More about Chemoprevention Numbers

I will respond to many questions about the statistics, specifically the reduction in breast cancer by 50%, in those taking tamoxifen, raloxifene or exemestane, that I used yesterday.

In all studies listed there was a reduction in the number of breast cancers in the treated group by about 50%.  This means a relative risk reduction (RRR) for the treated group of 50% compared to the control group.  The problem with this RRR number is that in order for us to make sense of the magnitude of the effect on the population, in this case the benefit of the medicines, we need to know the level of risk in the control group or how many bad outcomes happen without the treatment.  Treatments with large risk reductions have a small effect in conditions that are rare (very few bad outcomes in the control group).  On the other hand even a modest risk reduction can have a large effect if the bad outcome in the control group is large.  

Two examples will help, each with a 50% RRR.  In the first the bad outcome happens 80% of the time in the control group but only 40% in the treated group.  In the second the bad outcome happens 8% of the time but only 4% in the treated group.  In each case a 50% relative risk reduction but obviously the outcome in the first example is of greater magnitude and in the first case you treat 100 to help 40 people, but in the second you treat 100 to help only 4.

There is another way to help us understand the magnitude of effect when we consider treatment and very large studies with numbers not so easily managed, particularly in brains like mine.  Absolute risk reduction (ARR) is just the difference between to the two outcomes, but this then can be converted to the more useful Number Needed to Treat (NNT).  This number, which is the multiplicative inverse or reciprocal of ARR is another way to understand the magnitude of effect.   

For the first example the ARR 0.8-0.4=0.4 and 1/0.4=2.5.  2.5 is the Number Needed to Treat (NNT) to prevent one bad outcome (the same as treating 100 to help 40).  

In the second example ARR 0.08-0.04=0.04 and NNT then 1/0.04=25.  This is just another way to say treat 100 to help 4.  These measures are helpful when the numbers are more cumbersome.  The ideal NNT would be 1, where everybody treated saw a benefit.

In the NSABP P-1 study that showed a breast cancer risk reduction for those treated with tamoxifen, the control group of 6599 women had 175 invasive breast cancers and the tamoxifen group of 6576 had 89 invasive breast cancers.

The rate of cancer in the control group is 0.027 and in the tamoxifen group 0.014 so the RRR is 48%, but the ARR is 1.3 giving a NNT of 77.  This means 77 women need to take tamoxifen for one to benefit.  

That is part of the reason we offer treatment only to those at high risk (more likely to have breast cancer).  We also need to weigh adverse effects in all cases, but particularly when we prescribe for an asymptomatic person to prevent a bad outcome.  

The NNT for raloxifene in the CORE trial at 8 years is 67, but raloxifene has another benefit, reducing the risk of vertebral fractures.  In the MAP.3 trial the NNT for exemestane is 94. 

Again, this information is to prompt thoughtful discussion and consideration and is not intended as medical advice for any one person.  These prescription drugs have saved many lives and will continue to save lives when used according to guidelines.

For those who want even more about statistics and medicine consider the article in Bloomberg Businessweek http://www.businessweek.com/magazine/content/08_04/b4068052092994_page_2.htm

Together we can prevent 75,000 breast cancer cases each year.

Review of Chemoprevention for Breast Cancer

A recent review of chemoprevention trials for breast cancer was recently published online http://www.medscape.com/viewarticle/758953?src=nl_topic and I will summarize here.


There are now 3 FDA approved prescription drugs used for breast cancer prevention.  They are tamoxifen, raloxifene (Evista) and most recently exemastane (Aromasin).  There is ample evidence to support the use of these drugs since they have clearly been shown to decrease the numbers of breast cancers in all of the trials in high risk women.


First of all they have great names (all acronyms): NSABP P-1, IBIS I, CORE, MORE, STAR and NCIC CTG MAP.3.  


Important points:

• study time 1992- 2010
• over 50,000 women total in trials
• shortest trial reported 3 years
• Breast Cancer reduction is overall 50%
• reduction seems to be the same for each agent

Wow! So it has been demonstrated many times and with many women that the drugs do reduce breast cancer incidence, but are there other issues?

Yes!  Risks and quality of life issues.


The major risks:

• tamoxifen: blood clots and uterine cancer
• raloxifene: blood clots
• exemastane: bone loss, fatigue and joint pain

They each may cause vasomotor symptoms like hot flashes and night sweats.  Other side effects have been noted, but these are the most common.

It is estimated that 5 million US women could benefit from these medicines, but again this is an issue for you to discuss with your doctor.  I have provided some general information to begin the discussion if you are at high risk, but actual treatment decisions need to be made by you and your doctor.

Remember that everyone can benefit from being lean, not being sedentary and exercising regularly.

Together we can prevent 75,000 breast cancer cases each year!

Why you should participate in CPS-3

The American Cancer Society's Cancer Prevention Study 3 (CPS-3) is enrolling now.  I talked about how important this study and studies like it are to all of us who don't want to get cancer on YNN this am.  I think you can see it throughout the next 24 hours on News 8 Austin.


Studies like this one have demonstrated the link between smoking and lung cancer, obesity and increased death rates from many cancers, and that prolonged sitting shortens longevity.  These studies also inform me to let you know all the things you can do to prevent breast cancer.


This study aims to get 300,000 participants, ages 30-65 yo for a 20-30 year study.  You may make your appointment online and fill out most of the paper work at https://www.seeuthere.com/rsvp/invitation/invitation.asp?id=/m1c9c3bc-1I2OXR2SE2N44.  Then you make an appointment for waist measure, signing the forms and getting blood drawn--about 20 minutes.  After that you will get a form to complete at home every 2-3 years and the satisfaction of knowing you are helping!


Why is this important?

• to track the impact of obesity, nutrition and activity on death rates
• to identify NEW risk factors in the environment, lifestyle and medications
• to expand our knowledge of cancer risk factors
• to improve our understanding of cancer biology and causes
• to improve risk prediction

Why is CPS-3 different?

• Higher proportion of younger adults (age 30-65 years)
• Information from blood drawn (genetics, etc)
• Physical assessment (waist measure)
• Detailed baseline medical history
• Greater ethnic/racial diversity

Your participation might save your life or the life of a loved one.  This study is not just limited to women and breast cancer, but includes Men, Hispanics and African Americans, who have been under-represented in most population studies.

You may find out more at https://www.seeuthere.com/rsvp/invitation/invitation.asp?id=/m1c9c3bc-1I2OXR2SE2N44.  In Austin the times are February 29, March 1,4 and 6.  You may also call to make your appointment 888-604-5888.

Together we can prevent 75,000 breast cancer cases each year...and many others!

Omega3 Fish Oil Boosts Tamoxifen Therapy in Breast Cancer

We have already discussed a study showing that women who use omega3 fish oil have fewer breast cancers.  See DrWinsett.com: Fish oil (Omega3) reduces breast cancer risk!. 
Now we find that in an animal model, adding fish oil intensifies the therapeutic response to tamoxifen.


Researchers lead by A Manni at Fox Chase Cancer Center in Pa studied the effects of increasing doses of fish oil with or without tamoxifen in an animal model of induced breast cancer.  They studied the protein Ki67, which is a measure of proliferation.  In a dose dependent fashion, the fish oil reduced Ki67 expression, which is linked to tumor growth and metastasis.  So tamoxifen and fish oil were additive in there beneficial effects on breast cancer tumors.


This was presented at the American Association of Cancer Research 2011 available at http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=5ef6c8c5-09dc-48c5-b601-42fac30b2b2c&cKey=bc4ad1fe-88a0-4e09-a786-6500fe4f2798&mKey=%7b507D311A-B6EC-436A-BD67-6D14ED39622C%7d.


High quality fish oil is available and is safe.  Now we may have another indication for its use.  Discuss it with your doctor.




Together we can prevent 75,000 breast cancer cases each year.

Aspirin after Breast Cancer Diagnosis.

Studies have shown that aspirin may inhibit breast cancer metastasis in animals, so a group from Harvard looked at the effect of taking aspirin on women who were diagnosed with breast cancer.  You may find the article online at http://jco.ascopubs.org/content/28/9/1467.full.pdf+html.


This is another report of a subgroup from the Nurses' Health Study.  Data from 4164 women who were diagnosed with cancer between 1976 and 2002 were observed until death or 2006.


Aspirin use categories were never or past users, current one day a week use, aspirin 2-5 days a week and current use 6-7 days a week.


The aspirin users 2 or more days per week significantly reduced breast cancer death risk and reduced distant metastatic disease.


Relative risk of death was reduced:

• for 2-5 days per week          71%
• for 6-7 days per week          64%

Relative risk for distant metastatic disease was similarly reduced:

• for 2-5 days per week          60%
• for 6-7 days per week          43%

Importantly, these findings were present for Estrogen Receptor Positive and Negative tumors.

So, does this mean everyone should begin taking aspirin?  Not necessarily.  This is information for you to discuss with your doctor.  Aspirin has side effects and some people should not take aspirin.  Again, you and your doctor need to review this information and decide if aspirin would benefit you.

What has happened to menopausal hormone therapy?

We all remember 2002, when the large Women's Health Initiative (WHI) trial data was published.  The study of estrogen plus progesterone was stopped in July of 2002 because of too many cardiovascular events and too many breast cancers.  The risks of using combined conjugated equine estrogens with medroxyprogesterone in postmenopausal women was shown to outweigh the benefits.  With this finding came new guidelines from the FDA and other professional organizations that supported using as little as possible for the shortest period of time to treat menopausal symptoms.


A recent study published in Menopause: The Journal of The North American Menopause Society by Tsai, et al, evaluated the trend in hormone replacement from 2001 (before the report) and 2009.


Data from the IMS health survey of office-based physicians were extracted from a National Disease and Therapeutic Index that provides national cross-validated numbers.




The results are that menopausal hormone replacement therapy (MHT) has declined each year since 2002.  The greatest percentage decline was in the first year.  Declines were greatest for older women, but declined at all 3 ages studied


Declines:          women over 60 years          64%
                      women 50-59 years             60%
                      women under 50 years         59%


The use of combined estrogen and progesterone declined more than the use of estrogen alone.


Use of lower dose products increased about 30%.


What dose this mean?  The authors suggest that the increase in use of lower dose products does "reflect clinical recommendations" but has been "modest".  Furthermore they note that substantial use continues in the older women who are at increased cardiovascular and breast cancer risks.




Certainly there is more to learn about different subpopulation groups and well as dosage, timing and route of administration.


One other limitation of this study is lack of information on patient symptoms.  That is what those of us who write menopausal hormone replacement prescriptions also have to consider.  A second limitation is the lack of information about personal breast cancer risk.  We now have more tools to help us here like BREVAGen and HALO.  A third limitation is the lack of information about use of non-hormonal treatments that have shown less risk.  Not everyone is symptomatic without hormones.




So, it is a decision for the woman and her doctor to make, discussing her personal risk/benefit ratio.






Together, we can prevent 75,000 breast cancer cases each year!

The relation of age to the incidence of Breast Cancer

Or, "Can I ever quit these routine visits to see you?"




We try not to have our feelings hurt, but we do get asked questions like this one. And, "Won't I ever outgrow my risk for breast cancer?"


The answer is in the data.  The best US data is at The National Cancer Institute's website http://seer.cancer.gov/faststats/selections.php? and called the Surveillance Epidemiology and End Results data.


The incidence of breast cancer increases with age and in most countries peaks at 90 to 95 years!




This same SEER data clearly shows that there is a benefit for screening the breast and finding that smaller tumor at any age!




So, we will continue to invite you for your regular visit. 

Coconuts?

Monday, in the gym, a topic of conversation was a news release touting the benefits of coconut oil for Alzheimer's Dementia.  Since there has been periodic excitement about coconut oil as a cure for many things, including breast cancer, I thought it was worth a look.  The video can be viewed at http://www.cbn.com/media/player/index.aspx?s=/mp4/LJO190v1_WS. 


It describes how one patient who took coconut oil showed signs that the Alzheimer's "slowed considerably.  Some of his symptoms even reversed".  Isn't that, after all, what we all want.


BUT, when looking at a news release and the story of only one patient, I think, where is the data: the number of patients treated vs the controls, the risks and benefits, the evidence and verification, like being published in a peer review journal or several different labs reporting similar results?  I tried to find evidence elsewhere, in journals or by looking at the work of the two doctors in the video.  Perhaps there will be some evidence published in the future.  I was not convinced.




What do we know about coconut oil?  And could it have breast cancer prevention powers?  One tablespoon of pure coconut oil has 116 calories and 14 grams of fat!  Pure coconut oil is a source of plant saturated fat and most of that fat is medium chain triglycerides (MCT).  The "bad" saturated fats are from animals and are mostly long chain triglycerides (LCT).  MCT's have about 10% fewer calories by weight, are absorbed more readily, deposited in fat cells slower and are more quickly metabolized for energy.  So, some have studied coconut oil for weight loss, but the results have not been promising.  


The only study I could find specifically substituting coconut oil for cottonseed, sunflower or corn oil did show that changes in fat in rat diets could slow breast cancer development.  The authors note that other factors like differences in omega6 amounts might also be at work and I could find no follow-up studies from this 1996 article in Nutrition.  


So if you want to try coconut oil make certain that is is pure or virgin coconut oil and not processed.  It is when coconut oil is hydrogenated (processed to make it last longer on the shelf or look prettier on cakes, candies and coffee) that it becomes a trans fat, which is the worst kind of fat and to be avoided at all costs.




For now, lets stick with the best data we have:  


KEEP MOVING, BE LEAN and REGULARLY EXERCISE!

More doctors are recommending EXERCISE!

Midweek and time for recent news.  


A recent Center for Disease Control report from the National Health Interview Survey was published this month and shows that more physicians are recommending exercise (http://www.cdc.gov/nchs/data/databriefs/db86.htm). 


Specifically, the question was, "Did your physician recommend that you begin or continue to exercise?"


The answer is that more doctors are recommending exercise, 10% more in 2010 than in 2000.


In 2010 overall 32.4% said the doctor recommended exercise.  




For women alone the number was up to 34% in 2010 vs 23.9% in 2000.  These are women over 18 years.  When viewed by age, the largest single increase was for those women over 85 years: up from 15.3% to 28.9% (almost double!).




The recommendation varied by chronic disease:

• for cancer 36%
• cardiovascular disease 42%
• high blood pressure 44%
• diabetes 56%

There was also variation by BMI:

• Healthy weight (BMI <25) 22.6%
• Overweight (BMI 25-30) 30.5%
• Obese  (BMI >30) 46.9% 

It does look like we are all getting the picture.

Although the recognition of cancer prevention benefits seem to be lagging behind, we can all encourage our family, friends and coworkers to GET MOVING!  Data demonstrates that exercise is a big part of cancer prevention.

Together we can prevent 75,000 breast cancer cases each year!

An Update on Hereditary Breast Cancer Testing

We are learning just how different Hereditary Breast Cancer and/or Ovarian Cancer is from the more common varieties and learning more about who to test for the deleterious mutations.


The National Comprehensive Cancer Network updates the guidelines routinely and publishes guidelines online.  You may review them at http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.


It is not that Hereditary Breast Cancer is changing, but that we are understanding more about Hereditary Breast Cancer and who is at risk.  Fortunately, only about 7% of breast cancers are caused by these BRCA 1 & 2 gene mutations.  Another 23% may have a family history, but not in a pattern caused by these mutations, and finally the remaining 70% who are diagnosed with beast cancer do not have a family history.  Finding out who has one of the mutations may allow us a prevention opportunity.  


In general the hereditary component should be thought of in a woman with breast cancer who is young, has a family history of breast cancer in a close relative or a known BRCA 1 or 2 mutation, has ovarian cancer or a relative with ovarian cancer, has a male relative with beast cancer, has had breast cancer twice, and who has a personal history of triple negative breast cancer (TNBC) meaning negative for estrogen, progesterone and HER2 receptors. 


If you have, or know anyone with the following, you should ask your doctor if the test is right for you:

• breast cancer before the age of 45
• breast cancer by age 50 with a close relative with breast or ovarian cancer
• breast cancer two separate times by age 50
• triple negative breast cancer by age 60
• close male relative with breast cancer
• personal history of ovarian cancer
• Ashkenazi Jewish ethnicity
• a family history of any of the above

If you decide to be tested, contact your physician.  There are four tests, and your doctor will know which is right for you depending on your personal and family history.

A review of what you can do to reduce your breast cancer risk

Want to reduce your risk of ever getting breast cancer?


You might consider doing these things:

• Be lean
• Be active
• Exercise regularly
• Don't smoke
• Eat more vegetables
• Go heavy on cruciferous vegetables 
• Eat more fruit
• Eat NO processed foods
• Cut dietary fat
• Limit alcohol

We can all do these things without a prescription or doctor visit.  These next breast cancer reduction measures require input from your physician:

1. Omega 3
2. Aspirin
3. Tamoxifen
4. Raloxifene
5. Exemastane

Many of these have been covered in previous blogs.  Others will be covered in future ones.  If you have any questions, don't hesitate to call me 512-451-5788 or send me an email from the link at http://www.owenwinsettmd.com.


Together we can prevent 75,000 breast cancer cases each year!

Maybe the salt would be better in the wound

Let me take a break from breast cancer prevention to another prevention tactic for almost as many people.  

Americans eat too much salt!

According to a recent update of the National Health and Nutrition Examination Survey (NHANES) called "What we eat in America", we eat too much salt (online at http://www.cdc.gov/mmwr/mmwr_wk.html).

Let me reiterate the important points in the report:

• 90% of Americans consume more sodium than recommended.
• Recommended sodium intake for most is <2300mg.
• Recommended for blacks and over 51yo is <1500mg.
• Lower amounts for those with high blood pressure, diabetes and chronic kidney disease.
• Dietary sodium averages 3266mg per day, even excluding table salt added.
• The leading culprits are:

          bread and rolls

          cured meat and cold cuts

          pizza

          poultry

          soups

          sandwiches and burgers

          cheese

          pasta with meat sauce

          mixed meat dishes like meatloaf

          snacks like chips and pretzels

• Two thirds of this dietary sodium comes from supermarkets and convenience stores.
• One fourth from restaurants (the highest per calorie source).
• Reducing the sodium content of the ten foods listed by one fourth would reduce total dietary sodium intake by 10%, which could prevent 28,000 deaths per year and save $7 billion!
• Check out more http://www.cdc.gov/vitalsigns.

So, in a few words: CUT OUT THE PROCESSED FOODS!!!

Help for postmenopausal women who don't sleep well.

There is no question that sleep disturbances are a big part of menopause.  At least 50% of postmenopausal women note sleep problems.  Not getting a "good night's" sleep reduces the quality of life.  Just ask the postmenopausal woman with chronic sleep problems!  


There are a wide variety of treatment options, both prescription and nonprescription.  Hormone replacement is the first obvious choice, but because of stroke and breast cancer risk, not as many women are using that option.  Herbal remedies have been tried and reports have been inconsistent.  Today, I will discuss the first of it's kind, a report, published in Menopause: The Journal of the North American Menopause Society in Sept 2011, using valerian in a rigorous clinical trial of postmenopausal women. 


Researchers divided 100 postmenopausal women into two groups: one to receive placebo and one to receive valerian for four weeks.  The researchers and the participants were blinded during the study.  The women were matched for age, family size, education, occupation and economic status.


At four weeks 30% of the valerian group reported improvement in sleep quality, but only 4% of the placebo group noted any improvement.  This finding was confirmed by the Pittsburgh Sleep Quality Index.  Notably no adverse events were reported.


You have probably read in the news that not all supplements are made the same and that sometimes the amount or even the product on the label is not what is in the pill.  There is a source that lists reliable manufacturers and labels.  The Thompson Company in the PDR for Nonprescription Drugs, Dietary Supplements and Herbs and online, provides the testing to confirm that what the label says is what is in the pill.  This is the same company that does the testing for prescription medications and publishes the PDR (Physicians Desk Reference).


Call (512-451-5788) or email www.thedoctor@owenwinsettmd.com for more information.

The importance of skin retraction!

It is well known that a breast lump needs to be investigated, but there is another less common finding that needs evaluation, too.  This finding is skin retraction.  In the large series of patients collected by Haagensen, one of the early leaders in the study of breast disease, 3% of women presented to his breast clinic with skin retraction.


Skin retraction can be anything from a dimple to shrinkage of the entire breast.  It occurs because of abnormal traction on the Cooper's ligaments inside the breast.  When a process causes scaring inside the breast and "pulls" on these fascial septa retraction or dimpling can appear in the skin.  If the process involves the entire breast then the the skin appears distorted and even fixed to the underlying pectoralis muscle. 


The process that causes dimpling can be both benign and malignant.  Inflammation like an infection or fat necrosis after breast trauma can cause skin retraction.  Cancer can also cause skin retraction.  The finding can be subtle or only seen in certain positions.  This is why the first part of the clinical breast examination is inspection and with the arms in three different positions, like directing the airplane into its parking place at the airport some have said.  Dimpling is often difficult for the woman herself to see because of the vertical orientation of her eyes "above" her breasts and more often detected by the doctor who has a more horizontal orientation during inspection.


Dimpling may be an early symptom of breast cancer that can lead to early and breast-saving treatment.

Have some broccoli.

We have known for sometime that broccoli and other cruciforms (a cross can be seen in the just-sprouted seedling) contain cancer fighting compounds.  In addition to broccoli; Brussels sprouts, cabbage, cauliflower, collard greens, mustard greens, kale, kohlrabi, rutabaga, radishes and watercress are other cruciforms.

Now we are learning how these so called "super veggies" may work.  A recent study (http://pubs.acs.org/doi/abs/10.1021/jm101199t) by Wang and colleagues from Georgetown and Columbia medical schools explains at least one of the cancer fighters in the broccoli.

About 50% of human cancers, including breast cancer, are thought to be caused by a mutant p53 gene.  This gene normally codes for tumor suppressor proteins that actually prevent cancers from developing.  When the p53 gene has a mutation the proteins formed don't have the suppressor quality and allow tumors to grow.  Compounds in the broccoli called isothiocyanates or ITC's destroy the abnormal non-suppressor proteins and allow the normal proteins to suppress tumor growth.

I think I'll stop and get some fresh broccoli on the way home!

More dietary fiber means fewer breast cancers.

Dietary fiber has been linked to breast cancer risk reduction in the most recent report from Continuously Updated Project of The American Institute of Cancer Research and The world Cancer Research Fund.  See  www.aicr.org/research/continuous-update-project.html for the review.


Dr. D Aune, a nutritional epidemiologist from the Imperial College in London was the lead author in the paper published in Annals of Oncology http://annonc.oxfordjournals.org/content/early/2012/01/10/annonc.mdr589.full.pdf.  They reviewed 16 prospective studies of dietary fiber intake and breast cancer risk.  


They found that there was a 5% decrease in the numbers of breast cancers for each 10gm of fiber women eat each day.


So what is fiber and which is best.  There is not just one dietary fiber.  Many of us were taught that fiber was the outer layer of grains and skin of fruits and root vegetables, which just passed on through; but now we understand that there are two kinds of dietary fiber: soluble and insoluble.  

Soluble fibers are mostly carbohydrates that dissolve in water to make a gel in the stomach to slow digestion and make us feel full.  Examples of soluble fibers include oatmeal, fruits, nuts, and legumes (beans and peas).  These kinds of fiber slow digestion and produce favorable effects on glucose, insulin and cholesterol.


Insoluble fibers are plant cell walls that don't dissolve in water and are considered gut-healthy because they have a laxative effect by adding bulk and passing through relatively intact.  Examples are whole wheat, wheat bran, whole grains, seeds, some dark leafy vegetables and the skin of fruits and root vegetables.

The review examined papers including fruit fiber, vegetable fiber, cereal fiber and soluble versus insoluble fibers.  Dietary soluble fiber showed the greatest inverse relationship with breast cancer.


Dietary fiber may lead to fewer breast cancers by several mechanisms.  The fiber decreases absorption of estrogens by reducing the activity of an enzyme necessary for the process.  Fiber binds estrogen and increases excretion.  Fiber reduces insulin over secretion by delaying gastric emptying and increasing small bowel transit time.  High fiber diets may also reduce obesity, but in studies controlled for weight, the breast cancer reduction was still present (independent of weight).

Recommended amounts of daily fiber intake vary from 20 to 35 grams per day.  


Now we can figure out how much fiber we eat by looking at the Nutrition Facts label on most foods.  Dietary fiber is found just under total carbohydrates.  Or check out www.nal.usda.gov/fnic/foodcomp/search/.  For example: one medium apple has 4 grams of fiber, one medium banana has 3 grams, one cup beans has 10-15 grams and one tablespoon of wheat bran has 12 grams.


So let's eat our way to fewer breast cancers with more dietary fiber.