Immunohistochemical tests for diagnostics of infiltrative forms of breast cancer and identification of molecular subtype in women of different ages in Dnipro city
Abstract
The article presents the results of histological and immunohistochemical testing of women of different ages who are suffering from infiltrative forms of breast cancer in Dnipro. The study presents the distribution of receptors of estrogens and progesterone (ER, PR), HER-2/neu (necessary for prescribing treatment) and Кi-67 (reveals additional features of a tumour). Considering that luminal types of breast cancer include tumours whose receptors express to ER and PR, depending on the kind of expression HER2/neu, they are classified into A (do not express HER2/neu) and B (express HER2/neu). Tumours with hyperexpression of HER2/neu and lack of ER and PR are called HER2+. The research conducted has shown that duct cancer is by far the commonest form, at 81%. In duct cancer, undifferentiated stage and moderately-differentiated stage cancer prevails, whereas with nodule cancer the majority (80%) have moderately-differentiated stage cancer. We discovered a correlative link between the stage of differentiation and the percentage of metastasis both in duct and nodule breast cancer. But nodule breast cancer is more aggressive: with metastasis occurring in 31.2% of women even in cases of moderately-differentiated stage cancer. Only duct cancer is able to produce slime, which distinguishes it from other forms. Combined forms of cancer are rare, but they lead to metastases in all cases. Most women with infiltrative cancer in Dnipro are aged between 51 and 60. There has been observed the increase in cases of breast cancer among young women; the most widespread among infiltrated forms of breast cancer is subtype Luminal A, which has the best prognosis. As the research shows, women under 60 tend to have less aggressive subtypes, which are easy to treat, whereas in older patients their aggressiveness increases substantially, which means an unfavourable prognosis and lower effectiveness of treatment. Кі-67 marker increases substantially in the absence of ER and PR, which means a high level of tumour aggressiveness. Luminal A subtype in not aggressive in most cases, which means the most favourable prognosis. Luminal B is partly aggressive which leads to a high percentage of metastasis, but thanks to ER+ or PR+, it is successfully treated by hormone therapy, which can lead to a positive prognosis. Overall, HER2+ and triple negative are the most aggressive.References
Badve, S., Dabbs, D. J., Schnitt, S. J., Baehner, F. L., Decker, T., Eusebi, V., Fox, S. B., Ichihara, S., Jacquemier, J., Lakhani, S. R., Palacios, J., Rakha, E. A., Richardson, A. L., Schmitt, F. C., Tan, P. H., Tse, G. M., Weigelt, B., Ellis, I. O., & Reis-Filho, J. S. (2011). Basal-like and triplenegative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists. Modern Pathology, 24, 158–167.
Bardou, V. J., Arpino, G., Elledge, R. M., Osborne, C. K., & Clark, G. M. (2003). Progesterone receptor status significantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases. The Journal of Clinical Oncology, 2, 1974–1979.
Bertos, N. R., & Park, M. (2011). Breast cancer – one term, many entities. The Journal of Clinical Investigation, 121, 3788–3796.
Brenton, J. D., Carey, L. A., Ahmed, A. A., & Caldas, C. (2005). Molecular classification and molecular forecasting of breast cancer: Ready for clinical application. Clinical Oncology, 23, 7350–7359.
Castellano, I., Allia, E., Accortanzo, V., Vandone, A. M., Chiusa, L., Arisio, R., Durando, A., Donadio, M., Bussolati, G., Coates, A. S., Viale, G., & Sapino, A. (2010). Androgen receptor expression is a significant prognostic factor in estrogen receptor positive breast cancers. Breast Cancer Research and Treatment, 124(3), 607–616.
Cheang, M. C., Chia, S. K., Voduc, D., Gao, D., Leung, S., Snider, J., Watson, M., Davies, S., Bernard, P. S., Parker, J. S., Perou, C. M., Ellis, M. J., & Nielsen, T. O. (2009). Ki-67 index, HER2 status, and prognosis of patients with luminal B breast cancer. The Journal of the National Cancer Institute, 101(10), 737–750.
Clarke, R., Tyson, J. J., & Dixon, J. M. (2015). Endocrine resistance in breast cancer – an overview and update. Molecular and Cellular Endocrinology, 418, 221–234.
Fisher, B., Costantino, J., Redmond, C., Poisson, R., Bowman, D., Couture, J., Dimitrov, N. V., Wolmark, N., Wickerham, D. L., & Fisher, E. R. (1989). A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. The New England Journal of Medicine, 320, 480–784.
Geyer, C. E., Forster, J., Lindquist, D., Chan, S., Romieu, C. G., Pienkowski, T., Jagiello-Gruszfeld, A., Crown, J., Chan, A., Kaufman, B., Skarlos, D., Campone, M., Davidson, N., Berger, M., Oliva, C., Rubin, S. D., Stein, S., & Cameron, D. (2006). Lapatinib plus capecitabine for HER2-positive advanced breast cancer. The New England Journal of Medicine, 355, 2735–2742.
Gucalp, A., Isakoff, S. J., Tolaney, S. M., & Traina, T. A. (2013). Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clinical Cancer Research, 19, 5506–5511.
Haibe-Kains, B., Desmedt, C., Loi, S., Culhane, A. C., Bontempi, G., Quackenbush, J., & Sotiriou, C. (2012). A three-gene model to robustly identify breast cancer molecular subtypes. The Journal of the National Cancer Institute, 104, 312–324.
Holm, K., Hegardt, C., Staaf, J., Vallon-Christersson, J., Jönsson, G., Olsson, H., Borg, A.,& Ringnér, M. (2010). Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns. Breast Cancer Research, 12(3), 36.
Hu, Z., Fan, C., Oh, D. S., Marron, J. S., He, X., Qaqish, B. F., Livasy, C., Carey, L. A., Reynolds, E., Dressler, L., Nobel, A., Parker, J., Ewend, M. G., Sawyer, L.R., Wu, J., Liu, Y., Nanda, R., Tretiakova, M., Orrico, R. A., Dreher, D., Palazzo, J. P., Perreard, L., Nelson, E., Mone, M., Hansen, H., Mullins, M., Quackenbush, J. F., Ellis, M. J., Olopade, O. I., Bernard, P. S., & Perou, C. M. (2006). The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics, 7, 96.
Isola, J. J. (1993). Immunohistochemical demonstration of androgen receptor in breast cancer and its relationship to other prognostic factors. The Journal of Pathology, 170(1), 32–35.
Jordan, V. C. (2014). Tamoxifen as the first targeted long-term adjuvant therapy for breast cancer. Endocrine-Related Cancer, 21, 236–245.
Kim, H. S., Park, I., Cho, H. J., Gwak, G., Yang, K., Bae, B. N., Kim, K. W., Han, S., Kim, H. J., & Kim, Y. D. (2012). Analysis of the potent prognostic factors in luminal-type breast cancer. Journal Breast Cancer, 15, 402–405.
Lehmann, B. D., Bauer, J. A., Chen, X., Sanders, M. E., Chakravarthy, A. B., Shyr, Y., & Pietenpol, J. A. (2011). Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. The Journal of Clinical Investigation, 121, 2751–2766.
Loi, S., Piccart, M., & Sotiriou, C. (2007). The use of gene-expression profiling to better understand the clinical heterogeneity of estrogen receptor positive breast cancers and tamoxifen response. Critical Reviews in Oncology/Hematology, 61, 188–193.
Loi, S., Sotiriou, C., Haibe-Kains, B., Lallemand, F., Conus, N. M., Piccart, M. J., Speed, T. P., & Mc Arthur, G. A. (2009). Gene expression profiling identifies activated growth factor signaling in poor prognosis (Luminal-B) estrogen receptor positive breast cancer. BMC Medical Genomics, 2, 37.
Lonning, P. E. (2012). Poor-prognosis estrogen receptor–positive disease: Present and future clinical solutions. Therapeutic Advances in Medical Oncology, 4, 128–136.
Massarweh, S., Osborne, C. K., Creighton, C. J., Qin, L., Tsimelzon, A., Huang, S., Weiss, H., Rimawi, M., & Schif, R. (2008). Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function. Cancer Research, 68(3), 827–832.
Melchor, L., & Benítez, J. (2008). An integrative hypothesis about the origin and development of sporadic and familial breast cancer subtypes. Carcinogenesis, 29(8), 1476–1481.
Nadji, M., Gomez-Fernandez, C., Ganjei-Azar, P., & Morales, A. R. (2005). Immunohistochemistry of estrogen and progesterone receptors reconsidered: experience with 5,993 breast cancers. American Journal of Clinical Pathology, 123, 22–26.
Nishimura, R., Osako, T., Okumura, Y., Hayashi, M., Toyozumi, Y., & Arima, N. (2010). Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer. Expernal and Therapeutic Medicine, 1(5), 748–755.
Olopade, O. I., Grushko, T. A., Nanda, R., & Huo, D. (2008). Advances in breast cancer: Pathways to personalized medicine. Clinical Cancer Research, 14, 7987–7998.
Parker, J. S., Mullins, M., Cheang, M. U., Leung, S., Voduc, D., Vickery, T., Davies, S., Fauron, C., He, X., Hu, Z., Quackenbush, J. F., Stijleman, I. J., Palazzo, J., Marron, J. S., Nobel, A. N., Mardis, E., Nielsen, T. O., Ellis, M. J., Perou, C. M., & Bernard, P. S. (2009). Supervised risk predictor of breast cancer based on intrinsic subtypes. Journal of Clinical Oncology, 27, 1161–1166.
Perou, C. M., Sorlie, T., Eisen, M. B., van de Rijn, M., Jeffrey, S. S., Rees, C. A., Pollack, J. R., Ross, D. T., Johnsen, H., Akslen, L. A., Fluge, O., Pergamenschikov, A., Williams, C., Zhu, S. X., Lonning, P. E., Borresen-Dale, A. L., Brown, P. O., & Botstein, D. (2000). Molecular portraits of human breast tumours. Nature, 406, 748–751.
Polyak, K. (2011). Heterogeneity in breast cancer. The Journal of Clinical Investigation, 121, 3787–3788.
Prat, A., & Perou, C. M. (2011). Deconstructing the molecular portraits of breast cancer. Molecular Oncology, 5, 6–21.
Prat, A., Pineda, E., Adamo, B., Galván, P., Fernández, A., Gaba, L., Díez, M., Viladot, M., Arance, A., & Muñoz, M. (2015). Clinical implications of the intrinsic molecular subtypes of breast cancer. The Breast, 24, 25–34.
Rakha, E. A., Elsheikh, S. E., Aleskandarany, M. A., Habashi, H. O., Green, A. R., Powe, D. G., El-Sayed, M. E., Benhasouna, A., Brunet, J. S., Akslen, L. A., Evans, A. J., Blamey, R., Reis-Filho, J. S., Foulkes, W. D., & Ellis, I. O. (2009). Triple-negative breast cancer: Distinguishing between basal and nonbasal subtypes. Clinical Cancer Research, 15, 2301–2309.
Schnitt, S. J. (2010). Classification and prognosis of invasive breast cancer: From morphology to molecular taxonomy. Modern Pathology, 23, 61–64.
Siegel, R. L., Miller, K. D., & Jemal, A. (2016). Cancer statistics, 2016. CA: A Cancer Journal for Clinicans, 66(1), 7–30.
Sorlie, T., Perou, C. M., Tibshirani, R., Aas, T., Geisler, S., Johnsen, H., Hastie, T., Eisen, M. B., Van de Rijn, M., Jeffrey, S. S., Thorsen, T., Quist, H., Matese, J. C., Brown, P. O., Botstein. D., Lonning, P. E., & Borresen-Dale, A. L. (2001). Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proceeding of the National Academy of Sciences of the USA, 98, 10868–10873.
Sorlie, T., Tibshirani, R., Parker, J., Hastie, T., Marron, J. S., Nobel, A., Deng, S., Johnsen, H., Pesich, R., Geisler, S., Demeter, J., Perou, C. M., Lonning, P., Brown, P. O., Borresen-Dale, A., & Botstein, D. (2003). Repeated observation of breast tumor subtypes in independent gene expression data sets. Proceeding of the National Academy of Sciences of the USA, 100, 8419–8422.
Wirapati, P., Sotiriou, C., Kunkel, S., Farmer, P., Pradervand, S., Haibe-Kains, B., Desmedt, C., Ignatiadis, M., Sengstag, T., Schütz, F., Goldstein, D. R., Piccart, M., & Delorenzi, M. (2008). Meta-analysis of gene expression profiles in breast cancer: Toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Research, 10, 65.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons «Attribution» 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
