Skip to main content
Top
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Prediction of pathological complete response and prognosis in patients with neoadjuvant treatment for triple-negative breast cancer

Authors: Paul Gass, Michael P. Lux, Claudia Rauh, Alexander Hein, Mayada R. Bani, Cornelia Fiessler, Arndt Hartmann, Lothar Häberle, Jutta Pretscher, Ramona Erber, David L. Wachter, Rüdiger Schulz-Wendtland, Matthias W. Beckmann, Peter A. Fasching, Marius Wunderle

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

It has been reported that pathological complete response is an important surrogate marker for disease-free survival and overall survival in patients with triple-negative breast cancer. This study investigates predictors of the response to neoadjuvant platinum-based or anthracycline-based treatment, and of the prognosis, in patients with triple-negative breast cancer.

Methods

A total of 121 patients with triple-negative breast cancer received neoadjuvant treatment with either platinum or anthracycline between 2008 and 2013. Pathological complete response was assessed relative to different treatments using logistic regression models with age, clinical tumor stage, grading, and Ki-67 as predictors and interaction terms, to obtain adjusted and subgroup-specific results. The impact of the pathological complete response rate on disease-free survival and overall survival was also analyzed.

Results

The pathological complete response rate was higher after platinum/taxane treatment compared with anthracycline/taxane (50.0% vs. 41.8%), but this was not significant in the adjusted analysis (OR 1.44; 95% CI, 0.68 to 3.09). A high histological grade (G3) was a predictor for higher pathological complete response in platinum-based therapy (OR 2.27; 95% CI, 1.00 to 5.30). The effect of neoadjuvant chemotherapy on pathological complete response was significantly different for G1–2 vs. G3 (Pinteraction = 0.013), and additional subgroup-specific differences were noted. Pathological complete response was a predictor for improved disease-free survival and overall survival in both treatment groups, with and without platinum chemotherapy.

Conclusions

This retrospective study of patients with triple-negative breast cancer adds to the evidence that the treatment effect of platinum may be greatest particularly in G3 tumors. In addition, the effect of pathological complete response on the prognosis does not depend on the treatment used.
Literature
1.
go back to reference Robert-Koch-Institut: Krebs in Deutschland für 2013/2014. 2017, Version 11. Robert-Koch-Institut: Krebs in Deutschland für 2013/2014. 2017, Version 11.
2.
go back to reference Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.CrossRef Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747–52.CrossRef
4.
go back to reference Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869–74.CrossRef Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A. 2001;98(19):10869–74.CrossRef
5.
go back to reference Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A, Martiat P, Fox SB, Harris AL, Liu ET. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A. 2003;100(18):10393–8.CrossRef Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A, Martiat P, Fox SB, Harris AL, Liu ET. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A. 2003;100(18):10393–8.CrossRef
6.
go back to reference van ‘t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6.CrossRef van ‘t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530–6.CrossRef
7.
go back to reference Schneeweiss A, Lux MP, Janni W, Hartkopf AD, Nabieva N, Taran FA, Overkamp F, Kolberg HC, Hadji P, Tesch H, et al. Update breast cancer 2018 (part 2) – advanced breast cancer, quality of life and prevention. Geburtshilfe Frauenheilkd. 2018;78(3):246–59.CrossRef Schneeweiss A, Lux MP, Janni W, Hartkopf AD, Nabieva N, Taran FA, Overkamp F, Kolberg HC, Hadji P, Tesch H, et al. Update breast cancer 2018 (part 2) – advanced breast cancer, quality of life and prevention. Geburtshilfe Frauenheilkd. 2018;78(3):246–59.CrossRef
8.
go back to reference Untch M, Huober J, Jackisch C, Schneeweiss A, Brucker SY, Dall P, Denkert C, Fasching PA, Fehm T, Gerber B, et al. Initial treatment of patients with primary breast cancer: evidence, controversies, consensus: spectrum of opinion of German specialists at the 15th international St. Gallen breast cancer conference (Vienna 2017). Geburtshilfe Frauenheilkd. 2017;77(6):633–44.CrossRef Untch M, Huober J, Jackisch C, Schneeweiss A, Brucker SY, Dall P, Denkert C, Fasching PA, Fehm T, Gerber B, et al. Initial treatment of patients with primary breast cancer: evidence, controversies, consensus: spectrum of opinion of German specialists at the 15th international St. Gallen breast cancer conference (Vienna 2017). Geburtshilfe Frauenheilkd. 2017;77(6):633–44.CrossRef
9.
go back to reference Brenton JD, Carey LA, Ahmed AA, Caldas C. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 2005;23(29):7350–60.CrossRef Brenton JD, Carey LA, Ahmed AA, Caldas C. Molecular classification and molecular forecasting of breast cancer: ready for clinical application? J Clin Oncol. 2005;23(29):7350–60.CrossRef
10.
go back to reference Curigliano G, Burstein HJ, E PW, Gnant M, Dubsky P, Loibl S, Colleoni M, Regan MM, Piccart-Gebhart M, Senn HJ, et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen international expert consensus conference on the primary therapy of early breast cancer 2017. Ann Oncol. 2017;28(8):1700–12.CrossRef Curigliano G, Burstein HJ, E PW, Gnant M, Dubsky P, Loibl S, Colleoni M, Regan MM, Piccart-Gebhart M, Senn HJ, et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen international expert consensus conference on the primary therapy of early breast cancer 2017. Ann Oncol. 2017;28(8):1700–12.CrossRef
11.
go back to reference Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, et al. American Society of Clinical Oncology/college of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784–95.CrossRef Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S, Fitzgibbons PL, Francis G, Goldstein NS, Hayes M, et al. American Society of Clinical Oncology/college of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol. 2010;28(16):2784–95.CrossRef
12.
go back to reference Perou CM. Molecular stratification of triple-negative breast cancers. Oncologist. 2011;16(Suppl 1):61–70.CrossRef Perou CM. Molecular stratification of triple-negative breast cancers. Oncologist. 2011;16(Suppl 1):61–70.CrossRef
13.
go back to reference Prat A, Adamo B, Cheang MC, Anders CK, Carey LA, Perou CM. Molecular characterization of basal-like and non-basal-like triple-negative breast cancer. Oncologist. 2013;18(2):123–33.CrossRef Prat A, Adamo B, Cheang MC, Anders CK, Carey LA, Perou CM. Molecular characterization of basal-like and non-basal-like triple-negative breast cancer. Oncologist. 2013;18(2):123–33.CrossRef
14.
go back to reference Denkert C, Liedtke C, Tutt A, von Minckwitz G. Molecular alterations in triple-negative breast cancer-the road to new treatment strategies. Lancet. 2017;389(10087):2430–42.CrossRef Denkert C, Liedtke C, Tutt A, von Minckwitz G. Molecular alterations in triple-negative breast cancer-the road to new treatment strategies. Lancet. 2017;389(10087):2430–42.CrossRef
15.
go back to reference Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, 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(31):3997–4013.CrossRef Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Bilous M, Fitzgibbons P, 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(31):3997–4013.CrossRef
16.
go back to reference Bareche Y, Venet D, Ignatiadis M, Aftimos P, Piccart M, Rothe F, Sotiriou C. Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis. Ann Oncol. 2018;29(4):895–902.CrossRef Bareche Y, Venet D, Ignatiadis M, Aftimos P, Piccart M, Rothe F, Sotiriou C. Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis. Ann Oncol. 2018;29(4):895–902.CrossRef
17.
go back to reference Mancini P, Angeloni A, Risi E, Orsi E, Mezi S. Standard of care and promising new agents for triple negative metastatic breast cancer. Cancers. 2014;6(4):2187–223.CrossRef Mancini P, Angeloni A, Risi E, Orsi E, Mezi S. Standard of care and promising new agents for triple negative metastatic breast cancer. Cancers. 2014;6(4):2187–223.CrossRef
18.
go back to reference Bertucci F, Finetti P, Birnbaum D, Mamessier E. The PD1/PDL1 axis, a promising therapeutic target in aggressive breast cancers. Oncoimmunology. 2016;5(3):e1085148.CrossRef Bertucci F, Finetti P, Birnbaum D, Mamessier E. The PD1/PDL1 axis, a promising therapeutic target in aggressive breast cancers. Oncoimmunology. 2016;5(3):e1085148.CrossRef
19.
go back to reference Lord CJ, Ashworth A. PARP inhibitors: synthetic lethality in the clinic. Science. 2017;355(6330):1152–8.CrossRef Lord CJ, Ashworth A. PARP inhibitors: synthetic lethality in the clinic. Science. 2017;355(6330):1152–8.CrossRef
20.
go back to reference Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–21.CrossRef Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434(7035):917–21.CrossRef
21.
go back to reference Timms KM, Abkevich V, Hughes E, Neff C, Reid J, Morris B, Kalva S, Potter J, Tran TV, Chen J, et al. Association of BRCA1/2 defects with genomic scores predictive of DNA damage repair deficiency among breast cancer subtypes. Breast Cancer Res. 2014;16(6):475.CrossRef Timms KM, Abkevich V, Hughes E, Neff C, Reid J, Morris B, Kalva S, Potter J, Tran TV, Chen J, et al. Association of BRCA1/2 defects with genomic scores predictive of DNA damage repair deficiency among breast cancer subtypes. Breast Cancer Res. 2014;16(6):475.CrossRef
22.
go back to reference Lux MP, Janni W, Hartkopf AD, Nabieva N, Taran FA, Overkamp F, Kolberg HC, Hadji P, Tesch H, Ettl J, et al. Update breast cancer 2017 - implementation of novel therapies. Geburtshilfe Frauenheilkd. 2017;77(12):1281–90.CrossRef Lux MP, Janni W, Hartkopf AD, Nabieva N, Taran FA, Overkamp F, Kolberg HC, Hadji P, Tesch H, Ettl J, et al. Update breast cancer 2017 - implementation of novel therapies. Geburtshilfe Frauenheilkd. 2017;77(12):1281–90.CrossRef
23.
go back to reference Fasching PA, Ekici AB, Wachter DL, Hein A, Bayer CM, Haberle L, Loehberg CR, Schneider M, Jud SM, Heusinger K, et al. Breast cancer risk - from genetics to molecular understanding of pathogenesis. Geburtshilfe Frauenheilkd. 2013;73(12):1228–35.CrossRef Fasching PA, Ekici AB, Wachter DL, Hein A, Bayer CM, Haberle L, Loehberg CR, Schneider M, Jud SM, Heusinger K, et al. Breast cancer risk - from genetics to molecular understanding of pathogenesis. Geburtshilfe Frauenheilkd. 2013;73(12):1228–35.CrossRef
24.
go back to reference Couch FJ, Hart SN, Sharma P, Toland AE, Wang X, Miron P, Olson JE, Godwin AK, Pankratz VS, Olswold C, et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol. 2015;33(4):304–11.CrossRef Couch FJ, Hart SN, Sharma P, Toland AE, Wang X, Miron P, Olson JE, Godwin AK, Pankratz VS, Olswold C, et al. Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. J Clin Oncol. 2015;33(4):304–11.CrossRef
25.
go back to reference Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26(8):1275–81.CrossRef Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, Symmans WF, Gonzalez-Angulo AM, Hennessy B, Green M, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26(8):1275–81.CrossRef
26.
go back to reference von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796–804.CrossRef von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012;30(15):1796–804.CrossRef
27.
go back to reference Hahnen E, Lederer B, Hauke J, Loibl S, Krober S, Schneeweiss A, Denkert C, Fasching PA, Blohmer JU, Jackisch C, et al. Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer: secondary analysis of the GeparSixto randomized clinical trial. JAMA Oncol. 2017;3(10):1378–85.CrossRef Hahnen E, Lederer B, Hauke J, Loibl S, Krober S, Schneeweiss A, Denkert C, Fasching PA, Blohmer JU, Jackisch C, et al. Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer: secondary analysis of the GeparSixto randomized clinical trial. JAMA Oncol. 2017;3(10):1378–85.CrossRef
28.
go back to reference Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015;33(1):13–21.CrossRef Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione CT, Tolaney SM, Kuzma CS, Pluard TJ, Somlo G, Port ER, et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J Clin Oncol. 2015;33(1):13–21.CrossRef
29.
go back to reference Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, Mierzwa T, Szwiec M, Wisniowski R, Siolek M, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol. 2010;28(3):375–9.CrossRef Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, Mierzwa T, Szwiec M, Wisniowski R, Siolek M, et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol. 2010;28(3):375–9.CrossRef
30.
go back to reference von Minckwitz G, Timms K, Untch M, Elkin EP, Hahnen E, Fasching PA, Schneeweiss A, Salat CT, Rezai M, Blohmer J-U, Zahm D-M, Jackisch C, Gerber B, Klare P, Kümmel S, Paepke S, Schmutzler R, Chau S, Reid J, Hartman A-R, Nekljudova V, Weber KE, Loibl S. Homologous repair deficiency (HRD) as measure to predict the effect of carboplatin on survival in the neoadjuvant phase II trial GeparSixto in triple-negativeearly breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium. Cancer Res. 2017;77(4 Suppl):Abstract nr P1-09-02. von Minckwitz G, Timms K, Untch M, Elkin EP, Hahnen E, Fasching PA, Schneeweiss A, Salat CT, Rezai M, Blohmer J-U, Zahm D-M, Jackisch C, Gerber B, Klare P, Kümmel S, Paepke S, Schmutzler R, Chau S, Reid J, Hartman A-R, Nekljudova V, Weber KE, Loibl S. Homologous repair deficiency (HRD) as measure to predict the effect of carboplatin on survival in the neoadjuvant phase II trial GeparSixto in triple-negativeearly breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium. Cancer Res. 2017;77(4 Suppl):Abstract nr P1-09-02.
31.
go back to reference Von Minckwitz G, Loibl S, Schneeweiss A, Salat CT, Rezai M, Zahm D-M, Klare P, Blohmer J-U, Tesch H, Khandan F, Fasching PA, Jakisch C, Nekljudova V, Untch M. Abstract S2-04: Early survival analysis of the randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto). Cancer Res. 2016;76:S2-04. https://doi.org/10.1158/1538-7445.SABCS15-S2-04. Von Minckwitz G, Loibl S, Schneeweiss A, Salat CT, Rezai M, Zahm D-M, Klare P, Blohmer J-U, Tesch H, Khandan F, Fasching PA, Jakisch C, Nekljudova V, Untch M. Abstract S2-04: Early survival analysis of the randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto). Cancer Res. 2016;76:S2-04. https://​doi.​org/​10.​1158/​1538-7445.​SABCS15-S2-04.
32.
go back to reference Fasching PA, Loibl S, Eidtmann H, Tesch H, Untch M, Hilfrich J, Schem C, Rezai M, Gerber B, Costa SD, Blohmer JU, Fehm TN, Huober J, Liedtke C, Müller V, Nekljudova V, Weber K, Rack B, Rübner M, Wang L, Ingle JN, Weinshilboum RM, von Minckwitz G, Couch F. BRCA mutations, therapy response and prognosis in the neoadjuvant GeparQuinto study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium. Cancer Res. 2016;76(4 Suppl):Abstract nr S5-06. Fasching PA, Loibl S, Eidtmann H, Tesch H, Untch M, Hilfrich J, Schem C, Rezai M, Gerber B, Costa SD, Blohmer JU, Fehm TN, Huober J, Liedtke C, Müller V, Nekljudova V, Weber K, Rack B, Rübner M, Wang L, Ingle JN, Weinshilboum RM, von Minckwitz G, Couch F. BRCA mutations, therapy response and prognosis in the neoadjuvant GeparQuinto study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium. Cancer Res. 2016;76(4 Suppl):Abstract nr S5-06.
33.
go back to reference Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong CO, Calogrias D, Buraimoh A, et al. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol. 2010;28(7):1145–53.CrossRef Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong CO, Calogrias D, Buraimoh A, et al. Efficacy of neoadjuvant cisplatin in triple-negative breast cancer. J Clin Oncol. 2010;28(7):1145–53.CrossRef
34.
go back to reference Gluz O, Nitz U, Liedtke C, Christgen M, Grischke EM, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, et al. Comparison of neoadjuvant nab-paclitaxel+carboplatin vs nab-paclitaxel+gemcitabine in triple-negative breast cancer: randomized WSG-ADAPT-TN trial results. J Natl Cancer Inst. 2018;110(6):628–37.CrossRef Gluz O, Nitz U, Liedtke C, Christgen M, Grischke EM, Forstbauer H, Braun M, Warm M, Hackmann J, Uleer C, et al. Comparison of neoadjuvant nab-paclitaxel+carboplatin vs nab-paclitaxel+gemcitabine in triple-negative breast cancer: randomized WSG-ADAPT-TN trial results. J Natl Cancer Inst. 2018;110(6):628–37.CrossRef
35.
go back to reference von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, Blohmer JU, Jackisch C, Paepke S, Gerber B, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014;15(7):747–56.CrossRef von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, Blohmer JU, Jackisch C, Paepke S, Gerber B, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014;15(7):747–56.CrossRef
36.
go back to reference Von Minckwitz G, Hahnen E, Fasching P, Hauke J, Schneeweiss A, Salat C, Rezai M, Blohmer J-U, Zahm D, Jackisch C. Pathological complete response (pCR) rates after carboplatin-containing neoadjuvant chemotherapy in patients with germline BRCA (g BRCA) mutation and triple-negative breast cancer (TNBC): results from GeparSixto. J Clin Oncol. 2014;32(15 Suppl):1005. Von Minckwitz G, Hahnen E, Fasching P, Hauke J, Schneeweiss A, Salat C, Rezai M, Blohmer J-U, Zahm D, Jackisch C. Pathological complete response (pCR) rates after carboplatin-containing neoadjuvant chemotherapy in patients with germline BRCA (g BRCA) mutation and triple-negative breast cancer (TNBC): results from GeparSixto. J Clin Oncol. 2014;32(15 Suppl):1005.
37.
go back to reference Zhang J, Powell SN. The role of the BRCA1 tumor suppressor in DNA double-strand break repair. Mol Cancer Res. 2005;3(10):531–9.CrossRef Zhang J, Powell SN. The role of the BRCA1 tumor suppressor in DNA double-strand break repair. Mol Cancer Res. 2005;3(10):531–9.CrossRef
38.
go back to reference Bhattacharyya A, Ear US, Koller BH, Weichselbaum RR, Bishop DK. The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. J Biol Chem. 2000;275(31):23899–903.CrossRef Bhattacharyya A, Ear US, Koller BH, Weichselbaum RR, Bishop DK. The breast cancer susceptibility gene BRCA1 is required for subnuclear assembly of Rad51 and survival following treatment with the DNA cross-linking agent cisplatin. J Biol Chem. 2000;275(31):23899–903.CrossRef
39.
go back to reference Beheshti F, Hassanian SM, Khazaei M, Hosseini M, ShahidSales S, Hasanzadeh M, Maftouh M, Ferns GA, Avan A. Genetic variation in the DNA repair pathway as a potential determinant of response to platinum-based chemotherapy in breast cancer. J Cell Physiol. 2018;233(4):2752–8.CrossRef Beheshti F, Hassanian SM, Khazaei M, Hosseini M, ShahidSales S, Hasanzadeh M, Maftouh M, Ferns GA, Avan A. Genetic variation in the DNA repair pathway as a potential determinant of response to platinum-based chemotherapy in breast cancer. J Cell Physiol. 2018;233(4):2752–8.CrossRef
40.
go back to reference Sharma P, Barlow WE, Godwin AK, Pathak H, Isakova K, Williams D, Timms KM, Hartman AR, Wenstrup RJ, Linden HM, et al. Impact of homologous recombination deficiency biomarkers on outcomes in patients with triple-negative breast cancer treated with doxorubicin-based adjuvant chemotherapy (SWOG S9313). Ann Oncol. 2018;29(3):654–60. Sharma P, Barlow WE, Godwin AK, Pathak H, Isakova K, Williams D, Timms KM, Hartman AR, Wenstrup RJ, Linden HM, et al. Impact of homologous recombination deficiency biomarkers on outcomes in patients with triple-negative breast cancer treated with doxorubicin-based adjuvant chemotherapy (SWOG S9313). Ann Oncol. 2018;29(3):654–60.
41.
go back to reference Telli ML, Hellyer J, Audeh W, Jensen KC, Bose S, Timms KM, Gutin A, Abkevich V, Peterson RN, Neff C, et al. Homologous recombination deficiency (HRD) status predicts response to standard neoadjuvant chemotherapy in patients with triple-negative or BRCA1/2 mutation-associated breast cancer. Breast Cancer Res Treat. 2018;168(3):625–30.CrossRef Telli ML, Hellyer J, Audeh W, Jensen KC, Bose S, Timms KM, Gutin A, Abkevich V, Peterson RN, Neff C, et al. Homologous recombination deficiency (HRD) status predicts response to standard neoadjuvant chemotherapy in patients with triple-negative or BRCA1/2 mutation-associated breast cancer. Breast Cancer Res Treat. 2018;168(3):625–30.CrossRef
42.
go back to reference Zhao EY, Shen Y, Pleasance E, Kasaian K, Leelakumari S, Jones M, Bose P, Ch'ng C, Reisle C, Eirew P, et al. Homologous recombination deficiency and platinum-based therapy outcomes in advanced breast cancer. Clin Cancer Res. 2017;23(24):7521–30.CrossRef Zhao EY, Shen Y, Pleasance E, Kasaian K, Leelakumari S, Jones M, Bose P, Ch'ng C, Reisle C, Eirew P, et al. Homologous recombination deficiency and platinum-based therapy outcomes in advanced breast cancer. Clin Cancer Res. 2017;23(24):7521–30.CrossRef
43.
go back to reference Beckmann MW, Brucker C, Hanf V, Rauh C, Bani MR, Knob S, Petsch S, Schick S, Fasching PA, Hartmann A, et al. Quality assured health care in certified breast centers and improvement of the prognosis of breast cancer patients. Onkologie. 2011;34(7):362–7.CrossRef Beckmann MW, Brucker C, Hanf V, Rauh C, Bani MR, Knob S, Petsch S, Schick S, Fasching PA, Hartmann A, et al. Quality assured health care in certified breast centers and improvement of the prognosis of breast cancer patients. Onkologie. 2011;34(7):362–7.CrossRef
44.
go back to reference Kowalski C, Ferencz J, Brucker SY, Kreienberg R, Wesselmann S. Quality of care in breast cancer centers: results of benchmarking by the German cancer society and German society for breast diseases. Breast. 2015;24(2):118–23.CrossRef Kowalski C, Ferencz J, Brucker SY, Kreienberg R, Wesselmann S. Quality of care in breast cancer centers: results of benchmarking by the German cancer society and German society for breast diseases. Breast. 2015;24(2):118–23.CrossRef
45.
go back to reference Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. the value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19(5):403–10.CrossRef Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. the value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991;19(5):403–10.CrossRef
46.
go back to reference Fasching PA, Heusinger K, Haeberle L, Niklos M, Hein A, Bayer CM, Rauh C, Schulz-Wendtland R, Bani MR, Schrauder M, et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer. 2011;11:486.CrossRef Fasching PA, Heusinger K, Haeberle L, Niklos M, Hein A, Bayer CM, Rauh C, Schulz-Wendtland R, Bani MR, Schrauder M, et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer. 2011;11:486.CrossRef
47.
go back to reference Sauter G, Lee J, Bartlett JM, Slamon DJ, Press MF. Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol. 2009;27(8):1323–33.CrossRef Sauter G, Lee J, Bartlett JM, Slamon DJ, Press MF. Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol. 2009;27(8):1323–33.CrossRef
48.
go back to reference Telli ML, Timms KM, Reid J, Hennessy B, Mills GB, Jensen KC, Szallasi Z, Barry WT, Winer EP, Tung NM. Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer. Clin Cancer Res. 2016;22(15):3764–73.CrossRef Telli ML, Timms KM, Reid J, Hennessy B, Mills GB, Jensen KC, Szallasi Z, Barry WT, Winer EP, Tung NM. Homologous recombination deficiency (HRD) score predicts response to platinum-containing neoadjuvant chemotherapy in patients with triple-negative breast cancer. Clin Cancer Res. 2016;22(15):3764–73.CrossRef
49.
go back to reference von Wahlde MK, Timms KM, Chagpar A, Wali VB, Jiang T, Bossuyt V, Saglam O, Reid J, Gutin A, Neff C, et al. Intratumor heterogeneity of homologous recombination deficiency in primary breast cancer. Clin Cancer Res. 2017;23(5):1193–9.CrossRef von Wahlde MK, Timms KM, Chagpar A, Wali VB, Jiang T, Bossuyt V, Saglam O, Reid J, Gutin A, Neff C, et al. Intratumor heterogeneity of homologous recombination deficiency in primary breast cancer. Clin Cancer Res. 2017;23(5):1193–9.CrossRef
50.
go back to reference Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, Budczies J, Huober J, Klauschen F, Furlanetto J, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.CrossRef Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, Budczies J, Huober J, Klauschen F, Furlanetto J, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.CrossRef
51.
go back to reference Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, Kronenwett R, Pfitzner BM, Salat C, Loi S, Schmitt WD, et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015;33(9):983–91.CrossRef Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, Kronenwett R, Pfitzner BM, Salat C, Loi S, Schmitt WD, et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015;33(9):983–91.CrossRef
52.
go back to reference Tun N, Villani G, Ong K, Yoe L, Bo Z. Risk of having BRCA1 mutation in high-risk women with triple-negative breast cancer: a meta-analysis. Clin Genet. 2014;85(1):43–8.CrossRef Tun N, Villani G, Ong K, Yoe L, Bo Z. Risk of having BRCA1 mutation in high-risk women with triple-negative breast cancer: a meta-analysis. Clin Genet. 2014;85(1):43–8.CrossRef
53.
go back to reference Mavaddat N, Barrowdale D, Andrulis I, Domchek S, Eccles D, Nevanlinna H, Ramus S, Spurdle A, Robson M, Sherman M. HEBON; EMBRACE; GEMO study collaborators; kCon-fab investigators; SWE-BRCA collaborators; consortium of investigators of modifiers of BRCA1/2. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomark Prev. 2012;21:134–47.CrossRef Mavaddat N, Barrowdale D, Andrulis I, Domchek S, Eccles D, Nevanlinna H, Ramus S, Spurdle A, Robson M, Sherman M. HEBON; EMBRACE; GEMO study collaborators; kCon-fab investigators; SWE-BRCA collaborators; consortium of investigators of modifiers of BRCA1/2. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the consortium of investigators of modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomark Prev. 2012;21:134–47.CrossRef
54.
go back to reference Krammer J, Pinker-Domenig K, Robson ME, Gonen M, Bernard-Davila B, Morris EA, Mangino DA, Jochelson MS. Breast cancer detection and tumor characteristics in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2017;163(3):565–71.CrossRef Krammer J, Pinker-Domenig K, Robson ME, Gonen M, Bernard-Davila B, Morris EA, Mangino DA, Jochelson MS. Breast cancer detection and tumor characteristics in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2017;163(3):565–71.CrossRef
55.
go back to reference Davies H, Glodzik D, Morganella S, Yates LR, Staaf J, Zou X, Ramakrishna M, Martin S, Boyault S, Sieuwerts AM, et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat Med. 2017;23(4):517–25.CrossRef Davies H, Glodzik D, Morganella S, Yates LR, Staaf J, Zou X, Ramakrishna M, Martin S, Boyault S, Sieuwerts AM, et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat Med. 2017;23(4):517–25.CrossRef
56.
go back to reference Chen X, He C, Han D, Zhou M, Wang Q, Tian J, Li L, Xu F, Zhou E, Yang K. The predictive value of Ki-67 before neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis. Future Oncol. 2017;13(9):843–57.CrossRef Chen X, He C, Han D, Zhou M, Wang Q, Tian J, Li L, Xu F, Zhou E, Yang K. The predictive value of Ki-67 before neoadjuvant chemotherapy for breast cancer: a systematic review and meta-analysis. Future Oncol. 2017;13(9):843–57.CrossRef
57.
go back to reference Balmativola D, Marchio C, Maule M, Chiusa L, Annaratone L, Maletta F, Montemurro F, Kulka J, Figueiredo P, Varga Z. Pathological non-response to chemotherapy in a neoadjuvant setting of breast cancer: an inter-institutional study. Breast Cancer Res Treat. 2014;148(3):511–23.CrossRef Balmativola D, Marchio C, Maule M, Chiusa L, Annaratone L, Maletta F, Montemurro F, Kulka J, Figueiredo P, Varga Z. Pathological non-response to chemotherapy in a neoadjuvant setting of breast cancer: an inter-institutional study. Breast Cancer Res Treat. 2014;148(3):511–23.CrossRef
58.
go back to reference Vörös A, Csörgő E, Kővári B, Lázár P, Kelemen G, Rusz O, Nyári T, Cserni G. Different methods of pretreatment Ki-67 labeling index evaluation in core biopsies of breast cancer patients treated with neoadjuvant chemotherapy and their relation to response to therapy. Pathol Oncol Res. 2015;21(1):147–55.CrossRef Vörös A, Csörgő E, Kővári B, Lázár P, Kelemen G, Rusz O, Nyári T, Cserni G. Different methods of pretreatment Ki-67 labeling index evaluation in core biopsies of breast cancer patients treated with neoadjuvant chemotherapy and their relation to response to therapy. Pathol Oncol Res. 2015;21(1):147–55.CrossRef
59.
go back to reference Würfel F, Erber R, Hübner H, Hein A, Lux M, Jud S, Kremer A, Kranich H, Mackensen A, Häberle L, et al. TILGen: a program to investigate immune targets in breast cancer patients - first results on the influence of tumor-infiltrating lymphocytes. Breast Care. 2018;13:8–14.CrossRef Würfel F, Erber R, Hübner H, Hein A, Lux M, Jud S, Kremer A, Kranich H, Mackensen A, Häberle L, et al. TILGen: a program to investigate immune targets in breast cancer patients - first results on the influence of tumor-infiltrating lymphocytes. Breast Care. 2018;13:8–14.CrossRef
60.
go back to reference Nitiss JL. Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer. 2009;9(5):338–50.CrossRef Nitiss JL. Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer. 2009;9(5):338–50.CrossRef
61.
go back to reference Misteli T, Soutoglou E. The emerging role of nuclear architecture in DNA repair and genome maintenance. Nat Rev Mol Cell Biol. 2009;10(4):243–54.CrossRef Misteli T, Soutoglou E. The emerging role of nuclear architecture in DNA repair and genome maintenance. Nat Rev Mol Cell Biol. 2009;10(4):243–54.CrossRef
Metadata
Title
Prediction of pathological complete response and prognosis in patients with neoadjuvant treatment for triple-negative breast cancer
Authors
Paul Gass
Michael P. Lux
Claudia Rauh
Alexander Hein
Mayada R. Bani
Cornelia Fiessler
Arndt Hartmann
Lothar Häberle
Jutta Pretscher
Ramona Erber
David L. Wachter
Rüdiger Schulz-Wendtland
Matthias W. Beckmann
Peter A. Fasching
Marius Wunderle
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4925-1

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine