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Key Clinical Updates in Carcinoma of the Female Breast

Three additional agents became available in 2021 for use in the curative setting for patients with high-risk breast cancer: olaparib, abemaciclib, and pembrolizumab.

Hormonally driven breast cancer may be particularly sensitive to inhibition of cell cycle regulatory proteins, called cyclin dependent kinases 4 and 6 (CDK 4/6). Three oral CDK4/6 inhibitors—palbociclib, ribociclib, and abemaciclib—are FDA-approved for treatment of HR-positive, HER2-negative metastatic breast cancer.

Two poly(ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) are FDA-approved for the treatment of BRCA-associated metastatic breast cancer. The NCCN guidelines include adjuvant olaparib for select patients and recommend germline genetic testing for any patient who may be a candidate for adjuvant olaparib.

Schmid P et al; KEYNOTE-522 Investigators. N Engl J Med. [PMID: 32101663]

Tutt ANJ et al; OlympiA Clinical Trial Steering Committee and Investigators. N Engl J Med. [PMID: 34081848]

ESSENTIALS OF DIAGNOSIS

  • Risk factors: Age, nulliparity, childbirth after age 30, family history of breast cancer or deleterious mutations (BRCA1, BRCA2, or others), and personal history of breast cancer or some types of proliferative conditions.

  • Early findings: Mammographic abnormalities and no palpable mass, or single, nontender, firm to hard mass with ill-defined margins.

  • Later findings: Skin or nipple retraction; axillary lymphadenopathy; breast enlargement, erythema, edema, pain; fixation of mass to skin or chest wall.

INCIDENCE & RISK FACTORS

Breast cancer will develop in one of eight American women. Next to skin cancer, breast cancer is the most common cancer in women; it is second only to lung cancer as a cause of death. In 2021 there were approximately 281,550 new cases and 43,600 deaths from breast cancer in the United States. The highest rates of death are in non-Hispanic Black women in the United States. Worldwide, breast cancer is diagnosed in approximately 2.3 million women, and about 685,000 die of breast cancer each year, with the highest rates of diagnosis in Australia/New Zealand, Europe, and North America and lowest rates in Eastern/Middle Africa and South Central Asia. These regional differences in incidence are likely due to the variable availability of screening mammography as well as differences in reproductive, nutrition, and hormonal factors. In western countries, incidence rates decreased with a reduced use of postmenopausal hormone therapy and mortality declined with increased use of screening and improved treatments. In contrast, incidence and mortality from breast cancer in many African and Asian countries have increased as reproductive factors have changed (such as childbirth after age 30) and as the incidence of obesity has risen.

The most significant risk factor for the development of breast cancer is age. A woman’s risk of breast cancer rises rapidly until her early 60s, peaks in her 70s, and then declines. A significant family history of breast or ovarian cancer imparts a high risk of developing breast cancer. Germline mutations in the BRCA family of tumor suppressor genes or ...

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