A feasibility study to evaluate the relationships between endocrine symptoms, drug adherence and genetic polymorphisms in breast cancer patients receiving tamoxifen therapy
Carmen WH Chan PhD 1, Ka Ming Chow DN 1, Alexandra McCarthy PhD 2, Judy YW Chan PhD 1 , Mary MY Waye PhD 1 , Stephen KW Tsui PhD 3, Winnie Yeo MBBS, MD 4, K C Choi PhD 1, Winnie KW So PhD 1, Winnie Soo MbChB, FHKAM 4, Christine Miaskowski PhD 5
1 The Nethersole School of Nursing, The Chinese University of Hong Kong
2 School of Nursing, The University of Auckland
3 School of Biomedical Sciences, The Chinese University of Hong Kong
4 Department of Clinical Oncology, The Chinese University of Hong Kong
5 Department of Physiological Nursing, University of California
A common practice to prevent cancer recurrence after treatment is to prescribe
adjuvant tamoxifen, an anti-hormonal therapy, for at least five years.
1 Despite the acknowledged benefits in terms of reduced recurrence rates associated with its use,
adherence to tamoxifen is less than ideal. Approximately 1 in 5 patients who are
prescribed adjuvant tamoxifen do not achieve the optimal adherence threshold of
≥80% during the first year of treatment.
2-3 The most significant factor contributing to non-adherence is the tamoxifen-related endocrine (hormone deprivation) symptom
profile. Symptoms include sudden, severe, and often permanent vasomotor symptoms,
and related insomnia, somatic symptoms, depression and sexual dysfunction.
4-5 Toxicities, and the way that tamoxifen is metabolized, are largely influenced by
individual genetic makeup. Different forms of some genes found in the population
(i.e. polymorphisms) which are involved in the metabolism of tamoxifen (e.g.
CYP3A4 and CYP2D6) may influence the toxicity, side effects, and symptom
experiences of tamoxifen.
6-7 We want to explore if, and how, endocrine symptoms of tamoxifen correlate with both
drug adherence and polymorphisms in genes that regulate the metabolism of 2
tamoxifen in Chinese women with breast cancer. This is a collaborative study among
colleagues from the Chinese University of Hong Kong, University of California at
San Francisco, and the University of Auckland. Our research team comprises
oncology specialists, credentialed oncology nurses, molecular geneticists, a
biostatistician and technical staff. We plan to conduct a cohort study to follow 200
Chinese women over 12 months and assess their clinical symptoms and genetic
variations. Endocrine symptoms and drug adherence will be scored during interviews
with standardized questionnaires including the Greene Climacteric Scale (GCS), the
Functional Assessment of Cancer Therapy-Endocrine subscale (FACT–ES)
questionnaire (Version 4), the Medication Possession Ratio. Polymorphisms in
significant target genes will be determined using commercial assays of saliva samples.
Participants will also maintain a logbook to record their intake of tamoxifen and any
other compounds, such as Chinese medicines, on a daily basis for 12 months.
In the past 3 months, our group has conducted a pilot study and successfully recruited
30 participants (response rate: 68.2%). Based on the data collected to date, some
allelic variations in some candidate SNPs, including ABCB1 rs1128503, UGT2B15
rs4148269, ABCC2 rs717620, CYP3A5 rs776746, CYP1A2 rs2470890, ABCC1
rs35628, CYP2B6 rs3745274, CYP2C19 rs4244285, showed considerably large
differences, with standardized mean differences of > 1 in endocrine-related symptom
score. This pilot study demonstrated the feasibility of recruitment and data collection.
The participants reported that the study design is simple and not time consuming.
This study will be the first to uncover any unique profile or gene(s) that are associated
with tamoxifen-related endocrine symptoms and other important outcomes. We will
pioneer exploration of the associations between genotypes, endocrine symptoms and
drug adherence in Chinese women with breast cancer.
1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG) (2005). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15- year survival: an overview of the randomized trials. Lancet 2005; 365: 1687-717.
2. Hershman, D.L., Shao, T., Kushi, L.H., Buono, D., Tsai, W.Y., Fehrenbacher, L., Kwan, M., Gomez, S.L., Neugut, A.I. (2011) Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Research and Treatment 126: 529–537.
3. McCowan, C., Shearer, J., Donnan, P.T. (2008) Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer. British Journal of Cancer 99: 1763–1768.
4. Barron, T.I., Connolly, R., Bennett, K., Feely, J., Kennedy, M.J. (2007) Early discontinuation of tamoxifen: a lesson for oncologists. Cancer 109: 832–839.
5. Cluze, C., Rey, D., Huiart, L. (2012) Adjuvant endocrine therapy with tamoxifen in young women with breast cancer: determinants of interruptions vary over time. Annual Oncology 23:882-90.
6. Briest, S., Stearns, V. (2009) Tamoxifen metabolism and its effect on endocrine treatment of breast cancer. Clin Adv Hematol Oncol. 7:185–192.
7. Cronin-Fenton, D.P., Damkier, P., Lash, T.L. (2014) Metabolism and transport of tamoxifen in relation to its effectiveness: new perspectives on an ongoing controversy. Future Oncology 10:107–122.
A Perspective: Geriatric Oncology Becoming the Masterpiece of the Art of Oncology Care
By Cynthia Abarado DNP, APRN, GNP-BC; Independent Consultant, Sugar Land, Texas
Why is geriatric oncology evolving as the mainstream in cancer care?
The world’s population among people 60 years of age will increase from 900 million to 2 billion between 2015 and 2050, (World Health Organization, 2017). In the USA, 60% of those affected by cancer are 65 years of age and older. This population also comprise most of deaths from cancer. There are insurmountable financial, personal and social costs involved in geriatric oncology care continuum. In addition, the impacts of health and aging generally have significant burden globally. Please see: http://www.who.int/ageing/events/world-report-2015-launch/healthy-ageing-infographic.jpg?ua=1
The change in the tapestry of the population poses significant challenges on the care of older cancer patients. The advanced technology and diagnostics have improved early cancer detection and prevention leading to early treatment. At times, cancer is diagnosed at later stages affecting the treatment, goals of care and outcomes. The complexed care of cancer in an older patient is also affected by co morbidities. Recent improvements in treatment modalities have changed the trajectory of cancer illness posing significant financial, care-giving, acute and chronic care challenges. While there are issues in the management of cancer treatment, cancer-related symptoms there is also evidence of increased five-year survival. According to the Center for Disease Control and Prevention (2017), there are 15 million Americans alive today who had a diagnosis of cancer. The presence of co-morbidities among survivors makes the care of the older cancer patient even more complexed. A comprehensive geriatric care model is proposed to encourage nurses and other health team members ensure a well-coordinated care that promotes patient-centered, personalized care plan.
What are the unique attributes of the older cancer patient or population that are essential in a comprehensive geriatric oncology care?
The geriatric oncology patient or population has unique characteristics which can be the basis of identifying their needs, develop individualized plan of care that are meaningful to the patient and family, attain outcomes aligned with the patient goals and foster a patient-centered high-quality care. These attributes include biological, physiological, psychological, sociological, pharmacogenomics, and molecular components. Each attribute is unique to each older cancer patient. The support system of an older cancer patient determines the patient’s ability to cope cancer, cancer treatment and cancer treatment related side-effects. A person’s perception of his quality of life is significantly affected by his knowledge of his disease process, prognosis and goals of cancer treatment. Moreover, this population comes from diverse global and unique multicultural background influencing each individual’s perception of health, illness and quality of life.
Example of the Comprehensive Geriatric Oncology Care Assessment Model
||Aspects of Attributes
||Cancer Diagnosis, Presence of co-morbid conditions, Geriatric Syndromes, Frailty
||Depression, neurodevelopmental disabilities, psychiatric and behavioral conditions, dementia, cognition
||Drug allergies, drug interactions, laboratory evaluation
||Polypharmacy, insurance profile re coverage
||Family/ community support, living arrangements, financial needs
||Genotype profile, histology and liquid biopsy profile
The model is based upon the assumption that the geriatric oncology population requires a comprehensive oncology care in the presence of co morbidities, frailty and geriatric syndromes. It is also based upon the knowledge that each geriatric oncology patient has unique characteristics unique to each subset of this population that would affect types and goals of treatment. The model views cancer care as complex. It requires collaboration and coordination across systems and locations. Moreover, the model is based upon the assumption of a collaboration between each health team member and functions within a multidisciplinary approach.
A perspective on the Proposed Comprehensive Geriatric Oncology Care Model
The comprehensive geriatric oncology care assessment proposed in this model uses the Comprehensive Geriatric Assessment (CGA) as a framework. CGA is defined as “multidisciplinary evaluation in which multiple problems of older persons are uncovered, described, and explained, if possible, and in which the resources and strengths of the person are catalogued, need for services assessed, and a coordinated care plan developed to focus in the person’s problems (Solomon, 1988). A meta-analysis analyzing 28 controlled trials of five types of geriatric assessments in various settings was done in 1993. It demonstrated that CGA programs that link geriatric assessment with strong long-term follow-up and management are effective for improving survival and functions in older adults (Suck, 1993). The utilization of CGA in cancer care has not been fully established. However, assessments of different components have been studied in various settings in Europe.
In this model, the geriatric oncology patient and population are the most important focus of care. The dynamic interactions between the environments, nurse, person to attain the state of health constantly changes. An assessment of the diverse attributes that is unique to each person utilizes several established tools that have established internal validity and have been utilized in different research endeavors. Biophysiological attributes include cancer diagnosis, geriatric syndromes, pain, fluid/electrolyte imbalances, abnormal biomarkers, cancer treatment related toxicities, co morbidities and educational needs related to disease process. The Symptom Distress Scale developed by McCorkle and Young has been widely used to assess symptom distress among oncology patients. It is reported to have a Cronbach’s alpha co-efficient of 0.70-0.92 (McCorkle, 2000). The role of co morbidity in cancer management and decision-making is yet to be studied more extensively in this population. Charlton Comorbidity Index and Cumulative illness rating scale index-geriatrics have been proposed to assess comorbidities although none has been validated for use in older adults with cancer. Psychological and sociocultural factors include depression, ineffective coping, lack of support systems, impaired self-care, lack of financial resources and educational needs. Utilization of the Geriatric Depression Scale has been recommended. It is reported to be 84% sensitive and 95% specific for diagnosing clinical depression. Assessment of social support is markedly important as it plays in a cancer patient’s health and linked to mortality. Caregiving in cancer has shifted to family members giving rise to caregiver burden. Caregiver Reaction Assessment is a 24-item instrument that assesses reactions of family members caring for older patients with physical impairments, cancer and Alzheimer’s. Utilization of Elder Assessment Instrument to review signs, symptoms, complaints of elder abuse, neglect, exploitation and abandonment among at risk population maybe warranted. Functional status can be measured Katz Index of Activities of Daily Living, Instrumental Activities of Daily Living and the Eastern Cooperative Oncology Group Performance Status (ECOG PS). Cognition includes assessment for dementia, delirium, decision-making ability and identification of a surrogate decision-maker. The Holstein Mini-Mental State Examination (MMSE) is one of the most widely used. The Confusion Assessment Method (CAM) has been widely used and validated as an instrument for assessing delirium. Advance directives should be discussed initially or at an early stage of treatment but should not be mistaken as stopping treatments. Pharmacogenomics include assessments related to biomarkers, liver function tests and renal functions. These are necessary to adjust treatment doses and determine types of treatments. Pharmacy profile review includes evaluation for polypharmacy and identification of financial/ insurance coverage for treatments. Reconciliation of medications, review of medication interactions and incompatibilities are also important components of this aspect. This model could be utilized efficiently using evidence-based practice assessment tools with established internal validity and tested using randomized clinical trials. The comprehensive geriatric oncology assessment is also based on nursing process, interdisciplinary care approach and collaboration. It proposes utilization of assessment tools that have established internal validity and reliability to increase its internal and logical adequacy.
The utilization of this model could be expanded to other chronic care coordination programs. The model requires a comprehensive assessment and is multidimensional. Demonstration projects to measure that the application of a comprehensive geriatric oncology practice model would decrease overall cancer expenditure would be necessary. The economic impact of this model can also be demonstrated by decreased hospitalization and readmissions. Other outcome measures are related to decreased mortality from treatments and complication and most of all improved oncology care coordination through utilization of evidence-based guidelines and informatics.
Implications to Advanced Practice Nurses
I have used this model in an acute care setting. Roy’s Adaptation Model plays a role in some aspects of my practice model. Nursing process and nursing interventions are the fundamental guiding principles. Future nursing research based upon the model could investigate the impact of evidence-based cancer care management on survivorship of cancer patients particularly among the older population. The global consultative role of the DNP based on this model could open opportunities for the DNP. Overall the application of this model expands the role of the DNP to a global health care environment for geriatric oncology patients.
The Comprehensive Geriatric Oncology Care Model proposes the comprehensive geriatric oncology assessment, a modified version of the CGA to be incorporated in cancer care. Assessment of the specific domains using established tools would lead to a comprehensive care plan and efficient care coordination across systems. The model is multidimensional and utilizes chronic care model, application of nursing process.
There is a need for more educational training among nurses to care for older patients with cancer. The use of assessment tools to evaluate each attribute of older patient eith cancer require special training among multidisciplinary team members. Although using a comprehensive geriatric care model is a tedious process, identification of problems during initial assessment of each attribute can lead to safe, timely, effective, efficient, patient centered and equitable quality of care throughout the cancer care continuum.
Opportunities and Resources
The proposed Comprehensive Geriatric Oncology Care Model can be applied to daily clinical practice, nurse navigation, case management, and global care coordination.
Some resources for geriatric oncology are available on the following websites:
The International Conference on Cancer Nursing (ICCN 2017) was held in Anaheim, CA, USA with the theme ‘Merging Research and Practice across the Globe’. In total, five nursing staff from Zhejiang Cancer Hospital of China attended the conference, including Wan-ying Wu, Zi-fang Jiang, Yi Tu, Guan-mian Liang, and Xia Shen. Four delivered oral presentations, one was poster presenter. This multidisciplinary team was comprised of nursing managers, medical professionals, administrating experts who actively participated in the whole process. What was shared regarding cancer clinical practice, administration experience, as well as research findings were highly appraised and was a great deal of interest to each of them. The following is a short interview of their experience at ICCN 2017.
Interviewer: Hi guys, what do you think of this conference?
Wu: I was really excited about this meeting. It remains one of the most important opportunities for cancer nurses across the globe to share our experiences and network. This is an amazing program which highlights how cancer nurses’ advance and continue to interpret evidence into practice.
Jiang: This was actually the second time I have attended ICCN. The highlight was meeting acquaintances and making new friends and colleagues to collaborate with. My topic was “The qualitative research of sexual status in breast cancer patients”.
Liang: My presentation was focused on “how to motivate nurses on continuing nursing education”. I attended seven presentations including professional issues, methods /measurements/tool development and quality & safety. They were all very interesting and I feel I really benefited a lot by attending ICCN 2017.
Tu: This was a fabulous chance that I could exchange ideas on cancer nursing with other representatives who were engaged in the same research areas.
Shen: I was so honored and excited when I received the invitation from the Conference Organizing Committee as an oral presenter. I could share what we’ve done for our patients with cancer nursing experts from all over the world. I suppose it will be one of the most unforgettable memories for me. By having access to the cutting-edge advances in cancer care, I was able to broaden my horizon and seek cooperation opportunities with other delegates in the future.
Photo: Five delegates from Zhejiang Cancer Hospital of China
Author: Xia Shen
Head Nurse, Abdominal Surgery Department of Zhejiang Cancer Hospital, China
I am so delighted and grateful to the ISNCC for nominating me for the 2017 Conference Scholarship Award to attend ICCN 2017 in Anaheim, California. The conference was really an unforgettable event for me, being the first time I will attend a gathering of nurses from all over the globe to share experiences and learn from young nurses and from leaders in cancer nursing. I had the great privilege to meet internationally recognized oncology academics and scholars that are not easily accessible in my country. I also want to express my deep appreciation to my mentor and my supervisor, Professor Sally Thorne who gave me the inspiration to apply for the scholarship award. I also acknowledge the support and encouragement given to me by Fuchsia Howard, an Assistant Professor, and my cosupervisor.
The first session I attended was the preconference workshop two about peer review for the academic journal where I what constitutes a quality peer review. This experience helped me to evaluate a couple of studies posted at the exhibition. I was inspired by the different, innovative ideas, new interventions, theories, and interesting research topics presented during the concurrent sessions. The experience has broadened my horizons and has equipped me with an advanced information about oncology nursing. I was challenged to reflect on the role of oncology nursing in knowledge translation and their activities to ensure that nurses deliver patient care by using the best available evidence across the globe.
The plenary sessions and the concurrent session were all informative and educative. I have learned about different research interventions and findings. I learned about new evidence which may improve the nursing care of cancer patients and how research findings in nursing have advanced in nursing care of cancer patients. I gained experience in developing research topics and how to conduct studies that will be beneficial to cancer patients and my institution. It was amazing how nurses have advanced in knowledge translation across the globe. The postal exhibition was also interesting. Furthermore, the conference has provided me with the opportunities to learn, share, and connect with graduate nurses who specialize, my interaction with them has inspired my confidence in conducting nursing research.
Finally, the conference has inspired me to take up the challenge of establishing a cancer nursing association in Nigeria to improve the nursing care of cancer patients and their families. Although an oncology nursing training is yet to be established in my country. The “meet your mentor” session provided me with an adequate information regarding the establishment of oncology nursing association. I intend to share my experience at the ICCN 2017 with the director of my institution, my colleagues and other nurses caring for oncology patients. Once again, I am grateful to ISNCC.
Photo: Abosede Catherine Ojerinde is in the centre, between fellow scholarship recipients, Elaine Barros Ferreira and Angela Knox.
Attending the International Conference on Cancer Nursing (ICCN) 2017 was a great opportunity for me. I thank the International Society of Nurses in Cancer Care for giving the scholarship to me which enabled me to attend the ICCN 2017 in Anaheim, California from the 9th-12th of July 2017. To be part of this conference allowed me to meet experienced nurses from different parts of the world and get to know about the oncology nursing role in different settings.
During the congress I presented the work “Assessing the effectiveness of urea cream as a prophylactic agent for radiation dermatitis” in the oral modality. The presentation room had other speakers with works in the same theme. This moment allowed to share our studies, to know the interventions evaluated in other centers of studies and to discuss about the practices adopted for the care of the radiation dermatitis. The presentations were chaired by the Nurse Pauline Rose, of Australia, who led the way enriching the discussion.
The existing demands in the field of oncology nursing require an international collaboration among oncologist nurses, aiming to disseminate best practices and evidences between different countries and scenarios of professional performance. Developing or underdeveloped countries need this exchange of knowledge and support from other countries so that care for patients is equally effective. In addition, the development of research should be viewed globally, increasing the scope of the practices evaluated. In this way, knowing the different researches that have been developed and exchanging experiences with researchers who studies subjects similar to mine increasing the networks of studies, the partnerships and the knowledge acquired. It will be very important for me and my institution to know more about the research and ideas being developed and presented by oncologist nurses around the world.
I was privileged to be part of the conference. During the conference I had the honor of personally meeting an important co-author, Dr. Raymond Chan, of an article that had been published in partnership with the study group of which I am a member. I look forward to work together with oncology nursing experts from across the world. I’m sure the experiences at the conference will influence my future research. I look forward to continuing to share experiences and having the opportunity to learn more and more with experienced oncologist nurses. The advancement of oncological nursing depends on these collaborative working relationships, in which professionals can train themselves by enabling the development of quality care for all patients, based on the best available scientific evidence.
Lastly, I am very grateful to be a participant at this very important conference. I thank my supervisor, Dra. Paula Elaine Diniz dos Reis, a Professor of Nursing at the University of Brasília, Federal District, Brazil, who encouraged me to join the conference. For sure, the experience was incredible and very enriching.
Elaine Barros Ferreira
University of Brasília
Photo: Elaine Barros Ferreira (in the striped dress), is pictured speaking with a colleague at the President’s Social at ICCN 2017.