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ESSAY 156 - OVARIAN CANCER

Posted by jyoti D.
the incidence of ovarian cancer is 1in 70 and 5-10% of those are due to hereditary cancer syndromes.
in this particular case the women\'s risk of ovarian cancer is increased as 2 first degree relatives have ovarian cancer.history of other cancers like breast,colon ,endometrial and age when both had ovarian cancer is important.
for the risk assesment the women should be refered to the clinical genetist and a family pedigree is drawn and advice on BRCA1 BRCA2 mutant gene testing after through pretest councelling as it can arise ethical issues because other menmbers of family might not want to know the results also have social,financial and insurance implications.Reassure her that even though her risk of ovarian cancer increases she may be disease free because of variable penetrance of the gene and other risk factors include use of ovulation induction drugs ,nulliparity.
the advice on risk reduction depends upon patients desire for fertility,contraception and choice.screening in form of transvaginal ultrasound for size of ovary and volume and ca125 hasnt shown to be effective as disease doesnt have premalignant state.though screen for mammography and self breast examnition is promoted if mutant gene positive.because brca1 is associated with 90%of ovarian cancer and50%of breast cancer.brca2 with 10% of breast cancer.
if willing for contraception combined oral pills can be considered after ruling out other contraindications for its use like smoking,migrain,thromboembolism.40% reduction in ovarian cancer,encourage for breast feeding,if family is completed advice
on tubal ligation reduces relative risk.bilateral oophorectomy to those who completed the family and can be performed laparoscopically depending upon expertise so quick recovery and cosmotically better but associated with risk of ureter,bladder and bowel injury,if comorbidity can consider hysterectomy.
councel about long term hrt ,raloxifen breast friendly but doesnt control vasomotor symtoms.life style changes and bisphosphonates for bone protection.the condition wil have lot of social and psychological impact so patient should be provied with leaflets and support group information.
counselling should be after through joint consultation with multidisciplinary team involving genetist.,gynaecologist,and psychologist.
Posted by jyoti D.
1% risk of peritoneal cancer should be explained .even after bilateral oophorectomy
Posted by uma M.
Ovarian cancer is commonest cause of mortality from gynaecological cancers with a life time risk of 1 in 100
in general population. This risk is high in certain group of women wth high risk genetic predispositions like in BRCA1&2 MUTATIONS.
THIS 35 YR WOMAN is at increased risk of ca.ovary ,from history and needs evaluatioin.
Multi disciplinary team involving cancer geneticist, gynaecologist, counsellor ,clinical psychologist ,GP should be involved in her care.
Her risk of developing cancer depends on her genetic predisposition .she should be reffered to regional genetic centre for risk assessment. For risk assessment Note family history, a family tree till 3rd degree relative is built,taking into account age of affected relatives, type of cancer, age of unaffected relatives any h/o of male cancers-- prostate,pancreas, colon outcome of treatment. Any cancer history should be verified as far as possible from case records, death certificates with permission from living relatives or patient.
Note personal history of ca.breast, obstetric history if any ,her desire for future pregnancies,any use of ovulation induction drugs, contraception usage.
When high risk genetic susceptibility is suspected she should be offered testing for genetic predisposition genes,
after pretest councelling that testing is assosiated with increased anxiety in tested positive woman,falsely reassuring if tested negative,impact on fertility,risk of tansmission to her children.It also has social & financial implications ,with reference to insurance.But mutation testing provides information wether or not individual is at increased risk so that screening&risk reduction
stategies are considered.
If she is tested positive for BRCA1/2 explian her the test result, give her life time risk of she developing ca.ovary & breast (With BRCA1 50% ca .ovary,80% ca breast, BRCA2-45% for ca breast,10% for ca.ovary).
Although risk is high she might be cancer free due to variable penetrance, which can\'t be predicted.
If woman is tested negative , she can be reassured ,but explain her that yet unidentified genetic mutation may still be present which increase her risk.
Councelling regarding risk reduction involves explation regarding screenig and prevention.
There is no effective screenig programme for ca.ovary.Screening with CA-125 ,TVS can provide some degree of reassurance and may identify early stage disease if done every 6-12 m, but it should be explained that efficacy is unproven and also natural h/o ca ovary not known.Encourage her to participate in UKFOCSS .
Risk reducing stategies include -having children with ~60% reduction and breastfeeding ~20% reduction are associated with reduced risk
Use of COCP for 5 yrs is associated with 40% reduction in risk of ovarian cancer but 24% increase in risk of breast cancer. There is no effective screening test for ovarian cancer and the
prognosis is poor (~25% 5 year survival) whereas breast cancer can be screened for and carries a better prognosis.
but not any contraindications for use like Thromboplilia before advising.
If woman has completed her child bearing advise her about prophylactic ooporectomy(( bilateral). This reduces the risk of ca ovary by 98% . 1%Risk of peritoneal carcinoma persists.This procedure also confers protection against ca. breast.But this is assosiated with loss of ovarian activity with menopausal symptoms,risk of osteoporosis and so may need long term HRT for her menopausal symptoms which increases risk of ca breast, VTE, cardiovascular disease.Discuss about nonhormonal alternatives like tibolone,raloxifene available. This also carries procedure related risk -as it is a surical procedure .It can be performed via laparotomy/laparoscopy.As cancer develops at earlier age than general population mean, ooporectomy needs to be done early,recommended after age of 35 yrs or after child bearing has been completed.
Tubal ligation and hysterectomy are assosiated with significant reduction of risk in general population.
Explain her importance of self breast examination and refer her for mammography from 35 yrs.
There should be good comunication between specialists so that there are no contradictory statements made .Contradictory advice from breast surgeons / gynaecologists about the use of COCP for instance may cause significant distress .
She is also at increased risk of colon cancer and so refer her to appropriate specialist for advise.
She requires long term psychological councelling and should be arranged through clinical psychology services.
Give her adequate written information, and follow up appointments.
Give information about cancer support groups like ovacome which support this group of woman with increased predisposition.




Posted by Farzana N.
Epithelial ovarian cancer is the fifth commonest cause of cancer in women. The lifetime risk of ovarian cancer in women in the UK is estimated to be 1 in 80.Epidemiological studies have shown that the incidence of several different types of cancers is significantly increased in first-degree relatives of women with ovarian cancer. About 7% of ovarian cancers have inherited basis.
Since the mother and sister, two first degree relatives of this woman had ovarian cancer, she has a significantly higher risk of developing ovarian cancer than the sporadic population.
Counseling should be given to this patient in a most sympathetic way, in a calm atmosphere, considering the stress she must be going through. The risk due to familial predisposition is explained and she should be advised to undergo genetic testing.
Identification of 2 inherited gene mutations, namely BRCA1 and BRCA2 predisposes to both ovarian and breast cancer. Both genes are autosomal dominant with high penetrance and can be both maternally and paternally inherited.
If the patient is found to be positive for these genes, risk of ovarian cancer with BRCA1
mutations the cumulative risk for ovarian cancer is 29% by age 50 ,and 44% by age 70.With BRCA2 the risk is less than for BRCA1. The cumulative risk is 0.45 by age 50 and 27% by age 70.
Taking the following preventive measures can reduce the risk of developing ovarian cancer
Primary prevention depends on chemoprophylaxis or.oophorectemy.Chemoprophylaxis is a proven method of preventing ovarian cancer and appears to be useful in this 35yrs old woman, if she has not completed her family. The combined oral contraceptives, if used for more than 6yrs reduces the risk of ovarian cancer by 60%, without increasing the rate of breast cancer. This effect has been shown in BRCA1gene carriers also. This woman should be offered COCP until such time as prophylactic oophorectomy becomes more appropriate.
The patient should be reassured that PO is relatively simple procedure, with a low morbidity. It has been strongly recommended for women with a. proven history of hereditary ovarian cancers. The major problems associated with PO are timing in relation to menopause and use of HRT,esp in women with BRCA! And BRCA2 mutations, who are predisposed to development of breast cancer.HRT has been reported to give relativerisk of1.3 with >5yrs use. The long term risks of surgical menopause may outweigh the risks of leaving ovaries in situ for premenopausal women.
If the woman opts for PO, she still runs 2-4% risk of primary ovarian cancer. Peritoneal washings should be taken for cytology and peritoneal cavity should be inspected in detail for occult tumors.
Options for HRT after PO include standard E2/P regimen, tibolone or raloxifen.
Raloxifene appears to be more promising because of its beneficial effects on breast cancer.
The other option for prevention is screening for early ovarian cancer. Serum CA125 measurement and transvaginal scans every 6-12 month can be done, but the woman should be explained that these have not proved to be effective. Low specificity of USS in pre-menopausal women will result in a high false-positive rate and a large proportion of women will suffer unnecessary anxiety and morbidity from laparoscpies done to confirm or refute the diagnosis. Screening procedures are also not very effective because there is no known premalignant phase and ovarian cancer metastasizes early and widely by transcoelomic spread
. Thus the best option available for this woman would be using COCP until menopause is reached ,then she can go for PO..


Posted by Nitin P.
Ovarian cancer is the cause of highest mortality amongst all the gynaecological cancers. It is also the most difficult to diagnose especially in the early stages. Family history increases the lifetime risk of developing ovarian cancer from the baseline risk of 1 in 70.
The type of ovarian cancer in her mother and sister is important to determine as only epithelial ovarian cancer has a familial incidence, sometimes a genetic basis and also increases the risk of breast cancer. The oral pill and any ovulation inhibiting contraception may offer some degree of protection. On the other hand the use of fertility inducing agents increases the risk. It is important to explore the issue of future fertility as radical surgery may not be appropriate in case fertility is desired.
The examination should determine her general fitness to undergo surgery and anaesthesia in case needed or desired. The BMI should be checked in case Laparoscopy is planned.
The specific investigation to screen for ovarian cancer is CA125. However this has a low specificity being raised in pregnancy, pelvic inflammatory disease and endometriosis. Transvaginal ultrasound though better than transabdominal scan has a high sensitivity for ovarian cysts but does not perform well for the diagnosis of cancer. The use of Doppler does not improve the detection rate either. The MRI performs better than the pelvis, but again its use is mostly limited to determine metastasis rather than early disease. In case, a cyst is diagnosed on scan, the Risk of Malignancy Index may be used to triage women to the appropriate management options.
Genetic studies in the form of BRCA gene may be offered. However, a consultation with a specialist geneticist must be arranged prior to the study. The test will have implications not only for her but to her immediate family and children too. It would also have implications for issues such as insurance.
In case no abnormality is detected, she may be offered routine screening. Enrolling in the Ovarian Cancer Study and yearly investigations is advisable. However, she must understand that, she may develop cancer between the screens and may then be diagnosed at a later stage. Also the screen tests themselves have a false negative rate. Unfortunately no medical management is available, other than the oral pill. Again, age and risk of Breast cancer may preclude its use.
The only remaining option is surgical removal of the ovaries. This may be done Laparoscopically or by a Laparotomy. The advantages of Laparoscopy are early recovery and less pain. However, there is risk fo bowel and blood vessel injury. Oophorectomy however will not prevent the occurence of peritoneal cancer. It would also subject her to menopause. Though HRT will not increase her risk beyond what it already is, she may not wish to take it in the absence of reassuring data, thus subjecting her to the effects of menopause.
The counselling must be in a non-directive way, using terms that the woman best understands. She must be given appropriate leaflets and enough time for her decision. A follow up visit to answer any further doubts is also advisable.
Posted by Shakira B.
A) She is on high risk of developing ovarian cancer. It is likely that a mutation predisposing to cancer is being transmitted through this family in Autosomal dominant fashion.
A mutation in BRCA1 is likely. These carry overall breast and ovarian cancer risk of up to 40% by age of 70 years. The risk in BRCA2 carrier for ovarian cancer is 25%. Her chance of cancer ovary with 2 first degree relatives with it is about 50%. If one first degree relatives affected 1 in 40 is her chance.
Patient?s family should be offered genetic counseling and mutation testing of BRCA1 and BRCA2 . If affected family members are found to have a mutation, then others including patient can be offered predictive testing. But this has implications on financial and insurance policies. Also moral questions raised for all family members if a mutated gene is found in family.
Screening for ovarian cancer are insensitive, poorly predictive and inapplicable to general population, not cost effective also pelvic examination, is inexpensive, non specific and depends on clinician?s ability to identify an adenexal mass. Another factor is how frequently this examination should be done. There is no premalignant state in ovarian cancer.
Ultrasound of ovaries and or Doppler Scanning of ovarian vessels are of poor sensitivity and unpredictable even in high risk population.
Biochemical Screening are non-specific, they are raised in all epithelial tumors, infections and endometriosis. Gene markers to identify those at risk of ovarian cancer, these are BRCA1 and BRCA2. To use these, 2 relatives must be known to have died of ovarian cancer or 1 dead and 1 alive relative with ovarian cancer.
Risk Reduction :-
If screen negative: She has a background life time risk of 1 in 80 for ovarian cancer.
If screen positive : Then various strategies for screening/management are proposed.
Psychological counseling concerning carrier status is a part of multidisciplinary management.
OCP decreases risk of ovarian cancer by 50%. She can use them if she is not planning for a family.
There is no insufficient data on its efficacy, bilateral oophorectomy ( Laparoscopic if possible ) is provided as an option during counseling. prophylactic oopherectomy cannot prevent the development of primary peritoneal carcinoma (2-4% risk).
In depth counseling is important. The patient should be aware that there are uncertainties over going risk of malignancy and HRT in thee women.
Patient should be given written leaflet also.


Posted by hoozy K.
answer
Posted by hassan M.
This patient must be very anxious about her risks of getting cancer to her self and her other members of family ,her fertility plans and passing the disease to her offsprings. Since two close realtives died of ov.cancer she is at approx 40%risk of getting ov cancer and referral to geneticist for screening is justified.
.Befor referral a detail history has to be taken and patient counceled in detail regarding the possible out come of screening.Family pedgree chart should be plotted after obtaining history and cause of deaths of male members with h/0 colon ,prostate and pancreas ca and female members for cancer colon ,breast and ovaries of upto 3 generation with the help of death records.
She should be informed that in case of screening negative for BRCA1/2 she will still have background risk of 1.4% of ov ca and this will increase with any factor causing increasing in ovulatory cycles ie nulliparity,ovulation induction and other environmental factors as use of peineal talcs ,high cholestral,obesity and high calcium diets.
If she is sreened positive for BRCA1/2 still it doesn?t mean that she will get ov cancer as there is a possibility of alteration in gene penetration causing mutation and she might escape the disease.
Her risks can be reduced by aiming at the reduction of ovarian cycles which can be done by pregnancy.If she is planning a family she should advice to start it soon as it decreases risk by 60% otherwise she is prescribed COCP for family planning as it decreases the risk by 40%when used for 5 years.Ovulation induction in case of treatment of infertility increases her risk whereas breast feeding(20%)and Tubal ligation and hysterectomy decreases it.
In case she is screened positive patient should be registered for screening with TVS ,CA125 and mammograms yearly.Limitations of these screening tools are informed that CA 125 might be increased in benign conditions and TVS though sensitive may will need expertise and no gaurentee can be given as natural history of disease is not known but may be helpful in giving some reassurance.
Patint should be educated about monthly self examination of breasts following menstruation due to increased risk of Ca breast.
Once she has completed her family she should be offered prophylactic BSO and hysterectomty.During preop coucelling she should be told that even after BSO and TAH she might have 1% chance of ov cancer dut to microscopic peritoneal or omental implants which may result in cancer later.
TAH &BSO will cause premature surgical menopause and need of HRT has to be discussed in view of WHI studies >she should be counceeld in liaison with breast surgeon and geneticist as she might be confused and anxious about getting CA breast with HRT. Tiblone will be the HRT of choice in a hysterectomized patient .If she doesn?t wish to take HRT she should be adviced about healthy life style,stopping smoking,Phytoestrogens ,biposphanates Rawwolfia alkolides ,calcium and vitamin D.
.Psychological implications should not be overlooked as screening positive will initiate the feeling of constant fear ,anxiety and depression .Screeninf of other family members may raise finanacial and moral issues and increase in premium of health insurance.Long term psychological concealing will be required .
All her wishes and fears should be documented with a sympathetic but positive attitude and reassuring manner.
She should be given wellbeing of women leaflet from RCOG and contacts of support groups.

Posted by Mangala sundari R.
Ovarian carcinoma (ca) is the fourth most common cancers in women. This particular patient has two first degree relatives affected by the disease. She needs to be counselled by a multidspeciality team consisting of gynaecologist,geneticist, GP, psychologist and counselor.

The genticist will make the pedigree tree with all the affected family members,their age of onset of any cancers, nature or histopathology of the cancers, the treatment, and the outcome of it. This includes the hereditary cancer syndrome ,which has ovarian , endometrial, breast and colorectal cancers(.Lynch 2 syndrome/NHPCC).

In her counseling she will be detailed about nature of the inheritance of the cancers, the methods available ,, and her risks of developing the disease if she has the mutations of the genes, the screening methods, and the treatment.\\

90% of Ovarian cancers are sporadic and 10% are genetic.
Herditary ovarian and breast cancers are due to the mutations of BRCA1 and BRCA 2 genes. and they are autosomal dominant.
If she is positive for mutation of BRCA 1 gene she has 40 to 60 % life time risk of developing Ca ovary and 20 ?30 % risk of developing Ca breast. If she is positive for BRCA 2 gene mutation she has 10 % life time risk of ca ovary and 40 % risk of Ca breast.Those who have mutations of this gene have 50% life time risk of developing endometrial/colorectal/breast. Ovarian cancers

The advantages of knowing her risks will make her plan or not to plan her family, and what lies ahead of her and to look for signs or symptoms of early disease. If she is negative she can be reassured.
The disadvantages are anxiety and depression, and may be she may be cancer free due to variable penetrance .and unnecessarily she is being investigated, or may have some guilt feeling of passing on the gene to her offspring or for the insurance purpose.

So she needs to do screening for both these cancers. For Ca breast she should do self breast examination regularly, and go for yearly mammography from 35 years ( now), if not already started. Pregnancy, breast feeding also reduce the risk of developing ca breastfor ca Ovary, there is no definite premalignant stage, and no screening tests for the general population. But since she is a high risk for developing the ca, the screening should be individualized for her. The serum markers ca 125 ( epithelial ovarian ca 90% of the ovarian ca) and transvaginal ultrasonography(TVS) should be done yearly or once in 6 months. Prostacin which is a serine protease is still to introduced as a serum marker in Ovarian Ca.
She will be explained, that nulliparity , ovulation induction drugs like clomiphene and gonadotrophins will increase her risks and so to avoid if possible.

The following are the factors which will reducw the risks;
Primary chemoprophylaxis by COCP for 5 years or more will reduce the risk by 60% and effective for upto 10 years of stopping th pills.But the use or COCP may increse her chance of Breast ca by 24 %

Tubal ligation, pregnancy, breast feeding all significantly reduce the risks.Her wishes for fertility will be taken into account ,before advising on Prophylactic bilateral oopherectomy.This can be done laparoscopically or by laparotomy .Salphingo oopherectomy to be done to avoid tubal cancer and remnant oavarian syndrome.She can be given HRT ,tibolone or ralxifene which are breast friendly.

With the above explanation, she can a have fairly good knowledge about the ovarian /Breast cancers, screening, and decisions and reassurance if negative.