An epidemic scale of the breast cancer (BC) prevalence is actually recognised as the reality of the early twenty-first century. Particularly alarming is that the sporadic BC (about 90% of all patients) creates currently unpredictable subpopulations in terms of disease predisposition, development and progression. Despite broad discussions run since years in BC area, no any plausible approach has been suggested so far to get the overall situation better controlled in the populations. Here, we present highly innovative concepts considering investigation of specific syndromes and symptoms underestimated till now in relationship with BC predisposition and development. Consequently, the purpose of our pilot project was to evaluate the prevalence of Flammer Syndrome (FS) in BC patient cohort. The results achieved here support the main hypothesis of the project clearly demonstrating the tendency of BC patients to the increased prevalence of FS symptoms compared to the disease-free individuals. Our study strongly indicates the relevance of FS symptoms for BC pathology such as feeling inadequately cold, deficient thermoregulation, altered sensitivity to different stimuli, potential dehydration, altered sleep patterns, tendency towards headache, migraine attacks and dizziness. Moreover, the symptoms' appearance is specifically linked to the individual BC subtypes. Potential mechanisms interconnecting FS with BC pathology are discussed.

Breast Cancer Research Centre Rheinische Friedrich Wilhelms University of Bonn Bonn Germany

Centre for Integrated Oncology Cologne Bonn Rheinische Friedrich Wilhelms University of Bonn Bonn Germany

Department of Histology and Embryology and Biomedical Center Faculty of Medicine in Plzen Charles University Prague Czech Republic

Department of Neurology Faculty Hospital Plzen Prague Czech Republic

Department of Obstetrics and Gynaecology Jessenius Faculty of Medicine Martin University Hospital Martin Slovak Republic

Department of Ophthalmology University of Basel Basel Switzerland

Division of Oncology Biomedical Centre Martin Jessenius Faculty of Medicine Comenius University in Bratislava Bratislava Slovak Republic

Radiological clinic Rheinische Friedrich Wilhelms University of Bonn Sigmund Freud Str 25 53105 Bonn Germany

Zobrazit více v PubMed

Golubnitschaja O, Debald M, Yeghiazaryan K, Kuhn W, Pešta M, Costigliola V, Grech G. Breast cancer epidemic in the early 21st century: evaluation of risk factors, cumulative questionnaires and recommendations for preventive measures. Tumor Biol. 2016;37(10):12941–12957. doi: 10.1007/s13277-016-5168-x. PubMed DOI

Golubnitschaja O. Feeling cold and other underestimated symptoms in breast cancer: anecdotes or individual profiles for advanced patient stratification? EPMA J. 2017;8(1):17–22. doi:10.1007/s13167-017-0086-6. PubMed PMC

Konieczka K, Ritch R, Traverso CE, Kim DM, Kook MS, Gallino A, et al. Flammer syndrome. EPMA J. 2014;5(1):11. doi: 10.1186/1878-5085-5-11. PubMed DOI PMC

Yeghiazaryan K, Flammer J, Orgül S, Wunderlich K, Golubnitschaja O. Vasospastic individuals demonstrate significant similarity to glaucoma patients as revealed by gene expression profiling in circulating leukocytes. Mol Vis. 2009;15:2339–2348. PubMed PMC

Flammer J, Konieczka K, Flammer AJ. The primary vascular dysregulation syndrome: implications for eye diseases. EPMA J. 2013;4(1):14. doi: 10.1186/1878-5085-4-14. PubMed DOI PMC

Yeghiazaryan K, Flammer J, Golubnitschaja O. Predictive molecular profiling in blood of healthy vasospastic individuals: clue to targeted prevention as personalised medicine to effective costs. EPMA J. 2010;1(2):263–272. doi: 10.1007/s13167-010-0032-3. PubMed DOI PMC

Golubnitschaja O, Yeghiazaryan K, Flammer J. Key molecular pathways affected by glaucoma pathology: is predictive diagnosis possible? EPMA J. 2010;1(2):237–244. doi: 10.1007/s13167-010-0031-4. PubMed DOI PMC

Golubnitschaja O, Yeghiazaryan K, Costigliola V, Trog D, Braun M, Debald M, et al. Risk assessment, disease prevention and personalised treatments in breast cancer: is clinically qualified integrative approach in the horizon? EPMA J. 2013;4(1):6. doi: 10.1186/1878-5085-4-6. PubMed DOI PMC

Flammer J, Konieczka K. Retinal venous pressure: the role of endothelin. EPMA J. 2015;6:21. doi: 10.1186/s13167-015-0043-1. PubMed DOI PMC

Fang L, Baertschi M, Mozaffarieh M. The effect of flammer-syndrome on retinal venous pressure. BMC Ophthalmol. 2014;14:121. doi: 10.1186/1471-2415-14-121. PubMed DOI PMC

Fraenkl SA, Mozaffarieh M, Flammer J. Retinal vein occlusions: the potential impact of a dysregulation of the retinal veins. EPMA J. 2010;1(2):253–261. doi: 10.1007/s13167-010-0025-2. PubMed DOI PMC

Konieczka K, Flammer AJ, Todorova M, Meyer P, Flammer J. Retinitis pigmentosa and ocular blood flow. EPMA J. 2012;3(1):17. doi: 10.1186/1878-5085-3-17. PubMed DOI PMC

Konieczka K, Koch S, Binggeli T, Schoetzau A, Kesselring J. Multiple sclerosis and primary vascular dysregulation (Flammer syndrome) EPMA J. 2016;7:13. doi: 10.1186/s13167-016-0062-6. PubMed DOI PMC

Konieczka K, Fränkl S. Primäre vaskuläre dysregulation und Glaukom (primary vascular dysregulation and glaucoma). Z Prakt Augenheilkd. 2013;34:207–15.

Konieczka K. Flammer syndrome, in: Brähler E, Hoefert H-W. Lexikon der Modernen Krankheiten. 2014, Medizinisch Wissenschaftliche Verlagsgesellschaft. Berlin. Deutschland.

Konieczka K, Choi HJ, Koch S, Schoetzau A, Küenzi D, Kim DM. Frequency of symptoms and signs of primary vascular dysregulation in Swiss and Korean populations. Klin Monatsbl Augenheilkd. 2014;231:344–347. doi: 10.1055/s-0034-1368239. PubMed DOI

Konieczka K, Koch S, Schoetzau A, Todorova MG. Increased prevalence of Flammer syndrome in patients with retinitis pigmentosa. Klin Monatsbl Augenheilkd. 2016;233(4):448–452. doi: 10.1055/s-0041-111802. PubMed DOI

Konieczka K, Todorova MG, Chackathayil TN, Henrich PB. Cilioretinal artery occlusion in a young patient with Flammer syndrome and increased retinal venous pressure. Klin Monatsbl Augenheilkd. 2015;232:576–578. doi: 10.1055/s-0035-1545774. PubMed DOI

Konieczka K, Flammer J, Sternbuch J, Binggeli T, Fraenkl S. Leber’s hereditary optic neuropathy, normal tension glaucoma, and Flammer syndrome: long term follow-up of a patient. Klin Monatsbl Augenheilkd. 2017 PubMed

Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ. WHO classification of tumours of the breast. 4. Lyon: IARC; 2012.

Elston CW, Ellis IO. 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. 1991;19(5):403–10. PubMed

Edge SB, Compton CC. The American joint committee on cancer: the American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–1474. doi: 10.1245/s10434-010-0985-4. PubMed DOI

Hammond MEH, Haves DF, Wolff AC, Mangu PB, Temin S. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. Arch Pathol Lab Med. 2010;134:E1–E16. PubMed PMC

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, Hayes DF, et al. American Society of Clinical Oncology; College of American Pathologists. 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. PubMed DOI

Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, Allred DC, Bartlett JM, 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. Arch Pathol Lab Med. 2014;138(2):241–256. doi: 10.5858/arpa.2013-0953-SA. PubMed DOI PMC

Golubnitschaja O, Flammer J. What are the biomarkers in glaucoma? Surv Ophthalmol. 2007;52(Suppl 2):S155–S161. doi: 10.1016/j.survophthal.2007.08.011. PubMed DOI

Kokolus K, Hing CC, Repasky EA. Feeling too hot or cold after breast cancer: is it just a nuisance or a potentially important prognostic factor? Int J Hyperth. 2010;26(7):662–680. doi: 10.3109/02656736.2010.507235. PubMed DOI PMC

Mencalha A, Victorino VJ, Cecchini R, Panis C. Mapping oxidative changes in breast cancer: understanding the basic to reach the clinics. Anticancer Res. 2014;34(3):1127–1140. PubMed

Liu X, Feng D, Liu D, Wang S, Yu X, Dai E, Wang J, Wang L, Jiang W. Dissecting the origin of breast cancer subtype stem cell and the potential mechanism of malignant transformation. PLoS One. 2016;11(10):e0165001. doi: 10.1371/journal.pone.0165001. PubMed DOI PMC

Kurzrock R. The role of cytokines in cancer-related fatigue. Cancer. 2001;92(S6):1684–1688. doi: 10.1002/1097-0142(20010915)92:6+<1684::AID-CNCR1497>3.0.CO;2-Z. PubMed DOI

Mitochondria-based holistic 3PM approach as the 'game-changer' for individualised rehabilitation-the proof-of-principle model by treated breast cancer survivors

Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine

Caution, "normal" BMI: health risks associated with potentially masked individual underweight-EPMA Position Paper 2021

Risks associated with the stroke predisposition at young age: facts and hypotheses in light of individualized predictive and preventive approach

Vaginal dryness: individualised patient profiles, risks and mitigating measures

"Dry mouth" and "Flammer" syndromes-neglected risks in adolescents and new concepts by predictive, preventive and personalised approach

IDH1 mutation is associated with lower expression of VEGF but not microvessel formation in glioblastoma multiforme

Pregnancy-associated breast cancer: the risky status quo and new concepts of predictive medicine

"Pre-metastatic niches" in breast cancer: are they created by or prior to the tumour onset? "Flammer Syndrome" relevance to address the question

Postmenopausal breast cancer: European challenge and innovative concepts