The Impact of Tumour Characteristics on Hereditary Breast Cancer Screening

In the Western world breast cancer is a fairly common disease in women, nearly one in ten is diagnosed with breast cancer during her life. Worldwide 1.200.000 women are diagnosed with breast cancer annually, in the Netherlands about 12.000, 25% of them before age 50 years 1. Worldwide the incidence doubled between 1975 and 2000, with the steepest increase in developing countries. Survival has clearly improved the last decade, mainly as a result of earlier detection by women’s awareness and mammography screening, and also by increased use of adjuvant hormonal and chemotherapy 2,3. The diagnosis is still frightening as approximately 3.500 women die annually of breast cancer metastases in the Netherlands, but an increasing number of women survives after the disease. The main risk factors for breast cancer are associated with; increasing age, a family history for the disease and previous breast cancer. Only a small fraction, about 20%, of all breast cancer deaths in the western world and worldwide are estimated to be caused by preventable behavioural risk-factors like physical inactivity, obesity, alcohol consumption and use of hormonal replacement therapy (HRT) 4. These factors influence the hormonal balance, leading for instance to early menarche and late menopause, hormonal factors that are known to inc

Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173 797 patients

Objectives To assess the influence of stage at breast cancer diagnosis, tumour biology, and treatment on survival in contemporary times of better (neo-)adjuvant systemic therapy. Design Prospective nationwide population based study. Setting Nationwide Netherlands Cancer Registry. Participants Female patients with primary breast cancer diagnosed between 1999 and 2012 (n=173 797), subdivided into two time cohorts on the basis of breast cancer diagnosis: 1999-2005 (n=80 228) and 2006-12 (n=93 569). Main outcome measures Relative survival was compared between the two cohorts. Influence of traditional prognostic factors on overall mortality was analysed with Cox regression for each cohort separately. Results Compared with 1999-2005, patients from 2006-12 had smaller (≤T1 65% (n=60 570) v 60% (n=48 031); P<0.001), more often lymph node negative (N0 68% (n=63 544) v 65% (n=52 238); P<0.001) tumours, but they received more chemotherapy, hormonal therapy, and targeted therapy (neo-adjuvant/adjuvant systemic therapy 60% (n=56 402) v 53% (n=42 185); P<0.001). Median follow-up was 9.8 years for 1999-2005 and 3.9 years for 2006-12. The relative five year survival rate in 2006-12 was 96%, improved in all tumour and nodal stages compared with 1999-2005, and 100% in tumours ≤1 cm. In multivariable analyses adjusted for age and tumour type, overall mortality was decreased by surgery (especially breast conserving), radiotherapy, and systemic therapies. Mortality increased with progressing tumour size in both cohorts (2006-12 T1c v T1a: hazard ratio 1.54, 95% confidence interval 1.33 to 1.78), but without a significant difference in invasive breast cancers until 1 cm (2006-12 T1b v T1a: hazard ratio 1.04, 0.88 to 1.22), and independently with progressing number of positive lymph nodes (2006-12 N1 v N0: 1.25, 1.17 to 1.32). Conclusions Tumour stage at diagnosis of breast cancer still influences overall survival significantly in the current era of effective systemic therapy. Diagnosis of breast cancer at an early tumour stage remains vita

Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173 797 patients

Objectives To assess the influence of stage at breast cancer diagnosis, tumour biology, and treatment on survival in contemporary times of better (neo-)adjuvant systemic therapy. Design Prospective nationwide population based study. Setting Nationwide Netherlands Cancer Registry. Participants Female patients with primary breast cancer diagnosed between 1999 and 2012 (n=173 797), subdivided into two time cohorts on the basis of breast cancer diagnosis: 1999-2005 (n=80 228) and 2006-12 (n=93 569). Main outcome measures Relative survival was compared between the two cohorts. Influence of traditional prognostic factors on overall mortality was analysed with Cox regression for each cohort separately. Results Compared with 1999-2005, patients from 2006-12 had smaller (≤T1 65% (n=60 570) v 60% (n=48 031); P<0.001), more often lymph node negative (N0 68% (n=63 544) v 65% (n=52 238); P<0.001) tumours, but they received more chemotherapy, hormonal therapy, and targeted therapy (neo-adjuvant/adjuvant systemic therapy 60% (n=56 402) v 53% (n=42 185); P<0.001). Median follow-up was 9.8 years for 1999-2005 and 3.9 years for 2006-12. The relative five year survival rate in 2006-12 was 96%, improved in all tumour and nodal stages compared with 1999-2005, and 100% in tumours ≤1 cm. In multivariable analyses adjusted for age and tumour type, overall mortality was decreased by surgery (especially breast conserving), radiotherapy, and systemic therapies. Mortality increased with progressing tumour size in both cohorts (2006-12 T1c v T1a: hazard ratio 1.54, 95% confidence interval 1.33 to 1.78), but without a significant difference in invasive breast cancers until 1 cm (2006-12 T1b v T1a: hazard ratio 1.04, 0.88 to 1.22), and independently with progressing number of positive lymph nodes (2006-12 N1 v N0: 1.25, 1.17 to 1.32). Conclusions Tumour stage at diagnosis of breast cancer still influences overall survival significantly in the current era of effective systemic therapy. Diagnosis of breast cancer at an early tumour stage remains vita

Proteomic characterization of microdissected breast tissue environment provides a protein-level overview of malignant transformation

Both healthy and cancerous breast tissue is heterogeneous, which is a bottleneck for proteomics‐based biomarker analysis, as it obscures the cellular origin of a measured protein. We therefore aimed at obtaining a protein‐level interpretation of malignant transformation through global proteome analysis of a variety of laser capture microdissected cells originating from benign and malignant breast tissues. We compared proteomic differences between these tissues, both from cells of epithelial origin and the stromal environment, and performed string analysis. Differences in protein abundances corresponded with several hallmarks of cancer, including loss of cell adhesion, transformation to a migratory phenotype, and enhanced energy metabolism. Furthermore, despite enriching for (tumor) epithelial cells, many changes to the extracellular matrix were detected in microdissected cells of epithelial origin. The stromal compartment was heterogeneous and richer in the number of fibroblast and immune cells in malignant sections, compared to benign tissue sections. Furthermore, stroma could be clearly divided into reactive and nonreactive based on extracellular matrix disassembly proteins. We conclude that proteomics analysis of both microdissected epithelium and stroma gives an additional layer of information and more detailed insight into malignant transformation

Experiences, expectations and preferences regarding MRI and mammography as breast cancer screening tools in women at familial risk

Background: Several studies have investigated MRI breast cancer screening in women at increased risk, but little is known about their preferences. In this study, experiences, expectations and preferences for MRI and mammography were evaluated among women undergoing screening with MRI and/or mammography in the randomized FaMRIsc trial. Methods: A 17-item questionnaire was sent to 412 women in the FaMRIsc trial. Participants were aged 30–55 years, had a ≥20% cumulative lifetime risk, but no BRCA1/2 or TP53 gene variant, and were screened outside the population-based screening program. Women received annual mammography (mammography-group), or annual MRI and biennial mammography (MRI-group). We asked whether women trust the screening outcome, what they consider as (dis)advantages, which screening they prefer and what they expect of the early detection by the screening tools. Results: 255 (62%) women completed our questionnaire. The high chance of early cancer detection was the most important advantage of MRI screening (MRI-group: 95%; mammography-group: 74%), while this was also the main advantage of mammography (MRI-group: 57%; mammography-group: 72%). Most important disadvantages of MRI were the small tunnel and the contrast fluid (for 23–36%), and of mammography were its painfulness and X-radiation (for 48–60%). Almost the whole MRI-group and half the mammography-group preferred screening with MRI (either alone or with mammography). Discussion: Most women would prefer screening with MRI. The way women think of MRI and mammography is influenced by the screening strategy they are undergoing. Our outcomes can be used for creating information brochures when MRI will be implemented for more women

Proteomic characterization of microdissected breast tissue environment provides a protein-level overview of malignant transformation

Both healthy and cancerous breast tissue is heterogeneous, which is a bottleneck for proteomics-based biomarker analysis, as it obscures the cellular origin of a measured protein. We therefore aimed at obtaining a protein-level interpretation of malignant transformation through global proteome analysis of a variety of laser capture microdissected cells originating from benign and malignant breast tissues. We compared proteomic differences between these tissues, both from cells of epithelial origin and the stromal environment, and performed string analysis. Differences in protein abundances corresponded with several hallmarks of cancer, including loss of cell adhesion, transformation to a migratory phenotype, and enhanced energy metabolism. Furthermore, despite enriching for (tumor) epithelial cells, many changes to the extracellular matrix were detected in microdissected cells of epithelial origin. The stromal compartment was heterogeneous and richer in the number of fibroblast and immune cells in malignant sections, compared to benign tissue sections. Furthermore, stroma could be clearly divided into reactive and nonreactive based on extracellular matrix disassembly proteins. We conclude that proteomics analysis of both microdissected epithelium and stroma gives an additional layer of information and more detailed insight into malignant transformation