HOW TO PREVENT CANCERS

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Practicing Prevention: Using Produce from a Farm Share

Wednesday, June 30, 2010 0 comments

As someone who spent a lot of childhood summers on a dairy farm (my grandfather’s), I became accustomed to the (superior) taste of freshly picked fruit and vegetables and missed them when I made the move to the big city. I also believe in supporting family farms. When I was single, this meant trekking to farmers markets when I could, but weekends I was often on the road or otherwise occupied and couldn’t make it on a Saturday morning. Unfortunately, Wegmans (www.wegmans.com) hadn’t made it to any of the cities I was living in during my 20s and none of the stores I shopped at made it a practice of buying from local farmers the way Wegmans admirably has for years.

Thankfully, a colleague in Chicago introduced me to community-supported agriculture (CSA) (http://www.localharvest.org/csa/) and farm shares. Once we started having family dinners on a regular basis, it seemed that enough vegetables would be consumed in our family to support our participation, and we signed up.

Meal preparation is a bit different with a CSA. Instead of planning my meals and then doing shopping, I now start with what’s in the weeks’ box, find recipes that use those items up before they spoil (since they were picked ripe, my window is short for some items) and supplement with items from the grocery store. This process is made SUPER easy in the internet age as you can go to any number of recipe sites and enter your ingredient (e.g. zucchini) and get a long list of ideas – with something to meet everyone’s mood and taste preferences. Or, if you’re like me and have a rather large binder of recipes you’ve gathered and been meaning to try, you cull through piles of recipes as you watch the game/match to put meals together. Sometimes I improvise, substituting an item in the recipe for one I have. Our box comes on Thursday afternoons so I plan my menus on Friday night and go shopping Saturday morning. My main criteria in choosing a recipe are finding something that uses what comes from the farm, “healthy” and likely to be declared “yummy” by my family. This can be a challenge in a house where I think “yummy” means tasting the vegetables and other people think life would be grand eating Alfredo sauce every night! So there is a balance and some tweaking – we aren’t all about plain raw veggies!

Can you show me what you mean?

SURE!

This week, we had a few gorgeous zucchini in our box so I went looking for recipes that used zucchini in my pile. I found a yummy looking pasta dish I had ripped out of some magazine while on an airplane. It called for zucchini (check), onion (had some in the pantry), lemon (always have those), Parmesan cheese (always in the fridge), tiny frozen green beans (which I misread as tiny frozen peas, check) and heavy cream. The recipe mostly met the Your Disease Risk cancer prevention guidelines i.e. eat vegetables, limit red meat) but was a little heavier on the cream and cheese (i.e. limit saturated fats) than I’d like so I just scaled back a bit on those items. It came together quickly and easily.

Chop up a zucchini.

And an onion.

Grate some Parmesan cheese.

(that looks like a lot in the photo but it was maybe 1/2 cup)

Thaw some frozen peas (because that’s what you have even though the recipe says green beans)

Zest and juice a lemon.
Saute the zucchini and onion together with a little olive oil, salt and pepper until tender.

Toss it together with the cooked pasta, a little cream, the Parmesan cheese, lemon zest and juice and a bit of the pasta cooking liquid.

Fast, easy and delicious.

And if you’re lucky like those of us who participate in the Yellow Wood Farms CSA, your weekly box sometimes contains mulberries! Mulberries (which apparently grow on trees not bushes) don’t transport well from what I’ve read so you won’t find them in stores. So unless you’re doing some urban foraging, you won’t find them… unless you’ve got a great farm share!

Pedal Power: Modest Amounts of Bicycling Show Big Benefits for Weight Control

Tuesday, June 29, 2010 0 comments

Walking has long been the preferred mode of exercise for a good many people, but the results of a new study may have bicycling give it some competition.

The large Harvard study published this week in the Archives of Internal Medicine (study) found that modest amounts of bicycling could help significantly stem weight gain in pre-menopausal women, particularly in those who are already overweight.

Weight gain is a huge battle for most people and simply slowing the regular weight gain most of us experience over the years can have huge health benefits, lowering the risk of cancer, heart disease, stroke, and diabetes.

The study - part of the Nurses Health Study II - followed over 18,000 pre-menopausal women over six years and found that 30 minutes a day of bicycling and 30 minutes a day of brisk walking each had very similar and significant weight control benefits. Yet, while lean women were much more likely to go on a brisk walk than overweight or obese women, both overweight and lean women were similarly likely to go for a ride on their bikes.

The real standout finding in the paper, though, was the weight control benefit of riding just five minutes a day. While riding greater amounts had even more benefit, steadily riding just five minutes a day had a real impact on weight over the six year period.

Exercise can be a daunting challenge for many, but as this paper helps show, it really doesn't have to be. Any amount of activity is better than none, and can even have big benefits.

Of course, to get the full health benefits of exercise, and to actually lose weight and maintain it, requires more effort - 30-60 minutes a day - and these are levels we should all shoot for. But we don't need to get there in a single bound. Five minute could be a good place to start.

Cell phone towers and cancer risk

Saturday, June 26, 2010 0 comments

A detailed analysis of some 1397 children with cancer between ages 0 and 4 evaluated the exposure of mothers to cell phone towers based on residence at birth of the child (see study). These children with cancer were compared to 5588 children born on the same day who were free from cancer. This detailed study compared exposures for a range of childhood cancers including brain, central nervous system, leukemia, non Hodgkin lymphoma and all cancers combined ¹.

The investigators analyzed the data controlling for socioeconomic deprivation and the population density. The observed no significant relation between exposure and total cancer risk. Total output as well as power density from the transmitter were evaluated. In fact the overall association was null and showed little suggestion of any reliant for the subtypes of cancer. Further more there was no association between increasing levels of exposure and risk.

These reassuring data add further evidence that childhood cancer rates are not explained by this in utero radiofrequency exposure.

As the President’s Cancer Panel noted there is much concern in the community that increasing exposure to cell phone technology may adversely effect the risk of cancer in children. These data from a rigorous evaluation found no association between the exposure of mothers during pregnancy to radiofrequency from to cell phone base stations and risk of cancer in young children. A detailed review by the National Academy ² of radiofrequency exposure reported no evidence for adverse effects at levels of exposure across a broad range.

How should one interpret this study of base station exposure in relation to other sources of radiofrequency? It has been estimated that one day’s exposure from a base station at an incident level of about 2-10mW/m2 corresponds to about the first 4 seconds of local exposure to the head and about 30 minutes of whole body exposure arising from the use of a mobile phone ³. Theoretical concerns persist, however, about the effects on children. Given their size and the potential for exposure to add over a lifetime, it is still recommended that exposure of children to cell phones should be minimized.

1. Elliott P, Toledano MB, Bennett J, et al. Mobile phone base stations and early childhood cancers: case-control study. BMJ. 2010;340:c3077.

2. Committee to Assess Potential Health Effects from Exposures to PAVE PAWS Low-Level Phased-Array Radiofrequency Energy NRC. An Assessment of potential health effects from exposure to PAVE PAWS low-level phased-array raadiofrequency energy. Washington, DC: The National Academies Press; 2005.

3. Regel SJ, Negovetic S, Roosli M, et al. UMTS base station-like exposure, well-being, and cognitive performance. Environ Health Perspect. Aug 2006;114(8):1270-1275.

Preventing Cancer: Who Has Time?

Thursday, June 24, 2010 0 comments

In honor of Father’s Day, the New York Times reports that fathers are now just as stressed out as their wives over balancing work and family. As we struggle to deliver 200% at work each day and come home and offer the same to our children and spouses, it can be easy to let the choices we talk about for cancer prevention -- cutting down on processed food, eating vegetables (i.e. doing battle at the dinner table to get everyone to eat their vegetables), being active -- slip by.

The CNiC team doesn’t have all the answers, and we struggle like everyone else, but we’ve developed a few strategies that help us fit cancer prevention into each day.

1) Plan the week’s menu out ahead of time. Knowing what is “on tap” for dinner each night makes coming home and needing to get dinner on the table less stressful. It also means you can plan in the vegetables in a way that works for your family – whether it is mixing them into a yummy pasta dish or making sure to have little Jane’s favorite, peas, on hand.

2) Keep fruits and vegetables within arm’s reach. OK, this is a slight exaggeration, but making sure the counters, desks, and fridge are filled with fruits and vegetables makes them an easy and convenient choice to make for everyone.

3) Exercise in the morning before work, school, or family obligations. You’ll be sure to fit it in before the day gets too hectic, and you’ll only have to shower once – another time saver. To boost the chances you’ll actually heed the alarm clock, put your sneakers next to bed as a not-so-subtle reminder of your plans. We even know of some folks who sleep in their running clothes to remove even one more step. A bit wacky, yes, but you do what works for you.

4) Make exercise time family time. Head out with your young ones in a jogging stroller or have your older ones get on their bikes to keep pace! And don’t let the weather get in your way – crank up the stereo and dance around with your kids. You’ll be amazed at how much fun they have seeing mom and dad acting silly (well, at least until that age where everything mom and dad do is horribly embarrassing).

5) Stash spare workout shoes and clothes at work, school, in the car. You never know when you’ll have a spare 30 minutes to get a walk or run in, so it’s good to have your workout stuff close at hand. The meeting could let out early or be rescheduled later; kids could have an unplanned play date; or the stars could just align and create an unexpected opening in your day. So it’s good to be ready to go at any time.

6) Call on friends. When you’re home alone with three young kids and just can’t see how you’re going to get out for a quick walk or swim, ask a friend if they could look after your kids for a little bit. It’s not something you’ll want to do regularly, most likely, but it’s something a lot of friends would be happy to do, and if they have kids as well, they’ll feel free to call on you when they need to fit in a quick walk some day.

7) Say “no” at the supermarket. Advertising has a huge pull on our kids and if we’re honest on us as well. Sure, it’s not the most positive stance to take, but telling your kids “no” to their pleading for nutritionless and calorie-packed cereals, snacks, and treats is a quick, if not always easy, way to keep your family on the right nutrition track. It may cause a meltdown in aisle three, something no one ever wants, but it’s worth every bit of time and energy you put into it. Maintaining a healthy weight should be a family priority, especially for our kids who set their healthy habits early in life.

Genetic Predisposition to Cancer: Family History is Important and Often Under Recorded

Tuesday, June 22, 2010 0 comments

This week the New York Times (editorial) again points to the realization that after 10 years of extensive research that has advanced scientific understanding of human genetics we are still a long way off from quantifiable clinical benefits. Importantly, the value of a family history in clinical practice has received much attention from NIH consensus panel and other opinion leaders in clinical medicine (report). However, recent data from Australia highlights just how large a gap we have between clinical recommendations and actual practice. This is not a problem limited to family history but the data point to the challenge of moving from recommendations to high quality care.

As Emery and colleagues note, a family history may aid in diagnosis, risk assessment, and preventive counseling for many chronic conditions. Review of charts for patients admitted to a tertiary care hospital in Australia showed that family history was recorded in only 16% of patient charts. Clearly, a major contributor to disease risk and a guide for identifying those who can gain substantially from preventive interventions was omitted from the majority of patient charts. This is not a problem limited to Australia, but rather these data reflect that lack of attention is too often focused on this important marker of disease risk that can be used to help focus prevention messages.

For all of us it is important to remember to bring our family history of disease to the attention of our primary care provider so that medical decisions and recommendations can take account of our genetic predisposition as summarized by our family history. For many cancers and other chronic disease the benefits of lifestyle changes and other prevention strategies give a greater reduction in total risk to those with a family history. This opportunity to reduce risk should not be missed.

Crimson Tide: Change in the Navy's Submarine Smoking Policy

Monday, June 21, 2010 0 comments

The US navy announced last week that smoking would no longer be allowed on submarines. As reported in the New York Times (link), the military has a long history with the tobacco industry and was responsible for starting a generation of smokers through the issuance of cigarettes to soldiers in their meals ready to eat (MRE) packets. The financial implications of that implicit and explicit support are coming home to roost as the government now bears responsibility for the myriad of smoking related health complications those veterans now face.

The decision to ban smoking on submarines was made because the military realized that even their best air filtration systems could not sufficiently clean the submarine air to protect non smokers from the deleterious health effects of smoking. What makes this an important story for those of us who aren’t submariners? There are several reasons:

1) Opponents of clean indoor air laws, particularly those laws requiring smoke-free workplaces for those in the food and beverage industry, have argued that filtration systems clean the air adequately enough to protect workers. If the military can’t buy or build a system to do this, we should all realize these systems don’t work. The only thing that keeps bars and restaurants and workplaces free from the harms of tobacco smoke are smoke-free workplaces

2) The military intends to keep smoking in place on other navy ships and in all other areas of service arguing that the stress of military service is sufficient that smoking should remain a tolerated coping tool. While we at CNiC would never dispute the incredibly stressful nature of military service, particularly in a time of war, research shows that smoking isn’t always an effective stress reducing approach. In fact, there is some evidence that smoking cessation reduces stress.

3) As taxpayers, we bear the health costs associated with permissive smoking policies for active duty members of the military as we commit, rightly so, to providing our veterans medical care for life. Thus, the costs of smoking-related disease over the life time are the federal government’s, and thus the taxpayers’. Policies that decrease the permissibility of smoking and build a culture around healthy choices and coping strategies benefit the nation as a whole.

The tobacco ban on submarines is a notable and very positive step in fighting the scourge of tobacco and improving the health of our soldiers and ultimately their families. Many of the young men and women entering the military become smokers only after they enlist. Furthering such tobacco bans to other settings would help keep these soldiers smoke-free while enticing others to stop smoking. We already ask our young people in uniform to risk their lives on the battlefield. Shouldn’t we do what we can to help them live long and healthy lives off the battlefield as well?

Obesity, Diabetes, and Cancer

Friday, June 18, 2010 0 comments

With the release this week of the ACS report on Diabetes and Cancer risk, we return to the growing cancer burden caused by obesity and excess weight gain during adult years. We might approach this problem from several angles. First, which cancers are caused by obesity and second, by focusing on diabetes, we might ask does this disease give added insights to the pathway from weight gain to cancer?

Weight, weight gain, and risk of cancer

While evidence shows that adult overweight and obesity are related to risk of many cancers, the growing epidemic of obesity provides a challenge to clinical practice and the implementation of guidelines for management of weight. Historical data from the past 25 years point to obesity as a cause of approximately 14% of cancer deaths in men and up to 20% of cancer deaths in women (1). These may be conservative estimates as the US population has gained substantial weight over this time period and the prevalence of overweight and obesity has increased from 15% in 1980 to 35% in 2005 (2). It is now estimated that the total health burden of overweight and obesity exceeds that for cigarette smoking (3).

A major review of weight, physical activity, and cancer incidence by the International Agency for Research on Cancer (IARC) used obesity prevalence data from Europe and relative risks from a meta-analysis of published studies and concluded in 2002 that obesity is a cause of 11% of colon cancer; 9% of postmenopausal breast cancer; 39% of endometrial cancer; 25% of kidney cancer; and 37% of esophageal cancer (4). In addition, data from the American Cancer Society (ACS) suggested that overweight and obesity were related to mortality from liver cancer, pancreatic cancer, non-Hodgkin lymphoma, and myeloma (1). This effect on mortality reflects both excess incidence and excess mortality among those with cancer.

Since the 2002 IARC report, substantial new evidence supports a cause and effect relation between overweight, obesity, and the onset of these cancers further increasing the burden of cancer due to obesity (5). The American Institute for Cancer Research (AICR) and World Cancer Research Fund (WCRF) reported there is convincing evidence for a relation between obesity and esophageal, pancreatic, colorectal, postmenopausal breast, endometrial and kidney cancers with probable evidence for gallbladder. In addition, they found probable evidence that abdominal fatness in particular increases risk of pancreas, endometrial and postmenopausal breast cancer. Finally, emerging evidence suggests that obesity increases risk of aggressive prostate cancer (6). Overall we estimate that overweight and obesity causes approximately 20% of all cancer. Previously Doll and Peto (7) included overnutrition (overweight) with diet causing a combined 35% of all cancer.

To conclude that a cause and effect relation exists between obesity and cancer at each cancer site scientists pursue studies of mechanism that confirm the underlying biology of this relation and provide insights to guide prevention strategies. Take for example postmenopausal breast cancer. Among postmenopausal women obesity is directly related to circulating estradiol levels (8) which themselves are directly related to breast cancer risk (9-10). When the action of estrogens is interrupted by estrogen receptor modulators in randomized controlled trials, breast cancer incidence is reduced by approximately 50% (11-12).

Just as smoking cessation leads to a reduction in risk of lung cancer adding to the evidence of a cause and effect relation, so documenting a 50% reduction in risk of breast cancer among women who lost 10kg or more after menopause and kept it off (13) adds to both our understanding of this causal relation. In addition, focusing on weight loss after menopause, a time in life when obesity clearly increases risk of breast cancer, provides important evidence on the time frame for change in cause (weight) and subsequent change in cancer incidence. This reduction in incidence of postmenopausal breast cancer will follow the decline in circulating estrogen after weight loss.

For colon cancer, growing evidence points to insulin pathways mediating the effect of BMI and risk (14). Studies of blood glucose levels and colon cancer show a direct relation between higher glucose and subsequent risk (14). Providing further biologic rationale, c-peptide (15), a marker of insulin production, also shows this positive relation and animal models using insulin injection vs. saline show significant increases in colon cancer among those injected with insulin (16). Finally, preclinical data provides additional support for the insulin-IGF hypothesis of cancer risk, as outlined in several excellently detailed recent reviews (17-18). The PI3K/Akt pathway likely compromises the downstream target of insulin and is one of the most commonly altered in epithelial tumors.(18-19) In sum, strong evidence points to hyperinsulinemia as the direct pathway from adiposity to colon cancer.

Returning to the ACS committee report the concensus committee convened by ACS and the American Diabetes Association concluded that Diabetes (primarily type 2) is associated with an increased risk of liver, pancreas, endometrium, colon/rectum, breast, and bladder cancers. Furthermore, the association between diabetes and some cancers may be due in part to shared risk factors between the 2 diseases such as aging, obesity, diet, and physical inactivity. Possible mechanisms for a causal pathway between diabetes and cancer include hyperinsulinemia, hyperglycemia, and inflammation.

Building on this summary and the extensive work by Dr Renehan and colleagues revieweing the evidence linking obesity to cancer, we present summary estimates of relative risk from the rigorous meta-analysis by Renehan (5) and the likely pathway or mechanism for a causal relation between obesity and cancer (see Table 1 and 2).

Table 1. Relative Risk of Cancer per 5 kg/m² Increase in BMI, Males, and most likely causal mechanism
Cancer	RR	Causal mechanism
Oesophageal adenocarcinoma	1.52***	Reflux esophagitis and chronic irritation
Thyroid	1.33*	Unknown
Colon	1.24***	Insulin
Renal	1.24***	In part though hypertension
Liver	1.24	Fatty liver cirrhosis
Malignant melanoma	1.17**	?
Multiple myeloma	1.11***	Inflammatory pathways – IL6
Rectum	1.09***	?
Gallbladder	1.09	Chronic secretion-gallstones and irritation
Leukemia	1.08**	?
Pancreas	1.07	Possible insulin pathway
Non-Hodgkin lymphoma	1.06***	Inflammatory pathways – IL6
Prostate¶	1.03	?
Lung	0.76***	Smoking leads to leanness and causes lung cancer
Esophageal squamous	0.71***	Smoking leads to leanness and causes squamous esophageal cancer
Relative risk for a 5 point increase in BMI. For example, the relative risk linked to a BMI of 28 compared to a BMI of 23; or a BMI of 32 compared to 27.
*p < .0001; p < .01; *p < .05 ¶ biased to null as this includes predominantly low grade lesions
Adapted from Renehan et al, 2008; Fig 3 (5).

Table 2. Relative Risk of Cancer with RR per 5kg/m²Increased BMI, Females, and most likely causal mechanism
Cancer	RR	Causal mechanism
Endometrium	1.59***	Endogenous Estrogen
Gallbladder	1.59*	Chronic secretion-gallstones and irritation
Oseophageal adenocarcinoma	1.51***	Reflux esophagitis and chronic irritation
Renal	1.34***	In part through hypertension
Leukemia	1.17*	Unknown
Thyroid	1.14**	Unknown
Breast (postmenopausal)	1.12*	Endogenous estrogen
Pancreas	1.12*	Possible insulin pathway
Multiple myeloma	1.11***	Inflammatory pathways – IL6
Colon	1.09***	Insulin
Non-Hodgkin lymphoma	1.07	Inflammatory pathways – IL6
Liver	1.07	Fatty liver cirrhosis
Breast (premenopausal)	0.92**	Irregular menstrual cycles- hormones
Lung	0.8*	Smoking leads to leanness and causes lung cancer
Esophageal squamous	0.57***	Smoking leads to leanness and causes squamous esophageal cancer
Relative risk for a 5 point increase in BMI. For example, the relative risk linked to a BMI of 28 compared to a BMI of 23; or a BMI of 32 compared to 27.
*p < .0001; p < .01; *p < .05
Adapted from Renehan et al, 2008; Fig 4 ⁵.

Impact of obesity among cancer patients
Obesity also impacts outcomes among cancer patients. Growing evidence also points to benefits of physical activity for breast and colon cancers. Dosing of chemotherapy and radiation therapy among obese patients may also be impacted and therapy related toxicity may vary with level of obesity. These issues will be addressed in a subsequent post.

The burden of obesity on society continues to increase and warrants closer attention by health care providers, by policy makers, and within our communities. .

References

1. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. Apr 24 2003;348(17):1625-1638.

2. Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA. 2002;288(14):1723-1727.

3. Stewart ST, Cutler DM, Rosen AB. Forecasting the effects of obesity and smoking on U.S. life expectancy. N Engl J Med. Dec 3 2009;361(23):2252-2260.

4. International Agency for Research on Cancer. Weight Control and Physical Activity. Vol 6. Lyon: International Agency for Research on Cancer; 2002.

5. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. Feb 16 2008;371(9612):569-578.

6. Freedland SJ, Platz EA. Obesity and prostate cancer: making sense out of apparently conflicting data. Epidemiol Rev. 2007;29:88-97.

7. Doll R, Peto R. The Causes of Cancer: Quantitative Estimates of Avoidable Risks of Cancer in the United States Today. New York: Oxford University Press; 1981.

8. Hankinson SE, Colditz GA, Hunter DJ, et al. Reproductive factors and family history of breast cancer in relation to plasma estrogen and prolactin levels in postmenopausal women in the Nurses' Health Study (United States). Cancer Causes Control. May 1995;6(3):217-224.

9. Key TJ, Appleby PN, Reeves GK, et al. Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst. Aug 20 2003;95(16):1218-1226.

10. Missmer SA, Eliassen AH, Barbieri RL, Hankinson SE. Endogenous estrogen, androgen, and progesterone concentrations and breast cancer risk among postmenopausal women. J Natl Cancer Inst. Dec 15 2004;96(24):1856-1865.

11. Fisher B, Costantino J, Wickerham D, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst. 1998;90:1371-1388.

12. Martino S, Cauley JA, Barrett-Connor E, et al. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst. Dec 1 2004;96(23):1751-1761.

13. Eliassen AH, Colditz G, Rosner B, Willett W, Hankinson SE. Adult weight change and risk of postmenopausal breast cancer. JAMA. 2006;296:193-201.

14. Giovannucci E. Metabolic syndrome, hyperinsulinemia, and colon cancer: a review. Am J Clin Nutr. Sep 2007;86(3):s836-842.

15. Wei E, Ma J, Pollak M, et al. A prospective study of C-peptide, insulin-like growth factor-I, insulin-like growth factor binding protein-1, and the risk of colorectal cancer in women. Cancer Epidemiol Biomarkers Prev. 2005;14:850-855.

16. Giovannucci E. Insulin and colon cancer. Cancer Causes Control. 1995;6:164-179.

17. Roberts DL, Dive C, Renehan AG. Biological mechanisms linking obesity and cancer risk: new perspectives. Annu Rev Med. 2010;61:301-316.

18. Hursting SD, Lashinger LM, Wheatley KW, et al. Reducing the weight of cancer: mechanistic targets for breaking the obesity-carcinogenesis link. Best Pract Res Clin Endocrinol Metab. Aug 2008;22(4):659-669.

19. Carling D. The AMP-activated protein kinase cascade--a unifying system for energy control. Trends Biochem Sci. Jan 2004;29(1):18-24.

Breast Cancer Prevention

Tuesday, June 15, 2010 0 comments

New data from long term follow-up of women participating in the STAR trial, a study comparing Tamoxifen and Raloxifene (known as SERMS) for prevention of breast cancer, show strong and persisting benefits of reduced breast cancer risk after stopping therapy (see abstract). This is an important addition to our understanding. Based on follow-up of 18,747 women in the STAR trial the updated results highlight the value of extended follow-up of participants in trials to better understand the overall impact of interventions for cancer prevention. We summarized these key questions for cancer prevention in an earlier blog posting and in a recent article.

Moving from the results of the STAR trial to implementing prevention requires that we have an approach to identify women who are at increased risk of breast cancer. While numerous models have been developed to prediction of breast cancer, it is worth remembering that any of these models does not tell us who will get cancer and who will not, but rather we can place women according to their level of risk, much above average, above average, average, etc. This is the approach we use in Your Disease Risk and is based on evidence from communication science about understanding of risk. For decisions regarding use of a drug to prevent cancer, the challenge is balancing the risks of side effects against the known benefits. The higher the risk group taking the preventive agent the stronger the balance of benefits exceeding risks. This balance, of course, applies throughout medicine whether we talk about drugs, surgery, or other medical interventions.

Take for example the strong genetic predisposition to breast cancer that is present in women who carry the BRCA1 or BRCA2 mutation. Lifetime risk in these women is around 50 to 60% so among those with the mutation we have about a 50/50 chance of knowing who will get breast cancer. On the other hand the combined data from 10 studies now clearly show that for these high risk women bilateral oophorectomy halves their risk of breast cancer (see article).

To bring results from a randomized trial of efficacy to the patient population we must weigh risks of side effects against the expected benefits of therapy for individual patients (Glasziou and Irwig set out an approach for evidence based individualized treatment). We previously estimated a scenario to weight risks and benefits under the assumption that we wanted to prevent more breast cancers than major medical events that might be caused as side effects from taking drugs, see article. We show that among the 26 million women in the US between ages 50 and 69, 7.8 million have risk above a break even point and that over 22,000 cases of breast cancer can be avoided each year by using a SERM in this group. The new data add a refinement to these estimates as the benefit of taking a SERM persists after stopping and the side effects are reduced after stopping. This tips the ratio of benefits to risks more strongly in favor of taking drug to prevention breast cancer. The overall reduction in risk remains at about 50%, or halving the risk of breast cancer during the years the drug is taken and this benefit continuing after stopping.

What are the side effects? Tamoxifen causes endometrial cancer while Raloxifene does not. Pulmonary embolism and deep-vein thrombosis are now well recognized side effects of Tamoxifen. Raloxifene had significantly lower rates of these events in the STAR trial. Overall 2.47 thromboembolic events were reported per 1000 women per year among those taking Raloxifene. One approach to estimating benefits and risks assumes women have a 4% risk of breast cancer over the next 5 years. See related report. The benefits and risks are summarized below for 1000 women over 7 years

	Raloxifene	Tamoxifen
Invasive breast cancer prevented	15	20
Noninvasive breast cancer prevented	16	20
Endometrial cancer caused	0	2.25
Thromboembolic events caused	2.47	3.3
Benefit to risk ratio	31 vs. 2.47 or 13:1	40 vs. 5.55 or 7:1

If we rerun these numbers using a lower cut point for the 5-year risk of breast cancer, the benefit to risk ratio will come closer to 1.

Of course the importance placed on side effects from SERMS may differ among women. In our estimate, we assumed a deep vein thrombosis (a side effect of SERMS) was equal to a prevented breast cancer. Other options may apply in individual decision making. Tools to help women and their health care providers balance risks and benefits may soon help lay out these considerations.

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