Association of P-glycoprotein expression and response to anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer

Authors

  • Erwin Danil Yulian Department of Surgery, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia
  • Filipus Dasawala Department of Surgery, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia https://orcid.org/0000-0002-6875-7910
  • Nurjati Chairani Siregar Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia https://orcid.org/0000-0002-7333-1164

DOI:

https://doi.org/10.13181/mji.oa.225863

Keywords:

breast cancer, neoadjuvant chemotherapy, p-glycoprotein, treatment outcome

Abstract

BACKGROUND Neoadjuvant chemotherapy (NACT) has been shown to improve the overall survival of locally advanced breast cancer (LABC) patients with pathological complete response. However, the efficacy may be reduced due to chemoresistance mediated by P-glycoprotein (Pgp). This study aimed to explore the association between Pgp expression and patients’ response to NACT.

METHODS A prospective cohort study was carried out from May 2018 to October 2019 at Cipto Mangunkusumo Hospital and Koja Hospital. Treatment-naïve LABC patients were consecutively enrolled in the study. Immunohistochemistry analysis of the biopsy samples was done to semi-quantitatively measure Pgp expression. The clinical response was evaluated after 3 cycles of NACT, while the pathological response was evaluated for subjects who underwent surgery post-NACT.

RESULTS Mean age of the subjects was 46.2 (9.6) years old, and most of the cases were invasive ductal (78%) and luminal B subtype (61%). Pgp was strongly expressed in 21/27 subjects (78%). There were no differences between Pgp-positive and -negative subjects for clinical response (relative risk [RR] 1.1, 95% confidence interval [CI] 0.33–4.01, p = 0.61) and pathological response (RR 1.3, 95% CI 0.8–1.9, p = 0.22). Other clinicopathologic variables were not associated with either clinical or pathological responses.

CONCLUSIONS These results showed that Pgp is expressed in most LABC patients, but its role as a predictive factor could not be established. However, due to the limited subjects and a lack of standardized Pgp measurement, careful consideration must be done when interpreting these results.

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References

Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384(9938):164-72. https://doi.org/10.1016/S0140-6736(13)62422-8

Clarke R, Leonessa F, Trock B. Multidrug resistance/p-glycoprotein and breast cancer: review and meta-analysis. Semin Oncol. 2005;32(6 Suppl 7):S9-15. https://doi.org/10.1053/j.seminoncol.2005.09.009

Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM. Revisiting the role of efflux pumps in multidrug-resistant cancer. Nat Rev Cancer. 2018;18(7):452-64. https://doi.org/10.1038/s41568-018-0005-8

Faneyte IF, Kristel PM, van de Vijver MJ. Determining MDR1/P-glycoprotein expression in breast cancer. Int J Cancer. 2001;93(1):114-22. https://doi.org/10.1002/1097-0215(20010701)93:1<114::AID-IJC1309>3.0.CO;2-J

Rudas M, Filipits M, Taucher S, Stranzl T, Steger GG, Jakesz R, et al. Expression of MRP1, LRP and Pgp in breast carcinoma patients treated with preoperative chemotherapy. Breast Cancer Res Treat. 2003;81(2):149-57. https://doi.org/10.1023/A:1025751631115

Chintamani, Singh JP, Mittal MK, Saxena S, Bansal A, Bhatia A, et al. Role of p-glycoprotein expression in predicting response to neoadjuvant chemotherapy in breast cancer-a prospective clinical study. World J Surg Oncol. 2005;3:61. https://doi.org/10.1186/1477-7819-3-61

Mehrotra M, Anand A, Singh KR, Kumar S, Husain N, Sonkar AA. P-glycoprotein expression in Indian breast cancer patients with reference to molecular subtypes and response to anthracycline-based chemotherapy-a prospective clinical study from a developing country. Indian J Surg Oncol. 2018;9(4):524-9. https://doi.org/10.1007/s13193-018-0797-8

Anwar SL, Raharjo CA, Herviastuti R, Dwianingsih EK, Setyoheriyanto D, Avanti WS, et al. Pathological profiles and clinical management challenges of breast cancer emerging in young women in Indonesia: a hospital-based study. BMC Womens Health. 2019;19(1):28. https://doi.org/10.1186/s12905-019-0724-3

Gondhowiardjo S, Silalahi M, Manuain DA, Sekarutami SM, Christina N, Octavianus S, et al. Cancer profile in Central Jakarta: a 5-year descriptive study. Radioter Onkol Indones. 2018;9:34-42. https://doi.org/10.32532/jori.v9i2.90

Shintia C, Endang H, Diani K. Assessment of pathological response to neoadjuvant chemotherapy in locally advanced breast cancer using the Miller-Payne system and TUNEL. Malays J Pathol. 2016;38(1):25-32.

Manuaba IBTW, editor. Indonesian Society of Surgical Oncology (ISSO) 2010 solid cancer management guidelines. Jakarta: Sagung Seto; 2010. Indonesian.

Nicolini A, Ferrari P, Duffy MJ. Prognostic and predictive biomarkers in breast cancer: past, present and future. Semin Cancer Biol. 2018;52(Pt 1):56-73. https://doi.org/10.1016/j.semcancer.2017.08.010

Amin MB, Edge SB, Greene FL, Byrd DR, Brookland RK, Washington MK, editors. AJCC cancer staging manual. 8th ed. New York: Springer; 2017. https://doi.org/10.1007/978-3-319-40618-3

Haagensen CD, AP. S. Carcinoma of the breast. II-criteria of operability. Ann Surg. 1943;118(6):1032-51. https://doi.org/10.1097/00000658-194312000-00010

Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47(1):207-14.

https://doi.org/10.1002/1097-0142(19810101)47:1<207::AID-CNCR2820470134>3.0.CO;2-6

Ogston KN, Miller ID, Payne S, Hutcheon AW, Sarkar TK, Smith I, et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: prognostic significance and survival. Breast. 2003;12(5):320-7. https://doi.org/10.1016/S0960-9776(03)00106-1

Veneroni S, Zaffaroni N, Daidone MG, Benini E, Villa R, Silvestrini R. Expression of P-glycoprotein and in vitro or in vivo resistance to doxorubicin and cisplatin in breast and ovarian cancers. Eur J Cancer. 1994;30A(7):1002-7. https://doi.org/10.1016/0959-8049(94)90132-5

Prajoko YW, Aryandono T. The effect of p-glycoprotein (P-gp), nuclear factor-kappa B (Nf-kb), and aldehyde dehydrogenase-1 (ALDH-1) expression on metastases, recurrence and survival in advanced breast cancer patients. Asian Pac J Cancer Prev. 2019;20(5):1511–8. https://doi.org/10.31557/APJCP.2019.20.5.1511

Trock BJ, Leonessa F, Clarke R. Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J Natl Cancer Inst. 1997;89(13):917-31. https://doi.org/10.1093/jnci/89.13.917

van der Heyden S, Gheuens E, De Bruijn E, Van Oosterom A, Maes R. P-glycoprotein: clinical significance and methods of analysis. Crit Rev Clin Lab Sci. 1995;32(3):221-64. https://doi.org/10.3109/10408369509084685

Lehne G, De Angelis P, Clausen OP, Egeland T, Tsuruo T, Rugstad HE. Binding diversity of antibodies against external and internal epitopes of the multidrug resistance gene product P-glycoprotein. Cytometry. 1995;20(3):228-37. https://doi.org/10.1002/cyto.990200306

Lacueva FJ, Teruel A, Calpena R, Medrano J, Mayol MJ, Perez-Vazquez MT, et al. Detection of P-glycoprotein in frozen and paraffin-embedded gastric adenocarcinoma tissues using a panel of monoclonal antibodies. Histopathology. 1998;32(4):328-34. https://doi.org/10.1046/j.1365-2559.1998.00381.x

Beck WT, Grogan TM, Willman CL, Cordon-Cardo C, Parham DM, Kuttesch JF, et al. Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: consensus recommendations. Cancer Res. 1996;56(13):3010-20.

Tóth K, Vaughan MM, Slocum HK, Arredondo MA, Takita H, Baker RM, et al. New immunohistochemical "sandwich" staining method for MDRI P-glycoprotein detection with JSB-1 monoclonal antibody in formalin-fixed, paraffin-embedded human tissues. Am J Pathol. 1994;144(2):227-36.

Decker DA, Morris LW, Levine AJ, Pettinga JE, Grudzien JL, Farkas DH. Immunohistochemical analysis of P-glycoprotein expression in breast cancer: clinical correlations. Ann Clin Lab Sci. 1995;25(1):52-9.

Rastogi P, Anderson SJ, Bear HD, Geyer CE, Kahlenberg MS, Robidoux A, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;26(5):778-85. https://doi.org/10.1200/JCO.2007.15.0235

National Comprehensive Cancer Network. Breast cancer (version 2.2022) [Internet]. [updated 2021 Dec 20 cited 2022 Jan 24]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.

Indonesian Society of Surgical Oncology (ISSO). 2020 cancer management guidelines. Handojo D, Haryono SJ, Sudarsa IW, Panigoro SS, Setiaji K, Tanggo EH, et al, editors. Jakarta: PERABOI; 2020. Indonesian.

Kuroi K, Toi M, Ohno S, Nakamura S, Iwata H, Masuda N, et al. Prognostic significance of subtype and pathologic response in operable breast cancer; a pooled analysis of prospective neoadjuvant studies of JBCRG. Breast Cancer. 2015;22(5):486-95. https://doi.org/10.1007/s12282-013-0511-1

Makki J. Diversity of breast carcinoma: histological subtypes and clinical relevance. Clin Med Insights Pathol. 2015;8:23-31. https://doi.org/10.4137/CPath.S31563

Nedeljkovi? M, Tani? N, Prvanovi? M, Milovanovi? Z, Tani? N. Friend or foe: ABCG2, ABCC1 and ABCB1 expression in triple-negative breast cancer. Breast Cancer. 2021;28(3):727-36. https://doi.org/10.1007/s12282-020-01210-z

Published

2022-04-22

How to Cite

1.
Yulian ED, Dasawala F, Siregar NC. Association of P-glycoprotein expression and response to anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer. Med J Indones [Internet]. 2022Apr.22 [cited 2024Nov.22];31(1):62-9. Available from: https://mji.ui.ac.id/journal/index.php/mji/article/view/5863

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Section

Clinical Research
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