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INTRODUCTION AND BACKGROUND

CONCEPTUAL AND BIOLOGICAL ISSUES OF BREAST CANCER

Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast. In the year 2020, approximately a quarter million cases of invasive and 61,000 cases of in situ breast cancer were diagnosed in the United States, with nearly 41,000 deaths. Epithelial malignancies of the breast are the most common cause of cancer in women (excluding skin cancer), accounting for about one-third of all cancer in women. As a result of earlier detection and improved treatments, the mortality rate from breast cancer decreased by more than one-third over the past three decades in high- and middle-income countries. This chapter does not consider rare malignancies presenting in the breast, such as sarcomas and lymphomas, but focuses on the epithelial cancers.

Breast cancer has served as a paradigm for several oncologic principles related to solid tumors. It spans a spectrum of conditions for which different clinical considerations must be made, including risk assessment, prevention, screening, evaluation of breast abnormalities, local and adjuvant systemic treatments, metastatic therapies, and survivorship issues (Fig. 79-1).

FIGURE 79-1

Breast cancer continuum conceptual model. Most breast cancers begin in epithelial cells within the lobules or ducts. They proceed through a continuum of atypia and hyperplasia to in situ malignancy to invasion into surrounding normal tissues followed by intravasation into lymph and blood channels to local lymph nodes and distant organs, culminating in distant metastases. This is a conceptual model. Not all metastatic breast cancers have progressed through these stages, and many lesions do not progress to the next.

The unique biology of breast cancer has rendered it amenable to a variety of therapeutic “targeted” strategies based on the appreciation of differences in subtypes that reflect the need for differences in assessment and therapy. These subtypes include expression of the estrogen receptor (ER) and the human epidermal growth factor receptor type 2 (HER2), as well as germline or somatic mutations in inherited tumor suppressor genes, such as BRCA1 and BRCA2. Identifiable somatic mutations in genes that appear to drive the cancer, including mammalian target of rapamycin (mTOR), cyclin-dependent kinase 4 and 6 (CDK4/6), and S-phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) make it susceptible to specific therapeutic interventions directed against each of these targets (Table 79-1). Furthermore, immune checkpoint inhibition has been applied to specific types of breast cancers.

TABLE 79-1Breast Cancer Molecular Features and Associated Targeted Therapies

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