TIME Health Care

The Global Problem With Overdiagnosis and Overtreatment

Equipment in a doctors office
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Two new studies make a case against too much medicine

It’s a public health conundrum: Current screening guidelines lead to an overdiagnosis of diseases like cancer, which results in overtreatment for ailments that might never seriously impact a person’s health.

We’ve heard the overdiagnosis argument in the U.S. before, especially surrounding breast cancer; in 2009, the United States Preventive Services Task Force recommended against annual breast cancer screening starting at age 40 and instead advised women get mammograms starting at age 50.

Now, two new studies published Monday in the medical journal The BMJ highlight the global problem with overtreatment in both breast cancer and heart disease.

In a new analysis report, a team of researchers conclude that hypertension is being overtreated in people with mild cases of the disease. The researchers write that about 40% of adults worldwide have hypertension, and more than half of those people have mild cases of the disease (meaning they’re low risk and don’t have existing cardiovascular disease). But more than half of people with mild hypertension are being treated with blood pressure-lowering drugs–even though the research on whether this reduces cardiovascular-related disease and death is not established. The researchers argue that the practice is unnecessary and costs $32 billion each year in the U.S. alone.

Instead of recommending lifestyle modifications proven to work, like cutting back on alcohol and exercising more, many doctors opt for drugs because they want to do something right away without having to rely on the often-unhealthy environment beyond their office walls, says study author Vikas Saini, president of the Lown Institute. “[Doctors] need the confidence that we have systems in place that encourage a healthy lifestyle,” he says.

“Most doctors feel a little under siege; they see blood pressure rising and weight going up and they want to do something, but they know they have huge headwinds,” says Saini. “Prescribing a pill is the path of least resistance, but it’s a lot of money.” According to the researchers, the clinical treatment for mild hypertension needs to shift away from a heavy emphasis on drugs.

The second study adds to a growing body of research that supports later initiation into breast cancer screenings. The study authors argue that screening older women over age 70 for breast cancer doesn’t offer enough benefit to be worth it.

In 1998, the upper age limit for breast cancer screening in the Netherlands was extended from age 69 to age 75. The researchers wanted to see if the change actually resulted in fewer late-stage cancers among 70 to 75 year olds, so they looked at about 25,500 new breast cancer patients in a Dutch cancer registry between 1995 to 2011. What they found was that early-stage breast cancer in women 70 to 75 rose sharply after the screening recommendations changed, and while the number of new cases of advanced-stage breast cancer fell significantly, the absolute decrease of those cases was small. For every advanced-stage cancer detected by screening among women over age 70, about 20 “extra” cases were also diagnosed, the researchers concluded.

“Those numbers need to be told to women,” says study author Gerrit Jan Liefers, a surgical oncologist at Leiden University Medical Centre. “We are not voting against screening, but you should individualize your screening to women. To use it as a population-wide tool is wrong. You end up screening women who would never be affected by the cancer.”

The message both studies send to doctors is that physicians need to consider each patient individually and inform men and women of their options.

The two studies are part of the 2014 Preventing Overdiagnosis Conference in Oxford. The BMJ has also launched a “Too Much Medicine” campaign you can follow here.

TIME Cancer

No, Wearing a Bra Will Not Give You Breast Cancer, Study Shows

Ladies, that swath of fabric snapped around your rib cage is not a death trap. A new study published in Cancer Epidemiology, Biomarkers & Prevention found that among 1,500 women, there was no association between bra wearing and breast-cancer risk.

The study authors asked women with and without breast cancer nearly every conceivable question about their lingerie — cup size, how many hours they wore their bras per day, how many of their bras contained underwire, how old they were when they started wearing a bra — and found that none of the factors were associated with cancer.

Why would anyone think the intimates might be connected to tumors in the first place? For that we can thank the very first study on the subject done in 1991 (which makes this just the second). That analysis found that women who didn’t wear bras had a lower risk of breast cancer. The authors were quick to attribute that to more obvious, well-established risk factors like obesity. Thinner women with smaller breasts, after all, are those most likely to go braless.

But somehow the myth spread. On its website, the American Cancer Society (ACS) traces it back to an obscure book called Dressed to Kill. ACS wholly dismisses the book, stating that there are no scientifically valid studies demonstrating that wearing a bra causes any kind of breast cancer. And in the new paper, study author Lu Chen dismisses the false notion that bras impede lymph circulation and drainage, trapping toxins in your breasts that can trigger tumors.

Still, Chen says, undergarments may be an easy target because some people grapple with explaining why breast-cancer rates are higher in the U.S. than in developing countries. “They think one reason breast cancer is more common in developed countries is due to the differences in bra-wearing patterns,” she says — even though far more likely risk factors, like a lack of physical activity and being overweight, not to mention exposure to carcinogens, are more likely to blame.

The rumors clearly aren’t bothering the vast majority of bra wearers. Of the 1,500 women Chen studied, more than 75% wore a bra for at least eight hours per day. And only one woman — who had to be excluded from the analysis because she had no peers — had never worn a bra.

TIME Cancer

Double Mastectomies Are on the Rise, but They Don’t Result in Fewer Deaths

More women have opted for double mastectomies than in the past but new research questions their effectiveness

New research shows that double mastectomies are increasingly used to treat cancer in a single breast, and it doesn’t always result in fewer deaths.

In a new paper published in the journal JAMA, a team of researchers looked at data from a cancer registry in California and found that double mastectomies for early-stage breast cancer increased significantly from 1998 to 2011. When the researchers compared the mortality rates of 189,734 patients who underwent either double/bilateral mastectomies, unilateral mastectomies or breast conserving surgery plus radiation, they found that double mastectomies were not associated with a lower risk of death compared to surgery plus radiation. Unilateral mastectomy had the highest mortality rate.

The researchers also found that double mastectomies increased the most among women who were under age 40 when they were diagnosed. Though the researchers can’t confirm, they suspect that the numbers may be due to the women’s relatively high likelihood of carrying genetic mutations like BRCA1 and BRCA2, as well as the greater likelihood that they have younger children and therefore want to extend their lives for as long as possible. The researchers call this “an emotional rather than evidence-based decision.”

“The increase in bilateral mastectomy use despite the absence of supporting evidence has puzzled clinicians and health policy makers,” the study authors write. “Although fear of cancer recurrence may prompt the decision for bilateral mastectomy, such fear usually exceeds the estimated risk.”

Given the rising numbers and growing concern about over-treatment, the researchers say physicians should really stop and consider how to respond to a patient’s request for double mastectomy, given that it’s an incredibly invasive procedure.

TIME Cancer

Angelina Jolie’s Surgery May Have Doubled Genetic Testing Rates at One Clinic

Actress Angelina Jolie leaves Lancaster House after attending the G8 Foreign Minsters' conference on April 11, 2013 in London.
Actress Angelina Jolie leaves Lancaster House after attending the G8 Foreign Minsters' conference on April 11, 2013 in London. Oli Scarff—Getty Images

When Jolie announced her surgery to prevent cancer due to a genetic predisposition, she encouraged other women to get checked too, study says

In 2013, actress Angelina Jolie announced that she had undergone a preventive double mastectomy because she was a BRCA1 gene mutation carrier, which puts her at very high risk for breast and ovarian cancer. Jolie also had a family history of these cancers.

Soon after, TIME wrote a cover story–“The Angelina Effect“–looking at what impact her decision could have on women who carry the dangerous BRCA1 and BRCA2 genes and therefore may be at risk for breast and ovarian cancers. Now, a new study being presented at the 2014 Breast Cancer Symposium shows that the Angelina effect is indeed real.

The study authors did a retrospective review of records from a cancer center in Canada and discovered that in the six months following Jolie’s highly publicized surgeries, testing and counseling around genetic testing nearly doubled. The researchers compared the number of counseling sessions and testings in the six months before and after the announcement and found that the number of women referred to genetic counselors by physicians increased 90%, and the number of women who qualified for genetic testing increased 105%. The researchers say this led to a two-fold increase in identified BRCA1 and BRCA2 mutation carriers.

“After Angelina Jolie’s story was released, physicians were probably more proactive and referred more patients; at the same time, patients were more likely to request and seek genetic counseling,” said study author Dr. Jacques Raphael, a clinical fellow at Sunnybrook Odette Cancer Centre in Toronto, Canada, in a statement.

Estimates vary, but BRCA1 and BRCA2 gene mutations are said to increase a woman’s risk for breast cancer by well over 50%. Only about two to four of every 1,000 women carry the gene mutation (men can have it too) and it is more common among women with histories of ovarian and breast cancer in their families, as well as people of Ashkenazi Jewish descent.

Jolie isn’t the only celebrity with a known health “effect.” In 2000, TV personality Katie Couric underwent a colonoscopy on live television, which prompted a surge of 20% more colonoscopies across the U.S. (dubbed “The Katie Couric Effect.”) This recent study, although small, suggests that Jolie’s announcement and the resulting media coverage encouraged more women to opt into genetic testing–and that prominent figures like Jolie can impact how women approach their health in real, measurable ways.

TIME Cancer

How Aspirin Can Prevent Breast Cancer

Among overweight and obese women, the painkiller could help to prevent tumors from recurring

Doctors are beginning to learn that body weight could have a role in determining a woman’s risk for breast cancer as well as her ability to survive it — and according to new research, a surprisingly simple over-the-counter drug could help with prevention.

“Obesity by itself is the worst prognostic factor,” says Linda deGraffenried, an associate professor of nutritional sciences at the University of Texas at Austin. “Obese women do worse on hormone therapy, chemotherapy and radiation therapy. We used to think that the mechanism involved the fact that they had [other] conditions such as diabetes or heart disease, but now we are starting to appreciate that the obese patient has a different biological disease.”

And that understanding led deGraffenried and her colleagues to the surprising finding that among women with a higher body mass index (BMI), nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin can actually lower their risk of breast cancer.

In a report published Friday in the journal Cancer Research, deGraffenried found that obese and overweight breast cancer patients who used NSAIDs regularly lowered their risk of getting additional tumors by 52% compared with women who didn’t take the pills. “I’ve been doing cancer research for 20 years, and there has been nothing that was able to give that kind of benefit,” says deGraffenried. “So yes, I was extremely surprised that by just reducing inflammation you could get that significant a benefit.”

What’s happening in obese patients, she says, is that their larger volume of fat tissue promotes production of aromatase, an enzyme involved in producing a form of estrogen called estradiol. Because estrogen is part of the fuel that drives breast-cancer growth, having elevated levels of aromatase is associated with higher rates of breast cancer. The mechanism also explains why drugs that inhibit the enzyme aren’t as effective in obese or overweight women. The fat tissue also promotes release of other factors that are important for tumor survival, creating a feedback loop that keeps the cancer growing in heavier women.

But NSAIDs, which block another enzyme that stimulates aromatase production, could counter this effect. And that’s what deGraffenried and her colleagues found. Among a group of 440 women diagnosed with breast-cancer tumors containing estrogen receptors, those with a BMI greater than 30 and who used NSAIDs regularly had a much lower rate of breast cancer.

Whether women with other types of breast cancer, including tumors without estrogen receptors, can benefit from NSAIDs isn’t clear, but the team is studying those populations as well.

As for whether an aspirin a day should become part of women’s breast-cancer prevention efforts, deGraffenried notes that many already take low-dose aspirin — the same does that most of the women in the study took — to protect against heart disease and colon cancer. “If you are not already on an NSAID or if there is no contraindication for an NSAID, there is reason to consider asking your doctor about it,” she says.

MORE: Osteoporosis Drugs Do Not Prevent Breast Cancer After All

MORE: Breast-Cancer Drug Has a Surprising New Application, Study Finds

TIME Breast Cancer

Osteoporosis Drugs Do Not Prevent Breast Cancer After All

Some studies had hinted that the bone-building treatments may also have an added benefit in fighting tumors, but the latest study doesn’t support that connection

In recent years, several large studies involving tens of thousands of women found a potentially useful connection between bisphosphonates, the popular bone drugs, and a lower risk of breast cancer. But new research published Monday in JAMA Internal Medicine challenges that long-held belief.

In previous observational studies, women who reported taking medications like alendronate (Fosamax) or zoledronic acid (Reclast) to treat osteoporosis also seemed to have lower rates of breast cancer compared to women who didn’t take the medications. There was biological evidence to support the association as well – bisphosphonates were also correlated with lower rates of cell death and hampered cancer cell activity.

But Trisha Hue, an epidemiologist at the University of California, San Francisco, and her colleagues, wondered if the connection could truly be attributed to the osteoporosis medications, or whether there was something else about the women taking these drugs that could explain the cancer trend.

MORE: Combining Bone-Building Drugs Key to Making Bones Stronger

Indeed, when they focused their attention on two studies that randomly assigned women to either a bisphosphonate or placebo, and followed them for up to four years, they found no difference between the women taking the drug and those who did not when it came to their breast cancer rates.

So why the strong connection in previous studies? Hue points out that those analyses, which were not randomized controlled trials, but rather observational studies, could not account for the fact that the drug-taking group may have been biased in some way. And in fact that’s likely what occurred – women who are prescribed bisphosphonates have low bone mineral density, and they also have low levels of the hormone estrogen, which is known to fuel tumor growth. So the earlier studies were not finding a correlation between bisphosphonate use and a lower risk of breast cancer, but instead were picking up the fact that bisphosphonate users were likely to have lower rates of breast cancer to begin with.

MORE: How Often Do Women Really Need Bone Density Tests?

It’s not the first time the benefits of the bone drugs have been called into question. In 2011, some studies found that the therapies could increase the risk of rare bone fractures in the strong bones such as the thigh.

While some doctors and patients may have turned to the bone-building drugs to potentially avoid getting cancer, Hue says “our take-home message is that if you are already on bisphosphonates for prevention of fractures, it’s very effective for preventing fractures. But they shouldn’t be taken specifically for the primary prevention of breast cancer.”

TIME Breast Cancer

Promising Cancer Drug Fails to Slow Breast Cancer

NEXAVAR
Nexavar Bayer Pharmaceuticals Corporation

Researchers had hoped to add breast cancer to the list of cancers for which the drug is already approved

A Phase 3 trial of cancer drug Nexavar in patients with advanced breast cancer failed to delay progression of the disease, according to the drug’s makers, Bayer and Onyx Pharmaceuticals, Inc., an Amgen subsidiary.

The study, called Reslience, evaluated Nexavar in combination with capecitabine, an oral chemotherapeutic agent, in patients with HER2-negative breast cancer.

The drug is approved to treat certain types of liver, kidney and thyroid cancer and works by targeting signalling pathways that tumor cells use to survive. Researchers hoped that Nexavar would have the same tumor-stalling effect on breast growths.

“We are disappointed that the trial did not show an improvement in progression-free survival in patients with advanced breast cancer,” Dr. Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development, said in a statement. “While the primary endpoint of this trial was not met, the trial results do not affect the currently approved indications for Nexavar. We would like to thank the patients and the study investigators for their contributions and participation in this study.”

Data from the study will be presented at an upcoming scientific conference.

TIME Breast Cancer

Removing Both Breasts May Not Improve Survival From Breast Cancer

The latest study adds support to the data suggesting that in some cases, less may be more in treating breast cancer

Researchers at the University of Minnesota confirm that when it comes to treating some forms of breast cancer, drastic surgery to remove breast tissue may not help in improving survival from the disease.

Reporting in the Journal of the National Cancer Institute, the scientists describe a model for calculating life expectancy based on recent rates of recurrent cancers among women with stage 1 or stage 2 disease. Although previous studies found that among women diagnosed with breast cancer in one breast, removing the other breast can lower risk of breast cancer in that breast by up to 90%, few studies have documented whether that also translated into greater survival of breast cancer, which can recur in other organs.

According to the researchers’ model, the overall difference in survival at 20 years after diagnosis for both women who had their opposing, unaffected breast removed and those who did not, was less than 1%.

The data confirm recent findings from a study of women with metastatic disease, which also showed that women who received additional surgery to remove lymph nodes and their breasts did not survive any longer than those who were treated with chemotherapy only. As TIME wrote about that study,

Researchers from Tata Memorial Hospital in Mumbai, India, recruited 305 women between 2005 and 2013, all of whom had metastatic breast cancer and had responded to six cycles of chemotherapy. The women were split into two groups. One group of 173 women received additional surgery and radiation treatment, and 177 did not. The women who received surgery had partial or total removal of their breasts and lymph nodes followed by radiotherapy.

After just over two and a half years, the scientists found no overall difference in survival between the two groups; in fact, there was a slight, but not significantly significant, increase in risk of death for the women undergoing surgery and radiation. The lack of difference remained strong even after the scientific team adjusted for the types of breast cancer the women had, and the extent to which their cancer had spread to other organs. The findings should provide more confidence to both doctors and patients who choose not to go under the knife or receive radiation in an effort to prolong their lives, since the evidence suggests that the added measures don’t provide significant benefit, and may only expose the women to more complications.

In the current study, the researchers note that survival is only one factor that women may take into account when debating whether to remove an unaffected breast. In an accompanying editorial, other researchers echoed the distinction, saying that quality of life and peace of mind factors may be important reasons for supporting the continued use of prophylactic mastectomy surgery.

TIME Cancer

Breast-Cancer Drug Has a Surprising New Application, Study Finds

An early study shows that gel-based tamoxifen may be as effective as the oral drug, and have fewer side effects

Tamoxifen is a mainstay of breast cancer treatments: it blocks the effects of the female hormone estrogen on the breast, inhibiting estrogen’s tendency to encourage breast tissue to grow uncontrollably. Now, Dr. Seema Khan, professor of surgery at Northwestern University Feinberg School of Medicine, reports in Clinical Cancer Research that putting the drug in a gel, and applying it directly to the breast tissue, where it needs to work, may have merit.

Doctors generally prescribe tamoxifen for women diagnosed with early breast cancer, including very early-stage ductal carcinoma in situ (DCIS), to prevent recurrent growths. But the drug has also been linked to an increased risk of stroke, blood clots and cancers in other tissues, including the uterus. That’s why more women, including those who have not yet had cancer but are at high risk for the disease could benefit from the drug but are reluctant to take it.

MORE: Why Mammograms Are Less Effective Among Breast Cancer Survivors

Dr. Khan’s study was small—only 26 women—but it provides proof that the principle of applying tamoxifen directly on the breast may be worth investigating. All of the women were diagnosed with DCIS, which generally does not spread. But 30% of DCIS can recur even after surgery and proper treatment, so most women are prescribed tamoxifen. In the current study, about half of the women in the study were randomly assigned to take the oral form of the drug, while the other half were given doses of a tamoxifen gel to apply directly to the breast tissue for six to 10 weeks before their surgery. Khan analyzed the breast tissue after surgery to study markers for tumor growth, and conducted blood tests for levels of tamoxifen metabolites as well.

At the end of the study, the women in both groups showed similar decreases in tumor-related proteins, but blood levels of tamoxifen were five times lower among the women using the gel than those taking the oral pill. That, says Dr. Khan, suggests that the major side effects of the drug, which occur in the blood and other reproductive organs, may be largely avoided if women use the gel.

MORE: High-Tech 3D Mammograms Probably Saved This Woman’s Life

“Our study showed that applying the drug through the breast skin leads to high concentrations in the breast and low concentrations in the rest of the body,” she says. “The biological effect on the breast is consistent with the benefit of oral tamoxifen, so for that reason, we hope that this kind of approach would make preventive medication more acceptable to women with non-invasive breast cancer and how may be at high risk of developing breast cancer.”

Dr. Khan says that the breast may be uniquely designed for such transdermal therapy, since it is essentially an appendage of the skin, with its own internal lymphatic circulation. That may keep things applied to the breast skin within the breast tissue, and could explain the higher concentrations of tamoxifen metabolites she and her team found after the gel applications.

Still, she says that the small number of participants in the study means more research is needed to confirm the results. Right now, the gel version is not available. The company that provided the experimental doses for the study stopped making that formulation, so Dr. Khan is studying a related, similar metabolite called endoxifen that may have similar cancer-fighting effects on breast tissue.

If the strategy proves effective, it’s possible that cancer treatments, or at least breast cancer treatments, may become useful in preventing cancer as well, as more women at high risk who have yet to be diagnosed with the disease take advantage of them. Applying a gel with relatively few side effects may help more women to eliminate small tumors before they have a chance to grow. And if other types of drugs can be used on the skin as well, that could significantly broaden the therapies available to women looking for ways to prevent the disease.

“For high-risk women who need better prevention strategies, delivering the drug to the breast is a very desirable solution,” says Dr. Khan.

TIME Breast Cancer

Why Statins Could Be the Next Treatment for Breast Cancer

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Photodisc—Getty Images

Research connects high cholesterol levels with increased risk of breast cancer.

Cholesterol and cancer may not seem to have much in common, but scientists are increasingly seeing some intriguing connections between the two. In the latest study on the topic, presented at the Frontiers in Cardiovascular Biology in Barcelona, Spain, researchers report on preliminary but strong evidence that women with high cholesterol levels had a 1.6 times greater risk of developing breast cancer over 14 years than women with lower levels.

While the association doesn’t prove that cholesterol can cause breast cancer, the strength of the study comes from its numbers – the data emerged from 664,000 women enrolled in an ongoing study in the UK.

MORE: The Serious Heart Risks That Come With Chemo

Earlier studies have suggested that obesity may be tied to an increased risk of breast cancer, but more recent trials raised the possibility that cholesterol was the driving factor in this correlation – animal studies found, for example, that lowering cholesterol can inhibit tumor cell growth.

So Dr. Rahul Potluri, from Aston University in the UK, decided to investigate the relationship with the database he had established known as the Algorithm for Comorbidities, Associations Length of Stay and Mortality (ACALM) study, focusing on a subset of data from among 1.2 million women in the UK between 2000 and 2013. And indeed, those whose records showed cholesterol levels of 200mg/dL or more were more likely to develop breast cancer. (In the U.S., recent changes to cholesterol guidelines by the American Heart Association and the American College of Cardiology mean that doctors no longer focus on target cholesterol levels but include cholesterol as part of a heart disease risk calculation that includes age, smoking history, blood pressure and diabetes. In previous guidelines, levels between 200mg/dL and 239 mg/dL were considered borderline high.)

MORE: High-Tech 3D Mammograms Probably Saved This Woman’s Life

“It’s a starting point for looking at the relationship in human populations,” says Potluri, who is cautious about overstating what the correlation means. He says that the database did not include information on medications, for example, so he and his colleagues could not adjust for other factors that could explain the association, such as whether the women smoked, or their exposure to other things that could increase their risk for breast cancer.

MORE: Treating Cancer With A Malaria Drug

Still, says Dr. Clifford Hudis, chief of the breast cancer medicine service at Memorial Sloan Kettering Cancer Center who was not involved in the study, “I think this is an important observation. It’s interesting when a big study like this supports some evolving basic science.”

Hudis suspects that the explanation for how cholesterol is involved in breast cancer – or potentially in other types of cancers – may be quite complex, and certainly requires deeper investigation. His own work, for example, explores how obesity and its related metabolic syndrome, which involves resistance to the effects of insulin and low levels of inflammation, could be activating some tumor triggers in breast tissue. Cholesterol is also part of the body’s steroid hormone pathways, which can play a role in certain cancers.

MORE: New Guidelines for Cholesterol Treatments Represent “Huge Change”

“The problem of obesity is going to have profound public health repercussions,” says Hudis; these results are just another reminder of how insidious the health effects of obesity can be.

 

 

 

 

 

 

 

 

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