Role of PARP Inhibitors in BRCA-Related Malignancies

Sana Iqbal, PharmD; Mohammad A. Rattu, PharmD, BCOP, BCPS, BCGP; Neal Shah, PharmD

Disclosures

US Pharmacist. 2018;43(9):HS10-HS17. 

In This Article

Epidemiology and Etiology

Breast Cancer

Breast cancer is the second leading cause of cancer-related death among women in the United States.[7] The likelihood of developing breast cancer increases with age (the majority are diagnosed after age 50 years), with the highest mortality rate observed between ages 65 and 74 years.[7,8] The lifetime risk for women to develop breast cancer is about 1 in 8 (12.5%).[7] There is a 5-year survival rate of 90% among all races with breast cancer, with a much greater survival rate (99%) observed with localized disease.[7] There is a high incidence of breast cancer in non-Hispanic white and non-Hispanic black women, and the mortality rate is greatest in non-Hispanic black women.[7] The American Cancer Society (ACS) estimates that about 268,670 new cases and 41,400 deaths from breast cancer will occur this year in the U.S.[7] Breast cancer mortality has declined over the last two decades, predominantly because of reductions in smoking and advances in early cancer detection and treatment.[7]

According to the CDC, there are numerous, identifiable risk factors for developing breast cancer.[8] These include female gender; advanced age; genetic mutations (BRCA1 or BRCA2); early menarche (before age 12 years); late pregnancy (after age 30 years); nulliparity; late menopause (after age 55 years); physical inactivity; postmenopausal overweight/obesity; increased mammographic breast density; hormone replacement therapy (e.g., estrogen, progestin); oral contraceptives; personal/family (first-degree relative) history of breast cancer; proliferative breast disease (e.g., atypical hyperplasia, lobular carcinoma in situ); prior treatment with radiation therapy to the chest wall before age 30; and alcohol use.[8] In the U.S., around 7% to 10% of cases, including triple-negative (i.e., ER/PR/HER2-negative) breast cancer, are thought to occur due to gBRCAm.[9–11]

Ovarian Cancer

Ovarian cancer is the fifth leading cause of cancer-related deaths among women in the U.S.[7] The likelihood of developing ovarian cancer increases with age (the majority are diagnosed between ages 55 and 64 years), with the highest mortality rate observed between ages 65 and 74 years.[7,12] The lifetime risk of developing ovarian cancer is about 1 in 77 (1.3%).[13] There is a 5-year survival rate of 47% among all races with ovarian cancer, with a much greater survival rate (93%) observed with localized disease.[7,13] There is a relatively higher incidence and mortality rate of ovarian cancer in non-Hispanic white women.[13] The ACS estimates that about 22,240 new cases and 14,070 deaths from ovarian cancer will occur this year in the U.S.[7,13] Ovarian cancer cases and mortality have also declined over the last decade.[13]

According to the CDC, multiple risk factors exist for developing ovarian cancer.[12] These include advanced age; family (first-degree relative) history of ovarian cancer; genetic mutations (e.g., BRCA1, BRCA2, Lynch syndrome); personal history of breast/uterine/colorectal cancer; Eastern European or Ashkenazi Jewish background; endometriosis; nulliparity, and long-term (more than 10 years) estrogen use without concomitant progesterone.[12] In the U.S., around 10% to 15% of ovarian cancer cases are thought to occur due to gBRCAm.[9,14]

Conversely, certain factors have been associated with a decreased risk of developing ovarian cancer.[15] These include combined oral contraceptive use for greater than 5 years; childbirth; breastfeeding for greater than 1 year; and certain surgical procedures (e.g., tubal ligation, oophorectomy, hysterectomy).[15]

Fallopian tube and primary peritoneal cancers are often subgrouped with ovarian cancer, but they are rare.[16] These have also been associated with BRCA mutations.[16]

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