HER2 Pozitif Meme Kanserinde Neoadjuvan Tedaviye Patolojik Yanıtı Belirleyen Klinikopatolojik Faktörler

Amaç: Çalışmamızda HER2 pozitif meme kanserinde neoadjuvan kemoterapi sonrası patolojik yanıtı etkileyen klinikopatolojik faktörleri saptamayı amaçladık. Gereç ve Yöntem: Bu çalışmaya HER2 ekspresyonu pozitif toplam 54 olgu dahil edildi. Hastaların tamamına trastuzumab içeren neoadjuvan kemoterapi rejimi uygulandı. Hastaların yaşı, cinsiyeti, hastalığın evresi, tümör boyutu ve lenf nodu durumu, östrojen ve progesteron reseptör durumu, Ki-67 proliferasyon indeksi, tümörün grade’i, menopoz durumu ve neoadjuvan tedavi sonrası patolojik tam yanıt durumu, neoadjuvan tedavi rejimi ve tümörün histolojik alt tipi ile arasındaki ilişki incelendi. Bulgular: Grade III tümör, hormon reseptör negatifliği, Ki-67 skor yüksekliği, T3 veya T4 tümör varlığı daha iyi patolojik tam yanıt ile ilişkili bulundu (sırasıyla p=0,036, p=0,033, p=0,021, p=0,048). Yüksek tümör grade’i, hormon reseptör negatifliği ve yüksek Ki-67 skoru patolojik tam yanıtı belirleyen bağımsız risk faktörleri olarak saptandı (sırasıyla p=0,043, p=0,047, p=0,035). Sonuç: HER2 pozitif meme kanserli 54 olguluk bu seride neoadjuvan tedavi sonrası patolojik tam yanıtı belirleyen parametreler yüksek Ki-67 proliferasyon indeksi, grade III tümör varlığı ve hormon reseptör negatifliğidir.

Clinicopathological Factors Determining the Pathological Response to Neoadjuvant Therapy in HER2 Positive Breast Cancer

Aim: In our study, we aimed to determine the clinicopathological factors affecting the pathological response after neoadjuvant chemotherapy inHER2 positive breast cancer.Materials and Methods: A total of 54 HER2 expression positive cases were included in this study. Neoadjuvant chemotherapy regimen containingtrastuzumab was applied to all patients. Patients’ age, gender, disease stage, tumor size and lymph node status, estrogen and progesterone receptorstatus, Ki-67 proliferation index, tumor grade, menopausal status and pathological complete response status after neoadjuvant therapy, neoadjuvanttreatment regimen and the relationship between the tumor and histological subtype were examined.Results: Grade III tumor, hormone receptor negativity, high Ki-67 score, and the presence of T3 or T4 tumor were found to be better associated withpathological complete response (p=0.036, p=0.033, p=0.021, p=0.048, respectively). High tumor grade, hormone receptor negativity and high Ki-67score were found as independent risk factors determining pathological complete response (p=0.043, p=0.047, p=0.035, respectively).Conclusion: In this series of 54 cases with HER2 positive breast cancer, the parameters determining pathological complete response after neoadjuvanttreatment are high Ki-67 proliferation index, grade III tumor and hormone receptor negativity.

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1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209-49.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7-30.
3. Kaufmann M, Hortobagyi GN, Goldhirsch A, Scholl S, Makris A, Valagussa P, et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update. J Clin Oncol. 2006;24:1940-9.
4. Mamtani A, Barrio AV, King TA, Van Zee KJ, Plitas G, Pilewskie M, et al. How Often Does Neoadjuvant Chemotherapy Avoid Axillary Dissection in Patients With Histologically Confirmed Nodal Metastases? Results of a Prospective Study. Ann Surg Oncol. 2016;23:3467-74.
5. Fowler AM, Mankoff DA, Joe BN. Imaging Neoadjuvant Therapy Response in Breast Cancer. Radiology. 2017;285:358-75.
6. Untch M, Konecny GE, Paepke S, von Minckwitz G. Current and future role of neoadjuvant therapy for breast cancer. Breast. 2014;23:526-37.
7. Klapper LN, Glathe S, Vaisman N, Hynes NE, Andrews GC, Sela M, et al. The ErbB-2/ HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci U S A. 1999;96:4995- 5000.
8. Karunagaran D, Tzahar E, Beerli RR, Chen X, Graus-Porta D, Ratzkin BJ, et al. ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer. EMBO J. 1996;15:254-64.
9. King CR, Kraus MH, Aaronson SA. Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science. 1985;229:974-6.
10. Nicolini A, Ferrari P, Duffy MJ. Prognostic and predictive biomarkers in breast cancer: Past, present and future. Semin Cancer Biol. 2018;52:56-73.
11. Walker RA, Bartlett JM, Dowsett M, Ellis IO, Hanby AM, Jasani B, et al. HER2 testing in the UK: further update to recommendations. J Clin Pathol. 2008;61:818-24.
12. Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31:3997-4013.
13. Gralow JR, Burstein HJ, Wood W, Hortobagyi GN, Gianni L, von Minckwitz G, et al. Preoperative therapy in invasive breast cancer: pathologic assessment and systemic therapy issues in operable disease. J Clin Oncol. 2008;26:814-9.
14. Fayanju OM, Ren Y, Thomas SM, Greenup RA, Plichta JK, Rosenberger LH, et al. The Clinical Significance of Breast-only and Node-only Pathologic Complete Response (pCR) After Neoadjuvant Chemotherapy (NACT): A Review of 20,000 Breast Cancer Patients in the National Cancer Data Base (NCDB). Ann Surg. 2018;268:591-601.
15. Spring LM, Fell G, Arfe A, Sharma C, Greenup R, Reynolds KL, et al. Pathologic Complete Response after Neoadjuvant Chemotherapy and Impact on Breast Cancer Recurrence and Survival: A Comprehensive Meta-analysis. Clin Cancer Res. 2020;26:2838-48.
16. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164-72.
17. Esserman LJ, Berry DA, DeMichele A, Carey L, Davis SE, Buxton M, et al. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL--CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012;30:3242-9.
18. Untch M, Fasching PA, Konecny GE, Hasmüller S, Lebeau A, Kreienberg R, et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. 2011;29:3351-7.
19. Cortazar P, Geyer CE Jr. Pathological complete response in neoadjuvant treatment of breast cancer. Ann Surg Oncol. 2015;22:1441-6.
20. Jarząb M, Stobiecka E, Badora-Rybicka A, Chmielik E, Kowalska M, Bal W, et al. Association of breast cancer grade with response to neoadjuvant chemotherapy assessed postoperatively. Pol J Pathol. 2019;70:91-9.
21. Spring L, Greenup R, Niemierko A, Schapira L, Haddad S, Jimenez R, et al. Pathologic Complete Response After Neoadjuvant Chemotherapy and Long-Term Outcomes Among Young Women With Breast Cancer. J Natl Compr Canc Netw. 2017;15:1216- 23.
22. Karatas F, Erdem GU, Sahin S, Aytekin A, Yuce D, Sever AR, et al. Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients. Breast. 2017;32:237-44.
23. Silva LRD, Vargas RF, Shinzato JY, Derchain SFM, Ramalho S, Zeferino LC. Association of Menopausal Status, Expression of Progesterone Receptor and Ki67 to the Clinical Response to Neoadjuvant Chemotherapy in Luminal Breast Cancer. Rev Bras Ginecol Obstet. 2019;41:710-7.
24. Untch M, Rezai M, Loibl S, Fasching PA, Huober J, Tesch H, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010;28:2024-31.