HISTOPATHOLOGICAL PARAMETERS AND INTRATUMORAL LYMPHOCYTES: CORRELATION WITH SURVIVAL OUTCOMES IN TRIPLE-NEGATIVE BREAST CANCER - A COMPREHENSIVE RETROSPECTIVE ANALYSIS

Year 2024, , 208 - 213, 29.04.2024

Neslihan Kaya Terzi

https://doi.org/10.18229/kocatepetip.1300967

Abstract

OBJECTIVE: Triple-negative breast cancer (TNBC) is a subtype characterized by aggressive tumor behavior and limited treatment options. This study aimed to investigate the relationship among age, pathological stage, proliferative index, presence of tumor infiltrating lymphocytes (TILs), and survival outcomes in TNBC.
MATERIAL AND METHODS: Tumoral slides and blocks of 31 patients with triple negative breast cancer were retrieved from the pathology archive and retrospectively re-evaluated. The relationship among patient age, histopathological subtype of the tumor, tumor grade, lymph node grade, Ki-67 proliferation index and survival was evaluated. TILs were scored as mild, moderate and severe and the relationship with survival was evaluated.
RESULTS: Regarding age and tumor stage, there was no significant correlation found (p=0,81 and p=0,89 respectively). However, when analyzing the N stage, a clear association was observed, with a higher proportion of patients aged 65 years or older displaying advanced N3 stage breast cancer (p=0.000013). A significant relationship was found between TILs and the Ki-67 proliferative index, with cases exhibiting high TILs also demonstrating a high proliferative index (p=0.003). Furthermore, increased TIL concentration was associated with a positive response to therapy and improved overall survival in TNBC patients (p=0.001).
CONCLUSIONS: These findings emphasize the importance of considering age, pathological stage, proliferative index, and the presence of TILs in TNBC prognosis. Evaluation of TILs in routine histopathologic examination and inclusion in pathology reports, particularly in postmenopausal patients, could provide valuable information for future studies and guide treatment decisions. Additional research on immune-modulating therapies targeting TILs may hold promise for improving outcomes in TNBC patients.

Keywords

Triple negative breast cancer, Tumor infiltrating lymphocytes, Grade, Survival

Project Number

Yok

HİSTOPATOLOJİK PARAMETRELER VE İNTRATÜMÖRAL LENFOSİTLER: ÜÇLÜ NEGATİF MEME KANSERİNDE SAĞKALIM SONUÇLARI İLE KORELASYON - KAPSAMLI RETROSPEKTİF BİR ANALİZ

Abstract

AMAÇ: Üçlü-negatif meme kanseri (TNBC) agresif tümör davranışı ve sınırlı tedavi seçenekleriyle karakterize bir alt tiptir. Bu çalışmanın amacı TNBC'de yaş, patolojik evre, proliferatif indeks, tümör infiltre eden lenfositlerin (TIL) varlığı ve sağkalım sonuçları arasındaki ilişkiyi araştırmaktır.
GEREÇ VE YÖNTEM: Üçlü negatif meme kanserli 31 hastanın tümör lamları ve blokları patoloji arşivinden alındı ve retrospektif olarak yeniden değerlendirildi. Hasta yaşı, tümörün histopatolojik alt tipi, tümör derecesi, lenf nodu derecesi, Ki-67 proliferasyon indeksi ve sağkalım arasındaki ilişki değerlendirildi. TIL'ler hafif, orta ve şiddetli olarak skorlandı ve sağkalım ile ilişkisi değerlendirildi.
BULGULAR: Yaş ve tümör evresi ile ilgili olarak, anlamlı bir korelasyon bulunmamıştır (sırasıyla p=0,81 ve p=0,89). Bununla birlikte, N evresi analiz edildiğinde, 65 yaş ve üzeri hastaların daha yüksek bir oranının ileri N3 evresi meme kanseri göstermesiyle açık bir ilişki gözlenmiştir (p=0,000013). TIL'ler ile Ki-67 proliferatif indeks arasında anlamlı bir ilişki bulunmuş, yüksek TIL sergileyen vakalar aynı zamanda yüksek proliferatif indeks de göstermiştir (p=0,003). Ayrıca, artmış TIL konsantrasyonu TNBC hastalarında tedaviye olumlu yanıt ve genel sağkalımda iyileşme ile ilişkilendirilmiştir (p=0.001).
SONUÇ: Bu bulgular, TNBC prognozunda yaş, patolojik evre, proliferatif indeks ve TIL varlığının dikkate alınmasının önemini vurgulamaktadır. TIL'lerin rutin histopatolojik incelemede değerlendirilmesi ve özellikle postmenopozal hastalarda patoloji raporlarına dahil edilmesi, gelecekteki çalışmalar için değerli bilgiler sağlayabilir ve tedavi kararlarını yönlendirebilir. TIL'leri hedefleyen immün modüle edici tedaviler üzerine ek araştırmalar, TNBC hastalarında sonuçları iyileştirmek için umut vaat edebilir.

Keywords

Üçlü negatif meme kanseri, Tümör infiltre eden lenfositler, Evre, Sağkalım

Supporting Institution

Yok

Project Number

Yok

References

• 1. DeSantis CE, Ma J, Gaudet MM, et al. Breast cancer statistics, 2019. CA Cancer J Clin. 2019;69(6):438-51.
• 2. Dent R, Trudeau M, Pritchard KI, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15):4429–34.
• 3. Trivers KF, Lund MJ, Porter PL, et al. The epidemiology of triple-negative breast cancer, including race. Cancer Causes Control. 2009;20(7):1071-82.
• 4. Yu, J., Zayas, J., Qin, B., & Wang L Targeting DNA methylation for treating triple-negative breast cancer. Pharmacogenomics, 2019;20(16):151–57.
• 5. Ali HR, Provenzano E, Dawson SJ, Blows FM, et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol. 2014;25:1536–43.
• 6. Mahmoud SM, Paish EC, Powe DG, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol. 2011;29:1949–55.
• 7. Matkowski R, Gisterek I, Halon A, et al. The prognostic role of tumor-infiltrating CD4 and CD8 T lymphocytes in breast cancer. Anticancer Res. 2009;29:2445–51.
• 8. Aaltomaa S, Lipponen P, Eskelinen M, et al. Lymphocyte infiltrates as a prognostic variable in female breast cancer. Eur J Cancer. 1992;28A:859–64.
• 9. Jamiyan T, Kuroda H , Yamaguchi R, et al. Prognostic impact of a tumor-infiltrating lymphocyte subtype in triple negative cancer of the breast. Breast Cancer (Tokyo, Japan), 2020;27(5): 880–92.
• 10. Denkert C, Von Minckwitz G, Darb-Esfahani S, et al. (2018). Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. The Lancet Oncology. 2018;19(1): 40–50.
• 11. Cserni, G, Chmielik E, Cserni B, Tot T. The new TNM-based staging of breast cancer. Virchows Archiv : an International Journal of Pathology. 2018; 472(5): 697–703.
• 12. Inwald EC, Klinkhammer-Schalke M, Hofstädter F, et al. (2013). Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Research and Treatment. 2013;139(2): 539–52.
• 13. Unlu O, Kiyak D, Caka C, Yagmur M, Yavas HG, et al. Risk factors and histopathological features of breast cancer among women with different menopausal status and age at diagnosis. J BUON. 2017;22(1): 184–91.
• 14. Botteri E, Bagnardi V, Goldhirsch A, Viale G, Rotmensz N. Axillary lymph node involvement in women with breast cancer: does it depend on age? Clin Breast Cancer . 2010;10:318-21.
• 15. Wildiers H, Van Calster B, van de Poll-Franse LV, et al. Relationship between age and axillary lymph node involvement in women with breast cancer. J Clin Oncol. 2009;27:2931-37.
• 16. Liu S Lachapelle, LeungS, Gao D Foulkes, et al. CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer. Breast Cancer Res. 2012;(14):1–14.
• 17. Mersin H, Yildirim E, Berberoglu U, Gulben K. The prognostic importance of triple negative breast carcinoma. Breast. 2008;17:341–6.
• 18. Marginean F, Rakha EA, Ho BC, Ellis IO, Lee AH. Histological features of medullary carcinoma and prognosis in triplenegative basal-like carcinomas of the breast. Mod Pathol. 2010;23:1357–63.
• 19. Kurozumi S, Matsumoto H, Kurosumi M, et al. Prognostic signifcance of tumour-infltrating lymphocytes for oestrogen receptor-negative breast cancer without lymph node metastasis. Oncol Lett. 2019;17:2647– 56.
• 20. Ibrahim EM, Al-Foheidi ME, Al-Mansour MM, Kazkaz GA. The prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancer: a meta-analysis. Breast Cancer Res Treat. 2014;148:467–76.