Impact of status of ER, PR, HER2 and Ki-67 index on axillary lymph node metastasis of breast cancer

Abstract

Aim: Axillary status evaluation and, if present, the number of metastatic lymph nodes is important in staging and adjuvant therapy planning of breast cancer. A number of clinical and pathological variables were analyzed to detect factors affecting nodal status. Methods: A total of 298 women with unilateral breast cancer operated with axillary lymph node dissection or sentinel lymph node biopsy, were retrospectively analyzed for age, localization, BIRADS category, pathological features, subtypes as Luminal A, Luminal B, HER2 positive, triple negative, Ki-67 index and number of lymph nodes involved. Results: The mean age was 54.7 years. BIRADS 5 was the most detected category in 208 (69.8%) patients. The most common pathological type was invasive ductal carcinoma in 265 patients (88.9%). The most detected tumor grade was grade 2 in 160 (31.2%). Luminal B was the most common subtype and detected in 173 patients (58.1%). Ki-67 indexes were detected between 0-14% in 69 patients (23.3%), between 15-19% in 31patients (10.4%) and above 20% in 198 patients (66.4%). Conclusions: HER2 positivity, Ki-67 index,>

Keywords

• breast cancer
• axillary lymph node metastasis
• hormonal status

Meme kanserinin aksiller metastazlarında ER, PR, HER2 ve Ki-67 indeksinin etkisi

Öz

Amaç: Aksiller lenf nodu metastazı değerlendirmesi ve varsa lenf nodu sayısı meme kanserinin evrelemesi ve adjuvan tedavi planlamasında önemlidir. Amacımız lenf nodu metastazını etkileyen faktörleri saptamak için bir dizi klinik ve patolojik değişkeni araştırmaktır. Yöntemler: Aksiller lenf nodu diseksiyonu veya sentinel lenf nodu biyopsisi ile opere edilen tek taraflı meme kanseri olan 298 kadın hastanın yaş, lokalizasyon, BIRADS kategorisi, patolojik özellikler, Luminal A, Luminal B, HER2 pozitif, tripl negatif subtipleri, Ki-67 indeksi verileri ile metastatik lenf nodu sayısı arasındaki ilişkisi analiz edildi. Bulgular: Yaş ortalaması 54,7 yıl idi. BIRADS 5, 208 (% 69,8) hastada en fazla saptanan kategori idi. En sık görülen patolojik tip 265 hastada (% 88,9) invaziv duktal karsinomdu. En fazla saptanan tümör evresi 2 olup, 160 hastada (% 31,2) tespit edildi. Luminal B en sık görülen subtipti ve 173 (% 58,1) hastada tespit edildi. Ki-67 indeksi 69 hastada (% 23,3) % 0-14, 31 hastada (% 10,4) % 15-19 ve 198 hastada (% 66,4) % 20'nin üzerinde saptandı. Sonuçlar: HER2 pozitifliği, Ki-67 indeksi ve progesteron reseptör negatifliği aksiller lenf nodu metastazını etkileyen en önemli faktörlerdir.

Anahtar Kelimeler

• meme kanseri
• aksiller lenf nodu metastazı
• hormonal durum

References

1. References1. Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101(10):736-50.
2. 2. Aitken E, Monzir O. Factors affecting nodal status in invasive breast cancer. A retrospective analysis of 623 patients. The breast Journal. 2010;16(3):271-8
3. 3. Kayahan M, İdiz UO, Gucin Z, Erözgen F, Memmi N, Müslümanoğlu M. Clinical Significance of Androgen Receptor, CK-5/6, Ki 67 and Molecular subtypes in Breast Cancer. J. Breast Health. 2014;10:201-8.
4. 4. Hui L, Huang T, Lian J, Zhou F, Gao C, Lin Y, et al. Potential prognostic value of clinical characteristics, hormone status and major depressive disorder in breast cancer. Future Oncol. 2017; 13(17):1493-1503.
5. 5. Alco G, Bozdogan A, Selamoglu D, Pilanci KN, Tuzlali S, Ordu C, et al. Clinical and histopathological factors associated with Ki-67 expression in breast cancer patients. Oncology letters. 2015;9:1046-54.
6. 6. Ling Li, Zhang Chen. Factors influencing axillary lymph nodes metastasis in invasive breast cancer. Asian Pac J Cancer Prev.2012;13(1):251-4.
7. 7. Azizun-Nisa, Bhurgri Y, Raza F, Kayani N. Comparison of ER, PR & HER-2/neu (C-erb B 2) Reactivity Pattern with Histologic Grade, Tumor Size and Lymph Node Status in Breast Cancer. Asian Pacific journal of cancer prevention: APJCP. 2008;9:553-6.
8. 8. Gutierrez C, Schiff R. HER2: biology, detection and clinical implications. Arch Pathol Lab Med. 2011;135(1):55-62.

9. 9. Urruticoechea A, Smith IE, Dowsett M: Proliferation marker Ki-67 in early breast cancer. J Clin Oncol. 1;23(28):7212-20.
10. 10. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ et al; Panel members. 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 2011;22:1736-47.
11. 11. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B, et al; 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;24:2206-23.
12. 12. Stuart-Harris R, Caldas C, Pinder SE, Pharoah P: Proliferation markers and survival in early breast cancer: a systematic review and meta-analysis of 85 studies in 32,825 patients. Breast. 2008;17:323-34.
13. 13. Scottish Intercollegiate Guidelines Network (SGIN) Guideline 84: Management of breast cancer in women, NHS Quality Improvement, Edinburgh, Scotland 2005.
14. 14. Kondov B, Kondov G, Spirovski Z, Milenkovikj Z, Colanceski R, Petrusevska G, et al. Prognostic factors on the positivity for metastases of the axillary lymph nodes from primary breast cancer. Pril (Makedon Akad Nauk Umet Odd Med Nauki). 2017;38(1):81-90.
15. 15. Chengshuai Si, Yiting Jin, Hongying Wong, Qiang Zou, Association between molecular subtypes and lymph node status in invasive breast cancer. Int. J Clin Exp Pathol. 2014;7:6800-6.
16. 16. Markopoulos C, Kouskos E, Gogas H,Mandas D, Kakisis J, Gogas J. Factors affecting axillary lymph node metastases in patients with T1 breast carcinoma Am Surg. 2000;66:1011-3.
17. 17. Tan LGL, Ton YY, Heng D, Chan MY. Predictors of axillary lymph node metastases in women with early breast cancer in Singapore. Singapore Med J. 2005;46:693-7.
18. 18. Yang XR, Figueroa JD, Hewitt SM, Falk RT, Pfeifer RM, Lissowska J, and et al. Estrogen receptor and progesterone receptor expression in normal terminal duct lobular units surrounding invasive breast cancer Breast Cancer Res Treat. 2013;137:837-47.
19. 19. Oh H, Eliassen AH, Beck AH, Rosner B, Schnitt SJ, Collins LC, et al. Breast cancer risk factors in relation to estrogen receptor, progesterone receptor, insulin-like growth-factor-1 receptor, Ki 67 expression in normal breast tissue. NPJ Breast Cancer. 2017;3:39.
20. 20. Cuzick J, Dowsett M, Pineda S, Wale C, Salter J, Quinn E, et al. 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. 2011;29:4273-8.
21. 21. Chua B, Ung O, Taylor R, Boyages J. Frequency and predictors of axillary lymph node metastasis in invasive breast cancer. ANZ J Surg. 2001;71:723-8.
22. 22. Bevilacque JLB, Cody HS, Macdonald KA, Tan LK, Borgen PI, van Zee KJ. A model for predicting axillary node metastasis on 2000 sentinel node procedures and tumour position. EJSO. 2002;28:490-500.
23. 23. Viale G, Zurrida S, Maiorano E, Mazzarol G, Pruneri G, Paganelli G, et al. Predicting the status of axillary sentinel lymph nodes in 4351 patients with invasive breast carcinoma treated im a single institution. Cancer. 2005;103:492-500.
24. 24. Rivadeneria DE, Simmons RM, Christos PJ, Hanna K, Daly DE, Osborne C. Predictive factors associated with axillary lymph node metastasis in T1a and T1b breast carcinoma. J Am Coll Surg. 2000;191:1-6.
25. 25. Bertelli G, Nelmes DJ, Al-Allak A. Biomarkers in the management of breast cancer: great expectations, hard times. Appl Immunohistochem Mol Morphol. 2013;21:481–4.
26. 26. Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, et al. 5 year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early stage HER 2 positive breast cancer( NeoSphere): a multicenter open-label , Phase 2 randomized trial. Lancet Oncol. 2016;17;791-800.
27. 27. Hadgu E, Seifu S, Tigneh W,Bokretsion Y, Abebe B, Abebe M, et al. Breast cancer in Ethiopia: evidence for geographic difference in the distribution of molecular subtypes in AfricaBMC Womens Health. 2018;18:40.Published online 2018 Feb 14.
28. 28. Mehdi I, Monem AA, Bahrani B, Ramadhan FA. Breast cancer molecular subtypes in oman: correlation with age, histology, and stage distribution - analysis of 542 cases. Gulf J Oncolog. 2014;1:38-48.
29. 29. Costa OF Neto, Castro RB, Oliveira CV, Feitosa TVN, Alves JJ Júnior, Cavalcante FP, et al. Predictive factors of axillary metastasis in patients with breast cancer and positive sentinel lymph node biopsy. Rev Col Bras Cir. 2017;44:391-6.
30. 30. Jin J, Zheng D, Liu Y. Correlation between the Expression of Topo IIα and Ki67 in breast cancer and its clinical Pathological characteristics. Pak J Med Sci. 2017;33:844-8.