Sign up
Healthed-White-on-Blue

Oncology

shutterstock_793155814
Dr Linda Calabresi
Clinical Articles iconClinical Articles

Podcast series for patients with advanced cancer

Cancer Council NSW has developed a fantastic new podcast series specifically for patients with advanced cancer.The series, entitled ‘The Thing About Advanced Cancer’ provides evidence-based information and practical tips for this group of patients who are often hungry for answers and guidance beyond the usual facts and statistics currently available for their condition.

Expert/s: Dr Linda Calabresi
shutterstock_1370971718
Dr Linda Calabresi
Clinical Articles iconClinical Articles

Melanoma in pregnancy

Did you know that melanoma is the most common malignancy in pregnancy? It accounts for one third of pregnancy-associated malignancies in Australia. Terrifying stuff isn’t it?Fortunately, melanoma occurring in a pregnant woman remains a very rare occurrence. But no one wants to be the doctor that misses it, especially as we all know picking it up early can, quite literally, be the difference between life and death.The really tricky part is that pregnancy does add an extra dimension to detecting and managing melanoma. For a start melanocytic naevi darken during pregnancy in one in ten women.

Expert/s: Dr Linda Calabresi
shutterstock_70475242
Dr Linda Calabresi
Clinical Articles iconClinical Articles

Alcohol – the ignored breast cancer risk factor

Drinking alcohol has been proven to increase the risk of developing breast cancer in over 100 studies, but both the general public and health professionals continue to ignore the issue.According to UK researchers, alcohol use is now estimated to be a major causative factor in between 5% to 11% of all breast cancer cases, but in their study, published in BMJ Open, less than one in five women attending a mammogram knew of the risk of alcohol, and – perhaps more worrying – less than half of the staff at the breast centre identified alcohol as a breast cancer risk factor.The mixed methodology study included over 200 woman attending a breast clinic for breast imaging – about half were symptomatic and the other half presented just for routine screening. These woman were surveyed along with over 30 staff. Following the survey a series of focus groups were conducted with both the women and the staff.Looking at different risk factors, almost one third of all participants identified obesity as a risk, and almost half recognised smoking as problematic. But alcohol? Only 16% in the screening group and 23% in the symptomatic group knew of any association between alcohol and breast cancer.“The study confirms that knowledge of alcohol as a modifiable risk factor for breast cancer is low,” the study authors said.The survey and focus groups also showed that many women did not know how much alcohol was in a standard drink such as a pint of beer or a glass of wine.So, as the authors point out, the dilemma is how will we ever modify this modifiable risk factor if people don’t even know about it and are unaware how to even assess their own alcohol consumption.The researchers suggest that the routine mammogram represents an ideal opportunity to intervene. Here is the time and the place where breast cancer will be front of mind – here is the time and place to increase awareness of alcohol as a breast cancer risk factors, assess a woman’s current alcohol consumption and suggest ways and means of reducing this if appropriate.Concerns that incorporating such a preventative strategy into a routine breast screening appointment might deter women from attending, appeared unfounded, the study noted.“Many women participating in this study reacted positively to the suggestion of adding information on cancer prevention, in general, to . . . breast screening or clinic attendances, although there was ambivalence by staff delivering it,” the researchers said.This ambivalence appeared to stem from a degree of uncertainty in relation to cancer risk factors, a lack of time available to discuss these issues with patients and a sense that it wasn’t their role to be providing this intervention.The other major barrier to conducting these assessments and implementing these preventative measures is motivation. In this study, two thirds of all participants drank alcohol. This is fairly representative of the population as a whole, with previous UK research showing that almost 80% of women had drunk alcohol in the past year, and more than one fifth of women aged 45 to 64 drank more than two standard drinks a day on average.“Home drinking is an embedded social practice, which may be resistant to change, and this normalisation of alcohol use by health professionals may account for some of the ambivalence they have to discuss alcohol consumption as a risk factor for breast cancer with patients,” they said.But this needs to change. There is plenty of evidence that alcohol brief interventions can be effective in reducing alcohol consumption. In fact the authors say, simply answering questions on alcohol consumption can result in behaviour change.“It is interesting to note that while it has become routine practice to assess patients in breast clinics for a possible inherited susceptibility to breast cancer and refer on for family history or genetics investigation, there is currently no equivalent pathway for patients who have potentially modifiable lifestyle risk factors, including alcohol use,” the researchers said. ReferenceSinclair J, McCann M, Sheldon E, Gordon I, Brierley-Jones L, Copson E. The acceptability of addressing alcohol consumption as a modifiable risk factor for breast cancer: a mixed method study within breast screening services and symptomatic breast clinics. BMJ open 2019 Jun 17; 9(6): e027371. DOI: 10.1136/bmjopen-2018-027371

Expert/s: Dr Linda Calabresi
shutterstock_89254516
Prof Mariano Barbacid
Clinical Articles iconClinical Articles

New research gives hope in the fight against pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, is the third most common cause of death from cancer in the United States and the fifth most common in the United Kingdom. Deaths from PDAC outnumber those from breast cancer despite the significant difference in incidence rates.Late diagnosis and ineffective treatments are the most important reasons for these bleak statistics.PDAC is an aggressive and difficult malignancy to treat. Until now, the only chance for cure is the complete surgical removing of the tumor. Unfortunately, because PDAC is usually asymptomatic, by the time it is diagnosed 80% to 90% of patients have disease that is surgically incurable. PDAC thus remains one of the main biomedical challenges today due to its low survival rate – just 5% of patients are still alive five years after diagnosis.However, in recent decades a number of studies have shed light on the molecular mechanisms responsible for the initiation and progression of PDAC. Our recent research has shown that progress toward a cure is possible.

Ineffective treatments

The molecular mechanisms responsible for pancreatic cancer are complex. This is why recent advances in personalized medicine and immunotherapy (which helps the immune system fight cancer) have failed to improve the treatment of pancreatic cancer. This is mainly due to two characteristics:
  • 95% of these tumors are caused by mutations in KRAS oncogenes. Oncogenes are genes that, once mutated, are capable of inducing the transformation of a normal cell into a cancerous cell. KRAS is a gene that acts as an on/off switch. Normally, KRAS controls cell proliferation. When it is mutated, however, the cells start to grow uncontrollably and proliferate – a hallmark of cancer cells. So far, KRAS oncogenes have not been able to be targeted by drugs.
  • PDACs are surrounded by abundant fibrous connective tissue that grows around some tumor types. In the case of PDAC, this tissue forms a barrier that prevents cells that recognize and attack tumor cells, called cytotoxic T lymphocytes, from reaching the inside of the tumor mass and killing its cells. This renders immunotherapy treatments useless.
For these reasons, PDAC continues to be treated with drugs that destroy cancerous cells but can also destroy healthy ones. Options include Demcitabine, approved in 1997, and Nab-paclitaxel, a new paclitaxel-based formulation. Even if such a treatment is an option, it typically only extends the patients’ lives a few weeks, a marginal improvement at best.In recent years, however, a number of studies have shed light regarding the molecular mechanisms responsible for the initiation and progression of PDAC.Today we know that most of these tumors are caused by mutations in the KRAS oncogene. They lead to benign alterations that cause additional mutations in a range of tumor-suppressor genes, which usually repair DNA mistakes, slow down cellular division or tell cells when to die. Mutated cells can grow out of control, and in this context progress to malignant PDAC.While this process is relatively well known, it has not had an immediate impact on the development of new and more effective treatments.

In search of new strategies

Multiple strategies are currently being studied in an attempt to inhibit the growth of these tumors by blocking the growth of either the tumor cells or their surrounding “shielding” connective tissue. In our laboratory, we focused on blocking the signaling pathways that mediate the oncogenic activity of the initiating KRAS oncogenes.A decade ago, our lab decided to use genetically engineered mouse-tumor models capable of reproducing the natural history of human PDAC. We did this in order to analyze the therapeutic potential of the main components of the KRAS signaling pathways. These studies have unveiled the reason why the drugs tested so far have intolerable toxic effects, with mice dying within several weeks: they target some proteins that are essential for the dynamic state of equilibrium that is the condition of optimal functioning of the cells. This is called normal homeostasis.These crucial proteins are mainly kinases, enzymes that are able to modify how other molecules function. They play a critical and complex role in regulating cellular signaling and orchestrate processes such as hormone response and cell division. These results might explain why the KRAS-signaling inhibitors tested so far have failed in clinical trials. On the other hand, the removal of other signaling kinases did not have toxic side effects, but also had no impact on tumor development.Of the more than 15 kinases involved in the transmission of signals from the KRAS oncogene, only three displayed significant therapeutic benefits without causing unacceptable side effects. These are: RAF1, the epidermal growth factor receptor (EGFR) and CDK4.

It works! (in mice)

In initial studies, we observed that the elimination (via genetic manipulation) of the expression of some of these three kinases prevented the onset of PDAC caused by the KRAS oncogene. However, its elimination in animals with advanced tumors had no significant therapeutic effects. These results caused us to question whether it would be possible to eliminate more than one kinase simultaneously without increasing the toxic effects.As described in our recent work published in the journal Cancer Cell, the elimination of RAF1 and EGFR expression induced the complete regression of advanced PDACs in 50% of the mice. We are currently studying whether we can increase this by also eliminating CDK4.The analysis of the pancreas of animals in which we were no longer able to observe tumors by imaging techniques revealed the complete absence of lesions in two of them. Two mice showed some abnormal ducts, probably residual scarring from the tumor. The others had tumor micro-masses of one-thousandth the size of the original tumor. The study of these revealed the presence of tumor cells, in which the expression of the two targets, EGFR and RAF1, had not been completely eliminated, a common technical problem in this type of study.It is significant that these results were observed not only in mice. The inhibition of the expression of these two proteins in cells derived from nine out of ten human PDACs were also capable of blocking their proliferation in vivo when transplanted into immunosuppressed mice as well as in vitro cultures.

What now?

While these results have only been observed in a subset of mice for now, their importance lies in the fact that it is the first time that it has been possible to completely eliminate advanced PDAC tumors by eliminating a pharmacologically directed target.These observations are clearly important for the development of treatments based on the inhibition of RAF1 and EGFR, but they only represent a first step on a long, hard road ahead.First, it is important to identify the differences between the PDACs that respond to the combined elimination of RAF1 and EGFR and those that are resistant. As described in our work, the analysis of these two tumor types revealed that they are not active in the same way – more than 2,000 genes are expressed differently.Identifying additional targets in resistant tumors that do not increase treatment toxicity is not going to be an easy task.To continue our tests with genetically engineered mice, the immediate but no less difficult task is the development of specific RAF1 inhibitors. Indeed, we only currently have potent drugs against the second target, EGFR. In principle, there are four possible approaches:
  • Generate selective inhibitors for its kinase activity.
  • Generate inhibitors for its binding to the KRAS oncogene.
  • Generate inhibitors for its interaction with effector targets that transmit oncogenic signaling mediated by RAF1.
  • Degrade the RAF1 protein with drugs.
Designing inhibitors of the RAF1 kinase activity would seem to be the most affordable option, given the experience of the pharmaceutical industry in designing this molecule type.The problem resides in the fact that there are two other kinases of the same family, ARAF and BRAF, whose catalytic centers (the “active core” of the enzymes) are nearly identical. RAF1 kinase inhibitors are also targeting these other kinases, which causes collateral damage. The ones tested to date have caused high toxicities and the clinical trials had to be stopped.Continuing to develop effective molecules that are capable of blocking RAF1 activity in patients with PDAC will not be easy. It will surely take more time than we hope, but at least a road map has already been outlined that shows us how to keep moving forward.Created in 2007 to help accelerate and share scientific knowledge on key societal issues, the AXA Research Fund has been supporting nearly 600 projects around the world conducted by researchers from 54 countries. To learn more about this AXA Research Fund project, please visit the dedicated page.This article was translated from the original Spanish by Sara Crespo, Calamo & Cran.The ConversationMariano Barbacid, profesor e investigador AXA-CNIO de Oncología Molecular, Centro Nacional de Investigaciones Oncológicas CNIOThis article is republished from The Conversation under a Creative Commons license.Read the original article.
Expert/s: Prof Mariano Barbacid
shutterstock_1273442329
Dr Linda Calabresi
Clinical Articles iconClinical Articles

Anorexia and cancer risk

You’d think having anorexia nervosa was bad enough. But among all the negative effects it can have on your body, could it also increase your risk of cancer? Or does the condition perversely mimic the caloric restriction and fasting that have been demonstrated to benefit the prevention of some malignancies - meaning could it protect against cancer?That's what European oncology researchers wanted to find out through their systematic review and meta-analysis of a series of studies involving more than 42,000 people with the eating disorder.The result was both encouraging and intriguing.It appears that overall there was no association of anorexia nervosa with risk of cancer.But that’s not the whole story.On further analysis it appears anorexia nervosa was associated with some cancers and not others. In some cases the condition increased the risk and in others it appeared protective, hence the balancing out effect of no association overall.“Findings from our meta-analysis suggest that anorexia nervosa was associated with decreased breast cancer incidence compared with the general female population, with high confidence,” said the study authors in JAMA Network Open.And on the down side, the researchers found anorexia nervosa appeared to be associated with an increased risk of developing lung and oesophageal cancer, although the evidence was less compelling than that for breast cancer.As the authors point out, the breast cancer protection makes sense in terms of physiology.Anorexia notoriously interferes with a woman’s hormones, reducing her levels of oestradiol as well as insulin-like growth factor 1. Women with anorexia often have delayed puberty, early menopause and an overall decreased lifetime exposure to oestrogen so it stands to reason that a hormone-sensitive cancer, such as breast cancer is less likely to develop.But the increased risk of lung and oesophageal cancer is harder to explain. One might think, given the types of cancer we’re talking about that perhaps there was a greater prevalence of smoking among people with anorexia nervosa.But no.“[T]he increased risk of developing lung or oesophageal cancer does not seem to be attributable to a higher prevalence of smoking among women with anorexia nervosa,” they said.Interestingly the authors refer to a 2016 meta-analysis that determined smoking prevalence was much higher among people with bulimia nervosa than the general population, but not anorexia nervosa.The researchers offer no explanation for the association between anorexia and lung and oesophageal cancer, conceding the evidence isn’t strong. However they do warn that the findings suggest perhaps a need for greater vigilance in investigating symptoms suggestive of cancers of either the respiratory tract or the GIT in anorexia nervosa patients.As with most studies, the study authors call for further research to confirm or refute these associations, suggesting that the findings have possibly important implications.“Understanding the mechanisms underlying these associations could have important preventive potential,” they concluded. 

Reference:

Catalá-López F1, Forés-Martos J, Driver JA, Page MJ, Hutton B, Ridao M, et al. Association of Anorexia Nervosa With Risk of Cancer: A Systematic Review and Meta-analysis. JAMA Netw Open. 2019; 2(6): e195313. DOI: 10:1001/jamanetworkopen.2019.5313
Expert/s: Dr Linda Calabresi
shutterstock_1295693164
Dr Linda Calabresi
Clinical Articles iconClinical Articles

Pancreatic cancer support

It’s still probably one of medicine’s most devastating diagnoses – pancreatic cancer.Despite all the scientific advances that have been made in treating so many malignancies, the prognosis for pancreatic cancer is most often pretty bleak. Consequently, patients presented with this diagnosis are most likely to be in need of significant support.PanSupport (pansupport.org.au) is a newly-developed site, produced by the University of Melbourne that is likely to prove incredibly valuable to patients battling this condition, and their families. This resource not only provides valuable information about pancreatic cancer and its treatment, but it also gives practical advice with regard aspects of management such as diet and exercise. Importantly it also directs patients to any potential clinical trials for which they may be eligible.In keeping with the very practical and realistic approach of the entire site, Pansupport also includes information about palliative care and Advanced Care directives, allowing patients to access what they need to know in their own time frame.The PanSupport website has been developed in collaboration with the Pancare Foundation, RMIT University and the Peter MacCallum Cancer Centre. It has been funded with a Cancer Grant Initiative funded by the Australian Government.>> Find out more about PanSuport here 

Expert/s: Dr Linda Calabresi
shutterstock_1032241918
Dr Linda Calabresi
Clinical Articles iconClinical Articles

Stop drinking and lose weight to prevent breast cancer

The spectre of breast cancer looms large for the majority of Australian women.But now researchers say if we tackle obesity and overweight as well as cutting out regular alcohol consumption we can prevent thousands of cases of this disease which is our most common cancer in women and second leading cause of cancer death.A new study has quantified how much these modifiable risk factors contribute to the incidence of breast cancer and predicts how many future cases they will cause. And it’s a bit frightening.According to this large Australian collaborative study, published in the international Journal of Cancer, if all Australian women maintained a healthy weight we could prevent 17,500 breast cancers in the next 10 years. And if women stopped drinking alcohol regularly (even one drink a day) it was estimated 11,600 future breast cancers could be avoided over the next decade.The researchers from University of NSW’s Centre for Big Data Research in Health were able to quantify the burden of these two risk factors after pooling six Australian cohort studies that included over 200,000 women. They were also able to differentiate the contribution of the various factors in premenopausal as opposed to postmenopausal breast cancers.“Regular alcohol consumption is the potentially modifiable risk factor responsible for the largest burden of breast cancer for premenopausal women in Australia, accounting for 12.6% of the burden and 2,600 cases of breast cancer over the next 10 years,” the study authors said. Body weight, or more accurately ‘body fatness’ was not a major factor for developing breast cancer before menopause.Apparently, this is the first time that regular alcohol consumption has been shown to be the leading modifiable contributing factor to breast cancer risk in this age group.And even though the finding would suggest that reducing the number of drinks per day would lessen the risk, the researchers found that the increased risk held true even with an average of one drink a day. Certainly bad news for more than half of Australian women who currently report drinking alcohol regularly, even if they are keeping to the current Australian recommendation not to drink more than two drinks a day on average.Among postmenopausal women, body fatness represents the biggest danger, accounting for 12.8% of the burden (17,500 breast cancer cases) over a decade. Given that three in five postmenopausal women in Australia are currently estimated to be overweight or obese this represents a key target for intervention. And alcohol consumption too, still made a substantial contribution to the risk in this cohort (6.6% or 9,000 breast cancer cases).Other modifiable risk factors included taking the oral contraceptive pill premenopause, and, among postmenopausal women taking menopausal hormone therapy (MHT).As the researchers point out, the issue of oral contraceptives as a breast cancer risk is a little complicated as it has to be weighed up against the protective effect these medications have against endometrial, ovarian and colorectal cancers as well as their reproductive health benefits.And as for MHT, the major breast cancer risk was for women taking MHT for five years or more.“Our findings thus support the current Australian and international recommendations of using MHT for the shortest duration possible, and only to alleviate menopausal symptoms, not for the prevention of chronic disease,” they said.Interestingly, for postmenopausal women at least, being physically active or having a history of breast feeding didn’t seem to alter the risk of developing breast cancer in the future.However, what the study has highlighted is the importance of targeting weight and alcohol as the most effective means to reduce the incidence of breast cancer.“The findings provide evidence to support targeted and population-level cancer control activities in Australia and beyond,” the study authors said. 

Reference

Arriaga ME, Vajdic CM, Canfell K, MacInnis RJ, Banks E, Byles JE, et al. The preventable burden of breast cancers for premenopausal and postmenopausal women in Australia: A pooled cohort study. Int. J. Cancer. 2019 Feb 25. DOI: 10.1002/ijc.32231
Expert/s: Dr Linda Calabresi
shutterstock_1295693164
Suzanne Mahady
Clinical Articles iconClinical Articles

What’s Behind the Increase in Bowel Cancer Among Younger Australians?

Bowel cancer mostly affects people over the age of 50, but recent evidence suggests it’s on the rise among younger Australians.Our study, published recently in Cancer Epidemiology, Biomarkers and Prevention, found the incidence of bowel cancer, which includes colon and rectal cancer, has increased by up to 9% in people under 50 from the 1990s until now.Our research examined all recorded cases of bowel cancer from the past 40 years in Australians aged 20 and over. Previous studies assessing bowel cancer incidence in young Australians have also documented an increase in the younger age group.This trend is also being seen internationally. A study from the United States suggests an increase in bowel cancer incidence in people aged 54 and younger. The research shows rectal cancer incidence increased by 3.2% annually from 1974 to 2013 among those aged age 20-29.Bowel cancers are predicted to be the third most commonly diagnosed cancer in Australia this year. In 2018, Australians have a one in 13 chance of being diagnosed with bowel cancer by their 85th birthday.Our study also found bowel cancer incidence is falling in older Australians. This is likely, in part, to reflect the efficacy of the National Bowel Cancer Screening Program, targeted at those aged 50-74. Bowel cancer screening acts to reduce cancer incidence, by detecting and removing precancerous lesions, as well as reducing mortality by detecting existing cancers early.This is important, as bowel cancer has a good cure rate if discovered early. In 2010 to 2014, a person diagnosed with bowel cancer had a nearly 70% chance of surviving the next five years. Survival is more than 90% for people who have bowel cancer detected at an early stage.That is why screening is so effective – and we have previously predicted that if coverage rates in the National Bowel Screening Program can be increased to 60%, around 84,000 lives could be saved by 2040. This would represent an extraordinary success. In fact, bowel screening has potential to be one of the greatest public health successes ever achieved in Australia.

Why the increase in young people?

Our study wasn’t designed to identify why bowel cancer is increasing among young people. However, there are some factors that could underpin our findings.The increase in obesity parallels that of bowel cancer, and large population based studies have linked obesity to increased cancer risk.Unhealthy lifestyle behaviours, such as increased intake of highly processed foods (including meats), have also been associated with increased bowel cancer risk. High quality studies are needed to explore this role further.Alcohol is also thought to be a contributor to increasing the risk of bowel cancer.So, should we be lowering the screening age in Australia to people under the age of 50?Evaluating a cancer screening program for the general population requires a careful analysis of the potential benefits, harms, and costs.A recent Australian study modelled the trade-offs of lowering the screening age to 45. It showed more cancers would potentially be detected. But there would also be more colonoscopy-related harms such as perforation (tearing) in an extremely small proportion of people who require further evaluation after screening.A lower screening age would also increase the number of colonoscopies to be performed in the overstretched public health system and therefore could have the unintended consequence of lengthening colonoscopy waiting times for people at high risk.

How to reduce bowel cancer risk

One of the most common symptoms of bowel cancer is rectal bleeding. So if you notice blood when you go to the toilet, see your doctor to have it checked out.A healthy lifestyle including adequate exercise, avoiding smoking, limiting alcohol intake and eating well, remains most important to reducing cancer risk.Aspirin may also lower risk of cancer, but should be discussed with your doctor because of the potential for side effects including major bleeding.Most importantly, we need to ensure eligible Australians participate in the current evidence-based screening program. Only 41% of the population in the target 50-74 age range completed their poo tests in 2015-2016. The test is free, delivered by post and able to be self-administered.The Conversation This article is republished from The Conversation under a Creative Commons license. Read the original article.
Expert/s: Suzanne Mahady, Eleonora Feletto, Karen Canfell
shutterstock_1032241918
Dr Linda Calabresi
Clinical Articles iconClinical Articles

Body Fat more Important than BMI in Breast Cancer

Women with a normal BMI can no longer tick off weight as breast cancer risk factor, US researchers say.According to their study, published in JAMA Oncology, it’s body fat that increases the risk even if the woman falls into a healthy weight range.The study was in fact a secondary analysis of the Women’s Health Initiative clinical trial along with observational study cohorts involving almost 3500 post-menopausal, healthy BMI women who at baseline had their body fat analysed (by DXA) and were then followed up for a median duration of 16 years.What the researchers discovered was that women in the highest quartile for total body fat and trunk fat mass were about twice as likely to develop ER-positive breast cancer.“In this long-term prospective study of postmenopausal with normal BMI, relatively high body fat levels were associated with an elevated risk of invasive breast cancers,” the study authors spelled.Perhaps less surprisingly, the analysis also found that the breast cancer risk increased incrementally as the body fat levels increased.“We found a 56% increase in the risk of developing ER-positive breast cancer per 5-kg increase in trunk fat, despite a normal BMI,” they said.The proposed mechanism that explains why high body fat levels increases the risk of breast cancer, is much the same as the known mechanism that explains the link between obesity and breast cancer risk.People with high body fat levels tend to have adipocyte hypertrophy and cell death which means the adipose tissue is chronically although sub-clinically inflamed. This inflammation triggers the production of a number of factors including an increased ratio of oestrogens to androgens which is believed to predispose to the development of oestrogen-dependent breast cancer.Basically the study authors believe these women with high body fat but normal BMI, are ‘metabolically obese’ even though they do not fit the standard definition of obese.And while using DXA to determine body fat levels is highly accurate, such an assessment is rarely used in everyday practice.Most doctors look only at BMI measurements or they may also assess waist measurement which has variable sensitivity in terms of diagnosing excess body fat. Consequently, the researchers say, many non-overweight women who are at increased risk of breast cancer because of their high adiposity may be going unrecognised.So where does that leave us? Here the study authors were less definitive. The link between body fat and breast cancer is clear but, they say, more research is needed to determine the most appropriate management for this cohort of women with high body fat levels and normal BMI.“Future studies are needed to determine whether interventions that reduce fat mass, such as diet and exercise programs or medications including aromatase inhibitors, might lower the elevated risk of breast cancer in this population with normal BMI,” they concluded.

Reference

Iyengar NM, Arthur R, Manson JE, Chlebowski RT, Kroenke CH, Peterson L, et al. Association of Body Fat and Risk of Breast Cancer in Postmenopausal Women With Normal Body Mass Index: A Secondary Analysis of a Randomized Clinical Trial and Observational Study. JAMA 2018 Dec 6. DOI: [10.1001/jamaoncol.2018.5327] [Epub ahead of print]
Expert/s: Dr Linda Calabresi
shutterstock_577395964
Dr Linda Calabresi
Clinical Articles iconClinical Articles

Not Missing Ovarian Cancer

No one wants to miss ovarian cancer especially in its early stages when you have a chance of successful treatment.But should we be regularly monitoring women who have had a simple ovarian cyst detected on ultrasound, as most guidelines recommend to avoid missing this particularly deadly cancer?That is what US researchers investigated in a nested case controlled study, recently published in JAMA.The study was based on a cohort of adult women from the Kaiser Permanente Washington health care system who had had a pelvic ultrasound at some stage over a 12-year period starting in 1997, and looked at the association of the ultrasound finding with the risk of being diagnosed with ovarian cancer within three years.On analysing the data from the 72,000 women who underwent the investigation, the first finding was that ovarian cysts were very common, particularly simple ovarian cysts, occurring in more than 15,000 women. Simple cysts were detected in almost one in four women aged younger than 50, and just over one in 12 women aged 50 and over.Complex cyst structures were far less common, which is fortunate as the study also confirmed that most of the 212 women who were eventually diagnosed with ovarian cancer had a complex cyst structure on ultrasound.According to their analysis, the detection of a complex cystic ovarian mass on ultrasound increased the likelihood of cancer eight-fold, and if they were 50 or over and found to have ascites as well, the finding was practically diagnostic with the likelihood of having ovarian cancer being over 70 times greater than normal.Ultrasound detection of solid masses was not as dangerous a finding, but the one in ten association with ovarian cancer certainly warranted further investigation.But what of the women found to have a simple cyst on ultrasound? How many of them went on to be diagnosed with ovarian cancer? Well, among those aged under 50 – none! And among the older women only one – and the researchers suspect that the simple cyst found in this case was, in fact an incidental finding.As the study authors point out, this finding shouldn’t be surprising as it is well-known that ‘simple cysts are almost universally benign.’But the majority of guidelines still recommend on-going surveillance, mainly because of a reluctance to make a definitive diagnosis on the basis of the ultrasound appearance or interpretation alone.“One of the justifications for the surveillance of simple cysts is that imaging may be inaccurate and might miss complex features,” the researchers explain.But such concerns are not warranted according to this study. What’s more, the authors suggest the constant monitoring of these benign cysts may in fact not only be useless but may cause harm.“While surveillance may not seem harmful, there is a growing realisation across all areas of medicine that unnecessary imaging is associated with morbidity, including wasted time, false-positive results, over diagnosis, unnecessary surgery and anxiety,” the study authors concluded. 

Reference

Smith-Bindman R, Poder L, Johnson E, Miglioretti DL. Risk of Malignant Ovarian Cancer Based on Ultrasonography Findings in a Large Unselected Population. JAMA Intern Med. Published online November 12, 2018. doi:10.1001/jamainternmed.2018.5113.
Expert/s: Dr Linda Calabresi
shutterstock_1006005280
Dr Linda Calabresi
Clinical Articles iconClinical Articles

Bowel Cancer Screening: Who, When, How?

New NHMRC guidelines put age and family history up front and centre in determining who should be screened for bowel cancer with colonoscopy and who needs iFOBT.It has been known for some time that family history can influence the risk of developing bowel cancer, Australia’s second most common cause of cancer death. But it is also known that specific, identified genetic mutations causing conditions such as Lynch syndrome or familial adenomatous polyposis are rare, accounting for less than 5% of all bowel cancers diagnosed. At most, the researchers say, this only explains half of the reasons why family history is a risk factor for bowel cancer.“The remainder of the observed increases in familial risk could be due in part to mutations in yet to be discovered colorectal cancer susceptibility genes, polygenic factors such as single-nucleotide polymorphisms, or dietary and other lifestyle factors shared by family members,” the guideline authors said in the Medical Journal of Australia.Therefore, the researchers, led by Professor Mark Jenkins, director of the Centre for Epidemiology and Biostatistics, in the University of Melbourne’s School of Population and Global Health, analysed all the available cohort studies to determine the risk of developing colorectal cancer based on age and family history. They categorised cohorts into one of three levels of risk and this determined at what age screening would be worthwhile starting and which screening method was most appropriate. The screening guidelines exclude people with a known or suspected cancer-causing genetic syndrome, as these people require much more intensive screening and should be managed in a family cancer clinic.The majority of Australians (90%) fall into the lowest risk category, category 1, which puts their risk at age 40 of developing colorectal cancer in the next 10 years at about 0.25% (one in 400). As with most other cancers age is a risk factor, so it is unsurprising that at age 50 the risk of developing this cancer has risen to 0.9%.Screening for this category 1 group should be the two-yearly iFOBT test that is currently available via the National Bowel Screening program for adults between the ages of 50 and 74 years. Interestingly, people aged 75 and older still develop bowel cancer but there have been no studies to determine the cost-effectiveness or benefit vs risk analysis of screening in this age group which is why the program and the guideline recommendations stop at 74 years.One of the differences in these new guidelines, a revision from the previous ones published back in 2005, is that people with a first degree relative who has had or has a bowel cancer at age 55 or older are still considered at average risk (category 1).However, people with this history might consider starting the iFOBT screening at a younger age (45 years), the guideline authors suggest.Category 2 includes people with a moderately increased risk of developing colorectal cancer, 3-6 times higher than average. This will mean having a first degree relative diagnosed with a bowel cancer before the age of 55 or having two first degree relatives who developed bowel cancer at any age (or one first degree and two second degree relatives).Category 2 people are recommended to have iFOBT every two years for the decade between ages 40 and 50 and then switch to five yearly colonoscopies until the age of 75.Finally, the high risk, category 3 is for all those patients without a genetic syndrome whose family history is even stronger than those people in category 2. Their risk is between 7-10 times higher than average.This includes people with at least three first-degree relatives who have been diagnosed with colorectal cancer at any age or people who have multiple relatives with the cancer including at least one diagnosed before aged 55.These high-risk people need to start screening earlier, with the guidelines recommending iFOBT every two years starting at age 35 and continuing for 10 years and then having a colonoscopy every five years between the ages of 45 and 75.Of note is that the revised guidelines have deleted the reference in the previous guidelines to starting screening 10 years before the earliest age colorectal cancer was diagnosed in a first degree relative.“There have been no studies conducted to determine the utility of beginning screening 10 years before the earliest diagnosis in the family, which was a recommendation in the 2005 guidelines and, therefore, it is not included in these guidelines,” they said.The new guidelines aim not only to more strongly define risk based on the latest evidence, but also to determine the most appropriate screening method based on that risk, taking into consideration cost-effectiveness and rationalisation of available services, in particular, colonoscopies. ReferenceJenkins MA, Ouakrim DA, Boussioutas A, Hopper JL, Ee HC, Emery JD, et al. Revised Australian national guidelines for colorectal cancer screening: family history. Med J Aust. 2018 Oct 29.doi: 10.5694/mja18.00142. [epub ahead of print]

Expert/s: Dr Linda Calabresi
shutterstock_1679644147
Dr Linda Calabresi
Clinical Articles iconClinical Articles

Detecting Liver Cancer Early

GPs can make a significant difference in curbing the rising rates of liver cancer deaths in Australia, experts say.According to an analysis of over 270 cases of newly diagnosed cases of hepatocellular cancer presenting at seven Melbourne tertiary hospitals over one year, researchers say survival rates could be improved with earlier diagnosis of cirrhosis and better adherence to recommended screening  schedules among those known to be at high risk.“[T]he number of liver cancer-related deaths has been the most rapid for any cancer type in Australia over the past 40 years,” the study authors said in the MJA.And of all the types of liver cancer, hepatocellular carcinoma is by far the most common, accounting for 82%. Even though treatments are available, both curative and palliative survival remains very poor with the Australian 12-month survival rate estimated to be only 62%. In this particular study, conducted over 2012/2013 the mean survival was only 18 months.As one would expect, the patients who did better, who generally survived the longest were those whose tumours were detected at an earlier stage. These were usually the patients who were known to be at high risk of developing liver cancer and were participating in a surveillance program.But this was only 40% of the 272 cases, even though 89% would have qualified for surveillance based on their risk factors.Why was this?Well firstly, many of these people did not know they were at risk. And that’s where GPs fit in.In the study the most common risk factors for liver cancer were found to be hepatitis C infection (41%), alcohol-related liver disease (39%), hepatitis B infection (22%) and non-alcoholic fatty liver disease (14%). Many had more than one risk factor.Most telling was the finding that, even though the vast majority of patients (83%) had cirrhosis when they were diagnosed with hepatocellular carcinoma, for one third of them that was the first they knew of it.The study authors suggest clinicians need to be alert for risk factors for chronic liver disease such as excess alcohol use, chronic HCV and HBV infections and even non-alcoholic liver disease in certain groups. In these people, checking for cirrhosis is likely to be worthwhile.“An aspartate transaminase to platelet ratio index (APRI) value greater than 1.0 predicts cirrhosis with 76% sensitivity and 72% specificity, and the test is simple to undertake,” the researchers said.The other major barrier to the earlier detection of liver cancer identified in the study was the poor adherence to surveillance among those people identified as being at high risk. Researchers found patients with alcohol-related liver disease or decompensated liver disease were the least likely to get regular monitoring.A surveillance program for this particular cancer involves a 6-monthly liver ultrasound and serum alpha-fetoprotein assessment.The study authors are advocating a national hepatocellular cancer surveillance program for those who are at high risk of developing the disease, which would include all patients with cirrhosis, Asian men over 40, women over 50, Africans over 20 years of age, and patients with a family history of [hepatocellular carcinoma] without cirrhosis but with chronic HBV infections.A national program to screen for hepatocellular carcinoma amongst this particular group would be worthwhile, the researchers said, as the incidence of the cancer is high, the screening is non-invasive and inexpensive and, perhaps most importantly early detection has been shown to improve survival.However, until such a national program is developed, researchers are encouraging GPs to ensure that their at-risk patients are enrolled in a surveillance program in order to hopefully improve their health outcomes. Reference:Hong TP, Gow PJ, Fink M, Dev A, Roberts SK, Nicoll A, et al. Surveillance improves survival of patients with hepatocellular carcinoma: a prospective population-based study. Med J Aust [Internet]. 2018 Sep 24; 209(8): 1-7. Available from: https://www.mja.com.au/journal/2018/209/8/surveillance-improves-survival-patients-hepatocellular-carcinoma-prospective doi: 10.5694/mja18.00373

Expert/s: Dr Linda Calabresi

Discover

Healthed

CPD platform

Upcoming Healthed Webcast

New Brain Health Guidelines – What GPs Can Do

Tuesday 4th August, 7pm - 9pm AEST

Speaker

Scientia Prof Kaarin Anstey

Psychologist; Director, UNSW Ageing Futures Institute; ARC Laureate Fellow; Senior Principal Research Scientist, NeuRA

Scientia Prof Kaarin Anstey translates the WHO's updated 2026 dementia risk-reduction guidelines changes into concrete actions for opportunistic risk assessment and targeted advice in everyday general practice.

Register for webcast