Abstract
Platinum agents such as cisplatin and carboplatin are DNA-damaging agents with activity in breast cancer (BC), particularly in the triple negative (TN) subgroup. The utility of platinum agents, in addition to standard neoadjuvant chemotherapy (NAC), is controversial. To assess the activity of platinum agents in patients with TNBC treated with NAC, we performed a systematic review and meta-analysis of all published studies. A search of PubMed, EMBASE, the Web of Science, SCOPUS, and the Cochrane Central Register of Controlled Trials was performed to identify studies that investigated platinum-based NAC in patients with TNBC. Random effect models were adopted to estimate the summary risk ratio (RR), and the publication bias was evaluated using a funnel plot and Egger’s regression asymmetry test. The primary endpoints were the pooled rate of the pathologic complete response (pCR) and the RR to obtain a pCR in patients treated versus not treated with NAC containing platinum agents. 28 studies were included (six randomized controlled trials and 22 retrospective or prospective studies) for a total of 1,598 TNBC patients. Overall, the pooled rate of pCR in patients treated with platinum-based NAC was 45 %. In randomized trials, NAC containing cisplatin or carboplatin significantly increased the rate of pCR compared with nonplatinum agents (RR = 1.45, 95 % CI 1.25–1.68; P < 0.0001). Compared with non-TN, TNBCs were associated with a threefold increase in the pCR rate when treated with platinum-based NAC (RR 3.32, 95 % CI 2.39–4.61; P < 0.0001). In conclusion, pCR rates increase significantly with the addition of cisplatin or carboplatin in TNBC compared with NAC containing no platinum drugs. TN status is a predictor of benefit from platinum-based NAC.
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Liedtke C, Mazouni C, Hess KR et al (2008) Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 26(8):1275–1281
Carey LA, Dees EC, Sawyer L et al (2007) The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8):2329–2334
von Minckwitz G, Untch M, Blohmer JU et al (2012) Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 30(15):1796–1804
Cortazar P, Zhang L, Untch M et al (2012) Meta-analysis results from the collaborative trials in neoadjuvant breast cancer (CTNeoBC). Cancer Res 72:93
Perou CM (2010) Molecular stratification of triple-negative breast cancer. Oncologist 15(5s):39–48
Byrski T, Gronwald J, Huzarski T et al (2010) Pathologic complete response rates in young women with BRCA 1 positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol 28(375–379):18
Silver DP, Richardson AL, Eklund AC et al (2010) Efficacy of neoadjuvant cisplatin in triple negative breast cancer. J Clin Oncol 28:1145–1153
Sikov WM, Berry DA, Perou CM et al Impact of the addition of carboplatin (Cb) and/or bevacizumab (B) to neoadjuvant weekly paclitaxel (P) followed by dose-dense AC on pathologic complete response (pCR) rates in triple-negative breast cancer (TNBC): CALGB 40603(Alliance). http://www.abstracts2view.com/sabcs13/view.php?nu=SABCS13L_458&terms. Accessed 20 Dec 2013
Von Minckwitz G, Schneeweiss A, Salat C et al (2013) A randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive early breast cancer (GeparSixto). J Clin Oncol 31(suppl abstr):1004
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188
Alba E, Chacon JI, Lluch A et al (2012) A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study. Breast Cancer Res Treat 136(2):487–493
Chang HR, Glaspy J, Allison MA et al (2010) Differential response of triple-negative breast cancer to a docetaxel and carboplatin-based neoadjuvant treatment. Cancer 116(18):4227–4237
Chen XS, Nie XQ, Chen CM et al (2010) Weekly paclitaxel plus carboplatin is an effective nonanthracycline-containing regimen as neoadjuvant chemotherapy for breast cancer. Ann Oncol 21(5):961–967
Sikov WM, Dizon DS, Strenger R et al (2009) Frequent pathologic complete responses in aggressive stages II to III breast cancers with every-4-week carboplatin and weekly paclitaxel with or without trastuzumab: a Brown University Oncology Group Study. J Clin Oncol 27(28):4693–4700
Yerushalmi R, Hayes MM, Gelmon KA et al (2009) A phase II trial of a neoadjuvant platinum regimen for locally advanced breast cancer: pathologic response, long-term follow-up, and correlation with biomarkers. Clin Breast Cancer 9(3):166–172
Frasci G, Comella P, Rinaldo M et al (2009) Preoperative weekly cisplatin–epirubicin–paclitaxel with G-CSF support in triple-negative large operable breast cancer. Ann Oncol 20(7):1185–1192
Torrisi R, Balduzzi A, Ghisini R et al (2008) Tailored preoperative treatment of locally advanced triple negative (hormone receptor negative and HER2 negative) breast cancer with epirubicin, cisplatin, and infusional fluorouracil followed by weekly paclitaxel. Cancer Chemother Pharmacol 62(4):667–672
Julka PK, Chacko RT, Nag S et al (2008) A phase II study of sequential neoadjuvant gemcitabine plus doxorubicin followed by gemcitabine plus cisplatin in patients with operable breast cancer: prediction of response using molecular profiling. Br J Cancer 98(8):1327–1335
Sinclair NF, Abu-Khalaf NN, Rizack T et al (2012) Neoadjuvant weekly nab-paclitaxel (wA), carboplatin (Cb) plus bevacizumab (B) with or without dose-dense doxorubicin-cyclophosphamide (ddAC) plus B in ER+/HER2-negative (HR plus) and triple-negative (TN) breast cancer (BrCa): A BrUOG study. J Clin Oncol 30(15):1045
Shinde AM, Yim JH, Kruper L et al (2012) Pathologic complete response rates observed in women with locally advanced and inflammatory breast cancer receiving neoadjuvant carboplatin and paclitaxel. J Clin Oncol 30(15):1035
Rahal MM, Ramadan H, Hassan E et al (2010) Neoadjuvant platinum containing regimen for locally advanced triple negative breast cancer. Ann Oncol 21(8s):114–115
Diaz-Correa E, Singh C, Pereira S (2011) Neoadjuvant chemotherapy (NAC) consisting in dose-dense doxorubicin plus cyclophosphamide followed by cisplatin plus taxane for locoregional advanced triple-negative breast cancer (LATNBC). J Clin Oncol 29(suppl; abstr e11562)
Fei F, Du Y, Gu X et al (2012) A retrospective analysis of platinum-based neoadjuvant chemotherapy for local advanced triple negative breast cancer. Ann Oncol 23(9s):130
Mayer IA, Jovanovic B, Abramson VG et al A randomized phase II neoadjuvant study of cisplatin, paclitaxel with or without everolimus (an mTOR inhibitor) in patients with stage II/III triple-negative breast cancer (TNBC). http://www.abstracts2view.com/sabcs13/view.php?nu=SABCS13L_397&terms. Accessed 20 Dec 2013
Rugo HS, Olopade O, DeMichele A et al Veliparib/carboplatin plus standard neoadjuvant therapy for high-risk breast cancer: First efficacy results from the I-SPY 2 TRIAL. http://www.abstracts2view.com/sabcs13/view.php?nu=SABCS13L_1400&terms
Kern P, Kolberg HC, Halisch A et al (2013) Updated results of neoadjuvant chemotherapy with carboplatin AUC 6 and docetaxel 75 mg/m2 in triple-negative breast cancer (TNBC). J Clin Oncol 31(suppl 26; abstr 149)
Zhang P, Yin Y, Xu B et al Carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer: a phase II clinical trial. http://www.abstracts2view.com/sabcs13/view.php?nu=SABCS13L_127&terms
Sirohi B, Arnedos M, Popat S et al (2008) Platinum-based chemotherapy in triple-negative breast cancer. Ann Oncol 19(11):1847–1852
Kim HR, Jung KH, Im SA et al (2013) Multicentre phase II trial of bevacizumab combined with docetaxel–carboplatin for the neoadjuvant treatment of triple-negative breast cancer (KCSG BR-0905). Ann Oncol 24(6):1485–1490
Hurley J, Reis IM, Rodgers SE et al (2013) The use of neoadjuvant platinum-based chemotherapy in locally advanced breast cancer that is triple negative: retrospective analysis of 144 patients. Breast Cancer Res Treat 138(3):783–794
Roy V, Pockaj BA, Allred JB et al (2013) A phase II trial of docetaxel and carboplatin administered every 2 weeks as preoperative therapy for stage II or III breast cancer NCCTG study N0338. Am J Clin Oncol 36(6):540–544
Ithimakin S, Ratanawichitrasin A, Veerasarn V et al (2013) A phase II study of the combination of gemcitabine plus carboplatin as the neoadjuvant treatment in locally advanced breast cancer. J Med Assoc Thail 96(suppl 2):S67–S74
Snider JN, Sachdev JC, Allen JW et al (2012) Pathologic complete response (pCR) with weekly nanoparticle albumin bound (nab-P) plus carboplatin (C) followed by doxorubicin plus cyclophosphamide (AC) with concurrent bevacizumab (B) for triple-negative breast cancer (TNBC). J Clin Oncol 31(suppl): abstr 1068
Tiley S, Raab RE, Bellin LS et al (2012) Results of the East Carolina Breast Center phase II trial of neoadjuvant metronomic chemotherapy in triple-negative breast cancer (NCT00542191). J Clin Oncol 30(15 suppl 1):e11550
Telli ML, Kurian AW, Jensen KC et al (2011) A phase II study of gemcitabine and carboplatin (GC) plus iniparib (BSI-201) as neoadjuvant therapy for triple-negative and BRCA1/2 mutation-associated breast cancer. Cancer Res 71(24 suppl 3):abstract P3-14-08
Mrozek E, Lustberg MB, Knopp MV et al (2010) Phase II trial of neoadjuvant chemotherapy (NCT) with weekly nanoparticle albumin-bound paclitaxel (Nab-P), carboplatin (CBP), and bevacizumab (BEV) in women with clinical stages II-III breast cancer (BC): Pathologic response prediction by changes in angiogenic volume (AV) by dynamic contrast magnetic resonance imaging (DCE-MRI). J Clin Oncol 28(15 suppl 1):abstr 604
Gianni L, Pienkowski T, Im YH et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13(1):25–32
Piccart-Gebhart M, Holmes AP, de Azambuja E et al The association between event-free survival and pathological complete response to neoadjuvant lapatinib, trastuzumab or their combination in HER2-positive breast cancer. Survival follow-up analysis of the NeoALTTO study (BIG 1-06). http://www.abstracts2view.com/sabcs13/view.php?nu=SABCS13L_877&terms. Accessed 20 Dec 2013
Greenup R, Buchanan A, Lorizio W et al (2013) Prevalence of BRCA mutations among women with triple-negative breast cancer (TNBC) in a genetic counselling cohort. Ann Surg Oncol 20(10):3254–3258
Bayraktar S, Gutierrez-Barrera AM, Liu D et al (2011) Outcome of triple-negative breast cancer in patients with or without deleterious BRCA mutations. Breast Cancer Res Treat 130(1):145–153
Lips EH, Mulder L, Oonk A et al (2013) Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers. Br J Cancer 108(10):2172–2177
Masuda H, Baggerly KA, Wang Y et al (2013) Differential response to neoadjuvant chemotherapy among 7 triple-negative breast cancer molecular subtypes. Clin Cancer Res 19(19):5533–5540
Gerber B, Loibl S, Eidtmann H et al (2013) Neoadjuvant bevacizumab and anthracycline–taxane-based chemotherapy in 678 triple-negative primary breast cancers; results from the geparquinto study (GBG 44). Ann Oncol 24(12):2978–2984
Bernsdorf M, Ingvar C, Jörgensen L et al (2011) Effect of adding gefitinib to neoadjuvant chemotherapy in estrogen receptor negative early breast cancer in a randomized phase II trial. Breast Cancer Res Treat 126(2):463–470
von Minckwitz G, Blohmer JU, Costa SD et al (2013) Response-guided neoadjuvant chemotherapy for breast cancer. J Clin Oncol 31(29):3623–3630
Balko JM, Giltnane J, Wang K et al (2013) Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Cancer Discov 19(23):6353
Koolen BB, Pengel KE, Wesseling J et al (2014) Sequential (18)F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy. Eur J Nucl Med Mol Imaging 41(1):32–40
Groheux D, Hindié E, Giacchetti S et al (2012) Triple-negative breast cancer: early assessment with 18F-FDG PET/CT during neoadjuvant chemotherapy identifies patients who are unlikely to achieve a pathologic complete response and are at a high risk of early relapse. J Nucl Med 53(2):249–254
Denkert C, Loibl S, Müller BM et al (2013) Ki67 levels as predictive and prognostic parameters in pretherapeutic breast cancer core biopsies: a translational investigation in the neoadjuvant GeparTrio trial. Ann Oncol 24(11):2786–2793
Abdel-Fatah TM, Perry C, Dickinson P et al (2013) Bcl2 is an independent prognostic marker of triple negative breast cancer (TNBC) and predicts response to anthracycline combination (ATC) chemotherapy (CT) in adjuvant and neoadjuvant settings. Ann Oncol 24(11):2801–2807
Dennison JB, Molina JR, Mitra S et al (2013) Lactate dehydrogenase B: a metabolic marker of response to neoadjuvant chemotherapy in breast cancer. Clin Cancer Res 19(13):3703–3713
Li XR, Liu M, Zhang YJ et al (2011) CK5/6, EGFR, Ki-67, cyclin D1, and nm23-H1 protein expressions as predictors of pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer patients. Med Oncol 28(Suppl 1):S129–S134
Sakuma K, Kurosumi M, Oba H et al (2011) Pathological tumor response to neoadjuvant chemotherapy using anthracycline and taxanes in patients with triple-negative breast cancer. Exp Ther Med 2(2):257–264
Huober J, von Minckwitz G, Denkert C et al (2010) Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat 124(1):133–140
Liu M, Mo QG, Wei CY et al (2013) Platinum-based chemotherapy in triple-negative breast cancer: a meta-analysis. Oncol Lett 5(3):983–991
Carrick S, Ghersi D, Wilcken N, Simes J (2004) Platinum containing regimens for metastatic breast cancer. Cochrane Database Syst Rev 3:CD003374
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Petrelli, F., Coinu, A., Borgonovo, K. et al. The value of platinum agents as neoadjuvant chemotherapy in triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat 144, 223–232 (2014). https://doi.org/10.1007/s10549-014-2876-z
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DOI: https://doi.org/10.1007/s10549-014-2876-z