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 increase breast cancer risk. Like in postmenopausal hormonal replacement therapy, and nulliparity, the harmful effect seems to be the cumulative exposure to ovarian hormones/ ovulatory cycles. While also the preventive effect of prolonged breast-feeding may be caused by reduced ovulatory cycles, the protective effect of a first full-term pregnancy at a relatively young age seems associated with early terminal differentiation of the breast epithelium. The increase in breast cancer risk with increasing ovulatory cycles and the decrease associated with terminal differentiation are explained by their influence on the number of cell divisions of the breast epithelial cells and accumulation of molecular and DNA damage.

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