Wednesday, May 20, 2015

Modest Weight Gain Increases Breast Cancer Risk in Premenopausal Women

by Graham A. Colditz, MD, DrPH

In a recent detailed analysis of weight change across the life course (funded by our NCI TREC center addressing obesity and cancer), we reported that short-term weight gain, defined as change over a 4-year time frame, significantly increased risk of both premenopausal and postmenopausal breast cancer (see report for free download – link Previous literature has largely focused on weight gain and weight loss in relation to postmenopausal breast cancer. Here, for the first time, we draw out detailed categories of weight change and consider change over 4 years and risk of breast cancer in the next 2-year interval of follow-up. While our TREC funded data analysis was ongoing and we were writing our manuscript a new report from Europe addressed weight change over approximately 4.7 years and subsequent risk of breast cancer.(2) That study had fewer premenopausal breast cancer cases than we had, but found largely similar results for short-term weight gain and increased risk of breast cancer. 

With 736 premenopausal breast cancer cases in the Nurses’ Health Study, we show that a weight gain of 10 or more pounds in just 4 years is associated with significantly higher risk of breast cancer in the subsequent years after the weight gain. Why does this matter? Well, lots of women gain weight through their premenopausal years. Based on previous findings, it's likely many of these women did not think that this could impact their risk of breast cancer? Here we show that short-term gain does increase risk, and that this risk is more important for receptor negative (that is ER-ve PR-ve) breast cancer – the type that is more common in premenopausal women and the type for which we don't have effective treatments. Weight gain of 10 or more pounds in 4 years during premenopausal life, more than doubles risk of this hard to treat type of breast cancer. In additional analyses, we observed that the adverse effect of weight gain was present among premenopausal women regardless of their starting BMI (body mass index), a measure of adiposity. Normal weight and overweight women all experienced the increase in risk of breast cancer.

In context, the majority of epidemiologic studies of breast cancer have focused on postmenopausal breast cancer. Fully 75 percent of breast cancer is diagnosed after menopause. On the other hand, waiting until menopause to begin screening (early detection) and to consider prevention strategies for higher risk women, misses any hope of prevention for the almost 1 in 4 breast cancers diagnosed before age 50. Weight gain in the premenopausal years may be contributing importantly to the burden of premenopausal disease. Furthermore, in Asia, rates of premenopausal breast cancer are rapidly rising. They are now approaching the rates in the US for women of similar ages.(3) ER-negative breast cancer is more common in premenopausal women – representing 30% of breast cancer diagnosed among women 35 to 44 but only about 12% among women age 65 and older.(4)

Global data attest to the growing obesity epidemic among women and men around the world. One consequence of this weight gain in women through their early adult years now looks to be increased breast cancer. As low and middle income countries develop, they also transition to higher rates of breast cancer. Adding strategies to prevent premenopausal breast cancer remains our highest priority, as this cancer has the highest societal burden, being diagnosed among women in their peak years of work productivity and family care.

The good news is that we can avoid weight gain through increasing physical activity and making healthier food choices.

  • Integrate physical activity and movement into your life.
  • Eat a diet rich in fruits, vegetables and whole grains.
  • Choose smaller portions and eat more slowly.
  • Use your bathroom scale regularly, so you keep surprise weight gain at bay.
  • Get a pedometer and work up to 10,000 or more steps per day.
For Parents and Grandparents
  • Limit children’s TV and computer time.
  • Encourage healthy snacking on fruits and vegetables.
  • Encourage activity during free time.
For more weight control tips, visit our colleagues' site at the Harvard School of Public Health: The Nutrition Source.


1. Rosner B, Eliassen AH, Toriola AT, Hankinson SE, Willett WC, Natarajan L, Colditz GA. Short-term weight gain and breast cancer risk by hormone receptor classification among pre- and postmenopausal women. Breast cancer research and treatment. 2015;150(3):643-53. doi: 10.1007/s10549-015-3344-0. PubMed PMID: 25796612; PMCID: 4383816.

2. Emaus MJ, van Gils CH, Bakker MF, Bisschop CN, Monninkhof EM, Bueno-de-Mesquita HB, Travier N, Berentzen TL, Overvad K, Tjonneland A, Romieu I, Rinaldi S, Chajes V, Gunter MJ, Clavel-Chapelon F, Fagherazzi G, Mesrine S, Chang-Claude J, Kaaks R, Boeing H, Aleksandrova K, Trichopoulou A, Naska A, Orfanos P, Palli D, Agnoli C, Tumino R, Vineis P, Mattiello A, Braaten T, Borch KB, Lund E, Menendez V, Sanchez MJ, Navarro C, Barricarte A, Amiano P, Sund M, Andersson A, Borgquist S, Olsson A, Khaw KT, Wareham N, Travis RC, Riboli E, Peeters PH, May AM. Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study. Int J Cancer. 2014. doi: 10.1002/ijc.28926. PubMed PMID: 24771551.

3. Jung KW, Won YJ, Kong HJ, Oh CM, Seo HG, Lee JS. Prediction of cancer incidence and mortality in Korea, 2013. Cancer research and treatment : official journal of Korean Cancer Association. 2013;45(1):15-21. doi: 10.4143/crt.2013.45.1.15. PubMed PMID: 23613666; PMCID: 3629359.

4. Colditz GA, Rosner BA, Chen WY, Holmes MD, Hankinson SE. Risk factors for breast cancer according to estrogen and progesterone receptor status. Journal of the National Cancer Institute. 2004;96(3):218-28. Epub 2004/02/05. PubMed PMID: 14759989.

Tuesday, May 19, 2015

When are risk factors good for identifying women at high risk of cancer

Media coverage this week draws attention to a well-known fact in epidemiologic research. A risk factor alone does not always identify the top stratum of risk for a disease. Kerlikowske and colleagues from the NCI-funded breast cancer surveillance consortium draw on prospective data to demonstrate for women that a mammographic report of dense breasts is not sufficient on its own to identify woman at high risk for breast cancer (see the story). This principle applies to heart disease, cancer and other illnesses. Professor Wald wrote eloquently on this more than a decade ago when he showed that the relative risk for any risk factor had to be huge to on its own identify a stratum at very high risk of disease.(1) A detailed presentation is available at the British Medical Journal. If we use a risk factor as a screening test to classify those who will get disease and those who will not, we may need a large relative risk. For example, using 2.8 as the relative risk (comparable to the top 10% of women scored on the Gail model in the Nurses’ Health Study), we will detect or predict only 15% of cancers.(2) To detect more than 50% of cancers with less than 5% false positive rate, we need a relative risk of more than 100. This is beyond the ability of lifestyle and genomic risk factors combined for most of our common major illnesses. Even women with BRCA 1 or 2 have only about 50% chance of developing breast cancer in their lifetime.

We might remember that many risk factors combine to increase (or decrease) risk of disease. Holding age constant (since we cannot change our age at any given time), we can see that for breast cancer several common risk factors such as family history may double a woman's risk. Never having children increases risk compared to women who have one or more children. A history of dense breasts (see recent media coverage) may increase risk 3-fold compared to those with the extreme of no dense breast tissue on mammography. This increase in risk is about the same as that seen in the subset of women with benign breast disease. For women with benign breast disease (BBD) confirmed by breast biopsy and whose pathology review (under the microscope) shows proliferative changes that include cells with atypia, the relative risk is 4 to 5 when their risk is compared to that of a women who has not had benign breast disease.(3-5)

To summarize risk, we multiply out the risk (increase or decrease) for each factor. In the Nurses’ Heath Study when we do this, we see that women in the top 10% of risk have more than 6 times the rate of breast cancer of those in the lowest 10 percent of risk.(6) This is true in each 5-year age group. Importantly, 25% of all breast cancers are diagnosed among the women in the top 10% of risk. Hence this group may be a subset of women for women prevention strategies should be emphasized. Our model for calculating breast cancer risk, validated in independent prospective data, outperforms the commonly used Gail model (7). This is in part because it includes several risk factors omitted from the Gail model – such as later age at menopause, use of postmenopausal hormones, alcohol, and obesity – all well known causes of breast cancer. (8-10)

What does this mean?

Being smart about how to interpret studies is important. Living a healthy lifestyle is the best insurance against getting cancer, heart disease diabetes, and other major illnesses. In fact, women who followed the American Cancer Society diet and physical activity guidelines (11) had significantly lower risk of cancer and all cause mortality during following than those who did not. Women in the lowest category of risk, following all the guidelines, had more than a 20% reduction in their risk of breast cancer over 12 years and more than 50% reduction in their risk of colorectal cancer. Put simply, during 12 years of follow-up, women who maintained a healthy weight, were physically active, consumed a diet with emphasis on plant sources, and limited alcohol to 1 drink or less per day, had significantly lower cancer risk compared to those who did not follow the guidelines.(12)

For tips on cancer prevention visit: 8IGHT WAYS to Stay Healthy and Prevent Disease


1. Wald NJ, Hackshaw AK, Frost CD. When can a risk factor be used as a worthwhile screening test? BMJ. 1999;319(7224):1562-5.
2. Rockhill B, Spiegelman D, Byrne C, Hunter DJ, Colditz GA. Validation of the Gail et al. model of breast cancer risk prediction and implications for chemoprevention. Journal of the National Cancer Institute. 2001;93(5):358-66. Epub 2001/03/10. PubMed PMID: 11238697.
3. London SJ, Connolly JL, Schnitt SJ, Colditz GA. A prospective study of benign breast disease and the risk of breast cancer. JAMA. 1992;267(7):941-4. Epub 1992/02/19. PubMed PMID: 1734106.
4. Marshall LM, Hunter DJ, Connolly JL, Schnitt SJ, Byrne C, London SJ, Colditz GA. Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 1997;6(5):297-301. Epub 1997/05/01. PubMed PMID: 9149887.
5. Dyrstad SW, Yan Y, Fowler AM, Colditz GA. Breast cancer risk associated with benign breast disease: systematic review and meta-analysis. Breast cancer research and treatment. 2015;149(3):569-75. doi: 10.1007/s10549-014-3254-6. PubMed PMID: 25636589.
6. Chen WY, Rosner B, Colditz GA. Moving forward with breast cancer prevention. Cancer. 2007;109(12):2387-91. PubMed PMID: 17464950.
7. Rosner BA, Colditz GA, Hankinson SE, Sullivan-Halley J, Lacey JV, Jr., Bernstein L. Validation of Rosner-Colditz breast cancer incidence model using an independent data set, the California Teachers Study. Breast cancer research and treatment. 2013;142(1):187-202. doi: 10.1007/s10549-013-2719-3. PubMed PMID: 24158759.
8. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2007: Lyon France). Alcohol consumption and ethyl carbamate. Lyon, France: International Agency for Research on Cancer; Distributed by WHO Press; 2010.
9. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans., World Health Organization. IAfRoC. Combined estrogen-progestogen contraceptives and combined estrogen-progestogen menopausal therapy. Lyon, France. Geneva: International Agency for Research on Cancer ; Distributed by WHO Press; 2007. ix, 528 p. p.
10. International Agency for Research on Cancer. Weight Control and Physical Activity. Lyon: International Agency for Research on Cancer; 2002. 315 p.
11. Kushi LH, Doyle C, McCullough M, Rock CL, Demark-Wahnefried W, Bandera EV, Gapstur S, Patel AV, Andrews K, Gansler T, American Cancer Society N, Physical Activity Guidelines Advisory C. American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2012;62(1):30-67. doi: 10.3322/caac.20140. PubMed PMID: 22237782.
12. Thomson CA, McCullough ML, Wertheim BC, Chlebowski RT, Martinez ME, Stefanick ML, Rohan TE, Manson JE, Tindle HA, Ockene J, Vitolins MZ, Wactawski-Wende J, Sarto GE, Lane DS, Neuhouser ML. Nutrition and Physical Activity Cancer Prevention Guidelines, Cancer Risk, and Mortality in the Women's Health Initiative. Cancer Prev Res (Phila). 2014;7(1):42-53. doi: 10.1158/1940-6207.CAPR-13-0258. PubMed PMID: 24403289.

Saturday, April 18, 2015

CNiC's Colditz Honored for Contributions to Prevention - Highlights Importance of Early Life in Breast Cancer Risk

Cancer News in Context's Graham Colditz is being honored tonight at the American Association for Cancer Research Annual Meeting in Philadelphia, Pennsylvania as an AACR 2014-2015 Scientific Awardee.

In the announcement of his 2014 Award for Outstanding Achievement in Cancer Prevention, AACR describes the honor and Colditz's contributions to the field:
The award is given annually to a scientist residing in any country in the world for his or her seminal contributions to the field of cancer prevention. Such investigations must have been conducted in basic, translational, clinical, epidemiological, or behavioral science in cancer prevention research. Further, these studies must have had not only a major impact on the field, but must also have stimulated new directions in this important area.

Colditz is an internationally recognized leader in cancer prevention. Colditz’s research includes developing statistical models to more accurately classify levels of risk for several cancers, and to clarify the importance of adolescent lifestyle in the prevention of breast cancer.
In his related blog post on the ACCR site -- A Youthful Approach: Expanding the Reach of Breast Cancer Prevention -- Colditz detailed the growing evidence showing that early life behaviors play a key role in later adult breast cancer risk.  The post was the site's number three most popular post of 2014.

Building on this evidence, Colditz has co-authored a forthcoming ebook on breast cancer that highlights a generational approach to preventing the disease.  Titled Together: Every Woman's Guide to Preventing Breast Cancer, the book is filled with engaging messages for mothers, daughters, grandmothers and women at all stages of life.  It is written for a general audience and is expected to be released late spring of this year.

More on early life and breast cancer.

Friday, April 3, 2015

New Dietary Recommendations Take Innovative Approach - and Not Everyone's Happy About It

By Yikyung Park, ScD
Editor's note: Not surprisingly, the recently released report from the Dietary Guidelines for Americans Advisory Committee was met with both praise and scorn.  Many in the medical and health fields lauded the report for its innovative approach to considering both the food environment and sustainability, as well as for its healthy eating recommendations, which focussed largely on consuming more plant-based foods. The food industry, however, took issue with many aspects of the report, with the meat industry seeming particularly up-in-arms to fight the report's recommendation to cut back on both red meat and processed meat.  A recent Op-Ed in New York Times highlights the hot-button issue red meat and health has become since the report's release.  CNiC's Yikyung Park explains these new recommendations, the process behind them, and some details about the new red meat guidelines.   
A recent report from the 2015 Dietary Guidelines Advisory Committee (DGAC) is gathering much attention from the public as well as from the food industries. Why and what is in this report?

Since 1980, the Department of Agriculture (USDA) and the Department of Health and Human Services (DHHS) jointly published the Dietary Guidelines for Americans every 5 years. To update the Guidelines, the Dietary Guidelines Advisory Committee (DGAC) is assembled and
reviews scientific and medical literature. The Committee submits a report that includes recommendations (not the actual guidelines) for a new set of dietary guidelines to the Secretaries of the USDA and DHHS. The USDA and DHHS write the actual guidelines after reviewing the report and comments submitted by the public. A new 2015 Dietary Guidelines for Americans is scheduled for release at the end of this year.

The recommendations for healthy eating that make up the Guidelines have been largely consistent through the years, but new scientific evidence results in some changes from edition to edition. Of note, the 2015 Guidelines Committee makes a recommendation that emphasizes dietary patterns and foods over nutrients and in doing so considers the importance of food environments and sustainability. The committee recognizes “the significant impact of food and beverages on environmental outcomes, from farm to plate to waste disposal, and, therefore, the need for dietary guidance to include the wider issue of sustainability.” The committee also highlights the importance of the food environment– those external factors that influence our food choices, from advertising to cafeteria menus – in making healthy choices.

In the report, the Committee recommends a healthy diet which is higher in vegetables, fruits, whole grains, low-fat (or non-fat) dairy, seafood, legumes, and nuts; moderate in alcohol; lower in red meat and processed meats; and low in sugar-sweetened foods and drinks and refined grains. The report also recommends actions for not only individuals and families, but also for communities, industry, and government to achieve and maintain healthy dietary patterns and the levels of physical activity needed to promote a healthy U.S. population. Among those are:
  • Aim to make healthy lifestyles and prevention a national and local priority and reality.
  • Establish healthy food environments.
  • Seek a paradigm shift in health care and public health toward a greater focus on prevention and integration with food systems.
  • Establish healthy food environments.
  • Support and expand access to healthy built environments and advocate wide community use.
  • Maintain strong support for federal food and nutrition programs.
  • Recognize and place priority on moving toward a more sustainable diet consistent with the healthy dietary pattern options described in this DGAC report. Access to sufficient, nutritious, and safe food is an essential element of food security for the U.S. population. A sustainable diet helps ensure this access for both the current population and future generations.

The Committee’s recommendation for eating less red meat and processed meat is strongly supported by a large body of scientific evidence on its adverse effects. Diets high in red meat and processed meat have been found to increase the risk of cardiovascular disease, diabetes, and cancer, especially colorectal cancer, as well as an increased risk of premature death. In addition, accumulating evidence as summarized in the report indicates that “in general, a dietary pattern that is higher in plant-based foods, such as vegetables, fruits, whole grains, legumes, nuts, and seeds, and lower in animal based foods is more health promoting and is associated with lesser environmental impact (GHG emissions and energy, land, and water use) than is the current average U.S. diet.”

This new report, however, is being heavily criticized by the meat industry, especially for taking environmental sustainability into consideration in making recommendations. But food industry’s attack on the dietary guidelines is not new. Whenever the DGA is updated, the food industry actively lobbies to influence the recommendation. Why? Because the Guidelines inform a host of governmental nutrition programs, including National School Lunch Program and meals in the military, and also influences food-related policies and laws. A new guideline emphasizing a healthy diet pattern which is mostly plant based and low in red and processed meat may cause the meat industry a huge business loss.

The Committee’s recommendations are based on convincing scientific evidence on diet and health as well as food environments and sustainability. At the same time, the Committee’s report is purely advisory. Whether the final guideline released at the end of this year by the USDA and DHHS will include these exact recommendations remains to be seen. Although historically USDA policies have been heavily influenced by the food industry, public comments can make a difference. The Committee report is currently available on the dietary guidelines website for public comments until May 8, 2015.

Wednesday, February 18, 2015

John Oliver Skewers Big Tobacco's Heavy-Handed Global Efforts (Video)

We're not prone to posting video clips from satirical news programs, but this weekend's piece from Last Week Tonight with John Oliver really captured why it is so important to keep up the fight against Big Tobacco.  While we still have a great deal of work to do to get tobacco under control in the United States, the situation is even more pressing across the globe, where tobacco companies use heavy-handed tactics to squelch anti-tobacco efforts.  Mr. Oliver deconstructs these tactics in great - and humorous - detail, finishing with his own campaign idea to subvert their efforts.

Warning: video contain [EXPLICIT] language.

Wednesday, February 11, 2015

Study Finds Tobacco is Even Deadlier Than Typically Estimated. Fighting It Should Remain "Our Highest Priority"

Photo (Creattive Commons): Flickr/jeffjose
It can be easy to think that we've won the fight against tobacco.  Rates of smoking have plummeted since the 1960s.  Most restaurants, bars, and workplaces across the country are now largely smoke-free.  And many of us may have trouble coming up with a single family member or close friend who smokes.

Yet, the reality is that tobacco remains a persistent and insidious problem.   Over 40 million adult Americans still smoke.  That's 18 percent of the population, and rates can vary wildly, with some groups of people in the single digits and others closer to 50 percent.  Smoking rates in adults with  advanced college degrees hovers around 6 percent, while rates in those with GEDs is over 40 percent.  Smoking rates break across income as well, with those making more money smoking at significantly lower rates than those making less.

Now, a new paper published today in the New England Journal of Medicine finds that the ill-effects of tobacco likely reach well beyond what we've typically understood.  It's estimated that in the United States there are approximately 480,000 deaths per year from the 21 broad diseases said to be caused by smoking.  This new study by Carter et al pulls together data from five large cohort studies and reveals that a number of additional categories of diseases should likely be included in the smoking mortality estimates - things like breast cancer, prostate cancer, infections, and kidney failure.  When these diseases are taken into account, the number of deaths each year in the United States from smoking balloon by an additional 60,000 to 120,000 deaths.

Cancer News in Context's Graham Colditz, MD, DrPh writes in an accompanying editorial that:
A total of 60,000 excess deaths is a number that by itself would have an important public health impact, since it is in line with annual deaths in the United States from excessive alcohol intake or low fruit and vegetable intake.

When combined with the existing estimates of smoking-related deaths it becomes abundantly clear that while there have been great successes in tobacco control there is still a great deal of work to accomplish.  Colditz continues in the editorial to highlight the complexities of tobacco use in society and that successful efforts to curb use and aid smoking cessation will take wide-ranging efforts that cut across issues of policy and healthcare, among others.

He concludes by reaffirming the need to keep up the vigorous fight against tobacco - not only for society and for the United States, but for individuals and for other countries as well:
Tobacco control must be our highest priority here and globally to advance population health, to reduce economic burden, and to extend years of health and productive life for all citizens.

More CNiC posts on tobacco, included the latest evidence on smoking and breast cancer.


Smoking and Mortality — Beyond Established Causes
Brian D. Carter, M.P.H., Christian C. Abnet, Ph.D., Diane Feskanich, Sc.D., Neal D. Freedman, Ph.D., Patricia Hartge, Sc.D., Cora E. Lewis, M.D., Judith K. Ockene, Ph.D., Ross L. Prentice, Ph.D., Frank E. Speizer, M.D., Michael J. Thun, M.D., and Eric J. Jacobs, Ph.D.
N Engl J Med 2015; 372:631-640

Smoke Alarm — Tobacco Control Remains Paramount
Graham A. Colditz, M.D.
N Engl J Med 2015; 372:665-666