Learning Objectives:
- Learn the prevalence, prognosis, and types of ovarian cancer.
- Learn about the genes involved in ovarian cancer.
- Learn who is at risk for having ovarian cancer.
- Learn the options for patients with a strong family history of breast or ovarian cancer.
- Discuss what screening tests could be offered for high-risk patients.
Pretest Questions:
1. All of the following are risk factors for the development of ovarian cancer except:
a.) A personal history of breast cancer.
b.) Nulliparity.
c.) Oral contraceptive pill long-term use.
d.) Delayed childbearing.
e.) Late onset of menopause.
2. Which tumor maker correlates with progression and regression epithelial ovarian tumors?
a.) CEA
b.) CA-125
c.) PSA
d.) AFP (alpha-fetoprotein)
e.) HCG
3. Of the gynecological cancer, which has the highest mortality worldwide.
a.) Epithelial ovarian
b.) Endocervical
c.) Endometrial
d.) Fallopian tube cancer
1.C, 2. B, 3. B.
Case Study:
Ms. V was referred for genetic counseling because of a positive family history of ovarian cancer. For this reason, she is considering prophylactic oophorectomy (surgical removal of the ovaries). She is 36 years old with one healthy daughter, age 2. Her family is of Ashkenazi (Eastern European) Jewish descent. She has one sister, age 32, and one brother, age 30, both in good health. Her mother died at age 50 from ovarian cancer that was diagnosed at age 46. Ms. V has no uncles and only one aunt, her mother's sister, who underwent a total hysterectomy and oophorectomy at age 37 for unknown reasons. This aunt is alive and well at age 60. Ms. V's maternal grandmother died from ovarian cancer in her early 50s.
Questions:
- Explain the epidemiology and prevalence of Ovarian Cancer?
- What are the risk factors for ovarian cancer?
- What are the types of ovarian cancer?
- What is the typical presentation of ovarian cancer?
- What is the treatment and prognosis for ovarian cancer?
- Is ovarian cancer genetic? If so what genes are involved with inherited forms of ovarian cancer?
- What tumor markers are used for evaluation of the presence of ovarian cancer?
- What genetic counseling could you offer Ms.V?
- Draw a pedigree of Ms. V’s family.
1. Explain the epidemiology and prevalence of Ovarian Cancer?
Ovarian cancer is the 5th leading cause of cancer deaths and #1 most common gyn cancer in the US.
Ovarian cancer accounts for about 4% of cancer diagnoses among women.
Approximately 27,000 new cases are diagnosed every year.
Epithelial is the most common type, accounting for about 90%.
Most diagnoses are in post-menopausal women, about 50% after age 65.
Lifetime risk is 1-2%.
Early stages are often asymptomatic and early detection is difficult, hence more than 50% of patients die of their disease.
2. Risk Factors
Influenced by both hormonal and environmental factors; these appear to be correlated with the number of ovulatory cycles.
Increased risk associated with:
- positive family history of ovarian cancer
- positive family history of breast cancer
- infertility
- use of infertility drugs
Decreased risk associated with:
- Pregnancy
- lactation
- long term oral contraceptive use without getting pregnant
- tubal ligation
3. What are the histological types of ovarian cancer and which is most common?
Many histological types of ovarian tumors are described. However, more than 90% of malignant tumors are epithelial tumors. Of the epithelial tumors, serous tumors are the most common. Other epithelial tumors include mucinous, endometroid, clear cell carcinoma, and Brenner tumors, undifferentiated and mixed.
Germ cell & sex cord less common.
Ovarian sarcomas are rare but aggressive tumors.
4. What is the typical presentation of ovarian cancer?
Early disease causes minimal, nonspecific, or no symptoms. Therefore, most patients are diagnosed in an advanced stage. The more common early symptoms include lower abdominal discomfort or pressure, gas, bloating, constipation, irregular menstrual cycles/abnormal vaginal bleeding, low back pain, fatigue, nausea, indigestion, urinary frequency, or dyspareunia. Advanced disease is typically associated with abdominal distention, nausea, anorexia, or early satiety due to the presence of ascites and omental or bowel metastases.
5. What is the treatment and prognosis for ovarian cancer?
Overall, prognosis for these patients remains poor. Standard treatment involves aggressive debulking surgery followed by chemotherapy.
6. Is ovarian cancer genetic? If so what genes are involved with inherited forms of ovarian cancer?
Most ovarian cancer cases are sporadic. Approximately 5-10% of cases are thought to be inherited. Ovarian cancer is a feature of several familial cancer syndromes:
- familial site-specific ovarian cancer (BRCA2)
- familial breast and ovarian cancer
- hereditary non-polyposis colorectal cancer
In general, a woman who has a first degree relative (mother or sister) diagnosed with ovarian cancer has a 3-4 fold increased risk to develop the condition herself. If she has multiple affected family members, her risk may be as high as 50%. In Ashkenazi Jewish women with an affected first degree relative, the risk may be as high as 10%, and the chance that a detectable mutation will be found in these families is 10-30%.
The most common cause of heritable breast and ovarian cancer is a mutation in either the BRCA1 or BRCA2 gene.
- ~ 1 in 500 to 1 in 800 people in the general population have a mutation in BRCA1.
- Ashkenazi Jews have a 1 in 100 or greater prevalence of a BRCA1 mutation.
- BRCA1 and BRCA2 mutations are inherited in an autosomal dominant fashion.
BRCA1 is located on the long arm, or q arm, of chromosome 17. BRCA2 is located on the long arm, or q arm, of chromosome 13. The BRCA1 and 2 genes are expressed in many tissues, including the testis, breast, and ovary. The normal gene products are essential to cellular functioning. They are thought to protect the cells from genetic damage, acting as a tumor suppressor gene. Mutations in these genes typically results in a truncated form of the protein which interfere with the DNA repair function of the normal gene, thus resulting in the accumulation of chromosomal abnormalities and a propensity to develop malignancy.
7. What tumor markers are used for evaluation of the presence of ovarian cancer?
Measurement of the serum glycoprotein CA 125 concentration is done in patients with a high suspicion for ovarian cancer. The level of CA 125 is elevated in 80% of women with epithelial ovarian cancer. The incidence of an elevated serum CA 125 is highest in women with serous histology (the most common type of EOC, and lowest in those with mucinous tumors. It is not a recommended screening tool for premenopausal low suspicion patients.
Germ cell tumor markers include AFP, hCG and LDH.
8. What genetic counseling could you offer Ms.V?
Ms. V's family appears to have a dominant inheritance pattern of ovarian cancer. Ms. V's risk to develop ovarian cancer is related to the chance that there is a mutation segregating in her family.
This family fits most closely into the classification of a site-specific ovarian cancer, and therefore BRCA1 and BRCA2 testing were discussed with Ms. V. According to the BRCAPRO risk assessment model, her risk to carry a mutation is approximately 47%. While the risks, benefits, and limitations of genetic testing for BRCA1 and BRCA2 mutations are similar for both breast and ovarian cancer, there are some distinct issues in Ms. V’s case:
In Ashkenazi Jewish individuals, there are three frequent mutations (two in BRCA1 and one in BRCA2) associated with hereditary breast and ovarian cancer. These are thought to occur in about 2% of the Ashkenazi Jewish population. While, in general, it is preferable to start gene testing in an affected individual, in Ashkenazi Jewish families it may be appropriate to test someone who does not have cancer because of the increased mutation frequency. If Ms. V is screened and no mutation found, her risk for a mutation could be reduced by 90%.
Ms. V is already weighing the possibility of prophylactic oophorectomy against her desire for additional children. Gene testing may provide additional information about her genetic risks to develop ovarian cancer. In her particular case, a mutation-positive result would be the most informative: if a mutation is found, Ms. V may want not want to delay having another child, or she may even feel that she would rather have the surgery and forgo having additional children. A mutation-negative result will reduce the risk for a known mutation, but will not eliminate the chance that there is an inherited form of ovarian cancer in her family.
9. What are the options for women at increased risk for ovarian cancer?
Options for women at risk for ovarian cancer include increased surveillance, which raises controversial issues. Currently available screening methods include clinical examination, transvaginal ultrasound with or without color Doppler, and tumor marker studies. None of these is completely reliable, with both false positive and false negative results occurring. Other options include long-term use of oral contraceptives and prophylactic oophrectomy, which substantially reduces the risk to develop ovarian cancer. However, a small percentage of women have developed papillary serous carcinoma of the ovarian lining even after prophylactic oophrectomy.
10. Draw a pedigree of Ms. V’s family.
Ovarian Cancer Support Groups:
Ovarian Cancer National Alliance
The Ovarian Cancer National Alliance is a national, consumer-led advocacy and educational organization working to increase public and professional...
www.ovariancancer.org/
Gilda Radner Familial Ovarian Cancer Registry - Home
An international registry of families with two or more relatives with ovarian cancer.
www.ovariancancer.com/
Ovarian Cancer Research Fund
Charitable organization aimed at research and awareness. Includes educational materials, a hotline and fundraising products.
www.ocrf.org/
Educational Resource:
National Cancer Institute: http://www.cancer.gov/cancertopics/types/ovarian
Genetic Solutions http://www.geneticsolutions.com
Online Mendelian Inheritance in Man (OMIM): http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
GenTests – National Institute of Health: http://www.genetests.org/
References:
Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., Copyright © 2005 Elsevier. Retrieved from MD Consult on June 2, 2005. Website www.mdconsult.com
Chen, L. and Berek, JS. (2005).Clinical manifestations, diagnosis and staging of ovarian cancer. Retrieved from Up to date online on June 2, 2005. Website: www.utdol.com.
Fletcher, SW. (2005). Overview of genetics in breast and ovarian cancer. Retrieved from Up to date online on June 2, 2005. Website: www.utdol.com.
Isaacs, C. and Fletcher, SW. (2005). Options for women with a genetic predisposition to breast and ovarian cancer. Retrieved from Up to date online on June 2, 2005. Website: www.utdol.com. |
