- Email: [email protected]
Perceptions and needs of women with metastatic breast cancer: A focus on clinical trials
The Breast 22 (2013) 370e373
Contents lists available at SciVerse ScienceDirect
The Breast journal homepage: www.elsevier.com/brst
Perceptions and needs of women with metastatic breast cancer: A focus on clinical trials Zeina A. Nahleh a, *, Nancy U. Lin b, Antonio C. Wolff c, f, Fatima Cardoso d, g, on behalf of the BIG-NABCG collaboratione a
Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, 4800 Alberta Avenue, El Paso, TX 79905, United States Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States Breast Cancer Program, The Johns Hopkins Kimmel Comprehensive Cancer Center, 1650 Orleans Street, CRB1-189, Baltimore, MD 21287, United States d Champalimaud Cancer Center, Av. De Brasília e Doca de Pedrouços, 1400-048 Lisbon, Portugal b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 30 October 2012 Received in revised form 5 January 2013 Accepted 24 February 2013
Many patients are living longer with Metastatic Breast Cancer (MBC) than ever before. However, complete responses remain uncommon, and progression of disease is often inevitable. The experience of living with MBC exposes patients to a wide variety of clinical, psychological, social and spiritual issues. Although much research effort has focused on decision-making and coping strategies among women with early breast cancer, relatively little attention has been given to the needs, experiences, and perceptions of women living with MBC. Furthermore, there are major research gaps in understanding and prioritizing the types of psycho-social interventions that would make the most difference in the lives of these patients. Fortunately, the tide is turning. This communication represents a joint effort of the Breast International Group and the National Cancer Institute (NCI)-sponsored North American Breast Cancer Group (BIG-NABCG) to highlight perceptions and needs of patients living with MBC and current obstacles facing them, and recommends strategies for better addressing some of these unmet needs. Ó 2013 Elsevier Ltd. All rights reserved.
Keywords: Perceptions Metastatic Breast Cancer BIG-NABCG
Introduction Over the past two decades, significant advances have been achieved in the treatment of metastatic breast cancer (MBC). Many patients are living longer with MBC than ever before, with a currently reported median overall survival (OS) of 4e5 years.1,2 However, complete responses remain uncommon, and for the vast majority of patients, progression of disease is inevitable. Moreover, the experience of living with metastatic cancer exposes patients to a wide variety of clinical, psychological, social and spiritual issues which may directly impact their lives. When caring for patients with metastatic breast cancer, the goals of treatment, as traditionally set forth by health care professionals and the research community, are to control symptoms and to prolong survival (when possible) with the least disruption of quality of life. Often, there is no clear data from randomized trials to support the choice of one
* Corresponding author. Tel.: þ1 915 545 6618; fax: þ1 915 545 6634. E-mail addresses: [email protected] (Z.A. Nahleh), Nancy_Lin@ dfci.harvard.edu (N.U. Lin), [email protected] (A.C. Wolff), fatimacardoso@ fundacaochampalimaud.pt (F. Cardoso). e Breast International Group-North American Breast Cancer Group. f Tel.: þ1 410 614 4192; fax: þ1 410 614 4073. g Tel.: þ351 (210) 480004. 0960-9776/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.breast.2013.02.017
systemic treatment versus another for an individual patient, particularly beyond the first-line setting. Patients may feel significant stress in weighing treatment options based on individual and often unclear perceptions and expectations. Although much research effort has focused on decision-making and coping strategies among women with early breast cancer, relatively little attention has been given to the needs and experiences of women living with MBC. Furthermore, there are major research gaps in understanding and prioritizing the types of psycho-social interventions that would make the most difference in the lives of patients and their families. Addressing research gaps The BRIDGE (Bridging Gaps, Expanding Outreach) Metastatic Breast Cancer Patient Survey was one of the first large-scale attempts to address some of the research gaps in our knowledge about MBC. This survey was conducted among 1342 women in 13 countries to assess the needs, experiences and attitudes of women living with MBC.3 To offer a balance between low and high-resource countries, approximately 100 women from each of 13 countries were recruited through physician referral, including Australia, Latin America (Argentina, Brazil, Mexico, Venezuela), Europe (Belgium, France, Spain, the United Kingdom), North Africa (Egypt), and North
Z.A. Nahleh et al. / The Breast 22 (2013) 370e373
America (Canada, US). The survey was conducted between September 16, 2008 and February 18, 2009 using a combination of telephone, mail or in-person methods. Total sample data was representative of the individuals interviewed. The main survey results were as follows: (1) one in two women (53 percent) with MBC believe the disease receives too little public attention, (2) most women (75 percent) proactively seek out information on MBC, yet 51 percent find available information is often insufficient or ineffective and (3) despite the large number of women living with MBC, their needs often go unreported.3 In a complementary effort, Living Beyond Breast Cancer (LBBC) conducted an internet-based survey focusing on the use of and preferences for services of women with MBC in three domains: information, support and practical resources.4 Data was obtained from 618 online respondents reflecting the demographics of internet users, with 70% between the ages of 40 and 59. Patients with MBC expressed high interest in information about their diagnosis and treatment options and described seeking information in multiple ways, from printed materials, websites, online communities, teleconferences, to in-person educational meetings. However, many reported that they did not know how to locate ongoing community or internet-based educational programs.4 Messages taken from the findings in these two surveys can inform services and programs designed for people living with MBC.5 The most urgent need expressed by patients and their families is for accurate and accessible information about their disease, standard and emerging treatments, realistic treatment goals, ways of coping with side effects and symptoms, and ways of communicating the news with loved ones (particularly children and partners). The good news is that more initiatives have been launched over the past few years, not only to identify the needs of patients with MBC and current obstacles facing them, but also to discuss solutions and ideas for better addressing these unmet needs.6e9 One of the first such initiatives was an MBC Advocacy Working Group,8 created in 2008 and comprised of 16 patient advocates from seven countries. The group issued important recommendations in three major areas: (a) improve access to information, resources and support services; (b) heighten attention to the MBC community; and (c) increase understanding of, and access to clinical trials. The recommendations also called for the design of clinical trials that include underserved segments of the MBC community, such as heavily pretreated women and women with certain metastases.8 Additionally, advocate collaboration has been introduced as a new standard in the design of breast and other cancer clinical trials.6,7 The advocates’ main role is to bring the perspectives of those most affected by cancer to the work of the cancer research community. In 2007, the U.S. National Cancer Institute (NCI) initiated the Advocates in Research Working Group (ARWG) in order to develop recommendations on how NCI can most effectively and consistently engage individual advocates in the research process to accelerate progress and benefit patients.7 The final NCI-approved recommendations and the final ARWG Executive Summary and Recommendations were released in March 2011.7 An important message of the patient surveys and of the MBC Advocacy Working Group is the value placed on education and information about treatment options, particularly with respect to clinical trials. Given the high level of interest in clinical trials expressed by many patients, and the high priority designated to clinical trial access by investigators and patient advocates, it is concerning that only around 3% of adult cancer patients actually participate in trials in the U.S, a dismal percentage that is essentially unchanged over the last decade.10,11 Also an analysis of more than 500 NCI Cancer Therapy Evaluation Program (CTEP) trials in the U.S. revealed that 40 percent of trials failed to achieve minimum patient enrollment, and more than three of five phase III trials failed to do so.10
371
In Europe, where the tradition of clinical research is less institutionalized, statistics of cancer patients participation in clinical trial appear to be slightly but not overwhelmingly better, reported at less than 5% overall, but may vary depending on cancer site and centers of treatment.12e14 More recently, The National Cancer Research Network (NCRN) in the UK has been recognized as one of the best examples for improvement, since it has succeeded in increasing the accrual rate from 3.75% to more than 10% in a few years.11 This increase had to do with the massive public investment, which has allowed, among other things, the recruitment of a large number of research staff, such as clinical trials practitioners, data managers and research nurses. However, overall only around 31% of multicentre randomized controlled trials in the UK that were recruiting between 1994 and 2002 achieved their original recruitment target.12 Insights into breast cancer clinical trial participation was gained from the results of the BRIDGE survey.15 Clinical trial participation varied greatly by country, with Venezuela having the lowest percentage (1%) and Canada and Mexico having the highest (both 35%). In Europe and the UK, Belgian women had the highest level of participation (27%), followed by Poland (21%), Spain (19%), United Kingdom (13%), and France (7%). Women in Australia and the United States were most proactive about looking for information relating to clinical trials.15 The failure of clinical trials to enroll enough patients moves health care further away from evidence-based practice and represents a tremendous amount of wasted effort. In addition, with the move to “personalized medicine” involving targeted therapies for small subsets of cancers, the need to involve the larger breast cancer community in clinical trials becomes ever greater, in order to achieve accrual goals and move the field forward. Cancer clinical trials issues Some of the cited obstacles to clinical trial participation include a low level of physician referrals, inaccurate perceptions on the part of patients and their families regarding the nature of clinical trials, geographic, financial, and/or insurance barriers, and concerns about side effects, time burden, or trial design.16e19 It is important to note that most results in the literature regarding barriers to participation in cancer clinical trials have been extracted from North American studies.20 More international studies are needed since it would be important to consider other healthcare systems and cultures and to explore which factors are invariant across situations. A common obstacle, however, cited in both the North American as well as European literature is the quality and quantity of communication occurring among the oncologist, patient, and family/companion when trials are discussed and its major influence in the patient’s decision-making process.18,20 Another clear barrier, cited in North American literature, is the legalistic approach to consent forms. Despite efforts to simplify the process,19 consent forms for cancer clinical trials continue to be written as long legal forms with pages describing not only the risks presented for the entire regimen but often toxicities listing the risks for each specific drug or procedure that comprise the intervention. However, when presenting the alternatives, we ask the patient merely to discuss these treatments with their doctor. How to improve patients participation in MBC clinical trials? There are several opportunities for improvement. One area for improvement involves the education and engagement of physicians and nurses. Patients look to their providers to initiate discussions about clinical trials. For patients with a close relationship with their primary care physician or general practitioner (GP), the GP may also play a key role in the clinical trial decision-making process. In some
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countries, the GP often “falls out” of the care team once a patient is diagnosed with metastatic disease; however, this model denies patients the additional care and support that can be provided by the GP. In addition, this model contributes to inaccurate perceptions on the part of some GPs regarding the quality and length of life in patients with metastatic breast cancer. However, many GPs may feel challenged by the many issues related to patients with stage IV breast cancer.21Caring for patients with advanced cancer may cause even greater concern. To be able to accept more responsibility in the care of cancer patients, additional training, and role definition as well as improved communication with oncology specialists may be important first steps. In many countries, clinical trial access is also highly regional, and localized to academic medical centers. Thus, more significant outreach efforts to oncology providers outside of traditional clinical trial networks are critical. Even among physicians affiliated with a supportive clinical trial infrastructure, not all are actively engaged in the research process.16,17 Looking to the future, medical students in the U.S., Canada and several European countries are now required to learn basic principles of clinical and translational research, including how such research is conducted, evaluated, explained to patients, and applied to patient care.22 Another area that has historically been overlooked is the essential role of oncology nurses and/or nurse practitioners and nurse navigators in the care of patients; hence, specific education, training, and engagement of nurses are essential. Nurses and nurse navigators can serve as an invaluable additional source of communication and information, functioning quite often as a bridge between the physician and the patient. Next, the approach to presenting clinical trials needs reshaping. The presentation of information varies greatly and can confuse and overwhelm even highly educated women. A number of clinical trials now utilize novel approaches (interactive DVDs, web-based approaches, short informational decision aids) to supplement the traditional consent forms. Further research into the most effective communication approaches is much needed. Finally, despite many changes in clinical trial eligibility and design, the idea of enrolling on a trial still has an air of a “last resort” choice for many patients with MBC. When combined with long and confusing consent forms, lack of adequate communication, concerns about being placed in the placebo arm or only receiving the “standard” of care and not the investigative treatment, limited clinical trial participation is undoubtedly prevalent. However, as noted in the 2 large surveys,3,4 a large majority of patients with MBC are motivated to seek clinical trials information. This may have implications for the broader dissemination of trials information in a format integrated with other kinds of information of interest to patients with advanced cancer.5 The proliferation of online communities and patient-directed websites, as well as the wide utilization of hospital and organizational cancer websites, is a progressive venue for such efforts. For patients who are not able to use the Internet or prefer printed materials, brochures and pamphlets can easily be developed by health care providers and posted online for printing and distribution to patients. Videos live meetings, and teleconferences can make good information accessible to everyone.5 Above all, however, there is no substitute for a clear communication with messages that help build a sense of an alliance, provide support (tangible assistance and reassurance about managing adverse effects), and provide medical content in language that patients and family/companions understand.18,23 Under these circumstances, it is estimated that 75% of cancer patients would assent to participate in offered clinical trials, based on a study assessing 235 video recorded outpatient interactions among oncologists, cancer patients and family/companions in two comprehensive cancer centers.18 Communications about Phase II
and III clinical trial offers significantly influenced accrual decisions.18 A final but important area of improvement is further education of both clinicians and research participants about a greater acceptance of research biopsies as an essential component of clinical trials for MBC. Correlative research biospecimens often aim at establishing the association between a molecular feature of the cancer and a clinical outcome of interest. They may have no impact on the management of the trial participant and no direct benefit to participants but they may convey vital information in a clinical trial. However, using tissue samples from patients for particular molecular characteristics has introduced a new level of scientific and logistic complexity to clinical trials. Nevertheless, as we have entered the era of targeted therapy and personalized medicine, the traditional research model for MBC trials designed to evaluate outcomes across a broader population of patients should be revised. These types of analyses should no longer be considered a secondary goal of a trial. Instead, obtaining research biopsies should be an integral component of many, if not most cancer research trials conducted in MBC. There is a greater need to understand and address the concerns that may arise regarding these issues so that the rights of patients and trial participants can be protected while also allowing for research biospecimens to be included in cancer research on a solid and ethical foundation.24 Conclusion Women with MBC face bewildering choices at a time when they are experiencing highly stressful circumstances and many might not be, therefore, able to take part in treatment decisions. Large surveys targeting patients with MBC suggest many women do not feel well-informed and/or do not have well defined guidance on how to obtain data.3,8,9 Current practices to provide patients with information about treatment options, available clinical trials, educational materials, coping strategies, and supportive services vary widely and are frequently suboptimal. Improving on how information about MBC is delivered, including exploration of both new and traditional communication formats, is of paramount importance. Fortunately, the tide is turning. The challenges facing patients with MBC are being increasingly recognized by the media, the public and the medical and research communities. Multiple initiatives from professional organizations, academic and community centers, governmental agencies like the ARWG,7 advocacy organizations like the Breast Cancer Network of Australia,25 and pharmaceutical partners, continue to raise awareness of the unique issues faced by patients with metastatic breast cancer. Improving the rate of participation in MBC clinical trials and greater acceptance of newer research designs and biospecimen research collection need to be emphasized. The role of close collaboration between the medical, research and advocacy worlds continues to be highlighted. This tide changing ultimately lead to the recent development of the 1st international consensus guidelines for the management of advanced breast cancer (ABC 1 Conference) which are now available26 and need to be widely implemented. By working together, we have great potential to convey a message of realistic hope for women living with MBC, and to improve care for women both today and in the future. Disclaimers None. Conflict of interest statement None (all authors).
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Acknowledgments Breast International Group-North American Breast Cancer Group. References 1. Dawood S, Broglio K, Ensor J, Hortobagyi GN, Giordano SH. Survival differences among women with de novo stage IV and relapsed breast cancer. Ann Oncol November 2010;21(11):2169e74. 2. Giordano SH, Buzdar AU, Smith TL, Kau SW, Yang Y, Hortobagyi GN. Is breast cancer survival improving? Cancer 1 Jan 2004;100(1):44e52. 3. Bridging Gaps, Expanding Outreach (BRIDGE) e metastatic breast cancer www. BridgeMBC.com [accessed 04.01.13]. 4. Living Beyond Breast Cancer (LBBC): http://lbbc.org/LBBC-Library. [accessed 27.04.11]. 5. Mayer M. Lessons learned from the metastatic breast cancer community. Semin Oncol Nurs 2010;26(3):00195e202. 6. Visco F. The National Breast Cancer Coalition: setting the standard for advocate collaboration in clinical trials. Cancer Treat Res 2007;132:143e56. 7. http://deainfo.nci.nih.gov/advisory/dclg/ARWG-execSum.pdf [accessed 27.04.11]. 8. Metastatic Breast Cancer Advocacy Working Group consensus report. Breast Oct 2009;18(5):273e5. 9. Cardoso F. Metastatic breast cancer patients: the forgotten heroes! Breast Oct 2009;18(5):271e2. 10. English R, Lebovitz Y, Griffin R. Transforming clinical research in the United States: challenges and opportunities: workshop summary. Forum on Drug Discovery, Development, and Translation; Institute of Medicine, ISBN 0-30915333-6; 2010 [chapter 3]. 11. Collyar D. The value of clinical trials from a patient perspective. Breast J 2000;6: 310e4. 12. Jenkins V, Fallowfield L. Reasons for accepting or declining to participate in randomized clinical trials for cancer therapy. Br J Cancer 2000;82:1783e8.
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13. National Cancer Research Institute. 3 Year progress report 2001e2004. London: NCRI; 2004. 14. McDonald AM, Knight RC, Campbell MK, Entwistle VA, Grant AM, Cook JA, et al. What influences recruitment to randomized controlled trials? A review of trials funded by two UK funding agencies. Trials 2006;7:9. 15. McSherry Dot M. Clinical trial participation in breast cancer patients. European www.european-hospital.com/en/article/7013-Clinicial_trial [accessed 02.01.13]. 16. Klabunde CN, Keating NL, Potosky AL, Ambs A, He Y, Hornbrook MC, et al. A population-based assessment of specialty physician involvement in cancer clinical trials. J Natl Cancer Inst 2011;103(5):384e97. 17. Minasian LM, O’Mara AM. Accrual to clinical trials: let’s look at the physicians. J Natl Cancer Inst 2 Mar 2011;103(5):357e8. 18. Albrecht TL, Eggly SS, Gleason MEJ, Harper FW, Foster TS, Peterson AM, et al. Influence of clinical communication on patients’ decision making on participation in clinical trials. J Clin Oncol 2008;26(16):2614e5. 19. http://www.nih.gov/news/pr/oct98/nci-22.htm, [accessed 02.06.12]. 20. Castel P, Négrier S, Boissel JP. Why don’t cancer patients enter clinical trials? A review. Eur J Cancer Aug 2006;42(12):1744e8. Epub Jun 14, 2006. 21. Kantsiper M, McDonald EL, Geller G, Shockney L, Snyder C, Wolff AC. Transitioning to breast cancer survivorship: perspectives of patients, cancer specialists, and primary care providers. J Gen Intern Med Nov 2009;24(Suppl. 2): S459e66. 22. Liaison Committee on Medical Education. Functions and structure of a medical school. Standards for accreditation of medical education program leading to the M.D. degree. http://www.lcme.org/functionslist.htm#educational%20program [accessed 27.04.11]. 23. Baer AR, Good M, Shapira L. A new look at informed consent for cancer clinical trials. J Oncol Pract 2011 Jul;7(4):267e70. 24. Peppercorn J, Shapira L, Collyar D, Deshields T, Lin N, Krop I, et al. Ethics of mandatory research biopsy for correlative end points within clinical trials in oncology. JCO 2010 May 20;28(15):2635e40. 25. http://www.bcna.org.au/hope-hurdles-pack, [accessed 02.06.12]. 26. Cardoso F, Costa A, Norton L, Cameron D, Cufer T, Fallowfield L, et al. 1st International consensus guidelines for advanced breast cancer (ABC 1). Breast. Apr 7: 22487206, Published online, 2012.
Contents lists available at SciVerse ScienceDirect
The Breast journal homepage: www.elsevier.com/brst
Perceptions and needs of women with metastatic breast cancer: A focus on clinical trials Zeina A. Nahleh a, *, Nancy U. Lin b, Antonio C. Wolff c, f, Fatima Cardoso d, g, on behalf of the BIG-NABCG collaboratione a
Texas Tech University Health Sciences Center, Paul L. Foster School of Medicine, 4800 Alberta Avenue, El Paso, TX 79905, United States Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, United States Breast Cancer Program, The Johns Hopkins Kimmel Comprehensive Cancer Center, 1650 Orleans Street, CRB1-189, Baltimore, MD 21287, United States d Champalimaud Cancer Center, Av. De Brasília e Doca de Pedrouços, 1400-048 Lisbon, Portugal b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 30 October 2012 Received in revised form 5 January 2013 Accepted 24 February 2013
Many patients are living longer with Metastatic Breast Cancer (MBC) than ever before. However, complete responses remain uncommon, and progression of disease is often inevitable. The experience of living with MBC exposes patients to a wide variety of clinical, psychological, social and spiritual issues. Although much research effort has focused on decision-making and coping strategies among women with early breast cancer, relatively little attention has been given to the needs, experiences, and perceptions of women living with MBC. Furthermore, there are major research gaps in understanding and prioritizing the types of psycho-social interventions that would make the most difference in the lives of these patients. Fortunately, the tide is turning. This communication represents a joint effort of the Breast International Group and the National Cancer Institute (NCI)-sponsored North American Breast Cancer Group (BIG-NABCG) to highlight perceptions and needs of patients living with MBC and current obstacles facing them, and recommends strategies for better addressing some of these unmet needs. Ó 2013 Elsevier Ltd. All rights reserved.
Keywords: Perceptions Metastatic Breast Cancer BIG-NABCG
Introduction Over the past two decades, significant advances have been achieved in the treatment of metastatic breast cancer (MBC). Many patients are living longer with MBC than ever before, with a currently reported median overall survival (OS) of 4e5 years.1,2 However, complete responses remain uncommon, and for the vast majority of patients, progression of disease is inevitable. Moreover, the experience of living with metastatic cancer exposes patients to a wide variety of clinical, psychological, social and spiritual issues which may directly impact their lives. When caring for patients with metastatic breast cancer, the goals of treatment, as traditionally set forth by health care professionals and the research community, are to control symptoms and to prolong survival (when possible) with the least disruption of quality of life. Often, there is no clear data from randomized trials to support the choice of one
* Corresponding author. Tel.: þ1 915 545 6618; fax: þ1 915 545 6634. E-mail addresses: [email protected] (Z.A. Nahleh), Nancy_Lin@ dfci.harvard.edu (N.U. Lin), [email protected] (A.C. Wolff), fatimacardoso@ fundacaochampalimaud.pt (F. Cardoso). e Breast International Group-North American Breast Cancer Group. f Tel.: þ1 410 614 4192; fax: þ1 410 614 4073. g Tel.: þ351 (210) 480004. 0960-9776/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.breast.2013.02.017
systemic treatment versus another for an individual patient, particularly beyond the first-line setting. Patients may feel significant stress in weighing treatment options based on individual and often unclear perceptions and expectations. Although much research effort has focused on decision-making and coping strategies among women with early breast cancer, relatively little attention has been given to the needs and experiences of women living with MBC. Furthermore, there are major research gaps in understanding and prioritizing the types of psycho-social interventions that would make the most difference in the lives of patients and their families. Addressing research gaps The BRIDGE (Bridging Gaps, Expanding Outreach) Metastatic Breast Cancer Patient Survey was one of the first large-scale attempts to address some of the research gaps in our knowledge about MBC. This survey was conducted among 1342 women in 13 countries to assess the needs, experiences and attitudes of women living with MBC.3 To offer a balance between low and high-resource countries, approximately 100 women from each of 13 countries were recruited through physician referral, including Australia, Latin America (Argentina, Brazil, Mexico, Venezuela), Europe (Belgium, France, Spain, the United Kingdom), North Africa (Egypt), and North
Z.A. Nahleh et al. / The Breast 22 (2013) 370e373
America (Canada, US). The survey was conducted between September 16, 2008 and February 18, 2009 using a combination of telephone, mail or in-person methods. Total sample data was representative of the individuals interviewed. The main survey results were as follows: (1) one in two women (53 percent) with MBC believe the disease receives too little public attention, (2) most women (75 percent) proactively seek out information on MBC, yet 51 percent find available information is often insufficient or ineffective and (3) despite the large number of women living with MBC, their needs often go unreported.3 In a complementary effort, Living Beyond Breast Cancer (LBBC) conducted an internet-based survey focusing on the use of and preferences for services of women with MBC in three domains: information, support and practical resources.4 Data was obtained from 618 online respondents reflecting the demographics of internet users, with 70% between the ages of 40 and 59. Patients with MBC expressed high interest in information about their diagnosis and treatment options and described seeking information in multiple ways, from printed materials, websites, online communities, teleconferences, to in-person educational meetings. However, many reported that they did not know how to locate ongoing community or internet-based educational programs.4 Messages taken from the findings in these two surveys can inform services and programs designed for people living with MBC.5 The most urgent need expressed by patients and their families is for accurate and accessible information about their disease, standard and emerging treatments, realistic treatment goals, ways of coping with side effects and symptoms, and ways of communicating the news with loved ones (particularly children and partners). The good news is that more initiatives have been launched over the past few years, not only to identify the needs of patients with MBC and current obstacles facing them, but also to discuss solutions and ideas for better addressing these unmet needs.6e9 One of the first such initiatives was an MBC Advocacy Working Group,8 created in 2008 and comprised of 16 patient advocates from seven countries. The group issued important recommendations in three major areas: (a) improve access to information, resources and support services; (b) heighten attention to the MBC community; and (c) increase understanding of, and access to clinical trials. The recommendations also called for the design of clinical trials that include underserved segments of the MBC community, such as heavily pretreated women and women with certain metastases.8 Additionally, advocate collaboration has been introduced as a new standard in the design of breast and other cancer clinical trials.6,7 The advocates’ main role is to bring the perspectives of those most affected by cancer to the work of the cancer research community. In 2007, the U.S. National Cancer Institute (NCI) initiated the Advocates in Research Working Group (ARWG) in order to develop recommendations on how NCI can most effectively and consistently engage individual advocates in the research process to accelerate progress and benefit patients.7 The final NCI-approved recommendations and the final ARWG Executive Summary and Recommendations were released in March 2011.7 An important message of the patient surveys and of the MBC Advocacy Working Group is the value placed on education and information about treatment options, particularly with respect to clinical trials. Given the high level of interest in clinical trials expressed by many patients, and the high priority designated to clinical trial access by investigators and patient advocates, it is concerning that only around 3% of adult cancer patients actually participate in trials in the U.S, a dismal percentage that is essentially unchanged over the last decade.10,11 Also an analysis of more than 500 NCI Cancer Therapy Evaluation Program (CTEP) trials in the U.S. revealed that 40 percent of trials failed to achieve minimum patient enrollment, and more than three of five phase III trials failed to do so.10
371
In Europe, where the tradition of clinical research is less institutionalized, statistics of cancer patients participation in clinical trial appear to be slightly but not overwhelmingly better, reported at less than 5% overall, but may vary depending on cancer site and centers of treatment.12e14 More recently, The National Cancer Research Network (NCRN) in the UK has been recognized as one of the best examples for improvement, since it has succeeded in increasing the accrual rate from 3.75% to more than 10% in a few years.11 This increase had to do with the massive public investment, which has allowed, among other things, the recruitment of a large number of research staff, such as clinical trials practitioners, data managers and research nurses. However, overall only around 31% of multicentre randomized controlled trials in the UK that were recruiting between 1994 and 2002 achieved their original recruitment target.12 Insights into breast cancer clinical trial participation was gained from the results of the BRIDGE survey.15 Clinical trial participation varied greatly by country, with Venezuela having the lowest percentage (1%) and Canada and Mexico having the highest (both 35%). In Europe and the UK, Belgian women had the highest level of participation (27%), followed by Poland (21%), Spain (19%), United Kingdom (13%), and France (7%). Women in Australia and the United States were most proactive about looking for information relating to clinical trials.15 The failure of clinical trials to enroll enough patients moves health care further away from evidence-based practice and represents a tremendous amount of wasted effort. In addition, with the move to “personalized medicine” involving targeted therapies for small subsets of cancers, the need to involve the larger breast cancer community in clinical trials becomes ever greater, in order to achieve accrual goals and move the field forward. Cancer clinical trials issues Some of the cited obstacles to clinical trial participation include a low level of physician referrals, inaccurate perceptions on the part of patients and their families regarding the nature of clinical trials, geographic, financial, and/or insurance barriers, and concerns about side effects, time burden, or trial design.16e19 It is important to note that most results in the literature regarding barriers to participation in cancer clinical trials have been extracted from North American studies.20 More international studies are needed since it would be important to consider other healthcare systems and cultures and to explore which factors are invariant across situations. A common obstacle, however, cited in both the North American as well as European literature is the quality and quantity of communication occurring among the oncologist, patient, and family/companion when trials are discussed and its major influence in the patient’s decision-making process.18,20 Another clear barrier, cited in North American literature, is the legalistic approach to consent forms. Despite efforts to simplify the process,19 consent forms for cancer clinical trials continue to be written as long legal forms with pages describing not only the risks presented for the entire regimen but often toxicities listing the risks for each specific drug or procedure that comprise the intervention. However, when presenting the alternatives, we ask the patient merely to discuss these treatments with their doctor. How to improve patients participation in MBC clinical trials? There are several opportunities for improvement. One area for improvement involves the education and engagement of physicians and nurses. Patients look to their providers to initiate discussions about clinical trials. For patients with a close relationship with their primary care physician or general practitioner (GP), the GP may also play a key role in the clinical trial decision-making process. In some
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countries, the GP often “falls out” of the care team once a patient is diagnosed with metastatic disease; however, this model denies patients the additional care and support that can be provided by the GP. In addition, this model contributes to inaccurate perceptions on the part of some GPs regarding the quality and length of life in patients with metastatic breast cancer. However, many GPs may feel challenged by the many issues related to patients with stage IV breast cancer.21Caring for patients with advanced cancer may cause even greater concern. To be able to accept more responsibility in the care of cancer patients, additional training, and role definition as well as improved communication with oncology specialists may be important first steps. In many countries, clinical trial access is also highly regional, and localized to academic medical centers. Thus, more significant outreach efforts to oncology providers outside of traditional clinical trial networks are critical. Even among physicians affiliated with a supportive clinical trial infrastructure, not all are actively engaged in the research process.16,17 Looking to the future, medical students in the U.S., Canada and several European countries are now required to learn basic principles of clinical and translational research, including how such research is conducted, evaluated, explained to patients, and applied to patient care.22 Another area that has historically been overlooked is the essential role of oncology nurses and/or nurse practitioners and nurse navigators in the care of patients; hence, specific education, training, and engagement of nurses are essential. Nurses and nurse navigators can serve as an invaluable additional source of communication and information, functioning quite often as a bridge between the physician and the patient. Next, the approach to presenting clinical trials needs reshaping. The presentation of information varies greatly and can confuse and overwhelm even highly educated women. A number of clinical trials now utilize novel approaches (interactive DVDs, web-based approaches, short informational decision aids) to supplement the traditional consent forms. Further research into the most effective communication approaches is much needed. Finally, despite many changes in clinical trial eligibility and design, the idea of enrolling on a trial still has an air of a “last resort” choice for many patients with MBC. When combined with long and confusing consent forms, lack of adequate communication, concerns about being placed in the placebo arm or only receiving the “standard” of care and not the investigative treatment, limited clinical trial participation is undoubtedly prevalent. However, as noted in the 2 large surveys,3,4 a large majority of patients with MBC are motivated to seek clinical trials information. This may have implications for the broader dissemination of trials information in a format integrated with other kinds of information of interest to patients with advanced cancer.5 The proliferation of online communities and patient-directed websites, as well as the wide utilization of hospital and organizational cancer websites, is a progressive venue for such efforts. For patients who are not able to use the Internet or prefer printed materials, brochures and pamphlets can easily be developed by health care providers and posted online for printing and distribution to patients. Videos live meetings, and teleconferences can make good information accessible to everyone.5 Above all, however, there is no substitute for a clear communication with messages that help build a sense of an alliance, provide support (tangible assistance and reassurance about managing adverse effects), and provide medical content in language that patients and family/companions understand.18,23 Under these circumstances, it is estimated that 75% of cancer patients would assent to participate in offered clinical trials, based on a study assessing 235 video recorded outpatient interactions among oncologists, cancer patients and family/companions in two comprehensive cancer centers.18 Communications about Phase II
and III clinical trial offers significantly influenced accrual decisions.18 A final but important area of improvement is further education of both clinicians and research participants about a greater acceptance of research biopsies as an essential component of clinical trials for MBC. Correlative research biospecimens often aim at establishing the association between a molecular feature of the cancer and a clinical outcome of interest. They may have no impact on the management of the trial participant and no direct benefit to participants but they may convey vital information in a clinical trial. However, using tissue samples from patients for particular molecular characteristics has introduced a new level of scientific and logistic complexity to clinical trials. Nevertheless, as we have entered the era of targeted therapy and personalized medicine, the traditional research model for MBC trials designed to evaluate outcomes across a broader population of patients should be revised. These types of analyses should no longer be considered a secondary goal of a trial. Instead, obtaining research biopsies should be an integral component of many, if not most cancer research trials conducted in MBC. There is a greater need to understand and address the concerns that may arise regarding these issues so that the rights of patients and trial participants can be protected while also allowing for research biospecimens to be included in cancer research on a solid and ethical foundation.24 Conclusion Women with MBC face bewildering choices at a time when they are experiencing highly stressful circumstances and many might not be, therefore, able to take part in treatment decisions. Large surveys targeting patients with MBC suggest many women do not feel well-informed and/or do not have well defined guidance on how to obtain data.3,8,9 Current practices to provide patients with information about treatment options, available clinical trials, educational materials, coping strategies, and supportive services vary widely and are frequently suboptimal. Improving on how information about MBC is delivered, including exploration of both new and traditional communication formats, is of paramount importance. Fortunately, the tide is turning. The challenges facing patients with MBC are being increasingly recognized by the media, the public and the medical and research communities. Multiple initiatives from professional organizations, academic and community centers, governmental agencies like the ARWG,7 advocacy organizations like the Breast Cancer Network of Australia,25 and pharmaceutical partners, continue to raise awareness of the unique issues faced by patients with metastatic breast cancer. Improving the rate of participation in MBC clinical trials and greater acceptance of newer research designs and biospecimen research collection need to be emphasized. The role of close collaboration between the medical, research and advocacy worlds continues to be highlighted. This tide changing ultimately lead to the recent development of the 1st international consensus guidelines for the management of advanced breast cancer (ABC 1 Conference) which are now available26 and need to be widely implemented. By working together, we have great potential to convey a message of realistic hope for women living with MBC, and to improve care for women both today and in the future. Disclaimers None. Conflict of interest statement None (all authors).
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