Three questions to ask about calls to widen breast cancer screening

Three questions to ask about calls to widen breast cancer screening

August 30, 2017 4.29pm AEST

It’s easy to assume the earlier women are screened for breast cancer, the better. And a recent US study, which found screening women with mammography from the age of 40 saved the most lives, generated headlines around the world.

We need to be cautious, however, when interpreting studies like this and the media reports they create. That’s because with screening, its benefits – less risk of dying of cancer – are clear, and are easily exaggerated. But the potential harms of screening are harder to recognise and readily overlooked.


Read more: When talking about cancer screening, survival rates mislead


The recent US study compared an intensive screening strategy (strategy a) of annual mammograms for women starting at age 40 all the way to 84 years of age, with two less-intensive screening strategies.

Strategy b) offered annual mammograms from 45-54 years, then every two years until age 79. Strategy c) offered mammograms every two years from 50-74, the same screening policy we have in Australia.

Strategy a) has become known in the media as “screening from age 40” but it is really screening more often, and until an older age (when breast cancer is more common), as well as starting earlier. It prevented the most deaths, according to the modelling. But at what “price”?

By screening longer and more often, the more intensive strategy a) required women to have three times as many mammograms. It caused three times as many false positives or false alarms (when women didn’t end up having a breast cancer despite an abnormal mammogram), as the least intensive strategy c). In a major omission, the authors did not address potential harms of overdiagnosis and overtreatment (more below).

So what questions do you need to consider when reading reports about studies like this?

1. Who’s giving the advice?

Three specialist radiologists and a medical physicist, all employed by departments of imaging or radiology, authored this study. Screening mammography in the US is big business. The total annual cost of screening mammography there was estimated to be US$7.8 billion in 2010.

So, why should we be concerned? Because previous research has found financial conflicts of interest increase the risk of bias, and lead committees towards recommendations that are more favourable towards mammography screening.

Non-financial conflicts of interest can also affect recommendations. Guideline panels with radiologist members are more likely to recommend screening for women from age 40 years than recommendations issued by panels without radiologist members.

2. What aren’t they telling me?

A mammogram may seem harmless, but it can cause long-term problems that many people would never think of. An important one is finding harmless, idle or dormant cancers, a major factor in overdiagnosis.

Overdiagnosis is common not just in breast cancer, but in screening for prostate, thyroid and lung cancer. How common? When a UK panel carried out an independent assessment of the benefit and harms of screening mammography, it found the chance of a woman being overdiagnosed by screening was three times greater than the chance screening would save her from dying of breast cancer.

Even the chief medical officer of the American Cancer Society urges accepting overdiagnosis and overtreatment as harms of breast cancer screening.

Yet the authors of this latest US study didn’t consider overdiagnosis and overtreatment when concluding annual screening from age 40-84 years is best.


Read more: Five commonly over-diagnosed conditions and what we can do about them


Overdiagnosis is important because it isn’t a good idea to have cancer treatments (surgery, radiotherapy and antihormone pills) for a harmless cancer (overtreatment).

Each of these treatments comes with risks of side-effects, as UK woman Elizabeth Dawson describes in her blog. Two and a half years after starting treatment she was still wondering whether the cancer that was found by screening was overdiagnosed or not, and whether she needed all, or even any, of the treatments she’d had. She hates that the drugs she’s still taking to prevent a recurrence make her bones frailer. She’s been told not to go out when it’s icy because she might fall and fracture, but she hates the idea of being housebound at 56 when she feels so well and active.

The US study did include false positives in its calculations, but may not have recognised fully the impact. Being recalled for an abnormal mammography is scary. But what is less well known is that even three years after being declared free of suspected cancer, women with false positives consistently report worse psychosocial outcomes; they report feeling more dejected and more anxious, and report worse sleep and negative impacts on sexuality than women with normal mammograms.

Mammography uses radiation, so there’s a small chance the screening process itself may induce cancers over time. But starting screening from 50 and screening every two years is estimated to reduce the number of induced cancers five-fold compared to annual screening from age 40.

3. What’s the health-care context?

The US has a very different health-care context to Australia. In the US, mammography screening costs are paid by many different organisations. So debates over recommendations may have implications for whether health plan organisations cover services or not.

In contrast, as part of our national cancer screening programs, BreastScreen Australia provides mammograms in a national, publicly funded program that offers high-quality screening to eligible women, for free.

The health-care context is also relevant when we consider an individual woman’s risk of breast cancer. This debate (about when to start screening and how often) is relevant to women at average risk of breast cancer. For women with a strong family history, or who know they carry a breast cancer genetic mutation, screening more intensively offers greater benefits.

So which strategy really is best?

The ultimate aim of screening is to reduce deaths from breast cancer. Yet, whichever screening strategy we use, screening is not 100% effective.

It probably reduces the risk of dying from breast cancer by about 20%, at most by 40%, and perhaps as little as only a few percent.

So we must balance this limited benefit with a clearer picture of harms like overdiagnosis and overtreatment to avoid tipping over into net harm.

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Harvard study strengthens link between breast cancer risk and light exposure at night

Harvard study strengthens link between breast cancer risk and light exposure at night

August 18, 2017 7.36pm SAST Updated August 21, 2017 6.16pm SAST

A new study from Harvard has found greater risk of breast cancer in women who live in neighborhoods that have higher levels of outdoor light during the night.

The findings are based on the Nurses’ Health Study (NHS), which has for decades been advancing our understanding of risks to women’s health.

For this study, epidemiologist Peter James and colleagues followed nurses in the NHS for breast cancer occurrence from 1989 to 2013. The home of each of 109,672 nurses was geocoded, and the average light level in the immediate neighborhood at night was estimated from satellite images taken by the Defense Meteorological Satellite Program. These estimates were updated over the 15-year follow-up period. By 2013, a total of 3,549 new cases of breast cancer had been diagnosed, about what’s expected among this number of women.

The study found a direct relationship between a woman’s neighborhood nighttime light level before diagnosis and her later risk of developing breast cancer: The higher the light level, the higher the risk. These findings held even when taking into account many other factors that may also affect risk such as age, number of children, weight, use of hormone medications and a long list of additional potential confounders.

Of importance if confirmed in more studies, the relationship was strongest in young women diagnosed before menopause. James also conducted many further subgroup analyses after the primary objective of the study had been verified; these subgroup findings may or not be seen in future studies. Two that stood out are that the association was confined to current and former smokers, and nurses with a history of night work.

The study is significant because it adds a strong piece of evidence to the growing body of studies supporting the idea that excessive electric light exposure at night increases a woman’s risk of breast cancer.

Why was the study done?

The idea that electric light at night (LAN) might explain a portion of the breast cancer pandemic dates back to 1987. It was pretty far-fetched at the time because light doesn’t seem toxic in any way that could cause cancer. It can’t break chemical bonds and damage DNA, and it’s not a hormone like estrogen, which, in excess, can cause changes in the breast that can lead to cancer. Light is, by definition, the visible part of the electromagnetic spectrum, and so it does not include X-rays or even ultraviolet radiation, which can burn skin.

Light is an exposure that challenges the conventional definition of a toxic substance. If a little asbestos is bad for you, more is certainly worse. The same holds for ionizing radiation (like X-rays), dioxin and lead.

The difference is that the effects of exposure to light on human health depend crucially on timing. Over millions of years, we have evolved with a daily cycle of about 12 hours of bright light (the sun) and about 12 hours of dark. So during the day, our body expects light, whereas during the night it expects dark. There is a deep biology to this, and electric light is throwing it out of kilter.

One perplexing possible consequence of this light exposure is an increased risk of breast cancer in women. Researchers, including me, have been exploring this possible link in part because breast cancer has no single known major cause. This is unlike many of the other common cancers such as lung, liver, cervix and stomach, for which a major cause has been identified for each; these major causes are, respectively, smoking, hepatitis viruses, human papilloma virus and the bacterium Helicobacter pylori.

Satellites

But how could the nighttime light level outside a woman’s home in her neighborhood affect her risk of breast cancer?

The rationale for studying the outside light level is the assumption that communities that shine brightly to a satellite at night are composed of people who in general are bathed in LAN: They have greater exposure in their home, outside on the street, and for evening entertainment in the city. So, the satellite data are thought to be a surrogate, or a proxy, for this actual LAN exposure to each woman, particularly in the evening before sleep.

Blue light is more likely to delay the body’s transition to nighttime physiology and the natural rise in melatonin, which has been shown in rats to have a strong anti-cancer effect. Shutterstock

Too much evening light can delay the normal transition to nighttime physiology that should begin at dusk. An important part of this transition is a substantial rise in the hormone melatonin in the blood. Melatonin has been shown to have strong anti-cancer effects in lab rats. The shorter the wavelength of the light – that is, light that has more blue relative to other colors – the greater impact on lowering melatonin and delaying transition to nighttime physiology.

My colleagues and I did a similar analysis using satellite data in the state of Connecticut. We also found a stronger effect in younger women, as did another study from 2014 conducted among teachers in California. The studies from Harvard and from California are superior to ours because they both had individual-level data on many more potential confounders than just age, which we did not. Yet all three studies do point in the same direction.

Two concerns

The estimate of elevated risk of breast cancer in the new Harvard study is modest, at only 14 percent for the most highly lit neighborhoods, compared to the least.

If true, it would still account for many cases. However, there are two concerns about this estimate’s validity, which are actually opposites of each other.

On the one hand, the apparently elevated risk may be due to other factors that go along with more highly lit neighborhoods, and the LAN actually has no impact. This is called confounding. The Harvard study is one of the best-equipped studies ever conducted of women’s health to deal with this possibility because it has individual-level data on so many characteristics recorded for each subject, such as age, weight, smoking, body mass index, income and on and on.

The researchers included these factors into their statistical models, and it did not change their estimate of the effect for LAN on breast cancer risk. However, the information on these other factors is not perfect, and there may still have been some of what is called “residual confounding.”

On the other side, if evening and late-night electric light exposure actually does increase a woman’s risk of breast cancer, then this estimate of 14 percent probably understates the true effect, and maybe by a lot.

The reason is that the estimate of LAN exposure from the satellite images is only a surrogate for the light that would actually matter, which is each woman’s individual exposure to light in her eyes during the evening and night whether she is home or out and about.

Another limitation of epidemiological studies, like the Harvard one, is an effect known as exposure misclassification, which tends to underestimate the level of health risk when using a surrogate to measure the real exposure.

In this case, the satellite images act as a surrogate for actual nighttime light exposure to each woman. The poorer the surrogate (satellite images) is correlated with the actual exposure (light to eyes of women at night), the lower the estimate of risk will be from an epidemiological study that uses that surrogate. And it is unclear how accurate a stand-in these satellite images are for actual light exposure to each individual woman.

A modern marvel turned urban blight

The Harvard study comes closely on the heels of a very public warning from the American Medical Association on potential health problems from “white” LED street lights. It is important to note that the nighttime light levels used in this new study were recorded before any widespread use of “white” LED street lighting.

If the results from Harvard are real, and too much light at night from any and all sources does increase a woman’s risk of breast cancer, then retrofitting street lighting all across America should be done in a way that does not further contribute to the problem. It would be best to select luminaires that are as dim as possible, and weak in the short wavelengths (e.g., blue), yet still consistent with accomplishing their intended purpose.

Electric light is one of the signature inventions of an inventive species. But its overuse has caused an obliteration of night in much of the modern world. The loss of night has consequences for all forms of life, including us. And the mounting evidence for a connection to breast cancer is alarming.

This article was updated on August 21 to indicate that the association between light level and risk of breast cancer was found in current and former smokers and nurses with a history of night work

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Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder

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What’s happening in our bodies as we age?

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What’s happening in our bodies as we age?

January 23, 2017 6.10am AEDT

As we reach adulthood, we notice changes in our bodies at every stage of ageing. We might find we need glasses when we hit our thirties, we can’t keep weight off as easily into our forties, we mightn’t feel as strong playing sport with the kids in our fifties, and we can’t hear a conversation across a crowded dinner table in our sixties.

All of these occur because the cells and processes in our bodies have existed for longer and longer periods of time. There are many theories as to why our body ages, but two main explanations are that the DNA within our genes determine how long we will live; the other is that over time, our body and DNA are damaged until they can no longer function as before, often referred to as “wear and tear”.

The ageing brain

As we age, the volume of the brain declines. There are many explanations for this, including cell death, in which the brain cells’ structure declines over time.

Although the precise reasons for the decline in brain volume remain unclear, some research indicates it may be due to hormone levels, and wear and tear.

Some also believe that the volume of blood reaching the brain decreases due to conditions within the blood vessels and associated systems. However, this doesn’t have a great impact on a person’s ability to remember, as the brain has the ability to compensate for these changes.

You may have heard of neuroplasticity. This is the term used to explain how the brain can rewire itself by creating new pathways within the nerve cells to compensate for damage to an area. These new pathways are created when new experiences occur. So doing crosswords all of your life won’t increase the number of pathways, but if you add a new activity that you need to learn and practise, then new pathways can form.

While the risk of dementia increases with age due to many of the hundreds of causes being more present as we age, it is not a normal part of the ageing process. It is a result of damage to the brain. The reason why it is more likely to occur as we age is simply because the longer we live, the longer we expose ourselves to possible damage to the body through disease or injury, which are the main causes of dementia.

Doing crosswords in old age will only improve brain function if it’s a new activity. from http://www.shutterstock.com

Alzheimer’s Disease, the most common cause of dementia in Australia, occurs when there is plaque build-up in the brain. This is as a result of protein build-up over time that inevitably causes tangles in the neurons (brain cells).

Changes in muscle strength

As we age, there’s a decrease in the amount and strength of muscle tissue, due mostly to the influence of decreasing hormones. To make up for the muscle mass lost during each day of strict bed rest, older people may need to exercise for up to two weeks.

However, additional decreases in muscle occur due to a decrease in activity, not just as part of the normal ageing process.

Decrease in bone density

As the body ages it absorbs less calcium from food, a vital mineral for bone strength. At the same time, changes in hormone levels affect the density of the bones.

Ageing people also often spend less time in the sun, thereby reducing their Vitamin D intake. This in turn reduces calcium absorption.

It is important people continue to exercise as they age. Exercise will not only help to maintain muscle strength, but also assist in combatting the decrease in bone density that occurs as the body ages, thereby reducing the risk of falls and hip fractures.

Exercise will help to combat common fractures in old age. from http://www.shutterstock.com

Changes to our senses

Changes that occur directly as a result of ageing include those to vision, hearing, taste and smell. Impacts of the changes in vision are usually the first things noticed, making a person feel that they are ageing.

Changes to the eye that occur as part of the ageing process include stiffening and colouring of the lens, a reduction in the number of nerve cells, and a decrease in fluid in the eye. These lead to difficulty in focusing on close objects, seeing in low light becomes more difficult, and the ability to adapt to changes in light decline.

Some people appear clumsy, as their ability to judge the distance between objects – a cup and table, for example, or the height of stairs – becomes a problem. Many people do not realise their spills and trips are occurring as a result of shifts in their vision, known as depth perception changes. Eyes can also become drier, making them feel irritated. This can be treated with lubricating drops.

Changes in hearing include changes in registering high-pitched sounds, and words may become difficult to understand. Speaking more loudly to someone in this circumstance does not help, as the pitch is the problem, not the volume. Instead speaking slightly slower and concentrating on complete words can be helpful.

Taste and smell often decrease as part of the normal ageing process, as the cells responsible decrease in number and the ability to regenerate worn out cells decreases with age. The results make food less tasty and people less likely to eat. In addition, people’s taste can change altogether, so people who loved chocolate as a young person may prefer chilli as they age.

Overall there are many changes to the body as part of the normal ageing process as well as many that occur as a result of lifestyle factors. We are not all fated to age in a negative spiral. Many lifestyle choices made earlier in life can assist us in the future. With proactive decisions and community understanding, we can look forward to adapting to a positive ageing process

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HRT reduces risk of getting Diabetes

 Estrogen in women is a gift that just keeps giving. I do not need to tell you that diabetes is in epidemic proportion in Australia as well.
Endocr Rev. 2017 Jun 1;38(3):173-188. doi: 10.1210/er.2016-1146.

Menopausal Hormone Therapy and Type 2 Diabetes Prevention: Evidence, Mechanisms, and Clinical Implications.

Mauvais-Jarvis F1, Manson JE2,3, Stevenson JC4, Fonseca VA1.

Author information

1
Department of Medicine, Division of Endocrinology and Metabolism, School of Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana 70112.
2
Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115.
3
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115.
4
National Heart and Lung Institute, Imperial College London, Royal Brompton Hospital, London SW3 6NP, United Kingdom.

Abstract

Type 2 diabetes has reached epidemic proportions in the United States. Large, randomized controlled trials suggest that menopausal hormone therapy (MHT) delays the onset of type 2 diabetes in women. However, the mechanisms and clinical implications of this association are still a matter of controversy. This review provides an up-to-date analysis and integration of epidemiological, clinical, and basic studies, and proposes a mechanistic explanation for the effect of menopause and MHT on type 2 diabetes development and prevention. We discuss the beneficial effects of endogenous estradiol with respect to insulin secretion, insulin sensitivity, and glucose effectiveness; we also discuss energy expenditure and adipose distribution, both of which are affected by menopause and improved by MHT, which thereby decreases the incidence of type 2 diabetes. We reconcile differences among studies that investigated the effect of menopause and MHT formulations on type 2 diabetes. We argue that discrepancies arise from physiological differences in methods used to assess glucose homeostasis, ranging from clinical indices of insulin sensitivity to steady-state methods to assess insulin action. We also discuss the influence of the route of estrogen administration and the addition of progestogens. We conclude that, although MHT is neither approved nor appropriate for the prevention of type 2 diabetes due to its complex balance of risks and benefits, it should not be withheld from women with increased risk of type 2 diabetes who seek treatment for menopausal symptoms.

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Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis.

One of the many benefits of estrogen to women is that it reduces the risk of getting bowel cancer by about 30%.
Am J Med. 1999 May;106(5):574-82.

Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis.

Grodstein F1, Newcomb PA, Stampfer MJ.

Author information

1
Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

PURPOSE:

Colorectal cancer is the fourth most common cancer and the second leading cause of cancer death in the United States. Accumulating evidence indicates that postmenopausal hormone therapy may reduce the risk of colorectal cancer in women.

METHODS:

Through MEDLINE computer searches (January 1966 to September 1998) and a review of references, we identified English-language articles with quantitative data on the relation of postmenopausal hormone therapy to colorectal cancer. We reviewed the studies and made summary estimates of relative risks (RR) by weighting the results of each study in proportion to its precision, using a general variance-based, fixed-effects model.

RESULTS:

In our meta-analysis of 18 epidemiologic studies of postmenopausal hormone therapy and colorectal cancer, we found a 20% reduction [RR = 0.80, 95% confidence interval (CI), 0.74 to 0.86] in risk of colon cancer and a 19% decrease (RR = 0.81, 95% CI, 0.72 to 0.92) in the risk of rectal cancer for postmenopausal women who had ever taken hormone therapy compared with women who never used hormones. Much of the apparent reduction in colorectal cancer was limited to current hormone users (RR = 0.66, 95% CI, 0.59 to 0.74).

CONCLUSION:

Observational studies suggest a reduced risk of colorectal cancer among women taking postmenopausal hormones. There is biologic evidence to support this association

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Verbal memory and menopause

 

  • Menopausal hormone therapy should not be prescribed for the sole purpose of improving cognition.
  • Midlife women should be advised that memory complaints are common during the menopausal transition and memory problems appear to return to baseline during the postmenopausal period.
  • Midlife women should be advised that dementia is rare at this age and referral to a neurologist should only be recommended if memory problems significantly disrupt daily function.
  • Women should be advised to practice healthy sleep habits and engage in cardiovascular exercise to improve memory.

Abstract

Midlife women frequently report memory problems during the menopausal transition. Recent studies validate those complaints by showing significant correlations between memory complaints and performance on validated memory tasks. Longitudinal studies demonstrate modest declines in verbal memory during the menopausal transition and a likely rebound during the postmenopausal stage. Clinical studies that examine changes in memory following hormonal withdrawal and add-back hormone therapy (HT) demonstrate that estradiol plays a critical role in memory. Although memory changes are frequently attributed to menopausal symptoms, studies show that the memory problems occur during the transition even after controlling for menopausal symptoms. It is well established that self-reported vasomotor symptoms (VMS) are unrelated to objective memory performance. However, emerging evidence suggests that objectively measured VMS significantly correlate with memory performance, brain activity during rest, and white matter hyperintensities. This evidence raises important questions about whether VMS and VMS treatments might affect memory during the menopausal transition. Unfortunately, there are no clinical trials to inform our understanding of how HT affects both memory and objectively measured VMS in women in whom HT is indicated for treatment of moderate to severe VMS. In clinical practice, it is helpful to normalize memory complaints, to note that evidence suggests that memory problems are temporary, and to counsel women with significant VMS that memory might improve with treatment.

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