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June 3, 2019
Alpelisib Approved for PIK3CA Mutated Breast Cancers: Alpelisib (Piqray®) is the first PI3K inhibitor approved by the FDA and is indicated for adults with hormone receptor (HR) positive and human epidermal growth factor (HER2) negative advanced or metastatic breast who have progressed on prior endocrine therapy. PIK3CA mutations are common, occurring in about 35% of all breast cancers. In the SOLAR-1 trial, the median progression free survival was 11.0 months in the alpelisib arm compared to 5.7 months in the placebo group (HR 0.65, 95% CI 0.50–1.25, P=.00065). Overall response rate is 36%, compared to 16% in the placebo group. The most common adverse effects are hyperglycemia, nausea and rash.
Upon completion of the chapter, the reader will be able to:
Explain the relative importance of various risk factors.
Summarize the surrogate definitions of the intrinsic breast cancer subtypes.
Articulate some of the reasons for improved patient survival.
Recognize signs and symptoms related to early and late stages of the disease.
Distinguish between good and poor prognostic factors.
Determine treatment goals for early stage, locally advanced, and metastatic breast cancers.
State the rationale for inclusion of adjuvant and neoadjuvant therapies.
Describe the relevance of hormone and HER2 receptors.
Discuss the benefits and risks associated with various endocrine therapies.
The increasing prevalence of breast cancer in the United States is related to a number of factors including the predominance of early stage disease at diagnosis, better understanding of tumor biology, improvements in treatment outcomes and survival, and the relatively high incidence rate. Of note, the incidence, which has been increasing slightly over the past decade, appears to be driven almost exclusively by new breast cancer diagnoses in nonwhite women.
EPIDEMIOLOGY AND ETIOLOGY
Breast cancer is the most common type of cancer and second only to lung cancer as a cause of cancer death in American women. In 2018, female breast cancer will account for 99% of the projected 269,000 new cases; the median age at diagnosis will be 62 years; and approximately 41,000 deaths will occur as a result of the disease.1 Even though the disease occurs more frequently in white women than any other ethnic group, the mortality rate is highest among African Americans.
Tumor size of most breast cancers at diagnosis is usually small (< 2 cm); and localized disease predominates in all racial and ethnic groups. However, African American women have proportionally more cases of advanced disease compared with white women. It has been suggested that reduced access to proper medical care, including breast cancer screening programs, as well as certain biological factors, contribute to late diagnoses.
The etiology of breast cancer remains largely unknown though a number of factors have been associated with risk of developing the disease. Evidence also strongly suggests that breast cancer biology involves complex interactions between sex hormones, genetic factors, environment, and lifestyle. The intrinsic and extrinsic components associated with the disease are discussed further.