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INTRODUCTION

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The American Cancer Society estimated that there were 226 870 new cases of invasive breast cancer diagnosed in the United States in 2012 and more than 1 million new cases worldwide [1]. Despite newer treatments and improvements in screening, more than 39 000 will die from this disease each year in the United States. Breast cancer remains a major health issue for all women, and, therefore, the concept of prevention is an attractive addition to screening and treatment.

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Although some factors that appear to contribute to breast cancer risk, such as postmenopausal obesity, dietary fat intake, and alcohol consumption, may be modifiable, the factors that put a woman at greatest risk - gender, age, and family history [2] - are not amenable to lifestyle modifications. Prophylactic mastectomy is an effective strategy for some women at high risk for the disease, but it is a drastic and irreversible choice [3].

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This chapter will focus on the chemoprevention of breast cancer using targeted agents. Hong and Sporn [4] have defined chemoprevention as: 'the use of pharmacologic or natural agents that inhibit the development of invasive cancer either by blocking the DNA damage that initiates carcinogenesis or by arresting or reversing the progression of premalignant cells in which such damage has already occurred' (Box 3.1).

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Box 3.1 Definition of chemoprevention

"Chemoprevention is the use of pharmacologic or natural agents that inhibit the development of invasive cancer either by blocking the DNA damage that initiates carcinogenesis or by arresting or reversing the progression of premalignant cells in which such damage has already occurred."

From: Hong WK, Sporn MB [4]

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Breast cancer chemoprevention has already demonstrated substantial clinical success [5-8]. Hormones appear to play a significant role in the development of this disease, and current chemoprevention strategies have targeted hormonally responsive breast cancers.

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THERAPIES IN CURRENT USE IN BREAST CANCER PREVENTION

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The targeted chemoprevention agent with the greatest clinical use to date is the selective estrogen receptor modulator (SERM) tamoxifen. This drug is a well-established treatment for receptor-positive breast cancer and is among the most commonly prescribed breast cancer drugs in the world. It has a demonstrated effectiveness in reducing the risk of recurrence and reducing the risk of death from breast cancer [9]. Tamoxifen also has a well-defined safety profile and the added benefits that it helps maintain bone density in postmenopausal women and has a positive impact on lipid profiles. In the trials that demonstrated tamoxifen to be an effective treatment for breast cancer, there was also a substantial reduction in new primary cancers of the opposite breast that persisted for up to 15 years [10-13].

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THE NSABP BREAST CANCER PREVENTION TRIAL

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The treatment trial findings and extensive laboratory data ...

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