Ovarian cancer and ovarian cyst

Although ovarian cancer is the deadliest gynecological cancer, awareness among both women and health care professionals regarding the dangers of ovarian cancer remains inadequate. Ovarian cancer strikes 23,000 American women every year, and approximately 14,000 die of the disease annually. (1) Ovarian cancer accounts for 52% of all gynecological cancer deaths. (2) The death of comedienne Gilda Radner from ovarian cancer in 1991 brought the disease to the forefront for the American public. Unfortunately, since that time there has been an absence of publicity regarding this disease. In addition, managed care organizations impose hurdles to specialty care and often deny reimbursement when a woman pursues diagnostic screening for suspected ovarian cancer. (3)

Seventy-five percent of ovarian cancers are not diagnosed until the cancer has advanced to stage III or IV, giving a five-year survival rate of only 20%. (4) This statistic has not changed in the last three decades primarily because an adequate screening tool still is unavailable. Clinical guidelines for the diagnostic screening of ovarian cancer have not been developed yet. Ten thousand pelvic examinations have to be performed, on average, to identify one ovarian cancer. (5) The tumor marker, cancer antigen 125 (CA-125), is not specific and, therefore, is an inadequate screening tool.

Differentiating between benign and malignant ovarian masses is necessary because ovarian cancer is lethal, and there are no proven screening techniques. Clinicians must consider the patient's medical profile (ie, risk factors, size of the mass, clinical presentation) to critically evaluate the likelihood of an early ovarian cancer. Diagnostic screening must include three essential components: an accurate medical history, a careful physical examination, and the judicious use of diagnostic procedures (eg, ultrasound, computed tomography [CT] scan, laparoscopy). (6)

EPIDEMIOLOGY

Approximately 5% to 10% of American women will undergo a surgical procedure for suspected ovarian cancer some time during their lives. (7) The United States has higher surgical rates for benign ovarian tumors compared to European countries such as Britain and Wales. These differences may be attributed to health care system screening. In Britain, cervical Papanicolaou's (Pap) smears are performed every five years and do not necessarily include bimanual examinations. The United States recommends screening Pap smears and pelvic examinations annually. At least 60,000 surgical excisions of benign ovarian masses occur per year in the United States. (8) It is essential, therefore, to differentiate preoperatively between possible early malignancy versus a benign condition to avoid unnecessary surgery. Clinicians must be aware of the incidence, risk factors, and common presenting symptoms of ovarian cancer to make a competent diagnosis.

Incidence. One in 70 women will develop ovarian cancer. This represents a 1.7% lifetime risk of developing ovarian cancer. (9) Two genes, BRCA-1 and BRCA-2, are linked with hereditary breast and ovarian cancers. Blood tests can be performed to assess DNA in white blood cells to detect mutations in the BRCA genes. These genetic markers do not predict whether the patient will develop cancer, but rather they provide information regarding the risk of developing cancer. If a patient is BRCA positive, then her lifetime risk of developing ovarian cancer increases to between 16% and 60% versus the general population's risk of 1.7%.

Although there is much discussion regarding BRCA-1 and BRCA-2 gene testing, only 5% to 10% of ovarian cancers are linked to a positive familial history. (10) In general, inherited cancer accounts for 5% to 10% of all malignancies and usually occurs 10 to 15 years sooner than a sporadic cancer. Additionally, the incidence of ovarian cancer increases with age. The majority of ovarian cancer cases occur between the ages of 55 and 74, with the average age being 61.

Risk factors. Several studies have documented a decreased risk for ovarian cancer in women who use oral contraceptive pills (OCP). The mechanism probably is related to ovulation suppression and the inhibitory effect of OCP on ovarian activity. A recent study of 924 women in New York City demonstrated that use of an oral contraceptive was associated with a decreased risk of benign ovarian tumors, with the greatest reduction occurring in women who used them for more than two years. (11) One study showed an overall 40% risk reduction of ovarian cancer in women aged 20 to 54 who used oral contraceptives. (12) After four years of oral contraceptive use, the risk of ovarian cancer decreased by 50%, and after seven years, a 60% to 80% reduction in disease was noted. (13) These studies support the recommendation that health care providers prescribe OCP for women of reproductive age seeking contraception because of the large number of surgeries currently being performed for benign ovarian disease. (14) A recent study showed that in BRCA-1 and BRCA-2 carriers, the risk of ovarian cancer decreased by 12% with each live birth, but not with increased duration of oral contraceptive use. (15) Table 1 contains a list of risk factors.

Current literature, on the other hand, shows that in a sample of 211,581 postmenopausal women, there is an increased risk of ovarian cancer mortality for women who have a greater than 10-year history of estrogen replacement therapy (ERT). This increase was observed for both baseline users and for women who had used estrogen within 15 years before baseline. Less than 10 years of ERT was not associated with an increased risk for ovarian cancer. The effect of combined hormone replacement therapy (ie, using a combination of progestin and estrogen) on ovarian carcinoma is unknown. (16) These findings were similar to those reported for breast cancer mortality and ERT. (17)

Eighty-five percent of ovarian tumors are benign in women during their reproductive years. Of these benign ovarian masses, 66% occur in women aged 20 to 44 years. The chance of a primary ovarian tumor being malignant, therefore, in a woman less than 45 years of age is less than one in 15.

Types of tumors. Ovarian masses are classified as simple, borderline neoplastic, or neoplastic. Simple cysts can be functional or endometriomas. Functional adnexal masses consist of follicular, corpus luteum, and theca lutein cysts. These cysts usually are asymptomatic and resolve in four to eight weeks. Oral contraceptive pills, especially the monophasic type, decrease their development. Endometriomas or chocolate cysts do not resolve and usually are associated with endometriosis and pain. (18)

Borderline neoplastic ovarian cysts consist of

* dermoid tumors;

* cystic teratoma tumors; and

* epithelial tumors, such as serous cystadenomas, serous papillary cystadenomas, and mucinous cystadenomas.

Of these neoplastic ovarian cysts, dermoids and teratomas have the lowest malignant potential at only 2%. Eighty percent of dermoid and teratoma tumors occur in women during their reproductive years, with the median age for occurrence being 30.

Serous cystadenomas generally are benign, but 5% to 10% have a borderline malignancy risk, and 20% to 25% have a high malignancy risk. Mucinous cystadenomas have been known to be massive in size and are bilateral in 10% of cases. Additionally, 5% to 10% of mucinous cystadenomas are malignant. (19)

Neoplastic masses are classified according to the cell type from which they originate. Ninety percent of all ovarian cancers arise from the epithelial lining of the ovary, and 40% of these are of the serous type. These cancers typically are graded according to the degree of differentiation, with grade zero being well differentiated and grade three being poorly differentiated. Germ cell carcinoma (ie, cells that form the eggs) accounts for 5% of all ovarian cancers and generally occurs in women in their early twenties. Stromal carcinoma accounts for the remaining 5% of cancer cases and develops in the connective tissue cells that hold the ovary together and produce estrogen and progesterone. Fortunately, 70% of stromal carcinoma is diagnosed at stage I. The five-year survival for stage I and II ovarian cancer is 50% to 90%. (20)

Symptoms. Ovarian cancer usually is described as the silent killer, but this is not always true. Many medical textbooks indicate and health care professionals erroneously believe that ovarian cancer is asymptomatic. Current literature, however, indicates that early symptoms often are present. These most commonly include unusual bloating, abdominal fullness, and abdominal pressure. (21)

A 15-year retrospective study reviewed medical records of 72 patients who developed early stage ovarian carcinoma. The study showed that 78% of these patients presented with one or more of the following signs or symptoms:

* ascites (12.5%),

* bloatedness or increased abdominal girth (32%),