Can Estrogen Receptor, Progesterone Receptor, and Proliferative Index be Considered as Isolated Prognostic Factors of Overall Survival in Early luminal Breast Cancer?

Marija Karakolevska-Ilova; Milka  Zdravkovska; Djengis  Jasar; Gordana Petrushevska; Elena Simeonovska-Joveva

doi:10.3889/oamjms.2021.6102

Authors

Marija Karakolevska-Ilova Department of Oncology, Faculty of Medical Sciences, University Goce Delcev, Clinical Hospital Shtip, Shtip, Macedonia; Faculty of Medical Sciences, University Goce Delcev, Shtip, Macedonia https://orcid.org/0000-0001-7353-2110
Milka Zdravkovska Faculty of Medical Sciences, University Goce Delcev, Shtip, Macedonia
Djengis Jasar Department of Pathology, Faculty of Medical Sciences, University Goce Delcev Shtip, Clinical Hospital Acibadem-Sistina, Skopje, Macedonia
Gordana Petrushevska Institute of Pathology, University St. Cyril and Methodius, Skopje, Macedonia
Elena Simeonovska-Joveva Department of Neurology, Faculty of Medical Sciences, University Goce Delcev, Clinical Hospital Shtip, Shtip, Macedonia

DOI:

https://doi.org/10.3889/oamjms.2021.6102

Keywords:

Prognostic factors, Early breast cancer, Overall survival

Abstract

BACKGROUND: There are a number of proven molecular and pathological markers important for the prognosis for OS of early luminal type breast cancer, but there are still some deficiencies mainly due to the non-linear relationship between the markers and the outcome of the disease.

METHODS AND PATIENTS: In this retro-prospective study, clinical and pathological data were provided from 336 patients with breast cancer who underwent breast surgery and treatment between January 2010 and December 2013, and followed until December 2018. The aim of the study was an evaluation of ER, PR, and Ki-67 as independent prognostic factors for OS of early luminal breast cancer.

RESULTS: Early luminal breast cancers were not predictive of ER expression status (p = 0.699, p = 0.356), whereas only early Luminal B was predictive for PR expression (>10%: 72.2%). Ki-67 in most of the cases of early Luminal B was with expression of >14–20% (p = 0.056). Patients with ER of 1–10% survived over 80 months (p = 0.0020) in early Luminal A, but ER expression status did not show prognostic significance for OS of early Luminal B (p = 0.775). PR status did not show prognostic significance for OS in early luminal types (p = 0.257, p = 0.622). ER >1%/PR >1% was protective in early Luminal B (p = 0.00043), but not in early Luminal A.

CONCLUSION: Our results suggest ER, but not PR as independent prognostic factor for OS but only of early Luminal A. We did not prove Ki-67 as independent prognostic factor for OS of highly proliferative early breast cancer.

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References

Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374-403. https://doi.org/10.1016/j.ejca.2012.12.027 PMid:23485231 DOI: https://doi.org/10.1016/j.ejca.2012.12.027

Gamucci T, Vaccaro A, Ciancola F, Pizzuti L, Sperduti I, Moscetti L, et al. Recurrence risk in small, node-negative, early breast cancer: A multicenter retrospective analysis. J Cancer Res Clin Oncol. 2013;139(5):853-60. https://doi.org/10.1007/s00432-013-1388-2 PMid:23411686 DOI: https://doi.org/10.1007/s00432-013-1388-2

Gnant M, Thomssen C, Harbeck N. St. Gallen/Vienna 2015: A brief summary of the consensus discussion. Breast Care. 2015;10(2):124-30. https://doi.org/10.1159/000430488 PMid:26195941 DOI: https://doi.org/10.1159/000430488

Effi AB, Aman NA, Koui BS, Koffi KD, Traore ZC, Kouyate M. Breast cancer molecular subtypes defined by ER/PR and HER2 status: Association with clinicopathologic parameters in ivorian patients. Asian Pac J Cancer Prev. 2016;17(4):1973-8. https://doi.org/10.7314/apjcp.2016.17.4.1973 PMid:27221883 DOI: https://doi.org/10.7314/APJCP.2016.17.4.1973

Park C, Park K, Kim J, Sin Y, Park I, Cho H, et al. Prognostic values of negative estrogen or progesterone receptor expression in patients with luminal B HER2-negative breast cancer. World J Surg Oncol. 2016;14(1):244. https://doi.org/10.1186/s12957-016-0999-x PMid:27619909 DOI: https://doi.org/10.1186/s12957-016-0999-x

Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101(10):736-50. https://doi.org/10.1093/jnci/djp082 PMid:19436038 DOI: https://doi.org/10.1093/jnci/djp082

Mojarad S, Venturni B, Fulgenzi, Papaleo R, Brisgotti M, Monti F. Prediction of nodal metastasis and prognosis of breast cancer by ANN-based assessment of tumour size and p53, Ki-67 and steroid receptor expression. Anticancer Res. 2013;33(9):3925-33. Mid:24023330

Murphy LC, Watson P. Steroid receptors in human breast tumorigenesis and breast cancer progression. Biomed Pharmacother. 2002;56(2):65-77. https://doi.org/10.1016/s0753-3322(01)00157-3 PMid:12000137 DOI: https://doi.org/10.1016/S0753-3322(01)00157-3

Cui X, Schiff R, Arpino G, Osborne K, Lee A. Biology of progesterone receptor loss in breast cancer and its implications for endocrine therapy. J Clin Oncol. 2005;23(30):7721-35. https://doi.org/10.1200/jco.2005.09.004 PMid:16234531 DOI: https://doi.org/10.1200/JCO.2005.09.004

Bardou VJ, Arpino G, Elledge RM, Osborne CK, Clark GM. Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. J Clin Oncol. 2003;21(10):1973-9. https://doi.org/10.1200/jco.2003.09.099 PMid:12743151 DOI: https://doi.org/10.1200/JCO.2003.09.099

Inic Z, Zegarac M, Inic M, Markovic I, Kozomara Z, Djurisic I, et al. Difference between luminal A and luminal B subtypes according to Ki-67, tumor size, and progesterone receptor negativity providing prognostic information. Clin Med Insights Oncol. 2014;8:107-11. https://doi.org/10.4137/cmo.s18006 PMid:25249766 DOI: https://doi.org/10.4137/CMO.S18006

de Azambuja E, Cardoso F, de Castro G J, Colozza M, Mano MS, Durbecq V, et al. Ki-67 as prognostic marker in early breast cancer: A meta-analysis of published studies involving 12155 patients. Br J Cancer. 2007;96(10):1504-13. https://doi.org/10.1038/sj.bjc.6603756 PMid:17453008 DOI: https://doi.org/10.1038/sj.bjc.6603756

Urruticoechea A, Smith IE, Dowsett M. Proliferation marker Ki-67 in early breast cancer. J Clin Oncol. 2005;23:7212-20. https://doi.org/10.1200/jco.2005.07.501 Mid:16192605 DOI: https://doi.org/10.1200/JCO.2005.07.501

Van Asten K, Slembrouck L, Olbrecht S, Jongen L, Brouckaert O, Wildiers H, et al. Prognostic value of the progesterone receptor by subtype in patients with estrogen receptorpositive, HER-2 negative breast cancer. Oncologist. 2019;24(2):165-71. https://doi.org/10.1634/theoncologist.2018-0176 PMid:30171067 DOI: https://doi.org/10.1634/theoncologist.2018-0176

Pérez-López M, García-Gómez J, Alves M, Paradela A, García-Mata J, García-Caballero T. Ki-67 is a prognostic marker for hormone receptor positive tumors. Clin Transl Oncol. 2016;18(10):996-1002. https://doi.org/10.1007/s12094-015-1472-y PMid:26742937 DOI: https://doi.org/10.1007/s12094-015-1472-y

Ono M, Tsuda H, Yoshida M, Shimizu C, Kinoshita T, Tamura K. Prognostic significance of progesterone receptor expression in estrogen-receptor positive, HER2-negative, node-negative invasive breast cancer with a low Ki-67 labeling index. Clin Breast Cancer. 2017;17(1):41-7. https://doi.org/10.1016/j.clbc.2016.06.012 PMid:27477822 DOI: https://doi.org/10.1016/j.clbc.2016.06.012

Sinna HP, Kreipeb H. A brief overview of the WHO classification of breast tumors, 4th edition, focusing on issues and updates from the 3rd edition. Breast Care. 2013;8(2):149-54. https://doi.org/10.1159/000350774 PMid:24415964 DOI: https://doi.org/10.1159/000350774

Weiss A, King T, Hunt K, Mittendorf E. Incorporating biologic factors into the American joint committee on cancer breast cancer staging system: Review of the supporting evidence. Surg Clin North Am. 2018;98(4):687-702. https://doi.org/10.1016/j.suc.2018.03.005 Mid:30005768 DOI: https://doi.org/10.1016/j.suc.2018.03.005

Allison K, Hammond E, Dowsett M, McKernin S, Carey L, Fitzgibbons P, et al. Estrogen and progesterone receptor testing in breast cancer: ASCO/CAP guideline update. J Clin Oncol. 2020;38(12):1346-66. https://doi.org/10.1200/jco.19.02309 PMid:31928404 DOI: https://doi.org/10.1200/JCO.19.02309

Coates AS, Winer EP, Goldhirsch A, Gelber RD, Gnant M, Piccart-Gebhart M, et al. Tailoring therapies--improving the management of early breast cancer: St Gallen international expert consensus on the primary therapy of early breast cancer 2015. Ann Oncol. 2015;26:1533-46. https://doi.org/10.1016/j.breast.2003.09.007 PMid:25939896 DOI: https://doi.org/10.1016/j.breast.2003.09.007

Harbeck N, Thomssen C, Gnantc M. St. Gallen 2013: Brief preliminary summary of the consensus discussion. Breast Care. 2013;8(2):102-9. https://doi.org/10.1159/000351193 PMid:24000280 DOI: https://doi.org/10.1159/000351193

Nowikiewicz T, Chmielowska E, Andrusewicz H, Łysik-Miśkurka J, Głowacka I, Sowa M, et al. Prevalence of biological types of breast cancer and their influence on disease staging and therapeutic management a single-center study. Pol J Pathol. 2017;68(1):16-25. https://doi.org/10.5114/pjp.2017.67611 PMid:28547976 DOI: https://doi.org/10.5114/pjp.2017.67611

Cherbal F, Gaceb H, Mehemmai C, Saiah I, Bakour R, Rouis A, et al. Distribution of molecular breast cancer subtypes among Algerian women and correlation with clinical and tumor characteristics: A population-based study. Breast Dis. 2015;35(2):95-102. https://doi.org/10.3233/bd-150398 PMid:25736840 DOI: https://doi.org/10.3233/BD-150398

Prat A, Cheang M, Martín M, Parker J, Carrasco E, Caballero R, et al. Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal a breast cancer. J Clin Oncol. 2013;31(2):203-9. https://doi.org/10.1200/jco.2012.43.4134 PMid:23233704 DOI: https://doi.org/10.1200/JCO.2012.43.4134

Sturat-Harris R, Caldas C, Pinder E, Pharoah P. Proliferation markers and survival in early breast cancer: A systematic review and meta-analysis of 85 studies in 32,825 patients. Breast. 2008;17(4):323-34. https://doi.org/10.1016/j.breast.2008.02.002 PMid:18455396 DOI: https://doi.org/10.1016/j.breast.2008.02.002

Polley MY, Leung S, McShane L, Gao D, Hugh J, Mastropasqua M, et al. An international Ki67 reproducibility study. J Natl Cancer Inst. 2013;105(24):1897-906. PMid:24203987 DOI: https://doi.org/10.1093/jnci/djt306

Bravaccini S, Bronte G, Scarpi E, Ravaioli S, Maltoni R, Mangia A. The impact of progesterone receptor expression on prognosis of patients with rapidly proliferating, hormone receptor-positive early breast cancer: A post HOC analysis of the IBIS 3 trial. Ther Adv Med Oncol. 2020;12:1758835919888999. https://doi.org/10.1177/1758835919888999 Mid:32158505 DOI: https://doi.org/10.1177/1758835919888999

Purdie CA, Quinlan P, Jordan LB, Ashfield A, Ogston S, Dewar JA, et al. Progesterone receptor expression is an independent prognostic variable in early breast cancer: A population-based study. Br J Cancer. 2014;110(3):565-72. PMid:24300977 DOI: https://doi.org/10.1038/bjc.2013.756

Simone G, Diotaiuti S, Digennaro M, Sambiasi D, De Summa S, Tommasi S, et al. Comment on renewed interest in the progesterone receptor in breast cancer. Br J Cancer. 2017;117(2):e1. https://doi.org/10.1038/bjc.2017.90 PMid:28399113 DOI: https://doi.org/10.1038/bjc.2017.90

Nordenskjöld A, Fohlin H, Fornander T, Löfdahl B, Skoog L, Stål O. Progesterone receptor positivity is a predictor of long-term benefit from adjuvant tamoxifen treatment of estrogen receptor positive breast cancer. Breast Cancer Res Treat. 2016;160(2):313-22. https://doi.org/10.1007/s10549-016-4007-5 PMid:27722840 DOI: https://doi.org/10.1007/s10549-016-4007-5

Creighton CJ, Osborne C, van de Vijver MJ, Foekens JA, Klijn JG, Horlings HM, et al. Molecular profiles of progesterone receptor loss in human breast tumors. Breast Cancer Res Treat 2009;114(2):287-99. https://doi.org/10.1007/s10549-008-0017-2 PMid:18425577 DOI: https://doi.org/10.1007/s10549-008-0017-2

Mohsin S, Weiss H, Havighurst T, Clark G, Berardo M, Roanh le D, et al. Progesterone receptor by immunohistochemistry and clinical outcome in breast cancer: A validation study. Mod Pathol. 2004;17(12):1545-54. https://doi.org/10.1038/modpathol.3800229 PMid:15272277 DOI: https://doi.org/10.1038/modpathol.3800229

Inwald EC, Klinkhammer-Schalke M, Hofstädter F, Zeman F, Koller M, Gerstenhauer M, et al. Ki-67 is a prognostic parameter in breast cancer patients: results of a large population-based cohort of a cancer registry. Breast Cancer Res Treat. 2013;139(2):539-52. https://doi.org/10.1007/s10549-013-2560-8 Mid:23674192 DOI: https://doi.org/10.1007/s10549-013-2560-8

Viale G, Giobbie-Hurder A, Regan MM, Coates AS, Mastropasqua MG, Dell’Orto P, et al. Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: Results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol. 2008;26(34):5569-75. https://doi.org/10.1200/jco.2008.17.0829 PMid:18981464 DOI: https://doi.org/10.1200/JCO.2008.17.0829

Criscitiello C, Disalvatore D, De Laurentiis M, Gelao L, Fumagalli L, Locatelli M, et al. High Ki-67 score is indicative of a greater benefit from adjuvant chemotherapy when added to endocrine therapy in luminal B HER2 negative and node-positive breast cancer. Breast. 2014;23(1):69-75. https://doi.org/10.1016/j.breast.2013.11.007 PMid:24314620 DOI: https://doi.org/10.1016/j.breast.2013.11.007

Parise A, Caggiano V. Breast cancer survival defined by the ER/PR/HER2 subtypes and a surrogate classification according to tumor grade and immunohistochemical biomarkers. J Cancer Epidemiol. 2014;2014:469251. https://doi.org/10.1155/2014/469251 PMid:24955090 DOI: https://doi.org/10.1155/2014/469251

Ferguson NL, Bell J, Heidel R, Lee S, Vanmeter S, Duncan L, et al. Prognostic value of breast cancer subtypes, Ki-67 proliferation index, age, and pathologic tumor characteristics on breast cancer survival in Caucasian women. Breast J. 2013;19(1):22-30. https://doi.org/10.1111/tbj.12059 PMid:23240985 DOI: https://doi.org/10.1111/tbj.12059