Ovarian cancer accounts for 4% of cancers occurring in women. According to the CDC, there are >19,000 new cases of ovarian cancer annually in the United States, and approximately 14,000 deaths annually; thus, this the most lethal of gynecologic cancers, which accounts for 2.3% of all cancer deaths nationally.
Malignancy that arises from the epithelium (90–95%), sex cord stromal (5–8%), or germ cells (5%) of the ovary as well as tumors metastatic to the ovary. Histologic types include the following:
- Epithelial: serous (most common, 70–80%), mucinous, endometrioid, clear cell
- Sex cord stromal: granulosa, Sertoli-Leydig
- Germ cell: dysgerminoma (most common), teratoma, yolk sac
- Metastatic from: GI (Krukenberg, colon), melanoma, lymphoma
- In 2018, there were 19,679 new cases per year in the United States; 13,748 deaths per year
- Represents 1.1% of all new cancer cases in the United States
- Leading cause of gynecologic cancer death in women, fourth most common cause of death overall cancer death in women
- Majority of ovarian cancer is diagnosed at an advanced stage.
- Average age of diagnosis
- Epithelial: 63 years
- Sex cord stromal: 50 years
- Germ cell: 10 to 30 years
- In 2018, there were approximately 235,081 women living with ovarian cancer in the United States.
- Without a significant family history or known genetic mutation, women have a 1–2% lifetime risk of developing this disease. Although 5–10% of ovarian cancers may be attributed to hereditary syndromes, most ovarian cancers are sporadic in the general population.
Etiology and Pathophysiology
- Reproductive history and duration of reproductive career are the strongest predictors (low parity/infertility, early menarche, late menopause). Suppression of ovulation may prevent repetitive disruption of the epithelial lining and thereby preclude spontaneous mutations that unmask germline mutations.
- A higher percentage of ovarian cancers are now known to originate in the fallopian tube and other components of the secondary müllerian system, including primary peritoneal cancers.
- Hereditary breast ovarian cancer syndrome: early-onset breast or ovarian cancer, autosomal dominant transmission with variable penetrance, usually associated with BRCA-1 or BRCA-2 mutation. 10–14% of patients with ovarian cancer have BRCA-1 or BRCA-2. Lifetime risk of ovarian cancer with BRCA-1: 39%, BRCA-2: 11%
- Lynch syndrome: autosomal dominant inheritance; increased risk for colorectal, endometrial, stomach, small bowel, breast, pancreas, and ovarian cancers; defect in DNA mismatch repair genes. Lifetime risk of ovarian cancer with Lynch syndrome: 6–12%
- 90% is sporadic, but family history is the most significant risk factor. Multiple relatives with breast or ovarian cancer: Refer these patients for genetic counseling. Individuals with familial cancer syndromes have 20–60% risk of developing ovarian cancer.
- Risk factors: older age, white race, infertility, nulligravidity, early menarche or late menopause, endometriosis, postmenopausal estrogen replacement therapy, residence in an industrialized Western country
- Association between fertility medications and risk of ovarian cancer is controversial, but women with infertility who have a successful live birth do not have an increased risk of ovarian cancer.
- Obesity as a risk factor for ovarian cancer remains inconclusive; some studies do suggest an increased risk with BMI >30 and increased mortality related to BMI >35.
- Long-term use of oral contraceptives: 5 years of use decreases risk by 20%; 15 years of use decreases risk by 50%.
- Tubal ligation, salpingectomy, or hysterectomy
- Risk-reducing salpingo-oophorectomy (estimated to reduce the risk of BRCA-related gynecologic cancer by 96%)
- Protective effect of aspirin and NSAIDs in ovarian cancer is controversial.
- Recommendations for high-risk (family history of a hereditary ovarian cancer syndrome) population
- Women should undergo pelvic examinations, CA-125 level measurement, and transvaginal US every 6 to 12 months beginning at age 30 or 10 years prior to the earliest age of diagnosis of ovarian cancer in the family—although efficacy of this approach has not been established.
- Women with family histories of ovarian cancer or premenopausal breast cancer should be referred for genetic counseling.
- Prophylactic oophorectomy is advised for mutation carriers after childbearing is completed or by age 35 years.
- Risk of primary peritoneal carcinoma remains 1–2% after prophylactic oophorectomy.
- Screening: No effective screening exists for ovarian cancer in the general population.
- Routine use of CA-125 and transvaginal US for screening in women of average risk is NOT recommended. Annual pelvic examinations may be performed, particularly in postmenopausal women. An adnexal mass in a premenarchal female or a palpable adnexa in a postmenopausal female warrants further evaluation.
Commonly Associated Conditions
- Pelvic pain, ascites, pleural effusion
- Carcinomatosis, bowel obstruction
- Breast cancer, endometrial cancer
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