Early Breast Cancer: From Screening to Multidisciplinary Management, Third Edition

Book Preface

Worldwide breast cancer remains the most common malignancy in women, with over 1.3 million cases diagnosed annually and about 400,000 deaths from the disease. Globally, one-quarter of new female cancers have breast as the primary site, although this figure is up to one-third in the United Kingdom where the lifetime risk is 1 in 8. The annual number of cases has almost doubled over the past 3 decades within the United Kingdom (UK) where half of breast cancers are diagnosed within the screening age bracket. Introduction of the National Health Service Breast Screening Programme led to a surge in incidence of the disease which was confined to women of initial screening age. Rates have now fallen slightly for this age group but increased for women aged 65–69 years with age extension of screening. Breast cancer is a disease predominantly found in postmenopausal women, and the rising incidence of breast cancer during the 1990s has been attributed to increased usage of hormone replacement therapy amongstaffluent women. One-quarter of women aged 45–69 years took exogenous hormones at the start of the millennium, but this dramatically halved after 2002 and continues to fall. This reduction in hormone replacement therapy usage resulted in a transient decrease in breast cancer incidence after 2002 amongst white American women, but this decline has not persisted. Though more than three-quarters of breast cancers occur in women over 50 years of age, the disease occurs frequently in women under 35 years where genetic factors predominate etiologically. Breast cancers are now recognized to display epigenetic phenomena, which permit changes in gene expression without DNA sequence alterations, and to act translators between environment and genome.

Despite a higher prevalence of breast cancer in wealthy countries, incidence rates are rising steadily in less affluent societies, with contraction of historical differences in breast cancer rates based on income levels. Those countries which had moderate or low rates are now experiencing rapid rate increases which have more than doubled in Japan over the past 40 years and are rising inexorably in conurbations of mainland China. The high incidence rates within major industrialized nations have been attributed to lifestyle factors which now have relevance to increasing rates amongst the emerging economies.

These include changes in reproductive behaviour, altered dietary habits (increased consumption of polyunsaturated fats and alcohol), physical inactivity, and hormone replacement therapy usage. These are all potentially modifiable risk factors with the opportunity to impact favourably not only on incidence but also treatment outcomes and mortality. Indeed, there are claims that up to one-third of breast cancer cases in developed countries could be prevented by adoption of a healthier lifestyle with maintenance of optimum body weight and regular exercise. Obese patients may benefit from extended endocrine treatments due to higher risk of recurrence in those with estrogen receptor-positive disease, though ironically obesity may partially offset the therapeutic benefi t of adjuvant hormonal therapies.

Mortality rates for breast cancer have fallen over the past two decades despite the continued rise in incidence. This is testimony to the success of interventional strategies such as screening and adjuvant systemic therapies which permit diagnosis of breast cancer prior to de novo formation of micrometastases or obliteration of established foci of disease at distant sites. It is this burden of micrometastatic disease outside the breast and regional tissues that represents the most fundamental and challenging aspect of treatment for breast cancer—a disease which is heterogeneous with a variable and unpredictable natural history. We have entered a new era in breast cancer management where disease is “small” and more likely to be confi ned to the breast and regional nodes. Some of these tumours will have minimal proclivity for hematogenous dissemination and formation of micrometastases at an early stage in the neoplastic process. By contrast, some patients have micrometastatic diseases which can remain dormant and be activated many years after the diagnosis. A spectrum or intermediate paradigm is emerging which encompasses this variable capacity to form distant micrometastatic foci. Modern methods of molecular profiling may permit tumors to be assigned to one or other group based on biological behavior with appropriate intensities of locoregional and systemic treatments.