Qualitative cross-cultural exploration of breast symptoms and impacts associated with hormonal treatments for menopausal symptoms to inform the development of new patient-reported measurement tools
Introduction
The current standard of care for the treatment of menopausal symptoms in postmenopausal women with a uterus is estrogen plus progestin therapies (EPT). While highly efficacious for preventing osteoporosis and treating vasomotor symptoms and vulvar/vaginal atrophy, EPT is also associated with bothersome side effects, such as vaginal spotting/bleeding and breast tenderness [1]. Breast tenderness is reported to occur significantly more frequently in women receiving combined EPT compared with placebo or conjunctive estrogens alone [2] and is associated with increased mammographic breast density [3] and subsequent breast cancer risk [2]. In randomized clinical trials, incidence of breast tenderness in postmenopausal women after initiation of EPT has been reported to range from approximately 9% to 16% [1], [2], [4], [5], [6]. Many women who experience breast tenderness discontinue treatment, potentially due to concerns or fears of breast cancer [7] following publication of such risk in findings from the Women's Health Initiative trials [8]. Thus, there is evidence to suggest that side effects, specifically related to the breast, and worries about risks, especially breast cancer, associated with EPT can lead to non-adherence or discontinuation of treatment, suggesting there is an unmet need for treatments of menopausal symptoms with less burdensome side effects. To better evaluate the clinical benefit of novel therapies relative to existing therapies, validated patient-reported outcome (PRO) measures are required to assess not only the efficacy of the treatment (in terms of reduction in symptoms), but also any benefits in terms of tolerability.
Following a review of the literature, the Breast Sensitivity Questionnaire (BSQ) was identified as measuring hormone therapy (HT)-related breast symptoms and their impact on health-related quality of life (HRQL). Containing 11 symptom items and 10 impact items, the BSQ was developed in line with regulatory guidance, and involved patient focus groups [9]. However, use of a one-week recall period to assess symptoms that are likely to have daily variation was not considered appropriate because of potential recall bias. Moreover, changing the recall period to 24 hours for the daily assessment of 11 symptom items would represent a significant burden on patients and increase the risk of missing data. Thus there was a need to develop a new breast symptom assessment that included a 24 hour recall period and could be feasibly completed as a daily diary.
Additionally, focus groups conducted to inform the BSQ's development were only conducted in the United States (US); given the cultural differences in the experience of menopausal symptoms and impacts [10], [11], the BSQ's content validity for women outside of the US was unknown. Thus further evaluation of the BSQ was conducted in culturally diverse countries (Italy, Mexico and China) to evaluate the appropriateness of the BSQ impact items as a potential measure of EPT-related breast symptom impact, alongside qualitative concept elicitation interviews to support the development of the new daily breast symptom diary.
Section snippets
Overview of study
This paper summarizes findings from a three stage qualitative study (Fig. 1) to explore the two most common side effects experienced by postmenopausal women across different cultures taking EPT: vaginal bleeding/spotting and breast sensations (specifically breast pain/tenderness). This paper reports findings for breast sensations; findings on the symptoms and impacts of vaginal bleeding/spotting as a side effect of EPT are published in a separate companion paper [12]. In Stage 1, open-ended,
Demographic and clinical characteristics
A diverse sample of postmenopausal women on EPT was recruited for both interview stages (Table 1). In total, 79 women participated in the study. The US sample included good representation of non-Caucasian race/ethnicities in both stages. In China and Italy it is considered culturally inappropriate to ask about ethnicity, hence no ethnicity data was collected.
During screening, women reported the severity of EPT side effects they had experienced (Table 2). The mean rating of worst breast symptoms
Discussion
Open-ended, exploratory qualitative interviews in four different countries enabled in-depth exploration of postmenopausal women's experiences of the breast symptoms associated with EPT and associated impact on HRQL. The results provide evidence that breast sensations, specifically pain/tenderness, feeling swollen and sensitivity to contact, are commonly experienced and burdensome side effects of EPT for postmenopausal women. Moreover, these sensations were reported and described in a manner
Conclusions
Postmenopausal women in the US, China, Mexico and Italy reported experiencing breast sensations as a result of EPT. Rigorous qualitative research provided evidence that these side effects are frequently experienced and have a detrimental impact on postmenopausal women's HRQL in terms of their emotional well-being, choice of clothing, ability to move freely, activities with family and friends and sexual activity. Using the qualitative content generated, two new measures were developed to better
Contributors
Lucy Abraham participated in the design, methods, qualitative analysis, reviewing and contributing to manuscript. Louise Humphrey, Rob Arbuckle, Nicola Bonner, Steven Walmsley and Sophi Tatlock participated in the study design, data collection, analysis, key meetings, discussions and write up of the study. Lorraine Dennerstein, James A. Simon and Sebastian Mirkin participated in the study design, data analysis, writing and revision of the manuscript. Tara Symonds participated in the design,
Competing interest
This work was sponsored by Pfizer. Louise Humphrey, Rob Arbuckle, Nicola Bonner, Steven Walmsley and Sophi Tatlock were employees of Adelphi Values, a consultancy paid by Pfizer to perform the study and develop the manuscript. Lorraine Dennerstein and James Simon received payment as consultants for taking part in the research study, but not for involvement in the writing of the paper.
Funding
The study was funded by Pfizer Pharmaceuticals and was conducted by Adelphi Values. Rob Arbuckle, Louise Humphrey, Steven Walmsley, Nicola Bonner and Sophi Tatlock are consultants and employees of Adelphi Values (or were at the time the research was conducted). Lucy Abraham, Tara Symonds and Sebastian Mirkin are employees of Pfizer Pharmaceuticals (or were at the time the research was conducted). Lorraine Dennerstein and James A. Simon were engaged as key opinion leaders to provide clinical
Ethical approval
The study was conducted in accordance with the Declaration of Helsinki and was approved by an Independent Review Board (IRB) in the US for Stages 1 and 2. In Stage 1, ethical approval was also obtained in Italy and Mexico; ethical approval for a study of this nature was not required in China. Written informed consent was obtained from all participants prior to data collection.
Acknowledgements
In addition to the authors, the following linguists and interviewers also performed some aspects of the research: Bin Shi, Market Research and Consulting Director, Chinese Interviewer. Daniela Carboni, Consultant Psychologist, Italian Interviewer. Gaudalupe Riego, Mexican Interviewer. Felicitas Colombo, Director of Datos and Estragias, Mexican Interviewer.
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Cited by (0)
- 1
Now with Abacus International, Portland St, Manchester M1 3LF, UK.
- 2
Now with TherapeuticsMD, Boca Raton, FL 33487, USA.
- 3
Now with University of Western Sydney, Sydney, Australia.
- 4
Now with Clinical Outcomes Solutions, Folkestone, Kent, UK.