019) Prognostic value of Ki-67 in patients with resected triple-negative breast cancer: a meta-analysis. Front Oncol 17(9):1068. https://doi.org/10.3389/fonc.2019.01068

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Surgery, Faculty of Medicine, Gaziosmanpasa University, Tokat, Turkey

    Bulent Koca

  2. Department of General Surgery, Faculty of Medicine, Gaziosmanpasa University, Sevki Erek Yerleskesi, 60030, Tokat, Turkey

    Murat Yildirim

  3. Department of General Surgery, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey

    Bekir Kuru

Authors
  1. Bulent Koca
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Murat Yildirim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bekir Kuru
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

BK and MY planned the study, collected the data, drafted the article, and did the revision of the article; BK, MY, and BK drafted the article and revision of the article. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Murat Yildirim.

Ethics declarations

Ethics Approval

We have read and complied with the policy of the journal on ethical consent.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Koca, B., Yildirim, M. & Kuru, B. Prognostic Factors Affecting Disease-Free Survival in Triple-Negative Breast Cancer and Impact of Ki-67. Indian J Surg 84 (Suppl 3), 708–713 (2022). https://doi.org/10.1007/s12262-021-03066-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12262-021-03066-9

Keywords

Search

Navigation