Ovarian cancer refers to malignancies that begin in the ovaries, which are part of the female reproductive system. It is important to note that this term sometimes serves as an umbrella label, encompassing both fallopian tube and primary peritoneal cancers. These cancers are generally treated similarly due to their close biological relationship. The disease originates when abnormal cells in the ovaries begin to grow uncontrollably, forming a tumor. If left untreated, these tumors can metastasize to other parts of the body, leading to severe health complications.
Ovarian cancer is a complex and heterogeneous disease that arises from multiple cell types and origins. The traditional view of ovarian carcinogenesis is that the various different tumors are all derived from the ovarian surface epithelium (mesothelium) and that subsequent metaplastic changes lead to the development of the different cell types (serous, endometrioid, clear cell, mucinous and transitional cell [Brenner]) which morphologically resemble the epithelia of the fallopian tube, endometrium, gastrointestinal tract or endocervix and urinary bladder, respectively.
However, recent studies have challenged this view and proposed that the majority of ovarian carcinomas, which are high-grade serous carcinomas, arise from high-grade intraepithelial serous carcinomas in the fallopian tube which then spread to the ovary. This theory is supported by the observation that the fallopian tube epithelium is the site of origin for many highgrade serous ovarian carcinomas, particularly in *BRCA1/2* mutation carriers.
Additionally, some studies suggest that endometrioid and clear cell tumors develop from endometrial tissue (müllerian derived) that is implanted on the ovary and therefore the ovary is involved secondarily. Mucinous and transitional (Brenner) tumors are thought to arise from transitional type epithelial nests at the tubal mesothelial junction by a process of metaplasia.
The cell of origin of ovarian cancer is still a topic of ongoing research and debate. Some studies suggest that ovarian cancer can initiate from cells originating from various sites outside of the ovaries, including the fallopian tube, endometrium, and peritoneum. The exact mechanisms by which these cells migrate and establish ovarian cancer are not fully understood .
Overall, the science of ovarian cancer is complex and multifaceted, and further research is needed to fully understand the origins and mechanisms of this disease.
The signs and symptoms of ovarian cancer can be nonspecific and overlooked by medical professionals, making it challenging to diagnose in its early stages. However, some common symptoms include:
Top 4 Symptoms:
Additional Symptoms:
Important: These symptoms can also be caused by other conditions, and only a healthcare provider can determine if they are related to ovarian cancer. If you experience any of these symptoms, especially if they persist or worsen over time, consult a healthcare provider for proper evaluation and diagnosis.
The most common misconceptions about ovarian cancer symptoms include:
Myth: Ovarian cancer has no symptoms.
Reality: Ovarian cancer can cause symptoms like persistent stomach pain, bloating, difficulty eating, and frequent urination
Myth: Ovarian cancer symptoms are always severe.
Reality: Symptoms can be intermittent, mild and nonspecific, often mistaken for other conditions.
Myth: Ovarian cancer is a silent killer.
Reality: While symptoms may not always be severe, they can persist and worsen over time.
Myth: Ovarian cancer symptoms are only experienced by older women.
Reality: Ovarian cancer can affect women of all ages, including younger women.
Myth: Ovarian cancer symptoms are the same as those for other gynecological cancers.
Reality: Each type of gynecological cancer has distinct symptoms, and ovarian cancer symptoms are unique.
Myth: Ovarian cancer can be detected by a Pap smear.
Reality: Pap smears are a screening test for cervical cancer, and don’t reliably detect ovarian cancer.
Myth: Ovarian cysts are always cancerous.
Reality: Most ovarian cysts are benign and do not develop into cancer.
Myth: Ovarian cancer is incurable.
Reality: While the survival rate is lower for late-stage ovarian cancer, early detection and treatment can significantly improve outcomes.
The major risk factors for ovarian cancer include:
Older Age: The risk of ovarian cancer increases with age, particularly after the age of 50. The majority of ovarian cancer cases are diagnosed in women over 55 years old, with the median age at diagnosis being 63 years old.
Genetics: Inherited genetic mutations, such as BRCA1 and BRCA2, or genetic mutations associated with Lynch Syndrome, significantly increase the risk of ovarian cancer. The BRCA1 and BRCA2 mutations are associated with both breast and ovarian cancer.
Family History: A family history of breast, ovarian, uterine, or colorectal cancer, particularly in first degree relatives, increases the risk of ovarian cancer.
Reproductive History: Factors such as early menstruation, late menopause, nulliparity, and infertility are associated with a higher risk of ovarian cancer.
Hormone Replacement Therapy (HRT): Using estrogen only HRT after menopause increases the risk of ovarian cancer.
Obesity: Being overweight or obese, particularly in early adulthood, is linked to a higher risk of ovarian cancer.
Smoking: Smoking is associated with an increased risk of mucinous ovarian cancer.
Endometriosis: Women with endometriosis have a higher risk of clear cell and endometrioid ovarian cancers.
Previous Cancer: A history of breast, uterine, or colorectal cancer increases the risk of ovarian cancer.
Inherited Syndromes: Certain inherited syndromes, such as Lynch syndrome, also increase the risk of ovarian cancer.
While these factors increase the risk, most women with ovarian cancer do not have a known risk factor.
Family history plays a significant role in increasing the risk of ovarian cancer. Here are the key points:
First degree relatives: Having a first degree relative (mother, sister, or daughter) with ovarian cancer increases the risk of developing the disease. The risk is higher if the relative was diagnosed at a younger age or if there are multiple relatives with ovarian cancer.
Second-degree relatives: Having a second degree relative (grandmother, aunt, or niece) with ovarian cancer also increases the risk, although to a lesser extent.
Multiple relatives: If multiple relatives on either side of the family have ovarian cancer, the risk increases significantly.
BRCA1 and BRCA2 mutations: Inherited mutations in the BRCA1 and BRCA2 genes significantly increase the risk of ovarian cancer. These mutations are associated with both breast and ovarian cancer.
Lynch syndrome: Lynch syndrome, caused by mutations in genes such as MLH1, MSH2, MSH6, and PMS2 also increases the risk of ovarian cancer.
Other cancers: A family history of breast, uterine, or colorectal cancer may increase the risk of ovarian cancer.
Age of onset: The risk of ovarian cancer increases with age, particularly after the age of 50. The median age at diagnosis is 63 years old.
Genetic testing: Genetic testing can help identify individuals with inherited mutations that increase the risk of ovarian cancer. This can lead to early detection and prevention strategies.
Cascade testing: Cascade testing involves testing relatives of individuals with known genetic mutations to identify others who may be at risk.
Risk reduction: Women with a strong family history of ovarian cancer and/or a proven genetic link may consider from risk-reducing strategies such as: prophylactic oophorectomy; prophylactic salpingectomy (removal of the fallopian tubes), salpingo-oophorectomy (tubes and ovaries), and/or hysterectomy with bilateral salpingo-oophorectomy (uterus, cervix, tubes and ovaries) and/or chemoprevention.
A family history of breast cancer significantly increases the risk of ovarian cancer. Here are the key points:
First-degree relatives: Having a first-degree relative (mother, sister, or daughter) with breast cancer increases the risk of ovarian cancer. The risk is higher if the relative was diagnosed at a younger age or if there are multiple relatives with breast cancer.
Second-degree relatives: Having a second-degree relative (grandmother, aunt, or niece) with breast cancer also increases the risk of ovarian cancer, although to a lesser extent.
Multiple relatives: If multiple relatives on either side of the family have breast cancer, the risk of ovarian cancer increases significantly.
BRCA1 and BRCA2 mutations: Inherited mutations in the BRCA1 and BRCA2 genes, which are associated with breast cancer, also increase the risk of ovarian cancer. These mutations are more common in families with a history of both breast and ovarian cancer.
Age of onset: The risk of ovarian cancer increases with age, particularly after the age of 50. The median age at diagnosis is 63 years old.
Genetic testing: Genetic testing can help identify individuals with inherited mutations that increase the risk of ovarian cancer. This can lead to early detection and prevention strategies.
Risk reduction: Women with a strong family history of breast cancer may benefit from risk reducing strategies such as prophylactic oophorectomy or chemoprevention.
Overall, a family history of breast cancer is a significant risk factor for ovarian cancer, and genetic counseling and testing can help identify individuals at high risk.
In families with breast cancer, several specific genetic markers are linked to an increased risk of ovarian cancer. These include:
BRCA1 and BRCA2: These genes are the most well known genetic markers associated with both breast and ovarian cancer. Mutations in these genes significantly increase the risk of developing both cancers.
PALB2: Mutations in the PALB2 gene are known to increase the risk of breast, pancreatic, and likely ovarian cancer. PALB2 mutations are found in 14% of families negative for BRCA mutations.
CHEK2: CHEK2 mutations have sometimes been associated with an increased risk of breast and ovarian cancer. However, this association is not thought to increase risk relative to the general populations which is around 1.5%.
BRIP1: BRIP1 mutations are linked to an increased risk of ovarian cancer. These mutations are found in 0.9% of patients with ovarian cancer.
RAD51C and RAD51D: Mutations in these genes are associated with an increased risk of ovarian cancer. RAD51C mutations are found in 0.8% of patients with ovarian cancer, and RAD51D mutations confer a sixfold increased risk of ovarian cancer.
ATM: ATM mutations are linked to an increased risk of breast and ovarian cancer. These mutations are found in 0.7% of patients with breast cancer and 0.6% of patients with ovarian cancer. Risk reduction is not recommended in NCCN guidelines as of this writing.
NBN: NBN mutations are associated with an increased risk of breast and ovarian cancer. These mutations are found in 0.4% of patients with breast cancer.
Lynch Syndrome Genes (MLH1, MSH2, MSH6, PMS2, and EPCAM): Mutations in these genes are associated with Lynch syndrome, which increases the risk of ovarian cancer, particularly in women with a family history of colon cancer. Risk reduction measures are recommended by the NCCN for women in this category.
These genetic markers are important to consider in families with a history of breast cancer, as they can significantly increase the risk of ovarian cancer. Genetic testing and counseling can help identify individuals at high risk and guide preventive measures and treatment strategies.
In families with breast cancer, several non-BRCA genetic variants are associated with an increased risk of ovarian cancer. These include:
PALB2: Mutations in the PALB2 gene are known to increase the risk of breast and ovarian cancer. PALB2 mutations are found in 14% of families negative for BRCA mutations.
CHEK2: CHEK2 mutations are associated with an increased risk of breast and ovarian cancer. These mutations are found in 6% of patients with breast cancer and 4% of patients with ovarian cancer.
BRIP1: BRIP1 mutations are linked to an increased risk of ovarian cancer. These mutations are found in 0.9% of patients with ovarian cancer.
RAD51C and RAD51D: Mutations in these genes are associated with an increased risk of ovarian cancer. RAD51C mutations are found in 0.8% of patients with ovarian cancer, and RAD51D mutations confer a sixfold increased risk of ovarian cancer.
ATM: ATM mutations are linked to an increased risk of breast and ovarian cancer. These mutations are found in 0.7% of patients with breast cancer.
NBN: NBN mutations are associated with an increased risk of breast and ovarian cancer. These mutations are found in 0.4% of patients with breast cancer.
These genetic markers are important to consider in families with a history of breast cancer, as they can significantly increase the risk of ovarian cancer. Genetic testing and counseling can help identify individuals at high risk and guide preventive measures and treatment strategies.
The highest incidence of ovarian cancer is observed in non-Hispanic White women, followed by Hispanic women, and then by non-Hispanic Black and Asian/Pacific Islander women.
Ashkenazi Jewish women are at a higher risk of developing ovarian cancer due to their increased likelihood of carrying BRCA1 and BRCA2 gene mutations. These mutations significantly increase the risk of both breast and ovarian cancer. Studies have found that:
1 in 40 Ashkenazi Jewish women carries a BRCA1 or BRCA2 gene mutation, which is a much higher prevalence than in the general population.
29 to 41% of ovarian cancer in Ashkenazi Jewish women is attributed to inherited mutations in BRCA1 and BRCA2 genes.
66% risk of ovarian cancer by age 70 for BRCA1 mutation carriers and 27% for BRCA2 mutation carriers.
Higher risk of breast cancer is also associated with these mutations, with a lifetime risk of breast cancer between 50% and 80% for women with BRCA1 or BRCA2 mutations.
These genetic factors contribute to the higher incidence of ovarian cancer in Ashkenazi Jewish women.
One of the reasons that ovarian cancer is difficult to detect and treat is due to lack of adequate screening. This means that most ovarian cancers are caught too late, after the disease has progressed.
Following are some of the latest advancements towards eventually having effective ovarian cancer screening. We have work to do, but each step takes us closer to an answer.
Methylated DNA Markers: Researchers have discovered that methylated DNA markers can be used to identify endometrial cancer through vaginal fluid collected with a tampon. This technology may eventually be extended to ovarian cancer screening.
Protein Biomarkers: Scientists have identified proteins such as FRα, Claudin3, and TACSTD2 that can be isolated from small extracellular vesicles released by cancer cells. These proteins can serve as biomarkers for early-stage ovarian cancer detection.
Pan-Cancer Screening: The FDA has approved the FoundationOne Liquid CDx (F1LCDx) pan-cancer screening assay, which includes testing for ovarian cancer. This NGS-based test detects specific DNA mutations, copy number alterations, gene rearrangements, micro-satellite instabilities, and tumor mutational burden.
Emerging Diagnostic Approaches: New imaging based approaches, such as Doppler techniques and micro-bubble enhancement, are being developed to improve the accuracy of transvaginal ultrasound (TVU) in detecting ovarian cancer.
Genetic Testing: Genetic testing is becoming more comprehensive, with the ability to identify mutations in nonBRCA genes that can cause ovarian cancer. This allows for early detection and prevention strategies for individuals at high genetic risk.
Risk Prediction Models: Models like the BOADICEA algorithm are being refined to accurately identify at risk populations and guide them toward risk-reducing options such as RRSO or monitoring of biomarkers associated with HGSC development.
These advancements hold promise for improving early detection and treatment outcomes for ovarian cancer patients.
There is currently no recommended screening for ovarian cancer for those at average risk (those without personal or family history of ovarian or breast cancer).
For those who are at high risk, there are strategies that have been tested as possible screening tests for ovarian cancer including:
CA125 Blood Test: This test measures the level of CA125, a protein that is often elevated in the blood of women with ovarian cancer. However, it is not a perfect test and can be elevated in other conditions, such as endometriosis and fibroids.
Transvaginal Ultrasound (TVS): This imaging test uses sound waves to create images of the ovaries and can help detect abnormalities. It is often used in combination with the CA125 blood test.
MultiModal Screening: This approach involves using a combination of tests, including the CA125 blood test and TVS, to detect ovarian cancer. It has been shown to improve the detection of earlystage disease.
Methylated DNA Markers: Researchers have identified specific DNA markers that are methylated in ovarian cancer cells. These markers can be detected in blood samples and may provide an early indication of ovarian cancer.
Pan-Cancer Screening Strategies: Some studies are exploring the use of DNAbased pan-cancer screening strategies that can detect multiple types of cancer, including ovarian cancer, from a single blood sample.
Fallopian Tube Imaging: Researchers are investigating the use of imaging techniques, such as falloposcopy, to visualize the fallopian tubes and detect early-stage ovarian cancer.
Blood Tests for Specific Biomarkers: Several studies are focused on developing blood tests that can detect specific biomarkers associated with ovarian cancer, such as HE4, CA74, and osteopontin.
Genetic Testing: Genetic testing can identify women who are at high risk of developing ovarian cancer due to inherited mutations in genes such as BRCA1 and BRCA These women may benefit from early and frequent screening.
IMPORTANT: At the present moment, none of these strategies have been successful in preventing cancer and risk-reducing surgery is the only strategy proven to increase survival in a high risk population.