What Is Ovarian Cancer? What Causes Ovarian Cancer?

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Main Category: Ovarian Cancer
Also Included In: Cancer / Oncology;  Women's Health / Gynecology
Article Date: 04 Aug 2009 - 0:00 PDT

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Ovarian cancer is any cancerous growth that may occur in different parts of the ovary. The majority of ovarian cancers arise from the epithelium (outer lining) of the ovary. According to the American Cancer Society it is the 8th most common cancer among women in the USA (excluding non-melanoma skin cancers). In the UK ovarian cancer is the fifth most common cancer among females, after breast cancer, bowel cancer, lung cancer and uterine cancer (cancer of the uterus).

Approximately 5,500 women in the UK and 21,000 women in the USA are diagnosed with ovarian cancer each year. Worldwide, around 140,000 women die of ovarian cancer every year.

Tragically, the overall five year survival rate is only 46 per cent in most developed countries (it is lower for more advanced stages). However, according to the National Cancer Institute, if diagnosis is made early, before the tumor has spread, the five year survival rate is nearer 93 per cent. In 2009 scientists in the US said that current tests for diagnosing ovarian cancer are not good enough .

Even modern screening tests for ovarian cancer, which include a blood test for the CA 125 marker, combined with ultrasound, often result in unnecessary surgery and "..are failing to catch early signs of the disease..", a study at the University of Alabama at Birmingham Comprehensive Cancer Center revealed.

What are the ovaries?

The ovary is the female gonad, while the testis is the male gonad. A gonad is a reproductive gland that produces germ cells (gametes). A male sperm is a gamete, and a female egg is also a gamete. Each human gamete has 23 chromosomes, half the number of chromosomes contained in most types of human body cells.

The ovary, also known as the egg sac, is one of a pair of reproductive glands in women. The ovaries are located at either side of the uterus (womb), in the pelvis. Each ovary is about the size and shape of an almond. The ovaries produce ova (eggs) and female hormones, such as estrogen and progesterone. These hormones regulate the menstrual cycle, pregnancy, and control the development of female characteristics, such as body shape, body hair, breasts, etc.

During the female menstrual cycle, which lasts about one month, one egg is released from one of the two ovaries - the egg travels through the fallopian tube and into the uterus. This is known as ovulation.

Cancer of the ovary can spread to other parts of the reproductive system as well as surrounding areas, such as the stomach, vagina and uterus. Ovarian cancer more commonly occurs in women aged 65 or over, but can affect women of any age.

What is cancer?

Cancer is a class of diseases characterized by out-of-control cell growth. There are over 100 different types of cancer that occur in various parts of the body - each is classified by the type of cell that is initially affected.

Usually our cells divide (multiply, form new ones) only when old and dying ones need to be replaced. However, the controls that regulate when a cell divides as well as when a cell should die sometimes become faulty. This may result in cells not dying when they should, while additional cells are still being added - an uncontrolled accumulation of cells. Eventually a mass of cells is formed - a tumor.

Malignant and benign tumors

Tumors that stay in one place and demonstrate limited growth are usually considered to be benign. Malignant, or more dangerous tumors emerge when two things occur:

• Invasion - the cancerous cell manages to move throughout the body using the blood or lymph systems, destroying healthy tissue - this process is called invasion.


• Angiogenesis - the cancerous cells manage to divide and grow, making new blood vessels to feed themselves.

Metastasis

When a tumor manages to spread to other parts of the body and grows, invading and destroying other healthy tissues, it is said to have metastasized. This process itself is called metastasis, and the result is a serious condition that is extremely hard to treat.

Three main types of ovarian cancers (tumors)

Epithelial ovarian cancer is by far the most common form of ovarian cancer. Germ cell and stromal ovarian cancers are much less common. Ovarian cancer can also result from a cancer somewhere else in the body that has spread:

• Epithelial ovarian cancer (epithelial ovarian tumors) - derived from cells on the surface of the ovary. It occurs mainly in adults.


• Germ cell ovarian cancer (germ cell ovarian tumors) - derived from the egg-producing cells within the body of the ovary. This rare type of cancer more commonly affects children and teenage girls.


• Stromal ovarian cancer (sex cord stromal tumors) - develops within the cells that hold the ovaries together.


• Cancers from other organs in the body can spread to the ovaries - metastatic cancers - a metastatic cancer is one that spreads from where it first arose as a primary tumor to other locations in the body.

What are the symptoms of ovarian cancer?

In the early stages, ovarian cancer usually has vague symptoms which are not easy to recognize. In fact, doctors used to think that ovarian cancer had no symptoms (unfortunately, many still do). Even though healthcare professionals are much better at identifying ovarian cancer symptoms these days, patients often attribute their symptoms to other conditions, such as pre-menstrual syndrome, irritable bowel syndrome, or a temporary bladder problem.

The main difference between ovarian cancer and other possible disorders is the persistence and gradual worsening of symptoms. While most digestive disorders have fluctuating symptoms, those of ovarian cancer are more constant and steadily advancing.

The following are examples of possible early symptoms of ovarian cancer:

• Pain in the pelvis
• Pain on the lower side of the body
• Pain in the lower stomach
• Back pain
• Indigestion or heartburn
• Feeling full rapidly when eating
• More frequent and urgent urination
• Pain during sexual intercourse
• Changes in bowel habits, such as constipation

As ovarian cancer progresses these symptoms are also possible:

• Nausea
• Weight loss
• Breathlessness
• Fatigue (tiredness)
• Loss of appetite

Ovarian cancer is not a silent killer. A study by the National Breast and Ovarian Cancer Centre, Australia, found that 83% of women experience at least one symptom of ovarian cancer in the year prior to their diagnosis. The researchers also found that 17% of women waited more than three months after the onset of their symptoms before visiting their doctor, with 8% waiting more than six months. The most common symptoms, experienced by half of the study participants, were abdominal symptoms such as fullness and pain. Bloating, bowel or urinary symptoms were reported by approximately one third of participants.

If you experience bloating, pressure or pain in the abdomen or pelvis that persists for more than a few weeks you should see your doctor immediately. If you have already been to the doctor and ovarian cancer was not diagnosed, but treatment is not relieving symptoms, either see your doctor again or get a second opinion. It is important that the evaluation includes a pelvic examination.

People with close family members who have/had ovarian or breast cancer should see a doctor who is trained to detect ovarian cancer.

What are the causes of ovarian cancer?

Although we know that ovarian cancer, like many other cancers, is caused by cells dividing and multiplying in an unordered way, nobody completely understands why cancer of the ovary occurs. We know that the following risk factors are linked to a higher chance of developing the disease:

Family history

Most women who develop ovarian cancer do not have an inherited gene mutation. Women with close relatives who have/had ovarian cancer, as well as breast cancer, have a higher risk of developing ovarian cancer compared to other women. There are two genes - BRCA1 and BRCA2 - which significantly raise the risk. The BRCA1 and BRCA2 genes also raise the risk of breast cancer. Those genes are inherited. The BRCA1 gene is estimated to increase ovarian cancer risk by 35% to 70%, and the BRCA2 by 10% to 30%. People of Ashkenazi Jewish descent are at particularly high risk of carrying these types of gene mutations.

Women with close relatives who have/had colon cancer, prostate cancer or uterine cancer are also at higher risk of ovarian cancer.

Genetic screening can determine whether somebody carries the BRCA1 and/or BRCA2 genes. Although a test for gene mutations known to significantly increase the risk of hereditary breast or ovarian cancer has been available for more than a decade, a study by researchers from Massachusetts General Hospital found that few women with family histories of these cancers are even discussing genetic testing with their physicians or other health care providers.

After eight years of searching, an international team of scientists found that a single nucleotide polymorphisms (SNP) on chromosome 9 that is uniquely linked to ovarian cancer. The scientists estimated that women carrying that particular version of the SNP on both copies of chromosome 9 have a 40 per cent higher lifetime risk of developing ovarian cancer than women who do not carry it on either copy of chromosome 9, while women with only one copy of the variant have a 20 per cent higher lifetime risk of developing ovarian cancer than women who have none.

Age

The majority of ovarian cancers occur in women over 65 years of age. A higher percentage of post-menopausal women develop ovarian cancer compared to pre-menopausal women.

High number of total lifetime ovulations

There is a link between the total number of ovulations during a woman's life and the risk of ovarian cancer. Four principal factors influence the total:

• Never having been pregnant - women who have never become pregnant have a higher risk of developing ovarian cancer compared to women who have became pregnant. The more times a woman has become pregnant the lower her risk is.


• Never having taken the contraceptive pill - women who have never been on the contraceptive pill have a higher risk of developing ovarian cancer compared to women who have. Taking the Pill for 15 years halves the risk of ovarian cancer, a study by the Collaborative Group on Epidemiological Studies of Ovarian Cancer found.


• Early start of menstruation (early menarche) - women who started their periods at an early age have a higher risk of developing ovarian cancer.


• Late start of menopause - women whose menopause started at a later age than average have a higher risk of developing ovarian cancer.

Scientists at the Centers for Disease Control and Prevention (CDC) found that survival among women with ovarian cancer is also influenced by age of menarche (when periods start) and total number of lifetime ovulatory cycles.

Some gynecologic surgeries may reduce the risk

Women who have had their fallopian tubes tied (tubal ligation) are estimated to have a 67% lower risk of ovarian cancer. A hysterectomy is said to reduce the risk by about one third.

Infertility or fertility treatment

Some studies have found a link between infertility treatment and a higher risk of ovarian cancer. Nobody is yet sure whether the risk is linked to infertility treatment, just infertility itself, or both. A Danish study published in the peer-reviewed British Medical Journal concluded that the use of fertility drugs does not increase a woman's risk of developing ovarian cancer. The study involved 54,362 women with infertility problems referred to all Danish fertility clinics between 1963 and 1998.

Breast cancer

Women who have been diagnosed with breast cancer have a higher risk of developing ovarian cancer.

HRT (Hormone replacement therapy)

HRT slightly increases a women's risk of developing ovarian cancer. Experts say the risk grows the longer the HRT continues, and returns to normal as soon as treatment stops. Danish scientists reported that compared with women who have never taken hormone therapy, those who currently take it or who have taken it in the past are at increased risk of ovarian cancer, regardless of the duration of use.

A UK study that was published in the peer-reviewed medical journal The Lancet suggested that between 1991 and 2005, an extra 1,000 women in the UK died of ovarian cancer because they were on Hormone Replacement Therapy.

Foods high in acrylamide

A study in the Netherlands found a link between acrylamide, a carcinogenic compound found in cooked, and especially burned, carbohydrate rich foods, and increased risk of endometrial and ovarian cancer in postmenopausal women.

Obesity/overweight

Being obese or overweight increases the risk of developing many cancers. The more overweight you are, the higher the risk. Several studies have also shown that obese cancer patients are more likely to have faster advancing ones compared to cancer patients of normal weight. Obese older women who have never used hormone replacement therapy have nearly twice the risk of their normal weight peers of developing ovarian cancer, according to a study by the researchers at the National Cancer Institute.

Endometriosis

Women who develop endometriosis have an approximately 30% higher risk of developing ovarian cancer compared to other women. Endometriosis is a condition in which cells that are normally found inside the uterus (endometrial cells) are found growing outside of the uterus. Danazol, a medication used to treat endometriosis has been linked to ovarian cancer risk.

Diagnosis of ovarian cancer

There is a tragic myth among many health care professionals and patients in too many countries about early stage ovarian cancer having no symptoms. A UK study, called The Target Ovarian Cancer Pathfinder study which surveyed 400 UK general practitioners and over 1,000 women, including 132 with ovarian cancer, found that 80% of GPs in the UK were wrongly of the view that women have no symptoms in the early stages of ovarian cancer. Studies in countries with top healthcare services have come up with similar findings.

The GP (general practitioner) will carry out a vaginal examination and check for any visible abnormalities in the uterus or ovaries. The doctor will also check the patient's medical history and family history. Further tests will be ordered - these are usually done by a gynecologist - a doctor who specializes in treating diseases of the female reproductive organs.

If the woman is diagnosed with ovarian cancer the doctor will want to identify its stage and grade. The stage of a cancer refers to the cancer's spread while the grade refers to how aggressively it is spreading. By identifying the stage and grade of the cancer the doctor will be able to decide on the best treatment. The stage and grade of ovarian cancer alone cannot predict how it is going to develop.

The following tests are used to diagnose ovarian cancer:

• Blood test
  
  There is a cancer marker called CA 125 (cancer antigen 125) which is made by certain cells in the body. A high blood level of CA 125 may indicate the presence of cancer, but could also be due to something else, such as infections of the lining of the abdomen and chest, menstruation, pregnancy, endometriosis, or liver disease. This blood test is just one test among others, designed to help the doctor make a diagnosis. Normal blood levels of CA125 alone do not definitely mean there is no cancer either. They are just indications.


• Ultrasound
  
  This is a device that uses high frequency sound waves which create an image on a monitor of the ovaries and their surroundings. A transvaginal ultrasound device may be inserted into the vagina, while an external device may be placed next to the stomach. Ultrasound scans help doctors see the size and texture of the ovaries, as well as any cysts.


• Laparoscopy and possibly Endoscopy
  
  A laparoscope - a thin viewing tube with a camera at the end - is inserted into the patient through a small incision in the lower abdomen. The doctor can examine the ovaries in detail, and can also take a biopsy (extract a small sample of tissue for examination). The patient will undergo a general anesthetic for this procedure. The doctor may carry out an endoscopy to determine whether the cancer has spread to the digestive system.


• Colonoscopy
  
  If the patient has had bleeding from the rectum, or constipation the doctor may order a colonoscopy to examine the large intestine (colon). The colonoscope - a thin tube with a camera at the end - will be inserted into the rectum.


• Abdominal fluid aspiration
  
  If the patient's abdomen is swollen the doctor may decide to carry out this test. A build up of fluid in the abdomen might indicate that the ovarian cancer has spread. A thin needle goes through the skin into the abdomen and a sample of the liquid is extracted. Some of the liquid may be drained into a bag if there is a lot of it (abdominal tap). The fluid is checked in the laboratory for cancer cells.


• Chest X-ray
  
  This test will help the doctor see if the cancer has spread to the lungs, or to the pleural space surrounding the lungs.


• CT (computerized tomography) scan
  
  X-rays are used to create a 3-dimensional picture of the target area.


• MRI (magnetic resonance imaging) scan
  
  Magnets and radio waves produce 2-dimensional and 3-dimensional pictures of the target area.
  
  Combined positron emission tomography (PET) and computed tomography (CT) scanning of patients in the early stages of ovarian cancer can enable physicians to determine whether the cancer has spread to nearby lymph nodes without having to perform surgery, reported scientists at San Gerardo Hospital, Monza, Italy.

The 4 stages of ovarian cancer

Ovarian cancer is classified into four stages, with stage 4 being the most advanced.

• Stage 1 - the cancer is confined to one or both ovaries. This is subdivided into three groups:
  
  
  • Stage 1a - the cancer is confined to just one ovary (contained inside it).
  • Stage 1b - the cancer is confined to both ovaries (contained inside them).
  • Stage 1c - either 1a or 1b, but there is come cancer on the surface of one or both ovaries, or cancer cells are found in fluid extracted from inside the abdomen during surgery, or the ovary bursts during or before surgery.


• Stage 2 - the cancer has spread to the uterus, fallopian tubes or some other areas in the pelvis (tummy area). This is subdivided into 3 groups:
  
  
  • 2a - the cancer has spread into the uterus (womb) or the fallopian tubes.
  • 2b - the cancer has spread into other tissues in the pelvis, such as the rectum or bladder.
  • 2c - 2a and 2b, and there is cancer on the surface of one or both ovaries, or cancer cells are identified in fluid extracted from inside the abdomen during surgery, or the ovary bursts during or before surgery.


• Stage 3 - the cancer has spread into the peritoneum (the lining of the abdomen), or to the lymph nodes in the upper abdomen, groin or behind the uterus. Most ovarian cancers are diagnosed at this stage. This stage is divided into three subgroups:
  
  
  • 3a - an examination with a microscope of tissue taken from the peritoneum (lining of the abdomen) or the omentum (fatty layer over the top of the intestines) detects cancer cells.
  • 3b - tumor growths are identified in the peritoneum 2cm or smaller.
  • 3c - tumor growths larger than 2cm are identified in the peritoneum. Cancer is found in the lymph nodes in the groin, behind the womb or the upper abdomen.


• Stage 4 - the cancer has spread beyond the abdomen to other parts of the body, including such organs as the lungs or the liver. If cancer is just found on the surface of the liver, but not inside it, it is still stage 3.

What is the treatment for ovarian cancer?

Treatment for ovarian cancer consists of surgery, chemotherapy, a combination of surgery with chemotherapy, and sometimes radiotherapy. The kind of treatment depends on many factors, including the type of ovarian cancer, its stage and grade, as well as the general health of the patient.

Some studies have indicated that specialized hospitals tend to have better survival rates for ovarian cancer patients, compared to general hospitals. Dutch ovarian cancer patients who were treated at a semispecialized or specialized hospital survived longer than those treated at a general hospital, reported researchers at the University Medical Center Utrecht in The Netherlands.

Surgery

The surgical removal of the cancer is performed in the vast majority of ovarian cancer cases, and is often the first treatment the patient will undergo.

Unless the ovarian cancer is very low grade, the patient will require an extensive operation that includes the removal of both ovaries, the fallopian tubes, the uterus, nearby lymph nodes, and the omentum (a fold of fatty abdominal tissue). Cancer often spreads into the omentum. In most cases the operation will be carried out by a gynecologic oncologist surgeon - a specialist in surgery for women with cancer of the reproductive organs. This operation, sometimes referred to as a total hysterectomy, will mean that the woman will begin her menopause immediately. Recent research by Canadian scientists found that premature removal of the ovaries increases the risk of lung cancer.

If the cancer is confined to just one of the ovaries the surgeon may just remove the affected ovary and the adjoining fallopian tube. The woman will have a chance of being able to conceive. If both ovaries are removed it will not be possible to conceive.

Surgery for ovarian cancer will require a hospital stay of up to two weeks, plus a recovery period of at least six weeks when the patient gets back home.

Chemotherapy

Chemotherapy is the use of chemicals (medication) to treat any disease - more specifically in this text, it refers to the destruction of cancer cells. Cytotoxic medication prevents cancer cells from dividing and growing. When health care professionals talk about chemotherapy today, they generally tend to refer more to cytotoxic medication than others. Chemotherapy for ovarian cancer, as well as most other cancers, is used to target cancer cells that surgery cannot or did not remove.

Patients will typically receive a combination of carboplatin (Paraplatin) and paclitaxel (Taxol) intravenously (injected into the bloodstream). As it is injected into the bloodstream it can target cancer cells in the reproductive system, as well as any cancer cells that may have reached elsewhere in the body.

Treatment usually involves 6 to 12 chemotherapy sessions which will be given three to four weeks apart so that the body has time to recover. One session usually consists of a 3-hour gradual injection of the medicine into the body; sometimes it may be extended to 24 hours. Extended injections require an overnight stay in hospital.

Compounds in cranberries may help improve the effectiveness of platinum drugs that are used in chemotherapy to fight ovarian cancer, scientists at Rutgers University found.

Monitoring response to chemotherapy

Tests will be carried out to determine how well the chemotherapy is working. This will include blood tests to see if levels of CA125 have dropped, and imaging scans to see if tumors have shrunk. Sometimes the surgeon may want to have another look inside.

The patient will be in remission if all tests are clear of cancer. In remission means the cancer is under control.

If cancer is still present after chemotherapy treatment doctors will switch to other treatments. Patients who did not respond well to a specific type of chemotherapy treatment are unlikely to respond well if the same treatment is done again. This may involve another type of chemotherapy, such as intraperitoneal chemotherapy, in which the medication is aimed at the stomach, or radiotherapy.

Researchers in the Duke Comprehensive Cancer Center reported that the addition of a chemotherapeutic drug for leukemia - dasatinib (Sprycel) - to a standard regimen of two other chemotherapy drugs appears to enhance the response of certain ovarian cancers to treatment, according to a pre-clinical study. Study leader, Deanna Teoh, M.D. said "These findings indicate that we may be able to direct the use of a targeted therapy like dasatinib based on gene expression pathways in select ovarian cancers."

Side effects of chemotherapy

Chemotherapy targets rapidly dividing cells. Unfortunately, healthy rapidly dividing cells, such as red and white blood cells and hair follicles may also be affected. The severity and types of side effects depend on the type of medication, number of treatments, and some aspects of the patient and their general health. This may result in the following side effects:

• Nausea, vomiting - medication for this may be given intravenously during chemotherapy sessions.
• Diarrhea.
• Hair loss.
• Loss of appetite.
• Mouth sores.
• Anemia.
• Infections because the white blood cell count is low (leucopenia).

In the vast majority of cases the damaged healthy cells repair themselves rapidly after treatment is over and the side-effects will soon disappear.

Radiotherapy

Radiation is not the mainstay of ovarian cancer treatment - it is not generally considered effective for ovarian cancer. It may be used if there are small traces of cancer in the reproductive system, or to treat the symptoms of advanced cancer. External radiotherapy may be used to clear traces of cancer left after chemotherapy, while internal radiotherapy may be used for advanced cancer. Radiotherapy may cause the following symptoms; some symptoms may not appear until a long time after treatment is over:

• Bladder infections
• Diarrhea
• Constipation
• Irritation, darkening of your skin that the radiation beams hit
• Nausea
• Frequent urination
• Abdominal pain

Diptheria toxin-enconding DNA

Scientists at Lankenau Institute for Medical Research found that nanoparticle delivery of diphtheria toxin-encoding DNA selectively expressed in ovarian cancer cells reduced the burden of ovarian tumors in mice. Lead researcher, Janet Sawicki, Ph.D said "We now have a potential new therapy for the treatment of advanced ovarian cancer that has promise for targeting tumor cells and leaving healthy cells healthy.".

Written by Christian Nordqvist


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