Breast cancer risk reduction: Notable achievements and remaining challenges

Millions of women in the United States are at increased risk of breast cancer. Multiple prospective, randomized clinical trials have demonstrated both the efficacy and safety of selective estrogen receptor modulators and aromatase inhibitors in reducing substantially the risk of invasive breast cancer in women at increased risk. Published tables are available to aid clinicians in shared decision‐making regarding drug interventions with their patients who are at increased risk of breast cancer. Both professional and governmental agencies have advised that these interventions should be offered to women at increased risk of breast cancer. Doing so would reduce breast cancer morbidity substantially.     

Risk taking and tolerance of uncertainty: implications for surgeons

BACKGROUND: Adherence to evidence-based adverse outcome prevention techniques is a critical factor in providing high-quality patient care, but many of these interventions are not used by physicians. It is unclear if surgeons' risk attitudes and reactions to uncertainty influence their use of these or other interventions. MATERIALS AND METHODS: A systematic review of the literature was conducted to identify studies evaluating the effects of physicians' risk attitudes, reactions to uncertainty or ambiguity, and personality traits on clinical decision making. RESULTS: A variety of instruments to assess risk attitude and reactions to uncertainty have been developed and tested among physicians involved in critical care and emergency medicine. Scoring systems distinguish risk averse and risk seeking practitioners. In many studies, these characteristics were related to clinical decision making in situations of uncertainty. For example, among patients evaluated in the emergency room for chest pain, "risk-seeking" physicians admitted significantly fewer patients who did not have acute myocardial infarction than risk-avoiding physicians (29% and 47% of patients admitted, respectively). In contrast, risk-seeking physicians were no more likely to discharge a patient who eventually was found to have an acute myocardial infarction. CONCLUSIONS: There are very limited data on the extent to which surgical decision making is linked to risk taking behavior and "comfort with uncertainty". Understanding the behaviors, attitudes and beliefs that make up surgical "judgment" remains a challenge for those interested in influencing behavior.     

Breast Cancer Genetics and Psychosocial Issues

Abstract: Women are increasingly aware of the concept of cancer high-risk status and of the availability of genetic testing. In seeking to educate women on these issues the practitioner must become educated on the psychosocial, ethical, and legal implications involved in advising women about and documenting the details of their risk status. In addition, counseling for women regarding the availability of testing and aid for women as they move through the decision process regarding individual appropriateness of genetic testing must be made available by the practitioner or designee. This article details current understanding of the psychosocial issues regarding high risk status, genetic testing decision making, and emotional reactions to the results of that testing.     

Contralateral prophylactic mastectomy: A narrative review of the evidence and acceptability

The uptake of contralateral prophylactic mastectomy (CPM) has increased steadily over the last twenty years in women of all age groups and breast cancer stages. Since contralateral breast cancer is relatively rare and the breast cancer guidelines only recommend CPM in a small subset of patients with breast cancer, the drivers of this trend are unknown. This review aims to evaluate the evidence for and acceptability of CPM, data on patient rationales for choosing CPM, and some of the factors that might impact patient preferences. Based on the evidence, future recommendations will be provided. First, data on contralateral breast cancer risk and CPM rates and trends are addressed. After that, the evidence is structured around four main patient rationales for CPM formulated as questions that patients might ask their surgeon: Will CPM reduce mortality risk? Will CPM reduce the risk of contralateral breast cancer? Can I avoid future screening with CPM? Will I have better breast symmetry after CPM? Also, three different guidelines regarding CPM will be reviewed. Studies indicate a large gap between patient preferences for radical risk reduction with CPM and the current approaches recommended by important guidelines. We suggest a strategy including shared decision-making to enhance surgeons’ communication with patients about contralateral breast cancer and treatment options, to empower patients in order to optimize the use of CPM incorporating accurate risk assessment and individual patient preferences.     

Targeted Tailored Management of the Breast Cancer Patient at Risk for Harboring a Germline Mutation—Current Trends Affecting the Selection of Patients Considering Surgical Prophylaxis for Breast Cancer

Abstract:  Recent reports have documented the increasing use of mastectomy in women with breast cancer otherwise amenable to breast conservation. Similarly, other reports document an increase in the number of women undergoing contra-lateral prophylactic mastectomy for a single unilateral breast cancer. These trends are abetted by increasing use of MRI, inadequate risk counseling, and patient fear. Adequate and reliable risk assessment and genetic counseling are indispensable for the appropriate and personalized treatment of these individuals. In all of these instances, such counseling should be instituted well before the patients are submitted to any surgical intervention. An algorithm is presented which permits the orderly selection of patients who may benefit from such aggressive surgical intervention.     

Targeted Tailored Management of the Breast Cancer Patient at Risk for Harboring a Germline Mutation—Current Trends Affecting the Selection of Patients Considering Surgical Prophylaxis for Breast Cancer

Abstract: Recent reports have documented the increasing use of mastectomy in women with breast cancer otherwise amenable to breast conservation. Similarly, other reports document an increase in the number of women undergoing contra‐lateral prophylactic mastectomy for a single unilateral breast cancer. These trends are abetted by increasing use of MRI, inadequate risk counseling, and patient fear. Adequate and reliable risk assessment and genetic counseling are indispensable for the appropriate and personalized treatment of these individuals. In all of these instances, such counseling should be instituted well before the patients are submitted to any surgical intervention. An algorithm is presented which permits the orderly selection of patients who may benefit from such aggressive surgical intervention.     

Initial experience with surgical treatment planning in the newly diagnosed breast cancer patient at high risk for BRCA-1 or BRCA-2 mutation

Despite an abundance of information available for dealing with patients with BRCA-1 and BRCA-2 mutations, little guidance is available to assist the surgeon in dealing with the genetically high-risk patient recently diagnosed with breast cancer. A retrospective review was undertaken of 170 patients who underwent genetic counseling and testing over a 3-year period from March 2000 to March 2003. Forty-three of the 170 patients tested were diagnosed with breast cancer prior to genetic testing. Nine patients (20.9%) tested positive for a deleterious mutation. Fifty-eight percent underwent genetic counseling prior to definitive cancer surgery. Five of the 25 patients who underwent lumpectomy tested positive for a deleterious mutation. Testing results became available during systemic therapy or radiation was delayed until results were known. After counseling, all five patients testing positive went on to bilateral prophylactic mastectomy and reconstruction. None had radiation therapy. Because of a strong family history, eight patients elected to undergo prophylactic mastectomy and reconstruction prior to obtaining genetic test results; and despite compelling histories, all eight tested negative for a mutation. Treatment algorithms are developed to manage patients that are first discovered to be at high risk for a BRCA-1 or BRCA-2 mutation at the time they are diagnosed with breast cancer. Patients diagnosed with breast cancer who are discovered to be at high risk for a genetic mutation should undergo counseling prior to definitive surgery. This maximizes the time that patients have to consider options for prophylaxis and monitoring should their test be positive. It also prevents women who would otherwise be candidates for breast preservation from undergoing unnecessary radiation therapy should they chose prophylactic mastectomy in the face of a positive test.     

Risk Factors for Breast Cancer: A Case-Control Study from Taegu, Korea

Abstract: A hospital-based case-control study was carried out to identify reproductive risk factors for breast cancer in Taegu, Korea. Four hundred and eighty-one breast cancer patients and 491 age-matched control patients examined between 1988 and 1994 were included in this study. Eleven reproductive risk factors were selected for comparison using cross tabulation and chi-square method, and univariate and multivariate logistic regression analyses were used to evaluate the odds ratios for the risk of breast cancer. The mean age of the breast cancer patients in this study was 47.5 years. Analyses demonstrated that nulliparous women had a higher risk for breast cancer (odds ratio 3.46, p = 0.03) than women with one to four live births, and women who had an abortion during their first pregnancy had a slightly increased risk (odds ratio 1.86, p < 0.01) than women who had normal deliveries, but the age at menarche and menopause did not have any influence on the risk of developing breast cancer. Although there were similarities in risk factors between Western women and women in this study, such as a higher risk for nulliparous women, two key factors were found to contrast with those of Western women. First, the mean age of breast cancer patients in this study was only 47.5 years. Second, the age of menarche and menopause of these women did not have any influence on the risk of breast cancer.     

Benchmarking of a checklist for the identification of familial risk for breast and ovarian cancers in a prospective cohort

The detection of deleterious germline mutations in BRCA1 and BRCA2 considerably influences the clinical management of healthy and diseased carriers. Therefore, the identification of persons at risk who could uptake genetic counseling and testing is pivotal. We developed a checklist with validated criteria to improve the identification, and prospectively evaluate the incidence, of familial cancer history in 5091 breast cancer patients. The rate of 30.4% of patients at high genetic risk underpins the demand for care in risk identification and counseling. The easy‐to‐use instrument promotes the implementation and dissemination of risk counseling by physicians.     

Physicians' perceptions of breast density notification laws and appropriate patient follow-up

Breast density notification laws have been adopted in the absence of consistent guidelines for post-notification follow-up. This can lead to inconsistent and potentially deficient management of women's health due to inconsistent physician practices. We examined physicians’ knowledge and practices regarding follow-up for patients who receive density notifications. Physicians who referred patients to a Michigan hospital network for screening mammograms were recruited to participate in survey study; 105 (29.8%) responded. The survey assessed physicians’ demographics, knowledge, and awareness of breast density and breast cancer risk and of density notification laws, and perceptions of appropriate follow-up behaviors for their patients who received density notifications. Most physicians (75%) knew about the notification law, and they were generally comfortable responding to breast density questions and deciding on follow-up. Most indicated that additional breast imaging (68.0%), followed by assessing breast cancer risk (24.7%) were appropriate follow-up responses. Physicians who performed breast cancer risk assessments, and who were more comfortable with breast density questions and follow-up decision making, were more likely to propose additional imaging. Male physicians were less likely to propose assessing breast cancer risk, and less likely to propose clinical and/or breast self-examinations. Divergence between practice and guidelines when it comes to supplemental breast cancer screening, coupled with density notification language that promotes additional screening in the absence of consistent evidence, remains concerning. Improved understanding of how density notification recipients and their physicians make decisions about supplemental screening is warranted to ensure that breast cancer risk is properly considered.     

Managing the Breast in Patients Who Test Positive for Hereditary Breast Cancer

PURPOSE AND METHODS: The patient who tests positive for hereditary breast cancer has several important decisions to make regarding management of the breasts. Before making an informed decision, the physician must first review the screening assessment to make sure that the patient does not harbor an undiagnosed breast malignancy. In the absence of a malignancy, the management options for the breast range from nonoperative surveillance to prophylactic mastectomy to prevent cancer. In the event that a breast malignancy is diagnosed after a positive genetic test, implications for management of both the affected and the unaffected breast must be considered. RESULTS AND DISCUSSION: The clinical assessment of the patient who tests positive is discussed. If routine pretest mammograms were negative, should additional diagnostic studies be performed to exclude an undetected/occult malignancy, and if so, what are the roles of magnetic resonance imaging, ultrasonography, digital mammogram, and detection of breast cancer circulating tumor cells? Medical management may include increased surveillance and chemopreventative therapy, including tamoxifen and oral contraceptives. Surgical interventions may be undertaken to reduce risk in people with a genetic susceptibility gene for breast or ovarian cancer; risk-reducing surgical options include mastectomy with or without reconstruction and nipple-sparing techniques. Finally, we discuss management decisions for women who test positive and who are diagnosed with a primary breast cancer, compared to women who have no obvious primary tumor but test positive.     

Testing for hereditary breast and ovarian cancer in the southeastern United States

OBJECTIVES: To detail characterization of mutations and uncharacterized variants in the breast cancer susceptibility genes BRCA1 and BRCA2, as observed in a population of breast cancer patients from the southeastern United States, and to examine baseline characteristics of women referred for counseling and testing and provide a preliminary look at how counseling and testing affected intentions toward prophylactic surgery. BACKGROUND: Mutations in the BRCA1 and BRCA2 genes give rise to a dramatically increased risk of developing breast or ovarian cancer or both. There are many reports about special populations in which deleterious mutations are present at a high frequency. It is useful to study these genes in more heterogeneous populations, reflecting different geographic regions. Interest in preventive surgery for gene carriers is high in women and their surgeons. METHODS: Women were recruited through a prospective clinical trial of counseling and free genetic testing. BRCA1 and BRCA2 were screened for mutations using standard techniques, and results were given to participants. Baseline questionnaires determined interest in preventive surgery at the beginning of the study. Follow-up questionnaires for those who completed testing surveyed interest in prophylactic surgery after counseling and receiving test results. RESULTS: Of 213 women who completed counseling and testing, 44 (20.6%) had 29 separate mutations; there were 11 Jewish women carrying three founder mutations. Twenty-eight women (13.1%) had uncharacterized variants in BRCA1 or BRCA2; nine were not previously reported. Women overestimated their chances of possessing a deleterious gene mutation compared to a statistical estimate of carrier risk. A number of women changed their intentions toward preventive surgery after genetic counseling and testing. CONCLUSIONS: Hereditary breast cancer due to mutations in BRCA1 and BRCA2 was a heterogeneous syndrome in the southeastern United States. Most mutations were seen just once, and uncharacterized variants were common and of uncertain clinical significance. In general, positive test results tended to reinforce intentions toward prophylactic surgery. In contrast, women not interested in surgery at the time of entry tended to remain reluctant after testing and counseling.     

Risk counseling and management in patients with lobular carcinoma in situ

BACKGROUND: The understanding of lobular carcinoma in situ (LCIS) has evolved since it was first described. LCIS once was thought to be a premalignant condition, but now it is considered a marker for increased risk for developing invasive breast cancer. We evaluated patient perception of risk, counseling, and subsequent management. METHODS: A community cancer registry of 3,605 cases of breast cancer was reviewed. Fifty-five (1.5%) patients with LCIS as their sole diagnosis were identified and these patients were sent a questionnaire. RESULTS: Forty of 55 patients completed the questionnaire for a 73% response rate. The patients' perception of lifetime risk for invasive cancer was variable. Surgeons performed the majority of counseling. Fourteen patients (35%) were placed on a selective estrogen-receptor modulator. Eleven patients (28%) had bilateral mastectomy. Three patients had unilateral mastectomy. Screening recommendations included an annual mammography (64%), a professional examination (64%), and a monthly self-breast examination (75%). CONCLUSION: A patient's perception of risk for invasive breast cancer after a diagnosis of LCIS is widely variable. Patients will adhere to suggested screening recommendations. Surgeons are performing the majority of counseling and must stay abreast on current recommendations.     

Evidence-based surgery. Canadian Association of General Surgeons and American College of Surgeons Evidence Based Reviews in Surgery. 19. The effect of a decision aid on knowledge and treatment decision making for breast cancer.

Question: What is the impact of a decision aid outlining the different surgical options for stage I or stage II breast cancer on patient decision making? Design: Cluster randomized controlled trial. Setting: Twenty surgeons from communities in central-west and eastern Ontario. Patients: A total of 201 of 208 patients (97%) with newly diagnosed clinical stage I or stage II breast cancer agreed to participate in the trial. Of these women, 94 were randomized to the decision aid group and 107 to usual standard of care. Intervention: Patients assigned to the decision aid group were shown a decision board that presented information, including acute and long-term adverse effects associated with treatment and the effects of treatment on a patient''s breast, long-term survival and quality of life, for the different treatment options. As well, patients were able to express a preference for treatment. Main outcome measures: (1) Patient knowledge about surgical treatment of breast cancer, (2) decisional conflict, (3) satisfaction with decision making and (4) treatment decision after the consultation. Results: Patients in the decision aid group had higher knowledge scores about their treatment options (66.9 v. 58.7; p < 0.001), had less decisional conflict (1.40 v. 1.62; p = 0.02) and were more satisfied with decision making (4.50 v. 4.32; p = 0.05). Patients who used the decision board were more likely to choose breast conservation therapy (BCT) (94% v. 76%, p = 0.03). Conclusions: The decision aid was helpful in improving communication and patient knowledge. The use of the decision aid resulted in less decisional conflict and better patient satisfaction with their treatment decision.     

Understanding Mathematical Models for Breast Cancer Risk Assessment and Counseling

Abstract: Chemoprevention and prophylactic surgery are effective interventions for lowering breast cancer incidence. However, these approaches are associated with risks of their own. Accurate individualized breast cancer risk assessment is an essential component of the risk/benefit analysis that must take place prior to implementing either of these strategies. Several mathematical models for estimating individual breast cancer risk have been proposed over the last decade. The Gail model is the most generally applicable model; however, it neglects family history information in second-degree relatives, treats pre- and postmenopausal breast cancer the same, and ignores personal histories of lobular neoplasia. The Claus model is a better family history model, but it does not assign any special relevance to histories of bilateral breast cancer or ovarian cancer, and neglects all of the nonfamily history information accounted for by the Gail model. BRCAPRO is a Bayesian family history model that calculates individual breast cancer probabilities based on the probability that a family carries a mutation in one of the BRCA genes. Though its treatment of family history information is more thorough than the other models, it neglects the nonfamily history risk factors accounted for by the Gail model and may not appreciate familial clustering unrelated to BRCA gene mutation. A thorough understanding of the principles of risk analysis and the available mathematical models is essential for anyone wishing to perform intervention counseling. This review describes the basic components of risk analysis, explains how the mathematical models work and compares the strengths and weaknesses of the various models. CancerGene is a software tool for running all of these models. It may be obtained without charge at http://www.swmed.edu/home_pages/cancergene .     

Pilot trial of a computerized decision aid for breast cancer prevention

This study sought to evaluate a shared decision-making aid for breast cancer prevention care designed to help women make appropriate prevention decisions by presenting information about risk in context. The decision aid was implemented in a high-risk breast cancer prevention program and pilot-tested in a randomized clinical trial comparing standard consultations to use of the decision aid. Physicians completed training with the decision aid prior to enrollment. Thirty participants enrolled (15 per group) and completed measures of clinical feasibility and effectiveness prior to, immediately after, and at 9 months after their consultations. The decision aid was feasible to use during the consultations as measured by consultation duration, user satisfaction, patient knowledge, and decisional conflict. The mean consultation duration was not significantly different between groups (24 minutes for intervention group versus 21 minutes for control group, p = 0.42). The majority found the decision aid acceptable and useful and would recommend it to others. Both groups showed an improvement in breast cancer prevention knowledge postvisit, which was significant in the intervention group (p = 0.01) but not the control group (p = 0.13). However, the knowledge scores returned to baseline at follow-up in both groups. Decision preference for patients who chose chemoprevention post consultations remained constant at follow-up for the intervention group, but not for the control group. The decision framework provides access to key information during consultations and facilitates the integration of emerging biomarkers in this setting. Initial results suggest that the decision aid is feasible for use in the consultation room. The tendency for the decision choices and knowledge scores to return to baseline at follow-up suggests the need for initial and ongoing prevention decision support.     

PCA: Prostate Cancer,Patient‐Centred Approach or both?

What's known on the subject? and What does the study add? Several studies have explored patient‐specific expectations of prostate cancer management, while others have investigated physicians' perceptions. However, the opinions of both groups have seldom been compared in one study. Therefore, the present study compares the results of two surveys, one among physicians and one among patients, on patient–physician communication and patients' expectations of prostate cancer management. The present review aims to highlight the differences and similarities in opinion on prostate cancer management between physicians and patients. It reflects the most important results of two surveys on patient‐specific expectations in prostate cancer management, done among European prostate cancer specialists and patients with prostate cancer. These results are compared with published data. In addition, the authors' opinion on the survey results and on optimal prostate cancer management is included. To evaluate differences and similarities in opinions on and expectations of prostate cancer management between physicians and patients. Two surveys on patient‐specific opinions and expectations in prostate cancer management were done in 2011 among European prostate cancer specialists and patients with prostate cancer. Survey results were complemented with existing published data and with the authors' opinion. Most specialists spent 15–29 min on delivering the diagnosis, and about the same amount of time on explaining treatment options. This time was considered insufficient by 35% and 48% of patients, respectively. There was a large discrepancy between physicians' and patients' opinions about the type of provided prognostic and therapeutic information, indicating that patients may not have completely understood this information. Shared decision‐making was preferred by both patients and specialists. Treatment efficacy was the most important factor determining treatment choice for both groups, while the physician's opinion or experience also had a great impact on patients' treatment choice. Patient‐support groups have an important role in providing relevant information and in exchanging experiences between patients. The supportive role of partners/relatives was more appreciated when discussing treatment options than during diagnosis. Although patients' expectations are generally matched by their caring physician(s), physicians can still improve quality of care by taking adequate time for their patients, by using terminology that is easily understood by patients and by encouraging shared decision‐making. A multidisciplinary team may be an important part of the treatment paradigm, with the individual patient's needs and preferences as the centre of care.     

Relationship Between Relative Risk of Developing Breast Cancer and Absolute Risk in a Population of Rural, Older African American Women

Abstract: Relative risks computed from known breast cancer risk factors can be used to quantitate a woman's individual risk of developing breast cancer. However, among older women the absolute risk of developing breast cancer over a specified time interval may be more useful in risk-benefit counseling. The objective of this investigation is to characterize the relationships between relative risks and absolute risks of breast cancer among a population of rural, older African American women. Among 224 African American women aged 50–91 years, relative risks were computed from historical information on age at menarche, number of previous biopsies, age at first birth, and number of first-degree relatives with breast cancer. These estimates, combined with the woman's current age, average remaining life expectancy, age-specific mortality, and breast cancer incidence rates, were used to estimate lifetime probabilities of developing breast cancer. Most women in the cohort (72.8%) had weak relative risks of 1.01–1.5 and only 3.5% of the women had relative risks of greater than 3.0. The majority of the women (87.5%) had lifetime probabilities of developing breast cancer that were less than 5%. Although there is a marked increase in age-specific breast cancer incidence with age, the probability of developing breast cancer in this population is low, primarily due to the low relative risks and the effects of competing mortality at older ages. Screening mammography should be directed toward women with high risks who are not receiving regular screening mammograms.     

Is surgery always indicated in older women with breast cancer?

Although surgery has long been considered the main form of curative treatment for breast cancer, its use in older women may not always be indicated. Whilst surgery has been shown to provide superior local control for breast cancer, there is conflicting evidence on whether surgery offers a significant improvement on overall survival in these patients. The more indolent tumour biology commonly seen in older women with breast cancer, coupled with competing causes of death may alter the goals of treatment. The differing needs of older patients should be thoroughly assessed to consider their comorbidities, functional status and quality of life. A comprehensive geriatric assessment and quality of life assessment could identify pretreatment risk factors and guide clinical decision making, improving morbidity and prognosis. Alternatives to surgery include primary endocrine therapy and primary radiotherapy. Further research is required to identify different patient or tumour factors which can be used to individualize treatment for breast cancer in older women and to develop holistic assessment tools which take into account their individual quality of life, geriatric syndromes and functional needs. A dedicated multidisciplinary-led clinic may provide a suitable platform for the assessment, review and management of this distinctive set of patients.     

Establishing a Family Risk Assessment Clinic for Breast Cancer

Abstract:  Breast cancer is the most common cancer affecting European women and the leading cause of cancer-related death. A total of 15–20% of women who develop breast cancer have a family history and 5–10% a true genetic predisposition. The identification and screening of women at increased risk may allow early detection of breast cancer and improve prognosis. We established a family risk assessment clinic in May 2005 to assess and counsel women with a family history of breast cancer, to initiate surveillance, and to offer risk-reducing strategies for selected high-risk patients. Patients at medium or high risk of developing breast cancer according to NICE guidelines were accepted. Family history was determined by structured questionnaire and interview. Lifetime risk of developing breast cancer was calculated using Claus and Tyrer-Cuzick scoring. Risk of carrying a breast cancer-related gene mutation was calculated using the Manchester system. One thousand two hundred and forty-three patients have been referred. Ninety-two percent were at medium or high risk of developing breast cancer. Formal assessment of risk has been performed in 368 patients, 73% have a high lifetime risk of developing breast cancer, and 72% a Manchester score ≥16. BRCA1/2 mutations have been identified in 14 patients and breast cancer diagnosed in two. Our initial experience of family risk assessment has shown there to be a significant demand for this service. Identification of patients at increased risk of developing breast cancer allows us to provide individuals with accurate risk profiles, and enables patients to make informed choices regarding their follow-up and management.