Hostname: page-component-586b7cd67f-l7hp2 Total loading time: 0 Render date: 2024-11-27T02:55:12.192Z Has data issue: false hasContentIssue false
  • English
  • Français

A review of clinical and emerging biomarkers for breast cancers: towards precision medicine for patients

Published online by Cambridge University Press:  11 September 2020

Ernest Osei Open the ORCID record for Ernest Osei [Opens in a new window]
Ernest Osei*
Affiliation:
Department of Medical Physics, Grand River Regional Cancer Centre, Kitchener, ON, Canada Department of Physics and Astronomy, University of Waterloo, Waterloo, ON, Canada Department of Systems Design Engineering, University of Waterloo, Waterloo, ON, Canada Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada
*
Author for correspondence: Ernest Osei, Department of Medical Physics, Grand River Regional Cancer Centre, Kitchener, ON, Canada. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

Breast cancer is the most commonly diagnosed malignancy among women and accounts for about 25% of all new cancer cases and 13% of all cancer deaths in Canadian women. It is a highly heterogeneous disease, encompassing multiple tumour entities, each characterised by distinct morphology, behaviour and clinical implications. Moreover, different breast tumour subtypes have different risk factors, clinical presentation, histopathological features, outcome and response to systemic therapies. Therefore, any strategies capable of the stratification of breast cancer by clinically relevant subtypes are an important requirement for personalised and targeted treatment. Therefore, in the advancement towards the concept of precision medicine that takes individual patient variability into account, several investigators have focused on the identification of effective clinical breast cancer biomarkers that interrogate key aberrant pathways potentially targetable with molecular targeted or immunological therapies.

Methods and materials:

This paper reports on a review of 11 current clinical and emerging biomarkers used in screening for early detection and diagnosis, to stratify patients by disease subtype, to identify patients’ risk for metastatic disease and subsequent relapse, to monitor patient response to specific treatment and to provide clinicians the possibility of prospectively identifying groups of patients who will benefit from a particular treatment.

Conclusion:

The future holds promising for the use of effective clinical breast cancer biomarkers for early detection and personalised patient-specific targeted treatment and increased patient survival. Breast cancer biomarkers can potentially assist in early-staged, non-invasive, sensitive and specific breast cancer detection and screening, provide clinically useful information for identification of patients with a greater likelihood of benefiting from the specific treatment, offer a better understanding of the metastatic process in cancer patients, predict disease and for patients with the established disease can assist define the nature of the disease, monitor the success of treatment and guide the clinical management of the disease.

Keywords

breast cancerscancer metastasisemerging biomarkersprecision medicinetargeted therapy
Type
Literature Review
Information
Journal of Radiotherapy in Practice , Volume 21 , Issue 2 , June 2022 , pp. 245 - 258
Check for updates
Copyright
© The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Brenner, D R, Weir, H K, Demers, A A et al. for the Canadian Cancer Statistics Advisory Committee. Projected estimates of cancer in Canada in 2020. CMAJ 2020; 192 (9): E199–E205. http://dx.doi.org/10.1503/cmaj.191292 CrossRefGoogle ScholarPubMed
Canadian Cancer Society. Breast Cancer Statistics. 2020. https://www.cancer.ca/en/cancer-information/cancer-type/breast/statistics/?region=on. Accessed on 17th April 2020.Google Scholar
Dai, X, Xiang, L, Li, T, Bai, Z. Cancer hallmarks, biomarkers and breast cancer molecular subtypes. J Cancer 2016; 7 (10): 1281–1294.CrossRefGoogle ScholarPubMed
Weigel, M T, Dowsett, M. Current and emerging biomarkers in breast cancer: prognosis and prediction. Endocr Relat Cancer 2010; 17 (4): R245–R262.CrossRefGoogle ScholarPubMed
Duffy, M J, Harbeck, N, Nap, M et al. Clinical use of biomarkers in breast cancer: updated guidelines from the European Group on Tumor Markers (EGTM). Eur J Cancer 2017; 75: 284–298. http://dx.doi.org/10.1016/j.ejca.2017.01.017 CrossRefGoogle Scholar
Goossens, N, Nakagawa, S, Sun, X, Hoshida, Y. Cancer biomarker discovery and validation. Transl Cancer Res 2015; 4 (3): 256–269. http://dx.doi.org/10.3978/j.issn.2218-676X.2015.06.04 Google ScholarPubMed
Ballman, K V. Biomarker: predictive or prognostic? J Clin Oncol 2015; 33 (33): 3968–3971.CrossRefGoogle ScholarPubMed
Platet, N, Cathiard, A M, Gleizes, M, Garcia, M. Estrogens and their receptors in breast cancer progression: a dual role in cancer proliferation and invasion. Crit Rev Oncol Hematol 2004; 51 (1): 55–67.CrossRefGoogle ScholarPubMed
Ulaner, G A, Riedl, C C, Dickler, M N, Jhaveri, K, Pandit-Taskar, N, Weber, W. Molecular imaging of biomarkers in breast cancer. J Nucl Med 2016; 57 (Suppl. 1): 53S–59S.CrossRefGoogle ScholarPubMed
Chan, M, Chang, M C, Gonzalez, R et al. Outcomes of estrogen receptor negative and progesterone receptor positive breast cancer. PLoS One 2015; 10 (7).CrossRefGoogle ScholarPubMed
Burstein, H J, Lacchetti, C, Anderson, H et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol 2019; 37 (5): 423–438. http://dx.doi.org/10.1200/JCO.18.01160 CrossRefGoogle ScholarPubMed
Colleoni, M, Montagna, E. Neoadjuvant therapy for ER-positive breast cancers. Ann Oncol 2012; 23 (Suppl. 10): X243e8.CrossRefGoogle ScholarPubMed
Bardou, V-J, 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): 1973–1979.CrossRefGoogle ScholarPubMed
Dowsett, M, Houghton, J, Iden, C et al. Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status. Ann Oncol 2006; 17: 818–826.CrossRefGoogle ScholarPubMed
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies, C, Godwin, J, Gray, R et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level metaanalysis of randomised trials. Lancet 2011; 378: 771e84.Google Scholar
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 2015; 386 (10001): 1341–1352.CrossRefGoogle Scholar
Purdie, C J, Quinlan, P, Jordan, L B et al. Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study. Br J Cancer 2014; 110: 565–572.CrossRefGoogle ScholarPubMed
Rugo, H S, Rumble, R B, Macrae, E et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology Guideline. J Clin Oncol 2016; 34 (25): 3069–3103.CrossRefGoogle ScholarPubMed
Goss, P E, Ingle, J N, Pritchard, K I et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med 2016; 375 (3): 209–219. http://dx.doi.org/10.1056/NEJMoa1604700 CrossRefGoogle ScholarPubMed
Davies, C, Pan, H, Godwin, J et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 2013; 381: 805–816. http://dx.doi.org/10.1016/S0140-6736(12)61963-1 CrossRefGoogle ScholarPubMed
Villalobos, P, Wistuba, I I. Lung cancer biomarkers. Hematol Oncol Clin 2017; 31 (1): 13–29.CrossRefGoogle ScholarPubMed
Pillai, R N, Behera, M, Berry, L D et al. HER2 mutations in lung adenocarcinomas: a report from the Lung Cancer Mutation Consortium. Cancer 2017; 123 (21): 4099–4105. http://dx.doi.org/10.1002/cncr.30869 CrossRefGoogle ScholarPubMed
Osei, E, Lumini, J, Gunasekara, D et al. A review of predictive, prognostic and diagnostic biomarkers for non-small-cell lung cancer: towards personalised and targeted cancer therapy. J Radiother Pract 2019: 1–15. http://dx.doi.org/10.1017/S1460396919000876 Google Scholar
Dawood, S, Broglio, K, Buzdar, A U et al. Prognosis of women with metastatic breast cancer by HER2 status and trastuzumab treatment: an institutional-based review. J Clin Oncol 2010; 28 (1): 92–98. http://dx.doi.org/10.1200/JCO.2008.19.9844 CrossRefGoogle ScholarPubMed
Mitri, Z, Constantine, T, O’Regan, R. The HER2 receptor in breast cancer: pathophysiology, clinical use, and new advances in therapy. Chemother Res Pract 2012: 2012.Google ScholarPubMed
Arteaga, C L, Sliwkowski, M X, Osborne, C K et al. Treatment of HER2-positive breast cancer: current status and future perspectives. Nat Rev Clin Oncol 2012; 9 (1): 16–32.CrossRefGoogle Scholar
Burstein, H J. The distinctive nature of HER2-positive breast cancers. N Engl J Med 2005; 353 (16): 1652.CrossRefGoogle ScholarPubMed
Piccart-Gebhart, M J, Procter, M, Leyland-Jones, B et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005; 353 (16): 1659–1672.CrossRefGoogle ScholarPubMed
Pritchard, K I, Shepherd, L E, O’Malley, F P et al. HER2 and responsiveness of breast cancer to adjuvant chemotherapy. N Engl J Med 2006; 354 (20): 2103–2111.CrossRefGoogle ScholarPubMed
Ross, J S, Fletcher, J A. The HER-2/neu oncogene in breast cancer: prognostic factor, predictive factor, and target for therapy. Stem Cells 1998; 16 (6): 413–428.CrossRefGoogle ScholarPubMed
Fountzilas, G, Christodoulou, C, Bobos, M et al. Topoisomerase II alpha gene amplification is a favorable prognostic factor in patients with HER2-positive metastatic breast cancer treated with trastuzumab. J Transl Med 2012; 10: 212. http://dx.doi.org/10.1186/1479-5876-10-212 CrossRefGoogle ScholarPubMed
Colomer, R, Aranda-López, I, Albanell, J et al. Biomarkers in breast cancer: a consensus statement by the Spanish Society of Medical Oncology and the Spanish Society of Pathology. Clin Transl Oncol 2018; 20 (7): 815–826. http://dx.doi.org/10.1007/s12094-017-1800-5. Erratum in: Clin Transl Oncol 2018.CrossRefGoogle ScholarPubMed
Slamon, D, Eiermann, W, Robert, N et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011; 365 (14): 1273–1283.CrossRefGoogle ScholarPubMed
Konecny, G, Pauletti, G, Pegram, M et al. Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer. J Natl Cancer Inst 2003; 95: 142–153.CrossRefGoogle ScholarPubMed
Hu, Z, Fan, C, Oh, D S et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 2006; 7: 96.CrossRefGoogle ScholarPubMed
Romond, E H, Perez, E A, Bryant, J et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005; 353 (16): 1673–1684.CrossRefGoogle ScholarPubMed
Slamon, D J, Leyland-Jones, B, Shak, S et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344 (11): 783–792.CrossRefGoogle Scholar
Scholzen, T, Gerdes, J. The Ki 67 protein: from the known and the unknown. J Cell Physiol 2000; 182: 311–322.3.0.CO;2-9>CrossRefGoogle Scholar
Li, L T, Jiang, G, Chen, Q, Zheng, J N. Ki67 is a promising molecular target in the diagnosis of cancer (review). Mol Med Rep 2015; 11 (3): 1566–1572. https://doi.org/10.3892/mmr.2014.2914 CrossRefGoogle Scholar
Ingolf, J B, Russalina, M, Simona, M et al. Can ki-67 play a role in prediction of breast cancer patients’ response to neoadjuvant chemotherapy? Biomed Res Int 2014; 2014: 628217. https://doi.org/10.1155/2014/628217 CrossRefGoogle ScholarPubMed
Inwald, E C, Klinkhammer-Schalke, M, Hofstädter, F 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): 539–552. https://doi.org/10.1007/s10549-013-2560-8 CrossRefGoogle ScholarPubMed
Soliman, N A, Yussif, S M. Ki-67 as a prognostic marker according to breast cancer molecular subtype. Cancer Biol Med 2016; 13 (4): 496–504. https://doi.org/10.20892/j.issn.2095-3941.2016.0066 Google ScholarPubMed
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): 5569–5575. https://doi.org/10.1200/JCO.2008.17.0829 CrossRefGoogle Scholar
Fasching, P A, Heusinger, K, Haeberle, L et al. Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment. BMC Cancer 2011; 11 (1): 486.CrossRefGoogle ScholarPubMed
Wang, W, Wu, J, Zhang, P et al. Prognostic and predictive value of Ki-67 in triple-negative breast cancer. Oncotarget 2016; 7 (21): 31079–31087. https://doi.org/10.18632/oncotarget.9075 CrossRefGoogle ScholarPubMed
Banys-Paluchowski, M, Schneck, H, Blassl, C et al. Prognostic relevance of circulating tumor cells in molecular subtypes of breast cancer. Geburtshilfe Frauenheilkd 2015; 75 (03): 232–237.Google ScholarPubMed
Nadal, R, Lorente, J A, Rosell, R, Serrano, M J. Relevance of molecular characterization of circulating tumor cells in breast cancer in the era of targeted therapies. Expert Rev Mol Diagn 2013; 13 (3): 295–307.CrossRefGoogle ScholarPubMed
Wang, C H, Chang, C J, Yeh, K Y et al. The prognostic value of HER2-positive circulating tumor cells in breast cancer patients: a systematic review and meta-analysis. Clin Breast Cancer 2017; 17 (5): 341–349. https://doi.org/10.1016/j.clbc.2017.02.002 CrossRefGoogle ScholarPubMed
Yap, Y S, Leong, M C, Chua, Y W et al. Detection and prognostic relevance of circulating tumour cells (CTCs) in Asian breast cancers using a label-free microfluidic platform. PLoS One 2019; 14 (9): e0221305. https://doi.org/10.1371/journal.pone.0221305 CrossRefGoogle ScholarPubMed
Perakis, S, Speicher, M R. Emerging concepts in liquid biopsies. BMC Med 2017; 15: 75. https://doi.org/10.1186/s12916-017-0840-6 CrossRefGoogle ScholarPubMed
Ferreira, M M, Ramani, V C, Jeffrey, S S. Circulating tumor cell technologies. Mol Oncol 2016; 10 (3): 374–394. https://doi.org/10.1016/j.molonc.2016.01.007 CrossRefGoogle ScholarPubMed
Ashworth, T R. A case of cancer in which cells similar to those in the tumours were seen in the blood after death. Austr Med J 1869; 14: 146–147.Google Scholar
Osei, E, Al-Ani, N, Al-Asady, A, Dang, S. Liquid biomarkers for the management of paediatric neuroblastoma: an approach to personalised and targeted cancer therapy. J Radiother Pract 2020, 1–13. https://doi.org/10.1017/S1460396920000102 Google Scholar
Alemar, J, Schuur, E R. Progress in using circulating tumor cell information to improve metastatic breast cancer therapy. J Oncol 2013; 2013.Google ScholarPubMed
Bidard, F C, Proudhon, C, Pierga, J Y. Circulating tumor cells in breast cancer. Mol Oncol 2016; 10 (3): 418–430.CrossRefGoogle ScholarPubMed
Usiakova, Z, Mikulova, V, Pinterova, D et al. Circulating tumor cells in patients with breast cancer: monitoring chemotherapy success. In Vivo 2014; 28(4): 605–14.Google ScholarPubMed
Hartkopf, A D, Banys, M, Krawczyk, N et al. circulating tumor cells in early-stage breast cancer. Geburtshilfe Frauenheilkd 2011; 71 (12): 1067–1072. https://doi.org/10.1055/s-0031-1280463 Google ScholarPubMed
Bidard, F C, Michiels, S, Riethdorf, S et al. Circulating tumor cells in breast cancer patients treated by neoadjuvant chemotherapy: a meta-analysis. J Natl Cancer Inst 2018; 110 (6): 560–567.CrossRefGoogle ScholarPubMed
Pruneri, G, Vingiani, A, Denkert, C. Tumor infiltrating lymphocytes in early breast cancer. Breast 2018; 37: 207–214. https://doi.org/10.1016/j.breast.2017.03.010 CrossRefGoogle ScholarPubMed
Mao, Y, Qu, Q, Chen, X et al. The prognostic value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis. PLoS One 2016; 11 (4): e0152500. https://doi.org/10.1371/journal.pone.0152500 CrossRefGoogle ScholarPubMed
Demaria, S, Volm, M D, Shapiro, R L et al. Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy. Clin Cancer Res 2001; 7 (10): 3025–3030.Google ScholarPubMed
Wang, K, Xu, J, Zhang, T, Xue, D. Tumor-infiltrating lymphocytes in breast cancer predict the response to chemotherapy and survival outcome: A meta-analysis. Oncotarget 2016; 7 (28): 44288–44298. https://doi.org/10.18632/oncotarget.9988 CrossRefGoogle ScholarPubMed
Yu, X, Zhang, Z, Wang, Z et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis. Clin Transl Oncol 2016; 18 (5): 497–506. https://doi.org/10.1007/s12094-015-1391-y CrossRefGoogle ScholarPubMed
Denkert, C, Wienert, S, Poterie, A et al. Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group. Mod Pathol 2016; 29 (10): 1155–1164. https://doi.org/10.1038/modpathol.2016.109 CrossRefGoogle ScholarPubMed
Dushyanthen, S, Beavis, PA., Savas, P et al. Relevance of tumor-infiltrating lymphocytes in breast cancer. BMC Med 2015; 13: 202. https://doi.org/10.1186/s12916–015–0431–3 CrossRefGoogle ScholarPubMed
Stanton, S E, Adams, S, Disis, M L. Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: a systematic review. J Am Med Assoc Oncol 2016; 2 (10): 1354–1360. https://doi.org/10.1001/jamaoncol.2016.1061 Google ScholarPubMed
Stanton, S E, Disis, M L. Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J Immunother Cancer 2016; 4: 59. https://doi.org/ 10.1186/s40425-016-0165-6 CrossRefGoogle ScholarPubMed
Denkert, C, von Minckwitz, G, Brase, J C et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol 2015; 33: 983–991.CrossRefGoogle ScholarPubMed
Champoux, J J. DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem 2001; 70 (1): 369–413.CrossRefGoogle ScholarPubMed
Dekker, N H, Rybenkov, V V, Duguet, M et al. The mechanism of type IA topoisomerases. Proc Natl Acad Sci U S A 2002; 99 (19): 12126–12131. https://doi.org/10.1073/pnas.132378799 CrossRefGoogle ScholarPubMed
Heestand, G M, Schwaederle, M, Gatalica, Z, Arguello, D, Kurzrock, R. Topoisomerase expression and amplification in solid tumours: analysis of 24,262 patients. Eur J Cancer 2017; 83: 80–87. https://doi.org/10.1016/j.ejca.2017.06.019 CrossRefGoogle ScholarPubMed
Ren, L, Liu, J, Gou, K, Xing, C. Copy number variation and high expression of DNA topoisomerase II alpha predict worse prognosis of cancer: a meta-analysis. J Cancer 2018; 9 (12): 2082–2092. https://doi.org/10.7150/jca.23681 CrossRefGoogle ScholarPubMed
Romero, A, Martín, M, Cheang, M C et al. Assessment of Topoisomerase II α status in breast cancer by quantitative PCR, gene expression microarrays, immunohistochemistry, and fluorescence in situ hybridization. Am J Pathol 2011; 178 (4): 1453–1460. https://doi.org/10.1016/j.ajpath.2010.12.042 CrossRefGoogle ScholarPubMed
An, X, Xu, F, Luo, R et al. The prognostic significance of topoisomerase II alpha protein in early stage luminal breast cancer. BMC Cancer 2018; 18 (1): 331. https://doi.org/10.1186/s12885-018-4170-7 CrossRefGoogle ScholarPubMed
O’Malley, F P, Chia, S, Tu, D et al. Topoisomerase II alpha and responsiveness of breast cancer to adjuvant chemotherapy. J Natl Cancer Inst 2009; 101 (9): 644–650. https://doi.org/10.1093/jnci/djp067 CrossRefGoogle ScholarPubMed
Depowski, P L, Rosenthal, S I, Brien, T P et al. Topoisomerase IIalpha expression in breast cancer: correlation with outcome variables. Mod Pathol 2000; 13 (5): 542–547. https://doi.org/10.1038/modpathol.3880094 CrossRefGoogle ScholarPubMed
Duffy, M J, McGowan, P M, Harbeck, N et al. uPA and PAI-1 as biomarkers in breast cancer: validated for clinical use in level-of-evidence-1 studies. Breast Cancer Res 2014; 16: 428. https://doi.org/10.1186/s13058–014–0428–4 CrossRefGoogle ScholarPubMed
Gouri, A, Dekaken, A, Bairi, K E et al. Plasminogen activator system and breast cancer: potential role in therapy decision making and precision medicine. Biomarker Insights 2016: BMI-S33372.CrossRefGoogle ScholarPubMed
Harbeck, N, Kates, R E, Schmitt, M et al. Urokinase-type plasminogen activator and its inhibitor type 1 predict disease outcome and therapy response in primary breast cancer. Clin Breast Cancer 2004; 5 (5): 348–352. https://doi.org/10.3816/cbc.2004.n.040 CrossRefGoogle ScholarPubMed
Meijer-van Gelder, M E, Look, M P, Peters, H A et al. Urokinase-type plasminogen activator system in breast cancer: association with tamoxifen therapy in recurrent disease. Cancer Res 2004; 64 (13): 4563–4568.CrossRefGoogle ScholarPubMed
Banys-Paluchowski, M, Witzel, I, Aktas, B et al. The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer. Sci Rep 2019; 9 (1): 2318. https://doi.org/10.1038/s41598-018-37259-2 CrossRefGoogle ScholarPubMed
Look, M P, van Putten, W L J, Duffy, M J et al. Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. J Natl Cancer Inst (Bethesda) 2002; 94: 116–128.CrossRefGoogle ScholarPubMed
Mahmood, N, Mihalcioiu, C, Rabbani, S A. Multifaceted role of the Urokinase-Type Plasminogen Activator (uPA) and Its Receptor (uPAR): diagnostic, prognostic, and therapeutic applications. Front Oncol 2018; 8: 24. https://doi.org/10.3389/fonc.2018.00024 CrossRefGoogle ScholarPubMed
Harms, W, Malter, W, Krämer, S et al. Clinical significance of urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-1) for metastatic sentinel lymph node involvement in breast cancer. Anticancer Res 2014; 34 (8): 4457–4462.Google ScholarPubMed
Si, H, Sun, X, Chen, Y et al. Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol 2013; 139 (2): 223–229.CrossRefGoogle ScholarPubMed
Fu, S W, Chen, L, Man, Y G. miRNA biomarkers in breast cancer detection and management. J Cancer 2011; 2: 116–122.CrossRefGoogle ScholarPubMed
Heneghan, H M, Miller, N, Lowery, A J et al. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg 2010; 251 (3): 499–505.CrossRefGoogle ScholarPubMed
Heneghan, H M, Miller, N, Lowery, A J et al. MicroRNAs as novel biomarkers for breast cancer. J Oncol 2009; 2009: 950201. https://doi.org/10.1155/2010/950201 Google ScholarPubMed
Ng, E K, Li, R, Shin, V Y et al. Circulating microRNAs as specific biomarkers for breast cancer detection. PLoS One 2013; 8 (1): e53141.CrossRefGoogle ScholarPubMed
Kashyap, D, Kaur, H. Cell-free miRNAs as non-invasive biomarkers in breast cancer: significance in early diagnosis and metastasis prediction. Life Sci 2020; 246: 117417. https://doi.org/10.1016/j.lfs.2020.117417 CrossRefGoogle ScholarPubMed
Aaltonen, K, Blomqvist, C, Amini, R M et al. Familial breast cancers without mutations in BRCA1 or BRCA2 have low cyclin E and high cyclin D1 in contrast to cancers in BRCA mutation carriers. Clin Cancer Res 2008; 14 (7): 1976–1983. https://doi.org/10.1158/1078-0432.CCR-07-4100 CrossRefGoogle ScholarPubMed
Aaltonen, K, Amini, R M, Landberg, G et al. Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer. Breast Cancer Res Treat 2009; 113 (1): 75–82.CrossRefGoogle ScholarPubMed
Hui, R, Finney, G L, Carroll, J S et al. Constitutive overexpression of cyclin D1 but not cyclin E confers acute resistance to antiestrogens in T-47D breast cancer cells. Cancer Res 2002; 62 (23): 6916–6923.Google Scholar
Roy, P G, Thompson, A M. Cyclin D1 and breast cancer. Breast 2006; 15 (6): 718–727. https://doi.org/10.1016/j.breast.2006.02.005 CrossRefGoogle ScholarPubMed
Lodén, M, Stighall, M, Nielsen, N H et al. The cyclin D1 high and cyclin E high subgroups of breast cancer: separate pathways in tumorogenesis based on pattern of genetic aberrations and inactivation of the pRb node. Oncogene 2002; 21 (30): 4680–4690. https://doi.org/10.1038/sj.onc.1205578 CrossRefGoogle ScholarPubMed
Han, S, Park, K, Bae, B N et al. Prognostic implication of cyclin E expression and its relationship with cyclin D1 and p27Kip1 expression on tissue microarrays of node negative breast cancer. J Surg Oncol 2003; 83 (4): 241–247. https://doi.org/10.1002/jso.10268 CrossRefGoogle ScholarPubMed
Gómez Lahoz, E, Liegeois, N J, Zhang, P et al. Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo. Mol Cell Biol 1999; 19(1): 353–363. https://doi.org/10.1128/mcb.19.1.353 CrossRefGoogle ScholarPubMed
Elkon, K, Casali, P. Nature and functions of autoantibodies. Nat Clin Pract Rheumatol 2008; 4 (9): 491–498. https://doi.org/10.1038/ncprheum0895 CrossRefGoogle ScholarPubMed
Leslie, D, Lipsky, P, Notkins, A L. Autoantibodies as predictors of disease. J Clin Invest 2001; 108 (10): 1417–1422. https://doi.org/10.1172/JCI14452 CrossRefGoogle ScholarPubMed
Chapman, C, Murray, A, Chakrabarti, J et al. Autoantibodies in breast cancer: their use as an aid to early diagnosis. Ann Oncol 2007; 18 (5): 868–873. https://doi.org/10.1093/annonc/mdm007 CrossRefGoogle ScholarPubMed
Lacombe, J, Mangé, A, Jarlier, M et al. Identification and validation of new autoantibodies for the diagnosis of DCIS and node negative early-stage breast cancers. Int J Cancer 2013; 132 (5): 1105–1113. https://doi.org/10.1002/ijc.27766 CrossRefGoogle Scholar
Wang, J, Figueroa, J D, Wallstrom, G et al. Plasma autoantibodies associated with basal-like breast cancers. Cancer Epidemiol Prevent Biomark 2015; 24 (9): 1332–1340.CrossRefGoogle ScholarPubMed
Madrid, F F. Autoantibodies in breast cancer sera: candidate biomarkers and reporters of tumorigenesis. Cancer Lett 2005; 230 (2): 187–198.Google Scholar
Blixt, O, Bueti, D, Burford, B et al. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis. Breast Cancer Res 2011; 13 (2): R25. https://doi.org/10.1186/bcr2841 CrossRefGoogle ScholarPubMed
Zhong, L, Ge, K, Zu, J C et al. Autoantibodies as potential biomarkers for breast cancer. Breast Cancer Res 2008; 10 (3): R40.CrossRefGoogle ScholarPubMed
Yagihashi, A, Ohmura, T, Asanuma, K et al. Detection of autoantibodies to survivin and livin in sera from patients with breast cancer. Clin Chim Acta 2005; 362 (1–2): 125–130. https://doi.org/10.1016/j.cccn.2005.06.009 CrossRefGoogle ScholarPubMed