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Abstract

Objectives:

Many patients with hormone-receptor positive breast cancer undergo prolonged treatment. However, the long-term patient quality of life assessment has not been examined. Using community pharmacists’ assistance is one method for assessing long-term quality of life. Thus, this study aimed to understand the ongoing health-related quality of life and quality-adjusted life year among breast cancer patients so that community pharmacists may contribute to their pharmacotherapy.

Methods:

We conducted a prospective observational study with 22 breast cancer patients who had health-related quality of life at the initial measurement and 6 months later.

Results:

Regarding the health-related quality of life, quality-adjusted life year concerning all patients was 0.890 (95% confidence interval: 0.846–0.935). Quality-adjusted life year concerning those younger than 65 years was 0.907 (95% confidence interval: 0.841–0.973), and that for individuals older than 65 years was 0.874 (95% confidence interval: 0.804–0.943). The adjuvant chemotherapy group had a lower health-related quality of life at the initial measurement (0.887; 95% confidence interval: 0.833–0.941) but showed a higher quality of life 6 months later (0.951; 95% confidence interval: 0894–1.010). Quality-adjusted life year for individuals regarding adjuvant chemotherapy was 0.919 (95% confidence interval: 0.874–0.964). In contrast, the life-prolonged group had a higher health-related quality of life at the initial measurement, which was lower 6 months later.

Conclusions:

As a result of measuring quality of life using the EuroQol 5-dimensions-5-levels, this study revealed a decline in health-related quality of life in patients undergoing hormonal therapy for breast cancer. The study is expected to assist community pharmacists in managing outpatients.

Keywords

Quality of life quality-adjusted life years breast cancer

Introduction

Breast cancer is the most common of all site-specific cancers in Japan, as well as globally. The treatment of breast cancer includes surgery, radiation therapy, and chemotherapy. In Japan, 70% of breast cancer patients have positive hormone receptors. Breast cancer growth is known to be influenced by hormones such as estrogen and progesterone. Therefore, luteinizing hormone-releasing hormone agonists, aromatase inhibitors, and anti-estrogen drugs that inhibit hormone receptor function are used as treatments. These treatment methods include oral medication and injections once every few months. Most patients choose to be treated on an outpatient basis, and many patients with hormone-receptor-positive breast cancer are treated for a prolonged period, including 5–10 years of adjuvant hormonal therapy.

In previous studies, such as phase III clinical trials, health-related quality of life (QOL) has been measured to assess the status of cancer patients, which can be used regardless of the disease or drug. It has been reported that there are two ways to measure health-related QOL, namely profile-type and utility-value scales.¹ There are two methods of calculating the utility value: direct and indirect measurement. Between 1987 and 1991, an interdisciplinary five-country consortium created an indirect measurement instrument, which is the EuroQol 5-dimensions-3-levels (EQ-5D-3L) scale.² The EuroQol-5-dimensions-5-levels (EQ-5D-5L) tool was created after the EQ-5D-3L. Mobility, personal care, usual activities, pain/discomfort, and anxiety/depression are the five dimensions measured by the EQ-5Q-DL. The following is a representation of the five levels assessed: (1) “no problems”; (2) “slight problems”; (3) “moderate problems”; (4) “severe problems”, and (5) “unable.” Participant responses are converted into a single preference-based score (i.e., a utility value), based on the Japanese value set, where 0 represents death and 1 represents complete health. Both the EQ-5D-3L and EQ-5D-5L are frequently used, particularly in Europe. Quality-adjusted life year (QALY) can be calculated from health-related QOL based on the EQ-5D-5L and life years.³ For the Japanese version of the EQ-5D-5L, a scoring system has been developed, enabling the EQ-5D-5L to be used in Japan to assess health-related QOL.^4–6 Phase III clinical trials can be used to assess health-related QOL. The outcomes of assessing outpatient health-related QOL have already been reported by Japanese clinical hospital pharmacists.^7–9 However, long-term patient QOL assessment has not been performed in Japan. Using community pharmacists’ assistance represents one method of assessing long-term QOL. Few reports exist on continuous health-related QOL for patients receiving hormonal therapy for breast cancer for over 6 months during outpatient treatment. The results of a study on QOL in breast cancer patients suggested that efforts should be made to increase the visibility of health-related QOL results for all stakeholders to make the data more easily available to clinicians and patients.¹⁰ If we can understand the ongoing health-related QOL and its variability, it may be possible to recognize physical and mental changes in patients at an early stage. As a result, community pharmacists may contribute to an effective pharmacotherapy for breast cancer patients. Indeed, a past study showed that the incorporation of clinical pharmacist services helped to improve the QALY and decrease adverse drug reactions, reflecting a positive impact on patient care.¹¹ In addition, oncology pharmacists helped in enhancing QALY for individuals with breast cancer based on humanistic outcomes.¹²

We thus aimed to conduct a prospective observational study between October 2020 and March 2022 at 29 community pharmacies and 71 pharmacists in 12 regions and cities in Japan.¹³ In particular, the health-related QOL and QALY of patients undergoing hormonal therapy for breast cancer were assessed.

Methods

Study design

A prospective observational study was undertaken at 29 community pharmacies with 71 pharmacists in 12 regions and cities (Tokyo, Kanagawa, Saitama, Chiba, Gunma, Tochigi, Hokkaido, Aichi, Osaka, Kagawa, Tokushima, and Fukuoka) in Japan from October 2020 to March 2022. The health-related QOL of outpatients was measured by 71 community pharmacists using the EQ-5D-5L questionnaire. The EQ-5D-5L questionnaire has been validated for Japanese people living in Japan.⁵

The inclusion criteria were as follows:

At the time of obtaining consent, the age of the participant had to be at least 20 years;

Patients with written consent to participate in the study; and

Patients who have been issued a prescription by a healthcare provider.

The exclusion criteria were as follows:

Patients’ requests for cancellation

The study was interrupted due to the conditions of the research subjects (moving, changing doctor/hospital, busy, unfollowable).

It was judged that evaluation was not possible due to a serious deviation from protocol.

Patients were judged to be unsuitable for this study.

Outpatients administered with high-risk medications, such as anticancer medications, underwent this study after providing written informed consent. Community pharmacists validated the participants’ health-related QOL regardless of whether the prescription was a first, second, or recurrent one. Outpatients were enrolled in the study irrespective of whether they had already begun treatment. In this study, the community pharmacists did not review the medical records written by the physicians directly; they collected information from the medication history, and patients, and by questioning a prescribing physician instead.

The primary objective of this study was to clarify the health-related QOL and its variability in patients with breast cancer with positive hormone receptors. An observation period of 6 months or more was provided from the start of the registration. Health-related QOL was measured four or more times during the observation period.

Measurement of the health-related QOL using EQ-5D-5L

Outpatients were asked to respond to the questionnaire during their waiting time. A paper form of the Japanese version of the EQ-5D-5L questionnaire was used.^4–6 Community pharmacists administered the questionnaires, and the participants were not remunerated for their participation. The community pharmacist who received the EQ-5D-5L questionnaires recorded the answers together with pertinent medical information, such as age, sex, medications used, and medical history. A EuroQol group (Rotterdam, The Netherlands) license was obtained for research purposes.

Statistical analysis

Categorical variables were compared using the chi-square test or Fisher’s exact test. We calculated the average and 95% confidence interval (CI) for the two groups. The JMP® Pro 15.0.0 software (SAS Institute Inc., Cary, NC, USA) was used for statistical analysis, and the significance level was set at p < 0.05. There were no missing data for the evaluation objectives.

Results

Patient characteristics

Patients who exhibited no interrupted missing QOL values over a 6-month period were deemed eligible for inclusion in the study. A total of 929 patients were included. Of these, 39 were hormone receptor-positive breast cancer patients. Of these, 22 patients with hormone receptor-positive breast cancer had health-related QOL measured for 6 months. This implies that the follow-up duration has a mean of 6 months from the initial assessment of QOL. There were no missing data for the 22 eligible patients. There was no a priori estimation of the required sample size for breast cancer patients.

Table 1 summarizes the study population’s characteristics. During the survey, 22 outpatients with breast cancer undergoing hormone therapy were enrolled (average age, 62.7 years). The youngest breast cancer patient was 43 years old, and there were no adolescents or young adults. All 22 outpatients were taking 2.7 drugs on average. Furthermore, 19 patients were classified as having a performance status (PS) of 0, while 3 had a PS of 1. The purpose of hormone therapy was as follows: Adjuvant therapy had seven patients; neoadjuvant therapy, one patient; prolonged, nine patients; and not known, five patients. Regimens were as follows: Tamoxifen had eight patients; toremifene, two patients; anastrozole, three patients; letrozole, two patients; exemestane, one patient; palbociclib + letrozole, four patients; and abemaciclib + letrozole, two patients.

Table 1.

Patient characteristics.

Characteristics	n = 22
Age in years
Average	62.7
Median (range)	63 (43–86)
Sex
Male	0
Female	22
Family structure
Living with others	6
Living alone	7
Not known	9
Number of drugs
Average	2.7
Median (range)	2 (0–9)
PS
0	19
1	3
Purpose of hormone therapy
Adjuvant therapy	7
Neoadjuvant therapy	1
Life-prolonged	9
Not known	5
Regimens
Tamoxifen	8
Tremifene	2
Anastrozole	3
Letrozole	2
Exemestane	1
Palbociclib + letrozole	4
Abemaciclib + letrozole	2

PS, performance status.

Health-related QOL and QALY

Table 2 presents the health-related QOL and QALY for each outpatient. Health-related QOL concerning all patients was 0.901 (95% CI: 0.858–0.943) in the initial measurement. Health-related QOL at 6 months was 0.880 (0.807–0.953). QALY concerning all patients was 0.890 (0.846–0.935).

Table 2.

Health-related QOL and QALY.

	n (%)	Initial measurement (average (95% CI))	After 6 months (average (95% CI])	Quality-adjusted life year¹ (average (95% CI])	p Value²
All patients	22	0.901 (0.858–0.943)	0.880 (0.807–0.953)	0.890 (0.846–0.935)
Age stratification (years)
<65	11 (50.0%)	0.934 (0.890–0.978)	0.880 (0.744–1.016)	0.907 (0.841–0.973)	0.73
⩾65	11 (50.0%)	0.867 (0.792–0.942)	0.880 (0.795–0.965)	0.874 (0.804–0.943)	0.73
PS
0	19 (86.4%)	0.921 (0.881–0.962)	0.895 (0.816–0.974)	0.908 (0.864–0.952)	0.02
1	3 (13.6%)	0.770 (0.648–0.893)	0.784 (0.365–1.203)	0.777 (0.546–1.010)	0.02
Purpose of hormone therapy (excluding not known and neoadjuvant chemotherapy)
Adjuvant chemotherapy	7 (31.8%)	0.887 (0.833–0.941)	0.951 (0894–1.010)	0.919 (0.874–0.964)	0.72
Life-prolonged	9 (40.9%)	0.924 (0.847–1.001)	0.853 (0.687–1.020)	0.889 (0.805–0.972)	0.72

Calculated by approximation from the initial measurement to 6 months later

Results of χ² tests or Fisher’s exact test compared between groups.

CI, confidence interval; PS, performance status; QOL, quality of life; QALY, quality-adjusted life year.

Health-related QOL was higher in the younger group than in the 65-year-old group. Health-related QOL was higher in the PS 0 group than in the PS 1 group.

The adjuvant chemotherapy group had a lower health-related QOL at the initial measurement, but a higher health-related QOL 6 months later. Contrarily, the prolonged group had a higher health-related QOL at the initial measurement, but a lower health-related QOL 6 months later.

Values using 5-dimensions-5-levels

Table 3 presents the values using 5-dimensions-5-levels. Pain/discomfort was not significant. However, pain/discomfort affected health-related QOL in the participants.

Table 3.

Values using 5-dimensions-5-levels.

n = 22	Initial measurement n (%)	After 6 months n (%)	p Value*
Mobility
No problems	17 (77.3)	18 (81.8)	0.549
Sight problems	2 (9.1)	3 (13.6)
Moderate problems	3 (13.6)	1 (4.5)
Severe problems	0	0
Unable/extreme problems	0	0
Self-care
No problems	22 (100)	19 (86.4)	Not significant
Sight problems	0	1 (4.5)
Moderate problems	0	1 (4.5)
Severe problems	0	1 (4.5)
Unable/extreme problems	0	0
Usual activities
No problems	19 (86.4)	18 (81.8)	0.856
Sight problems	2 (13.6)	2 (9.1)
Moderate problems	0	1 (4.5)
Severe problems	0	1 (4.5)
Unable/extreme problems	0	0
Pain/discomfort
No problems	14 (63.6)	12 (54.5)	0.08
Sight problems	7 (31.8)	7 (31.8)
Moderate problems	1 (4.5)	2 (9.1)
Severe problems	0	1 (4.5)
Unable/extreme problems	0	0
Anxiety/depression
No problems	17 (77.3)	18 (81.8)	0.92
Sight problems	4 (18.2)	3 (13.6)
Moderate problems	1 (4.5)	0
Severe problems	0	1 (4.5)
Unable/extreme problems	0	0

Results of χ² tests or Fisher’s exact test compared between groups.

Calculation of QALY

QALY is demonstrated in Figure 1. It was calculated by multiplying health-related QOL and survival times. We calculated health-related QOL multiplied by the 6-month survival time for 22 breast cancer patients with positive hormone receptors. We connected the measured points and calculated the area under the curve.

Figure 1.

Calculation of QALY.

Discussion

Health-related QOL relating to the five dimensions of mobility, personal care, usual activities, pain/discomfort, and anxiety/depression were assessed for community pharmacy outpatients taking anticancer drugs for breast cancer with positive hormone receptors. This evaluation was related to the effects of each factor on the participants’ health-related QOL. Subsequently, we calculated their QALY. According to our knowledge, no previous study has reported such findings for patients with positive-hormone receptor breast cancer.

In this study, health-related QOL for those who received adjuvant chemotherapy was 0.887. After 6 months, health-related QOL increased to 0.951. Patients with hormone receptor+/early breast cancer who received adjuvant chemotherapy reported a QOL of 0.868.¹⁴ In this study, adjuvant chemotherapy increased health-related QOL over time.

However, when focusing on the health-related QOL in the 65 years or younger age group, health-related QOL declined 6 months later. A decreased QOL in some younger patients undergoing adjuvant chemotherapy has been reported as well.¹⁵ Although no details can be specified from the results, this may have been due to adverse events such as menopause and menstrual abnormalities specific to younger patients. Breast cancer patients receiving treatment for life-prolonging purposes were shown to have a lower QOL 6 months later. These patients might be anxious about their illnesses and spending the rest of their lives. Contrarily, the QOL of patients treated to prevent recurrence increased 6 months later. This was expected, as the hormone therapy was more acceptable than in the initial days. Using the EQ-5D-5L, this study revealed that health-related QOL declined in patients undergoing hormonal therapy for breast cancer. The study is expected to aid community pharmacists in managing outpatients. In support of this study, reports indicate that receiving long-term social support (after treatment has begun) is important for patients receiving hormone therapy.¹⁶ Indeed, oncology pharmacists’ interventions for patients with breast cancer were reported to improve QALY.¹²

Nevertheless, this study has some limitations. First, the participants in this prospective observational study were outpatients who gave their consent to participate; therefore, collaborating patients with a good health-related QOL were likely enrolled, which may have resulted in selection bias. In addition, it is possible that patients who communicate with pharmacists more easily were chosen, which could have added to the selection bias. Second, the period of drug administration was not taken into account in this study; some patients may have recently begun taking an anticancer medicine for breast cancer, while others may have been taking an anticancer drug for a considerable amount of time. The duration of treatment may have had an impact on the health-related QOL. The psychological stage that cancer patients were in at the time of the questionnaire (denial, anger, bargaining, depression, and acceptance) may have had an impact on their answers. Although treatment duration was not investigated in this study, it may be an important factor. Third, the small number of patients (i.e., n = 22) selected in this study was also a limitation. This number of cases is insufficient to utilize for health technology assessment, which investigates the costs of using medical technologies and the health benefits produced. Previous studies have been conducted for approximately over 100 patients.^11,12 Therefore, it is necessary to increase the number of cases and examine them using multivariate analysis.

This exploratory study was the first study wherein community pharmacists determined the health-related QOL of outpatients taking anticancer drugs for breast cancer with positive hormone receptors. In the future, we will measure health-related QOL by anticancer drugs with a therapeutic purpose to obtain more accurate values and suggest ways to prevent the decline in health-related QOL.

Conclusion

This study used the EQ-5D-5L to reveal a decline in health-related QOL in patients undergoing hormonal therapy for breast cancer. The findings are expected to be beneficial to community pharmacists in managing outpatients with similar issues.

Supplemental Material

sj-docx-1-smo-10.1177_20503121231164491 – Supplemental material for Community pharmacists’ measurement of health-related quality of life for breast cancer with positive hormone receptors: A prospective observational study

Supplemental material, sj-docx-1-smo-10.1177_20503121231164491 for Community pharmacists’ measurement of health-related quality of life for breast cancer with positive hormone receptors: A prospective observational study by Takenori Ichimura, Hisanaga Nomura and Hisanori Shimizu in SAGE Open Medicine

Footnotes

Acknowledgements

We would like to acknowledge the investigators among community pharmacists. We would also like to thank Editage () for English language editing. We are also thankful to the EuroQoL group (Rotterdam, the Netherlands) for permission to use the paper form of the Japanese EQ-5D-5L self-report questionnaire v1.1.

Authors’ contributions

Conception and design of the study: Takenori Ichimura, Hisanaga Nomura, and Hisanori Shimizu; analysis and interpretation of the data: Takenori Ichimura and Hisanaga Nomura; drafting of the manuscript: Takenori Ichimura and Hisanaga Nomura; critical revision of the manuscript for important intellectual content: Takenori Ichimura, Hisanaga Nomura, and Hisanori Shimizu. All authors read and approved the final manuscript for publication.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors received financial support from the Ministry of Health, Labor and Welfare (H30-Gantaisaku-Ippan-007), Health Labor Sciences Research Grant, and Geriatric Oncology Guideline-establishing (GOGGLE) Study Group, which is a public institution in Japan.

Ethical approval

The study was performed in accordance with the Declaration of Helsinki and was approved by the Ethics Committees of the School of Nursing and Rehabilitation Sciences, Showa University (Approval number: 528), and other participating centers.

Informed consent

Written informed consent was obtained from all subjects before the study.

Trial registration

Not applicable.

ORCID iD

Takenori Ichimura

Supplemental material

Supplemental material for this article is available online.

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