Olaparib shows improved survival in Phase 3 trial, FDA approval granted

"FDA Approves Olaparib for First-Line Maintenance of BRCA-Mutated, Advanced Ovarian Cancer

https://tinyurl.com/yayx3drb

On December 19, 2018, the U.S. Food and Drug Administration (FDA) approved the PARP inhibitor olaparib (Lynparza) for the maintenance treatment of adult patients with deleterious or suspected deleterious germ-line or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy.

The FDA also approved BRACA analysis CDx to be used by health-care professionals to identify patients with advanced ovarian cancer who have a germ-line BRCA mutation and are eligible for olaparib following response to platinum-based chemotherapy

Lynparza (olaparib), a poly ADP-ribose polymerase (PARP) inhibitor, co-developed by AstraZeneca and Merck (known as MSD outside the US and Canada), has succeeded in a phase 3 trial (SOLO-3) held in patients with relapsed BRCA-mutated (BRCAm) advanced ovarian cancer by meeting the primary endpoint.

https://tinyurl.com/y9fcbckz

SOLO-3 is the first Phase 3 trial for a PARP inhibitor to demonstrate a positive result versus chemotherapy in advanced ovarian cancer where effective options are needed".

(The third step in testing an experimental drug (or other treatment) in humans. Phase 3 trials are conducted to confirm and expand on safety and effectiveness results from Phase 1 and 2 trials, to compare the drug to standard therapies for the disease or condition being studied, and to evaluate the overall risks and benefits of the drug. This trial phase recruits a large group of people with the disease or condition, usually ranging from 1,000 to 3,000 participants. The Food and Drug Administration (FDA) reviews results from Phase 3 trials when considering a drug for approval.)

Does opportunistic salpingectomy save lives and money?

 

The cost-effectiveness of opportunistic salpingectomy versus standard tubal ligation at the time of cesarean delivery for ovarian cancer risk reduction

https://tinyurl.com/ybevpsa4

Opportunistic salpingectomy is a cost-effective strategy recommended for ovarian cancer risk reduction at the time of gynecologic surgery in women who have completed childbearing.

https://tinyurl.com/y79oseav

We aimed to evaluate the cost-effectiveness of opportunistic salpingectomy compared to standard tubal ligation (TL) during cesarean delivery.

In 10,000 women desiring sterilization with cesarean, opportunistic salpingectomy would result in 17 fewer ovarian cancer diagnoses, 13 fewer ovarian cancer deaths, and 25 fewer unintended pregnancies compared to TL.

In women undergoing cesarean with sterilization, opportunistic salpingectomy is likely cost-effective and may be cost saving in comparison to TL for ovarian cancer risk reduction.

Well, it’s Christmas!

 “Dietary fiber intake and reduced risk of ovarian cancer: a meta-analysis

https://nutritionj.biomedcentral.com/articles/10.1186/s12937-018-0407-1

To the best of our knowledge, this is the first meta-analysis to summarize evidence between total dietary fiber intake and different types or sources of dietary fiber intake and risk of ovarian cancer. The risk of ovarian cancer was reduced by 22% in the group of highest dietary fiber intake compared with the lowest”

http://www.eatingwell.com/recipes/17938/holidays-occasions/christmas/

'We bring gifts of gold, myrrh, and ovarian cancer treatment'

https://lra.le.ac.uk/handle/2381/39946

Extracts from Boswellia sp. (Frankincense), used for centuries as herbal medicine in Asia, have known anti-inflammatory properties and anti-cancer potential alone or in combination with other chemotherapies. This suggests that frankincense may be useful for overcoming drug resistance, and it could also lead to an improved survival rate for patients with late-stage ovarian cancer”.

“A Perspective on Ovarian Cancer Biomarkers: Past, Present and Yet-To-Come

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373023/

As one year closes and another begins, I find myself reflecting on ovarian cancer diagnostics. It is truly humbling how little we have accomplished in this field over the last half-century. So let us awake on a future Christmas morning with newfound clarity. Let us transform how we categorize ovarian cancer, how we identify ovarian cancer, how we treat ovarian cancer, and possibly how we screen for cancer in general. It did not take long for the Nuclear Age to change our worldview or for the Information Age to profoundly alter our daily lives; with any luck, it will not take long to revisit our approach to early diagnostics for ovarian cancer. If Ebenezer Scrooge can change his ways…”

Women of faith more often present with advanced ovarian cancer.

“Effect of Cultural Folk and Religious Beliefs and Practices on Delays in Diagnosis of Ovarian Cancer in African American Women

https://doi.org/10.1089/jwh.2018.7031

An individual's beliefs have the potential to affect cancer outcomes both positively and negatively. Religious practices and cultural/folk beliefs may be especially relevant for African Americans (AAs) with cancer. AAs are more likely than whites to have a religious affiliation and more likely to report praying, regardless of whether they identify with a specific religious affiliation.

We conducted analyses among AA women in a multicenter case control study of ovarian cancer. Because many cultural/folk beliefs are intertwined with religious beliefs, our analyses evaluated specific cultural/folk beliefs as well as measures of participation in religious practices. We examined whether these beliefs and practices were associated with delays in ovarian cancer diagnosis as indicated by a later stage at diagnosis or longer symptom duration before diagnosis.

This case only analysis comprised of 599 AA women with ovarian cancer from the African American Cancer Epidemiology Study. Participants completed an interviewer administered telephone survey that obtained risk factor information, including reproductive history, medical history, socio-demographic factors, and lifestyle characteristics. Stage at diagnosis was derived from pathology and medical records, and categorized as stage I–II versus III–IV.

Responses to questions on religiosity showed that a large majority of the women regularly participated in religious services and prayers. Religiosity showed a significant association with stage at diagnosis. There was a twofold increase in the odds of stage III–IV disease for women who reported attending religious services >1 × /week (OR = 1.98, 95% CI 1.11–3.53) and those who considered themselves very religious (OR = 2.35, 95% CI 1.07–5.18).

Our analyses showed that women who reported greater religiosity were more likely to have higher stage ovarian cancer, whereas there was no clear association with symptom duration before diagnosis. Endorsement of cultural/folk beliefs related to cancer or health showed little association with either stage at diagnosis or symptom duration”.

Chemotherapy issues

“Current Chemotherapy of Ovarian Cancer

https://tinyurl.com/yans2wcg

Optimal primary chemotherapy of advanced ovarian cancer has not substantially changed over the last few years, in spite of the extensive evaluation of new cytotoxic agents and diverse treatment strategies. The rapid development of drug resistance remains a major clinical challenge for the majority of patients

While the combination of carboplatin and paclitaxel remains a well-tolerated and effective standard treatment for newly diagnosed ovarian cancer, there is continued interest in the discovery of new targets, as well as new approaches for inhibiting old targets

When patients undergo complete surgical clearance and have a tumor that is limited to the ovary with the finding of clear cell histology, cure would be expected in the vast majority of cases. In contrast, early-stage serous tumors are often high-grade and have a greater risk of recurrence and are perhaps more likely to benefit from adjuvant chemotherapy.

The dominant pattern of chemotherapy resistance observed in ovarian cancer is related to platinum compounds (cisplatin and carboplatin). Currently, there are no compounds with the ability to specifically target platinum-resistant tumors in the clinical setting.

The integration of emerging biologic principles with the development of molecular-targeted reagents is starting to achieve meaningful results, especially with regard to inhibition of angiogenesis and interference with PARP-mediated DNA repair. This single-agent treatment strategy is well tolerated and effective in a proportion of women with BRCA1/2 mutations. However, inheritable germ-line mutations only account for perhaps 5% of all ovarian cancers”.

Medical Radiation and ovarian cancer.

“Nuclear Medicine Procedures in Women: Unappreciated Risks to Reproductive Organs?

https://doi.org/10.1148/radiol.2018172344

Radiation exposure in imaging include CT, PET, and an increasing number of newer diagnostic and therapeutic radio-pharmaceuticals, used primarily in cancer diagnosis, staging, and treatment are associated with a theoretical increase in the risk of secondary cancer, with younger patients at higher risk than the elderly.

Women are particularly vulnerable to medical imaging radiation exposure, although the nature and extent of this vulnerability vary over time and depend on what type of imaging was performed. Accumulating evidence suggests that hormonal changes associated with the menstrual cycle are an underappreciated but avoidable source of vulnerability and risk to female reproductive organs, specifically ovaries, endometrium, and breasts.

While it can be argued that the risks of diagnostic nuclear medicine procedures using relatively short-lived isotopes could be viewed as mostly hypothetical, this is definitely not the case for radio-pharmaceuticals in use and under development for targeted radionuclide therapy, which use high-energy nuclides with longer half-life and are specifically designed to inflict direct cell damage.

Clinical and research nuclear medicine procedure on young women should be performed in the least susceptible phase of the menstrual cycle to improve the safety and the diagnostic accuracy of nuclear medicine procedures in women. 

There is a need for new guidelines for radiotracer development and use, which are responsive to the greater risk to reproductive organs inherent in exposing reproductively competent women to administered radiopharmaceuticals”.

Simple cysts do not require follow-up

 

Evaluating an Asymptomatic Adnexal Cyst Found on Pelvic Ultrasonography

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2714297

“It is well recognized that simple adnexal cysts (thin-walled round or oval cysts with anechoic fluid and through transmission) are almost always benign, but there is hesitancy to ignore these common cysts and not recommend follow-up, particularly when cysts are large or when the patient is postmenopausal.

This study determines the risk for malignant ovarian cancer based on ultrasonographic characteristics of masses in the ovaries, including simple cysts. The researchers enrolled 72,093 women who underwent pelvic ultrasonography and identified 210 who were consequently diagnosed with ovarian cancer.

Normal ovaries were observed in most women. A simple cyst was the second most common ovarian finding among participants after a normal ovary. Nearly 25% of participants younger than 50 years had a simple cyst, as did 13% of women aged 50 years and older.

There was no significantly elevated risk for ovarian cancer among women with simple cysts both older and younger than 50 years compared with those with normal ovaries.

Simple cysts are frequently encountered incidental and normal findings on pelvic imaging, and additional evaluation of these findings is not warranted.”  

Lynch cancer syndrome is as common as BRCA1/2 yet is under-diagnosed

"Keys to identifying Lynch syndrome"

http://www.contemporaryobgyn.net/gynecologic-cancers/keys-identifying-lynch-syndrome

“Lynch syndrome is an autosomal-dominant hereditary cancer syndrome that has the same incidence in the general population as the BRCA1/2gene cancer syndrome: 1 in 400 people. Lynch syndrome is not rare, and yet it is under-diagnosed, only about 5% of Lynch syndrome carriers have been identified. The predominant risk associated is colon cancer.

Lynch syndrome is caused by a mutation in a DNA mismatch repair pathway.

Usually, our healthy genes can detect mistaken genes and repair them as they are growing and multiplying. However, with Lynch syndrome, the healthy cells cannot repair the errant cells, and the body continues to make more flawed cells, which will lead to a cancer.

A study from MD Anderson in 2005 reported that up to 71% of women identified as having Lynch syndrome will acquire endometrial cancer (20% risk by age 50) and 12% will acquire ovarian cancer. For these women, mean age at diagnosis of colorectal cancer was 40 and at diagnosis of endometrial or ovarian cancer was 44.

Obstet Gynecol. 2005;105:569-574

A woman who presents with abnormal uterine bleeding and has a family history of colorectal cancer could be at risk for having Lynch syndrome, particularly if the affected member is younger than age 50. Taking a careful cancer family history is the most effective way for a clinician to evaluate a patient for risk of having Lynch syndrome. Ordering a hereditary cancer screen that will test for multiple cancer syndromes at one time is now the standard of care.

Once a patient with Lynch syndrome has completed childbearing, it is appropriate to counsel her to consider a prophylactic hysterectomy and bilateral salpingo-oophorectomy”.

 Lynch syndrome. Because you deserve to know.

Ultrasound screening for ovarian cancer: high cost and low precision.

“Survival of Women With Type I and II Epithelial Ovarian Cancer Detected by Ultrasound Screening”

Obstetrics and Gynecology 132(5):1089-1090, November 2018

 “The University of Kentucky Ovarian Cancer Screening Trial was initiated in 1987 to determine the effect of annual trans vaginal ultrasonography on stage at detection and ovarian cancer mortality.  Since that time, free screening has been provided to more than 46,000 women (at high risk due to familial factors). 

Unscreened women with clinically detected epithelial ovarian cancer referred to the University of Kentucky-Markey Cancer Center for treatment from 1995 to 2017 served as the control group for this investigation.

Women who had a normal screen were scheduled to return in 12 months for a repeat screen. Women who had an abnormal screen underwent a repeat ultrasound examination in 4–6 weeks. Criteria for abnormality included an ovarian volume greater than 20cm³for premenopausal women and greater than 10 cm³ for postmenopausal women. 

A total of 699 women (1.5%) with persisting ovarian tumors on trans vaginal ultrasonography underwent surgery. Seventy-one women with invasive epithelial ovarian cancer were detected. (Precision 0.101)

Twenty-six women (37%) in the screening group had stage III ovarian cancer at the time of detection as compared with 70% of women in the unscreened group with stage III or IV.  The 10-year ovarian cancer mortality was reduced in women receiving screening by 31% and produced 416 life years gained at a cost of $40,851 per life year gained”. ($17M)

Do women suffer brain injury after ovarian surgery?

"every action has a reaction"

"Association of Bilateral Salpingo-Oophorectomy Before Menopause Onset With Medial Temporal Lobe Neurodegeneration"

jamaneurol.2018.3057

“Women who undergo bilateral salpingo-oophorectomy (BSO) before the onset of menopause have an accelerated accumulation of multimorbidity, with an increased risk of aging-associated neurological diseases, including dementia

Premenopausal oophorectomy–induced oestrogen deficiency is thought to be the primary cause of the increased risk of cognitive impairment or dementia in women with BSO before the onset of menopause.  Alzheimer Disease (AD) biomarker abnormalities have been observed more frequently in women undergoing menopause compared with premenopausal women, after controlling for age.

Neurology. 2007;69(11):1074-1083

In our study, 96% of the women with BSO were treated with estrogen (primarily oral conjugated equine estrogen), for a median of 10 years after BSO; however, this type and duration of hormonal treatment after BSO does not seem to be sufficient to prevent structural changes in the medial temporal lobe later in life.

In this study, women who underwent BSO before age 50 years and before reaching natural menopause had smaller amygdala volumes, thinner parahippocampal-entorhinal cortices, and lower entorhinal white matter fractional anisotropy values compared with control-participant women.

Abrupt hormonal changes because of BSO in premenopausal women may lead to medial temporal lobe structural abnormalities later in life. Because alterations in structural imaging biomarkers of neuro-degeneration in the medial temporal lobe precede clinical symptoms of dementia, enlargement and longitudinal follow-up of this cohort is needed ‘'.

Does the pill protect?

“Association between contemporary hormonal contraception and ovarian cancer… “

https://www.bmj.com/content/362/bmj.k3609

“Previous research has shown a reduced risk of ovarian cancer in users of combined oral contraceptives, an effect that persists for many years after stopping use.

Changes have occurred in formulations of combined oral contraceptives (notably reductions in oestrogen dose and the introduction of newer progestogens).

It is important for users of contemporary combined oral contraceptives to know whether they are likely to experience the same pattern of ovarian cancer benefit as users in the older studies.

The Danish Sex Hormone Register Study follows a national cohort of women aged 15-79 years. It was established to investigate the relation between hormone use and the risk of cancer or cardiovascular disease.

We calculated age standardised incidence rates of ovarian cancers per 100 000 person years, using the age distribution of the cohort as standard.

Conclusions

Based on results from our prospective study, contemporary combined hormonal contraceptives are still associated with a reduced risk of ovarian cancer in women of reproductive age, with patterns similar to those seen with older combined oral products”.

This is shocking!

World Ovarian Coalition

 

This information comes from: -

                 https://www.eurekalert.org/pub_releases/2018-10/wocc-doo101518.php

"The World Ovarian Cancer Coalition Every Woman Study is the largest ever review of the experiences of women with ovarian cancer and includes contributions from the clinical community. It presents a bleak picture of the challenges faced by women with ovarian cancer, and those who care for them.

Nine in ten of the women in the Every Woman Study experienced symptoms prior to diagnosis and of these, eight in ten consulted a doctor - though less than half within a month and one in ten waited six months.

Across the world, diagnosis took an estimated average of 31 weeks from a woman experiencing symptoms to her diagnosis; for one in ten women diagnosis came more than a year after visiting a doctor.

A survey participant in Australia said "Governments need to do more regarding GPs [family doctors] and their lack of diagnosis and interest in women with ovarian cancer. After diagnosis I Googled and all my symptoms were mentioned. GPs were not interested enough and made me feel like a hypochondriac. This went on for months!"

There are examples of best practice in prevention, diagnosis and treatment of ovarian cancer across the world, but no one country does well in all three areas. This means there are opportunities right now to transform survival in ovarian cancer, simply by learning from what others do well".

https://worldovariancancercoalition.org/wp-content/uploads/2018/10/THE-EVERY-WOMAN-STUDY-WOMENS-SURVEY-2018-FULL-RESULTS.pdf

Choose your mother carefully

“Familial risks of ovarian cancer….”

This information comes from:-

       https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205000

“Ovarian cancer risk increases with aging and peaks between the ages of 50 and 80 years. In the general Swedish population, the lifetime risk of ovarian cancer is 1%. 

Family history is a strong risk factor for ovarian cancer, and the relative risk is estimated to be 2.0 to 4.0 for those that have a first-degree relative affected by the disease

In this study, we use the recent national Swedish Family-Cancer Database, which included 16.1 million individuals, to estimate the familial risks of ovarian cancer by age at diagnosis, affected relative (mother or sisters) and histology.

In families of only mother, only sisters or both mother and sisters diagnosed with ovarian cancer, cancer risks for ovary were 2.40, 2.59 and 10.40, respectively; and were higher for cases diagnosed before the age of 50 years.

Histology in familial ovarian cancer is not specific, and if genes or polygenes contribute to familial clustering they may not define histology.”

Why does 75% of ovarian cancer start in the Fallopian tube?

This information comes from:-

https://today.uic.edu/crosstalk-between-fallopian-tube-ovary-may-drive-the-spread-of-ovarian-cancer-

-

https://www.cancer.gov/news-events/cancer-currents-blog/2017/ovarian-cancer-fallopian-tube-origins

"Over the last several years we have come to learn that ovarian cancer cells, specifically high-grade serous ovarian cancer cells, originate in the fallopian tube and migrate to the ovary where they become established as ovarian cancer. 

We don’t know yet what the fallopian tube signals to the ovary, but we know that it causes the ovary to release norepinephrine, which signals cancer cells to migrate.

-

There is a window of several years between the development of abnormal cells, or lesions, in the fallopian tubes and the start of ovarian cancer

Most of the genetic alterations seen in ovarian tumors in these patients were present in serous tubal intraepithelial carcinomas (STICs) that had formed years earlier in their fallopian tubes

Clinical trials could be done to determine whether removing the fallopian tubes, and not the ovaries, in women who are at high risk for cancer is sufficient to reduce their risk of the disease" 

All about PARP

"Poly (ADP-ribose) Polymerase Inhibitors(PARPi) in the Management of Ovarian Cancer" 

This information comes from

https://www.ptcommunity.com/journal/article/full/2018/9/549/poly-adp-ribose-polymerase-inhibitors-management-ovarian-cancer-drug

-

https://www.eurekalert.org/pub_releases/2018-09/waeh-dpw092618.php

"Familial and hereditary factors have been identified in the development of some cases of ovarian cancer, with approximately 10% to 15% of ovarian cancer cases associated with inherited mutations of the BRCA1 and BRCA2 genes.

Upon recurrence of disease, the goal of treatment is no longer curative, but instead becomes palliative, aimed at improving disease-related symptoms, prolonging survival, and trying to improve quality of life.

For patients harbouring a BRCA1/2 mutation, medications targeting PARP enzymes may be an effective therapeutic option. PARP is a family of enzymes that mediate DNA repair... PARP inhibition in the setting of BRCA1/2 mutations can cause tumour cells to lose 2 important DNA repair mechanisms leading to DNA damage and cell death.

-

PARPi is administered as maintenance therapy (with) some patients deriving durable benefit for more than 3 years

Australian scientists (using the Melbourne tissue bank) have revealed a better way  to identify which patients should respond to powerful ovarian cancer drugs called PARP inhibitors (PARPi), resolving an important question in ovarian cancer care about why some patients respond to these drugs, while others do not.

  

The study: -
                              https://www.nature.com/articles/s41467-018-05564-z

was led by Professor Clare Scott, Dr Olga Kondrashova, Dr Matthew Wakefield and Dr Monique Topp from the Walter and Eliza Hall Institute; in collaboration with Associate Professor Alexander Dobrovic from the Olivia Newton-John Cancer Research Institute and LaTrobe University School of Medicine".

(L-R) DR OLGA KONDRASHOVA AND PROFESSOR CLARE SCOTT

Is it talc or asbestos?

"FDA Funds Cosmetic Talc Study on Ovarian Cancer Risks"

This information comes from:-

https://www.drugjustice.com/news/talcum-powder/cosmetic-talc-study-ovarian-cancer/

"Cosmetic talc verdicts awarded billions to plaintiffs with ovarian cancer or mesothelioma over the past year. In all cases, the plaintiffs say regular talcum powder use (which contains cosmetic talc) led them to develop terminal cancer. However, some plaintiffs say asbestos (not cosmetic talc itself) may be the real culprit".

"Scientists published the first study linking talcum powder to ovarian cancer in 1971(J Obstet Gynaecol Br Commonw.). In the study, researchers dissected ovarian tumors and discovered talc particles embedded in 75% of them. Since then, dozens of different researchers validated that first study’s results. This includes a 2013 case-control study stating regular perineal talc use increased women’s ovarian cancer risk by 33%.(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3766843/)

But the FDA believes some study parameters may have flaws. As a result, they funded their own cosmetic talc study in 2017. The agency should publish the study’s results sometime in spring 2019".

Does fertility treatment increase the risk of cancer?

"Risks of ovarian, breast, and corpus uteri cancer in women treated with assisted reproductive technology in Great Britain, 1991-2010: data linkage study including 2.2 million person years of observation"

 This information is taken from:-

bmj.k2644

This is a massive study looking at the cancer risk in all women in the UK who underwent fertility treatment during the period 1991-2010. The incidence of breast, uterine and ovarian cancer in treated women was compared with the normal.

The conclusions were:-

"No increased risk of corpus uteri or invasive breast cancer was detected in women who had had assisted reproduction, but increased risks of in situ breast cancer and invasive and borderline ovarian tumours were found in this study. Our results suggest that ovarian tumour risks could be due to patient characteristics, rather than assisted reproduction itself, although both surveillance bias and the effect of treatment are also possibilities. Ongoing monitoring of this population is essential".

In addition it was noted that:-

"Increased risks of ovarian tumours were limited to women with endometriosis, low parity, or both".

Does risk reducing surgery increase survival and reduce the risk of ovarian cancer?

"Risk-reducing bilateral salpingo-oophorectomy 

in women with BRCA1 or BRCA2 mutations"

This information is taken from this source of reference:-

30141832

The decision whether to undertake major surgery has become a difficult choice for women who face the increased risk of  high grade serous ovarian (HGSC) and breast cancer due to genetic factors. The scientific basis remains unclear. This reference is a meta-analysis of the available literature. A meta-analysis is a review of all available information with statistical assessment to determine the significance. In this instance 10 studies were reviewed with about 3000 women who have the genetic mutations BRCA1 and/or BRCA2 (breast cancer 1 and 2 gene) and elected to have risk-reducing salpingo-oophorectomy (RRSO) and about 5000 women who also have BRCA1 or BRCA2 mutation who did not have the surgery.

The Author's conclusion included the following statement:-

"There is very low-certainty evidence that RRSO  may increase overall survival and lower HGSC  and breast cancer mortality for BRCA1 and BRCA2 carriers. Very low-certainty evidence suggests that RRSO reduces the risk of death from HGSC and breast cancer in women with BRCA1 mutations".

The conclusions are qualified as follows:-

"These results should be interpreted with caution due to questionable study designs, risk of bias profiles, and very low-certainty evidence".

Medicare-funded cancer genetic tests: a note of caution

This information is taken from 
https://www.mja.com.au/journal/2018/209/5/medicare-funded-cancer-genetic-tests-note-caution#tbox1

"these tests are now being mainstreamed and they can be ordered for selected patients, with a new Medicare benefit, by non-genetic specialists in either public or private practice".

 "Breast cancer genetic tests: key points"

"1.Genetic testing is not necessary for most women with breast cancer, but it should be considered in those with breast cancer at a younger age and those with a relevant family history

  2. From 1 November 2017, several new Medicare Benefits Schedule (MBS) item numbers cover the cost of breast and ovarian cancer-related genetic testing, when the defined criteria are met

  3. Eligibility for the MBS rebate is based on a quantitative algorithm indicating that the patient is at > 10% risk of having a pathogenic mutation identified

 4. The item numbers cover testing for heritable germ-line mutations in seven genes: the two major genes involved in breast and ovarian cancer predisposition (BRCA1 and BRCA2); the breast (but probably not ovarian) cancer predisposition gene PALB2; and four genes (STK11, PTEN, CDH1 and TP53) in which mutations are associated with breast cancer, but which often present with a non-breast cancer phenotype.

 5. Testing of these additional genes in the absence of the usual syndrome features should be approached with caution 

 6. Genetic testing is complex and the identification of variants of uncertain significance (VUS) in cancer genes is a major challenge. The more genes you test, the more VUS you will find

 7. The clinician who orders the test must be able to interpret the results and communicate the implications of the results, including the uncertainties, to the patient and their genetic relatives

8. Patients must be well informed and written consent is required before genetic testing"

A podcast with more information is available here

https://www.mja.com.au/podcast/209/5/mja-podcasts-2018-episode-75-genetic-testing-cancer-aprof-judy-kirk