14. Breast cancer prevention

Increased risk of breast cancer may result from potentially modifiable causes such as endogenous hormone levels, obesity, HRT, and non-lactation, or non-modifiable factors including genetic susceptibility and increasing age. The Gail model, based on known factors, may be useful for estimating lifetime risk in some individuals, but those risk factors that are easier to modify may have a limited impact on the totality of breast cancer. Tamoxifen prevention still remains contentious, with a significant reduction in risk of breast cancer in women given tamoxifen in the NSABP P1 study but no effect in the Italian and Royal Marsden trials. Raloxifene, tested in the MORE trial, reduced the incidence of breast cancer by 65% but this was restricted to oestrogen receptor positive tumours. Lifestyle factors such as diet, obesity, exercise and age at first full term pregnancy and number of pregnancies have a mild to moderate impact on risk, so may have little effect on the incidence of breast cancer. Reduction of alcohol intake could lead to a modest reduction in the risk of breast cancer but possibly adversely affect other diseases. Fat reduction and GnRH analogue reduce mammographic density but have not yet been shown to affect risk. For women with BRCA1/2 mutation, options include unproven surveillance and prophylactic mastectomy with an unquantified risk reduction. Interesting new candidates for chemoprevention include aromatase inhibitors, new generation SERMs, demethylating agents, non-selective COX inhibitors, tyrosine kinase inhibitors and polyamine synthetic inhibitors.     

Risk factors and health promotion in families of patients with breast cancer

Women with a family history of breast cancer have an increased risk of developing the disease. Women identified as "high risk" for developing breast cancer have been shown to exhibit increased levels of psychological distress and anxiety related to breast cancer. Oncology nurses can address this barrier and others, such as altered risk perception and lack of physician recommendation for screening. Oncology nurses also can identify high-risk families that may be candidates for genetic testing for breast cancer susceptibility, provide comprehensive teaching about breast self-examination (BSE), and clarify misconceptions about early detection. Primary prevention measures for hereditary breast cancer include prophylactic mastectomy and oophorectomy and chemopreventative agents. Secondary prevention measures include screening and early detection with mammography, clinical breast examinations, and BSE. Nurses have a responsibility to educate families of patients with breast cancer about risk factors, primary and secondary preventive measures, genetic testing, and screening recommendations.     

Prevalence of breast cancer predisposition gene mutations in Chinese women and guidelines for genetic testing.

BACKGROUND: Breast cancer is the most common cancer among Caucasian females. On average, 1 in 12 women will have breast cancer during their lifetime. There is a marked difference in breast cancer incidence in Chinese. In Hong Kong women, the lifetime risk is 1 in 29. BRCA1 and BRCA2 are high-penetrant cancer predisposition genes, but the prevalence and nature of mutations in these genes appear to be ethnic-specific. It is not clear if the differences in cancer incidence between Caucasians and Chinese are due to genetic or environmental factors. METHODS: In our investigation of BRCA1 mutations among Chinese female patients in Hong Kong, BRCA1 mutations were found in 3.8% (CI: 1.3-8.8%) of 130 breast cancer patients. The prevalence was higher in a separate group of 56 early onset patients, aged<45 years, (8%, CI: 2.2-19.2). Most of the mutations were different from those reported in Caucasians. A deletion 589delCT was found in three unrelated patients, which may represent a common mutation. Similar prevalence of mutations was reported in Taiwan and Singapore Chinese. Other low-penetrant cancer predisposition genes may be important in the pathogenesis of the majority of breast cancers. CONCLUSIONS: Although the epidemiology of breast cancer is different between Caucasians and Chinese, the prevalence of mutations in the high-penetrant cancer-predisposition gene of BRCA1 is comparable. It may indicate that the role of genetic contribution to breast cancer may be similar in the two ethnic groups and the difference in epidemiology may be contributed more heavily by environmental factors.     

Hereditary breast-ovarian cancer: clinical findings and medical management.

Approximately 5% to 10% of breast and ovarian cancers are related to an inherited gene mutation. Of these cases, 84% of hereditary breast cancer and more than 90% of hereditary ovarian cancer are caused by mutations in the BRCA1 or BRCA2 genes. Family histories of cancer are an essential tool in identifying features of and individuals at risk for hereditary breast-ovarian cancer syndrome. The risk to carry an identifiable BRCA gene mutation can be assessed by trained healthcare providers using various pre-test risk models. Individuals who carry a BRCA gene mutation have increased lifetime risks of developing hereditary breast and ovarian cancer syndrome-related cancers. Genetic testing for the BRCA gene mutations is offered in accordance with American Society of Clinical Oncology guidelines. In accordance with guidelines, patients are informed of the risks, benefits, and limitations of testing prior to electing to undergo the testing process. Upon receipt of results, healthcare providers offer the patient with appropriate medical management recommendations.     

18. Genetics of breast cancer

It is well known that breast cancer often occurs in clusters within families. This clustering can be attributed to mutations in the breast cancer susceptibility genes, BRCA1 and BRCA2, in 16% of familial cases. Women with a family history of breast cancer, in whom no mutation is identified, are still at increased risk of developing the disease. This review addresses methods for estimating and stratifying risk of developing breast cancer based on family history. It also indicates how to identify patients likely to carry mutations in BRCA1 or BRCA2 and gives recommendations for intervention for women with a family history of breast cancer.     

Breast cancer: genetics, risks, and strategies

Breast cancer is the most common cause of cancer among women, with 175,000 new cases diagnosed in 1999. The recent discovery of inherited mutations on the BRCA1 and BRCA2 genes and related research has increased our understanding of key risk factors. After identifying those who are at risk, health care providers must counsel women regarding appropriate prevention and early detection strategies. This article reviews the influence of genetics on breast cancer, identifies risk factors, discusses risk factor analysis, and suggests strategies for prevention and early detection of breast cancer.     

Assessing breast cancer risk: genetic factors are not the whole story

Genetic syndromes that convey a significant risk of breast cancer are responsible for a small but significant percentage of these cancers. However, the vast majority of breast cancers occur in women with no family history of the disease. Nongenetic risk factors include age, previous breast disease, breast tissue density, radiation exposure, and lifestyle factors, such as weight, exercise, and alcohol consumption. In this article, the authors outline genetic and other risk factors for breast cancer, explore risk-reduction strategies, and encourage primary care physicians to assess breast cancer risk in all their patients.     

Assessing breast cancer risk

PREVIEW

Genetic syndromes that convey a significant risk of breast cancer are responsible for a small but significant percentage of these cancers. However, the vast majority of breast cancers occur in women with no family history of the disease. Nongenetic risk factors include age, previous breast disease, breast tissue density, radiation exposure, and lifestyle factors, such as weight, exercise, and alcohol consumption. In this article, the authors outline genetic and other risk factors for breast cancer, explore risk-reduction strategies, and encourage primary care physicians to assess breast cancer risk in all their patients.     

Comprehensive breast cancer screening. Programs now include individual risk assessment

A comprehensive breast cancer screening program needs to include risk assessment in addition to clinical breast examination and mammography. Women identified as being at increased risk should have an individualized schedule of screening mammography and a proven prevention program tailored to their level of risk. In this article, Drs Cardenas and Frisch review risk factors, screening methods, and individual risk assessment, then explain how to use them in conjunction to identify tumors at an earlier, more curable stage.     

Hereditary breast cancer considering Cowden syndrome: a case study

Hereditary breast cancer and the BRCA1 and BRCA2 genes have received a great deal of publicity over the past few years. Patients and family members frequently ask if they can be tested to see whether they have the "breast cancer gene," assuming that all breast cancers can be linked to one chromosomal site. Although the BRCA1 and BRCA2 genes are the most common sites for hereditary breast cancer mutations, there are other hereditary gene mutations associated with breast cancer. Nurses should be aware of the spectrum of hereditary cancer syndromes and their associated "red flags." Important skills for the oncology nurse interested in genetic health include careful assessment of benign and malignant disease histories, alertness to physical findings, performance of risk assessments, and ability to access genetic health resources. The following case study describes the assessment process for a less common genetic disorder known as Cowden syndrome, or multiple hamartoma syndrome, a hereditary cancer syndrome associated with early-onset breast cancer, thyroid cancer, goiters, enlarged head size, and a variety of skin findings.     

Risk factors for breast cancer

Despite the numerous risk factors for the development of breast cancer that have been investigated, only a few demonstrate a clear association with breast cancer development. Female gender and increasing age are the most important factors, followed by factors involving a woman's menstrual, reproductive, and family history. The risks related to menstruation and reproduction are probably related to the duration of estrogenic breast stimulation. The relationship of family history and breast cancer risk is unclear, but there may be a true genetic basis. The previous occurrence of breast cancer (invasive or in situ), the presence of proliferative pathological changes, especially with atypia, and the presence of other malignancies (e.g., primary ovarian and endometrial cancer) are histological risk factors for the development of new or recurrent breast cancer. Radiation exposure, the use of exogenous estrogens (both estrogen replacement therapy and oral contraceptives), diet (especially fat consumption), and alcohol intake may all play a role in cancer risk. Certain medications as well as patient demographics may also have a weak association. Cigarette smoking, caffeine consumption, and stress presently have little support for an association with breast cancer risk. It should be noted that in only one in four patients can breast cancer be accounted for by the known risk factors. This demonstrates that although presently known risk factors may help in screening for the early detection of breast carcinoma, in its possible prevention by modulation of influenceable factors, and in advising patients about their risks, these factors are merely strong associations with breast cancer incidence and not actual causations. The mechanisms of the development of breast cancer are as yet unknown.     

Breast cancer chemoprevention: current clinical practice and future direction.

With the unblinding of the Breast Cancer Prevention Trial (BCPT) in 1998, the clinical management of breast cancer prevention patients has expanded from the time-honored triad of breast cancer screening to include breast cancer risk assessment and risk reduction. With a proven 49% reduction in the incidence of breast cancer, tamoxifen is now the gold standard in chemoprevention for breast cancer risk reduction for women at increased risk of the disease. The suggested 74% reduction in the incidence of breast cancer seen with raloxifene in the Multiple Outcomes of Raloxifene Evaluation (MORE) trial is the basis of the now ongoing Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer. Findings are anticipated in 2006.     

Management of women with a family history of breast cancer

Five to ten per cent of breast cancer results from an inherited germ line mutation. The main susceptibility genes are BRCA1 and BRCA2, but others include Cowden's disease, Li Fraumeni syndrome and ataxia-telangiectasia. For those with BRCA1 or BRCA2 mutations the lifetime probability of breast cancer is between 0.40 and 0.73. Genetic testing needs to be offered to young women with breast cancer before considering testing their relatives. The efficacy of surveillance in women with genetic susceptibility has yet to be proved. The value of tamoxifen as a preventive agent in women with genetic susceptibility has yet to be confirmed. Prophylactic bilateral mastectomy will probably reduce the risk of breast cancer but this may not be absolute because of the difficulty of removing all breast tissue. New approaches may enable the selective destruction of mammary epithelium without disturbance to breast architecture.     

Breast cancer diagnosis and screening

Approximately 180,000 new cases of breast cancer are diagnosed annually, accounting for about 48,000 deaths per year in the United States. The screening guidelines for the diagnosis of breast cancer are continually changing. Because of increased awareness of the signs and symptoms of breast cancer and the use of screening mammograms, breast cancers are increasingly being diagnosed at earlier stages. Annual mammograms and clinical breast examinations are recommended for women older than 40 years. Women older than 20 years should be encouraged to do monthly breast self-examinations, and women between 20 and 39 years of age should have a clinical breast examination every three years. These guidelines are modified for women with risk factors, particularly those with a strong family history of breast cancer. Ultrasonographic studies are most useful to evaluate cystic breast masses. For solid masses, diagnostic biopsy techniques include fine-needle aspiration, core biopsy and excisional biopsy.     

Type 2 diabetes and subsequent incidence of breast cancer in the Nurses' Health Study

OBJECTIVE: Hyperinsulinemia may promote mammary carcinogenesis. Insulin resistance has been linked to an increased risk of breast cancer and is also characteristic of type 2 diabetes. We prospectively evaluated the association between type 2 diabetes and invasive breast cancer incidence in the Nurses' Health Study. RESEARCH DESIGN AND METHODS: A total of 116,488 female nurses who were 30-55 years old and free of cancer in 1976 were followed through 1996 for the occurrence of type 2 diabetes and through 1998 for incident invasive breast cancer, verified by medical records and pathology reports. RESULTS: During 2.3 million person-years of follow-up, we identified 6,220 women with type 2 diabetes and 5,189 incident cases of invasive breast cancer. Women with type 2 diabetes had a modestly elevated incidence of breast cancer (hazard ratio [HR] = 1.17; 95% CI 1.01-1.35) compared with women without diabetes, independent of age, obesity, family history of breast cancer, history of benign breast disease, reproductive factors, physical activity, and alcohol consumption. This association was apparent among postmenopausal women (1.16; 0.98-1.62) but not premenopausal women (0.83; 0.48-1.42). The association was predominant among women with estrogen receptor-positive breast cancer (1.22; 1.01-1.47). CONCLUSIONS: Women with type 2 diabetes may have a slightly increased risk of breast cancer.     

Risk factors for chronic pain following breast cancer surgery: a prospective study.

Chronic pain following breast cancer surgery is associated with decreased health-related quality of life and is a source of additional psychosocial distress in women who are already confronting the multiple stresses of cancer. Few prospective studies have identified risk factors for chronic pain following breast cancer surgery. Putative demographic, clinical, and psychosocial risk factors for chronic pain were evaluated prospectively in 95 women scheduled for breast cancer surgery. In a multivariate analysis of the presence of chronic pain, only younger age was associated with a significantly increased risk of developing chronic pain 3 months after surgery. In an analysis of the intensity of chronic pain, however, more invasive surgery, radiation therapy after surgery, and clinically meaningful acute postoperative pain each independently predicted more intense chronic pain 3 months after surgery. Preoperative emotional functioning variables did not independently contribute to the prediction of either the presence or the intensity of chronic pain after breast cancer surgery. These findings not only increase understanding of risk factors for chronic pain following breast cancer surgery and the processes that may contribute to its development but also provide a basis for the development of preventive interventions. PERSPECTIVE: Clinical variables and severe acute pain were risk factors for chronic pain following breast cancer surgery, but psychosocial distress was not, which provides a basis for hypothesizing that aggressive management of acute postoperative pain may reduce chronic pain.     

Cytomorphology as a risk predictor: experience with fine needle aspiration biopsy, nipple fluid aspiration, and ductal lavage

Primary prevention of breast cancer requires identification and elimination of cancer-causing agents, which is an incredibly difficult task to follow. Secondary prevention involves screening individuals who are at increased risk for breast cancer in hopes that early intervention will affect survival. In the 1980s, chemoprevention received serious attention. This approach was aimed at reducing cancer risk by administration of natural or synthetic clinical compounds that prevent, reverse, or suppress carcinogenesis in individuals at increased risk for cancer. It was not until 1998, however, when the first report from the National Surgical Adjunct Breast and Bowel Project (Breast Cancer Prevention Trial BCPT; P-1) randomized clinical trial appeared in the literature supporting the hypothesis that breast can-cer can be prevented. This study showed that administration of tamoxifen reduced the risk for invasive and noninvasive breast cancer by almost 50% in all age groups. With the current availability of tamoxifen as a chemopreventive agent and with the increasing emphasis on early breast cancer detection and prevention, more women seek consultation to determine their risk for breast cancer. However, in the absence of any detectable breast lesion, clinically and mammographically, only a few women may volunteer to have their breasts sampled by surgical biopsy for risk assessment. Other non-surgical procedures include fine needle aspiration biopsy (FNAB), nipple aspirate fluid (NAF), and the recently introduced procedure, ductal lavage. These techniques may provide better alternatives. These minimally invasive procedures are capable of recruiting cellular material for cytomorphologic interpretation and biomarker studies.     

Identifying and counseling women at increased risk for breast cancer

Women at increased risk for breast cancer should be identified and counseled about options for risk reduction. Identifying such women is simplified with use of the National Cancer Institute Risk Assessment tool, a computer-based tool that incorporates information on 6 risk factors for estimating an individual's risk of developing breast cancer. However, the tool does not incorporate all known or possible risk factors and may underestimate risk, particularly among women with a complex family history of breast cancer for whom alternative models of risk assessment are more appropriate. Women found to have an increased risk of breast cancer should be counseled about options for management, including close surveillance, lifestyle modifications, chemoprevention with tamoxifen, enrollment in a breast cancer prevention clinical trial, and prophylactic mastectomy and/or oophorectomy. In the absence of consensus about which risk level is best suited to which option, decisions about risk reduction depend as much on an individual's priorities and risk aversion as on numerical risk estimates.     

Breast arterial calcifications as a cardiovascular risk marker in women

Cardiovascular disease and breast cancer are the two main causes of mortality in women. Mammography as a screening test for breast cancer is recommended for all women from the age of 40 to 50 years. Mammographically detected breast arterial calcifications are currently considered an incidental finding without clinical importance, since they are not associated with an increased risk of breast cancer. However, recent studies have shown that breast arterial calcifications on mammograms have been associated with cardiovascular risk factors and atherosclerotic cardiovascular disease. These results suggest that breast arterial calcifications, detected during routine mammography, are a noteworthy finding that could be valuable in identifying asymptomatic women at increased cardiovascular risk.