Breast cancer is the most frequent malignancy among western women. One of the major challenges in the management of breast cancer is its heterogeneity. Breast cancer patients at the same stage of disease may have markedly different life expectancies and responsiveness to therapy. This heterogeneity is not always evident from tumour morphology alone but may reflect the presence of complex molecular genetic alterations in breast cancer requiring additional analysis.
Morphological classification systems of breast cancer provide important but as yet insufficient prognostic information. Although several histological subtypes have been described, most invasive breast carcinomas are classified as either lobular (15%) or ductal (80%) carcinoma. The most obvious difference between lobular and ductal tumours is the invasive growth pattern: the latter grow in nests and may still show glandular differentiation, while lobular carcinomas have a diffuse and noncohesive infiltration pattern which might be related to loss of E-cadherin expression. At present, the clinical and biological relevance of discriminating lobular from ductal histology remains controversial. Breast cancers are further subdivided by tumour grade which is based on 3 morphological parameters: glandular differentiation, nuclear atypia and mitotic activity. However, this grading system is most appropriate for subclassifying ductal carcinomas since lobular tumours are devoid of glandular differentiation. Moreover, more than 40% of newly diagnosed breast cancers are classified as high-grade invasive ductal carcinoma and show variable disease outcomes.
Our current understanding of breast cancer has substantially improved with the introduction of molecular genetics. Genomic studies show similar genetic alterations in lobular and low-grade ductal carcinomas. By contrast, different and highly complex genetic alterations may be involved in the pathogenesis of high-grade ductal carcinomas. Gene expression profiling studies led to the identification of 4 “new” molecular breast cancer subtypes: the luminal A, luminal B,Summary
General Introduction: breast cancer classification
Hypothesis & Aims
Materials & Methods
Study 1: Expression differences underlying morphological breast cancer subtypes
Study 2: Evaluation of different techniques to determine the HER2 status in breast cancer
Study 3: Significance of polysomy 17 in breast cancer
Study 4: Checkpoint kinase 1 is highly expressed in triple negative breast carcinomas
Discussion & Perspectivesstatus: publishe