Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press67010.17650/1994-4098-2019-15-4-30-49MAMMOLOGY. REVIEWSМАММОЛОГИЯ. ОБЗОРНЫЕ СТАТЬИBiological rationale for patient-specific treatment of breast cancer. Analysis of new data for breast cancerБиологическое обоснование персонализации лечения рака молочной железы. Анализ новых данных используемых в рутинной практике маркеров рака молочной железыhttps://orcid.org/0000-0002-0871-9453PaltuevR. M.ПалтуевР. М.
Russian Federation

68 Leningradskaya St., Pesochnyy Settlement, Saint Petersburg 197758

Руслан Маликович Палтуев

197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68

paltuev@mail.ruN.N. Petrov National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава России12122019154304911032020110320202019https://ojrs.abvpress.ru/ojrs/article/view/670

Breast cancer is the most common malignancy in females. More than 1.7 million of cases are detected annually worldwide. The incidence of breast cancer in Russia has increased by 64 % over the last 20 years. There was a 1.43-fold increase in the prevalence of breast cancer (from 297 to 457cases per 100,000) between 2005 and 2017. A total of59,538 new cases were registered in the Russian Federation in 2012. In Russia, breast cancer is the most common malignancy among women aged 40—85years and the second most common cancer among women aged 15—39 (after cervical cancer). The disease is primarily detected in women aged between 40 and 54 years (29.5 %). More than 66,000 of new cases of breast cancer are registered in the Russian Federation annually. In 2017, there were 70,293 new cases of breast cancer; of them, 49,134 patients (69.9 %) hade stage I—II breast cancer. There was a 0.02 % increase in the proportion of new cases of stage I—II breast cancer in 2016—2017. For this reason, it is important to study in depth the markers of breast cancer used in everyday practice in order to personalize the treatment of patients with breast cancer.

Рак молочной железы (РМЖ) — наиболее часто встречающееся онкологическое заболевание в женской популяции. Более 1,7млн случаев в мире выявляется ежегодно. Заболеваемость РМЖ в РФ выросла на 64 % за последние 20 лет. Распространенность выросла в 1,43 раза (с 297 до 457 случаев на 100 000 населения) за период с 2005 по 2017 г. В 2012 г. в РФ было зарегистрировано 59538 новых случаев РМЖ. В структуре онкологической заболеваемости в РФ РМЖ занимает 1-е место среди женщин в возрастном диапазоне 40—85 лет, 2-е место (18,9 %) — в возрастном диапазоне 15—39 лет (после рака шейки матки). Наиболее частая встречаемость отмечается в группе 40—54 года (29,5 %). Ежегодно в РФ отмечается свыше 66 тыс. новых случаев РМЖ. В 2017г. на территории РФ зарегистрировано 70293 новых случая РМЖ. Число случаев с I—IIстадией РМЖв 2017г. составило 49134 (69,9 % от общего числа новых случаев). Увеличение доли новых случаев РМЖI—IIстадий в период с 2016 по 2017г. составило 0,02 %. По этой причине важно глубокое изучение маркеров РМЖ, используемых в рутинной практике для персонализации лечения пациенток с РМЖ.

breast cancerbreast cancer markerspatient-specific treatmentрак молочной железымаркеры рака молочной железыперсонализация леченияKalli S., Semine A., Cohen S. et al. American Joint Committee on Cancer’s Staging System for Breast Cancer, Eighth Edition: What the Radiologist Needs to Know. Radiographics 2018;38(7):1921—33. DOI: 10.1148/rg.2018180056.AJCC Cancer Staging Manual. Ed. by M.B. Amin. 8th edn. Springer International Publishing, 2017.TNM Classification of Malignant Tumours, 8th edn. Available at: https://www.wiley.com/en-us/TNM+Classification+of+Malignant+Tumours%2C+8fll+Edition-p-9781119263579.Blamey R.W., Hornmark-Stenstam B., Ball G. et al. ONCOPOOL - a European database for 16,944 cases of breast cancer. Eur J Cancer 2010;46(1):56—71. DOI: 10.1016/j.ejca.2009.09.009.Park S., Koo J., Park H.S. et al. Expression of androgen receptors in primary breast cancer. Ann Oncol 2010;21(3):488—92. DOI: 10.1093/annonc/mdp510.Ribnikar D., Cardoso F. Tailoring chemotherapy in early-stage breast cancer: based on tumor biology or tumor burden? Am Soc Clin Oncol Educ Book 2016;35:e31—8. DOI: 10.14694/EDBK_159077.Sparano J.A. TAILORx: trial assigning individualized options for treatment (Rx). Clin Breast Cancer 2006;4(7):347—50.Petkov V.I., Miller D.P., Howlader N. et al. Breast-cancer-specific mortality in patients treated based on the 21-gene assay: a SEER population-based study. NPJ Breast Cancer 2018;4:17. DOI: 10.1038/s41523-018-0069-3.Nitz U., Gluz O., Christgen M. et al. Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial. Breast Cancer Res Treat 2017;165(3):573—83. DOI: 10.1007/s10549-017-4358-6.Stemmer S.M., Steiner M., Rizel S. et al. Clinical outcomes in patients with nodenegative breast cancer treated based on the recurrence score results: evidence from a large prospectively designed registry. NPJ Breast Cancer 2017;3:33. DOI: 10.1038/s41523-017-0034-6.Fisher B., Bauer M., Wickerham D.L. et al. Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer 1983;52(9):1551—7.Howland N.K., Driver T.D., Sedrak M.P. et al. Lymph node involvement in immunohistochemistry-based molecular classifications of breast cancer. J Surg Res 2013;185(2):697—703. DOI: 10.1016/j.jss.2013.06.048.Dings PJ., Elferink M.A., Strobbe L.J., de Wilt J.H. The prognostic value of lymph node ratio in node-positive breast cancer: a Dutch nationwide population-based study. Ann Surg Oncol 2013;20(8):2607—14. DOI: 10.1245/s10 434-013-2932-7.Rosen P.R., Groshen S., Saigo P.E. et al. A long-term follow-up study of survival in stage I (T1N0M0) and stage II (T1N1M0) breast carcinoma. J Clin Oncol 1989;7(3):355-66.Wu S.G., He Z.Y., Li Q. et al. Prognostic value of metastatic axillary lymph node ratio for Chinese breast cancer patients. PLoS One 2013;8(4):e61410. DOI: 10.1371/journal.pone.0061410.Axelsson C.K., Mouridsen H.T., Zedeler K. Axillary dissection of level I and II lymph nodes is important in breast cancer classification. The Danish Breast Cancer Cooperative Group (DBCG). Eur J Cancer 1992; 8—9(28A):1415—8.Recht A., Gray R., Davidson N.E. et al. Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: experience of the Eastern Cooperative Oncology Group. J Clin Oncol 1999;17(6):1689—700. DOI: 10.1200/JCO.1999.17.6.1689.Cil T., Hauspy J., Kahn H. et al. Factors affecting axillary lymph node retrieval and assessment in breast cancer patients. Ann Surg Oncol 2008;15(12):3361—8. DOI: 10.1245/s10434-008-9938-6.Schaapveld M., de Vries E.G., van der Graaf W.T. et al. The prognostic effect of the number of histologically examined axillary lymph nodes in breast cancer: stage migration or age association? Ann Surg Oncol 2006;13(4):465-74.Chagpar A.B., Camp R.L., Rimm D.L. Lymph node ratio should be considered for incorporation into staging for breast cancer. Ann Surg Oncol 2011;18(11):3143—8. DOI: 10.1245/s10434-011-2012-9.Vinh-Hung V., Verkooijen H.M., Fioretta G. et al. Lymph node ratio as an alternative to pN staging in nodepositive breast cancer. J Clin Oncol 2009;27(7):1062-8. DOI: 10.1200/JCO.2008.18.6965.Beadle B.M., Woodward W.A., Buchholz T.A. The impact of age on outcome in early-stage breast cancer. Semin Rad Oncol 2011;1(21):26—34.Prat A., Ellis M.J., Perou C.M. Practical implications of gene-expression-based assays for breast oncologists. Nat Rev Clin Oncol 2011;1(9):48—57.Snrlie T., Perou C.M., Tibshirani R. et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001;98(19):10869—74. DOI: 10.1073/pnas.191367098.Aleskandarany M.A., Green A.R., Benhasouna A.A. et al. Prognostic value of proliferation assay in the luminal, HER2-positive, and triple-negative biologic classes of breast cancer. Breast Cancer Res 2012;14(1):R3. DOI: 10.1186/bcr3084.Francis P.A. Optimal adjuvant therapy for very young breast cancer patients. Breast 2011;4(20);297—302.Rosenberg S.M., Partridge A.H. Management of breast cancer in very young women. Breast 2015; (24 Suppl 2):S154—8.Anders C.K., Hsu D.S., Broadwater G. et al. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol 2008;26(20):3324-30. DOI: 10.1200/JCO.2007.14.2471.Warner E.T., Colditz G.A., Palmer J.R. et al. Reproductive factors and risk of premenopausal breast cancer by age at diagnosis: are there differences before and after age 40? Breast Cancer Res Treat 2013;142(1):165—75. DOI: 10.1007/s10549-013-2721-9.Azim H.A., Michiels S., Bedard P.L. et al. Elucidating prognosis and biology of breast cancer arising in young women using gene expression profiling. Clin Cancer Res 2012;18(5):1341-51. DOI: 10.1158/1078-0432.CCR-11-2599.Jenkins E.O., Deal A.M., Anders C.K. et al. Age-specific changes in intrinsic breast cancer subtypes: a focus on older women. Oncologist 2014;19(10):1076—83. DOI: 10.1634/theoncologist.2014-0184.Cui X., Harada S., Shen D. et al. The utility of phosphohistone H3 in breast cancer grading. Appl Immunohistochem Mol Morphol 2015;23(10):689—95. DOI: 10.1097/PAI.0000000000000137.Liedtke C., Rody A., Gluz O. et al. The prognostic impact of age in different molecular subtypes of breast cancer. Breast Cancer Res Treat 2015;152(3):667—73. DOI: 10.1007/s10549-015-3491-3.Chollet-Hinton L., Anders C.K., Tse C.K. et al. Breast cancer biologic and etiologic heterogeneity by young age and menopausal status in the Carolina Breast Cancer Study: a case-control study. Breast Cancer Res 2016;18(1):79. DOI: 10.1186/s13058-016-0736-yBollet M.A., Sigal-Zafrani B., Mazeau V. et al. Age remains the first prognostic factor for loco-regional breast cancer recurrence in young (<40 years) women treated with breast conserving surgery first. Radiother Oncol 2007;82(3):272-80.Loibl S., Jackisch C., Lederer B. et al. Outcome after neoadjuvant chemotherapy in young breast cancer patients: a pooled analysis of individual patient data from eight prospectively randomized controlled trials. Breast Cancer Res Treat 2015;152(2):377—87. DOI: 10.1007/s10549-015-3479-z.Collins L.C., Marotti J.D., Gelber S. et al. Pathologic features and molecular phenotype by patient age in a large cohort of young women with breast cancer. Breast Cancer Res Treat 2012;131(3):1061—6. DOI: 10.1007/s10549-011-1872-9.Elston C.W., Ellis I.O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 2002;3A(41):151—2, discussion 152—3.Rakha E.A., El-Sayed M.E., Lee A.H. et al. Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol 2008;26(19):3153—8. DOI: 10.1200/JCO.2007.15.5986.Green A.R., Soria D., Powe D.G. et al. Nottingham prognostic index plus (NPI+) predicts risk of distant metastases in primary breast cancer. Breast Cancer Res Treat 2016;157(1):65—75. DOI: 10.1007/s10549-016-3804-1.Semiglazov V.F., Paltuev R.M., Semiglazov V.V. et al. General guidelines for the treatment of early breast cancer St. Gallen-2015, adapted by experts of the Russian Society of Oncomammologists. Opukholi zhenskoy reproduktivnoy systemy = Tumors of female reproductive system 2015;(3):43 — 60. (In Russ.).Семиглазов В.Ф., Палтуев Р.М., Семи-глазов В.В. и др. Общие рекомендации по лечению раннего рака молочной железы St. Gallen-2015, адаптированные экспертами Российского общества онкомаммологов. Опухоли женской репродуктивной системы 2015;(3):43 — 60.Lambertini M., Pinto A.C., Ameye L. et al. The prognostic performance of Adjuvant!Online and Nottingham Prognostic Index in young breast cancer patients. Br J Cancer 2016;115(12):1471—8. DOI: 10.1038/bjc.2016.359.Pereira H., Pinder S.E., Sibbering D.M. et al. Pathological prognostic factors in breast cancer. IV: Should you be a typer or a grader? A comparative study of two histological prognostic features in operable breast carcinoma. Histopathology 1995;27(3):219—26. DOI: 10.1111/j.1365-2559.1995.tb00213.x.Henson D.E., Ries L., Freedman L.S., Carriaga M. Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index. Cancer 1991;68(10):2142—9. DOI: 10.1002/1097-0142(19911115)68:10<2142::aid-cncr2820681010>3.0.co;2-d.Desmedt C., Haibe-Kains B., Wirapati P. et al. Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res 2008;14(16):5158—65. DOI: 10.1158/1078-0432.CCR-07-4756.Rakha E.A., El-Sayed M.E., Green AR. et al. Biologic and clinical characteristics of breast cancer with single hormone receptor positive phenotype. J Clin Oncol 2007;25(30):4772-8.Schwartz A.M., Henson D.E., Chen D., Rajamarthandan S. Histologic grade remains a prognostic factor for breast cancer regardless of the number of positive lymph nodes and tumor size: a study of 161 708 cases of breast cancer from the SEER Program. Arch Pathol Lab Med 2014;138(8):1048-52. DOI: 10.5858/arpa.2013-0435-OA.FDA-NIH Biomarker Working Group BEST (Biomarkers, EndpointS, and other Tools) Resource. FDA-NIH Biomarker Working Group, Silver Spring (MD): Food and Drug Administration (US), 2016.Harris L.N., Ismaila N., McShane L.M. et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2016;34(10):1134—50. DOI: 10.1200/JCO.2015.65.2289.Moore H.M., Kelly A.B., Jewell S.D. et al. Biospecimen reporting for improved study quality (BRISQ). Cancer Cytopathol 2011;119(2):92—101. DOI: 10.1002/cncy.20147.Group F.-N.B.W. Glossary. F.-N.B.W. Group, Food and Drug Administration (US), 2018.Hammond M.E., Hayes D.F., Wolff A.C. et al. American society of clinical oncology/college of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract 2010;6(4):195—7. DOI: 10.1200/JOP.777003.Wilson F.R., Coombes M.E., Wylie Q. et al. Herceptin® (trastuzumab) in HER2-positive early breast cancer: protocol for a systematic review and cumulative network meta-analysis. Syst Rev 2017;6(1):196. DOI: 10.1186/s13643-017-0588-2.Van Poznak C., Somerfield M.R., Bast R.C. et al. Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2015;33(24):2695—704. DOI: 10.1200/JCO.2015.61.1459.Van de Vijver M.J. Molecular tests as prognostic factors in breast cancer. Virchows Arch 2014;464(3):283—91. DOI: 10.1007/s00428-014-1539-0.Rakha E.A., Elsheikh S.E., Aleskandarany M.A. et al. Triplenegative breast cancer: distinguishing between basal and nonbasal subtypes. Clin Cancer Res 2009;15(7):2302—10. DOI: 10.1158/1078-0432.CCR-08-2132.Harvey J.M., Clark G.M., Osborne C.K., Allred D.C. Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol 1999;17(5):1474—81.Kalkman S., Barentsz M.W., Witkamp A.J. et al. Brief fixation does not affect assessment of hormone receptor expression in invasive breast carcinoma biopsies: paving the road for same-day tissue diagnostics. Am J Surg Pathol 2014;38(8):1071—8. DOI: 10.1097/PAS.0000000000000207.Dekker T.J., ter Borg S., Hooijer G.K. et al. Quality assessment of estrogen receptor and progesterone receptor testing in breast cancer using a tissue microarray-based approach. Breast Cancer Res Treat 2015;152(2):247—52. DOI: 10.1007/s10549-015-3444-x.Motamedolshariati M., Memar B., Aliakbaian M. et al. Accuracy of prognostic and predictive markers in core needle breast biopsies compared with excisional specimens. Breast Care 2014;9(2):107—10. DOI: 10.1159/000360787.Dowsett M., Sestak I., Buus R. et al. Estrogen receptor expression in 21-gene recurrence score predicts increased late recurrence for estrogen-positive/her2-negative breast cancer. Clin Cancer Res 2015;21(12):2763—70. DOI: 10.1158/1078-0432.CCR-14-2842.Holst F., Moelans C.B., Filipits M. et al. On the evidence for ESR1 amplification in breast cancer. Nat Rev Cancer 2012;12(2):149. DOI: 10.1038/nrc3093-c3.Yi M., Huo L., Koenig K.B. et al. Which threshold for ER positivity? А retrospective study based on 9639 patients. Ann Oncol 2014;25(5):1004—11. DOI: 10.1093/annonc/mdu053.Park C., Park K., Kim J. 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. DOI: 10.1186/s12957-016-0999-x.Sopik V., Sun P., Narod S.A. The prognostic effect of estrogen receptor status differs for younger versus older breast cancer patients. Breast Cancer Res Treat 2017;2(165):391 — 402.Bardou VJ., Arpino G., Elledge R.M. et al. 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. DOI: 10.1200/JCO.2003.09.099.Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;9472(365):1687—717.Gerdes J., Lemke H., Baisch H. et al. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki- 67. J Immunol 1984;133(4):1710—5.Fonatsch C., Duchrow M., Rieder H. et al. Assignment of the human Ki- 67 gene (MK167) to 10q25-qter. Genomics 1991;11(2):476-7. DOI: 10.1016/0888-7543(91)90163-9.Isola J., Helin H., Kallioniemi O.P. Immunoelectron-microscopic localization of a proliferation-associated antigen Ki-67 in MCF-7 cells. Histochem J 1990;9(22):498-506.Heidebrecht H.J., Buck F., Haas K. et al. Monoclonal antibodies Ki-S3 and Ki-S5 yield new data on the “Ki-67” proteins. Cell Prolif 1996;29(7):413—25. DOI: 10.1111/j.1365-2184.1996.tb00984.x.Beresford M.J., Wilson G.D., Makris A. Measuring proliferation in breast cancer: practicalities and applications. Breast Cancer Res 2006;6(8):216.Viale G., Giobbie-Hurder A., Regan M.M. 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. DOI: 10.1200/JCO.2008.17.0829..Ruiz C., Seibt S., Al Kuraya K. et al. Tissue microarrays for comparing molecular features with proliferation activity in breast cancer. Int J Cancer 2006;118(9):2190—4.Harper-Wynne C., Ross G., Sacks N. et al. Effects of the aromatase inhibitor letrozole on normal breast epithelial cell proliferation and metabolic indices in postmenopausal women: a pilot study for breast cancer prevention. Cancer Epidemiol Biomarkers Prev 2002;11(7):614—21.Allred D.C., Mohsin S.K., Fuqua S.A. Histological and biological evolution of human premalignant breast disease. Endocr Relat Cancer 2001;1(8):47—61.Wiesner F.G., Magener A., Fasching P.A. et al. Ki-67 as a prognostic molecular marker in routine clinical use in breast cancer patients. Breast 2009;18(2):135—41. DOI: 10.1016/j.breast.2009.02.009.De Azambuja E., Cardoso F., de Castro G.Jr. et al. Ki-67 as prognostic marker in early breast cancer: a metaanalysis of published studies involving 12,155 patients. Br J Cancer 2007;96(10):1504—13. DOI: 10.1038/sj.bjc.6603756.Stuart-Harris R., Caldas C., Pinder S.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. DOI: 10.1016/j.breast.2008.02.002.Klintman M., Bendahl P.O., Grabau D. et al. The prognostic value of Ki67 is dependent on estrogen receptor status and histological grade in premenopausal patients with node-negative breast cancer. Mod Pathol 2010;23(2):251—9. DOI: 10.1038/modpathol.2009.167.Pinto A.E., Andre S., Pereira T. et al. Prognostic comparative study of S-phase fraction and Ki-67 index in breast carcinoma. J Clin Pathol 2001;54(7): 543-9. DOI: 10.1136/jcp.54.7.543.Penault-Llorca F., Abrial C., Raoelfils I. et al. Changes and predictive and prognostic value of the mitotic index, Ki-67, cyclin D1, and cyclo-oxygenase-2 in 710 operable breast cancer patients treated with neoadjuvant chemotherapy. Oncologist 2008;13(12):1235—45. DOI: 10.1634/theoncologist.2008-0073.Gandini S., Guerrieri-Gonzaga A., Pruneri G. et al. Association of molecular subtypes with Ki-67 changes in untreated breast cancer patients undergoing presurgical trials. Ann Oncol 2014;25(3):618—23. DOI: 10.1093/annonc/mdt528.Elston C.W., Ellis I.O., Pinder S.E. Pathological prognostic factors in breast cancer. Crit Rev Oncol Hematol 1999;3(31):209—23.Galea M.H., Blamey R.W., Elston C.E., Ellis I.O. The Nottingham Prognostic Index in primary breast cancer. Breast Cancer Res Treat 1992;22(3):207—19. DOI: 10.1007/bf01840834.Cole B.F., Gelber R.D., Gelber S. et al. Polychemotherapy for early breast cancer: an overview of the randomised clinical trials with quality-adjusted survival analysis. Lancet 2001;3 58(9278):277— 86.Feng Y., Sun B., Li X. et al. Differentially expressed genes between primary cancer and paired lymph node metastases predict clinical outcome of node-positive breast cancer patients. Breast Cancer Res Treat 2007;103(3):319—29.Rakha E.A., Pinder S.E., Bartlett J.M. et al. Updated UK Recommendations for HER2 assessment in breast cancer. J Clin Pathol 2015;68(2):93—9. DOI: 10.1136/jclinpath-2014-202571.Ravdin P.M., Green S., Dorr T.M. et al. Prognostic significance of progesterone receptor levels in estrogen receptorpositive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study. J Clin Oncol 1992;10(8):1284 —91.Colomer R., Beltran M., Dorcas J. et al. It is not time to stop progesterone receptor testing in breast cancer. J Clin Oncol 2005;23(16):3868—9; author reply 3869—70.Regan M.M., Viale G., Mastropasqua M.G. et al. Reevaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays. J Natl Cancer Inst 2006;98(21):1571—81. DOI: 10.1093/jnci/djj 415.Regan M.M., Viale G., Mastropasqua M.G. et al. Re-evaluating adjuvant breast cancer trials: assessing hormone receptor status by immunohistochemical versus extraction assays. J Natl Cancer Inst 2006;98(21):1571—81. DOI: 10.1093/jnci/djj 415.Stendahl M., Ryden L., Nordenskjold B. et al. High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients. Clin Cancer Res 2006;12(15):4614—8. DOI: 10.1158/1078-0432.CCR-06-0248.Dandachi N., Dietze O., Hauser-Kronberger C. Chromogenic in situ hybridization: a novel approach to a practical and sensitive method for the detection of HER2 oncogene in archival human breast carcinoma. Lab Invest 2002;8(82):1007—14. DOI: 10.1097/01.lab.0000024360.48464.a4.Slamon D.J., Clark G.M., Wong S.G. et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 1987;235(4785):177—82.Bartlett J., Mallon E., Cooke T. The clinical evaluation of HER-2 status: which test to use? J Pathol 2003;4(199):411—7.Kaufmann M., von Minckwitz G., Bear H.D. et al. Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: new perspectives 2006. Ann Oncol 2007;18(12):1927—34. DOI: 10.1093/annonc/mdm201.Wolff A.C., Hammond M.E., Hicks D.G. et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 2013;31(31):3997—4013. DOI: 10.1200/JCO.2013.50.9984.Rakha E.A., Reis-Filho J.S., Ellis I.O. Combinatorial biomarker expression in breast cancer. Breast Cancer Res Treat 2010;2(120):293—308.Cuzick J., Dowsett M., Pineda S. et al. Prognostic value of a combined estrogen receptor, progesterone receptor, Ki-67, and human epidermal growth factor receptor 2 immunohistochemical score and comparison with the Genomic Health recurrence score in early breast cancer. J Clin Oncol 2011;29(32):4273—8. DOI: 10.1200/JCO.2010.31.2835.Carey L.A., Perou C.M., Livasy C.A. et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 2006;295(21):2492—502. DOI: 10.1001/jama.295.21.2492.Kreike B., van Kouwenhove M., Horlings H. et al. Gene expression profiling and histopathological characterization of triple-negative/basal-like breast carcinomas. Breast Cancer Res 2007;9(5):R65. DOI: 10.1186/bcr1771.Kurebayashi J., Moriya T., Ishida T. et al. The prevalence of intrinsic subtypes and prognosis in breast cancer patients of different races. Breast 2007;16 Suppl 2: S72—7.Bertucci F., Finetti P., Cervera N. et al. Gene expression profiling and clinical outcome in breast cancer. OMICS 2006;10(4):429—43. DOI: 10.1089/omi.2006.10.429.Cowin P.A., Anglesio M., Etemadmoghadam D., Bowtell D.D. Profiling the cancer genome. Annu Rev Genomics Hum Genet 2010;11:133—59. DOI: 10.1146/annurev-genom-082509-141536.Sotiriou C., Neo S.Y., McShane L.M. et al. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A 2003;100(18):10393—8. DOI: 10.1073/pnas.1732912100.Yadav B.S., Chanana P., Jhamb S. Biomarkers in triple negative breast cancer: A review. World J Clin Oncol 2015;6(6):252—63.Blows F.M., Driver K.E., Schmidt M.K. et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med 2010;7(5):e1000279. DOI: 10.1371/journal.pmed.1000279.Nielsen T.O., Hsu F.D., Jensen K. et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 2004;10(16):5367—74. DOI: 10.1158/1078-0432.CCR-04-0220.Rakha E.A., El-Sayed M.E., Reis-Filho J.S., Ellis I.O. Expression profiling technology: its contribution to our understanding of breast cancer. Histopathology 2008;52(1):67—81. DOI: 10.1111/j.1365-2559.2007.02894.x.Cheang M.C., Chia S.K., Voduc D. et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009;101(10):736–50. DOI: 10.1093/jnci/djp082.Morigi C. Highlights from the 15th St Gallen International Breast Cancer Conference 15-18 March, 2017, Vienna: tailored treatments for patients with early breast cancer. E Cancer Medical Science 2017;(11):732.Viale G., Slaets L., Bogaerts J. et al. High concordance of protein (by IHC), gene (by FISH; HER2 only), and microarray readout (by TargetPrint) of ER, PgR, and HER2: results from the EORTC 10041/BIG 03-04 MINDACT trial. Ann Oncol 2014;25(4):816-23. DOI: 10.1093/annonc/mdu026.Livasy C.A., Karaca G., Nanda R. et al. Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma. Mod Pathol 2006;19(2):264–71.. Viale G., Slaets L., Bogaerts J. et al. High concordance of protein (by IHC), gene (by FISH; HER2 only), and microarray readout (by TargetPrint) of ER, PgR, and HER2: results from the EORTC 10041/BIG 03-04 MINDACT trial. Ann Oncol 2014;25(4):816–23. DOI: 10.1093/annonc/mdu026.