OVARIAN CANCER

OR
Cancer of the Ovary
Malignant Neoplasm of the Ovary
Malignant Tumor of the Ovary
Ovarian Carcinoma

VAISHVI AGRAWAL 1
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 WHAT IS OVARIAN CANCER?

• In this form of cancer, certain cells in the ovary become

abnormal and multiply uncontrollably to form a tumor.
• The ovaries are the female reproductive organs in which egg
cells are produced. In about 90 percent of cases, ovarian
cancer occurs after age 40, and most cases occur after age 60.
• Most cases of ovarian cancer are not caused by inherited
genetic factors. 
• A predisposition to cancer caused by a Germline Mutation is
usually inherited in an Autosomal Dominant Pattern.

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 HISTORY.
• According to Hamilton, the concept that epithelial ovarian cancers
arise from ovarian surface epithelial (OSE) cells was proposed by
Sir Spencer Wells in 1872.  More than a century later, this
hypothesis remains controversial
•  The OSE cells are mesothelial‐like cells that share embryological
origin with the Müllerian tract epithelium, which eventually gives
rise to tubal, endometrial and endocervical epithelium.
• In 1999 Dubeau refuted the hypothesis that epithelial cancers arise
from the OSE cells, and suggested that these cancers arise from
secondary Müllerian tract structures. Dubeau’s argument was based
on the fact that these cells are indistinguishable from adjacent
mesothelial cells that line the peritoneum, yet epithelial ovarian
cancers do not resemble mesothelial tumours.
• Piek et al. proposed that the origin of many epithelial ovarian
cancers indeed arise from the fallopian tube, and may implant on
the peritoneum and the ovarian surface.  5
 TYPES OF OVARIAN CANCER.
There are more than 30 different types of
ovarian cancer, which are classified by the type
of cell from which they start. Cancerous ovarian
tumors start from three common cell types:
• Surface Epithelium - cells covering the outer
lining of the ovaries
• Germ Cells - cells that are destined to form eggs
• Stromal Cells - Cells that release hormones and
connect the different structures of the ovaries
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 PREVALENCE.
• Rate of New Cases and Deaths per 100,000: The rate of new cases of ovarian cancer
was 11.2 per 100,000 women per year. The death rate was 6.9 per 100,000 women per
year. These rates are age-adjusted and based on 2013–2017 cases and deaths.
• Ovarian cancer is diagnosed in about 22,000 women in the United States each
year. A woman's lifetime risk of developing ovarian cancer is about 1 in 75.
• Prevalence of This Cancer: In 2017, there were an estimated 233,364 women living
with ovarian cancer in the United States.
• Ovarian cancer constitutes 3rd most common cancer and contributes to about
6% of total cancer cases among the Indian women.
• It is estimated that in India by the year 2020, the incidence of Ovarian cancer
cases will be around 36200 and the prevalent cases will be around 100,000.
Early detection of cases and provision of early treatment of cases may go a long
way to reduce the prevalence of Ovarian cancer cases in India.

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 CLINICAL SYMPTOM.
The most common symptoms include:
•Bloating
•Pelvic or abdominal (belly) pain
•Trouble eating or feeling full quickly
•Urinary symptoms such as urgency (always feeling like you have to go) or frequency (having to
go often)
These symptoms are also commonly caused by benign (non-cancerous) diseases and by cancers of
other organs. If you have these symptoms more than 12 times a month, see your doctor
Others symptoms of ovarian cancer can include:
•Fatigue (extreme tiredness)
•Upset stomach
•Back pain
•Pain during sex
•Constipation
•Changes in a woman's period, such as heavier bleeding than normal or irregular bleeding
•Abdominal (belly) swelling with weight loss

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 GENETICS.
• Most cases of ovarian cancer are not caused by inherited genetic
factors. These cancers are associated with somatic mutations that are
acquired during a person's lifetime, and they do not cluster in families.
• A predisposition to cancer caused by a germline mutation is usually
inherited in an autosomal dominant pattern, which means one copy
of the altered gene in each cell is sufficient to increase a person's
chance of developing cancer. Although ovarian cancer occurs only in
women, the mutated gene can be inherited from either the mother or
the father. It is important to note that people inherit an increased
likelihood of developing cancer, not the disease itself. Not all people
who inherit mutations in these genes will ultimately develop cancer.
• In many cases of ovarian cancer that clusters in families, the genetic
basis for the disease and the mechanism of inheritance are unclear.

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 GENES.
• Mutations in the BRCA1 or BRCA2 genes account for the majority of
hereditary ovarian cancers. About 15 per cent of women who develop
ovarian cancer have a mutation in either their BRCA1 or BRCA2 gene.
•  A woman with a mutation in the MLH1, MSH2 or MSH6 gene has an
estimated 10 to 17 per cent chance of developing ovarian cancer at
some point during her lifetime. 
• Mutations in RAD51C and RAD51D and BRIP1 genes
• Mutations in the STK11 gene may also increase the risk of
developing ovarian sex cord-stromal tumours– a different type of
ovarian cancer. Mutations in this gene cause Peutz-Jeghers syndrome.
• Recently  FANCM are being identified, which may slightly increase
susceptibility to high grade serous ovarian cancer.

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OVARIAN CANCER, EPITHELIAL, INCLUDED
Phenotype-Gene Relationships.
Location Phenotype Phenotype Gene/Locus
Mapping
3p22.1 Ovarian cancer, 3 CTNNB1
somatic

3q26.32 Ovarian cancer, 3 PIK3CA

somatic

6q26 Ovarian cancer, 3 PRKN

somatic

11q25 Ovarian cancer, 3 OPCML

somatic

14q32.33 Ovarian cancer, 3 AKT1

somatic

16q22.1 Ovarian 3 CDH1

cancer,somatic

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 MUTATION.
•GENE/LOCUS-PIK3CA,
CLOVE, MCAP, MCM,
MCMTC, CWS5, CLAPO
•GENE/LOCUS NAME-
Phosphatidylinositol 3-kinase,
catalytic, alpha polypeptide.
•PHENOTYPE- Ovarian
cancer, somatic and man more.

Chr3(q26,32)
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Light
micrographs
of the section
of human
ovarian tissue

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• Ovarian cancers, including mismatch repair (MMR)
(MLH1,MSH2, MSH6, MLH3, and PMS2)genes, TP53, and several
genes involved in double-strand breaks repair. To date, at least 16
genes are known to be involved in the mechanism of hereditary
ovarian tumorigenesis, but several mutations still remain unknown and
cannot be detected by specific tests .
• Defects in genes involved in the repair of double stranded breaks, other
than BRCA 1 and 2, represent alternative mechanisms of hereditary
ovarian carcinogenesis. BRCA negative tumors with a defect in the
homologous recombination system express the BRCAness profile, a
specific phenotype with features and behavior similar to BRCA-related
cancers . It is likely that these patients also might benefit from platinum-
based therapies and/or PARP inhibition like BRCA mutation carriers do,
but, to date, we still need to introduce validated tests into daily practice
in order to identify patients with “BRCAness” profiles who carry
mutations in genes such as ATM, CHEK2, RAD51, BRIP1, andPALB2.

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 TREATMENT.
• Local treatments
Meaning they treat the tumor without affecting the rest of the body. Types
of local therapy used for ovarian cancer include:

– Surgery for Ovarian Cancer

– Radiation Therapy for Ovarian Cancer
• Systemic treatments
– Drugs used to treat are considered systemic therapies because they
can reach cancer cells almost anywhere in the body. They can be given
by mouth or put directly into the bloodstream.
– Depending on the type of ovarian cancer, different types of drug
treatment might be used, including:
1. Chemotherapy.
2. Hormone Therapy.
3. Targeted Therapy.
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• Common approaches
– Typically, treatment plans are based on the type of
ovarian cancer, its stage, and any special situations. Most
women with ovarian cancer will have some type of
surgery to remove the tumor. Depending on the type of
ovarian cancer and how advanced it is, you might need
other types of treatment as well, either before or after
surgery, or sometimes both.
– Treatment of Invasive Epithelial Ovarian Cancers, by
Stage
– Treatment for Epithelial Tumors of Low Malignant
Potential
– Treatment for Germ Cell Tumors of the Ovary
– Treatment for Stromal Tumors of the Ovary, by Stage
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NEW STRATERGIES FOR TREATMENT
Chemotherapy
• New chemotherapy (chemo) drugs and drug combinations are being tested.
• When the drugs cisplatin and carboplatin stop working, the cancer is said to
be platinum resistant. Studies are looking for many ways to make these cancers
sensitive to these drugs again. Different strategies include:
• Looking closely at what specific mechanisms and proteins are involved in the
making ovarian cancer cells resistant.
• Developing drugs that can keep the cancer cells from becoming resistant to the
chemo by blocking channels that pump chemotherapy out of the cancer cell.
• Trying to determine the details of certain cancer cells where the DNA is not
damaged by chemotherapy which allows it to keep growing.
• Although carboplatin is preferred over cisplatin in treating ovarian cancer if the
drug is to be given IV, cisplatin is used in intraperitoneal (IP) chemotherapy.
Studies are looking at giving carboplatin for IP chemo.
• Another approach is to give IP chemo during surgery using heated drugs. This,
known as heated intraperitoneal chemotherapy or HIPEC, can be effective. More
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studies are showing this to be beneficial and may improve how long a woman lives.
• Genetic therapies
– For ovarian and breast cancers that are caused by the
BRCA 1 mutation, it has been shown that low levels of
the BRCA 1 mutation are associated with good
responses to PARP inhibitors and platinum drugs, like
cisplatin and carboplatin. New research shows that
microRNA, very small pieces of RNA (substances that
carry genetic messages for DNA), can also lower levels
of BRCA1 mutations. New drugs that can target these
tiny pieces of RNA are being investigated as possible
ways to treat these cancers.

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Targeted therapy
• Targeted therapy is a newer type of cancer treatment that uses drugs or other
substances to identify and attack cancer cells while doing little damage to normal
cells. Each type of targeted therapy works differently, but they all attack the cancer
cells' inner workings − the programming that makes them different from normal,
healthy cells. Bevacizumab (Avastin) is the targeted therapy that has been studied
best in ovarian cancer, but other similar drugs, like pembrolizumab, are being looked
at, as well.
• Catumaxomab is a drug being studied specifically for people with malignant ascites
(fluid buildup in the abdomen [belly] caused by cancer cells). It works by targeting
3 different cell types including tumor cells and white blood cells called T-cells.
• Poly(ADP-ribose) polymerases (PARPs) are enzymes that have been recently
recognized as key regulators of cell survival and cell death. Drugs that inhibit
PARP-1 (called PARP inhibitors) have been approved for patients with ovarian
cancer caused by mutations in BRCA1 and BRCA2. New evidence shows that
ovarian cancers can also become resistant to treatment with PARP inhibitors.
Research is trying to find ways to counteract this process.

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Janet
Rowley
Kathy
Bates

Manisha
Koriala

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• 8TH May is celebrated as ‘WORLD
OVARIAN CANCER DAY’.

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 SOCIETIES
• National Ovarian Cancer Coalition
(NOCC),Dallas
•  Ovarian Cancer Research Fund Alliance
(OCRFA),New York.
• Swastava Cancer Care,India
• Grace Cancer Foundation,Gujrat,India
• DEAN Foundation, Hospice and Palliative
Care Centre,Chennai,India
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 REFERENCE
• https://www.researchgate.net/publication/33
2910038_Status_of_Ovarian_Cancer_in_India
_2012-14
• https://www.cancer.org/cancer/ovarian-cance
r/about/what-is-ovarian-cancer.html
• https://ghr.nlm.nih.gov/condition/ovarian-can
cer#inheritance
• https://www.targetovariancancer.org.uk/infor
mation-and-support/hereditary-ovarian-cance
r/which-genes-are-most-likely-have-mutation
• https://www.cancer.org/cancer/ovarian-cance 27
THANK YOU
IT’S TIME FOR OVARY-ACTION

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