A small but important fraction of cancer are primarily due to a hereditary cancer predisposition, and their diagnosis has significant clinical implications for both index cases and their families. Germline BRCA1BRCA/2 pathogenic variants (PVs) can lead to the Hereditary Breast and Ovarian Cancer (HBOC) Syndrome and identification of both germline and somatic BRCA1/BRCA2 PVs have important treatment implications. In addition, endometrial cancer is closely associated with inherited PVs in the mismatch repair (MMR) genes which leads to Lynch syndrome. Both HBOC and Lynch syndrome affect around 1:300 people, most of whom are undiagnosed. Genetic panel testing is crucial to identifying PV carriers, before a sentinel cancer, who can then be offered prophylactic interventions such as risk reducing salpingo-oophorectomy (RRSO). Within this chapter we discuss the most common hereditary cancer syndromes associated with gynecological cancer. These include HBOC, Lynch syndrome, the moderate penetrant genes including RAD51C, RAD51D, BRIP1, PALB2, and ATM as well as rarer hereditary cancer syndromes including Cowden syndrome (PTEN), DICER1, Rhabdoid Tumor Predisposition syndrome (SMARCB1, SMARCA4) and Peutz-Jeghers syndrome (STK11).

A 43-year-old, gravida 3, para 3, with a known BRCA1 gene mutation presents to the office to discuss risk-reducing surgery. Her family history is significant for breast cancer diagnosed in her mother at age 42 years, ovarian cancer in a maternal aunt at age 53 years, and ovarian cancer in her maternal grandmother at age 49 years. Last month, she underwent genetic counseling and testing revealed a BRCA1 mutation. She is otherwise healthy with no significant past medical history or surgical history. She had three uncomplicated vaginal deliveries and has regular monthly periods. She used oral contraceptive pills for birth control for 15 years prior to her husband’s vasectomy. She denies any recent weight change, fever or chills, bowel or bladder dysfunction, nausea, early satiety, or abdominal or pelvic pain. She had a normal mammogram last week. She is not taking medications and has no known drug allergies.