Breast cancer is the most commonly diagnosed cancer in women, constituting more than 1 in 4 cancers in females in the United States. It is second only to lung cancer as a cause of cancer death in women, accounting for more than 40,000 deaths annually. Until recently, the incidence of breast cancer had been increasing year by year. Beginning in 2002, age-adjusted incidence rates began to decline.
The incidence of breast cancer in men is about 1% of the rate in women. In both genders, the incidence increases with age. Most of the cancers are invasive at the time of diagnosis; only about 20% represent carcinoma in situ. More than 85% of the invasive tumors are infiltrating ductal carcinoma. Other histologic types are infiltrating lobular, medullary, mucinous, and tubular carcinomas.
Age: Incidence increases sharply until age 45 to 50 years. Incidence continues to increase with age after menopause, but at a slower rate. The rate of increase in incidence stabilizes in later years and declines near age 80. Mean age at diagnosis is 65 years.
Socioeconomic status (SES): Individuals in higher SES categories generally have greater risk of developing breast cancer—as high as double the incidence in comparison with the lowest SES. The mediating factor is believed to be differing reproductive patterns in various SES groupings.
Family history: Risk increases with an increasing number of first- or second-degree relatives with breast cancer history. Women with one affected first-degree relative have an almost twofold increased risk of developing breast cancer and a have a threefold increased risk if they have two affected first-degree relatives.
Diet: Numerous studies have detected associations between diet and the development of colon cancer, as described below in Nutritional Considerations.
Obesity: The relationship between weight and breast cancer risk varies with menopausal status. In premenopausal women, an elevated BMI is associated with a lower risk of breast cancer. The reason for this is unclear.
The opposite is true for postmenopausal women; an elevated BMI or weight gain is associated with a higher risk of breast cancer. Elevated estrogen levels, presumably due to peripheral aromatization of androstenedione to 1-estrone in adipose tissue, may help explain this increased risk. Excess weight may also affect prognosis. Obese patients (BMI ≥ 30) with breast cancer have increased morbidity and mortality.
Elevated blood glucose: The Nurses’ Health Study found that postmenopausal women with diabetes had a slightly greater risk for breast cancer, compared with those who did not have diabetes. Other studies have found greater risk for breast cancer in nondiabetic women with higher levels of fasting glucose. ,
Insufficient vitamin D: In a pooled analysis of 2 studies examining vitamin D and risk of breast cancer, women whose serum 25(OH)D levels were in the lowest quintile (< 13 ng/dL) had twice the odds of developing breast cancer as those whose levels were in the highest quintile ( > 52 ng/dL). An inverse dose-response relationship was detected, suggesting that the lower the circulating vitamin D level, the higher the risk of breast cancer. The authors reported that a level of 50 ng/dL could be achieved by oral intake of 2,000 IU of vitamin D 3, coupled with moderate, regular sun exposure.
Genetic factors: Specific genetic mutations account for about 5% of breast cancer risk. These mutations include the presence of the BRCA1, BRCA2, p53, ATM, and PTEN gene mutations.
Previous breast cancer: A first breast cancer may increase risk for subsequent contralateral breast cancer.
Proliferative benign breast disease(with or without atypia): Women with mammographically dense breast tissue, generally defined as dense tissue comprising ≥ 75 percent of the breast, have a four to five times risk of breast cancer compared with women of similar age with less or no dense tissue.
Reproductive events: E arly menarche, late menopause, older age at first birth, nulliparity, and lower parity are associated with higher risk.
Higher endogenous serum estrogen concentrations: Women with higher concentrations of circulating estrogen have a higher risk of developing breast cancer. In a clinical trial with 7,705 women, those whose serum estradiol concentrations were in the highest tertile had twice the risk for invasive postmenopausal breast cancer, compared with women with lower estradiol concentrations.
Hormone replacement therapy (HRT): Long-term use of HRT has been associated with an increased risk for breast cancer. The Women’s Health Initiative (WHI) trial showed a higher risk of breast cancer (RR = 1.26) among women taking a combined estrogen-progestin preparation for approximately 5 years, compared with those who used a placebo. It has also been shown that the women who took HRT the longest were 3 times more likely to develop cancer than those who never received HRT. Unopposed estrogens may have a lesser risk in comparison with combination HRT for eligible women, but this treatment carries other risks, such as thromboembolism.
Physical activity: Physically active women are less likely to develop breast cancer, compared with sedentary women. Exercise may decrease risk by reducing circulating estrogen and androgen concentrations and increasing sex-hormone binding globulin concentrations. In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial involving nearly 39,000 women, roughly 4 hours per week of exercise was associated with a > 20% reduction in these women’s risk for breast cancer, compared with the risk for women reporting no physical activity. Some evidence indicates that exercise may reduce risk regardless of hormone receptor subtype (i.e., ER+/PR+ or ER-/PR-) or menopausal status.
Breastfeeding: Several cohort and case-control studies show protective benefits of breastfeeding. A multinational case-control study of nearly 150,000 women showed a decreased risk of 4.3% for each year of breastfeeding and 7% for each pregnancy.
Maintenance of healthy body weight: The WHI study, which included nearly 86,000 women, the Swedish Mammography Cohort study, involving nearly 52,000 women, and other studies have shown that breast cancer risk increases with overweight and obesity.
Reducing or eliminating alcohol: Alcohol intake is associated with a linear increase in incidence of breast cancer up to 5 drinks a day. Women who consumed 2 (approximately 30 g ethanol) or more drinks per day had a relative risk of 1.41 compared with nondrinkers. Even 1 drink daily increases risk 9% to 10%. The risk is additive with HRT. Increased risk of breast cancer due to alcohol use may be mediated by the effect on sex hormone levels.
Avoidance of a Western dietary pattern: Diets in Western countries, high in meat and fat (particularly saturated and omega-6 fatty acids) and low in fruits, vegetables, legumes, whole grains, and fiber, are linked to higher breast cancer risk, although the specific aspects of this dietary pattern that account for this risk have not been clearly separated. Breast cancer is less prevalent in countries where diets are mainly plant-based, high in fruits, vegetables, grains, and legumes. , Incidence increases successively in first- and second-generation immigrants to North America., Specific dietary factors under investigation for a potentially helpful role are described below. Research attention is currently focusing more on overall dietary patterns than on the effects of specific foods or single nutrients. (See Nutritional Considerations below.)
Mammography remains the primary method for breast cancer screening in average-risk women. Other tests, such as breast MRI, thermography, tomosynthesis, and breast ultrasound are mainly used as adjuncts for screening higher-risk individuals. Breast self-examination and clinical breast examinations are no longer recommended for routine screening.
Multiple guidelines have been published regarding breast cancer screening, with varying recommendations. , , , , These recommendation differ on the age to start screening mammography for average risk women (ranging from 40 to 50) and on the frequency of screening (1 to 2 years). Some of the issues that have been raised about the use of routine mammography in screening average-risk individuals are:
- Mammographic screening has a significant false positive rate, requiring some women to undergo undue worry, additional evaluations (e.g., biopsies, and expense.
- In women < 50 years of age, screening detects cancers, but does not change overall mortality.
- Mammography detects cancers that appear to require treatment, but that otherwise may never have been diagnosed and were, in theory at least, treated unnecessarily.
Screening decisions should take into consideration overall breast cancer risk and individual preferences. Women at higher risk may benefit from more frequent screening at an earlier age.
Presenting signs and symptoms of breast cancer may include palpable breast mass (most common), dimpling, or pain; nipple inversion or unilateral nipple discharge (especially when bloody or watery); and peau d’orange (“orange peel skin”), erythema, or other skin changes.
All breast lumps should be evaluated thoroughly with diagnostic mammography, ultrasound, or fine-needle aspiration biopsy (FNAB) to determine whether the lump is a simple cyst or a complex/solid mass. An FNAB with bloody aspirate must be cytologically evaluated.
A suspicious mass on mammogram requires tissue sample, and a mass not certainly benign requires ultrasound (or magnified or spot compression mammography). Complex cysts or solid masses on ultrasound need FNAB, core, or excisional biopsy for definitive evaluation.
Recurrent/residual lumps must be re-evaluated and may need core or excisional biopsy. Solid cysts may still be diagnosed with cells from the needle. Benign cells require a mammogram, and nondiagnostic cells require repeat FNAB, core, or excisional biopsy. It is important to follow up all masses that were determined to be benign, using appropriate guidelines.
Most patients who are diagnosed with breast cancer have early stage (60%) or locally advanced (30%) breast cancer. A small percentage (5%) have metastatic disease at presentation. This determination is based on the TNM staging system: primary tumor size, regional lymph node involvement, and presence of distant metastasis. Other factors that will affect the prognosis and preferred treatment of breast cancer include menopausal status, age, hormone receptor status, and other tumor markers such as presence of HER2/neu receptors. Tumor histology is less important than invasiveness.
Surgery, radiation, chemotherapy, and hormone therapy are involved in the primary treatment of breast cancer, depending on the stage. Many possible algorithms exist, and each patient’s presentation should be evaluated to determine the best treatment.
Breast-conserving procedures, such as lumpectomy or segmental mastectomy followed by radiation, have been shown to be just as effective in treating early stage cancer as mastectomy.
Evaluation of the axillary lymph nodes is also important for staging. This can involve the preoperative biopsy of clinically suspicious lymph nodes with subsequent axillary node dissection if positive. In the absence of clinically suspicious lymph nodes, a sentinel lymph node biopsy during breast surgery can be obtained. When axillary nodes are positive, adjuvant treatment with endocrine therapy, chemotherapy, and/or biologic therapy is generally recommended.
Invasive disease usually requires neoadjuvant systemic therapy, which is designed to shrink the tumor prior to surgery. These patients also typically receive adjuvant treatment.
Tumor characteristics predict which patients are likely to benefit from specific types of therapy. Tumors that are positive for the HER2 receptor should receive a HER2 directed agent, such trastuzumab. Women with estrogen-receptor-positive or progesterone-receptor-positive cancers benefit from endocrine therapy, such as tamoxifen and/or aromatase inhibitors such as exemestane or anastrozole. Conversely, women who are receptor-negative may benefit from adjuvant chemotherapy, particularly if they are under 50 years or premenopausal. Hormonal therapy or chemotherapy is often used in the treatment of recurrent or systemic disease. Genetic tests may also help identify those who are most likely to benefit from certain treatments.
Researchers have long noted the low incidence of breast cancer in countries where traditional diets based on plant foods prevail. , , A striking increase in breast cancer incidence has been noted in immigrants who have abandoned traditional diets (e.g., rice, vegetables, soy foods) and adopted Western diets high in meat, dairy products, and fat. These observations have led scientists to hypothesize that diet-related factors, particularly obesity, play a key role in breast cancer risk. Part of this risk may be related to an increase in estrogen production from adipose tissue and to eating fatty, low-fiber foods that maintain elevated circulating estrogen concentrations. , Although certain micronutrients such as vitamins C, D, and folate that are commonly found in vegetables and fruits may also play a protective role, a substantial body of research is now focusing on dietary patterns, rather than on intake of individual foods or nutrients.
Limiting or avoiding meat. A number of studies, including the Nurses’ Health Study II and the UK Women’s Cohort Study, have found significant associations between meat intake and breast cancer risk, with an approximately 65% greater risk for postmenopausal breast cancer when women who consumed processed meat (bacon, sausage, ham, deli meats) were compared with those who did not. The NIH-AARP study involving nearly 200,000 women found a 25% higher risk for breast cancer in those eating the most red meat, compared to those eating the least. When all published studies, which vary in quality, are combined in meta-analyses, results have been less clear. , ,
It is not yet clear whether these associations reflect the effect of meat-based diets on hormone concentrations, the presence of carcinogens (e.g., heterocyclic amines, polycyclic aromatic hydrocarbons), or other factors. Conversely, plant-derived foods appear to reduce breast cancer risk (see below).
Reducing fat. Many studies have examined the effect of fat intake on breast cancer risk. The greatest risk appears to come from saturated fat and animal fat. , , , Vegetable oils, such as olive oil, have not been shown to increase breast cancer risk. , , , However, high-fat diets in general (not just saturated fat) may promote weight gain, and this weight gain is associated with greater breast cancer risk, as noted above. Increased adiposity increases serum estrogen levels, which, in turn, may also be associated with greater breast cancer risk. Dietary factors may also influence the age of menarche, which can also increase lifetime estrogen exposure. Animal fat and animal protein intake are also associated with elevated levels of insulin-like growth factor-1 (IGF-1). IGF-1 may, in turn, be associated with other established risk factors for breast cancer (e.g., breast density).
The WHI Dietary Modification Trial, which included 48,835 women, tested a diet that aimed to reduce fat intake to 20% of energy and to increase vegetable and fruit consumption. Selected participants were consuming more fat than the US average at study baseline. The actual fat intake achieved by study participants averaged 24% of energy at 1 year and drifted upward toward baseline values by the study’s end. After 8.1 years of follow-up, breast cancer risk was 9% lower in the intervention group, compared with a control group, although this result did not reach statistical significance. One exception was for progesterone-receptor-negative tumors, for which the risk decreased by 24% (P = .001). While the study results fueled pessimism about the ability of dietary changes to significantly alter breast cancer risk, it should be noted that the intervention diet included much more fat, meat, and dairy products than the Asian diets associated with lower cancer risk.
High-fiber diets. Dietary fiber interrupts the enterohepatic circulation of estrogen by binding unconjugated estrogens in the gastrointestinal tract. High-fiber, low-fat diets reduce serum estradiol, which is known to be associated with breast cancer risk. In addition to its influence on circulating estrogens, fiber has other physiologic effects that may reduce cancer risk. High-fiber diets help keep blood glucose levels within normal limits and lower the risk for adult-onset diabetes, both of which have been related to increased breast cancer risk. A systematic review and meta-analysis of prospective studies concluded that dietary fiber intake was inversely associated with the risk for breast cancer.
Vegetables and legumes. Vegetables have a number of bioactive components, including folate and carotenoids, which may confer protection against breast cancer. Folate may be especially important in women who consume alcohol. Foods that contain folic acid (green leafy vegetables, legumes, oranges) have been found more effective than folate supplements, perhaps due to the presence of other protective factors (e.g., fiber, vitamin C, and phytochemicals). The European Investigation into Cancer and Nutrition (EPIC) study concluded that higher vegetable intakes were related to a 13% lower breast cancer risk compared with the lowest level of consumption, an effect that was more demonstrable for ER-/PR- cancers than ER+/PR+ ones. These effects may be due to vegetables high in carotenoids, higher concentrations of which were associated in the Nurses Health Study with 18%-28% lower risk of breast cancer and inversely associated with breast cancer recurrence and mortality from this disease, over a follow-up period of 20 years.
Consumption of legumes (including soy products) that are high in isoflavones and lignans is also associated with lower risk for breast cancer, an effect that is greater if intake of these foods begins before or during adolescence. A meta-analysis of soy intake and breast cancer risk found a roughly 35% lower risk for ER+/PR+ cancers and a roughly 40% lower risk for ER-/PR- types, as well as significant decreases in breast cancer recurrence and mortality in high versus low soy consumers. These effects have been attributed in part to inhibition of vascular endothelial growth factor (VEGF), proapoptotic effects, inhibition of tyrosine kinase, induction of tumor suppressor proteins, and down-regulation of HER2, among other mechanisms. Further evidence of the benefits of legumes was noted in the Nurses’ Health Study II, in which eating beans or lentils twice per week was associated with a 25% lower risk, compared with consuming those foods less than once per month. More recently, higher intakes of plant protein and nuts during adolescence have been associated with significantly lower breast cancer risk during adulthood when compared with lower intakes.
Nutrition and Breast Cancer Survival
The following considerations apply to recurrence and survival after diagnosis:
Lower body weight. Two recent systematic reviews and meta-analyses have found that initial body weight or weight gain after diagnosis of breast cancer are associated with higher all-cause mortality in breast cancer patients. In one of these, a weight gain of 10% or more of baseline weight was associated with a nearly 25% greater risk for mortality, although the association was not significant for women who were diagnosed at a healthy weight (i.e., BMI < 25). A previous study found that being obese at diagnosis (BMI > 30) was associated with a roughly 40% greater overall mortality risk; for breast cancer-specific mortality, the risk was 75% higher for premenopausal women and 34% higher for postmenopausal women, compared with normal weight women.
Lower-fat diets. A meta-analysis of studies involving nearly 10,000 women found a 23% lower risk for breast cancer recurrence and a 17% lower risk for breast cancer mortality in women consuming low fat diets. With regard to specific fat subtypes, most studies found that prediagnostic saturated fat intake was associated with increased risk of breast cancer-specific and all-cause mortality, while postdiagnostic trans fat intake was associated with a 45% and 78% increased risk of breast cancer specific and all-cause mortality, respectively. ,
Higher intake of soy-containing foods. Women previously diagnosed with breast cancer who then consume higher amounts of soy-based foods have significantly lower risk for both disease recurrence and mortality. The notion that soy products are associated with increased recurrence risk has been widely and mistakenly promoted; research findings show that soy consumption has a protective effect.
Fruits and vegetables. A secondary analysis of 3,080 breast cancer survivors enrolled in the Women’s Healthy Eating and Living (WHEL) study found a 30% reduction in mortality risk in women consuming the most vegetables compared to those eating the fewest. In women taking tamoxifen, the mortality risk was roughly 45% lower in the high vegetable group, and mortality risk was lowest (~ 50% reduction) in women who consumed higher amounts of cruciferous vegetables in addition to taking tamoxifen.
Certain fatty acids and micronutrients, including vitamins C and D, and folate, may be important in moderating mortality risk in breast cancer patients. Higher intakes of EPA and DHA were associated with a 25% reduction in breast cancer recurrence and improved overall mortality in a study of more than 3,000 women with early stage breast cancer followed for a median of 7 years.
A meta-analysis of prospective studies involving nearly 18,000 women found that both dietary and supplementary vitamin C intake were significantly associated with lower total and breast cancer-specific mortality. In a prospective study of roughly 7,300 women, those with the highest versus lowest dietary folate intake had a roughly 25% lower mortality risk. Meta-analyses of the association between vitamin D and breast cancer survival have reported that higher concentrations of 25(OH)D were related to improved survival, and HER2 + patients who received vitamin D supplements in combination with chemotherapy (trastuzumab) experienced statistically significantly improved disease-free survival, when compared to women who did not take a vitamin D supplement.
Regular physical activity (30 minutes per day of walking or equivalent energy expenditure)
A low fat, vegetable-rich, plant-based diet
Screening when appropriate
Avoiding or minimizing alcohol use
During active treatment, dietary orders should be written in consultation between the treating physician and a consulting dietitian
After treatment, a low-fat, vegetable-rich, plant-based diet
What to Tell the Family
The families of breast cancer patients play 2 key roles. The first is to assist the patient who is undergoing treatment, which can be arduous at times. Particularly important is helping the patient make diet and lifestyle changes that can support good health. Second, breast cancer sometimes runs in families. It is important for family members to not only have regular screening for the disease, but to also reduce their risk to the extent possible through the diet and lifestyle changes noted above.
Genetic counseling should be considered for family members of patients diagnosed with breast cancer who carry an inherited mutation, such as the BRCA1 or BCA2 gene or who are otherwise at high risk for hereditary breast cancer (breast cancer diagnosis before age 50 or bilateral breast cancer).
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