Molecular Characterisation of Male Breast Cancer and the Evolution of Breast and Ovarian Cancer in BRCA1/2 Mutation Carriers
Principal investigator; Hedenfalk, Ingrid, Associate Professor, PhD
Clinical speciality: Experimental oncology
Co-workers, Lund University: Hedenfalk Ingrid
Breast cancer is a morphologically, clinically and genetically heterogeneous disease, a belief that has been confirmed in the wide range of molecular profiling studies performed to date. Although considerable progress has been achieved in the understanding and management of breast cancer, many questions remain to be answered regarding the initiation, progression and development of the disease, in addition to genetic predisposition and treatment response. Little is known about the early stages of breast and ovarian cancer initiation and progression and whether advancing tumour grade reflects a continuum of cancer progression. Moreover, the interactions between cancer cells and the surrounding stromal tissue, as well as epigenetic events, are thought to play a critical role in tumorigenesis, but the attributes of these interactions largely remain to be elucidated. Knowledge of male breast cancer (MBC) is limited and despite its infrequent prevalence MBC causes significant morbidity/mortality. The incidence has been reported to increase over recent decades, but guidelines for patient management are extrapolated from current knowledge of female breast cancer.
Gene expression, SNP and methylation profiling, as well as next-generation sequencing of premalignant breast and ovarian epithelium and invasive cancers and metastases from genetically predisposed women (e.g. BRCA1/2 mutation carriers), as well as men diagnosed with breast cancer are used to improve our knowledge of the complex network of biological defects that underlie cancer initiation, progression and clinical outcome. Functional studies are performed and correlations to clinical factors are sought using in vitro model systems and tissue microarrays (TMAs) of tissue biopsies from large patient cohorts, respectively.
High throughput and targeted analyses are being used to elucidate genetic and epigenetic events, as well as microenvironmental influences, underlying malignant transformation and genetic predisposition to breast and ovarian cancer. A better understanding of the transition from pre-neoplastic epithelium to invasive and disseminated disease is in itself crucial, and may also lead to the identification of candidate genes whose products might serve as diagnostic/prognostic markers and/or as molecular targets for the development of novel treatment strategies.
In the era of personalized medicine improved understanding and management of male breast cancer is vital. We are therefore molecularly characterizing male breast cancers utilizing state-of-the-art profiling methods and a unique cohort in an effort to classify cases into comprehensive subgroups and identify diagnostic, prognostic and treatment predictive markers that may improve our understanding of the disease and also be translated into clinical practice.
Link to project homepage: http://www.med.lu.se/english/klinvetlund/canceromics/research/male_breast_cancer
5 recent original publications
Johansson, I., Nilsson, C., Berglund, P., Lauss, M., Ringnér, M., Olsson, H., Luts, L., Sim, E., Thorstensson, S., Fjällskog, M-L., Hedenfalk, I.
Gene Expression Profiling of Primary Male Breast Cancers Reveals Two Unique Subgroups and Identifies N-acetyl Transferase-1 (NAT1) as a Novel Prognostic Biomarker.
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Kimbung, S., Biskup, E., Johansson, I., Aaltonen, K., Ottosson-Wadlund, A., Gruvberger-Saal, S., Cunliffe, H., Fadeel, B., Loman, N., Berglund, P., Hedenfalk, I.
Co-targeting of the PI3K pathway improves the response of BRCA1 deficient breast cancer cells to PARP1 inhibition.
Cancer Letters. 2012; In press.:
Rennstam K, Ringberg A, Cunliffe HE, Olsson H, Landberg G, Hedenfalk I.
Genomic alterations in histopathologically normal breast tissue from BRCA1 mutation carriers may be caused by BRCA1 haploinsufficiency.
Genes Chromosomes Cancer. 2010; 49(1): 78-90.
Rennstam K, McMichael N, Berglund P, Honeth G, Hegardt C, Rydén L, Luts L, Bendahl PO, Hedenfalk I.
Numb protein expression correlates with a basal-like phenotype and cancer stem cell markers in primary breast cancer.
Breast Cancer Res Treat.. 2010; 122: 315-24
Aaltonen, K., Ebbesson, A., Wigerup, C., Hedenfalk I.
Laser capture microdissection (LCM) and whole genome amplification (WGA) of DNA from normal breast tissue - optimization for genome wide array analyses.
BMC Res Notes. 2011; 4: 69
Further publications here (new window)