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Breast cancer is the most common cancer in women and it is estimated that one in eight women in the United States will develop breast cancer in their lifetime. The American Cancer Society reported that in 2013 an estimated 232,340 new cases of invasive disease and 39,620 breast cancer deaths would occur.1 Every year more than 40,000 women die from breast cancer, making it the second leading cause of cancer-related deaths in women. Only lung cancer accounts for more cancer deaths in women. Historically, the increase in breast cancer incidence was thought to be a reflection of changes in reproductive patterns, such as delayed childbearing, no breast feeding, and giving birth to fewer children, which are recognized as risk factors. Since the early 1980s, the incidence of breast cancer among postmenopausal women was steadily rising due to improved detection with the widespread use of mammography. The rates stabilized in the late 1990s and then started to decrease; it has been hypothesized that the decline occurred due to a reduced use of hormone replacement therapy following the 2002 publication of the Women’s Health Initiative randomized trial results.2,3 In contrast the incidence of breast cancer in younger women has remained stable. Although breast cancer is a rare disease in young women, it is the most common cancer occurring in the age group. When it occurs in women <35 years, it brings forth unique clinical challenges for the clinician and personal challenges for the patient, especially when associated with pregnancy.4,5 With a rapidly aging population in the United States, the number of breast cancer is expected to increase over the next 20 years. Fortunately, breast cancer mortality rates have declined continuously since 1990, despite the larger and older U.S. population.6 Part of this decline in mortality is attributable to early diagnosis; however, a large part is due to advances in cancer treatment and the incorporation of adjuvant systemic therapy.

Breast cancer therapy requires a multidisciplinary team consisting of surgeons, medical oncologists, and radiation oncologists. All three specialties have seen significant advances, and each component of these treatments has been shown to independently offer survival benefits for selected patients. For patients with early-stage breast cancer, the outcomes associated with breast-conservation surgery, sentinel lymph node dissection, radiation, and systemic treatments are excellent. Treatment advances have also improved the prognosis for patients with more advanced disease at presentation. A particularly exciting such advance has been the use of trastuzumab and other anti-HER2-directed therapies, including lapatinib, pertuzumab, and ado-trastuzumab, for patients with HER2-positive disease. In the future, additional molecularly targeted treatments are likely to further improve breast cancer outcomes.

This chapter of this textbook consists of an overview highlighting the role of systemic therapy in the following settings: early-stage disease, locally advanced breast cancer (LABC), inflammatory breast cancer (IBC), special populations (elderly, male, pregnant), ductal carcinoma in situ, and in the preventative setting. In this chapter, important aspects of biology, pathogenesis, risk factors for the disease, and prognostic and predictive factors, including the molecular classification of disease, ...

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