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Preventing breast cancer now by acting on what we already know

Preventing breast cancer now by acting on what we already know www.nature.com/npjbcancer All rights reserved 2374-4677/15 PERSPECTIVE OPEN Preventing breast cancer now by acting on what we already know 1,2 1,2 Graham A Colditz and Kari Bohlke The age-specific rate of breast cancer rises rapidly through premenopausal years and significantly more slowly after menopause. Reproductive factors affect cell proliferation and the accumulation of genetic changes. Lifetime risk of breast cancer is linearly related to the length of the interval from menarche to first birth. Lifestyle changes that accompany industrialization, together with shifting reproductive patterns, drive up incidence rates. Prevention must begin early in the life as almost one-quarter of cases are diagnosed before age 50 in high-income countries. This requires greater emphasis on prevention across the life course to address the global burden of breast cancer. npj Breast Cancer (2015) 1, 15009; doi:10.1038/npjbcancer.2015.9; published online 22 July 2015 The burden of breast cancer is worldwide and growing. In 2012, hormones, whether endogenous or exogenous, promote tumor nearly 1.7 million new cases of breast cancer were diagnosed growth. Second, recent task force reports on breast cancer prevention worldwide, accounting for 25% of all new cancer cases in women. from the US National Institutes of Environmental Health Sciences The incidence of the disease has increased sharply in low- and jointly with the National Cancer Institute and the Institute of middle-income countries, a trend expected to continue as Medicine urge the nation to focus on risk factors at time periods economic development creates lifestyle factors that heighten in a woman’s life that are important in the etiology of breast breast cancer risk for women in those countries. Moreover, low- cancer. These time periods begin in childhood, before and during and middle-income nations cannot afford the costs of widespread first breast development, and before the full differentiation of technology-based medical care for their populations, whereas in breast tissue that occurs with the birth of a woman’s first baby. wealthy nations, projected expenses for clinical treatment are Breast cancer incidence models show breast tissue aging soaring. or the underlying rate at which the carcinogenic process is taking It is time to place more emphasis on breast cancer prevention, place occurs most rapidly from menarche to the first birth that is, lowering the risk or reducing the incidence of new cases. with cyclical production of estrogen and progesterone during Evidence from a wide range of studies—randomized trials, each menstrual cycle with increased mitotic rate during the luteal epidemiological, animal—has identified specific lifestyle and 10,11 phase of the cycle. After menarche, cell proliferation decreases behavioral factors that affect breast cancer risk. Researchers also with age through premenopausal years. The rate of breast now better understand that breast cancer risk develops early in cancer increases rapidly up to menopause and then far more life and accumulates across a woman’s entire lifespan. This article slowly after menopause. Early menopause (natural or due to discusses specific actions that women and their physicians can surgical removal of ovaries) reduces subsequent risk of breast take to reduce breast cancer risk, and argues that, depending on 10–13 cancer. when in her lifespan a woman integrates risk-reduction behaviors, Third, childhood exposure to three factors—excess energy as much as 50–70% of breast cancer can be prevented through intake leading to weight gain and obesity, high animal protein primary prevention. intake and low intake of fruits, vegetables, and whole grains, and What is heightening the risk of breast cancer? It is the interplay little or no physical activity—influences both onset of menarche of (1) increases in hormonal drivers, (2) the changes in women’s 14 and height growth rate. This is when breast tissue is most height growth rate and reproductive patterns, and (3) lifestyle susceptible to carcinogenesis. Height is related to increased risk of changes arising from economic development. These are not the breast cancer before and after menopause, and reflects nutrition only modifiable factors that affect breast cancer risk (exposure to intakes through childhood. Controlled trials show milk intake, for ionizing radiation, for example, also increases risk), but they are example, increases height growth rate. A prospective study of among the most common. Let us start with hormones. There is childhood diet and growth shows higher vegetable protein intake very strong evidence that hormones such as estrogen and at ages 3–5 is related to slower height growth rate and later age at progesterone are major drivers of breast cancer growth. For menarche, whereas higher animal protein intake is related to example, combination estrogen plus progestin therapy has been increased peak height growth velocity. In a prospective analysis classified as a carcinogen based on laboratory, epidemiologic, and of weight and height from school records of over 117,000 women randomized trial evidence. And data from randomized trials show in Denmark, height growth rate from 8 to 14 years of age that selective estrogen receptor modulators and aromatase independently predicted risk for beast cancer, accounting for 15% 6 17 inhibitors significantly reduce breast cancer incidence. These of the population of burden of breast cancer. Higher peak height 1 2 Division of Public Health Sciences, Department of Surgery, Washington University in St Louis, St Louis, MO, USA and Siteman Cancer Center, Washington University in St Louis, St Louis, MO, USA. Correspondence: GA Colditz (colditzg@wustl.edu) Received 28 April 2015; accepted 19 June 2015 © 2015 Breast Cancer Research Foundation/Macmillan Publishers Limited Preventing breast cancer GA Colditz and K Bohlke growth velocity is positively related to the risk of premenopausal and excess alcohol consumption create a toxic physiologic context and postmenopausal breast cancer indicating that growth rate, that is directly related to increased breast cancer risk at any 31,32 independent of age at menarche, has a direct influence on lifelong age. Women in the United States who followed the healthy 17,18 breast cancer risk. China Health and Nutrition Survey data lifestyle had significantly lower incidence of new breast cancers show that among ages 2–18 over the 20-year period from 1991 to (20% few cases) than those who did not, after controlling for all 2011, a marked decrease in intake of legumes (22% decrease) and other risk factors, education, and race/ethnicity. coarse grains (71% decrease) with an increase in animal-source Timing of prevention therefore matters. Because 22% of breast 19 33 foods (50% increase). Yet evidence supports higher fiber intake cancer is diagnosed in premenopausal women and is often more during adolescence protecting against benign breast disease and aggressive than cancers diagnosed in postmenopausal women, it 20–22 invasive breast cancer. makes sense to start prevention early in life when it can have These three factors plus alcohol have dramatically affected both maximum impact. For example, prevention begun in childhood the amount of hormones and the length of time women’s bodies and continuing through adolescence and early adult years can are exposed to them. Beginning three centuries ago in Europe, reduce development of premalignant or intermediate lesions that 21,34 then in the United States, economic development spurred are on the pathway to breast cancer. The evidence for this increases in these factors that have driven these endogenous comes from prospective data recorded in childhood, adolescence, hormonal exposures within women to new levels. For example, and early adult years and includes evidence for alcohol, a known in traditional rural life with menarche at 17, a typical woman had breast carcinogen. Women who avoided alcohol intake through perhaps 26 menstrual cycles (±2 years) between menarche and adolescence and early adult years have significantly lower the birth of her first baby. Now, with earlier menarche at, say, age incidence of premalignant and invasive breast cancers. 12 and a much later age of first birth (e.g., 30 years), a woman Recommendations for the reduction in breast cancer burden has about 234 cycles (18 years × 13 cycles/year), before the full from the U.S. Institute of Medicine, the World Cancer Research cellular differentiation that accompanies breast development Fund/American Institute for Cancer Research, and the American during first pregnancy; this is an increase of more than 200 cycles Cancer Society, when applied across the life course, generate the compared with pre-industrialization reproductive patterns. This following potential reductions in breast cancer burden (see means that she is exposed to over 200 additional luteal phase Table 1) to illustrate the potential benefit of beginning prevention proliferative cycles of breast cell growth and the potential to early. A large body of epidemiologic evidence suggests that up to accumulate genetic alterations. 68% of breast cancer could potentially be prevented by efforts Breast cancer in Asia over the past 50 years illustrates the that begin in childhood and adolescence; in contrast, if prevention impact of these factors, highlighting how changes within a were delayed until age 50, 22% of cancers would already be population can occur, and very quickly. In Korea, age at menarche diagnosed, and a smaller percentage of all cancers (up to 50%) decreased from an average of 16.9 among women born in would be potentially preventable. 1920–1924 to 13.8 among women born in 1980–1985 (ref. 25); Can adopting these changes really make a difference? There is fertility decreased from an average of 6 births per woman in precedent in the case of combination estrogen plus progestin 1960 to 5 in 1970 to 1.23 in 2010 (ref. 26) and age at first birth hormone therapy use. Following the publication of results from increased to 30, by 2010, on average. In Singapore, Hong Kong, the Women’s Health Initiative, a randomized trial that confirmed and China, similar changes have occurred. In association with previous epidemiologic data showing increasing risk for breast these societal changes, the incidence of breast cancer in Korea cancer with increasing duration of use of combination estrogen for women of age 45–49 has tripled from 45 cases/100,000 plus progestin, population and individual level data showed a among women in born 1943–1945 (ref. 10) to 140 cases/100,000 rapid decrease in use of combination estrogen plus progestin by among women born in 1960–1962 (ref. 29). China has followed women around the world, and incidence of breast cancer in 30 38,39 suit. women 50 years and older decreased. On the basis of these The how and when of breast cancer prevention. It is neither epidemiologic and randomized trial data, the International Agency desirable nor feasible to shift reproductive patterns back to pre- for Research on Cancer classified combination estrogen plus industrial levels. However, the nation can support women in progestin as a breast carcinogen. Rates of breast cancer in a tackling the same four factors that originally caused shifts in cohort of women undergoing mammographic screening declined societal reproductive patterns. Excess energy intake that leads to by 5% per year from 2000 to 2003 (ref. 38). Thus, changes in weight gain and obesity; high animal protein intake and low intake behavior can have positive effects on individual women and the of fruits, vegetable, and whole grains; little or no physical activity; aggregate of those effects can have a societal impact. Table 1. Population prevention strategies for breast cancer Recommended risk-reduction strategies Percentage of total breast cancers preventable in the United States (%) Establish and maintain childhood dietary intake of vegetables, fruits, and whole grains, and reduce 3 3,20,35,36 animal protein 35,36 Increase and maintain physical activity through childhood, adolescence, and adult years 11 35,36 Avoid and reduce weight gain during the adult years 25–32 Achieve a sustained 10% weight loss among postmenopausal women 25 35,36 Reduce or eliminate alcohol intake between menarche and first birth 3 35,36 Reduce or eliminate alcohol intake among adult women throughout the life course 3 Continue to reduce use of estrogen plus progestin hormone therapy (a known carcinogen) 3 For high-risk women, increase access to and use of drugs targeted to reduce breast cancer risk (e.g., 11 6,8 Tamoxifen) Reduction in breast cancer cases estimated from population prevalence of exposure and magnitude of observed associations to estimate population attributable risk. npj Breast Cancer (2015) 15009 © 2015 Breast Cancer Research Foundation/Macmillan Publishers Limited Preventing breast cancer GA Colditz and K Bohlke Building awareness of the potential for prevention works. ACKNOWLEDGMENTS Similar to the scientific evidence and prevention messaging that GAC is supported in part by an American Cancer Society Clinical Research led to the drop in the use of estrogen plus progestin therapy, Professorship, by the Breast Cancer Research Foundation, and the Foundation for another national effort to reduce and eliminate tobacco use has Barnes-Jewish Hospital. KB is supported by the Foundation for Barnes-Jewish Hospital. had significant impact on the health of women and men. Trials show that prevention works. Building on the Institute of Medicine report, one research COMPETING INTERESTS prevention priority is to better understand the lifestyle factors The authors declare no conflict of interest. (diet patterns, exercise, etc.) in childhood and in the critical window from menarche to first pregnancy that offer the greatest protections. Because breast cancer risk gathers across a woman’s REFERENCES lifetime, the scientific focus must move away from a concentration 1 International Agency for Research on Cancer GLOBOCAN 2012: Estimated Cancer on exposures immediately before diagnosis. In our view, and that 42 Incidence, Mortality and Prevalence Worldwide in 2012. International Agency for of Vogelstein, achieving the full promise of breast cancer Research on Cancer, World Health Organization: Lyon, France, 2012. http://glo- prevention calls for government and philanthropic organizations bocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Cited 26 January 2014. Section on to make a much greater allocation of resources to prevention; that Cancer Information. is, improving prevention messages and understanding for women, 2 Sullivan R, Peppercorn J, Sikora K, Zalcberg J, Meropol NJ, Amir E et al. Delivering their daughters, and mothers. This requires full implementation of affordable cancer care in high-income countries. 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This 21 Berkey CS, Willett WC, Tamimi RM, Rosner B, Frazier AL, Colditz GA. Vegetable protein subpopulation must be identified, limiting applicability. These and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign treatments would do little to stem the increasing incidence of breast disease in young women. Breast Cancer Res Treat 2013; 141:299–306. breast cancer globally. 22 Su X, Tamimi RM, Collins LC, Baer HJ, Cho E, Sampson L et al. Intake of fiber and If we act and act now, shifting the balance and focus to earlier nuts during adolescence and incidence of proliferative benign breast disease. life, supported by additional resources devoted to implementing Cancer Causes Control 2010; 21: 1033–1046. prevention, bringing messages and bolstering lifestyle and risk- 23 Weinberg RA. Multistep tumorigenesis. The Biology of Cancer. Garland Science, reduction behaviors during the critical time points in life, we stand Taylor & Francis Group, LLC: New York, NY, 2007, pp 399–462. a good chance of significantly reducing the burden of breast 24 OECD OECD Health Data 2010: Statistics and Indicators 2010, http://www.oecd.org/ cancer now and for future generations. els/soc/SF_2_3_Age_mothers_childbirth.pdf; accessed 20 April, 2015. © 2015 Breast Cancer Research Foundation/Macmillan Publishers Limited npj Breast Cancer (2015) 15009 Preventing breast cancer GA Colditz and K Bohlke 25 Cho GJ, Park HT, Shin JH, Hur JY, Kim YT, Kim SH et al. Age at menarche in a 37 Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML Korean population: secular trends and influencing factors. Eur J Pediatr 2010; 169: et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal 89–94. women: principal results From the Women’s Health Initiative randomized 26 Lim JW. The changing trends in live birth statistics in Korea, 1970 to 2010. Korean controlled trial. JAMA 2002; 288:321–333. J Pediatr 2011; 54:429–435. 38 Kerlikowske K, Miglioretti DL, Buist DS, Walker R, Carney PA. Declines in invasive 27 Keegan TH, Chang ET, John EM, Horn-Ross PL, Wrensch MR, Glaser SL et al. Recent breast cancer and use of postmenopausal hormone therapy in a screening changes in breast cancer incidence and risk factor prevalence in San Francisco mammography population. J Natl Cancer Inst 2007; 99:1335–1339. Bay area and California women: 1988 to 2004. Breast Cancer Res 2007; 9: R62. 39 Clarke CA, Glaser SL, Uratsu CS, Selby JV, Kushi LH, Herrinton LJ. Recent declines in 28 Perry CS, Otero JC, Palmer JL, Gross AS. Risk factors for breast cancer in East Asian hormone therapy utilization and breast cancer incidence: clinical and population- women relative to women in the West. Asa-Pacific J Clinical Oncology 2009; 5: based evidence. J Clin Oncol 2006; 24:e49–e50. 219–231. 40 Koh HK, Sebelius KG. Ending the tobacco epidemic. JAMA 2012; 308:767–768. 29 Jung KW, Won YJ, Kong HJ, Oh CM, Seo HG, Lee JS. Prediction of cancer incidence 41 de Ruyter JC, Olthof MR, Seidell JC, Katan MB. A trial of sugar-free or sugar-sweetened and mortality in Korea, 2013. Cancer Res Treat 2013; 45:15–21. beverages and body weight in children. NEnglJMed 2012; 367:1397–1406. 30 Shin HR, Joubert C, Boniol M, Hery C, Ahn SH, Won YJ et al. Recent trends and 42 Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr., Kinzler KW. patterns in breast cancer incidence among Eastern and Southeastern Cancer genome landscapes. Science 2013; 339: 1546–1558. Asian women. Cancer Causes Control 2010; 21: 1777–1785. 43 World Health Organization Global Action Plan for Prevention and Control of Non- 31 Thomson CA, McCullough ML, Wertheim BC, Chlebowski RT, Martinez ME, communicable Diseases, 2013-2020 2013. http://www.who.int/cardiovascular_ Stefanick ML et al. Nutrition and physical activity cancer prevention guidelines, diseases/15March2013UpdatedRevisedDraftActionPlan.pdf. 15 March 2013. cancer risk, and mortality in the women’s health initiative. Cancer Prev Res (Phila) 44 Atwood K, Colditz GA, Kawachi I. From public health science to prevention policy: 2014; 7:42–53. placing science in its social and political contexts. Am J Public Health 1997; 87: 32 Romaguera D, Vergnaud AC, Peeters PH, van Gils CH, Chan DS, Ferrari P et al. Is 1603–1606. concordance with World Cancer Research Fund/American Institute for Cancer 45 Campeau PM, Foulkes WD, Tischkowitz MD. Hereditary breast cancer: new genetic Research guidelines for cancer prevention related to subsequent risk of cancer? developments, new therapeutic avenues. Hum Genet 2008; 124:31–42. Results from the EPIC study. Am J Clin Nutr 2012; 96: 150–163. 46 Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates 33 American Cancer Society Breast Cancer Facts & Figures 2013-2014. American associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 muta- Cancer Society: Atlanta, GA, USA, 2013. tion carriers. J Natl Cancer Inst 2009; 101:80–87. 34 Liu Y, Colditz GA, Rosner B, Berkey CS, Collins LC, Schnitt SJ et al. Alcohol intake between menarche and first pregnancy: a prospective study of breast cancer risk. J Natl Cancer Inst 2013; 105: 1571–1578. This work is licensed under a Creative Commons Attribution 4.0 35 World Cancer Research Fund Food, Nutrition, Physical Activity, and the Prevention International License. The images or other third party material in this of Cancer: A Global Perspective. AICR: Washington, DC, USA, 2007. article are included in the article’s Creative Commons license, unless indicated 36 Kushi LH, Doyle C, McCullough M, Rock CL, Demark-Wahnefried W, Bandera EV otherwise in the credit line; if the material is not included under the Creative Commons et al. American Cancer Society Guidelines on nutrition and physical activity for license, users will need to obtain permission from the license holder to reproduce the cancer prevention: reducing the risk of cancer with healthy food choices and material. To view a copy of this license, visit http://creativecommons.org/licenses/ physical activity. CA Cancer J Clin 2012; 62:30–67. by/4.0/ npj Breast Cancer (2015) 15009 © 2015 Breast Cancer Research Foundation/Macmillan Publishers Limited http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png npj Breast Cancer Springer Journals

Preventing breast cancer now by acting on what we already know

npj Breast Cancer , Volume 1 (1) – Jul 22, 2015

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Abstract

www.nature.com/npjbcancer All rights reserved 2374-4677/15 PERSPECTIVE OPEN Preventing breast cancer now by acting on what we already know 1,2 1,2 Graham A Colditz and Kari Bohlke The age-specific rate of breast cancer rises rapidly through premenopausal years and significantly more slowly after menopause. Reproductive factors affect cell proliferation and the accumulation of genetic changes. Lifetime risk of breast cancer is linearly related to the length of the interval from menarche to first birth. Lifestyle changes that accompany industrialization, together with shifting reproductive patterns, drive up incidence rates. Prevention must begin early in the life as almost one-quarter of cases are diagnosed before age 50 in high-income countries. This requires greater emphasis on prevention across the life course to address the global burden of breast cancer. npj Breast Cancer (2015) 1, 15009; doi:10.1038/npjbcancer.2015.9; published online 22 July 2015 The burden of breast cancer is worldwide and growing. In 2012, hormones, whether endogenous or exogenous, promote tumor nearly 1.7 million new cases of breast cancer were diagnosed growth. Second, recent task force reports on breast cancer prevention worldwide, accounting for 25% of all new cancer cases in women. from the US National Institutes of Environmental Health Sciences The incidence of the disease has increased sharply in low- and jointly with the National Cancer Institute and the Institute of middle-income countries, a trend expected to continue as Medicine urge the nation to focus on risk factors at time periods economic development creates lifestyle factors that heighten in a woman’s life that are important in the etiology of breast breast cancer risk for women in those countries. Moreover, low- cancer. These time periods begin in childhood, before and during and middle-income nations cannot afford the costs of widespread first breast development, and before the full differentiation of technology-based medical care for their populations, whereas in breast tissue that occurs with the birth of a woman’s first baby. wealthy nations, projected expenses for clinical treatment are Breast cancer incidence models show breast tissue aging soaring. or the underlying rate at which the carcinogenic process is taking It is time to place more emphasis on breast cancer prevention, place occurs most rapidly from menarche to the first birth that is, lowering the risk or reducing the incidence of new cases. with cyclical production of estrogen and progesterone during Evidence from a wide range of studies—randomized trials, each menstrual cycle with increased mitotic rate during the luteal epidemiological, animal—has identified specific lifestyle and 10,11 phase of the cycle. After menarche, cell proliferation decreases behavioral factors that affect breast cancer risk. Researchers also with age through premenopausal years. The rate of breast now better understand that breast cancer risk develops early in cancer increases rapidly up to menopause and then far more life and accumulates across a woman’s entire lifespan. This article slowly after menopause. Early menopause (natural or due to discusses specific actions that women and their physicians can surgical removal of ovaries) reduces subsequent risk of breast take to reduce breast cancer risk, and argues that, depending on 10–13 cancer. when in her lifespan a woman integrates risk-reduction behaviors, Third, childhood exposure to three factors—excess energy as much as 50–70% of breast cancer can be prevented through intake leading to weight gain and obesity, high animal protein primary prevention. intake and low intake of fruits, vegetables, and whole grains, and What is heightening the risk of breast cancer? It is the interplay little or no physical activity—influences both onset of menarche of (1) increases in hormonal drivers, (2) the changes in women’s 14 and height growth rate. This is when breast tissue is most height growth rate and reproductive patterns, and (3) lifestyle susceptible to carcinogenesis. Height is related to increased risk of changes arising from economic development. These are not the breast cancer before and after menopause, and reflects nutrition only modifiable factors that affect breast cancer risk (exposure to intakes through childhood. Controlled trials show milk intake, for ionizing radiation, for example, also increases risk), but they are example, increases height growth rate. A prospective study of among the most common. Let us start with hormones. There is childhood diet and growth shows higher vegetable protein intake very strong evidence that hormones such as estrogen and at ages 3–5 is related to slower height growth rate and later age at progesterone are major drivers of breast cancer growth. For menarche, whereas higher animal protein intake is related to example, combination estrogen plus progestin therapy has been increased peak height growth velocity. In a prospective analysis classified as a carcinogen based on laboratory, epidemiologic, and of weight and height from school records of over 117,000 women randomized trial evidence. And data from randomized trials show in Denmark, height growth rate from 8 to 14 years of age that selective estrogen receptor modulators and aromatase independently predicted risk for beast cancer, accounting for 15% 6 17 inhibitors significantly reduce breast cancer incidence. These of the population of burden of breast cancer. Higher peak height 1 2 Division of Public Health Sciences, Department of Surgery, Washington University in St Louis, St Louis, MO, USA and Siteman Cancer Center, Washington University in St Louis, St Louis, MO, USA. Correspondence: GA Colditz (colditzg@wustl.edu) Received 28 April 2015; accepted 19 June 2015 © 2015 Breast Cancer Research Foundation/Macmillan Publishers Limited Preventing breast cancer GA Colditz and K Bohlke growth velocity is positively related to the risk of premenopausal and excess alcohol consumption create a toxic physiologic context and postmenopausal breast cancer indicating that growth rate, that is directly related to increased breast cancer risk at any 31,32 independent of age at menarche, has a direct influence on lifelong age. Women in the United States who followed the healthy 17,18 breast cancer risk. China Health and Nutrition Survey data lifestyle had significantly lower incidence of new breast cancers show that among ages 2–18 over the 20-year period from 1991 to (20% few cases) than those who did not, after controlling for all 2011, a marked decrease in intake of legumes (22% decrease) and other risk factors, education, and race/ethnicity. coarse grains (71% decrease) with an increase in animal-source Timing of prevention therefore matters. Because 22% of breast 19 33 foods (50% increase). Yet evidence supports higher fiber intake cancer is diagnosed in premenopausal women and is often more during adolescence protecting against benign breast disease and aggressive than cancers diagnosed in postmenopausal women, it 20–22 invasive breast cancer. makes sense to start prevention early in life when it can have These three factors plus alcohol have dramatically affected both maximum impact. For example, prevention begun in childhood the amount of hormones and the length of time women’s bodies and continuing through adolescence and early adult years can are exposed to them. Beginning three centuries ago in Europe, reduce development of premalignant or intermediate lesions that 21,34 then in the United States, economic development spurred are on the pathway to breast cancer. The evidence for this increases in these factors that have driven these endogenous comes from prospective data recorded in childhood, adolescence, hormonal exposures within women to new levels. For example, and early adult years and includes evidence for alcohol, a known in traditional rural life with menarche at 17, a typical woman had breast carcinogen. Women who avoided alcohol intake through perhaps 26 menstrual cycles (±2 years) between menarche and adolescence and early adult years have significantly lower the birth of her first baby. Now, with earlier menarche at, say, age incidence of premalignant and invasive breast cancers. 12 and a much later age of first birth (e.g., 30 years), a woman Recommendations for the reduction in breast cancer burden has about 234 cycles (18 years × 13 cycles/year), before the full from the U.S. Institute of Medicine, the World Cancer Research cellular differentiation that accompanies breast development Fund/American Institute for Cancer Research, and the American during first pregnancy; this is an increase of more than 200 cycles Cancer Society, when applied across the life course, generate the compared with pre-industrialization reproductive patterns. This following potential reductions in breast cancer burden (see means that she is exposed to over 200 additional luteal phase Table 1) to illustrate the potential benefit of beginning prevention proliferative cycles of breast cell growth and the potential to early. A large body of epidemiologic evidence suggests that up to accumulate genetic alterations. 68% of breast cancer could potentially be prevented by efforts Breast cancer in Asia over the past 50 years illustrates the that begin in childhood and adolescence; in contrast, if prevention impact of these factors, highlighting how changes within a were delayed until age 50, 22% of cancers would already be population can occur, and very quickly. In Korea, age at menarche diagnosed, and a smaller percentage of all cancers (up to 50%) decreased from an average of 16.9 among women born in would be potentially preventable. 1920–1924 to 13.8 among women born in 1980–1985 (ref. 25); Can adopting these changes really make a difference? There is fertility decreased from an average of 6 births per woman in precedent in the case of combination estrogen plus progestin 1960 to 5 in 1970 to 1.23 in 2010 (ref. 26) and age at first birth hormone therapy use. Following the publication of results from increased to 30, by 2010, on average. In Singapore, Hong Kong, the Women’s Health Initiative, a randomized trial that confirmed and China, similar changes have occurred. In association with previous epidemiologic data showing increasing risk for breast these societal changes, the incidence of breast cancer in Korea cancer with increasing duration of use of combination estrogen for women of age 45–49 has tripled from 45 cases/100,000 plus progestin, population and individual level data showed a among women in born 1943–1945 (ref. 10) to 140 cases/100,000 rapid decrease in use of combination estrogen plus progestin by among women born in 1960–1962 (ref. 29). China has followed women around the world, and incidence of breast cancer in 30 38,39 suit. women 50 years and older decreased. On the basis of these The how and when of breast cancer prevention. It is neither epidemiologic and randomized trial data, the International Agency desirable nor feasible to shift reproductive patterns back to pre- for Research on Cancer classified combination estrogen plus industrial levels. However, the nation can support women in progestin as a breast carcinogen. Rates of breast cancer in a tackling the same four factors that originally caused shifts in cohort of women undergoing mammographic screening declined societal reproductive patterns. Excess energy intake that leads to by 5% per year from 2000 to 2003 (ref. 38). Thus, changes in weight gain and obesity; high animal protein intake and low intake behavior can have positive effects on individual women and the of fruits, vegetable, and whole grains; little or no physical activity; aggregate of those effects can have a societal impact. Table 1. Population prevention strategies for breast cancer Recommended risk-reduction strategies Percentage of total breast cancers preventable in the United States (%) Establish and maintain childhood dietary intake of vegetables, fruits, and whole grains, and reduce 3 3,20,35,36 animal protein 35,36 Increase and maintain physical activity through childhood, adolescence, and adult years 11 35,36 Avoid and reduce weight gain during the adult years 25–32 Achieve a sustained 10% weight loss among postmenopausal women 25 35,36 Reduce or eliminate alcohol intake between menarche and first birth 3 35,36 Reduce or eliminate alcohol intake among adult women throughout the life course 3 Continue to reduce use of estrogen plus progestin hormone therapy (a known carcinogen) 3 For high-risk women, increase access to and use of drugs targeted to reduce breast cancer risk (e.g., 11 6,8 Tamoxifen) Reduction in breast cancer cases estimated from population prevalence of exposure and magnitude of observed associations to estimate population attributable risk. npj Breast Cancer (2015) 15009 © 2015 Breast Cancer Research Foundation/Macmillan Publishers Limited Preventing breast cancer GA Colditz and K Bohlke Building awareness of the potential for prevention works. ACKNOWLEDGMENTS Similar to the scientific evidence and prevention messaging that GAC is supported in part by an American Cancer Society Clinical Research led to the drop in the use of estrogen plus progestin therapy, Professorship, by the Breast Cancer Research Foundation, and the Foundation for another national effort to reduce and eliminate tobacco use has Barnes-Jewish Hospital. KB is supported by the Foundation for Barnes-Jewish Hospital. had significant impact on the health of women and men. Trials show that prevention works. Building on the Institute of Medicine report, one research COMPETING INTERESTS prevention priority is to better understand the lifestyle factors The authors declare no conflict of interest. (diet patterns, exercise, etc.) in childhood and in the critical window from menarche to first pregnancy that offer the greatest protections. 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npj Breast CancerSpringer Journals

Published: Jul 22, 2015

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