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Women at a high risk for breast cancer are offered choices for screening or prophylactic surgeries. Our aim was to evaluate opinions regarding screening and surgical strategies in high-risk women.
Women at our institution who received BRCA 1/2 testing before July 2005 were sent a follow-up patient survey. We compared responses of women who tested positive for a deleterious mutation with those who tested negative. Of those that expressed an opinion (agree vs. disagree), we used a 2-sided Fisher's Exact test to compare responses.
A total of 540 surveys were sent and 312 were returned (58%). Of these, 217 had breast cancer and 86 women tested positive for a mutation. No BRCA + women felt mammograms were difficult to get due to discomfort while 5.4% of the BRCA - group did (p=.039). Seventy percent of BRCA + women agreed that prophylactic mastectomy (PM) is the most effective means for reducing risk, compared to 40% of BRCA - women (p<.001). PM was felt to be the only way to reduce worry in 64.7% of BRCA +, and in 34.4% of BRCA - women (p<.001). PM was felt to be too drastic for 36.1% of BRCA + and 40.5% of BRCA - women (p=.562). Difficulty in deciding between screening and PM occurred in 23.9% of BRCA + and 12.5% of BRCA - women (p=.046). After excluding women with bilateral breast cancers, 81.0% of women who agreed that PM was best to reduce risk underwent a PM vs. 19.1% of those who disagreed (p<.001). Of women who felt PM was the only way to reduce worry, 84.2% underwent PM. Only 15.8% of women who did not feel that it was the only way to decrease worry underwent PM (p<.001).
BRCA mutation carriers were more likely to believe PMs were the best way to reduce both risk and worry of breast cancer. High-risk women who agreed that PM was more likely to reduce risk and worry of breast cancer were more likely to proceed with this intervention.
The BRCA genes were first described in families with breast and ovarian cancers through the use of genetic linkage analysis.1-3 Since that time, over 5000 different mutations in these genes have been identified including both private and founder mutations.4 Overall these mutations are estimated at 0.1% in the general population.5-7
A recent meta analysis of ten studies estimated the lifetime risk of breast cancer in BRCA1 mutation-carriers to be 47-66% and 40-57% in BRCA2 mutation-carriers. The ovarian cancer risk was estimated at 35-46% in BRCA1 mutation-carriers and 13-23% in BRCA2 mutation carriers.8 Other studies have estimated these risks to be even higher.9 Given this increasing risk of cancers, women with cancers in the family at young age, or multiple cases of breast and/or ovarian cancer have sought genetic testing, not only to further manage their own cancer risk, but also to share with their family members.
Risk management for women with a known deleterious mutation in either the BRCA1 or BRCA2 genes has included frequent screening with mammogram, breast MRI and clinical breast exams,10 tamoxifen therapy11, 12 and risk reduction surgeries including prophylactic oophorectomy13,14, 15 and prophylactic mastectomy. 16, 17
Tamoxifen therapy has been associated with a decrease in risk when used in women with BRCA mutations. Some data indicates that it is more effective in prevention when used in the BRCA2 mutation-carriers rather than in BRCA1 mutation-carriers who tend to have more triple-negative breast cancers, however, further investigation is necessary.12, 18 Risk-reducing salpingo-oophorectomy (RRSO) has been estimated to decrease the risk of ovarian cancer by up to 85% in BRCA1 and was suggested in BRCA2 mutation carriers.14 This same study did not show a statistically significant change in the decrease of breast cancer after RRSO in BRCA1 carriers, but it did show a 72% reduction in breast cancers in women with BRCA2 mutations. Other studies have been able to show a protective effect of RRSO in BRCA1 carriers up to a 56% decrease in breast cancer incidence.15 Prophylactic mastectomies have been estimated to decrease the risk of developing breast cancer in 90-95% of patients who carry a deleterious BRCA1 or 2 mutation.16, 17 Additionally breast cancer patients with a deleterious BRCA1 mutation can have up to a 43.4% 10-year risk of contralateral breast cancer while BRCA2 mutation-carriers can have up to a 34.6% 10-year risk.11
During counseling with either a genetic counselor or their primary medical and surgical oncologists, women may be provided all of these options and many have significant difficulty in making these decisions. Although prophylactic surgeries are offered, women and their physicians still struggle with these decisions. Perceptions of both the patient and the caregiver regarding these interventions may play important roles in the ultimate decision. In order to better aid both the patient and health care provider, we surveyed women who underwent genetic counseling at a single institution in order to evaluate their perception of these risk reduction strategies as well as to provide insight into these different emotional and physical factors. Perception was then matched with the ultimate clinical decision. Understanding of these factors may help provide better insight into this decision-making process for both the patient and her physicians.
Women who were seen at The University of Texas M.D. Anderson Cancer Center (MDACC) for genetic consultation and underwent BRCA testing from 1997 to June 2005 were identified. Patients were referred for genetic counseling by their medical or surgical oncologist if the patient warranted referral as per NCCN guidelines.19 At MDACC, patients receive both pre and post test counseling with genetic counselors who specialize in hereditary cancer syndromes. A follow-up patient survey was developed and was approved by the MDACC Institutional Review Board. The surveys were developed as part of a multi-departmental effort with Breast Medical Oncology, Gynecologic Oncology and Behavioral Science.
Surveys were sent to all 540 patients that were identified. There were two separate mailings. The first comprised all 540 patients. A second reminder survey was sent to those women that did not respond to the first mailing. Three hundred twelve surveys (58%) were completed and returned. Table 1 details the patient characteristics of those women who completed the surveys.
As part of the surveys, patients were asked to answer multiple questions regarding their perception of their genetic testing for breast and/or ovarian cancers. They were also counseled on screening techniques and risk reduction options, including chemoprevention and prophylactic surgeries, which were offered to them as part of their standard genetic consultation at our institution. They were asked to answer on a scale of 1-5 with 1=strongly agree, 2=agree, 3=no opinion, 4=disagree and 5=strongly disagree.
All of the surveys were coded into a main database. Comparisons of patient characteristics between groups were performed using either Pearson X2Analyses or a Fisher's exact test. A p value of <0.05 was considered statistically significant. All analyses were performed using SPSS 15.0 (Chicago, IL). We compared responses of women who tested positive for a deleterious BRCA mutation (BRCA+) with those who tested negative (BRCA-). For the purposes of this study, patients who tested positive for a variant of uncertain significance were excluded from this analysis.
Of the 312 patients who responded to this questionnaire, 217 (70%) women had breast cancer and 86 (28%) tested positive for a deleterious mutation in either the BRCA 1 or BRCA 2 gene. Table 1 describes the differences in baseline characteristics of the BRCA+ and BRCA- women who responded to the survey. We analyzed the data by including those women who responded to selected survey questions as either an agree (score of 1 or 2) or disagree (score of 4 or 5). Table 2 demonstrates the answers to these questions.
When asked if it was too difficult to get mammograms because the procedure was too uncomfortable, 280 women expressed an opinion. No BRCA+ women agreed with this statement and 11(5.4%) of the BRCA- women agreed. (p=0.039).
When asked if the benefits of monthly self breast exams outweigh the difficulties, or if monthly SBE were embarrassing, or they felt they were not good at performing SBEs, or if it was too difficult to remember to do SBE, there was no statistically significant difference between BRCA+ and BRCA- women.
When asked if the side effects of taking tamoxifen outweigh the benefits of reducing the risk of developing breast cancer, again there was no statistically significant difference with 37.9% of the BRCA+ and 46.5% of the BRCA- women (p=0.282).
Seventy percent of BRCA+ women felt that PMs were the most effective means of reducing risk of getting breast cancer when compared to 40% of the BRCA- women (p<0.001). Additionally when asked if PM is the only way to reduce the worry of developing breast cancer, 64.7% of BRCA+ agreed vs. 34.4.% of BRCA- women who agreed (p<0.001). Participants were also asked if they felt that prophylactic mastectomy was too drastic a measure to prevent breast cancer: 36.1% of BRCA+,women vs. 40.5% of BRCA- women agreed (p=0.562). When asked if the main reason for not undergoing PMs is the fear of surgery, 27.8% of BRCA+ vs. 21.9% of BRCA- women agreed (p=0.328). When asked whether the main reason for not undergoing PMs is that it is too disfiguring, 33.8% of BRCA+ and 27.7% of BRCA- women agreed (p=0.364). Finally, when asked if it was difficult to decide between screening and PMs, 23.9% of BRCA+ agreed and 12.5% of BRCA- women agreed (p=0.046).
When looking at those women who responded either positively or negatively to the above questions, we compared their answers using a 2-sided Fisher's exact test with their ultimate clinical decision. Women who underwent bilateral mastectomies for bilateral breast cancer at the time of their cancer treatment were excluded from this analysis. Of the 312 women who returned surveys, 89 underwent prophylactic mastectomy. Of the women who underwent PM, 47 (81%) agreed that PM was the most effective means of reducing the risk of breast cancer v. only 11 (35.6%) of those that disagreed with this statement (p<0.001). Of the women who underwent PM, 48 women (84.2%) believed it was the only way to reduce worry v. only 9 women (15.8%) that did not believe it was the only way to reduce worry (p<0.001).
When looking at factors that influenced the choice of PM, of the 312 responders, 217 had breast cancer and the 29 women who were excluded from the analysis because of bilateral mastectomy for bilateral cancers, leaving 283 responders. Table 3 shows the results of different demographic factors on the decision to undergo prophylactic mastectomies. Interestingly, patients with breast cancer had a higher rate of PM, but there was no difference based on age, parity, marital status, BRCA mutation status, menopausal status or family history. Of note, women of Ashkenazi Jewish ancestry had a significantly lower rate of PM than women of non-Ashkenazi ancestry in our study group.
Women who were seen through our institution's Clinical Cancer Genetics Program and underwent genetic testing of deleterious BRCA 1 or 2 mutations were surveyed regarding their perceptions of different screening and risk-reduction strategies. We evaluated the responses by comparing the women who had tested positive or negative and their opinions regarding these different strategies. Women who tested positive for a deleterious BRCA mutation tended to not have as much difficulty with screening or minding the discomfort of mammography. There was no significant difference in SBEs. However, opinions regarding PMs and the ultimate choice to undergo PM were dependent upon their genetic testing results.
Of the women that were BRCA+, PMs were viewed as the most effective means of decreasing ultimate risk and worry of breast cancer. The majority of women who agreed with these viewpoints went on to ultimately choose a PM. Previous studies have looked at smaller numbers of patients and described worry as a major factor in ultimate decision making in high risk women.20 Additionally, Scheuer, et al. have shown the importance of genetic counseling in promoting increased surveillance, earlier detection and even surgical intervention in mutation carriers.21 Genetic counseling often involves a detailed discussion of genetic test results (including positive, negative and uncertain results), cancer family history, and cancer risks and risk reduction options associated with each test result. Patients cite each of these points of discussion as influential factors in their risk reduction surgery decisions, including PM.22 Furthermore, although breast cancer risk reduction decision aids have proven to be useful in reducing patients' decisional conflict regarding their risk reduction options, they have not been shown to be effective in the absence of counseling, further reinforcing the importance of genetic counseling in the decision making process.23 Other studies have shown that when high-risk women undergo intensive screening they may not tend to want to undergo PM.24 Our study further evaluates these opinions regarding PMs in this patient population and expands the underlying perceptions of this surgery.
By acknowledging that although women are willing to undergo SBEs and mammography as well as with the recent American Cancer Society MRI screening guidelines,25 prophylactic surgeries are still significantly viewed in this patient population as the most effective means of decreasing risk and worry. Interestingly, the majority of both BRCA+ and BRCA- women did not feel that PMs were either too drastic, too scary or too disfiguring which is often a major concern of caregivers when counseling and providing this intervention as some analyses have shown mixed satisfaction to PM and reconstruction in high-risk poulations.20 However, more recent studies have shown similar quality of life between women who choose to undergo PM compared to women who do not, and overall satisfaction with the decision to undergo PM.26-29 This data in addition to the data presented in the current study suggest that caregivers may be overestimating patients' negative feelings regarding PM.
Limitations of our analysis include that this is a retrospective questionnaire and women who tended to return the questionnaire may have had stronger opinions either positively or negatively. The women were also answering the questionnaire at different time points after their screening or PM decision had been made or completed. Each of the women also underwent genetic counseling as per our institutional guidelines and may be influenced by the information provided in the counseling session. A prospective questionnaire both pre and post genetic testing may show more clearly the impact of genetic testing and results disclosure on these risk-reducing strategies.
Our analysis provides insight into the decision making regarding risk-reduction strategies in BRCA+ and BRCA- patients. Patients with a deleterious BRCA mutation may find PM as the only way to effectively reduce their worry. Health care providers and genetic counselors must take this in to account when assessing a woman's needs at the time of genetic testing and results disclosure.
Funding: Supported by the Nellie B. Connally Breast Cancer Research Fund and the NIH T32 Training Grant (5 T32 CA101642 02).
Presented in part at the 2007 ASCO Breast Symposium