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  • Ovarian cancer is a deadly disease that is challenging to diagnose and manage
  • Although it only accounts for 3% of cancers in women, it is the 5th leading cause of cancer death among women
  • If diagnosed and treated early before it spreads the 5-year survival rate is 92%
  • But only 15% of women with ovarian cancer are diagnosed early
  • The disease is hard to diagnose because it is rare, the symptoms are relatively benign, and there is no effective screening
  • Ovarian cancer is not one disease, but a collection of subtypes each demanding specific treatment pathways
  • Gold standard treatment is surgery followed by chemotherapy
  • A large proportion of patients develop resistance to chemotherapy
 
Improving ovarian cancer treatment

Part I
 
Are things beginning to improve for people living with ovarian cancer? When the British advertising magnate Lord Maurice Saatchi’s wife died of ovarian cancer in 2012 he described her treatment as, “degrading, medieval and ineffective” leading “only to death”. Ovarian cancer patients have long had limited treatment options, which have not changed much in the past two decades, but recently things have begun to change.

 
In this Commentary
 
This is the first of a 2-part Commentary on ovarian cancer, which briefly describes the condition, explains the difficulties of diagnosing it early, and discusses some of the challenges of developing effective screening mechanisms for the cancer in pre-symptomatic women. Part 2, which will follow separately next week, reports new studies, which hold out the prospect of improved treatment options for women living with ovarian cancer. It also suggests that improvements in ovarian cancer care are both organizational and scientific. Experts believe that they now have a number of treatment options available to them. Utilising and sequencing these appropriately can have a significant impact on the overall survival rates of patients. Multidisciplinary teams, which are not universally available to all ovarian cancer patients, bring together all specialisms involved in the therapeutic pathway to consider and suggest optimal treatment steps for individual patients, and make a significant contribution to improved ovarian cancer care. Both Commentaries draw on some of the world’s most eminent ovarian cancer clinicians and scientists.
 
Ovarian cancer: a complex and deadly disease
 
The ovaries are a pair of small organs located low in the stomach that are connected to the womb and store a woman’s supply of eggs. Ovarian cancer is driven by multicellular pathways, and is better understood as a collection of subtypes with changing origins and clinical behaviors, rather than as a single disease. The tumors often have heterogeneous cell populations, which form unique microcellular environments. The prevalence of ovarian cancer among gynecological malignancies is rising, and is one the most deadly and hard to treat malignancies. While the disease only accounts for about 3% of cancers in women, it is one of the most common types of cancer in women, the 5th leading cause of cancer-related death among women, and the deadliest of gynecologic cancers. The risk of ovarian cancer increases with age. It is rare in women younger than 40, most ovarian cancers develop after menopause. 50% of all ovarian cancers are found in women 63 or older. According to the American Cancer Society the five-year survival rate for all ovarian cancers is 45%. Most women are diagnosed with late-stage ovarian disease and, the 5-year survival rates for these patients are roughly 30%. Age adjusted survival rates of ovarian cancer are improving in most developed countries. For instance, between 1970 and 2010, the 10-year survival rates for ovarian cancer in England increased by 16%, and the 5-year survival rates have almost doubled. This is because of the favorable trends in the use of oral contraceptives, which were introduced early in developed countries. Declines in menopausal hormone use may also have had a favorable effect in older women as well as improved diagnosis, management and therapies. According to Public Health England, over the past 20 years the incidence of ovarian cancer in England has remained fairly stable, although it has decreased slightly in the last few years. Between 2008 and 2010 in England, 36% of some 14,000 women diagnosed with ovarian cancer died in the first year, and more than 1,600 died in the first month. There were 7,378 new cases of ovarian cancer in the UK in 2014 and more than 4,000 women died from the disease.
 
Benign symptoms difficult to diagnose

If ovarian cancer is diagnosed and treated early before it spreads from the ovaries to the abdomen, the 5-year relative survival rate is 92%. However, only 15% of all ovarian cancers are found at this early stage.  This is because it is hard to diagnose since the disease is so rare, the symptoms are relatively benign, and there is no effective screening. As a result, the illness tends not to be detected until the latter stages in around 60% of women, when the prognosis is poor. In about 20% of cases the disease is not diagnosed until it is incurable. Feeling bloated most days for three weeks or more is a significant sign of ovarian cancer. Other symptoms include: feeling full quickly, loss of appetite, pelvic or stomach pain, needing to urinate more frequently than normal, changes in bowel habit, feeling very tired, and unexplained weight loss.
 
“Tumors go from the earliest stage 1 directly to stage 3”
In the video below Hani Gabra, Professor of Medical Oncology at Imperial College, London; and Head of AstraZeneca’s Oncology Discovery Unit says, “Ovarian cancer is often diagnosed late because in many cases the disease disseminates into the peritoneal cavity almost simultaneously with the primary declaring itself. Unlike other cancers, the notion that ovarian cancer progresses from stage 1 to stage 2, to stage 3 is possibly mythological. The reality is, these cancer cells often commence in the fallopian tube with a very small primary tumor, which disseminates directly into the peritoneal cavity. In other words, the tumors go from the earliest of stage 1 directly to stage 3."
 
 
Ovarian cancer screening and CA-125

For years scientists have been searching for an effective screening test for ovarian cancer in pre-symptomtic women. The 2 most common are transvaginal ultrasound (TVUS) and the CA-125 blood test. The former uses sound waves to examine the uterus, fallopian tubes, and ovaries by putting an ultrasound wand into the vagina. It can help find a tumor in the ovary, but cannot tell if the tumor is cancerous or benign. Most tumors identified by TVUS are not cancerous. So far, the most promising screening method is CA-125, which measures a protein antigen produced by the tumor.
 
CA-125 studies
To-date, 2 large ovarian cancer screening studies have been completed: one in the US, and another in the UK. Both looked at using the CA-125 blood test along with TVUS to detect ovarian cancer. In these studies, more cancers were found in the women who were screened, and some were at an early stage. But the outcomes of the women who were screened were no better than the women who were not screened: the screened women did not live longer and were not less likely to die from ovarian cancer.

Another study published in 2017 in the Journal of Clinical Oncology screened 4,346 women over 3 years at 42 centers across the UK, undertook follow-up studies 5 years later, and came to similar conclusions as the 2 previous studies. Further, “there are a number of non-ovarian diseases, which can cause elevated CA-125’s. Breast cancer, endometriosis, and irritation of the peritoneal cavity can all cause elevated CA-125,” says Michael Birrer, Director of Medical Gynecologic Oncology at the Massachusetts General Hospital and Professor of Medicine at Harvard University.


Controversial findings
Findings from screening tests using CA-125 can give false positives for ovarian cancer, and this puts pressure on patients to have further, often unnecessary interventions, which sometimes include surgery. Also, the limitations of the CA-125 test mean that many women with early stage ovarian cancer will receive a false negative from testing, and not get further treatment for their condition. Thus, the potential role of CA-125 for the early detection of ovarian cancer is controversial, and therefore it has not been adopted for widespread screening in asymptomatic women.
 
In the video below Birrer explains that, “pre-operatively and during therapy physicians will usually check CA-125 as a measure of the effectiveness of the therapy. At the completion of therapy one would anticipate that the CA-125 would be normal. After that, it is somewhat controversial as to whether follow-up with CA-125 to test for recurring disease is clinically relevant,” says Birrer. Since the discovery of CA-125 in 1981, there has been intense research focus on novel biomarkers for cancer, and significant scientific advances in genomics, proteomic, and epigenomics etc., which have been extensively used in scientific discovery, but as yet no new major cancer biomarkers have been introduced to practicing oncologists. 

 
Limited treatment options

As most ovarian cancer patients are diagnosed late when the disease has already spread, treatment options are limited. The first line treatment is surgery called debulking, (also known as cytoreduction or cytoreductive surgery), which is the reduction of as much of the volume (bulk) of a tumor as possible. 
 
Be prepared for extensive surgery
Whether a patient is a candidate for surgery depends on a number of factors including the type, size, location, grade and stage of the tumor, pre-existing medical conditions, and in the case of a recurrence, when the last cancer treatment was performed, as well as general health factors such as age, physical fitness and other medical comorbidities. People diagnosed with ovarian cancer, “need to be prepared to have extensive surgery because the real extent of the tumor dissemination cannot be detected by conventional imagining pre-operatively,” says Professor Christina Fotopoulou, consultant gynaecological oncologist at Queen Charlotte's & Chelsea Hospital, London: see video below. 
 
 
Platinum resistance

Surgery is usually followed by chemotherapy. There are more than 100 chemotherapy agents used to treat cancer either alone or in combination. Chemotherapy drugs target cells at different phases of the process of forming new cells, called the cell cycle. Understanding how these drugs work helps oncologists predict, which drugs are likely to work well together. Clinicians can also plan how often doses of each drug should be given based on the timing of the cell phases. Chemotherapy drugs can be grouped by their chemical composition, their relationship with other drugs, their utility in treating specific forms of cancer, and their side effects.  
 
You can reduce chemotherapy resistance by using a combination of drugs that target different processes in the cancer so that the probability that the cancer will simultaneously become resistant to both drugs is much lower than if you use one drug at a time, ” says David Bowtell,  Professor and Head of the Cancer Genomics and Genetics Program at Peter MacCallum Cancer Centre, Melbourne, Australia: see video:
 
 
Improving the chemotherapy agent cisplatin
The standard chemotherapy treatment for ovarian cancer is a combination of a platinum compound, such as cisplatin or carboplatin, and a taxane, which represents a class of drug originally identified from plants. Since cisplatin’s discovery in 1965 and its FDA approval in 1978, it has been used continuously in treatments for several types of cancer, and is best known as a cure for testicular cancer. Scientists have searched for ways to improve the anti-tumor efficacy of platinum based drugs, reducing their toxicity, strengthening them against resistance by expanding the class to include several new analogues of cisplatin, and putting these through clinical studies to broaden the different types of cancers against which they can be safely used.
 
Slow progress transitioning research into clinical practice
Despite these endeavors, platinum resistance remains a significant clinical challenge. Between 55 and 75% of women with ovarian cancer develop resistance to platinum based chemotherapy treatments. Significant research efforts have been dedicated to understanding this, but there has been relatively slow progress transitioning the research into effective clinical applications. According to Birrer, “the mechanism of platinum resistance from a molecular standpoint has not been well defined. It is likely to be heterogeneous, which means that each patient’s tumor may be slightly different. The hope is for targeted therapies and personalised medicine to have a chance of overcoming this, in that we could characterize the mechanism of the platinum resistance and apply and target therapy.”
 
2 theories of platinum resistance
In the video below, Birrer posits 2 theories to explain platinum resistance. “One suggests that under the influence of platinum the tumor changes and becomes resistant. Another suggests that there are 2 groups of cells to begin with. The vast majority of the tumor is sensitive, but there are small clusters of resistant cells. Once you kill the sensitive cells you have only the resistant cells left. Although these 2 theories have been around for about 25 years, there are no definitive data to suggest which theory is right. I have a personal scientific bias to think that the resistant cells are present at the time that we start the therapy. Being able to identify and characterize these cells upfront would be a radical breakthrough because then we would be able to target them at a time when they are only a small portion of the tumor,” says Birrer.
 
 
Takeaways

Saatchi is right; for decades ovarian cancer treatment has been wanting, but studies we describe in part-2 of this Commentary suggest that the tide might be turning for people living with ovarian cancer. So don't miss part-2 next week!
 
 
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  • Each year about 1.7m women are diagnosed with breast cancer worldwide and over 0.5m die from the condition
  • Between 5% and 10% of these breast cancers result from harmful gene mutations
  • BRCA1 and BRCA2 gene mutations are the most common cause of hereditary breast cancer
  • 45% to 85% of women with a BRCA mutation will develop breast cancer in their lifetime compared to 12% of women in the general population
  • Most women do not know if they have a harmful BRCA mutation
  • Testing for the BRCA gene is now affordable, fast and accessible
  • Surgical interventions of women with BRCA mutations can significantly reduce their risk of developing breast cancer and substantially increase cancer survival
  • Genetic test results for breast cancer are fraught with uncertainty because testing reveals the likelihood of developing cancer rather than a certain fate
  • Research suggests that BRCA test results are not being clearly communicated to women
  • Best practice demands that expert counselors discuss genetic testing and help interpret results
 
Breast cancer and harmful BRCA gene mutations


Few things frighten women more than discovering a lump in one of her breasts The standard treatment: surgery, followed by radio- and chemotherapy, can be disfiguring, painful, sometimes unsuccessful, and the impact of the disease is felt by far more individuals than just those who have the diagnosis.The good news is that over the past 30 years breast cancer survival rates in most developed countries have been improving, largely due to screening, earlier diagnosis and improved treatments. The bad new is that in most developed countries it is twice as likely for a woman to be diagnosed with breast cancer than 60 years ago.
 
Harmful BRCA genes mutations

5 to 10% of breast cancers are thought to be due to gene mutations, and harmful BRCA mutations account for 20 to 25% of these. Women who inherit the BRCA1 mutations have a 60 to 90% risk of developing breast cancer in their lifetime, and those who inherit BRCA2 mutations increase their risk of breast cancer by 45 to 85%, compared to 12% of women in the general population. Most women do not know if they carry the harmful BRCA mutation, but if they discover they do, many elect to have a bilateral mastectomy. This is a significant procedure with potential risks and side effects, but can reduce your mortality risk by about 50%.
 
The gold standard screening for breast cancer is an x-ray picture of the breast (mammography), but increasingly women are turning to genetic testing as their awareness of the harmful BRCA mutations increase, and genetic testing becomes more accessible and affordable. However, results from these tests are not straightforward, and often not communicated well. This can increase the anxiety in women with suspected breast cancer, and make them elect to have unnecessary interventions and procedures.
 
This Commentary describes how advanced genetic testing together with expert counselling help women improve their management of breast cancer.
 

Breast Cancer
 
Cancer is a group of diseases that cause cells in your body to change and grow out of control: they mutate. Most types of cancer cells eventually form a lump or mass called a tumor, and are named after the part of the body where the tumor originates, e.g. “breast cancer”, although this convention is changing with the development of targeted personalized medicine. The exact cause of breast cancer is unknown, but the overwhelming majority result from some combination of environment, lifestyle, and genes. Breast cancer affects about 1 in 8 women at some point during their life, usually after the menopause, and is the most common cancer in women.  The majority of breast cancers begin in the parts of the breast tissue that are made up of glands for milk production, called lobules, and ducts that connect the lobules to the nipple. The remainder of the breast is made up of fatty, connective, and lymphatic tissue. Most invasive breast cancers (those that have spread from where they started) are found in women 55 and older. Women with a family history of the disease have an increased risk of getting breast cancer. Each year about 1.7m women are diagnosed with breast cancer worldwide, and over 0.5m die from the condition. However in developed economies more and more women survive the disease. In the US, for instance, the average 5-year survival rate for people with breast cancer is 89%. The 10-year rate is 83%, and the 15-year rate is 78%. Other developed countries have similar success rates. What makes breast cancer fatal is if it spreads to the bones, lungs, liver and other organs. Early detection in order to improve breast cancer outcomes remains the cornerstone of the condition’s management. Although breast cancer is thought to be a disease of the developed world, it is increasing rapidly in emerging countries where the majority of cases present later and die earlier than women in developed countries: almost 50% of breast cancer cases and 58% of deaths occur in emerging economies. This is because women generally have relatively poor knowledge of the risk factors, symptoms and methods for early detection. Also, they experience cancer fatalism, believe in alternative medicine, and lack of autonomy in decision making, which often results in delays in seeking or avoidance of evidence-based medicine.
 
Mammography
 
Mammography, which has long been the mainstay of breast cancer detection, is a specific type of breast imaging that uses low-dose x-rays to detect small changes in the breast before there are any other signs or symptoms of the disease when it is most treatable. Mammography is noninvasive, relatively inexpensive, and has reasonable sensitivity (72–88%), which increases with age. It can also be used to detect and diagnose breast disease in women experiencing symptoms such as a lump, pain, or nipple discharge. If breast cancer is found at an early stage, there is an increased chance for breast-conserving surgery and a better prognosis for long-term survival. Most developed countries operate breast-screening programs, which regularly provides mammography for women between certain ages.
 
Advances in mammography

In recent years, mammography has undergone increased scrutiny for false positives and excessive biopsies, which increase radiation dosage, cost and patient anxiety. In response to these challenges, new forms of mammography screening have been developed, including; low dose mammography, digital mammography, computer-aided detection, tomosynthesis, which is also called 3-D mammography, automated whole breast ultrasound, molecular imaging and MRI. Notwithstanding, there is increasing awareness of subpopulations of women for whom mammography has reduced sensitivity. More recently, women have turned to genetic testing to gain a better understanding of their risk of inherited breast cancer.
 
Genes

Every cell in your body contains genes. These contain the genetic code for your body, which not only determines the color of your eyes and hair etc., but also provides information that affects how the cells in your body behave: for example, how they grow, divide and die. Information in your genes is inherited from both parents, and you pass on this information to your children. A change in your genetic code that affects the function of a gene is called a mutation. Many inherited gene mutations do not have any effect on your health, but some do; the BRCA1 and BRCA2 mutations account for 20 to 25% of all inheritable female breast cancers and 15% of ovarian cancers.
  
BRCA genes

In normal cells, BRCA genes are tumor suppressor genes that assist in preventing cancer developing by making proteins that help to keep cells from growing abnormally. Mutated versions of BRCA genes cannot stop abnormal growth, and this can lead to cancer. Mutated BRCA genes have a higher prevalence in certain ethnic groups, such as those of Ashkenazi Jewish descent.

In the video below Professor Robert Leonard, a medical oncologist and an authority on breast cancer, describes how BRCA genes are influential in breast and ovarian cancer risk. BRCA1 runs in families and may also increase a woman’s risk of developing fallopian tube and peritoneal cancers. BRCA2 also runs in families, and is more breast cancer-specific, but a less commonly inherited abnormality. Both or either of these genes may not be detectably abnormal even in a family with a strong inherited pattern of breast cancer, but there is a significant possibility that you will find them in people with a family history of breast and ovarian cancer. Breast and ovarian cancers associated with BRCA mutations tend to develop at younger ages than their non-hereditary counterparts.

 
 
Enhanced risk when family members have cancer
 
In December 2013, the US Preventive Services Task Force recommended that women who have family members with breast, ovarian, fallopian tube, or peritoneal cancer be evaluated to see if they have a familial history that is associated with an increased risk of a harmful mutation in one of the BRCA genes. Compared to women without a family history of cancer, risk of breast cancer is about 2 times higher for women with a close female relative who has been diagnosed with cancer; nearly 3 times higher for women with two relatives, and nearly 4 times higher for women with three or more relatives. Risk is further increased when the affected relative was diagnosed at a young age. Notwithstanding, the Preventive Services Task Force recommends against BRCA testing for women with no family history of cancer.
  
The Angelina Jolie effect

The Hollywood actress and filmmaker Angelina Jolie lost her grandmother and aunt to breast cancer and her mother to ovarian cancer. After discovering that she carried a maternally inherited pathogenic BRCA1 mutation, and being told that she had an 87% chance of developing breast cancer, and a 50% chance of ovarian cancer, Jolie elected to have her breasts, ovaries and fallopian tubes removed. After surgery her risk of developing breast cancer in later life fell to 5%.
 
In May 2013, Jolie described her decision in a New York Times (NYT) article,  “I am writing about it now because I hope that other women can benefit from my experience . . . . . Cancer is still a word that strikes fear into people’s hearts, producing a deep sense of powerlessness. But today it is possible to find out through a blood test whether you are highly susceptible to breast and ovarian cancer, and then take action.”
 
Over testing of by low-risk women
 
Findings published in December 2016 in the British Medical Journal suggest that tests for the BRCA genes shot up by 64% following Jolie’s article. Researchers analysed data on US health insurance claims from more than 9m women between 18 and 64, and suggested that in just 2 weeks following Jolie’s NYT disclosure, 4,500 additional BRCA tests were carried out, which cost the US healthcare system some US$13.5m. Interestingly, increased testing rates were not accompanied by a corresponding increase in mastectomy rates, which suggests that additional testing did not identify new BRCA mutations. Thus, the Angela Jolie effect might have encouraged over-testing among low-risk women.
 
Mindful of her influence on women’s decisions, in 2015 Jolie wrote another NYT article in which she attempted to correct her earlier support for radical risk reduction surgery for women carriers of BRCA mutations. She said that because surgery worked for her, it is not necessarily the optimal therapeutic pathway for all women, and stressed that non-surgical treatments could be more appropriate.
 
Traditional genetic testing for breast cancer risk was slow and expensive

Genetic testing to detect BRCA mutations has been available since 1996, but for many years it was under-used because of its scarcity, high cost, and the length of time it took to produce a result. The rapid development and plummeting costs of genetic testing, and a 2013 US Supreme Court ruling, which invalidated the patents held by Myriad Genetics Inc., which restricted BRCA testing, have resulted in the growth and accessibility of genetic testing.
 
BRCA testing is not straightforward

There are hundreds of mutations in the BRCA1 and BRCA2 genes that can cause cancer. Several different tests are available, including tests that look for a known mutation in one of the genes (i.e., a mutation that has already been identified in another family member), and tests that check for all possible mutations in both genes. Commercial laboratories usually charge between US$450 and US$5,000 to carry out BRCA testing, depending on whether you are being tested for only a specific area(s) of a gene known to be abnormal or if hundreds of areas are being examined within multiple genes. Tests that use traditional technology take several months to report findings. This means that even if a woman is tested at the time of diagnosis, she might not know the results before she has to decide on treatment.
 
Importance of regulated testing laboratories

Testing for the BRCA genes usually involves a blood sample taken in a doctor’s clinic and sent to a commercial laboratory. In 1988, the US Congress passed the Clinical Laboratory Improvement Amendments (CLIA) to ensure quality standards, and the accuracy and reliability of results across all testing laboratories. Since then, all legitimate genetic testing in the US is undertaken in CLIA-approved facilities. During testing for BRCA mutations, the genes are separated from the rest of the DNA, and then scanned for abnormalities. Unlike other clinical screening such as HIV tests and colonoscopies, which provide a simple positive or negative result; genetic testing is fraught with uncertainty because it reveals the likelihood of developing cancer rather than a certain fate.
 
BRCA1 and BRCA2 genetic test results
 
A positive BRCA test result indicates that you have inherited a known harmful mutation in the BRCA1 or BRCA2 gene. This means that you have an increased risk of developing breast and ovarian cancers, but it does not mean that you will actually develop cancer. Some women who inherit a harmful BRCA mutation will never develop cancer. A positive test result may create anxiety and compel clinicians to perform further tests and women to undergo premature and unnecessary clinical interventions, other women in a similar situation will opt for regular screening.
 
The potential benefits of a true negative result include a sense of relief regarding your future risk of cancer, learning that your children are not at risk of inheriting the family's cancer susceptibility, and that a range of interventions may not be required. However, a negative result sometimes can be difficult to interpret because its meaning partly depends on your family’s history of cancer, and whether a BRCA mutation has been identified in a blood relative. Further, scientists continue to discover new BRCA1 and BRCA2 mutations, and have not yet identified all potentially harmful ones. Therefore, it is possible that although you have a “negative” test result you might have a harmful BRCA1 or BRCA2 mutation, which has not been identified.
 
Counselling
 
Because of these uncertainties and the agonising choices women with suspected breast cancer face, health providers in most developed countries recommend counselling as part of breast cancer treatment pathways. In the video below Dr John Green, a medical oncologist knowledgeable about the influence of inherited BRCA gene mutations on treatment options underlines the importance of expert genetic counselling to help women navigate their therapeutic pathways. Counselling is performed by a health professional experienced in cancer genetics, and usually includes the psychological risks and benefits of genetic tests, a hereditary cancer risk assessment based on a person’s personal and family medical history; a description of the tests, their technical accuracy and appropriateness, medical implications of a positive or a negative test result, the possibility of uncertain or ambiguous test results, cancer risk-reducing treatment options, and the risk of passing on a mutation to children. Because people are more aware of the genetic mutations linked to breast cancer, the demand for genetic testing and counselling have increased, and in some instances it is challenging for genetic counsellors to keep pace with demand.
 
 
The context in which genetic tests are carried out

A 2017 study published in the Journal of Clinical Oncology suggests that genetic test results for breast cancer are not being clearly communicated to women, and this could cause them to opt for treatments that are more aggressive than they actually need. To reduce this possibility the Royal Marsden NHS Trust Hospital in London has introduced the Mainstreaming Cancer Genetics programme. Since 2014 the Marsden has employed genetic counseling and used laboratories with enhanced genetic testing capabilities. This reduces processing time and costs, helps to meet the increased demand for rapid, accurate and affordable BRCA testing, and helps women make critical decisions about their treatment options.
 
There were two main problems with the traditional system for gene testing. Firstly, gene testing was slow and expensive, and secondly the process for accessing gene testing was slow and complex,” says Nazneen Rahman, Professor and Head of Cancer Genetics at the UK’s Institute for Cancer Research in London. “We used new DNA sequencing technology to make a fast, accurate, affordable cancer gene test, which is now used across the UK. We then simplified test eligibility and brought testing to patients in the cancer clinic, rather than making them have another appointment, often in another hospital,” says Rahman.

The Marsden is now offering tests to three times more patients a year than before the program started. The new pathway is faster, with results arriving within 4 weeks, as opposed to the previous 20-week waiting period. According to Rahman, “Many other centres across the country and internationally are adopting our mainstream gene testing approach. This will help many women with cancer and will prevent cancers in their relatives.”

 
Takeaways

The history of cancer is punctuated with overzealous interventions, many of which have had to be modified once it has been demonstrated that they could cause more harm than good.

As advanced genetic testing becomes affordable and more accessible it is important that their results are interpreted with the help of genetic counsellors in a broader familial context in order to help women make painfully difficult decisions about their treatment.
 
Migration to next generation genetic testing technologies has many benefits, but it also introduces challenges, which arise from, the choice of platform and software, and the need for enhanced bio-informatics analysts, which are in scarce supply. An efficient, cost-effective accurate mutation detection strategy and a standardized, systematic approach to the reporting of BRCA test results are central for diagnostic laboratories wishing to provide a service during a time of increasing demand and downward pressure on costs.
 
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David Bowtell

Head, Cancer Genomics and Genetics Program, Peter MacCallum Cancer Centre, Melbourne, Australia

Professor Bowtell is the Head of the Cancer Genomics and Genetics Program at Peter MacCallum Cancer Centre and PI for the Australian Ovarian Cancer Study (AOCS).

Professor Bowtell is one of Australia’s leading ovarian cancer and human molecular genetics researchers.

He was Director of Research at Peter Mac for the last decade, returning to fulltime research in 2010 to lead the ovarian cancer arm of the National Health and Medical Research Council’s (NHMRC) $27 million involvement in the International Cancer Genomics Consortium, a world-wide effort aimed at mapping all the significant mutations in common cancers.

 Professor Bowtell heads the Australian Ovarian Cancer Study, a nationally collaborative project involving over 2000 women with ovarian cancer and one of the largest cohort studies of ovarian cancer in the world.

He is a molecular biologist and his lab focuses on the genomic analysis of ovarian cancer, with a focus on primary and acquired drug resistance. His lab is also funded from Cancer Australia and the US DoD to investigate high-risk BRCA mutations in women with ovarian cancer.


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Robert Zeillinger

Associate Professor and Founder and Head, Molecular Oncology Group, Dep. of Obstetrics and Gynaecology, Medical University of Vienna

Professor Robert Zeillinger is an Associate Professor at the Ludwig Boltzmann Institute for Gynecology and Gynecological Oncology, Department of Obstetrics and Gynecology, University of Vienna.

A graduate in biochemistry, Professor Zeillinger is also the founder and the head of the Molecular Oncology Group at The Department of Obstetrics and Gynaecology at the Medical University of Vienna. The main objectives of the group's research are understanding gynaecological cancers at molecular levels, improving diagnosis and prognosis and defining novel therapeutic targets.

The interdisciplinary group is engaged in various national and international organizations and networks (e.g. TOC – Tumor Bank Ovarian Cancer; EUTROC – European Network for Translational Research in Ovarian Cancer; OCTIPS – Ovarian Cancer Therapy Innovative Models; OVCAD – Ovarian Cancer Diagnosis; Ludwig Boltzmann Gesellschaft – Cluster Translational Oncology).


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David Huntsman

Professor, Departments of Pathology and Laboratory Medicine and Obstetrics and Gynaecology, University of British Columbia

Dr. David Huntsman is a Professor in the Departments of Pathology and Laboratory Medicine and Obstetrics and Gynaecology at The University of British Columbia (UBC) and is the Dr. Chew Wei Memorial Professor of Gynaelcologic Oncology. He is a a Staff Pathologist at the BC Cancer Agency (BCCA), and a Consulting Pathologist at the Vancouver General Hospital (VGH).

Dr. Huntsman is currently the Director of the BC multidisciplinary ovarian cancer research team (OvCaRe), Medical Director of the Centre for Translational and Applied Genomics (CTAG) at the BCCA, and co-Director of the Genetic Pathology Evaluation Centre (GPEC) at the Jack Bell Research Centre, VGH.

Dr. Huntsman research has led to development of predictive and prognostic tissue based cancer biomarkers for ovarian cancer and a wide variety of other tumour types. His team created a blueprint for subtype specific ovarian cancer control and have been leaders in the application of novel genomics technologies to ovarian cancer. As collaboration is critical in his field, Dr. Huntsman happily leads and engages in a wide number of multidisciplinary research groups. Most recently he has been working on the creation of broad based personalized medicine initiative for British Columbia.

He is the leader of the TFRI sponsored program grant to study the genomes of rare cancers and to translate discoveries made into biomarkers and treatment opportunities. This team hopes to both improve the management of a cluster of rare cancers and develop strategies and ideas that will have broader clinical impact.


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James Brenton

Senior group leader, Cancer Research UK (CR-UK) Cambridge Institute and lead, Functional Genomics of Ovarian Cancer laboratory

James D. Brenton is a senior group leader at the Cancer Research UK (CR-UK) Cambridge Institute and leads the Functional Genomics of Ovarian Cancer laboratory. He qualified in medicine from University College London in 1988 and trained in medical oncology at the Royal Marsden Hospital, Princess Margaret Hospital, Toronto and the Department of Oncology, University of Cambridge. He has been an honorary consultant in medical oncology at Cambridge University Hospitals NHS Foundation Trust since 2001. His PhD work was carried out at the Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology and he held a Cancer Research UK Senior Clinical Research Fellow from 2001–2006 at the Hutchison/MRC Research Centre.

His research focuses on the identification of prognostic and predictive markers for therapy in ovarian cancer and identifying mechanisms of drug resistance, with particular emphasis on the genomic profiling of clinical samples and bioinformatic analysis.

He is the chair of the Informatics Advisory Group for the national CR-UK Stratified Medicine Programme and was previously Vice-Chair of the CR-UK Biomarkers and Imaging Discovery and Development Committee. He is a member of the international Ovarian Tumor Tissue Analysis (OTTA) Consortium project approval committee, the SGCTG Protocol Review Committee, NCRI ovarian cancer subgroup and the CR-UK Clinical Fellows Mentor Panel.


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