DOI QR코드

DOI QR Code

Correlation between Ki67 and Histological Grade in Breast Cancer Patients Treated with Preoperative Chemotherapy

  • Petric, Militza (Department of Oncologic and Maxillofacial Surgery, School of Medicine, Pontificia Universidad Catolica de Chile) ;
  • Martinez, Santiago (Pathology Department, School of Medicine, Pontificia Universidad Catolica de Chile) ;
  • Acevedo, Francisco (Haematology & Oncology Department, Cancer Programme, School of Medicine, Pontificia Universidad Catolica de Chile) ;
  • Oddo, David (Pathology Department, School of Medicine, Pontificia Universidad Catolica de Chile) ;
  • Artigas, Rocio (Haematology & Oncology Department, Cancer Programme, School of Medicine, Pontificia Universidad Catolica de Chile) ;
  • Camus, Mauricio (Department of Oncologic and Maxillofacial Surgery, School of Medicine, Pontificia Universidad Catolica de Chile) ;
  • Sanchez, Cesar (Haematology & Oncology Department, Cancer Programme, School of Medicine, Pontificia Universidad Catolica de Chile)
  • Published : 2015.01.06

Abstract

Background and Aim: Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). Materials and Methods: We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. Results: 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). Conclusions: In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

Keywords

References

  1. Acevedo F, Herrera ME, Madrid J, Sanchez C (2013). Neoadyuvant endocrine therapy in breast cancer. Revista Medica de Chile, 141, 367-74. https://doi.org/10.4067/S0034-98872013000300013
  2. Berry DA, Cronin KA, Plevritis SK, et al (2005). Effect of screening and adjuvant therapy on mortality from breast cancer. New Engl J Med, 353, 1784-92. https://doi.org/10.1056/NEJMoa050518
  3. Burstein HJ, Piccart-Gebhart MJ, Perez EA (2012). Choosing the best trastuzumab-based adjuvant chemotherapy regimen: should we abandon anthracyclines? J Clin Oncol, 30, 2179-82. https://doi.org/10.1200/JCO.2012.42.0695
  4. Cuzick J, Dowsett M, Pineda S, et al (2011). Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the genomic health recurrence score in early breast cancer. J Clin Oncol, 29, 4273-78. https://doi.org/10.1200/JCO.2010.31.2835
  5. De Azambuja E, Cardoso F, De Castro G Jr (2007). Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12,155 patients. Br J Cancer, 96, 1504-13. https://doi.org/10.1038/sj.bjc.6603756
  6. Elston CW, Ellis IO (2002). Pathological prognostic factors in breast cancer. i. the value of histological grade in breast cancer: experience from a large study with long-term followup. Histopathology, 41, 154-61. https://doi.org/10.1046/j.1365-2559.2002.14892.x
  7. Galea MH, Blamey RW, Elston CE, Ellis IO (1992). The nottingham prognostic index in primary breast cancer. Breast Cancer Res Treat, 22, 207-19. https://doi.org/10.1007/BF01840834
  8. Goldhirsch A, Winer EP, Coates AS (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. Ann Oncol, 24, 2206-23. https://doi.org/10.1093/annonc/mdt303
  9. Goldhirsch A, Wood WC, Coates AS, et al (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. Ann Oncol, 22, 1736-47. https://doi.org/10.1093/annonc/mdr304
  10. Jin SH, Kim SH, Kang BJ, et al (2014). Breast cancer recurrence according to molecular subtype. Asian Pac J Cancer Prev, 15, 5539-44. https://doi.org/10.7314/APJCP.2014.15.14.5539
  11. Khokher S, Qureshi MU, Mahmood S, Nagi AH (2013). Association of immunohistochemically defined molecular subtypes with clinical response to presurgical chemotherapy in patients with advanced breast cancer. Asian Pac J Cancer Prev, 14, 3223-28. https://doi.org/10.7314/APJCP.2013.14.5.3223
  12. Kilickap S, Kaya Y, Yucel B, et al (2014). Higher ki67 expression is associated with unfavorable prognostic factors and shorter survival in breast cancer. Asian Pac J Cancer Prev, 15, 1381-85. https://doi.org/10.7314/APJCP.2014.15.3.1381
  13. Kumaki N, Umemura S, Tang X, et al (2011). Alteration of immunohistochemical biomarkers between pre-and postchemotherapy: hormone receptors, HER2 and Ki-67. Breast Cancer, 18, 98-102. https://doi.org/10.1007/s12282-010-0238-1
  14. Paik S, Shak S, Tang G, et al (2004). A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. New England J Med, 351.
  15. Pathmanathan N, Balleine RL (2013). Ki67 and proliferation in breast cancer. J Clin Pathol, 66, 512-16. https://doi.org/10.1136/jclinpath-2012-201085
  16. Reis-Filho J, Pusztai L (2011). Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet, 378, 1812-23. https://doi.org/10.1016/S0140-6736(11)61539-0
  17. Rinat Y, Woods R, Ravdin PM, Hayes MM, Gelmon KA (2010). Ki67 in breast cancer: prognostic and predictive potential. Lancet Oncol, 11, 174-83. https://doi.org/10.1016/S1470-2045(09)70262-1
  18. Saroona H, Hashmi AA, Khurshid A, et al (2013). Ki67 index in breast cancer: correlation with other prognostic markers and potential in Pakistani patients. Asian Pac J Cancer Prev, 14, 4353-58. https://doi.org/10.7314/APJCP.2013.14.7.4353
  19. Stumpp J, Dietl J, Simon W, Geppert M (1992). Growth fraction in breast carcinoma determined by Ki-67 immunostaining: correlation with pathological and clinical variables. Gynecol Obstet Invest, 33, 47-50. https://doi.org/10.1159/000294846
  20. Gong T, Shak S, Paik S, et al (2011). Comparison of the prognostic and predictive utilities of the 21-gene recurrence score assay and adjuvant! for women with node-negative, ER-positive breast cancer: results from NSABP B-14 and NSABP B-20. Breast Cancer Res Treat, 127, 133-42. https://doi.org/10.1007/s10549-010-1331-z
  21. Tanriverdi O, Meydan N, Barutca S (2014). Reconsideration of clinical and histopathological prognostic factors in breast cancer patients: A single center experience. Asian Pac J Cancer Prev, 15, 807-12. https://doi.org/10.7314/APJCP.2014.15.2.807
  22. The Cancer Genome Atlas Research Network (2012). Comprehensive molecular portraits of human breast tumours. Nature, 490, 61-70. https://doi.org/10.1038/nature11412
  23. Viale Giuseppe, Anita Giobbie-Hurder, Meredith M Regan, et al (2008). Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from breast international group trial 1-98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol, 26, 5569-75. https://doi.org/10.1200/JCO.2008.17.0829
  24. Yoo C, Ahn J-H, Jung KH, et al (2012). Impact of immunohistochemistry-based molecular subtype on chemosensitivity and survival in patients with breast cancer following neoadjuvant chemotherapy. J Breast Cancer, 15, 203-10. https://doi.org/10.4048/jbc.2012.15.2.203

Cited by

  1. Conserved genes and pathways in primary human fibroblast strains undergoing replicative and radiation induced senescence vol.49, pp.1, 2016, https://doi.org/10.1186/s40659-016-0095-2
  2. Prognostic parameters of luminal A and luminal B intrinsic breast cancer subtypes of Pakistani patients vol.16, pp.1, 2018, https://doi.org/10.1186/s12957-017-1299-9
  3. Predictive value of primary tumor parameters using 18F-FDG PET/CT for occult lymph node metastasis in breast cancer with clinically negative axillary lymph node vol.32, pp.9, 2018, https://doi.org/10.1007/s12149-018-1288-2