Ovarian cancer
Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different cell types including epithelial cells, germ cells, and stromal cells. When these cells become abnormal, they have the ability to divide and form tumors. These cells can also invade or spread to other parts of the body. When this process begins, there may be no or only vague symptoms. Symptoms become more noticeable as the cancer progresses. These symptoms may include bloating, vaginal bleeding, pelvic pain, abdominal swelling, constipation, and loss of appetite, among others. Common areas to which the cancer may spread include the lining of the abdomen, lymph nodes, lungs, and liver.
The risk of ovarian cancer increases with age. Most cases of ovarian cancer develop after menopause. It is also more common in women who have ovulated more over their lifetime. This includes those who have never had children, those who began ovulation at a younger age and those who reach menopause at an older age. Other risk factors include hormone therapy after menopause, fertility medication, and obesity. Factors that decrease risk include hormonal birth control, tubal ligation, pregnancy, and breast feeding. About 10% of cases are related to inherited genetic risk; women with mutations in the genes BRCA1 or BRCA2 have about a 50% chance of developing the disease. Some family cancer syndromes such as hereditary nonpolyposis colon cancer and Peutz-Jeghers syndrome also increase the risk of developing ovarian cancer. Epithelial ovarian carcinoma is the most common type of ovarian cancer, comprising more than 95% of cases. There are five main subtypes of ovarian carcinoma, of which high-grade serous carcinoma is the most common. Less common types of ovarian cancer include germ cell tumors and sex cord stromal tumors. A diagnosis of ovarian cancer is confirmed through a biopsy of tissue, usually removed during surgery.
Screening is not recommended in women who are at average risk, as evidence does not support a reduction in death and the high rate of false positive tests may lead to unneeded surgery, which is accompanied by its own risks. Those at very high risk may have their ovaries removed as a preventive measure. If caught and treated in an early stage, ovarian cancer is often curable. Treatment usually includes some combination of surgery, radiation therapy, and chemotherapy. Outcomes depend on the extent of the disease, the subtype of cancer present, and other medical conditions. The overall five-year survival rate in the United States is 52%. Outcomes are worse in the developing world.
In 2020, new cases occurred in approximately 313,000 women. In 2019 it resulted in 13,445 deaths in the United States. Death from ovarian cancer increased globally between 1990 and 2017 by 84.2%. Ovarian cancer is the second-most common gynecologic cancer in the United States. It causes more deaths than any other cancer of the female reproductive system. Among women it ranks fifth in cancer-related deaths. The typical age of diagnosis is 63. Death from ovarian cancer is more common in North America and Europe than in Africa and Asia. In the United States, it is more common in White and Hispanic women than Black or American Indian women.
Signs and symptoms
Early symptoms
Early signs and symptoms of ovarian cancer may be absent or subtle. In most cases, symptoms exist for several months before being recognized and diagnosed. Symptoms can often be misdiagnosed as irritable bowel syndrome. The early stages of ovarian cancer tend to be painless which makes it difficult to detect it early on. Symptoms can vary based on the subtype. Ovarian borderline tumors, also known as low malignant potential ovarian tumors, do not cause an increase in CA125 levels and are not identifiable with an ultrasound. The typical symptoms of an LMP tumor can include abdominal distension or pelvic pain. Particularly large masses tend to be benign or borderline.The most typical symptoms of ovarian cancer include bloating, abdominal or pelvic pain or discomfort, back pain, irregular menstruation or postmenopausal vaginal bleeding, pain or bleeding after or during sexual intercourse, loss of appetite, fatigue, diarrhea, indigestion, heartburn, constipation, nausea, feeling full, and possibly urinary symptoms.
Later symptoms
Later symptoms of ovarian cancer are due to the growing mass causing pain by pressing on other abdominopelvic organs or from metastases. Because of the anatomic location of the ovaries deep in the pelvis, most masses are large and advanced at the time of diagnosis. The growing mass may cause pain if ovarian torsion develops. If these symptoms start to occur more often or more severely than usual, especially after no significant history of such symptoms, ovarian cancer is considered. Metastases may cause a Sister Mary Joseph nodule. Rarely, teratomas can cause growing teratoma syndrome or peritoneal gliomatosis. Some experience menometrorrhagia and abnormal vaginal bleeding after menopause in most cases. Other common symptoms include hirsutism, abdominal pain, virilization, and an adnexal mass.Children
In adolescents or children with ovarian tumors, symptoms can include severe abdominal pain, irritation of the peritoneum, or bleeding. Sex cord stromal tumors produce hormones which can lead to the premature development of secondary sex characteristics. Sex cord-stromal tumors in prepubertal children may be manifested by signs of early puberty; abdominal pain and distension are also common. Adolescents with sex cord-stromal tumors may experience amenorrhea. As the cancer becomes more advanced, it can cause an accumulation of fluid in the abdomen and lead to distension. If the malignancy has not been diagnosed by the time it causes ascites, it is typically diagnosed shortly thereafter. Advanced cancers can also cause abdominal masses, lymph node masses, or pleural effusion.Risk factors
There are many known risk factors that may increase a woman's risk of developing ovarian cancer. The risk of developing ovarian cancer is related to the amount of time a woman spends ovulating. Factors that increase the number of ovulatory cycles a woman undergoes may increase the risk of developing ovarian cancer. During ovulation, cells are stimulated to divide. If this division is abnormally regulated, tumors may form which can be malignant. Early menarche and late menopause increase the number of ovulatory cycles a woman undergoes in her lifetime and so increases the risk of developing ovarian cancer. Since ovulation is suppressed during pregnancy, not having children also increases the risk of ovarian cancer. Therefore, women who have not borne children are at twice the risk of ovarian cancer than those who have. Both obesity and hormone replacement therapy also raise the risk.The risk of developing ovarian cancer is less for women who have fewer menstrual cycles, no menstrual cycles, breast feeding, take oral contraceptives, have multiple pregnancies, and have a pregnancy at an early age. The risk of developing ovarian cancer is reduced in women who have had tubal ligation, both ovaries removed, or hysterectomy. Age is also a risk factor. Non-genetic factors such as diabetes mellitus, high body mass index, and tobacco use are also risk factors for ovarian cancer.
Hormones
The use of fertility medication may contribute to ovarian borderline tumor formation, but the link between the two is disputed and difficult to study. Fertility drugs may be associated with a higher risk of borderline tumors. Those who have been treated for infertility but remain nulliparous are at higher risk for epithelial ovarian cancer due to hormonal exposure that may lead to proliferation of cells. However, those who are successfully treated for infertility and subsequently give birth are at no higher risk. This may be due to shedding of precancerous cells during pregnancy, but the cause remains unclear. The risk factor may instead be infertility itself, not the treatment.Hormonal conditions such as polycystic ovary syndrome and endometriosis are associated with ovarian cancer, but the link is not completely confirmed. Postmenopausal hormone replacement therapy with estrogen likely increases the risk of ovarian cancer. The association has not been confirmed in a large-scale study, but notable studies including the Million Women Study have supported this link. Postmenopausal HRT with combined estrogen and progesterone may increase contemporaneous risk if used for over 5 years, but this risk returns to normal after cessation of therapy. Estrogen HRT with or without progestins increases the risk of endometrioid and serous tumors but lowers the risk of mucinous tumors. Higher doses of estrogen increase this risk. Endometriosis is another risk factor for ovarian cancer, as is pain with menstruation. Endometriosis is associated with clear-cell and endometrioid subtypes, low-grade serous tumors, stage I and II tumors, grade 1 tumors, and lower mortality. Ovarian cancer which coexists with endometriosis is known as endometriosis-associated ovarian cancer. The presence of transitional lesions linking endometriosis to its malignant transformation is termed endometriosis-correlated ovarian cancer while the simple presence of endometriosis and ovarian cancer without the proof of transition is termed endometriosis-incidental ovarian cancer.
Before menopause, obesity can increase a person's risk of ovarian cancer, but this risk is not present after menopause. This risk is also relevant in those who are both obese and have never used HRT. A similar association with ovarian cancer appears in taller women.
Genetics
A family history of ovarian cancer is a risk factor for ovarian cancer. Women with hereditary nonpolyposis colon cancer, and those with BRCA-1 and BRCA-2 genetic abnormalities are at increased risk.The major genetic risk factor for ovarian cancer is a mutation in BRCA1 or BRCA2 genes, or in DNA mismatch repair genes, which is present in 10% of ovarian cancer cases. Only one allele needs to be mutated to place a person at high risk. The gene can be inherited through either the maternal or paternal line, but has variable penetrance. Though mutations in these genes are usually associated with increased risk of breast cancer, they also carry a substantial lifetime risk of ovarian cancer, a risk that peaks in a person's 40s and 50s. The lowest risk cited is 30% and the highest 60%. Mutations in BRCA1 have a lifetime risk of developing ovarian cancer of 15–45%. Mutations in BRCA2 are less risky than those with BRCA1, with a lifetime risk of 10% to 40%. On average, BRCA-associated cancers develop 15 years before their sporadic counterparts because people who inherit the mutations on one copy of their gene only need one mutation to start the process of carcinogenesis, whereas people with two normal genes would need to acquire two mutations.
In the United States, five of 100 women with a first-degree relative with ovarian cancer will eventually get ovarian cancer themselves, placing those with affected family members at triple the risk of women with unaffected family members. Seven of 100 women with two or more relatives with ovarian cancer will eventually get ovarian cancer. In general, 5–10% of ovarian cancer cases have a genetic cause. BRCA mutations are associated with high-grade serous nonmucinous epithelial ovarian cancer.
A strong family history of endometrial cancer, colon cancer, or other gastrointestinal cancers may indicate the presence of a syndrome known as hereditary nonpolyposis colorectal cancer, which confers a higher risk for developing a number of cancers, including ovarian cancer. Lynch syndrome is caused by mutations in mismatch repair genes, including MSH2, MLH1, MLH6, PMS1, and PMS2. The risk of ovarian cancer for an individual with Lynch syndrome is between 10 and 12 percent. Women of Icelandic descent, European Jewish descent/Ashkenazi Jewish descent, and Hungarian descent are at higher risk for epithelial ovarian cancer. Estrogen receptor beta gene seems to be a key to pathogenesis and response to therapy. Other genes that have been associated with ovarian cancer are BRIP1, MSH6, RAD51C and RAD51D. CDH1, CHEK2, PALB2 and RAD50 have also been associated with ovarian cancer.
Several rare genetic disorders are associated with specific subtypes of ovarian cancer. Peutz–Jeghers syndrome, a rare genetic disorder, also predisposes women to sex cord tumour with annular tubules. Ollier disease and Maffucci syndrome are associated with granulosa cell tumors in children and may also be associated with Sertoli-Leydig tumors. Benign fibromas are associated with nevoid basal cell carcinoma syndrome.