Cancer Prevention for Women

C H A P T E R

82 Cancer Prevention for Women 

†

Heather Patrick and Karen Glanz†

Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD, USA Perelman School of Medicine and School of Nursing, University of Pennsylvania, Philadelphia, PA, USA

INTRODUCTION Despite major efforts to develop cancer therapies and improve prognosis, cancer remains a leading cause of mortality worldwide. It is the second leading cause of death in the US population for both men and women, and recent projections indicate that cancer will surpass cardiovascular disease as the leading cause of death in the next few years.1,2 A variety of biological, genetic, and environmental factors contribute to carcinogenesis. However, current estimates suggest that some 60% of all cancers could be avoided through primary prevention via lifestyle change.2 Thus, winning the war on cancer depends not only on finding improved treatments and potential cures but also on identifying effective preventive interventions that can be implemented on a large scale. Lifestyle factors that show the most promise for primary prevention of cancer are tobacco cessation, weight control, nutrition, physical activity, alcohol use and sun protection.3 Additionally, emerging research on cancers caused by viruses and immune responses suggests that vaccinations could play an important role in cancer prevention. Because screening is discussed elsewhere in the book, this chapter will focus primarily on behavioral and chemopreventive approaches to cancer prevention. Breast cancer is the most common cancer among US women, affecting 119.3 of every 100,000, followed by lung (56.0), colorectal (43.1), uterine (23.7) and thyroid (16.0) cancers. Although breast cancer has higher incidence, lung cancer is the leading cause of cancer mortality among women with 42.2 deaths per 100,000 nearly double the deaths from breast cancer (23.4); lung cancer deaths are on the rise among women, while they are declining for men. The next leading sites for cancer deaths among women are colorectal (14.5), pancreatic (9.5), and ovarian (8.5)

Women and Health. DOI: http://dx.doi.org/10.1016/B978-0-12-384978-6.00082-0

cancers.4 Given the incidence and mortality from breast, lung, and colorectal cancers among women, behaviors contributing to these cancer sites deserve special attention. Further, the incidence of skin cancer is increasing faster than any other cancer site, and the rate of increase is higher for women than for men. The purpose of this chapter is to provide an overview of actions that can be taken by women to reduce their cancer risk, and discuss strategies for encouraging their adoption.

CANCER PREVENTION: THE STATE OF THE SCIENCE A growing body of evidence points to several behaviors that have the potential to prevent a significant proportion of the cancer burden. This section summarizes the state of the science for cancer prevention through nutrition, physical activity, weight control, eliminating tobacco use and exposure, sun safety behaviors, limiting alcohol consumption, chemoprevention, vaccines and hormone replacement therapy. The existing evidence suggests that each of these behaviors can help to prevent cancer among women, and many show particular promise for preventing breast and gynecologic cancers. Table 82.1 summarizes the preventive factors or actions, major affected cancer sites, and some special issues for women.

Weight Control In the US, more than two-thirds of adults are overweight or obese, and rates are somewhat higher in women than men.5 According to the US Cancer

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Preventing Cancer Among Women: Affected Cancer Sites and Special Issues

Preventive Factor or Action

Affected Cancer Site(s)a

Special Issues for Women

Weight control

Breast

Overweight/obesity higher for women

Colorectal

Post-menopausal weight gain

Endometrial

Risk reduction for other chronic illnesses

Breast

Role in energy balance and weight control

Fruit and vegetables

Colorectal

Women’s roles in food purchase/preparation

Eggs, dairy, meat

Lung

Risk reduction for other chronic illnesses

Nutrition

Poultry, seafood

Data inconclusive on high-fat dairy

Fats and fatty acids

compounds: Polyphenols, lycopene, soy,

Compounds in foods

Luteolin

Physical activity

Breast Colorectal

Women less likely to be physically active Role in energy balance and weight control Barriers: time, convenience, social support, self-efficacy Realistic goals of moderate activity now an option

Tobacco use and exposure

Lung

Women may become addicted more rapidly

Cervix

Concerns about weight gain at cessation Stronger psychological ties to smoking: stress management, depression, etc Reproductive effects

Sun safety and indoor tanning

Skin

Greater engagement in sun-protection: sunscreen use, using shade Greater utilization of indoor tanning Increase of melanoma among young women Motivation to reduce photoaging or wrinkling

Alcohol consumption

Chemoprevention

Breast

Increasing consumption and binge-drinking among women

Colorectal

Balance with possible cardiovascular benefit of moderate drinking

Breast

Little is understood about dose needed for

Colorectal Cervix

cancer prevention Unclear how supplements interact with

Ovarian Vaccinations

broader diet

Cervix

High population-level HPV infection

Anogenital

Vaccines provide 100% protection Challenges with population-level dissemination and implementation

Hormone replacement therapy

Breast

Risk/benefit and duration of use

(HRT)

Endometrium

Appropriate prescribing decisions

Ovary

Relief from menopausal symptoms

a

Only major cancer sites for women and female cancers are shown.

Prevention Study II, as many as 20% of all cancer deaths in women and 14% of all cancer deaths in men may be attributable to obesity.6 A recent systematic review and standardized meta-analysis of prospective observational studies demonstrated that adiposity plays a role in several common cancers, including

endometrial, esophageal, colorectal, postmenopausal breast, prostate and renal cancers.7 Women who have a body mass index (BMI; weight adjusted for height) in the obese range have a three times greater risk for postmenopausal breast cancer8 and experience greater breast cancer mortality.9,10 This

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may be due, in part, to the greater likelihood of obese women having hormone-negative, stage III tumors.11 There are several potential biological mechanisms that may account for the association between BMI and cancer, including insulin and hormone metabolism, inflammation and oxidative stress. Circulating insulin levels positively correlate with BMI, and many obese persons are insulin resistant.12 Prolonged hyperinsulinemia reduces production of IGF binding protein, which results in increased levels of bioavailable IGF-I, changing the cellular environment in favor of carcinogenesis.12 Obese women have higher rates of conversion of androgenic precursors to estradiol.14 Most risk factors for breast cancer particularly postmenopausal breast cancer act through estrogen-related pathways and altered concentrations of estrogen-related hormones. Obesity also plays a role in inflammatory processes, characterized by abnormal cytokine production, increased synthesis of C-reactive protein, and activation of pro-inflammatory signaling pathways. Subclinical or low-grade chronic inflammation has been implicated in the development of insulin resistance, type 2 diabetes and obesity-related atherosclerosis, and emerging evidence suggests a role for inflammation in carcinogenesis.12 Obesity may also reduce the functionality of the body’s protective antioxidants, resulting in systemic oxidative stress.12 Obesity increases the risk of endometrial cancer, and the primary biological mechanism through which this is thought to function is hormonal. Although evidence suggests that obesity is a late-stage cancer promoter, little research is available on whether weight loss is effective for ’resetting’ the hormone levels implicated in the obesity-endometrial cancer pathway.13

Nutrition Much of the interest in understanding links between diet and cancer risk stems from variations in rates of specific cancers by country or geographical region and shifts in cancer incidence among people who migrate to these areas.15 However, the role of diet in cancer remains complex and controversial. Two primary difficulties have challenged the capacity of research to clarify these associations. First, it is not clear at what stage of carcinogenesis nutritional factors act. Second, it is not clear what dose of a particular nutritional factor is needed to positively impact carcinogenesis in humans or the particular nutrients or combinations of nutrients in foods that affect carcinogenesis.16 Further, research on dietary patterns and cancer causation is limited by the difficulty of measuring exactly what foods and nutrients have been consumed, in what amounts, and at what point(s) in a person’s lifetime and linking those factors to differences in cancer rates.

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Fruit and Vegetables Fruit and vegetable intake has been linked to various cancers, perhaps most strongly to colorectal cancer.17 For example, data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study demonstrated an approximately 42% reduced risk for colorectal cancer among those with the highest intake of dietary fiber, especially from fruits and vegetables .18 Fruit and vegetable intake has also been shown to be protective against lung cancer. Lung cancer risk is lower among those who frequently consume tomatoes, carrots, lettuce and other greens,19 and higher among those with low fruit intake.20 With regard to the role of nutrition in breast cancer risk, intake of phytoestrogens found in fruits and vegetables, as well as other foods such as soy, flaxseeds, grains and nuts during adolescence has been associated with decreased breast cancer risk.21 23 Thus, fruit and vegetable intake reduces the risk for several cancers relevant to women. It is worth noting that findings from cohort studies conducted over the past two decades have called into question the strength of the association between fruit and vegetable intake and cancer risk. However, there is evidence that some types of vegetables and fruit more generally likely protect against a number of cancers.15 Part of the association may be due to the roles of fruits and vegetables in people’s diets as a whole (i.e., people who have diets high in fruit and vegetables may have lower intakes of other nutrients such as fat), and in weight management. Eggs, Dairy, Meat, Poultry and Seafood Dairy, meat, poultry and fish intake have also been found to be associated with incidence of some cancers. Meat intake has been associated with greater colorectal cancer risk and mortality,24,25 while intakes of high-fat dairy foods, eggs, eel, shrimp, shellfish, poultry and fish are associated with lower colorectal cancer risk.26 28 Whole milk, red meat, and fried meat intake are associated with increased lung cancer risk29,30 whereas intake of fish, shellfish, margarine and cheese has been associated with decreased lung cancer risk.31,32 Intake of these foods has also been associated with breast cancer risk.33 36 In sum, red meat intake is associated with greater cancer risk, whereas intake of fish, shellfish, poultry and eggs has been associated with lower cancer risk. Data are least conclusive about the role of dairy products in cancer protection particularly for full-fat milk and other full-fat dairy products such as cheese. Fats and Fatty Acids Fat and fatty acid intake have been shown to have some association with cancer risk. For example, research

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has suggested greater risk for breast cancer among women with higher saturated fat intake compared to those with lower saturated fat intake37 and for those with higher intake of hydrogenated fats or vegetable and corn oils compared to olive or canola oil.38 With respect to fatty acids, some studies have shown a direct association between breast cancer risk and dietary intake for palmitic, γ-linoleic, palmitoleic, and vaccenic acids.39 Among smokers, diets high in fat have been associated with increased lung cancer risk.20 However, the Women’s Health Initiative the largest and longest randomized study to date investigating the role of dietary change in postmenopausal women found in a randomized controlled trial that a low fat diet did not prevent breast or colon cancer.40,41 Additional follow-up on this cohort will investigate whether the nearly-statistically significant differences in breast cancer rates at 8 years become significant after 10 years of follow-up.42 Compounds Found in Foods A variety of compounds found in foods have also been implicated in cancer prevention. For example, a group of polyphenols found in green and black tea may inhibit carcinogenesis at various organ sites.43 Lycopene the carotenoid that gives tomatoes their red color and is also found in guava, watermelon and pink grapefruits may also be chemopreventive for digestive track and cervical cancers.44,45 Soy isoflavones found in soybeans and soy products have been shown to be associated with decreased risk of breast and endometrial cancers.46 Luteolin, found in broccoli, celery, cabbage, green pepper and cauliflower, has been found to have anti-inflammatory and anti-cancer effects via induction of cell cycle arrest and apoptosis.47,48 The role of these compounds in cancer prevention depends on their effects when consumed in foods or as supplements, and these issues are active areas of continuing research.

Physical Activity Engaging in regular moderate-to-vigorous physical activity has been established as cancer-preventive, and some estimates indicate that regular physical activity may reduce cancer incidence by as much as 42%.49 The strongest evidence for physical activity as a means of preventing cancer is for breast and colorectal cancers.50,51 A recent review of the literature found evidence for decreased risk of breast cancer as a function of increased physical activity in 49 of 63 studies reviewed.52 Physical activity reduced breast cancer risk by 25 30%, and several studies found a doseresponse effect, with higher levels of physical activity associated with even greater decreases in breast cancer risk. The preponderance of evidence suggests that

lifetime moderate-to-vigorous physical activity is most protective against breast cancer risk, though high levels of physical activity later in life were also found to be protective.52 The biological mechanism through which physical activity impacts breast cancer risk seems to result largely from the role of physical activity in healthy weight management. In a review of the literature on the association between physical activity and colorectal cancer risk, evidence suggests a 20% reduction in colorectal cancer risk as a function of exercise, with more exercise yielding greater risk reduction.53 Physical inactivity is estimated to account for 13 14% of colon cancer incidence54 and may impact cancer risk through a variety of biological mechanisms including reduced gastrointestinal transit time, improved immune function and insulin levels, insulin-like growth factors and reduced obesity.49,54 Data from the 2007 Behavioral Risk Factor Surveillance System indicate that only 51% of US adult women meet recommendations to engage in moderately intense aerobic exercise for 30 minutes per day, five or more days per week, or to engage in vigorously intense aerobic exercise for 20 minutes per day, three or more days per week.55 Fully 26.2% of women report that they get no leisure time physical activity. Physical activity rates begin to decline for girls during adolescence, and this trend continues through adulthood, with girls and women evidencing lower physical activity levels than boys and men from adolescence throughout the remainder of life.

Tobacco Use Tobacco use accounts for at least 30% of cancer deaths in the United States including those attributable to secondhand smoke exposure in non-smokers.2,4 And although smoking has declined substantially in the US since the 1964 US Surgeon General’s Report on Smoking, the decrease has been more gradual among women than men.56 In the US, 24% of women over age 19 are regular smokers, and 32% of female high school seniors reported smoking within the past month.57,58 Smoking cessation may be especially difficult for women for several reasons. Whereas men are more likely to smoke in response to physiological cues associated with tobacco dependence and nicotine addiction, women’s smoking behavior often is more strongly influenced by conditioned cues (e.g., behavioral routines) and negative affect.59 Biologically, women metabolize nicotine faster than men do, which may contribute to women’s increased susceptibility to nicotine addiction at the onset of smoking and the difficulties women experience when trying to quit.60 Faster metabolism of nicotine is also associated with

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taking in more cigarette smoke each day and with more severe withdrawal symptoms.61,62 There is also some evidence to suggest that women experience greater weight gain when quitting,63 and given the societal pressures which equate women’s thinness with beauty, weight gain may be a major barrier to smoking cessation for women.

Skin Cancer Prevention: Sun Safety and Indoor Tanning Skin cancer is the most common cancer in the United States, with an estimated 1 million new non-melanoma and 71,000 new melanoma cases annually.64 Though it constitutes a relatively small percentage of skin cancer cases, melanoma is the deadliest form of skin cancer, accounting for 74% of skin cancer deaths.65 Skin cancer is also the only cancer whose incidence and prevalence continue to rise, especially among young women.66,67 Indeed, recent data indicate that the incidence of skin cancers among women under 42 years are markedly higher than among men in this same age group and are due, in large part, to women in this age group receiving excessive and repeated exposure to large amounts of UVA radiation.68 Primary prevention can play an important role in preventing skin cancer among women. The key preventive behaviors include: 1) Avoiding direct sunlight exposure, particularly between 10am and 2pm; 2) Using sun protective clothing (e.g., hats, sunglasses); 3) Using broad spectrum sunscreens with a minimum sun protection factor of 30; and 4) Avoiding tanning bed use. Compared to men, women are more likely to use sunscreen and other forms of sun protection (with the exception of wearing hats) including using sunscreen in a wider range of situations, reapplying sunscreen more frequently, and using shade.69,70 Women also evidence more positive attitudes toward sun protection, perceive fewer barriers to sun safety, and are more attuned to the severity of sun damage to which they have been exposed.71 Despite the indications that women are engaging in skin protective behaviors and view these behaviors positively, evidence also suggests that women are more likely than men to engage in skin cancer risk behaviors such as sunbathing and tanning bed use.72 Some recent intervention efforts to curtail sun and tanning bed exposure have focused on image-based messages.73,74 For example, use of photo-aging technology has been shown in some studies to change sun protection behaviors, at least in the short-term. Such

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approaches are hypothesized to be effective for promoting sun safety among women, because women report tanning primarily for image improvement. By demonstrating that ultraviolet (UV) exposure will have long-term negative consequences for their appearance, image-based interventions are thought to target the motivational mechanisms underlying women’s skin cancer risk behaviors. The past few years have also seen an increase in policy regulations regarding indoor tanning, including laws which stipulate age restrictions on indoor tanning in 32 states.75

Alcohol Consumption Alcohol consumption has also been directly tied to cancer risk, and ethanol, the active component in alcohol, has been classified as carcinogenic to humans. Typically, men consume more alcohol than women.76 However, recent data suggest that women’s intake and rates of binge drinking are increasing in much of the world.77 This is important because there is a linear (i.e., dose-response) relationship between alcohol intake and cancer risk. Alcohol use has been directly causally linked to increased risk for cancers of the mouth, pharynx, larynx, esophagus, breast, colon, rectum, and liver.15 Research also suggests that there may be a possible link between alcohol use and cervical cancer, and some studies have found an association between alcohol use and endometrial and ovarian cancers, though the evidence is somewhat mixed.78 Of particular importance for women is the emerging body of research on the role of alcohol consumption in breast cancer. In a recent review of the literature, Khan and colleagues79 reported a linear association between alcohol use and breast cancer risk, with the most substantial increases in risk appearing at moderate to high levels of alcohol intake (i.e. 3 drinks or more per day). The association between alcohol use and breast cancer risk was particularly strong among women with low BMI and those who had estrogen receptor positive tumors. Alcohol use is also more strongly implicated among women with invasive rather than in situ disease. Importantly, no major differences in this association emerged for type of alcohol consumed (i.e. wine, liquor, beer, or type of wine).

Chemoprevention and Vaccinations Chemoprevention Chemoprevention is the prophylactic use of chemicals and other agents that inhibit one or more steps in carcinogenesis. Research from epidemiological, in vitro, and animal studies confirms that chemicals and other agents can promote or inhibit cancer. The field of

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chemoprevention has seen a recent surge in research as a result of several major advances, including a shift in how oncology research views premalignancy and carcinogenesis. Specifically, oncology has moved to a more sophisticated view of these processes as heterogeneous, involving a variety of genetic alterations, inflammation, tissue injury and other processes.47,80 Advances in genetic engineering have also improved the capacity for mouse and other animal models to inform our understanding of the molecular mechanisms involved in the action of potential chemopreventive compounds. Natural compounds have received much attention in chemopreventive research due to their availability in the diet (described briefly, above) and tolerability. Cooper and colleagues81 recently completed a systematic review of randomized trials for chemoprevention of colorectal cancer and adenomatous polyps. Reviewed studies included non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin and cyclo-oxygenase-2 (COX-2) inhibitors; folic acid; calcium; vitamin D and antioxidants (including vitamin A, vitamin C, vitamin E, selenium and beta-carotene). Results suggested that aspirin reduces risk of colorectal cancer in the general population. Aspirin, celecoxib (a non-steroidal antiinflammatory drug), and calcium may reduce the number and recurrence of polyps in those with a history of polyps. Results from their economic analysis suggest that chemoprevention for colorectal cancer is most cost-effective when targeted at intermediate-risk populations (rather than the general population), following polypectomy. Research on other vitamins, minerals, and supplements has yielded interesting findings with respect to chemoprevention. For example, Vitamin A metabolites, such as retinoic acid, have been shown to have chemopreventive and therapeutic activity for certain cancers including head and neck, cervical, neuroblastoma and promyelocytic leukemia.82 Low Vitamin D and inadequate intake of calcium have also been implicated as a risk factor for cancer.83 Of particular relevance to women, oral intake of calcium has been associated with decreased risk for colorectal, breast, and ovarian cancers,85 though other studies have found no reduced risk for colorectal cancer as a function of calcium and vitamin D supplementation.84 Vaccinations The International Agency for Research on Cancer (IARC) estimates that nearly 20% of human cancers are caused by infection, with 12% being caused by one of seven different viruses.85 Thus, vaccinations may play an important role in preventing some cancers. Human papillomavirus (HPV) has been causally linked to cervical cancer, and cervical cancer is the first cancer to

be recognized as being 100% viral in etiology.86 HPV viruses also play a significant role in other female anogenital cancers, including vulvar, vaginal, and anal cancers.87,88 Genital HPV infection is extremely common, with 50 81% of sexually active individuals becoming infected in their lifetime.89 To date, two prophylactic HPV vaccines have been licensed, both of which require three individual injections on separate occasions within a 6-month period. One vaccine is bivalent, including antigens for HPV-16 and -18. The other is quadrivalent, containing antigens for HPV-16 and -18 for the prevention of cervical cancer and HPV6 and -11 for the prevention of genital warts. Phase I and II studies of both vaccines demonstrated 100% protection against type-specific persistent HPV-16 and -18 infections, and preliminary data suggest these vaccines also prevent cervical lesions. Both vaccines also demonstrated high levels of safety and tolerability.86 Larger Phase III trials have demonstrated similar positive outcomes, including a reduction in Pap abnormalities and gynecological procedures.86 Two ongoing randomized trials in Finland are testing the durability of protection offered by these vaccines at the population level.90,91 Wide use of HPV vaccines for adolescent females has begun in the US and continues to be debated.92

Exogenous Hormone Use Estrogen and progesterone are both known to play a critical role in the development of breast, endometrial, and ovarian cancers. These hormones have also been implicated as important components of prevention strategies for these same cancers.93 However, hormone replacement therapy (HRT) has also been implicated in cancer causation.93 Thus, use of hormones and HRT has remained quite controversial, and the mechanisms through which estrogen and progesterone contribute to carcinogenesis in some circumstances while serving as a preventive strategy in others are not fully understood. Breast Cancer Primary and secondary chemoprevention with hormones has shown quite a bit of promise for reducing risk of breast cancer. Analyses from the National Surgical Adjuvant Breast and Bowel Project (NSABP) revealed that, compared to placebo, tamoxifen (an antagonist of the estrogen receptor in breast tissue) reduced the risk of invasive and non-invasive breast cancer by nearly half. However, tamoxifen seems to affect only estrogen-receptor positive breast cancers. Importantly, tamoxifen was also shown to negatively impact other health outcomes, including more than doubling the risk

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for endometrial cancer, and increasing risk for thromboembolic disease, deep vein thrombosis, and stroke. Tamoxifen has also been compared to raloxifene (an oral selective estrogen receptor modulator). Both are equally effective for reducing incidence of invasive breast cancer though raloxifene does not appear to protect against non-invasive breast cancers. Raloxifene has lower risk for endometrial cancers and thromobembolic events compared with tamoxifen.13 Use of HRT was evaluated in the Women’s Health Initiative. The data suggest that, compared to placebo, women in the estrogen-alone treatment group evidenced no difference in risk for heart attack or colorectal cancer, increased risk of stroke and blood clots, and reduced risk of bone fracture. There was no clear effect for breast cancer. Compared to placebo, however, women in the estrogen-plus-progestin treatment evidenced increased risk for heart attack, stroke, blood clots and breast cancer, reduced risk of colorectal cancer, and fewer fractures.93,94 As the age of first full term pregnancy and the use of oral contraceptives have both increased in the Western world, in parallel with an increase in breast cancer burden, much research has focused on the role of oral contraceptives in breast cancer. In a recent review of the literature, including meta-analyses and data from longitudinal cohort studies (e.g., the Nurses’ Health Study), Cibula and colleagues95 reported that there was only a slightly increased risk of breast cancer among current users of oral contraceptives. Further, across these studies, evidence suggested that the effect of oral contraceptives on breast cancer disappears within 5 10 years of stopping use. Endometrial Cancer Endometrial cancers are distinguished on the basis of being estrogen-dependent (Type 1) or non-estrogendependent (Type 2). As Type 2 endometrial cancers tend to have poor prognosis because of the aggressive nature of these cancers (e.g., clear cell sarcoma), Type 1 endometrial cancers are most amenable to prevention efforts. Oral contraceptive use has been linked to decreased risk for Type 1 endometrial cancer, with a 20% reduction in risk after 1 year of use and an 81% reduction in risk with usage greater than 10 years.96 Ovarian Cancer In the US, epithelial ovarian cancer has the highest mortality rate of all gynecological cancers. American Cancer Society estimates indicate that 71% of those diagnosed with the disease will die from it.2 Oral contraceptive use has been shown to decrease risk for ovarian cancer.97 Effects have been seen in women using oral contraceptives for as little as 3 6 months, though more recent studies have demonstrated a linear

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dose-response effect whereby greater reduction in risk is experienced as a function of longer oral contraceptive use.98 This same pattern of results has been found for BRCA gene carriers.99 Thus, oral contraceptive use may be one means by which ovarian cancer can be prevented in the general population as well as among those at greatest risk. To date, data on the role of HRT in ovarian cancer has been somewhat conflicting, though the general consensus is that there is no strong association.100

Evidence Gaps The research summarized above shows that much can be done to prevent cancer by adopting specific behaviors and lifestyles. Chemopreventive agents, vaccines and hormonal treatments have also been shown to reduce cancer risk. Despite this evidence, very few people adhere to these recommendations and integrate them as part of a healthy lifestyle. Adherence to lifestyle recommendations is quite low, and long-term use of medications is also problematic. While much is understood about how people initiate behavior change and the types of interventions likely to be successful with these changes, very little research has demonstrated maintenance of behavior in the absence of ongoing intervention. The behaviors described above are interrelated and complex. Yet much research to date has focused primarily on changing behaviors individually, with little attention to how these behaviors are associated with each other and how effecting change in one behavior may accelerate or thwart change in others. More research is needed to understand how health risks and health promoting behaviors are associated with and affected by each other. Interventions are needed that target multiple health behaviors either simultaneously or sequentially. There is a substantial gap between the development and evaluation of efficacious interventions and their implementation into clinical practice and policy. Research that bridges clinical trials to translation (i.e., dissemination and implementation) is critical if these interventions are to effect behavior change on a large scale. Further efforts to engage communities, including primary care practices, community organizations, schools, and churches, in the initial design of interventions would also serve to facilitate translation of evidence-based research into practice.

UNIQUE ISSUES FOR WOMEN IN CANCER PREVENTION As noted at the beginning of this chapter, the role of behavior in cancer causation applies to both women and

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men. The primary prevention behaviors involved in diet, healthy weight management, physical activity, tobacco cessation, and sun safety are important for cancer prevention across genders. However, there are some aspects of these behaviors that may be uniquely relevant and/or particularly challenging for women (see Table 82.1). For example, as a result of various biological and psychological factors, women may be more likely to become tobacco-dependent than men and may have greater difficulty quitting smoking. Post-menopausal women are particularly susceptible to weight gain compared to both pre-menopausal women and men of the same age. Thus the role of weight in carcinogenesis may be particularly pronounced among women. Women are more likely than men to engage in sun protection behaviors, but they are also more likely to engage in behaviors that promote skin cancer, especially use of indoor tanning. Thus, although the behavioral recommendations for cancer prevention are generally the same for men and women, there are unique biological and psychological challenges that women face in adhering to them. Further, because of the role of female sex hormones in breast and gynecological cancers, use of oral contraceptives in premenopausal women and hormone therapies in postmenopausal women may be cancer preventive, particularly among those at high risk.

CHANGING CANCER RISK BEHAVIORS: FROM INDIVIDUALS TO POLICY At the individual level, behavior change is difficult, and researchers as well as the individuals who struggle with these issues have often lamented the challenges inherent in maintaining behavior change over time. Yet the behaviors described above must be sustained over time to yield desired health benefits. In response to the inability for most individually-based interventions to yield sustained behavior change, and given the economic and quality of life burden that results from failure to maintain lifestyle change, researchers and legislative bodies have turned to policy as a means to support sustained change. This is perhaps most clear in the area of tobacco control legislation, which has been credited for the dramatic decline in smoking in the US since the early 1970s.101 Similar attempts are currently being made with respect to use and taxation for use of indoor tanning facilities. Likewise, in an effort to combat the rising incidence of childhood overweight and obesity, schools have begun to adopt nutrition and physical activity policies limiting the availability of high-fat and high-sugar a la carte items in school lunchrooms and regulating the percentage of physical education classes during which students must be active.102 Although both individual

interventions and population-level policies are important for facilitating lifestyle change, to date, these areas of scientific inquiry have occurred largely in parallel, with less integration than is needed.103 Less research has focused on the intersection between policies and individuals how individuals respond to policy, how policy affects individuals’ behaviors and the populations that policies are most likely to reach and positively impact.

FUTURE DIRECTIONS More than half of all cancers could be prevented if current knowledge about the role of behavior in cancer were consistently applied. Avoiding tobacco use and exposure, eating a healthy diet, engaging in regular moderate to vigorous physical activity, maintaining a healthy weight, engaging in sun protective behaviors (e.g., sunscreen use) and avoiding UV risks (e.g., tanning bed use), and avoiding excessive alcohol intake have been demonstrated to promote health and to reduce cancer risk. Because lung, breast and colorectal cancers account for a large percentage of cancer cases and deaths among women, and because skin cancer is increasing particularly among women, these sites deserve special attention in prevention programs. Interventions that target issues that are salient to women in these health behaviors such as weight gain, appearance changes, family and child health, and reproductive concerns may be particularly efficacious in preventing cancer among women. Finally, many of these same behaviors have been implicated in a range of other disease processes including diabetes and cardiovascular disease. Thus, targeting these behaviors will not only reduce cancer risk but also reduce the incidence and burden of other chronic diseases that are ubiquitous in modern society.

References [1] National Cancer Institute. Cancer facts and the war on cancer. ,http://training.seer.cancer.gov/disease/war/. [accessed 06.06.11]. [2] American Cancer Society. Cancer facts and figures 2010. Atlanta: American Cancer Society; 2010. [3] Danaei G, Vander Hoorn S, Lopez AD, Murray CJ, Ezzati M. Causes of cancer in the world: comparative risk assessment of nine behavioral and environmental risk factors. Lancet 2005; 366(9499):1784 93. [4] US Cancer Statistics Working Group. United States Cancer Statistics: 1999 2007 Incidence and Mortality Web-based Report. Atlanta (GA): Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute; 2010. Available at: ,http://www.cdc.gov/ uscs. [accessed 06.06.11].

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