The utility of immunohistochemistry-based biomarkers in predicting the pathological complete response in early-stage triple-negative breast cancer

被引:0
作者
Funasaka, Chikako [1 ,2 ]
Kogawa, Takahiro [1 ,2 ,7 ]
Sakamoto, Naoya [4 ,5 ]
Kusuhara, Shota [1 ]
Nakao, Takehiro [1 ]
Nakajima, Hiromichi [2 ]
Kondoh, Chihiro [1 ]
Harano, Kenichi [1 ,2 ]
Matsubara, Nobuaki [1 ]
Hosono, Ako [1 ,3 ]
Naito, Yoichi [1 ,2 ]
Shimokawa, Mototsugu [8 ]
Watanuki, Rurina [6 ]
Yamashita, Yuji [6 ]
Yamauchi, Chisako [6 ]
Onishi, Tatsuya [6 ]
Ishii, Genichiro
Mukohara, Toru [1 ]
机构
[1] Natl Canc Ctr Hosp East, Dept Med Oncol, 6-5-1 Kashiwanoha, Kashiwa 2778577, Japan
[2] Natl Canc Ctr Hosp East, Dept Expt Therapeut, 6-5-1 Kashiwanoha, Kashiwa 2778577, Japan
[3] Natl Canc Ctr Hosp East, Dept Pediat Oncol, 6-5-1 Kashiwanoha, Kashiwa 2778577, Japan
[4] Natl Canc Ctr Hosp East, Dept Pathol, 6-5-1 Kashiwanoha, Kashiwa 2778577, Japan
[5] Natl Canc Ctr Hosp East, Dept Clin Labs, 6-5-1 Kashiwanoha,, Kashiwa 2778577, Japan
[6] Natl Canc Ctr Hosp East, Dept Breast Surg, 6-5-1 Kashiwanoha, Kashiwa 2778577, Japan
[7] Japanese Fdn Canc Res, Dept Adv Med Dev, Canc Inst Hosp, 3-8-31 Ariake,Koto Ku, Tokyo 1358550, Japan
[8] Yamaguchi Univ, Dept Biostat, Grad Sch Med, 1-1-1 Minamikogushi, Ube, Yamaguchi 7550046, Japan
关键词
Triple-negative breast cancer; TIL; neoadjuvant chemotherapy; TUMOR-INFILTRATING LYMPHOCYTES; VIMENTIN; CARCINOMAS; EXPRESSION;
D O I
10.1016/j.ctarc.2025.100941
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Triple-negative breast cancer (TNBC) is a highly aggressive subtype of BC. A pathological complete response (pCR) to neoadjuvant chemotherapy is strongly associated with a favorable TNBC prognosis; however, established predictors of pCR, including tumor-infiltrating lymphocytes (TILs), are often not adequately reliable in the clinic. This study evaluated the utility of immunohistochemistry (IHC)-based markers and TILs in predicting pCR in early-stage TNBC. This study enrolled 61 women with stage I-III TNBC who were treated at our institution between January 2013 and December 2019. Pathological data were collected from electronic medical records, while IHC data were obtained from preoperative biopsy specimens. Fisher's test, multivariable logistic regression, and correlation analyses were used to identify biomarker candidates and their interactions. The majority of the patients had stage II or III invasive ductal TNBC. The pCR rate was 31 % (19/61). High TIL frequencies (>= 40 %) and high Ki-67 (>= 40 %) levels were associated with pCR. Among the patients with high TIL frequencies, ARnegative patients had a higher pCR rate than AR-positive patients (55.0 % versus 16.7 %; p = 0.71). Vimentin negativity correlated with high TIL frequencies (p = 0.02). High TIL frequencies and high Ki-67 levels were independently associated with an increased likelihood of achieving a pCR. The combination of high TIL frequencies and high Ki-67 levels was predictive of pCR in patients with primary TNBC, while AR and vimentin represent candidate markers that require further validation. Further studies should evaluate the performance of these markers in combination with other biomarkers and in the context of immune-checkpoint blockade.
引用
收藏
页数:8
相关论文
共 34 条
[1]  
Abuhadra N, 2019, Beyond TILs: Predictors of pathologic complete response (pCR) in triple-negative breast cancer (TNBC) patients with moderate tumor-infiltrating lymphocytes (TIL) receiving neoadjuvant therapy, V37, P572, DOI [10.1200/JCO20193715suppl572, DOI 10.1200/JCO20193715SUPPL572]
[2]   Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199 [J].
Adams, Sylvia ;
Gray, Robert J. ;
Demaria, Sandra ;
Goldstein, Lori ;
Perez, Edith A. ;
Shulman, Lawrence N. ;
Martino, Silvana ;
Wang, Molin ;
Jones, Vicky E. ;
Saphner, Thomas J. ;
Wolff, Antonio C. ;
Wood, William C. ;
Davidson, Nancy E. ;
Sledge, George W. ;
Sparano, Joseph A. ;
Badve, Sunil S. .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :2959-+
[3]  
[Anonymous], 2023, Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients
[4]   The Expression of Programmed Death Ligand 1 and Vimentin in Resected Non-Metastatic Non-Small-Cell Lung Cancer: Interplay and Prognostic Effects [J].
Bravaccini, Sara ;
Bronte, Giuseppe ;
Petracci, Elisabetta ;
Puccetti, Maurizio ;
D'Arcangelo, Manolo ;
Ravaioli, Sara ;
Tumedei, Maria Maddalena ;
Maltoni, Roberta ;
Delmonte, Angelo ;
Cappuzzo, Federico ;
Crino, Lucio .
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2021, 9
[5]  
cancer, Triple-negative Breast Cancer | Details, Diagnosis, and Signs
[6]   Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis [J].
Cortazar, Patricia ;
Zhang, Lijun ;
Untch, Michael ;
Mehta, Keyur ;
Costantino, Joseph P. ;
Wolmark, Norman ;
Bonnefoi, Herve ;
Cameron, David ;
Gianni, Luca ;
Valagussa, Pinuccia ;
Swain, Sandra M. ;
Prowell, Tatiana ;
Loibl, Sibylle ;
Wickerham, D. Lawrence ;
Bogaerts, Jan ;
Baselga, Jose ;
Perou, Charles ;
Blumenthal, Gideon ;
Blohmer, Jens ;
Mamounas, Eleftherios P. ;
Bergh, Jonas ;
Semiglazov, Vladimir ;
Justice, Robert ;
Eidtmann, Holger ;
Paik, Soonmyung ;
Piccart, Martine ;
Sridhara, Rajeshwari ;
Fasching, Peter A. ;
Slaets, Leen ;
Tang, Shenghui ;
Gerber, Bernd ;
Geyer, Charles E., Jr. ;
Pazdur, Richard ;
Ditsch, Nina ;
Rastogi, Priya ;
Eiermann, Wolfgang ;
von Minckwitz, Gunter .
LANCET, 2014, 384 (9938) :164-172
[7]   Molecular adaptation to neoadjuvant immunotherapy in triple-negative breast cancer [J].
Denkert, Carsten ;
Schneeweiss, Andreas ;
Rey, Julia ;
Karn, Thomas ;
Hattesohl, Akira ;
Weber, Karsten E. ;
Rachakonda, Sivaramakrishna ;
Braun, Michael ;
Huober, Jens ;
Jank, Paul ;
Sinn, Hans-Peter ;
Zahm, Dirk-Michael ;
Felder, Barbel ;
Hanusch, Claus ;
Teply-Szymanski, Julia ;
Marme, Frederik ;
Fehm, Tanja ;
Thomalla, Jorg ;
V. Sinn, Bruno ;
Stiewe, Thorsten ;
Marczyk, Michal ;
Blohmer, Jens-Uwe ;
van Mackelenbergh, Marion ;
Schem, Christian ;
Staib, Peter ;
Link, Theresa ;
Muller, Volkmar ;
Stickeler, Elmar ;
Stover, Daniel G. ;
Solbach, Christine ;
Metzger-Filho, Otto ;
Jackisch, Christian ;
Geyer Jr, Charles E. ;
Fasching, Peter A. ;
Pusztai, Lajos ;
Nekljudova, Valentina ;
Untch, Michael ;
Loibl, Sibylle .
CELL REPORTS MEDICINE, 2024, 5 (11)
[8]  
DOMAGALA W, 1990, AM J PATHOL, V137, P1059
[9]   Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancer: The Future of Immune Targeting [J].
Garcia-Teijido, Paula ;
Luque Cabal, Maria ;
Pelaez Fernandez, Ignacio ;
Fernandez Perez, Yolanda .
CLINICAL MEDICINE INSIGHTS-ONCOLOGY, 2016, 10 :31-39
[10]   Phase II Trial of Bicalutamide in Patients with Androgen Receptor-Positive, Estrogen Receptor-Negative Metastatic Breast Cancer [J].
Gucalp, Ayca ;
Tolaney, Sara ;
Isakoff, Steven J. ;
Ingle, James N. ;
Liu, Minetta C. ;
Carey, Lisa A. ;
Blackwell, Kimberly ;
Rugo, Hope ;
Nabell, Lisle ;
Forero, Andres ;
Stearns, Vered ;
Doane, Ashley S. ;
Danso, Michael ;
Moynahan, Mary Ellen ;
Momen, Lamia F. ;
Gonzalez, Joseph M. ;
Akhtar, Arooj ;
Giri, Dilip D. ;
Patil, Sujata ;
Feigin, Kimberly N. ;
Hudis, Clifford A. ;
Traina, Tiffany A. .
CLINICAL CANCER RESEARCH, 2013, 19 (19) :5505-5512