A mixed method study on the prevalence, severity and experience of genitourinary symptoms and the impact on sexual function and QoL in postmenopausal women on endocrine therapy for early breast cancer MARIANA S. SOUSA ARE WE MISSING THE ISSUES THAT REALLY MATTER? 1 ARE WE MISSING THE ISSUES THAT REALLY MATTER? A mixed method study on the prevalence, severity and experience of genitourinary symptoms and the impact on sexual function and quality of life in postmenopausal women on endocrine therapy for early breast cancer Mariana de Souza e Sousa A thesis in fulfillment of the requirements for the degree of Doctor of Philosophy Prince of Wales Clinical School Faculty of Medicine University of New South Wales Australia 2015 iii PLEASE TYPE THE UNIVERSITY OF NEW SOUTH WALES Thesis/Dissertation Sheet Surname or Family name: de Souza e Sousa First name: Mariana Other name/s: N/A Abbreviation for degree as given in the University calendar: PhD School: Prince of Wales Clinical School Faculty: Medicine Title: Are we missing the issues that really matter? A mixed-method study on the prevalence, severity and experience of genitourinary symptoms and the impact on sexual function and Qol in postmenopausal women on endocrine therapy for early breast cancer Abstract 350 words maximum: (PLEASE TYPE) The underlying hypothesis of this PhD Is that the negative Impact of adjuvant endocrine therapy on genitourinary symptoms In postmenopausal women with early breast cancer has been underestimated In clinical trials and that there are a myriad of genitourinary symptoms related to or exacerbated by endocrine therapies that are commonly not reported by women to their oncologists. These symptoms can be troublesome and may lead to noncompliance with treatment, especially If associated with other side effects. This Issue has not been comprehensively addressed, resulting In uncertainty regarding the frequency and severity of genitourinary adverse effects associated with antlestrogens and their potential impact on quality of life (QoL). Furthermore, no studies have comprehensively and prospectively evaluated the full range of genitourinary symptoms from before therapy begins and over time. These symptoms include urinary frequency, urgency, Incontinence, dysuria, prolapse among others. This study fills an Important gap In the current literature and Is clinically Important as Interventions could be used to better manage and treat many of these symptoms. A number of data collection methods and Instruments were used In this project, selected on their ability to address the proposed research questions. Using a qualitative approach, with semi-structured Interviews, Study I sought an In-depth Insight of the genitourinary symptoms experienced by women with early breast cancer on antlestrogen therapy and an understanding on how symptoms Impact on dally life and sexual function. Study II employed a prospective design, using carefully selected validated instruments, to measure the prevalence and severity of genitourinary symptoms In postmenopausal women with breast cancer (prior to adjuvant endocrine therapy) and documented the trajectory of symptoms over time. The Impact of genitourinary symptoms on sexual function and QoL was also Investigated. The study attempted to Identify predictors for which women were more likely to develop significant genitourinary symptoms, and In particular, whether there Is an Identifiable sub-group of women at high-risk of developing severe genitourinary symptoms. This research project was conducted In the hope that the findings would Inform clinical practice and lead to greater efforta to early recognition and appropriate management of postmenopausal women who develop significant genitourinary symptoms as a result of adjuvant endocrine therapy. Declaration relating to disposition of project thesis/dissertation I hereby grant to the University of New South Wales or its agents the right to archive and to make available my thesis or dissertation in whole or in part in the University libraries in all forms of media, now or here after known, subject to the provisions of the Copyright Act 1968. I retain all property rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part of this thesis or dissertation . I also authorise University Micr films to use the 350 word abstract of my thesis in Dissertation Abstracts International (this is applicable to doctoral theses only) 1 ~.,.:_. ~ . J,.~ .. m. 16-o::!C The University recognises that there may be exceptional circumstances requiring restrictions on copying or cond ~ions on use. Requests for restriction for a period of up to 2 years must be made in writing. Requests for a longer period of restriction may be considered in exceptional circumstances and require the approval of the Dean of Graduate Research . FOR OFFICE USE DNLY Date of completion of requirements for Award: THIS SHEET IS TO BE GLUED TO THE INSIDE FRONT COVER OF THE THESIS ii iv “Often I think women who had breast cancer have very little opportunity to talk to people and a lot of the issues are very shaming so it is really important to offer them that chance.” ― Memorable quote from one of the participants in this research project [GT, Post, 06] v vi ABSTRACT The underlying hypothesis of this PhD is that the negative impact of adjuvant endocrine therapy on genitourinary symptoms in postmenopausal women with early breast cancer has been underestimated in clinical trials and that there are a myriad of genitourinary symptoms related to or exacerbated by endocrine therapies that are commonly not reported by women to their oncologists. These symptoms can be troublesome and may lead to noncompliance with treatment, especially if associated with other side effects. This issue has not been comprehensively addressed, resulting in uncertainty regarding the frequency and severity of genitourinary adverse effects associated with antiestrogens and their potential impact on quality of life (QoL). Furthermore, no studies have comprehensively and prospectively evaluated the full range of genitourinary symptoms from before therapy begins and over time. These symptoms include urinary frequency, urgency, incontinence, dysuria, prolapse among others. This study fills an important gap in the current literature and is clinically important as interventions could be used to better manage and treat many of these symptoms. A number of data collection methods and instruments were used in this project, selected on their ability to address the proposed research questions. Using a qualitative approach, with semi- structured interviews, Study I sought an in-depth insight of the genitourinary symptoms experienced by women with early breast cancer on antiestrogen therapy and an understanding on how symptoms impact on daily life and sexual function. Study II employed a prospective design, using carefully selected validated instruments, to measure the prevalence and severity of genitourinary symptoms in postmenopausal women with breast cancer (prior to adjuvant endocrine therapy) and documented the trajectory of symptoms over time. The impact of genitourinary symptoms on sexual function and QoL was also investigated. The study attempted to identify predictors for which women were more likely to develop significant genitourinary symptoms, and in particular, whether there is an identifiable sub-group of women at high-risk of developing severe genitourinary symptoms. This research project was conducted in the hope that the findings would inform clinical practice and lead to greater efforts to early recognition and appropriate management of postmenopausal women who develop significant genitourinary symptoms as a result of adjuvant endocrine therapy. vii viii ACKNOWLEDGEMENTS I have a lot of people to thank for their continued support and love over the past three years. Firstly I would like to acknowledge the brave and courageous women who were willing to give their time and share their very personal experiences with breast cancer and the impact on their lives. Your words and stories are illuminating and the experience has been humbling. Next I need to express my gratitude to Prof. Michael Friedlander, my supervisor, for mentoring me through this journey of research. Thank you for allowing me to stay close to my area of interest and your encouraging guidance throughout the process, especially when I thought I had no more strength to ‘hang in there’. Prof. Martha Hickey, thank you for sharing your deep knowledge and helping me to navigate the world of women’s needs. I would like to especially thank Dr Michelle Peate for guiding me through each and every step of this thesis, all the countless hours of technical and moral support, motivating and inspiring me. You are an encouraging and invaluable friend. I would like to acknowledge the support of the Breast Cancer Network Australia (BCNA) Consumer Representative, Ms Yvonne Shaw, for so much meaningful advice and input in this project. I would like to also thank Ms Sherin Jarvis, A/Prof. Craig Lewis, Dr. Marcus Carey and Prof. Richard Millard for the expertise that they contributed. On a more personal note, I would like to thank my parents, Miratan and Thais, for being so supportive of my career and giving me the will to chase my ambitions. I know that you are proud of me and that means so much. Thank you to my sister, Camila, you helped me reach my goal still smiling. One year ago, you and Ryan gave me the perfect gift, my little nephew William, who have brought