Chapter 30: Breast Cancer

LEARNING OBJECTIVES

1. Discuss the presentation, pathophysiology, screening, and diagnosis of breast cancer.

2. Identify high-risk patients, and discuss treatment options for appropriate breast cancer prevention therapy.

3. Compare and contrast therapeutic approaches for treatment of early-stage, locally advanced, and metastatic breast cancer, with a focus on pharmacologic interventions.

4. Develop an appropriate treatment plan in patients receiving adjuvant therapy for breast cancer.

5. Recommend appropriate follow-up for long-term survivors of breast cancer.

INTRODUCTION

Epidemiology and Incidence

Breast cancer is the most commonly diagnosed malignancy in American women, and is the fourth leading cause of cancer death in the United States.¹ In 2018, it is estimated that 266,120 women will be diagnosed with, and 40,920 women will die of the disease.¹ Breast cancer is a significant women’s health issue, as one in eight women will be diagnosed with the disease during their lifetime.¹ Although breast cancer incidence rates steadily increased over the past few decades, the incidence has started to plateau.¹ Mortality rates are declining, due to screening mammography and effective therapy.^1,2

Etiology and Risk Factors

The etiology for breast cancer is largely unknown, although several risk factors have been identified. The two most common risk factors are female gender and increasing age. The median age of diagnosis of breast cancer is 62 years.¹ The association between breast cancer and estrogen has been recognized for over a century, although the exact mechanism is not known. Experimental and human data strongly suggests that estrogen plays a role in the pathogenesis of breast cancer, through stimulation of cellular proliferation and increased mutation rates.³ Exogenous hormone replacement also increases risk, particularly estrogen plus progestin, as demonstrated by the results of the Women’s Health Initiative (WHI) Hormone Trials.^4,5 Thus, an increased risk of breast cancer is associated with factors that increase cumulative exposure of breast tissue to estrogen, such as early menarche, late menopause, older age at first live childbirth, and prolonged hormone replacement therapy. Other risk factors include: family history of breast cancer at a young age, exposure to therapeutic chest wall irradiation, benign proliferative breast disease, and genetic mutations in the breast/ovarian cancer susceptibility genes BRCA1 and BRCA2.⁶

Approximately 5% to 10% of breast and ovarian cancers are due to hereditary gene mutations, with the majority of these due to germline mutations in the BRCA1 or BRCA2 genes. In women with a known deleterious BRCA mutation, this may confer a 45% to 65% risk of breast cancer and 39% risk of ovarian cancer by age 70.⁷ This is significantly greater than the 12% risk of breast cancer and 1% to 2% risk of ovarian cancer in the general population.

Several risk assessment models exist to help estimate a woman’s risk of developing breast cancer. The Breast Cancer ...