Introduction Cancer is a disease that alters the cells of the body, causing them to grow uncontrollably (1).

Most cancer cells grow to form tumors, or lumps or masses, which are named after the part of the body where they develop. The most commonly diagnosed cancer in women is breast cancer, with about 1 in 4 United States (US) women being diagnosed (1). Breast tissue is made up of lobules, or milk glands, and ducts that connect the lobules to the nipple, and the remainder is made up of lymphatic tissue. This is where breast cancer begins, which may be restricted to within the ducts of the breast and named ductal carcinoma in situ (DCIS), or they are restricted to the lobules of the breast and named lobular carcinoma in situ (LCIS). Most all in situ breast cancers may be cured, but most cancers are invasive and start in situ then break through the duct or glandular walls to spread to surrounding tissues within the breast (1). The best strategy for a woman to decrease her risk of developing breast cancer is to avoid weight gain and obesity, take part in regular physical activity, and decrease alcohol intake (1). Several studies have been conducted showing that fruit and vegetable intake may be inversely associated with breast cancer incidence (2, 3, 4, 5). The purpose of this paper is to discuss the nutritional implications of breast cancer and treatment and how fruit and vegetable intake may help reduce the risk of developing breast cancer or may help increase survival rates of those who have already been diagnosed. Background Affected Population As mentioned previously, breast cancer is the most common type of malignancy in women. It is also the second leading cause of cancer death in women following lung

cancer (6). Rates of breast cancer vary by race and ethnicity (7). Beginning at age 45, white women are more likely to develop breast cancer than African American women, but before age 45, African American women are more likely to develop breast cancer than white women, and breast cancer mortality rates are higher in African American women at any age (1). Breast cancer predominantly affects women who are over age 40, and less than 5% of cases occur in younger women (6). In younger, premenopausal women, a mutation in the BRCA gene is most strongly correlated with the development of breast cancer (7). Risk Factors Greater than 70% of breast cancer cases occur in women with no particular risk factors except for being a woman and aging (6). Identifiable risk factors include age, family history, age at first pregnancy, early menarche, late menopause, and breast density, all of which are not easily modified. Risk factors that can be modified include postmenopausal obesity, use of estrogen and progestin menopausal hormones, alcohol intake, and physical inactivity (1). A family history of breast cancer in a first degree relative or multiple family members increases a womans risk, as does a first pregnancy age of over 35 years (6). About 5-10% of breast cancer cases are the result of an inherited mutation in the identified genes BRCA1 and BRCA2. Having a mutated gene increases a womans risk of developing breast cancer by 60-80% (6). Gene mutations may be caused by sun exposure, radiation exposure, and some chemical exposure. BRCA1, on chromosome 17, and BRCA2, on chromosome 13, are the likely mutated genes that account for early-

onset breast cancer cases. Other gene mutations may occur in TP53 and PTEN in the cell cycle-checkpoint kinase gene CHEK2 (2). Nutritional Implications of Chemotherapy Regardless of nodal status, chemotherapy may improve the overall survival of women with breast cancer up to age 70 years. Side effects of chemotherapy differ based on the specific regimen of treatment used. Common side effects include alopecia, nausea and vomiting, dysgeusia, mouth sores, myalgias and arthalgias, hypersensitivity, fatigue and peripheral neuropathy, neutropenia, anemia, and premature menopause. Dysgeusia may cause a metallic or other unpleasant taste in the mouth. Food may taste different and many patients have food cravings. Ulcers in the mouth are a rare side effect that cause pain and may interfere with eating and swallowing. Candidiasis, or thrush, is also common in patients being treated with chemotherapy. Anemia is seen commonly in patients being treated for a metastatic disease, but this may also be due to lacks of iron, Vitamin B12, and folic acid. Fatigue is one of the worst side effects of chemotherapy and may be worsened by anemia (6). Fruits and Vegetables Plant foods are assumed to contain a considerable amount of advantageous effects for the prevention of cancer (3). Several fruits and vegetables have protective substances like fiber, antioxidants, vitamins and minerals, and potentially anticarcinogenic compounds such as dithiolthiones, isothiocyanates, indole-3-carbinol, flavonols, and ligans (2). They are also sources of carotenoids, ascorbic acid, folate (4), and glucosinolates (5). Evidence has shown that particular subclasses of vegetables, like cruciferous and carotenoid-rich vegetables, may decrease the risk of breast cancer (5).

Cruciferous vegetables, such as broccoli, are sources of glucosinolates and are metabolized into indoles and isothiocyanates, which are potential chemoprotective compounds. Indoles have antiestrogenic effects and inhibit transcription of estrogenresponsive genes. Increased cruciferous vegetable intake has been shown to shift estrogen metabolism toward metabolites with decreased estrogenic potential. Glutathione S-transferases are phase II enzymes that are induced by isothiocyanates and play an important role in detoxifying carcinogens. Carotenoids, found in carrots and other yellow-orange vegetables, may prevent cancer by reducing oxidative DNA damage. Some are converted to Vitamin A, which may play a role in the prevention of cancer as it is involved in cell differentiation (5). Eleven observational studies have been conducted to examine the relationship between breast cancer reappearance and intakes of vegetables, fruits, and other related nutrients. Robien, Demark-Wahnefried, and Rock reported Kroenke and colleagues to have discovered that a prudent diet pattern, which is high in fruits, vegetables, whole grains, legumes, poultry, and fish, was associated with a 15% reduction in relative risk of overall mortality (8). Bissonauth and colleagues noted that the World Cancer Research Fund (WCRF) concluded from a meta-analysis of 23,038 women that vegetable intake had protective associations with breast cancer risk. WCRF found a 25% lower breast cancer risk in those who consumed high versus low amounts of vegetables (2). Breast cancer risk as associated with fruit and vegetable intake may vary depending on hormone receptor status of the tumor in the breast. Estrogen and progesterone receptor (ER and PR) tumors suggest that hormone receptor status may denote tumors with different risk factor profiles (4). Some identifiable risk factors for

breast cancer may be more strongly associated with positive hormone receptors than negative hormone receptors (4). Evidence from some studies has suggested that protective effects of fruits and vegetables are stronger in women with family histories of breast cancer or in women with ER-positive (+) tumors (2). ER-negative (-)/PR- tumors are associated with an increased 5-year mortality rate. African American women are more likely to be diagnosed with these tumors than white women. While black women consume fewer vegetables overall compared to white women, they tend to have greater amounts of cruciferous vegetable intake. A Black Womens Health Study examined 51,928 women between the ages of 21 and 69 years and the relationship of fruit and vegetable intakes with breast cancer risk. They found that total vegetable consumption was associated with a decreased risk of [ER-/PR-] breast cancer (5), and some evidence of cruciferous vegetable intake and carrot intake having inverse associations with breast cancer risk overall. They also found a prudent diet pattern to be inversely associated with premenopausal breast cancer and ER-/PRbreast cancer among black women, and their study suggests that the vegetable component of the prudent diet is the driving force for the inverse association (5). Lissowska J, et al (4), found an inverse association between breast cancer risk and high intakes of fruits and juices to be stronger in women with ER+ rather than ERtumors. They found no significant modification in breast cancer status with diet in PR status. They found high intakes of fruit to be most strongly correlated with decreased risk of breast cancer overall, which was consistent with their reviews of other studies (4). Evidence from the Greek EPIC cohort study shows an inverse association of the incidence of cancer with high intakes of fruits and vegetables, but statistical significance

is only associated with vegetable intake among women (3). In another cohort study of breast cancer survivors, those who consumed at least five servings of fruits and vegetables per day and had a physical activity level equal to 30 minutes of walking 6 days per week showed a 50% reduction in mortality over a follow-up of seven years. Findings from the Womens Healthy Eating and Living (WHEL) Study, as reported by Robien and colleagues, suggest that reproductive hormonal status may determine whether a high-vegetable, fruit, and fiber diet affects prognosis (8), and exposure to carotenoids was associated with breast cancer-free survival despite the assignment in the study group (8). Bissonauth and colleagues referenced to a cohort study from Zhang et al, which verified that intake of fruits and vegetables that are high in particular carotenoids and Vitamins A, C, and E may reduce the risk of breast cancer (2). Recommendations As stated by Robien and colleagues in the article, Evidence-Based Nutrition Guidelines for Cancer Survivors: Current Guidelines, Knowledge Gaps, and Future Research Directions (8), those who survive cancer are encouraged to follow primary cancer prevention recommendations that are consistent with those from the American Cancer Society (ACS). Robien and colleagues note that these recommendations as well as those from the WCRF/American Institute for Cancer Research (AICR) emphasize the achievement and maintenance of a healthy weight; participation in regular physical activity; a healthy diet rich in vegetables, fruits, and whole grains; and limitations of meat and alcohol consumption. The article also mentions that ACS and WCRF/AICR advocate the consumption of food for all nutrient sources as opposed to supplementation (8). The Johns Hopkins University health care professionals recommend that patients

consume a low-fat diet and maintain a body mass index (BMI) in a normal range for their age while increasing lean body mass (6). There are several knowledge gaps concerning nutritional interventions for cancer survivors that must be addressed before evidence-based recommendations can be made. Most research has only been focused on interventions for decreasing the recurrence of cancer, but more data are needed to understand how nutrition interventions can address non-cancer endpoints and costs of healthcare. Also, nutrition interventions need to be aimed at the prevention and management of cancer comorbidities and functional impairment, as well as improving patient quality of life (8). Conclusion Strong evidence from several studies suggests that fruit and vegetable intake are significantly associated with a decreased risk for breast cancer. The studies referenced in this paper have revealed that high intakes of specific types of vegetables, such as carotenoids and cruciferous vegetables, and high intakes of fruits are linked to lower risks of breast cancer overall. Particular types of fruits and vegetables may affect ER/PR tumors differently; vegetables have a more prominent inverse association with ER-/PRbreast cancer tumors, while high intakes of fruits and juices have more prominent inverse associations with ER+ tumors. It is plausible that the reason for these inverse associations is due to the protective substances that fruits and vegetables contain such as fiber, antioxidants, vitamins and minerals, carotenoids, folate, ascorbic acid, glucosinolate, and anticarcinogenic compounds. More research must be done to understand fully the effect of fruits and vegetables on hormone receptors and breast cancer tumors. Also, more data are needed to

understand and to better formulate nutrition interventions for not just those who have already developed and been diagnosed with breast cancer, but also to help prevent the development of breast cancer in those who are at risk. The studies presented in this paper are just the beginning of future research to be conducted, but have promising results that demonstrate inverse associations with breast cancer risk and diet, especially with fruit and vegetable consumption. Breast cancer patients and those at risk of developing breast cancer should consume a diet high in fruits and vegetables, a recommendation consistent with primary cancer prevention recommendations from ACS and WCRF/AICR.

References 1. American Cancer Society. Breast Cancer Facts and Figures 2009-2010. Atlanta: American Cancer Society, Inc.; 2009. 2. Bissonauth V, Shatenstein B, Ghadirian P. Nutrition and breast cancer among sporadic cases and gene mutation carries: an overview. Cancer Detect Prev. 2008; 32: 52-64. 3. Benetou V, Orfanos P, Lagiou P, Trichopoulos D, Bofetta P, Trichopoulou A. Vegetables and Fruits in Relation to Cancer Risk: Evidence from the Greek EPIC Cohort Study. Cancer Epidemiol Biomarkers Prev. 2008; 17: 387-392. 4. Lissowska J, Gaudet MM, Brinton LA, et al. Intake of fruits, and vegetables in relation to breast cancer risk by hormone receptor status. Breast Cancer Res Treat. 2008; 107: 113-117. 5. Boggs DA, Palmer JR, Wise LA, et al. Fruit and Vegetable Intake in Relation to Risk of Breast Cancer in the Black Womens Health Study. Am J Epidemiol. 2010; 172: 1268-1279. 6. Shockney LD, Tsangaris TN. The Johns Hopkins Breast Cancer Handbook: for Health Care Professionals. Mass.: Jones and Bartlett Publishers; 2008. 7. Bland KI, Copeland EM. The Breast: Comprehensive Management of Benign and Malignant Diseases. 4th ed. Penn.: Saunders Elsevier; 2009. 8. Robien K, Demark-Wahnefried W, Rock CL. Evidence-Based Nutrition Guidelines for Cancer Survivors: Current Guidelines, Knowledge Gaps, and Future Research Directions. J Am Diet Assoc. 2011; 111: 368-375.