Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2015

01-06-2015 | Clinical Trial

Relative dose intensity and therapy efficacy in different breast cancer molecular subtypes: a retrospective study of early stage breast cancer patients treated with neoadjuvant chemotherapy

Authors: Jia-qi Yuan, Shou-man Wang, Li–li Tang, Jie Mao, Yu-hui Wu, Jian Hai, Sha-yang Luo, Hui-ying Ou, Lei Guo, Li-qiu Liao, Jun Huang, Yan Li, Zhi Xiao, Ke-jing Zhang, Na Luo, Fei-yu Chen

Published in: Breast Cancer Research and Treatment | Issue 2/2015

Login to get access

Abstract

To investigate the relationship between chemotherapy dose intensity and therapy efficacy of different molecular subtypes. Clinical and pathological features of the patients with breast cancer were retreived from the hospital records. 315 patients were analyzed (251 showed clinical response, 38 acquired pCR). Patients with positive ER status, negative PR status, higher Ki67 level and higher RTDI had better therapy response. 13.5 and 84.5 % were identified the benchmark of Ki67 and RTDI, respectively. As the result of interior-subgroup comparison, luminal subgroups acquired better response rate when RTDI ≥ 84.5 %. In patients of luminal breast cancer, tumor size change arose from increasing of dose intensity and finally showed reached a plateau after RTDI ≥ 95 % (r 2 = 0.303, p < 0.001). As the result of intersubgroup comparison, TNBC patients were more likely to acquired better clinical and pathology response when RDTI < 84.5 %. Ki67 change arose sharply from increasing of dose intensity when RDTI < 84.5 % (r 2 = 0.656, p < 0.001), whereas the regression curve showed a terminal plateau in patients of RDTI ≥ 84.5 % (r 2 = 0.427, p < 0.001). Given lower RTDI, luminal patients are less likely to achieve response, and TNBC patients are associated with higher response rate. Dissimilar of therapy efficacy between luminal subtype and TNBC becomes inconspicuous as RTDI rises. Chemosensitivity may associate with dose intensity, especially in luminal subtypes, and tailored therapeutic strategies should be considered.
Literature
1.
2.
go back to reference Kaufmann M, von Minckwitz G, Bear HD et al (2007) Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol 18:1927–1934CrossRefPubMed Kaufmann M, von Minckwitz G, Bear HD et al (2007) Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol 18:1927–1934CrossRefPubMed
3.
4.
go back to reference Kim SI, Sohn J, Koo JS et al (2010) Molecular subtypes and tumor response to NAC in patients with locally advanced breast cancer. Oncology 79:324–330CrossRefPubMed Kim SI, Sohn J, Koo JS et al (2010) Molecular subtypes and tumor response to NAC in patients with locally advanced breast cancer. Oncology 79:324–330CrossRefPubMed
5.
go back to reference Sandy J, Della-Fiorentina S (2013) Relative dose intensity in early stage breast cancer chemotherapy: a retrospective analysis of incidence, risk factors and outcomes at a south-west Sydney cancer clinic. J Clin Oncol 9(4):365–372 Sandy J, Della-Fiorentina S (2013) Relative dose intensity in early stage breast cancer chemotherapy: a retrospective analysis of incidence, risk factors and outcomes at a south-west Sydney cancer clinic. J Clin Oncol 9(4):365–372
6.
go back to reference Loibl S, Skacel T, Nekljudova V et al (2011) Evaluation the impact of relative total dose intensity on patients` short and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer-a pooled analysis. BMC Cancer 11:131CrossRefPubMedCentralPubMed Loibl S, Skacel T, Nekljudova V et al (2011) Evaluation the impact of relative total dose intensity on patients` short and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer-a pooled analysis. BMC Cancer 11:131CrossRefPubMedCentralPubMed
7.
go back to reference Ring AE, Smith IE, Ashley S, Fulford LG, Lakhani SR (2004) Oestrogen receptor status, pathological complete response and prognosis in patients receiving NAC for early breast cancer. Br J Cancer 91:2012–2017CrossRefPubMedCentralPubMed Ring AE, Smith IE, Ashley S, Fulford LG, Lakhani SR (2004) Oestrogen receptor status, pathological complete response and prognosis in patients receiving NAC for early breast cancer. Br J Cancer 91:2012–2017CrossRefPubMedCentralPubMed
8.
go back to reference Yoo C, Ahn J-H, Jung KH et al (2012) Impact of immunohistochemistry based molecular subtypes on chemosensitivity and survival patients with breast cancer following NAC. J Breast Cancer 15(2):203–210CrossRefPubMedCentralPubMed Yoo C, Ahn J-H, Jung KH et al (2012) Impact of immunohistochemistry based molecular subtypes on chemosensitivity and survival patients with breast cancer following NAC. J Breast Cancer 15(2):203–210CrossRefPubMedCentralPubMed
9.
go back to reference 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 136:487–493CrossRefPubMed 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 136:487–493CrossRefPubMed
10.
go back to reference Urruticoechea A, Smith IE, Dowsett M (2005) Proliferation marker Ki67 in early breast cancer. J Clin Oncol 23:7212–7220CrossRefPubMed Urruticoechea A, Smith IE, Dowsett M (2005) Proliferation marker Ki67 in early breast cancer. J Clin Oncol 23:7212–7220CrossRefPubMed
11.
go back to reference Fasching PA, Heusinger K, Haeberle L, Niklos M, Hein A, Bayer CM et al (2011) Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer 11:486CrossRefPubMedCentralPubMed Fasching PA, Heusinger K, Haeberle L, Niklos M, Hein A, Bayer CM et al (2011) Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer 11:486CrossRefPubMedCentralPubMed
12.
go back to reference Matsubara N, Mukai H, Fujii S et al (2013) Different prognostic significance of Ki67 change between pre- and post-NAC in various subtypes of breast cancer. Breast Cancer Res Treat 137:203–212CrossRefPubMed Matsubara N, Mukai H, Fujii S et al (2013) Different prognostic significance of Ki67 change between pre- and post-NAC in various subtypes of breast cancer. Breast Cancer Res Treat 137:203–212CrossRefPubMed
13.
go back to reference Stewart DJ, Chiritescu G, Dahrouge S et al (2007) Chemotherapy dose-response relationships in non-small cell lung cancer and implied resistance mechanisms. Cancer Treat Rev 33(2):107–137CrossRef Stewart DJ, Chiritescu G, Dahrouge S et al (2007) Chemotherapy dose-response relationships in non-small cell lung cancer and implied resistance mechanisms. Cancer Treat Rev 33(2):107–137CrossRef
14.
go back to reference Stewart DJ, Raaphorst GP, Yau J et al (1996) Active vs. passive resistance, dose-response relationships, high dose chemotherapy, and resistance modulation: a hypothesis. Invest New Drugs 14(2):115–130CrossRefPubMed Stewart DJ, Raaphorst GP, Yau J et al (1996) Active vs. passive resistance, dose-response relationships, high dose chemotherapy, and resistance modulation: a hypothesis. Invest New Drugs 14(2):115–130CrossRefPubMed
15.
go back to reference Morrow T, Siegel M, Boone S, Lawless G, Carter W (2002) Chemotherapy dose intensity determination as a quality of care measurement for managed care organisations in the treatment of early-stage breast cancer. Am J Med Qual 17:218–224CrossRefPubMed Morrow T, Siegel M, Boone S, Lawless G, Carter W (2002) Chemotherapy dose intensity determination as a quality of care measurement for managed care organisations in the treatment of early-stage breast cancer. Am J Med Qual 17:218–224CrossRefPubMed
16.
go back to reference Moon HG, Im SA, Han W et al (2012) Estrogen receptor status confers a distinct pattern of response to NAC: implications for optimal durations of therapy: distinct patterns of response according to ER expression. Breast Cancer Res Treat 134(3):1133–1140CrossRefPubMed Moon HG, Im SA, Han W et al (2012) Estrogen receptor status confers a distinct pattern of response to NAC: implications for optimal durations of therapy: distinct patterns of response according to ER expression. Breast Cancer Res Treat 134(3):1133–1140CrossRefPubMed
17.
go back to reference Sotiriou C, Neo SY, McShane LM et al (2003) Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA 100:10393–10398CrossRefPubMedCentralPubMed Sotiriou C, Neo SY, McShane LM et al (2003) Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA 100:10393–10398CrossRefPubMedCentralPubMed
18.
go back to reference Sotiriou C, Wirapati P, Loi S et al (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98:262–272CrossRefPubMed Sotiriou C, Wirapati P, Loi S et al (2006) Gene expression profiling in breast cancer: understanding the molecular basis of histologic grade to improve prognosis. J Natl Cancer Inst 98:262–272CrossRefPubMed
19.
go back to reference McGhan LJ, McCullough AE, Protheroe CA et al (2014) Androgen receptor-positive triple negative breast cancer: a unique breast cancer subtype. Ann Surg Oncol 21(2):361–367CrossRefPubMed McGhan LJ, McCullough AE, Protheroe CA et al (2014) Androgen receptor-positive triple negative breast cancer: a unique breast cancer subtype. Ann Surg Oncol 21(2):361–367CrossRefPubMed
20.
go back to reference Teschendorff* AE, Miremadi† A, Pinder† SE et al (2007) An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer. Genome Biol 8(8):R157CrossRefPubMedCentralPubMed Teschendorff* AE, Miremadi† A, Pinder† SE et al (2007) An immune response gene expression module identifies a good prognosis subtype in estrogen receptor negative breast cancer. Genome Biol 8(8):R157CrossRefPubMedCentralPubMed
21.
22.
go back to reference Emens LA, Jaffee EM (2005) Leveraging the activity of tumor vaccines with cytotoxic chemotherapy. Cancer Res 65:8059–8064CrossRefPubMed Emens LA, Jaffee EM (2005) Leveraging the activity of tumor vaccines with cytotoxic chemotherapy. Cancer Res 65:8059–8064CrossRefPubMed
23.
go back to reference Obeid M, Tesniere A, Ghiringhelli F et al (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61CrossRefPubMed Obeid M, Tesniere A, Ghiringhelli F et al (2007) Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med 13:54–61CrossRefPubMed
24.
go back to reference Apetoh L, Ghiringhelli F, Tesniere A et al (2007) Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13:1050–1059CrossRefPubMed Apetoh L, Ghiringhelli F, Tesniere A et al (2007) Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med 13:1050–1059CrossRefPubMed
25.
go back to reference Falcone T, Bedaiwy MA (2005) Fertility preservation and pregnancy outcome after malignancy. Curr Opin Obstet Gynecol 17(1):21–26CrossRefPubMed Falcone T, Bedaiwy MA (2005) Fertility preservation and pregnancy outcome after malignancy. Curr Opin Obstet Gynecol 17(1):21–26CrossRefPubMed
26.
go back to reference Sun ZY, Shen K, Lang JH et al (2003) Effect of chemotherapy to ovary function in ovarian malignancy patients undergoing conservative surgery. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 25(4):431–433PubMed Sun ZY, Shen K, Lang JH et al (2003) Effect of chemotherapy to ovary function in ovarian malignancy patients undergoing conservative surgery. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 25(4):431–433PubMed
Metadata
Title
Relative dose intensity and therapy efficacy in different breast cancer molecular subtypes: a retrospective study of early stage breast cancer patients treated with neoadjuvant chemotherapy
Authors
Jia-qi Yuan
Shou-man Wang
Li–li Tang
Jie Mao
Yu-hui Wu
Jian Hai
Sha-yang Luo
Hui-ying Ou
Lei Guo
Li-qiu Liao
Jun Huang
Yan Li
Zhi Xiao
Ke-jing Zhang
Na Luo
Fei-yu Chen
Publication date
01-06-2015
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-015-3418-z

Other articles of this Issue 2/2015

Breast Cancer Research and Treatment 2/2015 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