Abstract
Breast cancer screening and presurgical diagnosis are currently based on mammography, ultrasound and more sensitive imaging technologies; however, noninvasive biomarkers represent both a challenge and an opportunity for early detection of cancer. An extensive number of potential breast cancer biomarkers have been discovered by microarray hybridization or sequencing of circulating DNA, noncoding RNA and blood cell RNA; multiplex analysis of immune-related molecules and mass spectrometry-based approaches for high-throughput detection of protein, endogenous peptides, circulating and volatile metabolites. However, their medical relevance and their translation to clinics remain to be exploited. Once they will be fully validated, cancer biomarkers, used in combination with the current and emerging imaging technologies, represent an avenue to a personalized breast cancer diagnosis.
Papers of special note have been highlighted as: • of interest
References
- 1 Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl Acad. Sci. USA 98(19), 10869–10874 (2001). • It reports the subtype classification of breast carcinoma based on variation of gene-expression pattern.
- 2 The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486(7403), 346–352 (2012).
- 3 The Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 490(7418), 61–70 (2012).
- 4 . Clinical management of breast cancer heterogeneity. Nat. Rev. Clin. Oncol. 12(7), 381–394 (2015).
- 5 Trastuzumab-containing regimens for metastatic breast cancer. Cochrane Database Syst. Rev. 6, CD006242 (2014).
- 6 The global burden of cancer. JAMA Oncol. 1(4), 505–527 (2013).
- 7 Challenges to effective cancer control in China, India, and Russia. Lancet Oncol. 15(5), 489–538 (2014).
- 8 The case for early detection. Nat. Rev. Cancer 3(4), 243–252 (2003).
- 9 Cancer Statistics, SEER Stat Fact Sheets: Breast Cancer (2015). http://seer.cancer.gov/statfacts/html/breast.html.
- 10 . Prioritizing targets for precision cancer medicine. Ann. Oncol. 25(12), 2295–2303 (2014).
- 11 . Cancer genome landscapes. Science 339(6127), 1546–1558 (2013).
- 12 . Translational implications of tumor heterogeneity. Clin. Cancer Res. 21(6), 1258–1266 (2015).
- 13 . Molecular evolution of breast cancer. J. Pathol. 205(2), 248–254 (2005).
- 14 . Future directions in cancer prevention. Nat. Rev. Cancer 12(12), 835–848 (2012).
- 15 . Immune targeting in breast cancer. Oncology 29(5), 375–85 (2015).
- 16 . Role of inflammatory infiltrates in triple negative breast cancer. J. Clin. Pathol. 68(7), 506–510 (2015).
- 17 . Assessment, origin, and implementation of breath volatile cancer markers. Chem. Soc. Rev. 43(5), 1423–1449 (2014).
- 18 . Onco-proteogenomics: cancer proteomics joins forces with genomics. Nat. Methods 11(11), 1107–1113 (2014).
- 19 . Proteomics retrenches. Nat. Biotechnol. 28(7), 665–670 (2010).
- 20 . Systems biology: metabonomics. Nature 455(7216), 1054–1056 (2008).
- 21 . Plasma protein profiling by MS for cancer diagnosis: opportunities and limitations. Clin. Cancer Res. 11(3), 963–965 (2005).
- 22 Use of ruquant BR radioimmunoassay for early detection of breast cancer recurrence in patients with stage II and stage III disease. J. Clin. Oncol. 15(6), 2322–2328 (1997).
- 23 . The evidence base for breast cancer screening. Prev. Med. 53(3), 100–102 (2011).
- 24 Pan-Canadian study of mammography screening and mortality from breast cancer. J. Natl Cancer Inst. 106(11), dju261 (2014).
- 25 International Agency for Research on Cancer Handbook Working Group. Breast-cancer screening – viewpoint of the IARC Working Group. N. Engl. J. Med. 372(24), 2353–2358 (2015).
- 26 . Why do purely intraductal cancers enhance on breast MR images? Radiology 253(2), 281–283 (2009). • It enables to improve sensitivity of MRI, even in preinvasive carcinoma.
- 27 . Breast MR imaging in women at high-risk of breast cancer. Is something changing in early breast cancer detection? Eur. Radiol. 17(4), 873–887 (2007).
- 28 US Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann. Intern. Med. 151(10), 716–726 (2009).
- 29 Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J. Clin. Oncol. 23(33), 8469–8476 (2005). • It is the first report focused on the relevance of MRI in early detection of breast carcinoma in high familial risk women.
- 30 . The randomized trials of breast cancer screening: what have we learned? Radiol. Clin. North. Am. 42(5), 793–806 (2004).
- 31 . Breast cancer screening in women: an integrative literature review. J. Am. Acad. Nurse Pract. 22(12), 668–673 (2010).
- 32 . Clinical utility of bilateral whole-breast US in the evaluation of women with dense breast tissue. Radiology 221(3), 641–649 (2001).
- 33 . Isolation of a tumor factor responsible for angiogenesis. J. Exp. Med. 133(2), 275–288 (1971). • It is the pioneer study on cancer angiogenesis and represents the biological basis of MRI interpretation.
- 34 High Breast Cancer Risk Italian 1 (HIBCRIT-1) Study. Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the High Breast Cancer Risk Italian 1 study): final results. Invest. Radiol. 46(2), 94–105 (2011). • It confirms the validity of MRI for diagnosis in mutation carrier women and endorses the role of MRI for dedicated programs of screening in women at high risk.
- 35 Prospective multicenter cohort study to refine management reccomendations for women at elevated familial risk of breast cancer: the EVA trial. J. Clin. Oncol. 28(9), 1450–1457 (2010).
- 36 . Early diagnosis of hereditary breast cancer by magnetic resonance imaging: what is realistic? J. Clin. Oncol. 28(9), 1441–1445 (2010).
- 37 . Magnetic resonance imaging reveals functional diversity of the vasculature in benign and malignant breast lesions. Cancer 104(4), 708–718 (2005).
- 38 . Dynamic contrast-enhanced breast MR imaging. Magn. Reson. Imaging Clin. N. Am. 17(2), 351–362 (2009).
- 39 Differentiation of clinically benign and malignant breast lesions using diffusion-weighted imaging. J. Magn. Reson. Imaging 16(2), 172–178 (2002).
- 40 . Clinical utility of proton magnetic resonance spectroscopy in characterizing breast lesions. J. Natl Cancer Inst. 94(16), 1197–1203 (2002).
- 41 . Utilisation of MR spectroscopy and diffusion weighted imaging in predicting and monitoring of breast cancer response to chemotherapy. J. Med. Imaging Radiat. Oncol. 59(3), 268–277 (2015).
- 42 Radiogenomic analysis of breast cancer using MRI: a preliminary study to define the landscape. AJR Am. J. Roentgenol. 199(3), 654–632 (2012).
- 43 . Radiogenomic analysis of breast cancer: luminal B molecular subtype is associated with enhancement dynamics at MR imaging. Radiology 273(2), 365–372 (2014).
- 44 Breast cancer: radiogenomic biomarker reveals associations among dynamic contrast-enhanced MR imaging, long noncoding RNA, and metastasis. Radiology 275(2), 384–392 (2015).
- 45 . The Clinical Relevance of Long noncoding RNAs in Cancer. Cancers 7(4), 2169–2182 (2015).
- 46 . Human body fluid proteome analysis. Proteomics 6(23), 6326–6253 (2006).
- 47 . Proteomics for breast cancer urine biomarkers. Adv. Clin. Chem. 63, 123–167 (2014).
- 48 . Peptidomics of urine and other biofluids for cancer diagnostics. Clin. Chem. 60(8), 1052–1061 (2014).
- 49 . Human saliva proteome analysis and disease biomarker discovery. Expert. Rev. Proteomics. 4(4), 531–538 (2007).
- 50 . The use of soluble, salivary c-erbB-2 for the detection and post-operative follow-up of breast cancer in women: the results of a five-year translational research study. Adv. Dent. Res. 18(1), 17–24 (2005).
- 51 . Biomarkers for risk assessment and prevention of breast cancer. Curr. Cancer Drug Targets. 9(4), 482–499 (2009).
- 52 . Emerging molecular biomarkers – blood-based strategies to detect and monitor cancer. Nat. Rev. Clin. Oncol. 8(3), 142–150 (2011).
- 53 Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol. 15(4), 406–414 (2014).
- 54 Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer. Br. J. Cancer 113(1), 150–158 (2015).
- 55 Gene expression profiling of peripheral blood cells for early detection of breast cancer. Breast Cancer Res. 12(1), R7 (2010).
- 56 RNA-seq of tumor-educated platelets enables blood-based pan-cancer, multiclass, and molecular pathway cancer diagnostics. Cancer Cell 28(5), 666–676 (2015). • It proposes platelets as a tool for cancer diagnosis and classification.
- 57 . Diagnosis and treatment of cancer using genomics. BMJ 350, h1832 (2015).
- 58 . Molecular profiling for breast cancer: a comprehensive review. Biomark. Cancer 5, 61–70 (2013).
- 59 . High-throughput sequencing technologies. Mol. Cell. 58(4), 586–597 (2015).
- 60 Analysis of circulating tumor DNA to monitor metastatic breast cancer. N. Engl. J. Med. 368(13), 1199–1209 (2013).
- 61 Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO Mol. Med. 7(8), 1034–1047 (2015).
- 62 Methylated circulating tumor DNA in blood: power in cancer prognosis and response. Endocr. Relat. Cancer. 23(3), R157–R171 (2016).
- 63 ESR1 gene promoter region methylation in free circulating DNA and its correlation with estrogen receptor protein expression in tumor tissue in breast cancer patients. BMC Cancer 14, 59 (2014).
- 64 . Noncoding RNA molecules as potential biomarkers in breast cancer. Adv. Exp. Med. Biol. 867, 263–275 (2015).
- 65 . Circulating miRNAs as new blood-based biomarkers for solid cancers. Future Oncol. 9(3), 387–402 (2013).
- 66 Circulating microRNAs as noninvasive cancer biomarkers in breast cancer. J. Lab. Autom. 20(5), 574–588 (2015).
- 67 Circulating DNA of HOTAIR in serum is a novel biomarker for breast cancer. Breast Cancer Res. Treat. 152(1), 199–208 (2015).
- 68 . Use of autoantibodies to detect the onset of breast cancer. J. Immunol. Res. 2014, 574981 (2014).
- 69 . Electrochemical immunosensors in breast and ovarian cancer. Clin. Chim. Acta 425, 128–138 (2013).
- 70 Multiplex serum cytokine immunoassay using nanoplasmonic biosensor microarrays. ACS Nano 9(4), 4173–4181 (2015).
- 71 . Cytokines and their relationship to the symptoms and outcome of cancer. Nat. Rev. Cancer 8(11), 887–899 (2008).
- 72 Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases. Proc. Natl Acad. Sci. USA 108(34), 14252–14257 (2011).
- 73 Pretreatment levels of circulating Th1 and Th2 cytokines, and their ratios, are associated with ER-negative and triple negative breast cancers. Breast Cancer Res. Treat. 139(2), 477–488 (2013).
- 74 . Advances in MS-based clinical biomarker discovery. Clin. Proteom. 13, 1 (2016).
- 75 Evaluation of a 4-protein serum biomarker panel-biglycan, annexin-A6, myeloperoxidase, and protein S100-A9 (B-AMP)-for the detection of esophageal adenocarcinoma. Cancer 120(24), 3902–3913 (2014).
- 76 . Oncoproteomics. Clin. Chim. Acta 412(3–4), 217–226 (2011).
- 77 . Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer 15(9), 540–555 (2015).
- 78 Microarray glycoprofiling of CA125 improves differential diagnosis of ovarian cancer. J. Proteome Res. 12(3), 1408–1418 (2013).
- 79 . Breast cancer classification by proteomic technologies: current state of knowledge. Cancer Treat. Rev. 40(1), 129–138 (2014).
- 80 Detection of elevated plasma levels of epidermal growth factor receptor before breast cancer diagnosis among hormone therapy users. Cancer Res. 70(21), 8598–606 (2010).
- 81 Differential exoprotease activities confer tumor-specific serum peptidome patterns. J. Clin. Invest. 116(1), 271–284 (2006). • It proposes proteolytic degradative patterns of the serum peptidome as surrogate marker for detection and classification of cancer.
- 82 Circulating proteolytic products of carboxypeptidase N for early detection of breast cancer. Clin. Chem. 60(1), 233–242 (2014).
- 83 . Peptidomics for cancer diagnosis: present and future. J. Proteome Res. 5(9), 2079–2082 (2006).
- 84 Hepcidin and ferritin blood level as noninvasive tools for predicting breast cancer. Ann. Oncol. 25(2), 352–357 (2014).
- 85 . Understanding the warburg effect: the metabolic requirements of cell proliferation. Science 324(5930), 1029–1033 (2009).
- 86 Diacetylspermine is a novel prediagnostic serum biomarker for non-small-cell lung cancer and has additive performance with pro-surfactant protein B. J. Clin. Oncol. 33(33), 3880–3886 (2015).
- 87 Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature 457(7231), 910–914 (2009).
- 88 . Metabolomics biomarkers for breast cancer. Pathobiology 82(3–4), 153–165 (2015).
- 89 . Diagnostic accuracy of canine scent detection in early- and late-stage lung and breast cancers. Integrative Cancer Therapies 5(1), 30–39 (2006).
- 90 Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon. Eur. Respir. J. 39(3), 669–676 (2012). • It provides strong evidence that breath indeed contains relevant biochemical information for cancer detection.
- 91 Volatile organic compounds in breath as markers of lung cancer: a cross-sectional study. Lancet 353(9168), 1930–1933 (1999).
- 92 Detection of lung cancer with volatile markers in the breath. Chest 123(6), 2115–2123 (2003).
- 93 Prediction of breast cancer using volatile biomarkers in the breath. Breast Cancer Res. Treat. 99(1), 19–21 (2006).
- 94 Volatile markers of breast cancer in the breath. Breast J. 9(3), 184–191 (2003).
- 95 Rapid point-of-care breath test for biomarkers of breast cancer and abnormal mammograms. PLoS ONE 9(3), e90226 (2014).
- 96 Thermal degradation of small molecules: a global metabolomic investigation. Anal. Chem. 87(21), 10935–10941 (2015).
- 97 . Volatile biomarkers in the breath of women with breast cancer. J. Breath. Res. 4(2), 026003 (2010).
- 98 Noninvasive detection of lung cancer by analysis of exhaled breath. BMC Cancer 9(1), 348 (2009).
- 99 . Proton-transfer reaction MS. Chem. Rev. 109(3), 861–896 (2009).
- 100 . Proton-transfer-reaction MS (PTR-MS): on-line monitoring of volatile organic compounds at pptv levels. Chem. Soc. Rev. 27(5), 347–354 (1998).
- 101 . Selected ion flow tube MS analysis of volatile metabolites in urine headspace for the profiling of gastro-esophageal cancer. Anal. Chem. 85(6), 3409–3416 (2013).
- 102 . Selected ion flow tube-MS analysis of headspace vapor from gastric content for the diagnosis of gastro-esophageal cancer. Anal. Chem. 84(21), 9550–9557 (2012).
- 103 . Analysis of formaldehyde in the headspace of urine from bladder and prostate cancer patients using selected ion flow tube MS. Rapid. Commun. Mass Spectrom. 13(14), 1354–1359 (1999).
- 104 Secondary electrospray ionization-MS and a novel statistical bioinformatic approach identifies a cancer-related profile in exhaled breath of breast cancer patients: a pilot study. J. Breath Res. 9(3), 031001 (2015).
- 105 . Fingerprinting breast cancer vs. normal mammary cells by mass spectrometric analysis of volatiles. Sci. Rep. 4, 5196 (2014).
- 106 . Data interpretation in breath biomarker research: pitfalls and directions. J. Breath. Res. 6(3), 036007 (2012).
- 107 . Si:WO3 sensors for highly selective detection of acetone for easy diagnosis of diabetes by breath analysis. Anal. Chem. 82(9), 3581–3587 (2010).
- 108 . Analysis of the exhalome: a diagnostic tool of the future. Chest 144(3), 746–749 (2013).
- 109 . Cancer biomarkers. Mol. Oncol. 6(2), 140–146 (2012).
- 110 Circulating microRNA signature as liquid-biopsy to monitor lung cancer in low-dose computed tomography screening. Oncotarget 6(32), 32868–32877 (2015).
- 111 Role of magnetic resonance imaging in prostate cancer screening: a pilot study within the Göteborg randomised screening trial. Eur. Urol.
doi:10.1016/j.eururo.2015.12.006 (2015) (Epub ahead of print).