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© 2003 American Society for Clinical Oncology Tamoxifen As Chemoprevention in BRCA1 and BRCA2 Mutation Carriers With Breast Cancer: A Pilot Survey of Physicians
From the Georgetown University, Lombardi Comprehensive Cancer Center, Cancer Control Program, Washington, DC. Address reprint requests to Beth N. Peshkin, MS, CGC, 2233 Wisconsin Ave, NW, Suite 317, Washington, DC 20007; e-mail: peshkinb{at}georgetown.edu.
Purpose: To assess physician recommendations about the use of tamoxifen in premenopausal BRCA1 and BRCA2 mutation carriers.
Methods: We mailed surveys to a stratified random sample of 1,286 physicians selected from the San Antonio Breast Cancer Symposium mailing list. Eligible participants were physicians whose practice consisted of Results: Of potentially eligible participants, 27% responded to the survey, and 260 participants were included in the final analysis. Physicians did not distinguish between BRCA1 and BRCA2 status in making recommendations about tamoxifen to breast cancer patients; however, in an unaffected woman, they were more likely to recommend tamoxifen to a BRCA2 mutation carrier than to a BRCA1 mutation carrier (73% v 57%; P < .0001). In newly diagnosed breast cancer patients, physicians were much more likely to recommend tamoxifen to an estrogen receptor (ER)–positive mutation carrier versus an ER-negative carrier (94% v 27%; P < .0001). When the mutation carrier was diagnosed 10 years ago, physicians were still much more likely to recommend tamoxifen if the tumor was ER-positive versus ER-negative (79% v 35%; P < .0001). Conclusion: Physicians’ recommendations about tamoxifen use in mutation carriers with a history of breast cancer seem to be heavily dependent on ER status. This finding suggests that among mutation carriers, physicians are influenced by adjuvant treatment guidelines more so than the potential role that tamoxifen might play in the reduction of risk for contralateral breast cancer.
THE LIFETIME risk of contralateral breast cancer (CBC) in BRCA1 and BRCA2 mutation carriers is between 40% and 65%, and over long follow-up periods, the risk for ipsilateral breast cancer after breast conservation therapy is also elevated.1–5 Some women opt to manage this risk via surveillance, although limited information exists about the efficacy of and mortality reduction associated with physical examination, mammography, or newer imaging techniques such as magnetic resonance imaging.6–9 Surgical options include prophylactic mastectomy, which reduces the risk of breast cancer in mutation carriers by more than 90%, and oophorectomy, which reduces breast cancer risk by 50% in mutation carriers younger than age 50 years.10–13 Studies have shown that among mutation carriers, the utilization rate for prophylactic oophorectomy is substantially higher than that for prophylactic mastectomy.7,14–16 Given the uncertain efficacy of surveillance and the reluctance of many mutation carriers to undergo prophylactic mastectomy, the use of tamoxifen is also a consideration. The benefits of tamoxifen in the adjuvant setting are well established.17 Similarly, results from randomized trials have demonstrated that tamoxifen reduces breast cancer risk by 30% to 50% among unaffected women at risk for breast cancer.18,19 However, evidence for the efficacy of tamoxifen among mutation carriers is less clear. In a matched case-control study comparing 209 BRCA1 and BRCA2 mutation carriers with bilateral breast cancer with 384 mutation carriers with unilateral disease, use of tamoxifen was associated with a 50% decrease in the odds of CBC among both BRCA1 and BRCA2 mutation carriers (95% CI, 0.28 to 0.89).20 In that study, there was insufficient information available to determine whether estrogen receptor (ER) status of the primary tumor was related to the contralateral risk reduction associated with tamoxifen. However, smaller studies have suggested that tamoxifen may have efficacy in BRCA1 mutation carriers regardless of ER status.21–24 In addition, the efficacy of oophorectomy in reducing breast cancer risk in BRCA1 and BRCA2 mutation carriers also supports the idea that tamoxifen will have a similar effect. Despite this initial evidence of the efficacy of tamoxifen in mutation carriers, long-awaited data from the National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial raised the possibility that tamoxifen may not be effective among BRCA1 mutation carriers.25 Importantly, however, these findings, which were published in the Journal of the American Medical Association,25 were based on only 19 BRCA1 and BRCA2 mutation carriers, in whom the use of tamoxifen was associated with a 62% decrease in breast cancer risk among BRCA2 mutation carriers (risk ratio, 0.38; 95% CI, 0.06 to 1.56), versus no risk reduction among the eight BRCA1 mutation carriers in the sample (risk ratio, 1.67; 95% CI, 0.32 to 10.70). Although these results were biologically plausible given that BRCA1 tumors tend to be ER-negative (82%) and BRCA2 tumors tend to be ER-positive (67%; reviewed in5), the wide confidence intervals, lack of statistical significance, and low number of BRCA1 mutation carriers in the sample make it difficult to draw definitive conclusions. For most women with breast cancer, the issue about whether to take tamoxifen arises at the time of diagnosis. Tamoxifen is usually recommended for patients with ER-positive tumors, whereas women with ER-negative cancers are generally not advised to take tamoxifen as adjuvant treatment because it is not effective in reducing rates of recurrence.17,26 In patients with sporadic breast cancer, other considerations may be factored into recommendations about tamoxifen use. For example, the ER status of the first cancer may be predictive of the ER status of the second cancer.27 Furthermore, a recent study suggests that tamoxifen does not seem to reduce CBC risks in ER-negative patients.28 However, these associations have not been established in mutation carriers; moreover, studies have suggested that there may be a role for tamoxifen in mutation carriers regardless of the ER status of their primary tumor or their propensity to develop (BRCA1 associated) ER-negative tumors.20–24 For patients with BRCA1 and BRCA2 mutations, the elevated risk of CBC is also an important consideration. Thus, for mutation carriers who are not interested in prophylactic mastectomy including those who have not received adjuvant tamoxifen (because they had an ER-negative tumor or an initial diagnosis prior to the widespread use of tamoxifen), the option of taking tamoxifen for chemoprevention may be a consideration. In other words, for mutation carriers with breast cancer, a key question arises as to whether tamoxifen use, if not appropriate as adjuvant treatment, is an appropriate consideration as a preventive agent. Given the uncertainty regarding the benefits of tamoxifen for BRCA1 and BRCA2 mutation carriers and the lack of standard recommendations to guide physicians, we sought to better understand the attitudes and practices of physicians toward tamoxifen use among mutation carriers. Our primary research question was whether physician recommendation for tamoxifen would be influenced by the patient’s ER status and time since diagnosis (for affected mutation carriers), and whether the patient had a BRCA1 versus a BRCA2 mutation. Specifically, we predicted that for newly diagnosed patients, physicians would be guided by adjuvant treatment guidelines and would be more likely to recommend tamoxifen for women with ER-positive tumors. For mutation carriers who were 10 years postdiagnosis, we predicted that physicians would still be influenced by ER status, but to a lesser degree than for newly diagnosed patients. For unaffected women, we hypothesized that physicians would be more likely to recommend tamoxifen to BRCA2 versus BRCA1 mutation carriers, on the basis of data from King et al.25 Using hypothetical vignettes, we designed a survey to test these hypotheses.
Participants Names and addresses of 8,097 people from the San Antonio Breast Cancer Symposium United States mailing list were obtained. We randomly selected 1,286 individuals (16%) stratified by sex (640 females, 646 males) for potential participation in this study. We chose to sample registrants of this meeting because it is typically attended by a large number of physicians involved in the clinical care of breast cancer patients. We excluded registrants who were not medical doctors. Physicians were eligible to participate if they reported that at least 10% of their practice was composed of breast cancer patients.
Procedures Mailings were conducted between April and July 2002. Responses were included in this analysis if they were obtained by November 30, 2002. All data were entered into a secure password-protected database. Study packets were mailed to 1,286 conference registrants; subsequently, 103 (8%) were excluded (eg, mailing returned because of wrong address). From the remaining 1,183 individuals, 366 (31%) responded and 817 (69%) did not respond. Of the 366 responders, 304 were eligible, and 62 were ineligible. Thus, of 1,121 potentially eligible participants, 304 (27%) completed the survey. To estimate the eligibility rate among the 817 individuals who did not return the questionnaire, we randomly selected 40 nonresponders to contact via telephone. Of the 40 nonresponders whose offices were telephoned, 31 responses were received. Of these, 23 (74%) were ineligible for the study. Thus, our reported response rate of 27% represents an extremely conservative estimate of the true response rate among eligible participants.
Survey Instrument Part II of the questionnaire consisted of 10 items regarding opinions about various issues in breast cancer management and genetic testing, in which participants were asked to use a 5-point Likert scale to rate how strongly they agreed or disagreed with the statements (these data are not included in this article).
The key feature of the survey was the presentation of four vignettes. These vignettes described a situation in which a premenopausal patient who is not interested in prophylactic mastectomy asks the physician for his or her recommendation about using tamoxifen. The first three vignettes involved breast cancer patients who tested positive for a deleterious BRCA mutation. This report focuses on only the first two of these three vignettes, which are displayed in Table 1
The final vignette presented the case of a 40-year-old woman without cancer who had a BRCA1 or BRCA2 mutation, who also asked about a recommendation regarding tamoxifen use (Table 1  ).
Outcome Variable
Sample Characteristics Of the 304 surveys returned from eligible individuals, 44 (14%) were excluded from this analysis because physicians indicated practice settings or medical specialties that could not be classified into one of the main categories of interest (n = 10) or they had incomplete data for three vignettes (n = 34). Characteristics of the final sample (N = 260) are listed in Table 2  . Eighty-four percent of the participants were Caucasian, and female physicians comprised 60% of the sample. Fifty-seven percent of the sample participants were medical oncologists, and 50% practiced within academic medical settings. The mean age was 48 years, and the mean self-reported percentage of breast cancer patients within the physicians’ practice was 58%.
Physician Recommendation for Tamoxifen by Mutation Status ( BRCA1 v BRCA2 mutation) in Patients With Breast Cancer We used  2 analysis to compare responses to version A (BRCA1) and version B (BRCA2) for the first two vignettes. For vignette 1, there was no association between version and physician recommendation for either ER-positive (21 [N = 260] = 1.35; P = .25) or ER-negative (21 [N = 260] = 1.56; P = .21) patients. Similarly, for vignette 2, analyses revealed no effect of version on physician recommendations for tamoxifen in either ER-positive (21 [N = 260] = 0.75; P = .39) or ER-negative (21 [N = 260] = 2.98; P = .08) patients. Therefore, in subsequent analyses, the two versions were combined.
Physician Recommendation for Tamoxifen by ER Status (within vignettes 1 and 2)
In vignette 2, in which the patient was premenopausal but diagnosed 10 years prior, 79% of doctors would recommend tamoxifen if her tumor was ER-positive compared with 35% who would recommend it if the tumor was ER-negative (McNemar S1 [N = 260] = 114.0; P < .0001). In this case, 45% of physicians would recommend tamoxifen to the ER-positive patient only, 34% would recommend it to both groups of patients, and 20% would not recommend it to either type of patient.
Physician Recommendation for Tamoxifen by Time Since Diagnosis (across vignettes 1 and 2) In the ER-negative patients (vignettes 1B and 2B), 73% of physicians would not recommend tamoxifen to the newly diagnosed patient, and 65% would not recommend it to the patient diagnosed 10 years ago (McNemar S1 [N = 260] = 15.2; P < .0001). In this comparison, only one fourth of physicians would recommend tamoxifen to both groups of patients, 64% would not recommend it to either patient, and 10% would recommend it to the patient diagnosed 10 years ago but not to the newly diagnosed patient.
Physician Recommendation for Tamoxifen by Mutation Status (BRCA1 v BRCA2 mutation) in Unaffected Patients
This study is the first to characterize physicians’ opinions about the use of tamoxifen in BRCA1 and BRCA2 mutation carriers. The primary aim of this study was to assess physicians’ attitudes about the role of tamoxifen in chemoprevention versus treatment in women affected with breast cancer. Importantly, the study questionnaire did not make this distinction explicit to avoid biasing participants. In breast cancer patients, as we hypothesized, the ER status of the patient’s tumor was a strong predictor of whether physicians would recommend tamoxifen. In general, the current practice is to prescribe tamoxifen to newly diagnosed premenopausal breast cancer patients with ER-positive tumors17; in fact, 94% of physicians would recommend tamoxifen to the 40-year-old mutation carrier presented in vignette 1A. In sporadic newly diagnosed patients, women with ER-negative tumors are generally not given tamoxifen because it is not effective in reducing the risk of metastases.17,26 However, because patients with BRCA mutations face a much higher risk of CBC, use of tamoxifen may be one approach to managing this risk, regardless of ER status.20–24 Nonetheless, less than one third of the physicians surveyed would recommend tamoxifen to the ER-negative newly diagnosed patient, and the majority who would recommend it to the ER-positive patient would not recommend it for the ER-negative patient (68%). Physicians’ recommendations about tamoxifen use in the newly diagnosed patient did not differ on the basis of mutation status (BRCA1 v BRCA2 mutation). This finding is not surprising given that guidelines for tamoxifen use to prevent metastases are based on ER status, and data support the role of tamoxifen in reducing CBC risks in both groups of mutation carriers.17,20 When the vignette depicted a premenopausal patient who was diagnosed with breast cancer 10 years ago, guidelines for adjuvant treatment do not apply. Rather, the primary consideration is the utility of tamoxifen for chemoprevention. Our results suggest that when more time has elapsed since the patient’s initial diagnosis, recommendations for tamoxifen are still heavily influenced by ER status, as we hypothesized. In this case, physicians were still much less likely to recommend tamoxifen if the tumor was ER-negative versus ER-positive, and slightly more likely to recommend tamoxifen to the ER-negative breast cancer survivor compared with the newly diagnosed patient (27% v 35%). Interestingly, physicians were significantly less likely to recommend tamoxifen to the ER-positive patient diagnosed 10 years ago than to the newly diagnosed ER-positive patient. In the former situation, it is possible that physicians were not fully convinced that the benefits of tamoxifen would outweigh the risks, whereas in the adjuvant setting, the benefits of tamoxifen clearly outweigh the risks.26 In ER-negative patients, regardless of when they were diagnosed, most physicians (64%) would not recommend tamoxifen. As with the newly diagnosed patient, physicians’ recommendations for the patient diagnosed 10 years ago did not differ on the basis of mutation status. In the vignette depicting an unaffected premenopausal woman, the tendency to recommend tamoxifen to the BRCA2 mutation carrier and not the BRCA1 mutation carrier suggests that physicians place considerable weight on data from the NSABP-P1 study, and have concluded that tamoxifen is not effective in BRCA1 mutation carriers.25 This is potentially problematic given the limited sample size and lack of statistical significance in that study. In addition to the article by Narod et al,20 additional data are emerging that suggest that tamoxifen may indeed reduce the risk of breast cancer in BRCA1 mutation carriers, although most of these studies were not published or accessible at the time the questionnaire was mailed (Metcalfe K et al, submitted for publication).21–24 It is possible that physicians considered the genetic results as a surrogate for the potential ER status of a future breast cancer, which in turn influenced their recommendations about tamoxifen use; again, there are no solid data to support this rationale. Overall, results from our study suggest that physician recommendations about tamoxifen in affected BRCA mutation carriers seem to be influenced more strongly by adjuvant treatment guidelines than by evidence suggesting the efficacy of tamoxifen in reducing the risk of CBC in affected mutation carriers. Among unaffected mutation carriers, the low rate of tamoxifen recommendations for BRCA1 mutation carriers suggests that physicians are being guided by the results of King et al,25 despite the tentative conclusions that can be drawn from that study. Overall, the lack of consensus for all vignettes, and the interesting polarization of responses for the unaffected mutation carrier, indicate that physicians may not be convinced of the benefits of tamoxifen in BRCA1 and BRCA2 mutation carriers. It seems that the NSABP data have raised sufficient uncertainty regarding the benefits of tamoxifen in BRCA1 mutation carriers, thus substantially limiting the number of physicians willing to recommend it to that group of mutation carriers. Some limitations in this study are important to mention. The selected sample is not representative of practicing oncologists given that registrants to the San Antonio Breast Cancer Symposium were often affiliated with academic medical centers and/or had an interest in attending a conference dedicated to current research in breast cancer. In addition, those who participated were likely to be more interested and well read in breast cancer genetics than most oncologists. Thus, among a more representative sample of physicians, it is likely that there would be less agreement on attitudes toward tamoxifen use in mutation carriers. With respect to the survey design and analysis, by dichotomizing physician responses (ie, would recommend tamoxifen versus would not recommend tamoxifen), we were not able to distinguish the group of physicians who would not make a recommendation for or against tamoxifen. Reasons why this response could have been selected may include the physician’s desire not to be directive in telling the patient what to do; the belief that current data are not conclusive enough to support a recommendation either way; or that an alternative option would be recommended in lieu of tamoxifen, such as prophylactic oophorectomy. The latter possibility adds even more complexity to decision making given that oophorectomy, when performed in women younger than age 50, significantly reduces breast cancer risk as well as ovarian cancer risk.12,13 Given that many mutation carriers younger than age 50 opt for oophorectomy,12–16 it is unclear whether any additional protective effect on breast cancer is obtained by the use of tamoxifen. Thus, physicians may favor a recommendation for oophorectomy over tamoxifen for these younger women. However, given the residual risk of breast cancer, additional management strategies, including tamoxifen use, are still important to consider.29 An additional strategy for assessing the impact of mutation carrier status on physician recommendation would have been to include another set of control group vignettes presenting the same clinical parameters in women who were not mutation carriers (ie, sporadic cases). It is also possible that concerns about risk for endometrial cancer30,31 may have been a reason why physicians did not recommend tamoxifen. Therefore, inclusion of a vignette in which the mutation carrier had undergone a hysterectomy could have eliminated this potentially confounding factor. Finally, the relatively low response rate also raises the possibility that the sample was biased. It is likely that there was differential participation by physicians most familiar with and interested in the management of hereditary breast cancer. Results of this study emphasize the complex issues involved in managing BRCA1 and BRCA2 mutation carriers. As additional longitudinal studies of screening and prevention modalities are completed, such data will inform clinical recommendations and allow patients and their physicians to make more knowledgeable decisions about management options. As more women pursue BRCA1 and BRCA2 testing, including newly diagnosed breast cancer patients, it is important to know what physicians are recommending to mutation carriers. Studies have shown that women want their doctor’s opinion and input about testing and management decisions.32,33 Our data from high-risk newly diagnosed breast cancer patients demonstrate that physician recommendation is a significant predictor of whether patients undergo genetic testing and what surgical management option they choose.34 Therefore, it is likely that physician recommendation will also be a significant predictor of whether women opt for tamoxifen use solely as a preventive measure (if patients are not inclined to undergo prophylactic mastectomy). Published data from a small sample of high-risk women indicate that many are reluctant to take tamoxifen because they perceive the risks associated with tamoxifen to outweigh the benefits.35 However, tamoxifen use may be more of a consideration in mutation carriers who have expressly stated that they do not wish to have prophylactic mastectomy, including those who are not candidates for adjuvant tamoxifen on the basis of ER status. Although this study is small and only begins to touch on the factors that influence physician recommendations, the findings suggest that future research could entail a more comprehensive survey, administered to a broader group of practitioners, and which could explore the reasoning behind specific recommendations. In addition, the role of tailored educational materials and/or a decision-making aid for physicians and patients could be assessed. Ultimately, such adjuncts could help physicians provide guidance to their patients that would be informed by an accurate interpretation of the literature. At present, we believe that the data are not conclusive enough to support an unequivocal recommendation for or against tamoxifen use. Rather, patients should be well informed about the studies performed thus far, the potential benefits and risks of tamoxifen,36 and the other available options for screening and risk reduction. This approach may enable women to choose avenues for risk management that they previously may not have considered. In addition, patients may be more satisfied with their decision-making process and their choice of management options.
The following authors or their immediate family members have indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. Received more than $2,000 a year from a company for either of the last 2 years: Claudine Isaacs, Astra Zeneca.
We thank Barbara Brogan and Tiffani DeMarco for their input and advice, and the surgeons and oncologists who provided feedback on a draft of the study questionnaire.
Supported by American Cancer Society Institutional Research grant no. IRG 97-152-04 (to B.N.P.) and the Cancer Genetics Network, NIH/NCI grant no. 1 U24 CA78146-04 (to C.I.).
1. Easton DF, Ford D, Bishop DT, et al: Breast and ovarian cancer incidence in BRCA1-mutation carriers. Am J Hum Genet 56:265–271, 1995[Medline]
2. Breast Cancer Linkage Consortium: Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91:1310–1316, 1999
3. Brose MS, Rebbeck TR, Calzone KA, et al: Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst 94:1365–1372, 2002 4. Haffty BG, Harrold E, Khan AJ, et al: Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359:1471–1477, 2002[CrossRef][Medline] 5. Robson ME, Boyd J, Borgen PI, et al: Hereditary breast cancer. Curr Probl Surg 38:387–480, 2001[CrossRef][Medline] 6. Burke W, Daly M, Garber J, et al: Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II: BRCA1 and BRCA2—Cancer Genetics Studies Consortium. JAMA 277:997–1003, 1997[Abstract]
7. Scheuer L, Kauff N, Robson M, et al: Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. J Clin Oncol 20:1260–1268, 2002
8. Stoutjesdijk MJ, Boetes C, Jager GJ, et al: Magnetic resonance imaging and mammography in women with a hereditary risk of breast cancer. J Natl Cancer Inst 93:1095–1102, 2001
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10. Hartmann LC, Sellers TA, Schaid DJ, et al: Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst 93:1633–1637, 2001
11. Meijers-Heijboer H, van Geel B, van Putten WLJ, et al: Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 345:159–164, 2001
12. Kauff ND, Satagopan JM, Robson ME, et al: Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346:1609–1615, 2002
13. Rebbeck TR, Lynch HT, Neuhausen SL, et al: Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346:1616–1622, 2002 14. Lerman C, Hughes C, Croyle RT, et al: Prophylactic surgery decisions and surveillance practices one year following BRCA1/2 testing. Prev Med 31:75–80, 2000[CrossRef][Medline]
15. Meijers-Heijboer H, Brekelmans CT, Menke-Pluymers M, et al: Use of genetic testing and prophylactic mastectomy and oophorectomy in women with breast or ovarian cancer from families with a BRCA1 or BRCA2 mutation. J Clin Oncol 21:1675–1681, 2003
16. Schwartz MD, Kaufman E, Peshkin BN, et al: Bilateral prophylactic oophorectomy and ovarian cancer screening following BRCA1/BRCA2 mutation testing. J Clin Oncol 21:4034–4041, 2003
17. Eifel P, Axelson JA, Costa J, et al: National Institutes of Health Consensus Development Conference Statement: Adjuvant therapy for breast cancer, November 1–3, 2000. J Natl Cancer Inst 93:979–989, 2001 18. Cuzick J, Forbes J, Edwards R, et al: First results from the International Breast Cancer Intervention Study (IBIS-I): A randomised prevention trial. Lancet 360:817–824, 2002[CrossRef][Medline]
19. Fisher B, Costantino JP, Wickerham DL, et al: Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90:1371–1388, 1998 20. Narod SA, Brunet J-S, Ghadirian P, et al: Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: A case-control study. Lancet 356:1876–1881, 2000[CrossRef][Medline] 21. Eisinger F, Charafe-Jauffret E, Jacquemier J, et al: Tamoxifen and breast cancer risk in women harboring a BRCA1 germline mutation: Computed efficacy, effectiveness and impact. Int J Oncol 18:5–10, 2001[Medline]
22. Foulkes WD, Goffin J, Brunet JB, et al: Tamoxifen may be an effective adjuvant treatment for BRCA1-related breast cancer irrespective of estrogen receptor status. J Natl Cancer Inst 94:1504–1506, 2002
23. Daidone MG, Veneroni S, Cappelletti V, et al: Estrogen receptor-beta expression in hereditary breast cancer. J Clin Oncol 20:3752–3753, 2002
24. Cappelletti V, Veneroni S, Coradini D, et al: Re: Tamoxifen may be an effective treatment for BRCA1-related breast cancer irrespective of estrogen receptor status. J Natl Cancer Inst 95:629–630, 2003
25. King M-C, Wieand S, Hale K, et al: Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 286:2251–2256, 2001 26. Early Breast Cancer Trialists’ Collaborative Group: Tamoxifen for early breast cancer: An overview of the randomised trials. Lancet 351:1451–1467, 1998[CrossRef][Medline] 27. Swain SM, Wilson J, Eleftherios M, et al: Estrogen receptor (ER) status of primary breast cancer is predictive of ER status of contralateral breast cancer (CBC). Proc Am Soc Clin Oncol 21:38a, 2002 (abstr 150)
28. Fisher B, Anderson S, Tan-Chiu E, et al: Tamoxifen and chemotherapy for axillary node-negative, estrogen receptor-negative breast cancer: Findings from the National Surgical Adjuvant Breast and Bowel Project B-23. J Clin Oncol 19:931–942, 2001
29. Peshkin BN, DeMarco TA, Schwartz MD. Oophorectomy in carriers of BRCA mutations. N Engl J Med 347:1037–1040, 2002 30. Cuzick J, Powles T, Veronesi U, et al: Overview of the main outcomes in breast-cancer prevention trials. Lancet 361:296–300, 2003[CrossRef][Medline]
31. Wysowski DK, Honig SF, Beitz J. Uterine sarcoma associated with tamoxifen use. N Engl J Med 346:1832–1833, 2002 32. Armstrong K, Stopfer J, Calzone K, et al: What does my doctor think? Preferences for knowing the doctor’s opinion among women considering clinical testing for BRCA1/2 mutations. Genet Test 6:115–118, 2002[CrossRef][Medline]
33. Audrain J, Rimer B, Cella D, et al: Genetic counseling and testing for breast-ovarian cancer susceptibility: What do women want? J Clin Oncol 16:133–138, 1998 34. Schwartz MD, Brogan B, Peshkin B, et al: Impact of BRCA1/2 testing on breast cancer treatment decisions. Ann Behav Med 24:S187, 2002 (abstr)
35. Port ER, Montgomery LL, Heerdt AS, et al: Patient reluctance toward tamoxifen use for breast cancer primary prevention. Ann Surg Oncol 8:580–585, 2001
36. Gail MH, Costantino JP, Bryant J, et al: Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. J Natl Cancer Inst 91:1829–1846, 1999 Submitted February 21, 2003; accepted August 20, 2003. This article has been cited by other articles:
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Copyright © 2003 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
10% breast cancer patients. Participants were asked to complete a three-part, 10-minute questionnaire. Demographics and responses to hypothetical patient vignettes were analyzed. 
