Expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients
Aim: To evaluate the efficacy ofthe application of various chemotherapy schemes based on the immunohistochemical study of expression patterns of proteins associated with the drug resistance P-glycoprotein (P-gp), glutathione-S-transferase (GST), metallothioneins (МТ) of breast cancer (BC) patients...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2009
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| Назва видання: | Experimental Oncology |
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| Цитувати: | Expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients / V.F. Chekhun, V.E. Zhylchuk, N.Yu. Lukyanova, A.L. Vorontsova, Yu.I. Kudryavets // Experimental Oncology. — 2009. — Т. 31, № 2. — С. 123–124. — назв. — англ. |
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irk-123456789-1357252018-06-16T03:11:16Z Expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients Chekhun, V.F. Zhylchuk, V.E. Lukyanova, N.Yu. Vorontsova, A.L. Kudryavets, Yu.I. Short communications Aim: To evaluate the efficacy ofthe application of various chemotherapy schemes based on the immunohistochemical study of expression patterns of proteins associated with the drug resistance P-glycoprotein (P-gp), glutathione-S-transferase (GST), metallothioneins (МТ) of breast cancer (BC) patients with the triple-receptor-negative (RE–, RP–, HER-2/neu–) cancer. Methods and Results: P-gp, GST and МТ expression in BC-biopsy samples from 60 BC patients was evaluated by immunohistochemical analysis. The results of the clinical observations showed that 3-years relapse-free survival rate of the patients of with P-gp, GST and МТ-positive tumors treated with taxoter + adriablastin / taxoter + cyclophosphamide (ТА/ТС), gemcitabine + carboplatin, or TC + bevacizumab was 61.5%, 78.6% and 81.2% respectively, vs 41.2% in the control group with P-gp, GST and МТ-negative tumors treated with adriablastin + cyclophosphamide (p < 0.05), while overall survival rates were 84.4%, 92.6% and 93.8% respectively vs 70.6% in the control group (p < 0.05). Conclusion: The study points on the possibility to elevate the efficiency of polychemotherapy by its individualization based on the expression patterns of Р-gp, GST and MT on tumor cells of the patients with the triple-receptor-negative BC. 2009 Article Expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients / V.F. Chekhun, V.E. Zhylchuk, N.Yu. Lukyanova, A.L. Vorontsova, Yu.I. Kudryavets // Experimental Oncology. — 2009. — Т. 31, № 2. — С. 123–124. — назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/135725 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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DSpace DC |
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English |
| topic |
Short communications Short communications |
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Short communications Short communications Chekhun, V.F. Zhylchuk, V.E. Lukyanova, N.Yu. Vorontsova, A.L. Kudryavets, Yu.I. Expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients Experimental Oncology |
| description |
Aim: To evaluate the efficacy ofthe application of various chemotherapy schemes based on the immunohistochemical study of expression
patterns of proteins associated with the drug resistance P-glycoprotein (P-gp), glutathione-S-transferase (GST), metallothioneins
(МТ) of breast cancer (BC) patients with the triple-receptor-negative (RE–, RP–, HER-2/neu–) cancer. Methods and Results: P-gp,
GST and МТ expression in BC-biopsy samples from 60 BC patients was evaluated by immunohistochemical analysis. The results
of the clinical observations showed that 3-years relapse-free survival rate of the patients of with P-gp, GST and МТ-positive tumors
treated with taxoter + adriablastin / taxoter + cyclophosphamide (ТА/ТС), gemcitabine + carboplatin, or TC + bevacizumab was
61.5%, 78.6% and 81.2% respectively, vs 41.2% in the control group with P-gp, GST and МТ-negative tumors treated with adriablastin
+ cyclophosphamide (p < 0.05), while overall survival rates were 84.4%, 92.6% and 93.8% respectively vs 70.6% in the control
group (p < 0.05). Conclusion: The study points on the possibility to elevate the efficiency of polychemotherapy by its individualization
based on the expression patterns of Р-gp, GST and MT on tumor cells of the patients with the triple-receptor-negative BC. |
| format |
Article |
| author |
Chekhun, V.F. Zhylchuk, V.E. Lukyanova, N.Yu. Vorontsova, A.L. Kudryavets, Yu.I. |
| author_facet |
Chekhun, V.F. Zhylchuk, V.E. Lukyanova, N.Yu. Vorontsova, A.L. Kudryavets, Yu.I. |
| author_sort |
Chekhun, V.F. |
| title |
Expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients |
| title_short |
Expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients |
| title_full |
Expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients |
| title_fullStr |
Expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients |
| title_full_unstemmed |
Expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients |
| title_sort |
expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2009 |
| topic_facet |
Short communications |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/135725 |
| citation_txt |
Expression of drug resistance proteins in triple-receptor-negative tumors as the basis of individualized therapy of the breast cancer patients / V.F. Chekhun, V.E. Zhylchuk, N.Yu. Lukyanova, A.L. Vorontsova, Yu.I. Kudryavets // Experimental Oncology. — 2009. — Т. 31, № 2. — С. 123–124. — назв. — англ. |
| series |
Experimental Oncology |
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2025-07-09T23:59:13Z |
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| fulltext |
Experimental Oncology 31, 123–124, 2009 (June) 123
The achievements of the modern genetics and mo
lecular biology have significantly broadened the know
ledge on the breast cancer (BC) [1]. Nowadays there are
5 types of this disease, one of which is estrogen receptor
(ER), progesterone receptor (PR), and HER2/neu
negative BC, socalled triplereceptornegative tumors.
The results of the clinical observations prove that this type
of BC is characterized by the negative forecast of the
disease course, high risk of relapse and remote metas
tasis and by the low survival of the patients respectively
[2]. As there are no receptors of steroid hormones and
HER2/neu, these tumors are irresponsive to hormonal
and targeted therapy. Usually during the treatment of this
type of the BC the polychemotherapy (PCT) scheme
involving anthracyclines, more often — the АС ones (with
further possible involvement of taxanes to the scheme),
is applied [3, 4]. At the same time, there are data accor
ding to which a rather substantial percent of the tumors
is irresponsive to the standard accepted chemotherapy
schemes [5]. Due to this fact, the researches directed
on individual chemotherapy with the patients with the
triplereceptornegative tumors are currently in spite
of interest. It is known that the BC resistance to the an
thracycline antibiotics, phytogenic alkaloids and taxanes
is connected with the increased expression of Pglyco
protein (Рgp). Expression of glutathioneStransferase
(GST) and metallothioneins (МТ) in the breast cancer
cells characterizes the low responsiveness to cisplatin,
chlorambucil and to other alkylating agents [6–9].
Thus, the aim of our research was the compara
tive study of the efficiency of the application of various
schemes of antitumor therapy selected by immunohis
tochemical study of peculiar features of the expression
of proteins associated with the drug resistance (Pgp,
GST and МТ) of the patients with the triplereceptor
negative (RE–, RP–, HER2/neu–) BC. Our research
included 60 patients suffering from the BC with triple
receptornegative tumors. All of these patients were
in the premenopause condition and the disease stage
corresponded to the criterion T1–2N0–2M0.
Immunohistochemical studies of the expression
of RE, RP, Pgp, GST and МТ were carried out on the
trepanbiopsy materials obtained prior to the beginning
of the treatment with the application of the generally ac
cepted method [10] with the use of specific MoAbs (Dako
Cytomation, Denmark, and Chemicon International,
Europe). At the beginning of the treatment all patients un
derwent a large fractional ТγТ and afterwards — a radical
surgery. Statistical analysis was carried out with the help
of the set of STATISTICA 6.0 software. Student’s tcrite
rion was used for evaluation defferences significance,
p < 0.05 was considered significant.
Depending on the expression patterns of Pgp,
GST and MT on BC cells, the BC patients were divided
into 4 groups:
1) Control group (n = 17): the patients were treated
according to the standard scheme adriablastin + cy
clophosphamide (АС); BC cells were negative by Pgp,
GST and МТ expression.
2) The patients (n = 13) were treated according
to the schemes taxoter + adriablastin (ТА) (n = 7) and
taxoter + cyclophosphamide (ТС) (n = 6); BC cells
express Pgp (40–80%), and GST and МТ (0–50%).
3) The patients (n = 14) were treated according to the
scheme gemcitabine + carboplatin; BC cells express
Pgp (40–80%), GST (10–50%), and МТ (0–20%).
4) The patients (n = 16) were treated according
to the scheme ТС + bevacizumab; BC cells express
Pgp (40–80%), GST (5–20%) and МТ (50–80%).
As a result of a comparative analysis, it was estab
lished that threeyear survival of the patients of the
ExprEssion of Drug rEsistancE protEins
in triplE-rEcEptor-nEgativE tumors as thE Basis
of inDiviDualizED thErapy of thE BrEast cancEr patiEnts
V.F. Chekhun, V.E. Zhylchuk, N.Yu. Lukyanova, A.L. Vorontsova, Yu.I. Kudryavets*
R.E. Kavetsky Intitute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
Aim: To evaluate the efficacy of the application of various chemotherapy schemes based on the immunohistochemical study of expression
patterns of proteins associated with the drug resistance P-glycoprotein (P-gp), glutathione-S-transferase (GST), metallothioneins
(МТ) of breast cancer (BC) patients with the triple-receptor-negative (RE–, RP–, HER-2/neu–) cancer. Methods and Results: P-gp,
GST and МТ expression in BC-biopsy samples from 60 BC patients was evaluated by immunohistochemical analysis. The results
of the clinical observations showed that 3-years relapse-free survival rate of the patients of with P-gp, GST and МТ-positive tumors
treated with taxoter + adriablastin / taxoter + cyclophosphamide (ТА/ТС), gemcitabine + carboplatin, or TC + bevacizumab was
61.5%, 78.6% and 81.2% respectively, vs 41.2% in the control group with P-gp, GST and МТ-negative tumors treated with adriablas-
tin + cyclophosphamide (p < 0.05), while overall survival rates were 84.4%, 92.6% and 93.8% respectively vs 70.6% in the control
group (p < 0.05). Conclusion: The study points on the possibility to elevate the efficiency of polychemotherapy by its individualization
based on the expression patterns of Р-gp, GST and MT on tumor cells of the patients with the triple-receptor-negative BC.
Key Words: breast cancer; drug resistance; polychemotherapy.
Received: May 5, 2009.
*Correspondence: E-mail: kudryavets@mail.ru
Abbreviations used: BC — breast cancer; GST — glutathione-S-
transferase; МТ — metallothioneins; PCT — polychemotherapy;
Р-gp — P-glycoprotein.
Exp Oncol 2009
31, 2, 123–124
124 Experimental Oncology 31, 123–124, 2009 (June)
2nd, 3rd and 4th group was significantly higher than that
of the control group.
The results of the clinical observations showed that
3years relapsefree survival rate of the patients of the
2nd, 3rd and 4th groups was 61.5%, 78.6% and 81.2% re
spectively, vs 41.2% in the control group (p < 0.05) (Table).
Analysis of overall survival of the patients with the triple
receptornegative BC has shown that in the 2nd, 3rd and
4th groups it reach 84.4%, 92.6% and 93.8% respectively,
vs 70.6% in the control group (p < 0.05). It is necessary
to note that the application of scheme TC + bevacizumab
was found to be the most efficient one. Thus, our study
has shown the possibility to elevate the efficiency of poly
chemotherapy by its individualization based on the expres
sion patterns of Рgp, GST and MT on tumor cells of the
patients with the triplereceptornegative BC.
Table. Treatment schedules and survival rate of breast cancer patients
Group PCT Scheme 3-year survival
Overall Relapse-free
1 (control) (n = 17) АС/CMF 70.6% 41.2%
2 (n = 13) ТА/ТС 84.6%* 61.5%*
3 (n = 14) Gemcitabine + carboplatin 92.6%* 78.6%*
4 (n = 16) TC + bevacizumab 93.8%* 81.2%*
*Statistically significant compared to control group.
rEfErEncEs
Sorlie T, Perou CM, Tibshirani R, 1. et al. Gene expression pa
tterns of breast carcinomas distinguish tumour subclasses with clini
cal implications. Proc Natl Acad Sci USA 2001; 98:10869–74.
Winer EP, Mayer EL. 2. Optimizing treatment of “triple
negative” breast cancer. 30th Annual San Antonio Breast Cancer
Symposium (SABCS), 2008.
Wasserman EJ, Tan AR. 3. Evolving strategies for the treat
ment of “triplenegative” breast cancer. ASCO Educational
Book; 2008.
Carey LA, Dees EC, Sawyer L, 4. et al. The triple nega
tive paradox: primary tumor chemosensitivity of breast cancer
subtypes. Clin Cancer Res 2007; 13: 2329–34.
Rouzier R, Perou CM, Symmans WF, 5. et al. Breast cancer
molecular subtypes respond differently to preoperative chemo
therapy. Clin Cancer Res 2005; 11: 5678–85.
Leonessa F, Clarke R. 6. ATP binding cassette transpor
ters and drug resistance in breast cancer. Endocrine Related
Cancer 2003; 10: 43–73.
Shpyleva SI, Yurchenko OV, Volkova KD, Lukyanova NYu, 7.
Kulik GI, Chekhun VF. Value of tumour biomarkers with the dif
ferent drug resistance phenotype for current of disease at breast
cancer patients. Oncologiya 2007; 2: 110–4 (In Russian).
Buser K, Joncourt F, Altermatt H-J, 8. et al. Breast cancer:
pretreatment drug resistance parameters (GSHsystem, ATase,
Pglycoprotein) in tumour tissue and their correlation with clinical
and prognostic characteristics. Ann Oncol 1997; 8: 335–41.
O’Driscoll L, Clynes M. 9. Molecular markers of multiple drug
resistance in breast cancer. Chemotherapy 2006; 52: 125–9.
Lukyanova NYu, Kulik GI, Yurchenko OV, 10. et al. Expression
of p53 and bcl2 proteins in epithelial ovarian carcinoma with
different grade of differentiation. Exp Oncol 2000; 22: 91–5.
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