Friday, October 10, 2014

Breast Cancer Prevention Now

By Graham A. Colditz, MD, DrPH


It is time to bring our focus back to lowering the risk or reducing the onset of new cases of breast cancer at all ages. Worldwide incidence of the disease is rising as societies across the globe modernize, which brings with it higher rates of breast cancer risk factors, such as overweight, lack of physical activity, and key reproductive factors like beginning families later in life and have fewer children.

While modernization has many important benefits, it is also directly driving up the risk of breast cancer. Globally, one in every four new cancers diagnosed in women is breast cancer, and over 1.7 million new cases are diagnosed each year.

We need a global breast cancer prevention strategy - now.

We currently understand how the longer interval from first menstrual period (menarche) to first baby increases lifetime risk for beast cancer. This interval has expanded over centuries in Western Europe following the Industrial Revolution, and - in dramatic fashion - over just a few decades in Asian countries. Data from China and Korea show a rapid decline in age at first menstrual period since World War II, as well as a decline in number of children, which has accelerated. The age women have their first babies is now above the Organization for Economic Cooperation and Development (OECD) average of 28 years old. This means that a typical woman has 16 or more years between her first period and her first baby (first birth at 28 minus first period at 12 years of age). In 1950 in China, this interval was just three years (first birth at 19 minus first period at 16).

Given these social movements, are there approaches early in life that can help mitigate the impact of these changes in reproductive factors? It appears so.

We, and others, have studied diet and physical activity as two key aspects of lifestyle, and then alcohol intake in later adolescence and early adult life.
  • Eating a diet high in fiber and vegetable protein is related to significantly lower risk of both premalignant breast lesions and breast cancer.
  • Being more physicaly active from ages 12 to 22 is powerfully protective against breast cancer.
  • Avoiding alcohol before first pregnancy is strongly protective against both benign breast lesions and invasive breast cancer.
Together, we need to work to improve diet in children, adolescents, and young adults – fostering access to, and consumption of, fruits, vegetables, and whole grains – as well as reducing alcohol intake among women under age. Especially for high school- and college-aged women, we must create an environment that encourages less alcohol intake. Also important is sustaining physically active lifestyles through the adolescent and early adult years, which has both immediate and long-term benefits.

Multifaceted approaches are needed to achieve such behaviors across a broad set of the population, but doing so will have lasting benefits, not only for breast cancer but also colon cancer, heart disease, stroke, as well as mental health. Momentum in this direction can take time to gather, but is achievable and important, and can have a positive impact for generations to come.

Related posts

Tuesday, September 23, 2014

PALB2 Mutation: A "New" Gene That Greatly Increases Breast Cancer Risk

Photo: Flickr/Micahb37
by Sarah Cortez

There’s been a recent surge in women asking for genetic testing for breast cancer, due in large part to Angelina Jolie’s public decision last year to get a prophylactic mastectomy after discovering she had a mutation in the BRCA1 gene. These days, another breast cancer gene has been making headlines, a gene called PALB2.

Mutations in BRCA1, and its related gene, BRCA2, are the two most important known genetic links to breast cancer risk. Well, new findings on PALB2 have some describing it as the “third gene” to be linked with breast cancer.

Previous studies have found that mutations in PALB2 combined with mutations in the BRCA genes increased the risk of breast cancer. PALB2 is even short for Partner and Localizer of BRCA2. What we didn’t know was how much the risk of breast cancer increased with a PALB2 mutation alone – that is without a related BRCA mutation.

In August, the New England Journal of Medicine published a study that characterized patients with only a PALB2 mutation. To do this, researchers identified patients who did not have a BRCA1/2 mutation but who had a history of breast cancer in at least one family member. These patients were then tested for the PALB2 mutation.

So, what did they find?

The results showed that a PALB2 mutation by itself increased the risk of breast cancer 9.5 times compared to the general population. They also showed that, for those with a mutation in PALB2, the risk of developing breast cancer by age 70 was about 33%, as compared to a 12% lifetime risk in the general population. Furthermore, for those with a PALB2 mutation who also had two first-degree relatives (like your mom and your sister) with breast cancer, the risk of developing breast cancer by age 70 increased to more than 50%. For comparison, a BRCA1 mutation increases your risk of developing breast cancer, by age 70, to 55-65%. So BRCA mutations are still considered more risky.

So what does all this new information mean to you?

Just like with the BRCA genes, it would only be recommended that you get screened for PALB2 mutation if you have a strong history of breast or ovarian cancer in your family, such as:
  • Breast cancer in more than one family member
  • Breast cancer diagnosed before the age of 50
  • Breast cancer diagnosed in both breasts (bilateral breast cancer)
  • Male breast cancer
  • Breast cancer plus ovarian or pancreatic cancer
  • Ashkenazi Jewish ethnicity
Many women at low risk for gene mutations are needlessly tested every year, which can cause a great deal of unnecessary anxiety.

If a woman tests positive for a BRCA mutation, we offer increased cancer screening, risk-reducing medications, prophylactic mastectomy, or some combination of these. While it’s likely such approaches will also help protect women with a PALB2 mutation, there is currently no evidence that they have benefit. More research is needed.

Genetic mutations like BRCA1/2 and PALB2 are frightening because they increase the risk of breast cancer by such a great degree. But it’s important to also keep in mind that they are rare. Around one in 400 women in the United States have a BRCA mutation, which translates to 0.25 percent of American women. And even women who have such mutations are not guaranteed to develop the disease.

For the large majority of women, the most important things they can do to improve their health and lower the risk of breast cancer is to focus on living an overall healthy lifestyle that includes: being physically active for at least 30 minutes a day, keeping weight in check, and drinking alcohol only moderately, if at all.


References
Antonis C. Antoniou, Ph.D., Silvia Casadei, Ph.D., Tuomas Heikkinen, Ph.D., Daniel Barrowdale, B.Sc., Katri Pylkäs, Ph.D., et al. Breast-Cancer Risk in Families with Mutations in PALB2. N Engl J Med 2014; 371:497-506.

Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. Journal of Clinical Oncology 2007; 25(11):1329–1333.

Tuesday, September 2, 2014

Hormonal IUDs and Breast Cancer: Is There a Link?


by Sarah Cortez

It certainly goes without saying that birth control has been a major news story the past couple of months. Much of this coverage, of course, has revolved around the recent Supreme Court ruling and reactions to it. Outside of that media storm, there have been some other health-related birth control stories as well, a number of which have focused on the potential of a specific type of IUD - the levonorgestrel IUD - to increase breast cancer risk. 

Photo: Flickr/Theilr
So what do the data actually say about this link? Let’s take a look.

In case you are unfamiliar with the levonorgestrel IUD (brand name Mirena or Skyla), it is a small, plastic, T-shaped device that is inserted into your uterus by a healthcare provider, usually your gynecologist. It prevents pregnancy by releasing a hormone called levonorgestrel and can be left in your uterus for up to five years.

Much of this recent interest in levonorgestrel-releasing IUDs was sparked by a study published in Obstetrics & Gynecology that looked at the records of all 30-49 year old women in Finland who used a levonorgestrel IUD to treat menorrhagia (heavy periods).

The study reports finding that the Finnish women who used the levonorgestrel IUD for 5 years had a 19% increased rate of breast cancer compared to the general Finnish population. That’s bad, right? Well, hold on.

The study also reports that, for these women, ovarian cancer was decreased by 40% and endometrial (uterine) cancer was decreased by 54%. Seeing if the IUD could decrease the risk for, or prevent, endometrial (uterine) cancer was the actual goal of the study.

Remember, these women were receiving a levonogrestrel IUD to treat very heavy periods. Periods, which if caused by endometrial hyperplasia (overgrowth of the uterine lining), put them at increased risk for endometrial cancer. So the study showed that it helped prevent endometrial (uterine) cancer in women who used it to treat very heavy periods.

But, what about the increase in breast cancer?

The authors of the study advised not being too quick to assume that this increase in breast cancer is real. Prior studies have never found an association between levonogrestrel IUD use and breast cancer. So, the finding could just be an outlier or something else could be going on. We don’t know, for example, whether a group of women with very heavy periods has the same breast cancer risk as the general population.

Exactly how this finding translates from Finnish women to American women is also unclear, since the IUDs available in Finland are not exactly the same as those available in the United States

So before you decide to get rid of your IUD because of concerns about breast cancer risk, have an in-depth talk to your doctor. Discuss your family-planning goals, your family history, and your personal risk for breast, endometrial, and ovarian cancer. If your overall risk for breast cancer is low, the levonogrestrel IUD isn’t likely to put you in the high-risk category.

The three most important things women of child-bearing age can do to prevent breast cancer are: be physically active, stay at a healthy weight, and drink only moderate amounts of alcohol – if at all.


Reference

Soini T, Hurskainen R, Grenman S, Maenpaa J, Paavonen J, Pukkala E. Cancer Risk in Women Using the Levonorgestrel-Releasing Intrauterine System in Finland. Obstet Gynecol 2014;124:292-299.

Friday, August 15, 2014

New Study Confirms Weight is a Major Cancer Risk Factor

Photo: Flickr/Kizette
The subjects of weight gain, the obesity epidemic, and their major impact on health are brought up so much these days that they're easy to tune out.  So, if a few articles and news reports here and there pass you by - on accident or on purpose - we understand.  But we won't let that keep us from continuing to write regularly about the topic because it's something we're passionate about here at CNiC.

Why?

That's simple.  Overweight really is one of the most important health issues of our time, and much like tobacco in the middle part of the last century - unless we make some big strides against today's weight problem, generations will experience a greatly decreased quality of life and greatly increased rates of conditions like heart disease, diabetes, stroke, and cancer.  By keeping the issue upfront in articles, journals, and on social media, we can help push for policy changes and shifts in public attitude that will help address the obesity epidemic - much like we did with tobacco.  We've seen some very small positive steps recently on the obesity front, but we need to keep up - and expand on - these efforts.  

A study out today further confirms why.  Building on results from previous studies, researchers with the London School of Hygiene and Tropical Medicine published an analysis in The Lancet showing that increases in weight raise the risk of 11 different cancer, including esophageal, colon, liver, gallbladder, pancreatic, breast (post-menopause), cervical, uterine, ovarian, and kidney cancers, as well as leukemia.  Even for those in the healthy weight range (BMI of 18.5 - 24.9; or someone 5' 9" weighing 125 - 168 pounds), an increase of just one BMI point, say from 23 up to 24, was linked to an increased risk of cancer.

The researchers also calculated the percent of specific cancers likely caused by being obese or overweight (figure).  Five percent of all breast cancers diagnosed after menopause were linked to weight, as well as 11 percent of all colon cancers.  Each of these cancers is quite common.  Less common - but still very important - cancers had much greater percentages linked to weight.

In an accompanying editorial, titled Obesity: a certain and avoidable cause of cancer, Peter Campbell of the American Cancer Society concludes:
"We have sufficient evidence that obesity is an important cause of unnecessary suffering and death from many forms of cancer, in addition to the well recognised increased risks of mortality and morbidity from many other causes. More research is not needed to justify, or even demand, policy changes aimed at curbing overweight and obesity."
We certainly agree.  It's time to act more forcefully for prevention.  Yet, even though disease prevention is increasingly listed as a public health priority, funding and political backing for prevention programs still often lag behind fields like treatment and diagnosis. If we are to truly make headway in the fight against obesity and other key risk factors, prevention needs funding and political will commensurate with its large potential to reduce future disease burden.

Tuesday, August 12, 2014

Evolution of the Science on Aspirin Use and Colon Cancer Prevention

Yesterday, we posted about a new analysis suggesting that long term aspirin use is likely to have an overall health benefit in the general population even when its side effects are taken into account.  At risk of being wonky, we wanted to follow up on that with a figure that shows the general evolution of the science on aspirin use and colon cancer prevention.  

Though it's the cardiovascular benefits that come to most people's minds when they think of reasons to take a daily aspirin, the Cuzick et al analysis shows that most of the benefits from regular aspirin use don't come from the prevention of heart attack and ischemic stroke, they actually come from the prevention of cancer - including colorectal, esophageal, and stomach cancer, and possibly breast, prostate, and lung cancer.  Of these, colorectal cancer is the most important, making up about a third of the total cancer and cardiovascular disease benefits of aspirin use.  

The figure below (full size PDF) shows the evolution of the evidence on aspirin and colon cancer prevention.  Though the science has taken a while to develop, the findings of a number of early positive studies have been confirmed in later studies, and it seems we're finally reaching a point where broad recommendations for daily aspirin use to prevent cardiovascular disease as well as cancer may become a reality.




Monday, August 11, 2014

An Aspirin a Day...May Have Overall Health Benefits

Photo: Flickr/JenR
The writing was on the wall a few years ago, but it seems that we may have finally reached a point
where the scientific evidence points pretty convincingly to the potential health benefits of long-term regular aspirin use outweighing the potential risks for most people. That's the conclusion of a new analysis appearing last week in the Annals of Oncology

While the heart attack and stroke benefits of aspirin use, especially in those at high risk of such events, has been accepted for years, the cancer prevention benefits have been slower to catch on - even though the evidence for colon cancer prevention alone has been quite convincing.

This new analysis confirms the cardiovascular benefits of aspirin use while solidifying its benefits in both preventing and lowering mortality for colorectal, esophageal, and stomach cancer - and possibly for breast, prostate, and lung cancer.

Bleeding is the main concern with regular aspirin use, and the analysis found - not surprisingly - that the risks of events such as bleeding strokes (hemorrhagic strokes) and GI (gastrointestinal) bleeding go up with regular use.

However, after looking at all the benefits and risks together, the researchers found that use of a daily 75 - 325 mg aspirin for 5 or more years starting between ages 50 - 65 years had overall positive benefits.

After 10 years of use, risk of cancer, heart attack, and stroke was 9 percent lower in men and 7 percent lower in women after 15 years. Lower rates of cancer made up the large majority of this benefit, with colon cancer by itself making up about a third of the total benefit from aspirin use. Taking the risks of bleeding events into account, the overall health benefit dropped to about 6 percent for men and women. Lower but still overall positive.

Of course there are still many unanswered questions about the best approach to aspirin use. Because risk of bleeding goes up with age, it's unclear at what age people should stop taking aspirin because the risks outweigh the benefits. Figuring out the best way to identify people at risk of bleeding issues is another important topic, as is the best dose to use. While there's good evidence that a low-dose baby aspirin provides most if not all the benefits of, and likely has fewer risks than, a higher dose 325 mg aspirin, there are not yet definitive studies that have looked at the issue.

While anyone interested in starting on daily aspirin should first talk with his or her doctor, the data are now clearer than they've ever been that such use is likely to have real and lasting health benefits for most people.

Tuesday, July 29, 2014

Missed Opportunities to Prevent Cervical Cancer: Use of HPV Vaccine Still Low

Photo: Flickr/Melissa Wiese 
To work in the field of cancer prevention one has to be an optimist at heart.  In the science, in the statistics, and in the news, you see not only the broad burden of cancer but also the vast opportunities that exist to lower risk and prevent the disease.

At the same time, we understand that shifting environments, attitudes, and behaviors in positive directions can take years, and most likely decades.  We didn't overnight become a nation where two-thirds of us are overweight/obese and half of us get little or no activity.  So it follows that shifting the pendulum in the other direction won't happen overnight either.  Such issues take daily efforts year after year to address both on a personal level and on a societal level.  There are no magic bullets.

Yet, however optimistic, there are two issues that leave many in the public health and medical professions scratching their heads over: the underuse of two relatively simple medical strategies that have vast potential for preventing cancer.

We've written at length about both of these strategies here in CNiC: the use of medications to prevent breast cancer in those at high risk of the disease (posts), and the use of the HPV vaccine to prevent cervical cancer (posts).

Of these two, the low use of the medications tamoxifen and raloxifene is perhaps the hardest to understand, given the large demonstrated benefits they have in preventing breast cancer in high risk women and the yawning gap between the number of women who likely stand to benefit from taking them (well over 2 million) and the number who actually do take them (just 117,000).

While new data on the HPV vaccine show there's been some progress in its use, the numbers also fall well short of what should be possible based on the use of other standard childhood vaccines. The vaccine is recommended for all girls and boys ages 11 or 12, given in a three dose course.  Its safety has been well-documented. Yet, only 57% of girls and 35% of girls get one or more doses of the vaccine.  Count only those who've received the full three doses, and the numbers fall to 38% for girls and 14% for boys.  Based on the number of children in this age-group cohort who receive other vaccines at their standard health care visits, and these percentages could realistically be as high as 91%.

The primary reasons parents give for not vaccinating their children were similar for both girls and boys, including the vaccine not being recommended by the health care provider, concerns about safety, and lack of knowledge of the vaccine or feeling it wasn't needed.

Both of these cases -  low use of the HPV vaccine and of tamoxifen/raloxifene - demonstrate just how important broad-based efforts at education are. It is not enough to demonstrate cancer prevention benefits - even benefits from activities as relatively simple as getting a vaccine or taking a pill.  Concerns of patients, parents, and health care providers must be appropriately addressed while we also move ahead fostering knowledge of, and demand for, the benefits the vaccine and preventive medications provide.

The trend in HPV vaccination show's we're making some progress on that front.  We have to be happy with that, but as usually, we'll keep striving for more.