Ovarian Cancer Latest Facts: Causes, Risk Factors, Symptoms, Treatment, and Prognosis

Ovaries are paired organs that form a part of the female reproductive system. They lie on either side of the uterus and are responsible for the production of ova and sex hormones such as estrogen and progesterone. The ovaries are made up of three types of cells: epithelial cells, germ cells, and stromal cells. An Ovarian cancer develops as a result of an abnormal and uncontrolled proliferation of any of these ovarian cells in one or both of the ovaries. There are three types of ovarian cancer depending on the type of ovarian cell involved, they are epithelial cell, sex cord-stromal, and germ cell cancers.

Ovary

Ovarian cancer most commonly develops in older women and the chances of survival depend on the extent cancer has spread to other parts of the body. More women die of ovarian cancer than any other type of reproductive cancer. In its treatment, most Doctors use surgery, chemotherapy, or targeted medical therapy. Drugs and cosmetic products such as fertility drugs, hormone therapy after menopause, or talcum powder may increase ovarian cancer risk.

Epidemiology

Ovarian cancer is the seventh most common cancer in women (and the 18th most common cancer overall) worldwide. About one in every 78 women develop ovarian cancer during their lifetime. In the USA, approximately 21,000 women are diagnosed with ovarian cancer, and 14,000 deaths from this disease are recorded annually.

Causes of ovarian cancer

Ovarian cancer occurs due to a mutation in the DNA of the Ovarian cells that causes the cells to proliferate uncontrollably and resist signals that try to regulate their growth. It is unclear how this occurs, however, doctors have identified things that can increase the risk of the disease.

Risk factors

Factors that increase the risk of developing ovarian cancer include:

Older age

The risk of ovarian cancer increases with age. Most ovarian cancers develop after menopause.

Being overweight or obese: Obesity has been linked with a higher risk of developing many cancers including ovarian cancer, and a reduction in the survival rate of women with ovarian cancer.

Family history of ovarian cancer

Ovarian cancer can run in the family. Having a blood relative who has been diagnosed with ovarian cancer increases the risk of developing the same condition in the woman

Inherited Gene changes

About 25% of cancers are due to changes (mutations) in certain inherited genes. This is known as inherited cancer syndromes. Examples include:

Hereditary breast and ovarian cancer syndrome (HBOC): HBOC is due to an inherited mutation in the BRCA1(Breast Cancer gene 1) and BRCA2 (BReast Cancer gene 2) genes. These genes are normally involved in the repair of damaged DNA before cell division. Everyone has a copy of these genes-one copy inherited from each parent. People who inherit a mutated form of this gene have an increased risk of developing several cancers including ovarian and breasts cancers.
Hereditary nonpolyposis colon cancer (HNPCC) or Lynch Syndrome: It occurs as a result of an inherited mutation in any of the following genes: MLH1, MSH2, MSH6, PMS2, and EPCAM. Women with a mutation in any of these genes are at a high risk of developing colon cancer and an increased risk of developing endometrial (uterine) and ovarian cancers.
MUTYH-associated polyposis: This syndrome is caused by a mutation in the MUTYH gene. MUTYH provides instructions for the synthesis of a protein involved in DNA repair. People with this syndrome develop polyps in their colon and small intestine and have a high risk of developing cancers of the colon and small intestine. They also have an increased risk of developing ovarian and bladder cancer.
Peutz-Jeghers syndrome: This is a rare genetic condition that predisposes affected individuals to cancers of the digestive tract and increases their risk of developing ovarian cancer. Individuals with this syndrome also have polyps in their intestines. It is caused by an inherited mutation in the STK11 gene.

Postmenopausal hormone replacement therapy

Women who take hormone replacements to control the signs and symptoms of menopause have an increased risk of developing ovarian cancer.

Endometriosis

This is a disorder in which tissue that normally lines the uterus grows outside the uterus. It is characterized by pains during menstruation, intercourse, and urination. It’s is also associated with excessive menstrual bleeding and may cause infertility. Women with endometriosis are at a higher risk of developing ovarian cancer.

Early menarche (first menstruation) and/or late menopause

Women who begin menopause at an early age and women who begin menopause at a later age in life have an increased risk of developing ovarian cancer.

Having children later or never having a full-term pregnancy

Women who have their first full-term pregnancy after the age of 35 years or who have never carried a pregnancy to term have an increased risk of developing ovarian cancers.

Factors with unclear effects on ovarian cancer

Talcum powder

There’s a rising concern that talcum powder applied on the genitals, sanitary pads, napkins, or condoms can cause ovarian cancer if the powder particles cross the bloodstream and reach the ovaries. However, studies so far have met with mixed results and so there is little evidence at this time.

Diet

It has also been suggested that diet may affect the development of ovarian cancer. Diets high in red meats, highly processed foods and refined sugar have been associated with an increased risk of ovarian cancer.

High levels of androgens in the body: Androgens are male sex hormones, for example, testosterone. Women also contain androgens and it is suggested that women with higher levels of androgen have an increased risk of developing breast cancers.

Types of ovarian cancer

Depending on the cells where cancer arises, ovarian cancer can be divided into three types.

Epithelial Ovarian cancer

Epithelial ovarian cancer accounts for most of the ovarian cancer types. This occurs due to a malignancy of the epithelial cells lining the ovaries. It may involve one or both ovaries. The cancer cells then spread to the pelvis and abdomen in the advanced stages.

Sex Stromal cancer

This makes up about one percent of ovarian cancers. It is cancer that develops due to abnormal and uncontrolled proliferation of the stromal cells of the ovary.

Germ cell cancer

Germ cell cancers account for less than two percent of ovarian cancers. It occurs due to uncontrolled proliferation of the germ cells of the ovary. These cells are involved in the production of mature female gametes.

Signs and symptoms of ovarian cancer

The signs and symptoms of ovarian cancer depend on several factors including the size, extent of invasion, and the metastasis of the cancer cells. Ovarian cancer may not be associated with any noticeable sign or symptom at first but later stages are associated with symptoms. These symptoms are non-specific and may be easily missed by the unsuspecting individual. The most common symptoms associated with ovarian cancer include:

Bloating: Bloating is a feeling of fullness or tightness around your belly. Individuals with a bloated stomach might feel the need to pass gas and often have a distended abdomen. In ovarian cancer, bloating occurs due to the build-up of fluid in the abdomen (ascites). This occurs when cancer cells spread to the peritoneum. These cancer cells irritate the peritoneal lining and cause the membrane lining the abdominal walls and viscera to secrete excess fluid.
Pelvic and abdominal pain: This may often be dismissed as menstrual cramps. Pain may be on one side or may involve both sides of the abdomen or pelvis.
Trouble eating and quickly feeling full after eating
Urinary symptoms such as urgency ( an overwhelming need to urinate) and frequency ( increased number of times one urinates)

Other symptoms associated with ovarian cancer include:

Fatigue
Stomach upset
Pain during sex
Menstrual problems such as pain during menstruation, excessive menstrual bleeding, etc
Back pain
Indigestion
Constipation

Metastasis of ovarian cancer

Like all other cancers, Ovarian cancers can metastasize or spread to other tissues of the body. Ovarian cancer is the most lethal gynecological malignancy. It is capable of metastasizing to the peritoneal cavity, omentum, and even to the parenchyma of the liver or lung. However, its spread is widely believed to occur via the peritoneal circulation, associated with ascites formation, instead of the classic patterns of metastasis via the hematogenous route.

Ovarian Cancer Seen on CT. Credit: James Heilman, MD

Diagnosis of ovarian cancer

Diagnosis starts with a detailed patient history taking and physical examination. The physical exam should include a pelvic and rectal examination. A series of other blood tests as recommended by the doctor may also be carried out during the diagnosis. A biopsy is also essential to determine the presence of cancer cells in the ovary. The doctor may also recommend a PET, CT, or MRI scan to view the abdomen and pelvis for the presence of any abnormal masses.

Staging of ovarian cancer

For effective treatment and to predict the prognosis, a doctor determines a person’s cancer stage using the results of imaging scans, blood tests, and tissue samples obtained from surgery.

The FIGO (International Federation of Gynecology and Obstetrics) classifies Ovarian cancer into four stages. They include Stages I, II, III, and IV

Stage I

This means that there are cancer cells in one or both ovaries.

It is divided into:

Stage IA: Cancer is limited to a single ovary, with no ascites

Stage IB: Cancer is limited to both ovaries, with no ascites

Stage IC: Cancer is found inside one or both ovaries. When the cancer is in this stage it is characterized by having either a broken capsule, cancer cells present outside the ovarian capsule, or ascites due to peritoneal infiltration by the cancer cells.

Stage II

This implies that cancer cells have been found in one or both ovaries and have metastasized into other areas of the pelvis.

It is sub-divided into:

Stage IIA: Cancer cells have metastasized to the uterus and fallopian tubes, with no visible ascites
Stage IIB: Cancer cells have metastasized to other pelvic tissues, with no visible ascites
Stage IIC: Cancer cells have metastasized to any of the above sites in Stage IIA or IIB with visible ascites

Stage III

This implies that cancer has been found in one or both ovaries and has spread to distant sites outside the pelvis into the abdomen

It is sub-divided into:

Stage IIIA: Cancer cells are grossly limited to the pelvis
Stage IIIB: Cancer infiltrates beyond the pelvis is less than 2cm
Stage IIIC: Cancer infiltrates beyond the pelvis is greater than 2cm

Stage IV

This implies that cancer has been found in one or both ovaries and has metastasized to distant sites beyond the pelvis and abdomen.

Management of ovarian cancer

Treatment of ovarian cancer depends on the stage and the genomic profile of cancer. Several treatment options exist, including surgery, chemotherapy, and radiation therapy.

Surgery

Surgery is often the initial treatment of choice for ovarian cancer, provided patients are medically fit.

Surgery aims to confirm the diagnosis, define the extent of the disease, and resect all visible tumors.

Different surgical approaches treatment of ovarian cancer exist however, the approach used depends on the visibility of cancer outside the ovaries.

Chemotherapy

Surgery is usually followed by chemotherapy. Medications can be injected into the veins or given through the abdomen.

Radiation therapy

Here the cancer cells are exposed to radiations that cause damage to the cells and induce death of the cancer cells.

Prognosis

A prognosis depends on the stage of ovarian cancer and the presence of BRCA genes. Drugs against mutated BRCA genes can be used against ovarian cancers which express a mutant form of these genes as such they show a good prognosis when present. Also, the 5-year survival rate of ovarian cancers detected at their early stage is very high, about 92%

Prevention

Currently, it is uncertain how ovarian cancer can be prevented, however, the following are associated with a lower chance of developing ovarian cancer:

Breastfeeding: Research has shown that women who breastfeed for above one year are at a lower risk of developing ovarian cancer.
Childbirth
Having had a tubal ligation (tying of one or both fallopian tubes), removal of ovaries, cervix, or the entire uterus.

Conclusion

Cancers have become some of the most dreaded diseases. A diagnosis of ovarian cancer does not imply a death sentence, especially when detected early. With a better understanding of what ovarian cancers are all about, you undoubtedly stand a better chance of detecting them early and taking the appropriate steps toward treatment.