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A 100 years ago, breast cancer struck 1 woman in 20. Since then, breast cancer incidence has increased steadily, not only because diagnostic modalities have become more sensitive and women and physicians are more aware of the disease, but because risk factors for the disease have become more pervasive. These include proliferation of the Western-style diet with its high proportion of animal fats, earlier menarche, delayed menopause, delayed first pregnancy, and decline of breastfeeding. These factors mainly affect developed countries but are increasingly evident in emerging countries, where, unfortunately, locally advanced breast cancers are usually diagnosed. At the end of the last century, 1 woman in 10 contracted breast cancer; now the figure is 1 in 8 in developed countries.1

Notwithstanding this alarming increase in breast cancer incidence (3 million new cases a year worldwide), we have seen a decrease in mortality for the disease in developed countries, and treatments have become much less aggressive, placing greater emphasis on the patient's quality of life.2

Italy, and the city of Milan with its 2 distinguished Cancer Institutes, has been at the forefront of breast cancer treatment and research for many years. The first pivotal clinical trials on less aggressive surgical approaches to the disease, which had a worldwide impact, were performed in the city. These trials marked the beginning of the shift in paradigm from maximum tolerated treatment to minimum effective treatment; from aggressive surgery and radiotherapy to targeted conservative treatments; from an anatomic concept of cancer spread toward a biologic concept. Today, breast cancer treatments are much more tolerable, personalized, and effective, encouraging women to present early for breast cancer screening so that the disease is diagnosed earlier and treatments are safer. More recently, the Milan Institutes have carried out important research in pharmaco-prevention, results of which are now applied to populations of women most exposed to breast cancer risk factors.

This chapter traces the history of the landmark studies on breast cancer carried out in Milan over the last 40 years. These studies were initiated in the 1970s by our team at the National Cancer Institute and have continued at the European Institute of Oncology (Italian: Istituto Europeo di Oncologia [IEO]) of Milan.

Up to the end of the 19th century, breast cancer was considered invariably fatal. However, the American surgeon W.S. Halsted became convinced that breast cancer spread by direct extension into muscle and skin and through lymphatic ducts to regional lymph nodes, which held the cancer cells in check prior to widespread dissemination. If this were true, it meant that breast cancer was a mainly locoregional disease that could be cured definitively by timely and radical surgery.

In 1898, Halsted presented 76 mastectomized cases to the American Surgical Association3 illustrating his thesis that breast cancer could be cured. Thereafter, radical mastectomy became the accepted treatment for breast cancer. In fact, in Western countries up to the ...

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