Breast Cancer Prevention: Patient Decision Making and Risk Communication in the High Risk Setting

Abstract: The purpose of this study was to investigate prevention decision making among women at high risk for breast cancer, including patient preferences for preventive interventions, patient understanding of disease risk, and patient preferences for risk communication methods, and the corresponding physician understanding of these factors. A prospective interview and survey study was conducted of consecutive new patients seen at a cancer risk and prevention clinic and their physicians. One hundred and forty‐six of 217 eligible patients participated and completed all components of the study (67%), and they were seen by a four physicians. Women’s preferences for prevention intervention varied widely across women but were stable across time. Physicians were very often unable to predict their patients’ preferences for prevention efforts. Patients overestimated their risk of disease, and physicians overestimated the decrease in perceived risk resulting from counseling (p < 0.001). As risk stratification for breast cancer improves, and prevention options become more tolerable, it becomes increasingly important to appropriately counsel women considering such options. This study provides insight into the decision making process of women at high risk for breast cancer and highlights the importance of addressing patient preferences for interventions and risk perception during risk assessment and counseling consultations.     

Rating the risk factors for breast cancer

OBJECTIVE: To update and summarize evidence of risk factors for breast cancer. SUMMARY BACKGROUND DATA: Women who are at high risk for breast cancer have a variety of options available to them, including watchful waiting, prophylactic surgery, and chemoprevention. It is increasingly important to accurately assess a patient's risk profile to ensure that the cost/benefit ratio of the selected treatment is favorable. METHODS: Estimates of relative risk for documented risk factors were obtained from seminal papers identified in previous reviews. These estimates were updated where appropriate with data from more recent reports using large sample sizes or presenting meta-analyses of previous studies. These reports were identified from a review of the Medline database from 1992 to 2002. RESULTS: Risk factors that have received a great deal of publicity (hormone use, alcohol consumption, obesity, nulliparity) present a relatively modest relative risk for breast cancer (<2). Factors associated with a prior history of neoplastic disease or atypical hyperplasia and factors associated with a genetic predisposition significantly affect the risk of breast cancer, with relative risks ranging from 3 (for some cases of positive family history) to 200 (for premenopausal women positive for a BRCA mutation). CONCLUSIONS: More precise tools, based on techniques of molecular biology such as microarray analysis, will be needed to assess individual risk for breast cancer.     

Breast cancer in the elderly.

OBJECTIVE/METHODS: To determine the clinical behavior and outcome of breast cancer in the elderly, a series of 184 women older than age 69 years who received treatment for locoregional breast cancer at The University of Texas M. D. Anderson Cancer Center between 1976 and 1985 were studied for a median of 80 months. RESULTS: The results indicate that elderly women can tolerate standard surgical therapy and survive disease-free for many years; the breast cancer-specific survival rate of patients in this study was 79% at 7 years. Although 33% of patients had stage I disease, only 10% underwent breast conservation surgery. Despite 46% of patients having stage II and 21% having stage III breast cancer, fewer than 13% received systemic adjuvant therapy. Noncompliance with breast screening guidelines was evident in that only 3% of patients had tumors detected by routine screening mammograms and only 12% by routine physical examinations. CONCLUSIONS: Women with breast cancer should be informed of treatment options and the advantages and disadvantages of each choice based on physiologic rather than chronologic age.     

Distress, coping, and social support among rural women recently diagnosed with primary breast cancer

This study examined distress, coping, and group support among a sample of rural women who had been recently diagnosed with breast cancer. We recruited 100 women who had been diagnosed with primary breast cancer at one of two time points in their medical treatment: either within a window up to 3 months after their diagnosis of breast cancer, or within 6 months after completing medical treatment for breast cancer. Their mean age was 58.6 years (SD = 11.6), and 90% were of white/European American ethnicity. Women completed a battery of demographic and psychosocial measures prior to being randomized into a psychoeducational intervention study, and then again 3 months later at a follow-up assessment. The focus of this article is on the women's self-reported psychosocial status at baseline. Many of the women experienced considerable traumatic stress regarding their breast cancer. However, this distress was not reflected in a standard measure of mood disturbance that is frequently used in intervention research (the Profile of Mood States). The average woman considered her diagnosis of breast cancer to be among the four most stressful life events that she had ever experienced. Also, women on average reported a high level of helplessness/hopelessness in coping with their cancer. On average, women felt that they "often" (but not "very often") received instrumental assistance, emotional support, and informational support. Women varied considerably in which kind of social group provided them with the most support, with as many reporting that they found the greatest support in spiritual/church groups or within their family units as with breast or general cancer groups. These results suggest that among these rural women with breast cancer, distress with the diagnosis of breast cancer must be carefully assessed, as women who are highly distressed about their breast cancer may not report general mood disturbance. Furthermore, the kinds of groups that rural women with breast cancer experience as most supportive need to be identified so that psychosocial interventions can be matched to breast cancer patients' individual needs.     

Management of women at increased risk for breast cancer secondary to high‐risk proliferative lesions and family history of the disease

Women with breast biopsies showing high‐risk proliferative lesions such as atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) have an increased risk of developing breast cancer. Other factors including age, family history of breast cancer, and extent of AH may play a role in increasing breast cancer risk. In addition to women with AH, there is a subset of women with a positive family history of breast cancer, without a known germline mutation, which places them also at an increased risk for breast cancer. Clinical management, screening, chemoprevention, and surgical risk‐reduction are discussed in this review to inform the management of these high‐risk women. Advanced imaging technology, pharmacologic research into different targets, and innovations in breast reconstruction are changing the way in which patients are counseled of their individual risk.     

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.     

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.     

Predictors of breast cancer development in a high-risk population

BACKGROUND: The purpose of this study was to investigate the strongest predictors of breast cancer in a high-risk population and to increase our understanding of the possible interactions between risk factors. METHODS: The Women At Risk High-Risk Registry provided the study population. The variables of interest included age at enrollment, presence of lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia, family history of breast cancer, body mass index, and Gail scores (5-year high-risk > or =1.7%). Univariate and multivariate analyses were conducted with the Cox proportional hazards regression model and years of follow-up evaluation as the time scale. RESULTS: Out of 1553 high-risk women, 79 (5%) developed breast cancer during a median follow-up period of 5 years. Results from the multivariate Cox model demonstrated that FHBC (hazard ratio [HR] = 1.76; 95% confidence interval [CI], 1.05-2.97), ADH (HR = 1.90; 95% CI, 1.16-3.13), LCIS (HR = 1.71; 95% CI, .99-2.95), and a body mass index > or =30 (HR = 2.22; 95% CI, 1.14-4.35) were statistically significant predictors of breast cancer within this high-risk population. CONCLUSIONS: These results support current literature showing the synergistic increase in risk for patients with ADH, LCIS, and a positive family history of breast cancer. Obesity was also a strong predictor of breast cancer risk, which suggests that there may be a potentiating effect of obesity on other risk factors. Obesity may represent a modifiable risk factor, providing women with an opportunity to reduce their risk with lifestyle modification. Women with a strong family history of breast cancer or a diagnosis of ADH or LCIS may benefit most from risk-reduction strategies, chemoprevention, and surveillance.     

A simple tool for identifying unaffected women at a moderately increased or potentially high risk of breast cancer based on their family history

Family history of breast cancer is a more important aspect of clinical management following the discovery of the genes BRCA1 and BRCA2. The authors developed a short questionnaire to categorize risk according to breast cancer history in close relatives. It was completed by 559 women attending for screening mammograms in Sydney, Australia. Twenty-three per cent reported a family history sufficient to be classified at a moderately increased or potentially high risk according to national guidelines (category II or III). Only 29 women (5%) made errors such that their risk category could not be determined. Validation of responses from 89 women, 44 from category II or III, found 100% agreement with classification after interview by a genetic counsellor. This questionnaire has the potential to accurately triage risk based on a woman's knowledge of her family history, and could be used in a variety of settings to identify women who may require further assessment, management and referral advice.     

Absolute risk of breast cancer for Australian women with a family history

BACKGROUND: The purpose of the present paper was to estimate the absolute risk of breast cancer over the remainder of a lifetime in Australian women with different categories of family history. METHODS: Age-specific breast cancer incidence rates were adjusted for screening effects, and rates in those with no family history were estimated using the attributable fraction (AF). Relative risks from a published meta-analysis were applied to obtain incidence rates for different categories of family history, and age-specific incidence was converted to cumulative risk of breast cancer. The risk estimates were based upon Australian population statistics and published relative risks. Breast cancer incidence was from New South Wales women for 1996. The AF was calculated using prevalence of a family history of breast cancer from data on Queensland women. The cumulative absolute risk of breast cancer was calculated from decade and mid-decade ages to age 79 years, not adjusted for competing causes of death. RESULTS: Lifetime risk is approximately 8.6% (1 in 12) for the general population and 7.8% (1 in 13) for those without a family history. Women with one relative affected have lifetime risks of 1 in 6-8 and those with two relatives affected have lifetime risks of 1 in 4-6. The cumulative residual lifetime risk decreases with advancing age; by age 60 years all groups with only one relative affected have well above a 90% probability of not developing breast cancer to age 79 years. CONCLUSIONS: These Australian risk statistics are useful for public information and in the clinical setting. Risks given here apply to women with average breast cancer risk from other risk factors.     

Prophylactic surgery to reduce breast cancer risk: a brief literature review

Prophylactic mastectomy reduces the likehood of developing breast cancer among women at heightened risk for breast cancer, but at significant personal cost.Women at increased breast cancer risk on the basis of hormonal history, family history and/or genetic mutation carrier status may consider bilateral prophylactic mastectomy with or without reconstruction to reduce their cancer risk and/or decrease their chances of cancer mortality. Women having received mastectomy as treatment for breast cancer may request contralateral mastectomy to decrease the chances of developing a second breast primary. The potential oncologic value of these procedures must be weighed carefully on a case -by-case basis against the operation's physical and psychological morbidity. The purppose of this literature review is to provide a practice-oriented summary of recent clinical studies attempting to address the relative risks and benefits of preventive surgery for breast cancer. Data are included regarding the psychological factors surrounding patient selection and quality of life outcomes, which become the cornerstone of patient satisfaction and acceptance. Taken together, these data support the Society of Surgical Oncology position statement regarding the proper application of prophylactic surgery for breast cancer.     

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.     

Reducing the risk of bone loss associated with breast cancer treatment

Women with breast cancer experience more fractures than their healthy peers. Fracture risk factors that are frequently observed in healthy postmenopausal women may already be present when breast cancer is diagnosed. Although low bone mineral density (BMD) significantly increases fracture risk, additional clinical risk factors that are independent of BMD, including age, previous fragility fracture, premature menopause, family history of hip fracture, use of corticosteroids, and low body mass index, also increase fracture risk. Additionally, cancer therapies can further increase fracture risk. Most notably, gonadotropin-releasing hormone analogues and aromatase inhibitor (AI) therapy increase bone loss and fracture incidence. Therefore, patients receiving AIs require a comprehensive fracture risk assessment including all risk factors and BMD when available. Zoledronic acid is an effective therapy for the prevention of AI-associated bone loss and, when combined with AI therapy, may provide the greatest clinical benefit without increasing fracture risk.     

Reasons for risk-reducing mastectomy versus MRI-screening in a cohort of women at high hereditary risk of breast cancer

Objective

To determine the reasons that motivate women in a cohort of women under intensive surveillance for breast cancer to undergo risk-reducing mastectomy (RRM).

Patients and methods

Women with a BRCA1 or BRCA2 mutation who were enrolled in an MRI-based breast screening study were eligible to participate in this survey. A self-administered questionnaire was given to women who did, and who did not terminate annual MRI-based surveillance in order to undergo RRM. The questionnaire included information on family history, risk perception and satisfaction with screening. In addition, women were asked to provide the principal reason for their choice of having preventive surgery or not, and were asked about their satisfaction with this choice.

Results

246 women without breast cancer participated in the study. Of these, 39 women (16%) elected to have RRM at some point after initiating screening. Although women who had a mother or sister with breast cancer were more likely to opt for RRM than were women with no affected first-degree relative (21% versus 10%) this did not reach statistical significance. Women who perceived their breast cancer risk to be greater than 50% were more likely to opt for RRM than were women who estimated their risk to be less than 50% (19% versus 6%). Fear of cancer was the most common reason cited for choosing to have RRM (38% of respondents) followed by having had a previous cancer, (25%), then concern over their children (16%).

Conclusion

Among women with a BRCA mutation who are enrolled in an MRI-based screening program, a high perception of personal breast cancer risk and a history of breast cancer in a first-degree relative are predictors of the decision to have RRM.     

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 .     

Coping With a Diagnosis of Breast Cancer-Literature Review and Implications for Developing Countries

Abstract:  Breast cancer is the most common cancer affecting women worldwide. Women are at an increased risk of developing both physical and psychological morbidity after diagnosis; however, many use different strategies to cope with the disease. The aim of this article is to review the available literature on the impact of breast cancer diagnoses and the strategies used by women to cope with this disease. The implications of these emerging findings are extrapolated within the context of health services provided in developing countries. Electronic databases were used to search the relevant literature. The findings showed that women who were diagnosed with breast cancer are at risk of developing several psychological morbidities such as depression, anxiety, fatigue, negative thoughts, suicidal thoughts, fear of dying, sense of aloneness, sexual and body images problems, as well as an overall decrease in the quality of life. Several strategies are used by women with breast cancer to cope with the disease, including positive cognitive restructuring, wishful thinking, emotional expression, disease acceptance, increased religious practice, family and social support, and yoga and exercise. Breast cancer diagnoses have been associated with several devastating psychological consequences; however, many women have used different coping strategies to adjust their lives accordingly. Healthcare professionals in developing countries, who work with women with breast cancer, should be aware of the different coping mechanisms that women use when diagnosed with cancer. Integrating a coping strategy into the treatment regimen would constitute an important milestone in the palliative care of patients with breast cancer.     

Review of risk factors for the development of contralateral breast cancer

Background

Women treated for breast cancer have an increased risk for developing metachronous contralateral breast cancer (CBC). Patient perception of this risk is often overestimated and has been found to contribute to the decision to undergo contralateral prophylactic mastectomy. An individual's risk is dependent on both patient and tumor characteristics. This review examines and summarizes the current literature on the factors that affect CBC risk.

Data Sources

English-language publications with the keyword “contralateral breast cancer” were identified through a MEDLINE literature search.

Conclusions

The global incidence of CBC is decreasing, a trend that is attributed to more effective adjuvant therapies. Patients with BRCA germ-line mutations demonstrate the highest risk for CBC. In the absence of known genetic mutations, patients with strong family histories who are diagnosed at young ages (<35 years) with estrogen receptor–negative index tumors appear to have a higher incidence of CBC.     

Breast cancer in women at high risk: The role of rapid genetic testing for BRCA1 and -2 mutations and the consequences for treatment strategies

Specific clinical questions rise when patients, who are diagnosed with breast cancer, are at risk of carrying a mutation in BRCA1 and -2 gene due to a strong family history or young age at diagnosis. These questions concern topics such as 1. Timing of genetic counseling and testing, 2. Choices to be made for BRCA1 or -2 mutation carriers in local treatment, contralateral treatment, (neo)adjuvant systemic therapy, and 3. The psychological effects of rapid testing. The knowledge of the genetic status might have several advantages for the patient in treatment planning, such as the choice whether or not to undergo mastectomy and/or prophylactic contralateral mastectomy. The increased risk of developing a second breast cancer in the ipsilateral breast in mutation carriers, is only slightly higher after primary cancer treatment, than in the general population. Prophylactic contralateral mastectomy provides a substantial reduction of contralateral breast cancer, although only a small breast cancer specific survival benefit. Patients should be enrolled in clinical trials to investigate (neo)-adjuvant drug regimens, that based on preclinical and early clinical evidence might be targeting the homologous recombination defect, such as platinum compounds and PARP inhibitors. If rapid testing is performed, the patient can make a well-balanced decision. Although rapid genetic counseling and testing might cause some distress, most women reported this approach to be worthwhile. In this review the literature regarding these topics is evaluated. Answers and suggestions, useful in clinical practice are discussed.     

The influence of family history on prostate cancer risk: implications for clinical management

? The most recent evidence for the link between a family history of prostate cancer and individual risk for future disease was examined, with the aim of understanding what the existence and nature of a family history of prostate cancer does to a man's risk of developing the disease. ? Our findings highlighted the clear association between a family history of prostate cancer and increased risk of developing the disease; with a greater proximity of relatedness, greater number of family members affected and/or earlier age at diagnosis of the family member elevating risk further. ? These findings have important clinical implications for the identification and subsequent management of men deemed to be at increased risk of developing prostate cancer. The evidence for prostate cancer risk reduction with the mono 5α-reductase inhibitor (5ARI) finasteride in a low-risk population and, more recently, with the dual 5ARI dutasteride in a population at increased risk of developing the disease, has potential to expand management options for men at risk of developing prostate cancer beyond more frequent and/or earlier surveillance. ? Given that family history can be easily assessed in routine clinical practice, it should be regarded as an important parameter to consider alongside PSA level for prostate cancer risk assessment.     

Prevalence of family history of breast and ovarian cancer in a single primary care practice using a self-administered questionnaire

Women at high risk of hereditary breast and/or ovarian cancer require specific management strategies for cancer prevention and early detection. The goal of this study was to determine the prevalence of familial breast and ovarian cancer among patients in a primary care practice. Questionnaires were mailed to the 608 women less than 81 years of age in a single primary care practice. Additional mailings and phone calls were used for nonresponders. Data were analyzed by bloodline, the degree of relative, age of diagnosis and cancer type. Women were grouped into three categories of breast/ovarian family history: "no family history,"insignificant family history," and "significant potentially high-risk family history" (women with two or more relatives in a single bloodline with breast and/or ovarian cancer, a single individual with bilateral breast cancer or breast and ovarian cancer, or breast and/or ovarian cancer at less than 40 years of age). A pedigree analysis of women categorized as "significant potentially high-risk family history" further classified these women as to the likelihood of being at risk for hereditary cancer. Data were obtained from 567 women (93%); 27 patients with a personal diagnosis of breast and/or ovarian cancer were excluded. Of the 540 remaining respondents, 351 (65%) had no family history of cancer, 138 (25.6%) had an insignificant family history, and 51 (9.4%) had a significant family history. Based on pedigree analysis of these 51 patients, 19 were unlikely to be at high risk for hereditary cancer, and 32 (6%) were likely to be at significant risk and warrant intensive evaluation. The large proportion of women identified with a significant family history of breast and/or ovarian cancer has major implications regarding the magnitude of a population-based process to identify and manage high-risk individuals.