Health-related quality of life in Asian patients with breast cancer: a systematic review.

OBJECTIVE: To summarise the evidence on determinants of health-related quality of life (HRQL) in Asian patients with breast cancer.
DESIGN: Systematic review conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and registered with PROSPERO (CRD42015032468).
METHODS: According to the PRISMA guidelines, databases of MEDLINE (PubMed), Embase and PsycINFO were systematically searched using the following terms and synonyms: breast cancer, quality of life and Asia. Articles reporting on HRQL using EORTC-QLQ-C30, EORTC-QLQ-BR23, FACT-G and FACT-B questionnaires in Asian patients with breast cancer were eligible for inclusion. The methodological quality of each article was assessed using the quality assessment scale for cross-sectional studies or the Newcastle-Ottawa Quality Assessment Scale for cohort studies.
RESULTS: Fifty-seven articles were selected for this qualitative synthesis, of which 43 (75%) were cross-sectional and 14 (25%) were longitudinal studies. Over 75 different determinants of HRQL were studied with either the EORTC or FACT questionnaires. Patients with comorbidities, treated with chemotherapy, with less social support and with more unmet needs have poorer HRQL. HRQL improves over time. Discordant results in studies were found in the association of age, marital status, household income, type of surgery, radiotherapy and hormone therapy and unmet sexuality needs with poor global health status or overall well-being.
CONCLUSIONS: In Asia, patients with breast cancer, in particular those with other comorbidities and those treated with chemotherapy, with less social support and with more unmet needs, have poorer HRQL. Appropriate social support and meeting the needs of patients may improve patients' HRQL. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

This systematic review included over 75 determinants of health-related quality of life in Asian patients with breast cancer.

Studies included had varying patient selection criteria, which may be the reason for discordance results in certain determinants.

We were not able to conduct a meta-analysis to provide a sense of the level of association, as the choice of statistical analysis varied across studies.

Introduction

In Asia, the number of breast cancer survivors is increasing, with 5-year survival rates exceeding 90% in early-stage disease.1–7 This is due to improved breast cancer treatments and early detection.8–11 As such, the number of survivors is increasing rapidly. Patient-reported outcomes on health-related quality of life (HRQL), such as physical and emotional functioning and treatment-related side effects including pain, nausea and fatigue, are increasingly important as it effects many breast cancer survivors.

Impaired HRQL is best represented as gap between an individual’s actual functional level and his or her ideal standard.12 Studies from the West reported reduced physical and emotional functioning in patients with breast cancer shortly after treatment.13–16 Breast-conserving surgery as compared with mastectomy, axillary clearance, radiotherapy and chemotherapy were associated with higher level of pain.17 Furthermore, younger patients with breast cancer reported better physical functioning but more impaired emotional functioning compared with older breast cancer patients.13–16 HRQL improves until up to 6–10 years following breast cancer diagnosis.18 In Asian population, determinants of HRQL are increasingly being studied.

So far, mainly studies from Western developed countries investigated HRQL following breast cancer.14–16 19 20 However, cultural and habitual practices such as the use of traditional medicine may limit the generalisability of results from HRQL studies in Caucasian patients with breast cancer to Asian patients with breast cancer.21 22 Drug tolerance is different across populations; paclitaxel in the Japanese population is less well tolerated than the USA.23 24 Furthermore, Asian patients with breast cancer tend to be younger at diagnosis and have more advanced stages at diagnosis than Caucasians.25 Even within Asian ethnicities, Malay patients with breast cancer were found to respond better to tamoxifen therapy than Chinese or Indian patients.26 Better understanding of risk factors for poorer HRQL in Asian patients with breast cancer would allow for targeted interventions.

As an overview of the literature on HRQL determinants in Asian breast cancer survivors is currently lacking, this review systematically summarises determinants of HRQL in breast cancer survivors from Eastern, South Central and Southeast Asia.

Methods

This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations and was registered with PROSPERO (CRD42015032468).27

Search strategy

Databases of MEDLINE (PubMed), Embase and PsycINFO were systematically searched, using the terms ‘breast cancer’, ‘quality of life’ and ‘Asia’ in the search strategy (table 1). The systematic search was last updated on 12 July 2017.

Table 1

Search strategy from MEDLINE filters: publication date from 1 January 2000 to 16 February 2016; English

	Search strategy (MEDLINE)
#1	“Breast Neoplasms”[MeSH] OR ((breast[Title/Abstract] OR mamma[Title/Abstract] OR mammary[Title/Abstract]) AND (carcinoma[Title/Abstract] OR carcinomas[Title/Abstract] OR carcinomatosis[Title/Abstract] OR tumor[Title/Abstract] OR tumors[Title/Abstract]) OR tumour[Title/Abstract] OR tumours[Title/Abstract] OR neoplasma[Title/Abstract] OR neoplasms[Title/Abstract]) OR cancer[Title/Abstract]) OR cancers[Title/Abstract]))
#2	“quality of life”[MeSH Terms] OR “quality of life”[Title/Abstract] OR hrHRQL[Title/Abstract] OR HRQL[Title/Abstract] OR hrql[Title/Abstract] OR “Functional Assessment of Cancer Therapy”[Title/Abstract] OR “FACT B”[Title/Abstract] OR “FACT-B”[Title/Abstract] OR “FACT G”[Title/Abstract] OR “FACT-G”[Title/Abstract] OR “European Organization for Research and Treatment of Cancer” OR “EORTC QLQ C30”[Title/Abstract] OR “EORTC”[Title/Abstract] OR “EORTC-QLQ-C30” [Title/Abstract]) OR “EORTC QLQ BR23”[Title/Abstract] OR “EORTC-QLQ-BR23”[Title/Abstract]
#3	“Asia, Southeastern”[Mesh] OR “India”[Mesh] OR ‘Far East’(Mesh) OR “Southeast asia” OR “South eastern asia” OR “South central” OR China OR Chine* OR Hong Kong OR Hong Kong* OR Macau OR Tibet OR Tibet* OR Japan OR Japan* OR Korea OR Korea* OR Mongolia OR Mongoli* OR Taiwan OR Taiwan* OR India OR India* OR Brunei OR Brunei* OR Indonesia OR Indonesia* OR Lao OR Lao* OR Malaysia OR Malay* OR Myanmar OR Burmese OR Philippin* OR Singapore OR Singapore* OR Thailand OR Thai* OR Timor-Leste OR Timor* OR Vietnam OR Vietnam*
#4	#1 AND #2 AND #3

Inclusion criteria

Studies were included based on the following criteria: (1) the study population was on women diagnosed with breast cancer living in Eastern Asia, South Central Asia or Southeast Asia; (2) the study was on demographics, clinical, treatments or other determinants of HRQL; (3) the study measured quality of life using European Organization for Research and Treatment of Cancer – Quality of Life Questionnaire, Breast cancer module, EORTC-QLQ-C30, (with or without the breast cancer module, EORTC-QLQ-BR23), or Functional Assessment of Cancer Therapy – General (FACT-G) or Functional Assessment of Cancer Therapy – Breast (FACT-B) questionnaires; (4) the outcome was HRQL measured quality of life using EORTC-QLQ-C30 (with or without EORTC-QLQ-BR23), or FACT-G or FACT-B questionnaires; and (5) the study design was either cross-sectional or observational longitudinal studies. Studies published before 2000, in language other than English, systematic reviews, meta-analyses, pilot studies and studies with qualitative analyses, were not included in the current review.

Data extraction

After removal of duplicates, all titles and abstracts of the remained retrieved articles were screened. Full-text articles of potentially relevant papers were assessed for eligibility by two authors independently (PJH and SAMG). Disagreement was resolved through consensus. Data extraction was performed by two authors independently (PJH and SAMG). The following determinants were collected for each study: (1) study characteristics (year and country of publication, study design, sample size, response, median follow-up and period), (2) demographics of the study population (age, ethnicity and time since diagnosis), (3) tumour characteristics (invasive or in situ and stage) and (4) past and current treatment.

Outcome extraction included HRQL, as measured by the global health status of the EORTC-QLQ-C30 and overall well-being subscales of FACT-G or FACT-B. The EORTC-QLQ-C3028–31 and FACT-G and FACT-B32–34 are validated in different populations in different languages. Other domains of the EORTC-QLQ-C30, physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, fatigue, pain, dyspnoea, insomnia, constipation, diarrhoea and financial difficulty were extracted where available. The EORTC-QLQ-BR23, an additional breast cancer module, assesses areas that are specific to patients with breast cancer: body image, sexual functioning, sexual enjoyment, future perspectives, systemic therapy side effects, breast symptoms and arm symptoms. Similarly, determinants of other domains of FACT-G, physical well-being, social well-being, emotional well-being and functional well-being were extracted. The FACT-B, an extended version of the FACT-G, has an additional breast cancer subscale.

Quality assessment

Critical appraisal was performed using the quality assessment scale for cross-sectional studies,35 and an adapted version of Newcastle-Ottawa Quality Assessment Scale for cohort studies.36 The maximum score attainable was 8 for each cross-sectional study and 6 for each longitudinal study. Four items on sample selection, one on comparability and three on outcome measurement, were assessed for cross-sectional studies (online supplementary table 1). Two items on sample selection, one on comparability (score of 0–2) and two on outcome measurement, were assessed for cohort studies (online supplementary table 2). Meeting all criteria in the category would confer a high score in the category. Except for the comparability criterion of cross-sectional study, studies that meet <50% of the criteria would be considered as having a low score.

Patient and public involvement

Patients and public were not involved in the development of the research question, choice of outcome measures or the design and conduct of this systematic review.

Results

The systematic search yielded a total of 3160 records including 2549 unique articles that were screened for title and abstract using the predefined inclusion and exclusion criteria (figure 1). After screening the full text of 182 articles, 126 articles did not meet our inclusion and exclusion criteria (figure 1). Cross-referencing identified one additional article. In total, 57 articles were included in the systematic review (43 cross-sectional studies and 14 longitudinal studies), including 24 538 women diagnosed with breast cancer from the following seven countries: Korea (n=17), China (n=14), India (n=8), Taiwan (n=6), Malaysia (n=6), Japan (n=5) and Thailand (n=1) (table 2).

Figure 1

Flow diagram of study selection. HRQL, health-related quality of life.

Table 2

Description of identified studies

Author, year	Study design	Questionnaire	Ethnicity	Sample size (response rate, %)	Period of recruitment	Time of questionnaire assessment	Age, mean (SD)	Tumour stage	Quality assessments (max 6 or 8)^
Noh et al, 200872	Cross-sectional	C30	Japanese	2085 (26)	2004	4.2 (1.3–11.9) years since surgery*	57.8% were aged ≥50 years	In situ, I–IV	7
Akechi et al, 201070	Cross-sectional	C30	Japanese	408 (97)	2006–2007	2.8 (3.7) years since diagnosis	56.1 (12.1)	In situ, I–IV	6
Edib et al, 201648	Cross-sectional	C30	Malay, Chinese and Indian	117 (80)	2014	42.7% were 1–2 years, 42.7% 2–5 years, 14.6% were >5 years since diagnosis	13.7% were aged <40 years, 24.8% were aged 40–49, 61.6% were aged ≥50 years	In situ, I–IV	6
Kim et al, 201291	Cross-sectional	C304	Korean	136 (83)	2010–2011	2.6 (2.1) years since diagnosis	50 (7.8)	In situ, I–III	6
Huang et al, 201750	Cross-sectional	C30	Chinese	252	–	5.6 (2.6) years since diagnosis	54.5 (8.3) age at time survey	I–IV	4
Liang et al, 201654	Cross-sectional	C303	Chinese	201	–	4.2 (5.4) years since diagnosis	53.6 (9.5)	In situ, I–IV	3
Jang et al, 201392	Longitudinal	C303	Koreans	284 (81)	2008–2009	Within 5 days of surgery	49.8 (9.5)	In situ, I–IV	5
Wani et al, 201239	Longitudinal	C30	Indian	81	–	During chemotherapy or radiotherapy	46.6 (10.2)	–	3
Yusuf et al, 201353	Cross-sectional	C30+BR23	Chinese, Malay (Malaysia)	79 (96)	2010–2011	Newly diagnosed before the start of treatment	Malay: 50.7 (95% CI 48.1 to 53.3) Chinese: 50.2 (95% CI 43.8 to 56.8)ᶣ	I–IV	6
Kim et al, 201561	Cross-sectional	C30+BR23	Korean	531 (61)	–	–	BCS: 48.4 (8.7), TM: 49.3 (7.5), TM-R: 43.5 (9.2)	In situ, I–III	6
Chui et al, 201521	Cross-sectional	C30+BR23	Chinese, Malay, Indian, other (Malaysia)	546 (89)	2012–2013	On chemotherapy	–	In situ, I–IV	6
Lee et al, 200767	Cross-sectional	C30+BR23	Korean	152	–	1.8 (0.5–10.7) years since recurrence*	65.8% were aged <50 years	I–III	6
Sun et al, 201462	Cross-sectional	C30+BR23	Korean	407 (80)	2011–2012	BCS: 4 (1.6), TM: 4.1 (1.8), TM-R: 4.7 (1.9)	BCS: 52.3 (8.5), TM: 51.9 (8.9), TM-R: 45.2 (7.5)	In situ, I–III	6
Okamura et al, 200593	Cross-sectional	C30+BR23	Japanese	59 (85)	2001–2002	–	53 (10)	All patients at first recurrence, with 98% stage IV	5
Huang et al, 201060	Cross-sectional	C30+BR23	Chinese (Taiwan)	130 (100)	2004–2007	Completed surgery or final course of chemotherapy for at least 9 months	BCS: 51.1 (22–78) TM: 55.1 (32–77)ᶣ	In situ, I–III	5
Kang et al, 201222	Cross-sectional	C30+BR23	Korean	399 (60)	2008–2009	CAM users: 2.7 (2.2), Non-CAM users: 2 (1.6) years since diagnosis	CAM users: 50.6 (9.4), non-CAM users: 50.6 (11.1)	In situ, I–IV	5
Park et al, 201258	Cross-sectional	C30+BR23	Korean	59 (30)	2007–2010	–	56.31 (94.5)	I–IV	5
Tang et al, 201673	Cross-sectional	C30+BR23	Chinese	6188	–	–	56.9 (9.0)	In situ, I–IV	5
Kang et al, 201794	Cross-sectional	C30+BR23	Korean	283 (81)	–	At least 1 year since diagnosis	48.5 (7.8) age at time of survey	In situ, I–III	5
Dubashi et al, 201059	Cross-sectional	C30+BR23	Indian	51 (51)	–	5 (2–11) years since diagnosisᶣ	35	I–III	4
Shin et al, 201795	Cross-sectional	C30+BR23	Korean	231	2012–2015	13.4% were 0.5–1 year, 74.5% 1–5 years, 11.7% ≥5 years since surgery	48.1 (8.4)	I–III	4
Chang et al, 201449	Cross-sectional	C30+BR23	Korean	126	2009	–	47.7 (8.1)	I–III	3
Sharma and Purkayastha, 201796	Cross-sectional	C30+BR23	Indian	60	2014–2016	On radiotherapy	Mean 47.6 (range 30–75)	II–III	2
Kao et al, 201546	Longitudinal	C30+BR23	Chinese (Taiwan)	408 (81)	2010–2012	Before surgery	52.2 (9.6)	In situ, I–IV	6
Munshi et al, 201038	Longitudinal	C30+BR23	Indian	255 (76)	–	During radiotherapy	–	In situ, I–III	5
Lee et al, 201178	Longitudinal	C30+BR23	Korean	299 (81)	2004–2006	Within days/weeks of diagnosis	46.6 (10)	I–IV	5
Shi et al, 201147	Longitudinal	C30+BR23	Chinese	132 (77)	2007–2008	Before surgery	BCS: 50.3 (8.6), TM: 53.84 (10.2), TM-R: 47.7 (8.2)	In situ, I–III	5
Ng et al, 201541	Longitudinal	C30+BR233	Chinese, Malay, Indian, other (Malaysia)	221	2011–2015	Newly diagnosed	55.1 (11.5)	In situ, I–IV	4
Munshi et al, 201297	Longitudinal	C30+BR23	Indian	188	–	During radiotherapy	–	In situ, I–III	3
Damodar et al, 201337	Longitudinal	C30+BR23	Indian	41	2011	During chemotherapy	46.1 (11.2)	–	3
Sultan et al, 201740	Longitudinal	C30+BR23	Indian	25 (76)	2014–2015	Newly diagnosed	Mean 40 (range: 28–65)	I	3
So et al, 2014†51	Cross-sectional	FACT-G	Chinese	163	2010–2011	1.2 (0.9–1.6) years since diagnosis*	51 (9.2)	In situ, I–IV	3
Wong and Fielding, 200756	Longitudinal	FACT-G	Chinese	249 (88)	–	–	48.4 (11.9)	In situ, I–IV	5
Yan et al, 201643	Cross-sectional	FACT-B	Chinese	1160 (64)	2013	15.0 (6.7) years since diagnosis	57.7 (11.5)	In situ, I–IV	7
Ohsumi et al, 200944	Cross-sectional	FACT-B	Japanese	93 (93)	2004–2005	7 (5–11) years since surgery*	58 (44–83) age at time of survey ᶣ	–	6
Park et al, 201142	Cross-sectional	FACT-B	Korean	1094 (88)	–	73.4% were ≤3 years since surgery	46.9 (8.8)	I–III	5
Park and Hwang, 201271	Cross-sectional	FACT-B	Korean	52 (94)	2007–2008	1.7 (1.8) years since recurrence	48.3 (8.3) age at recurrence	–	5
Thanarpan et al, 201598	Cross-sectional	FACT-B	Thai	127	2014–2014	–	51.9 (8.9)	In situ, I–III	5
He et al, 201263	Cross-sectional	FACT-B	Chinese	180 (90)	2000–2008	BCT: 5 (1.3–8.5), TM: 5.4 (1.3–9.6) years since diagnosis*	BCS: 44 (10), TM: 45 (9)	I–II	4
Hong-Li et al, 201455	Cross-sectional	FACT-B	Chinese	154	2008–2010	Group 1: 1 year (n=64), group 2: 2 years (n=48), group 3: 5 years since diagnosis (n=42)	Group 1: 47.4 (8.8), group 2: 43.3 (10.3), group 3: 59.1 (9.4)	I–III	4
Chang et al, 200799	Cross-sectional	FACT-B	Chinese (Taiwan)	235 (94)	–	3 (1–12) years since diagnosis*	49 (32–69)ᶣ	I–IV	4
Kim et al, 2013100	Cross-sectional	FACT-B	Korean	77	–	–	49.2 (7.7)	I–IV	4
So et al, 2013101†	Cross-sectional	FACT-B	Chinese	279 (80)	2007	–	–	In situ, I–IV	4
Zou et al, 201475	Cross-sectional	FACT-B	Chinese	156 (87)	–	–	47.7 (10.3)	–	4
Jiao-Mei et al, 201574	Cross-sectional	FACT-B	Chinese	93	2013–2013	5.6 (1.8) years since diagnosis	51.76 (88.9)	I–IV	4
Qiu et al, 2016102	Cross-sectional	FACT-B	Chinese	76 (76)	2014	52.97 months since diagnosis	Mean 45.8 (range 23–76) age at time of survey	–	4
Shin and Park, 201757	Cross-sectional	FACT-B	Korean	264 (94)	2014	56.1% were ≤1 year, 32.6% 1–5 years, 11.4% ≥5 years since diagnosis	4.2% were aged ≤39 years at time of survey, 29.9% 40–49, 53.8% 50%–59, 12.1% ≥60	?–III	4
So et al, 201145‡	Cross-sectional	FACT-B	Chinese	261	2006–2007	During chemotherapy or radiotherapy	21% were aged ≥60	In situ, I–IV	3
Park and Yoon, 201352§	Cross-sectional	FACT-B	Korean	200	–	During chemotherapy	45.6 (7.1)	I–IV	3
Pahlevan Sharif, 201776¶	Cross-sectional	FACT-B	Chinese, Malay, Indian, other	118 (93)	2016	2.9 (1.9) years since diagnosis	51.0 (9.4)	I–III	3
Sharif and Khanekharab, 201777¶	Cross-sectional	FACT-B	Chinese, Malay, Indian, other	130	–	3.0 (1.9) years since diagnosis	51.2 (9.3)	I–III	2
So et al, 2009103‡ **	Cross-sectional	FACT-B	Chinese	215 (75)	–	5.5 (3) years since diagnosis	51.65 (10.4)	I–IV	4
Pandey et al, 2005104††	Cross-sectional	FACT-B	Indian	504 (99)	–	–	47.6 (11)	I–IV	3
Cao et al, 2016105	Longitudinal	FACT-B	Chinese	486 (92)	2010–2013	Start hormone therapy	57.3 (range: 27–79)	–	6
Pandey et al, 200668	Longitudinal	FACT-B	Indian	254 (99)	2002–2003	Presurgery and postsurgery time points were used	45.6 (10.6)	?–IV	5
Taira et al, 201264	Longitudinal	FACT-B	Japanese	140	1998–2003	Less than 6 weeks since surgery	53 (24–77)	In situ, I–III	5
Gong et al, 201769	Cross-sectional	C30+FACT G	Chinese	3344 (65)	2013	8.5 (6.5) years since diagnosis	59.3 (7.9) age at time of survey	–	5

*Median (IQR).

†Same sample population.

‡Same sample population.

§Max score of 6 for longitudinal studies, while 8 for cross-sectional studies.

¶Same sample population.

**Significance of associations not reported.

††Direction of association not reported.

BR23, EORTC-QLQ-BR23; BCS, breast-conserving surgery; C30, EORTC-QLQ-C30; TM, mastectomy; TM-R, mastectomy with reconstruction.

Of the 43 studies with a cross-sectional design, none received the maximum score of the quality assessment (table 2). There were 22 articles with a low score for selection (score of 0–2) due to the use of convenience sampling and small (<300) sample size (online supplementary table 1). All cross-sectional studies described their study population, conferring a high score for comparability (figure 2). Reporting of outcome was an issue in cross-sectional studies: 20 studies did not report confidence intervals or standard errors and 27 had <70% response rate (online supplementary table 1). Nine of 14 longitudinal studies were of good quality having scores of 5–6 (max=6) (table 2). The remaining five studies of poorer quality with scores of 3 or 4, four did not have a representative sample of their target population,37–40 four had a follow-up of <70% but did not provide description of lost to follow-up and none controlled for additional determinants37–41 (online supplementary table 2).

Figure 2

Quality assessment using the quality assessment scale for cross-sectional studies or an adapted version of Newcastle-Ottawa Quality Assessment Scale for cohort studies. Selection was based on the representativeness of the study population or cohort. Comparability and outcome were based on method of determining and reporting exposure of interest and outcome, respectively.

Most determinants studied were consistent in the direction of association or were not associated with global health status and/or general well-being (table 3). In studies on global health status, marital status, household income, type of surgery, chemotherapy, radiotherapy and hormone therapy, conflicting results were found. Studies on general well-being, looking at time since diagnosis, age and unmet sexuality needs measured by short-form Supportive Care Needs Survey (SCNS) also reported conflicting results. Table 4 presents a summary of determinants which were found to be associated with global health status and/or overall well-being.

Table 3

Associations studied using EORTC-QLQ-C30/EORTC-QLQ-BR23 or FACT-G/FACT-B

First author, year of publication	QoL outcomes	Determinant	Type of association with QoL outcomes
Studies using the EORTC-QLQ-C30 questionnaire
Cross-sectional (n=5)
Noh, 200872*	Global health status and social functioning	Involved in decision making	Positive
		Reflection of own value to decision
	Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning	Experience of treatment toxicity	Negative
	Global health status, physical functioning, role functioning and social functioning	Hospitalisation with treatment toxicity	Negative
	Global health status, role functioning, emotional functioning, cognitive functioning and social functioning	Problem obtaining surgery	Negative
	–	Having regular follow-up	–
Akechi, 201070†	Global health status	Higher scores in the domains of SCNS: psychological, physical and daily living, sexuality, health system and information, care and support	Negative
Edib, 201648†	Global health status	Time since diagnosis (<2, 2–5 and >5 years)	Positive
		Ethnicity (Malay vs Chinese vs Indian)
		Higher household income (<RM2000, RM2000–RM4000 and >RM4000)
		Breast-conserving surgery versus mastectomy
		Immune therapy (yes vs no)
		Unmarried (Un) versus married (M) versus widowed/divorced (WD)	W/D<M < Un
		Older age (≤40, 40–49 and ≥50)	Negative
		Employed versus retired versus housewife
		Higher stage (0, 1, 2, 3 and 4)
		Radiotherapy (yes vs no)
		Chemotherapy (yes vs no)
		Hormone therapy (yes vs no)
		Higher scores in SCNS – physical needs
		Higher scores in SCNS – psychological needs
		Higher scores in SCNS – care and support needs
	–	SCNS – sexuality needs	–
	–	SCNS – health system and information needs	–
Kim, 201291*	Role functioning	Higher bone density	Positive
Huang, 201750†	Global health status	Time since diagnosis (2–3, 3–5 and ≥5 years)	Positive
		Higher household income (≤US$1000, US$1001–US$2000 and ≥US$2001)
		Tumour stage
		Comorbidities (0, 1, 2 and ≥3)	Negative
		Treatment (combinations of surgery (S), chemotherapy (C), radiotherapy (R), hormone therapy (H), targeted therapy (T))	C>S+C+H>S+C+R+H+T>S+C>others> S+R+ hour>S+C+R+ hour>S+C+R>S+H
	–	Illness duration (ref: 2–3, 3–5 and ≥5 years)	3–5 years>2–3 years
	–	Recurrence or metastasisation	–
Liang, 201654†	Global health status	Year of diagnosis	Negative
		Symptom distress
	Global health status	Symptom management self-efficacy	Positive
Longitudinal (n=2)
Jang, 201292†	–	Presence of religion	–
	–	Higher religious activity (at 5 days and 1 year postsurgery)	–
	–	Higher intrinsic religiosity at 5 days postsurgery	–
	Global health status	Higher intrinsic religiosity at 1 year postsurgery	Positive
Wani, 201239	Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning	Time at first chemotherapy treatment, 6, 12 and 24 months after first visit	Positive
	Fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea and financial difficulty		Negative
Studies using the EORTC-QLQ-C30 and EORTC-QLQ-BR23 questionnaire
Cross-sectional (n=13)
Yusuf et al 201353	Nausea and vomiting, dyspnoea, constipation and breast symptoms	Malay versus Chinese	Positive
Kim et al, 201561	Role functioning, social functioning, body image and fatigue	Breast-conserving surgery versus mastectomy	Positive
	Pain, insomnia and arm symptoms		Negative
	Body image and fatigue	Breast-conserving surgery versus mastectomy with reconstruction	Positive
	Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, body image, sexual functioning, sexual enjoyment and future perspective	Better subjectively measured cosmesis	Positive
	Fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, systemic therapy side effects, breast symptoms, arm symptoms and hair loss		Negative
	Body image	Objectively measured cosmesis (good vs poor)	Positive
	Body image and diarrhoea	Panel score for cosmesis (good vs poor)	Positive
Chui et al, 201521	–	Age (30–39, 40–49, 50–59 and ≥60)‡	–
	Global health status	Ethnicity (Malay vs Indian)‡	Positive
		Ethnicity (Chinese vs Indian)‡
		Education (tertiary vs primary/lower)‡
		Education (secondary vs primary/lower)‡
		Household income (≤RM3000 vs >RM3000)‡
		Single versus ever married‡
		Chemotherapy (postponed vs on schedule)‡
	–	Stage (early vs late)‡	–
	–	Chemotherapy cycles (2/3/4 vs 5/6)‡	–
	–	Complementary and complementary medicine (MBP vs MBP-NP vs MBP-NP-TMed)‡	–
	Financial difficulty, sexual enjoyment, systemic therapy side effects and breast symptoms	Complementary and complementary medicine (users vs non-users)	Positive
	Emotional functioning and cognitive functioning	Complementary and complementary medicine (single (S), dual (D), triple (T) modality)	S<T<D
	Body image and future perspective		S<D<T
	Upset by hair loss		D<T<S
	Systemic therapy side effects		T<D<S
Lee, 200767§	Global health status	Presence of religion	Negative
		Presence of one or more comorbidity
		Incomplete versus completed treatment
		Problems before surgery
		Involved in decision making	Positive
		Better perceived overall medical care
	–	Time since diagnosis (≥5 years vs <5 years)	–
	Global health status, physical functioning, role functioning, social functioning and sexual enjoyment	Treatment status: post versus ongoing versus non	Post > (Ongoing = Non)
	Fatigue, pain, insomnia, appetite loss and body image		Negative
Sun, 201462	Emotional functioning, social functioning and body image	Breast-conserving surgery versus mastectomy versus mastectomy with reconstruction	Positive
	Nausea and vomiting, financial difficulty, arm symptoms (score for mastectomy with reconstruction was lower than for those with breast-conserving surgery)		Negative
Okamura, 200593	Emotional functioning, body image and future perspective	Presence of psychiatric disorder	Negative
	Fatigue, nausea and vomiting, appetite loss and diarrhoea		Positive
Huang, 201060	Dyspnoea	Older age	Positive
	Role functioning	Married (yes vs no)	Negative
	Breast symptoms		Positive
	Global health status and role functioning	Breast-conserving surgery versus mastectomy	Negative
	Fatigue, pain, dyspnoea, insomnia, appetite loss, breast symptoms and arm symptoms		Positive
	Insomnia, breast symptoms and arm symptoms	Adjuvant therapy (yes vs no)	Positive
	Insomnia	Hormone therapy (yes vs no)	Positive
Kang, 201222	Arm symptoms	Use of complementary and complementary medicine	Positive
Park, 201258	Sexual functioning and sexual enjoyment	Older age	Negative
	–	Tumour size	–
	–	Lymph nodes involvement	–
	Global health status	Metastatic disease	Negative
	Physical functioning and role functioning		Positive
	–	Postsurgery versus presurgery	–
	–	Axillary clearance	–
	Pain	Chemotherapy (yes vs no)	Negative
	Appetite loss, sexual enjoyment	Radiotherapy (yes vs no)	Negative
	Future perspective	Hormone therapy (yes vs no)	Positive
	–	Self-massage	–
	–	Lymphoedema duration	–
Tang, 201673	Global health status, physical functioning, role functioning, emotional functioning, body image and future perspective	Diabetes mellitus (yes vs no)	Negative
	Fatigue, nausea and vomiting, pain, dyspnoea, insomnia, constipation, diarrhoea, financial difficulty, systematic therapy side effects, breast symptoms, arm symptoms and upset with hair loss		Positive
	Global health status, cognitive functioning, emotional functioning and constipation	Type 1 diabetes mellitus versus no diabetes mellitus	Negative
	Fatigue, nausea and vomiting, dyspnoea, insomnia, diarrhoea, systematic therapy side effects and breast symptoms		Positive
	Global health status, physical functioning, role functioning, sexual functioning, sexual enjoyment, future perspective, fatigue and constipation	Type 2 diabetes mellitus versus no diabetes mellitus	Negative
	Body image, pain, dyspnoea, insomnia, appetite loss, financial difficulty, systematic therapy side effects, breast symptoms, arm symptoms and upset with hair loss		Positive
Kang, 201794	Global health status, physical functioning, cognitive functioning, emotional functioning, role functioning, body image and future perspective	Happiness status (Subjective Happiness Scale)	Positive
	Fatigue, nausea and vomiting, pain, insomnia, appetite loss, constipation, financial difficulties, systemic therapy side effects, arm symptoms and upset with hair loss		Negative
Dubashi, 201059	Global health status, sexual functioning and sexual enjoyment	Breast-conserving surgery versus mastectomy	Negative
	Arm symptoms		Positive
	Sexual functioning and sexual enjoyment	Having had ovarian ablation	Negative
Shin, 201795	Fatigue and pain	Higher levels of physical activity (metabolic equivalent-hours per week) (tertiles)	Negative
	Sexual functioning		Positive
	Physical functioning (only among stage I)		Positive
Chang, 201449¶	Global health status	Education (more than high school vs less than middle school)	Positive
		Married versus single/divorced/separated/widowed
	Body image	Household income (>$3000 vs <$3000)	Positive
		Employed versus unemployed	Negative
	–	Stage (1, 2, 3 and unknown)	–
	–	Being on active treatment	–
	Body image	Breast-conserving surgery versus mastectomy	Positive
Sharma, 201796	–	Time of radiotherapy (every day for 5 days)	–
Longitudinal (n=7)
Kao, 201546**	Global health status, emotional functioning, body image, sexual functioning, sexual enjoyment and future perspective	Older age (years)	Negative
	Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, body image, sexual functioning, sexual enjoyment and future perspective	Longer time since diagnosis (at 6 months/1 year/2 years vs at time of diagnosis)	Positive
	Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, body image, sexual functioning, sexual enjoyment and future perspective	Charlson comorbidity index	Negative
	Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, body image, sexual functioning, sexual enjoyment and future perspective	Tumour stage (3/4 vs 0/1)	Negative
	Cognitive functioning and body image	Tumour stage (2 vs 0/1)	Negative
	Role functioning, emotional functioning, cognitive functioning and body image	Breast-conserving surgery versus mastectomy	Positive
	Physical functioning, emotional functioning, body image, sexual functioning and sexual enjoyment	Breast-conserving surgery versus mastectomy with reconstruction	Negative
	Global health status, physical functioning, emotional functioning, body image and future perspective	Chemotherapy (yes vs no)	Negative
	Global health status, emotional functioning, body image and future perspective	Radiotherapy (yes vs no)	Positive
	Global health status, body image and future perspective	Hormone therapy (yes vs no)	Positive
	Physical functioning, role functioning, emotional functioning, cognitive functioning, body image, sexual functioning and sexual enjoyment	Longer postoperative length of stay	Negative
Munshi, 201038	Social functioning and arm symptom	Breast-conserving surgery versus mastectomy prior to radiotherapy	Negative
	Sexual enjoyment and future perspective		Positive
Lee, 201178	Diarrhoea	Longer time since diagnosis (1 year postdiagnosis vs at diagnosis)	Negative
Shi, 201147	Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, body image, sexual functioning, sexual enjoyment and future perspective	Longer time since diagnosis (2 vs 1 year)	Positive
	Role functioning, emotional functioning, cognitive functioning and body image	Breast-conserving surgery versus mastectomy	Positive
	Physical functioning, emotional functioning, sexual functioning and sexual enjoyment	Breast-conserving surgery versus mastectomy with reconstruction	Negative
	Body image		Positive
	Global health status	Older age	Negative
	Body image, sexual functioning and sexual enjoyment		Positive
	Global health status, physical functioning, emotional functioning, body image and future perspective	Chemotherapy (yes vs no)	Negative
	Global health status, emotional functioning, body image and future perspective	Radiotherapy (yes vs no)	Positive
	Global health status and body image	Hormone therapy (yes vs no)	Positive
	Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, body image, sexual functioning, sexual enjoyment and future perspective	Preoperative quality of life score	Positive
Ng, 201541††	Emotional functioning	At 6 months postdiagnosis versus at time of diagnosis	Positive
	Physical functioning		Negative
	Global health status, emotional functioning and social functioning	At 12 months postdiagnosis versus at time of diagnosis	Positive
Munshi, 201297	–	Radiotherapy using cobalt machine versus linear accelerator at completion of radiotherapy	–
Damodar, 201337	Physical functioning, role functioning and future perspective	At ≥5 versus ≤2 cycles of chemotherapy	Negative
	Fatigue, insomnia, arm symptoms and upset with hair loss		Positive
Sultan, 201740	Global health status, physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning, sexual functioning, arm symptoms and breast symptoms	Chemotherapy (cycle ref: 1, 3, 6)	Negative
	Fatigue, pain, dyspnoea, appetite loss, diarrhoea, sexual enjoyment and upset with hair loss		Positive
Studies using the FACT-G questionnaire
Cross-sectional (n=1)
So, 201451‡	–	Age (years)	–
	–	Time since diagnosis (months)	–
	–	Comorbidity (yes vs no)	–
	–	Education (no formal/primary vs secondary or higher)	–
	–	Employed versus unemployed/retired/homemaker	–
	–	Household income (≤HK$10 000, HK$10 001–HK$30000 and >HK$30 000)	–
	–	Married/cohabitation versus single/divorced/widowed	–
	–	Living alone (yes vs no)	–
	–	Family history (yes vs no)	–
	–	Stage (≤2 vs ≥3)	–
	–	Cancer is under control versus progression (yes vs no/unsure)	–
	–	Number of treatment received (one vs ≥2)	–
	Overall well-being	Hormone therapy (yes vs no)	Positive
		Longer time needed to travel from home to hospital (minutes)	Negative
		Higher scores in the domains of SCNS – psychological, physical and daily living, sexuality, health system and information, care and support
Longitudinal (n=1)
Wong, 200756‡‡	Overall well-being, physical well-being and functional well-being	Longer time since diagnosis	Positive
	Overall well-being and physical well-being	Positive mood	Positive
	Overall well-being and functional well-being	Higher levels of boredom	Negative
Studies using the FACT-B questionnaire
Cross-sectional (n=15)
Yan, 201643	Overall well-being, social well-being and functional well-being	Age (≤44, 45–54, 55–64 and ≥65 years)	Negative
	Breast cancer subscale		Positive
	Overall well-being, social well-being, emotional well-being and functional well-being	Primary school or less (L) versus middle/high school (M) versus college or more (C)	L<M<C
	Physical well-being		M<L<C
	Social well-being	Married (Ma) versus single (S) versus widowed (W) versus divorced (D)	D<S<W<Ma
	Breast cancer subscale		Ma<D<W<S
	Overall well-being, physical well-being, emotional well-being and functional well-being	Working in the public sector (G) versus private sector (P) versus farmers/unemployed (U)	U<P<G
	Social well-being		P<U<G
	Breast cancer subscale		U<G<P
	Overall well-being, social well-being, emotional well-being and functional well-being	Household income (<1000, 1001–3000, 3001–5000, >5000 RMB)	Positive
	Physical well-being		Generally positive
	Overall well-being, physical well-being, functional well-being and breast cancer subscale	URBMI/NRCMS (UR) versus UEBMI health insurance (UE) versus undefined (Un)	UR<Un<UE
	Emotional well-being		UR<UE<Un
	–	Stage (0/1, 2, 3, 4, unknown)	–
	–	Breast-conserving surgery versus mastectomy	–
	Overall well-being, physical well-being, emotional well-being and breast cancer subscale	Chemotherapy (yes vs no)	Negative
	Overall well-being, physical well-being, social well-being, emotional well-being, functional well-being and breast cancer subscale	Traditional Chinese medication (yes vs no)	Positive
	Overall well-being, emotional well-being and breast cancer subscale	Time since diagnosis (<11.9 (A), 12–23.9 (B), ≥24 (C) months)	A<C<B
	Physical well-being, social well-being and functional well-being		A<B<C
	Overall well-being, physical well-being, social well-being, emotional well-being, functional well-being and breast cancer subscale	Family harmony status (good vs not so good)	Positive
		Interaction with friends/neighbours (never, sometimes and frequent)
	Overall well-being, social well-being, emotional well-being and functional well-being	Participation in healing club (yes vs no)	Positive
	Breast cancer subscale		Negative
	Overall well-being, social well-being, emotional well-being and functional well-being	Participation in peer-patient activities and communication	Positive
	Overall well-being, physical well-being, social well-being, emotional well-being and functional well-being	Score on Perceived Social Support Scale (<50, 50–69 and ≥70)	Positive
Ohsumi, 200944	Overall well-being and social well-being	Older age (>60 vs ≤60 years)	Negative
	–	Time since surgery (≥85 vs <85 months)	–
	Social well-being	Education (≥10 vs <10 years)	Positive
	–	Employed versus unemployed	–
	–	Household income (>10, 5–10 and ≤5 million yen)	–
	–	Married versus others	–
	–	Comorbidity (yes vs no)	–
	–	Lymph node status	–
	Breast cancer subscale	Breast-conserving surgery versus mastectomy	Positive
	–	Chemotherapy (yes vs no)	–
	–	Hormone therapy (yes vs no)	–
Park, 201142	Overall well-being, physical well-being, social well-being, functional well-being and breast cancer subscale	Older age (≥50 vs <50 years)	Negative
Park, 201271‡	–	Age (≥50 vs <50 years)	–
	–	Education	–
	–	Employment	–
	–	Economic status	–
	–	Single versus married	–
	–	Performance status	–
	–	Score in the domains of SCNS – health system and information, care and support	–
	Overall well-being	Higher score in the domains of SCNS – psychological, physical and daily living	Negative
		Higher score in the domains of SCNS – sexuality	Positive
Thanarpan, 201598	Functional well-being	Better subjectively measured cosmesis	Negative
	–	Objectively measured cosmesis	–
	–	Self-rated breast symmetry	–
He, 201263	Social well-being	Breast-conserving surgery versus mastectomy	Positive
	Overall well-being, physical well-being, emotional well-being and functional well-being	Satisfaction with treatment	Not specified
Chen, 201355	Emotional well-being	Older age (≥40 versus <40 years)	Positive
	Overall well-being, physical well-being, emotional well-being and breast cancer subscale	Time since treatment (1, 2 and 5 years)	Positive
	Social well-being	Can read and write versus illiterate	Positive
		Employed versus unemployed
	Physical well-being, emotional well-being and breast cancer subscale	Higher stage	Negative
	–	Breast-conserving surgery versus mastectomy versus mastectomy with reconstruction	–
	–	Chemotherapy (yes vs no)	–
	–	Radiotherapy (yes vs no)	–
	–	Hormone therapy (yes vs no)	–
Chang, 200799§§	–	–	–
Kim, 2013100	Functional well-being	Oestrogen receptor status positive	Positive
So, 2013101	Social well-being and functional well-being	Having social support	Positive
	Breast cancer subscale		Negative
Zou, 201475††	Overall well-being	Higher optimism	Positive
		Affront copping mode versus give-in coping mode
		Appraisal of illness (higher scores indicate more stress)	Negative
		Having distress symptoms
Jiao-Mei, 201574	–	Age (years)	–
	–	Time since diagnosis (months)	–
	–	Stage	–
	Overall well-being, physical well-being, social well-being, emotional well-being and functional well-being	Post-traumatic growth (low, moderate and high)	Positive
	Overall well-being and social well-being	Adverse childhood event (0, 1 and ≥2)	Negative
Qiu, 2016102		BRCA 1/2 carriers versus non-carriers	–
Shin, 201757		Age (≤39, 40–49, 50–59 and ≥60)	–
	Overall well-being	Education (middle school vs high school vs university)	Positive
		Employment (yes vs no)	Positive
	–	Marital status (single vs married)	–
	–	Religion (yes vs no)	–
	–	Time since diagnosis (≤1, 1–5 and ≥5)	–
	Overall well-being	Recurrence (yes vs no)	Negative
	–	Breast-conserving surgery versus mastectomy
	–	Breast-conserving surgery versus mastectomy with reconstruction	–
	Overall well-being	Empowerment	Positive
	–	Self-help group (yes versus no)	–
So et al, 201145	Overall well-being, physical well-being, emotional well-being and breast cancer subscale	Age (≥60 vs <60 years)	Positive
Park, 201352	–	Age (≤39 vs 40 – 49 vs 50–59 years)‡‡	–
	Overall well-being	Household income (<2, 2–4, >4 million KRW/month)‡‡	Positive
		Stage (1, 2, 3/4, unknown)‡‡	Negative
	–	Length of chemotherapy (<6, 6–12 and ≥12 months)‡‡	–
	Overall well-being	Satisfaction with family support (unsatisfied, moderate and satisfied)‡‡	Positive
		Frequency of sexual activity (none within 6 months, ≤3 in 6 months, 2–3 per month and ≥1 per week)
	Overall well-being, social well-being, emotional well-being, functional well-being and breast cancer subscale	Sexual function	Positive
	Overall well-being, physical well-being, social well-being, emotional well-being, functional well-being and breast cancer subscale	Experienced menopausal symptoms	Negative
Pahlevan Sharif, 201776	Overall well-being, social well-being, functional well-being and breast cancer subscale	Higher external locus of control	Negative
	Overall well-being and functional well-being	Higher internal locus of control	Positive
Sharif, 201777	Overall well-being, social well-being, emotional well-being, functional well-being and breast cancer subscale	Higher score on powerful others	Negative
	Overall well-being, social well-being and breast cancer subscale	Higher score on chance	Negative
	Breast cancer subscale	Avoidant emotional coping	Negative
	Overall well-being, social well-being and functional well-being	Active emotional coping	Positive
	Social well-being and functional well-being	Problem focused coping	Positive
So, 2009103	–	–	–
Pandey, 2005104	–	–	–
Longitudinal (n=3)
Cao, 2016105	Emotional well-being and social well-being	Age (>60 vs ≤60 years)	Positive
		Longer time since enrolment (for most comparison between 6/12/18/24 months vs time since enrolment)
		Mastectomy (yes vs no)
		Prior chemotherapy (yes vs no)
	Emotional well-being and social well-being	Axillary lymph node dissection (yes vs no)	Negative
Pandey, 200668	Overall well-being, physical well-being, functional well-being and breast cancer subscale	Postsurgery versus presurgery	Negative
Taira, 201264¶¶	–	Concomitant disease (compared at 6, 12 and 24 months)	–
	–	Nodal involvement (compared at 6, 12 and 24 months)	–
	–	Breast-conserving surgery versus mastectomy (compared at 6, 12 and 24 months)	–
	–	Intercostobrachial nerve perseverance (compared at 6, 12 and 24 months)	–
	Overall well-being and breast cancer subscale	Chemotherapy (yes vs no) (compared at 6 months)	Negative
	Breast cancer subscale	Chemotherapy (yes vs no) (compared at 12 and 24 months)	Negative
	–	Hormone therapy (compared at 6, 12 and 24 months)	–
Study using both the EORTC-QLQ-C30 and FACT-G questionnaire
Cross-sectional (n=1)
Gong, 201769	Global health status, physical functioning, role functioning, emotional functioning, social functioning, overall well-being, physical well-being, social well-being, emotional well-being and functional well-being	Exercisers versus non-exercisers	Positive
	Nausea and vomiting, pain, dyspnoea and appetite loss		Negative
	Global health status, role functioning, cognitive functioning, emotional functioning, overall well-being, physical well-being and functional well-being	Frequency of exercise among exercisers (<5 vs ≥5 times a week)	Positive
	Fatigue, nausea and vomiting, dyspnoea, appetite loss and diarrhoea		Negative
	Global health status, physical functioning, role functioning, cognitive functioning, emotional functioning, social functioning, overall well-being, social well-being and functional well-being	Vegetable intake (≤250 vs >250 g/day)	Positive
	Fatigue, nausea and vomiting, dyspnoea, appetite loss, constipation and financial difficulty		Negative
	Global health status, physical functioning, cognitive functioning, emotional functioning, overall well-being, physical well-being, social well-being, emotional well-being and functional well-being	Daily fruit intake (yes vs no)	Positive
	Dyspnoea, appetite loss and constipation		Negative
	Global health status, physical functioning, role functioning, cognitive functioning, emotional functioning, social functioning, overall well-being, physical well-being, social well-being, emotional well-being and functional well-being	Healthy behaviour (ref: 1 vs 0 vs 2 vs 3)	Positive
	Fatigue, nausea and vomiting, pain, dyspnoea, insomnia, appetite loss, constipation and financial difficulty		Negative

Positive association implies an increase in measured score based on the respective scoring manual of each questionnaire. Global health status and functioning status of EORTC-QLQ-C30/-BR23: positive association implies better quality of life and functioning. Symptoms scales of EORTC-QLQ-C30/EORTC-QLQ-BR23: positive association implies higher level of symptoms. All scales of FACT-G/-B: positive association implies better well-being

*Domains studied: global health status, physical functioning, role functioning, emotional functioning, cognitive functioning and social functioning.

†Domains studied: global health status.

‡Domains studied: overall well-being.

§Apart from determinant ‘treatment status’, domain studied: global health status.

¶Domains studied: global health status and body image.

**Domains studied: global health status, physical functioning, role functioning, emotional functioning, social functioning, body image, sexual functioning, sexual enjoyment and future perspective.

††Domains studied: global health status, physical functioning, role functioning, emotional functioning, social functioning, body image, breast symptoms and arm symptoms.

‡‡Domains studied: overall well-being, physical well-being, social well-being, functional well-being.

§§Significance not mentioned (JT Chang).

¶¶Domains studied: overall well-being and breast cancer subscale.

MBP, mind–body practices; NP, natural products; NRCMS, New Rural Cooperative Medical Scheme health insurance; SCNS, the short-form Supportive Care Needs Survey questionnaire; TMed, traditional medicine; UEBMI, Urban Employee Basic Medical Insurance; URBMI, Urban Resident Basic Medical Insurance.

Table 4

Determinants associated with global health status and/or overall well-being

Determinants studied	Better global health status (GHS)/overall well-being (OWB)	Poorer GHS/OWB	Others
Demographic
Time since diagnosis/surgery/ treatment/enrolment: GHS – CS: refs 48, 50 and 67 GHS – L: refs 41, 46, 47 and 78 OWB – CS: refs 43, 44, 51, 55, 74 and 95 OWB – L: refs 56 and 105	Longer time since diagnosis: GHS – CS: refs 39, 47, 48 and 50 GHS – L: ref 46 OWB – L: ref 56 12 months versus at time of diagnosis: GHS – L: ref 41 Longer time since treatment: OWB – CS: ref 55	–	Time since diagnosis (<11.9 months) < (≥24 months) < (12–23.9 months): OWB – CS: ref 43
Ethnicity: GHS – CS: refs 21, 48 and 53	–	–	Malay<Chinese<Indian: GHS – CS: ref 48 Malay>Indian GHS – CS: ref 21 Chinese>Indian GHS – CS: ref 21
Education: GHS – CS: refs 21 and 49 OWB – CS: refs 43, 44, 51, 55, 71 and 95	(Higher) Education: GHS – CS: refs 21 and 49 OWB – CS: ref 95	–	Primary school or less<middle/high school<college or more: OWB – CS: ref 43
Year of diagnosis: GHS – CS: ref 54	–	Year of diagnosis: GHS – CS: ref 54	–
Older age: GHS – CS: refs 21, 48, 58 and 60 GHS – L: refs 46 and 47 OWB – CS: refs 42–45, 51, 52, 55, 71, 74 and 95 OWB – L: ref 105	–	Older age: GHS – CS: ref 48 GHS – L: refs 46 and 47 OWB – CS: refs 42–45	–
Employment: GHS – CS: refs 48 and 49 OWB – CS: refs 43, 44, 51, 55, 71 and 95	Employed (yes): OWB – CS: ref 95	–	Employed>retired>housewife: GHS – CS: ref 48 Working in public sector>private sector>farmers/unemployed: OWB – CS: ref 43
Income: GHS – CS: refs 21 and 48–50 OWB – CS: refs 43 and 52	(Higher) Income: GHS – CS: refs 48 and 50 OWB – CS: refs 43 and 52	(Higher) Income: GHS – CS: ref 21	–
Marital status: GHS – CS: refs 21, 48, 49 and 60 OWB – CS: refs 43, 44, 51, 71 and 95	–	–	Widowed/divorced<married<unmarried GHS – CS: ref 48 Single<married GHS – CS: ref 21 Married<single/ divorced/separated/widowed: GHS – CS: ref 49
Religion: GHS – CS: ref 67 GHS – L: ref 92 OWB – CS: ref 95	Presence of religion: GHS – CS: ref 67 Higher intrinsic religiosity at 1 year postsurgery GHS – L: ref 92	–	–
Comorbidity: GHS – CS: refs 50, 67 and 73 GHS – L: ref 46 OWB – CS: refs 44 and 51 OWB – L: ref 64	–	Comorbidity (yes): GHS – CS: refs 50 and 67 Diabetes mellitus (yes): GHS – CS: ref 73 (Higher) Charlson comorbidity index: GHS – L: ref 46	GHS – CS: Type 1 <no diabetes mellitus: GHS – CS: ref 73 Type 2 <no diabetes mellitus: GHS – CS: ref 73
Clinical
Tumour stage: GHS – CS: refs 21, 48–50 and 58 GHS – L: ref 46 OWB – CS: refs 43, 51, 52, 55 and 74	–	(Higher) stage: GHS – CS: refs 48 and 50: OWB – CS: ref 52 Metastatic disease: GHS – CS: ref 58 Stage 3/4 versus 0/1: GHS – L: ref 46	–
Recurrence: GHS – CS: ref 50 OWB – CS: ref 95	–	Recurrence (yes): OWB – CS: ref 95	–
Treatment
(Type of surgery) BCS versus TM: GHS – CS: refs 48, 49 and 59–61 GHS – L: refs 38, 46 and 47 OWB – CS: refs 43, 44 and 63 OWB – L: ref 64 BCS versus mastectomy with reconstruction (TM-R): GHS – CS: refs 47 and 61 OWB – CS: ref 95 BCS versus TM versus TM-R GHS – CS: ref 62 OWB – CS: ref 55 TM (yes): OWB – L: ref 105	–	–	BCS>TM: GHS – CS: refs 48, 59 and 60
Chemotherapy GHS – CS: refs 21, 48 and 58 GHS – L: refs 37, 40, 46 and 47 OWB – CS: refs 43, 44, 52 and 55 OWB – L: refs 64 and 105	–	Chemotherapy (yes): GHS – CS: ref 48 GHS – L: refs 46 and 47 OWB – CS: ref 43	Chemotherapy on schedule<postponed: GHS – CS: ref 21 At cycle 1>3>6: GHS – L: ref 40 Chemotherapy (yes)<no (compared at 6 months) OWB – L: ref 64
Radiotherapy: GHS – CS: refs 48, 58 and 96 GHS – L: refs 46, 47 and 97 OWB – CS: ref 55	Radiotherapy (yes): GHS – L: refs 46 and 47	Radiotherapy (yes): GHS – CS: ref 48	–
Hormone therapy: GHS – CS: refs 48 and 58 GHS – L: refs 46 and 47 OWB – CS: refs 44, 51 and 55 OWB – L: ref 64	Hormone therapy (yes): GHS – L: refs 46 and 47 OWB – CS: ref 51	Hormone therapy (yes) GHS – CS: ref 48	–
Immune therapy: GHS – CS: ref 48	Immune therapy (yes): GHS – CS: ref 48	–	–
Treatment combination: (surgery (S), chemotherapy (C), radiotherapy (R), hormone therapy (H), targeted therapy (T)): GHS – CS: ref 50	–	–	C>S+C+H > S+C+R+H+T>S+C>others>S+R+ hour>S+C+R+ hour>S+C+R > S+H: GHS – CS: ref 50
Treatment status: GHS – CS: refs 49 and 67	–	Treatment status (incomplete): GHS – CS: ref 67	Post-treatment>ongoing treatment=non-treatment: GHS – CS: ref 67
Lifestyle
Exercise: GHS – CS: refs 69 and 95 OWB – CS: ref 69	Exerciser (yes): GHS and OWB – CS: ref 69 (Higher) Frequency of exercise: GHS and OWB – CS: ref 69	–	–
Diet: GHS and OWB – CS: ref 69	(Higher) Vegetable intake: GHS and OWB – CS: ref 69 Daily fruit intake (yes): GHS and OWB – CS: ref 69	–	–
Healthy behaviour: GHS and OWB – CS: ref 69	(More) Healthy behaviour: GHS and OWB – CS: ref 69	–	–
Unmet needs
Short-form Supportive Care Needs Survey (SCNS) – psychological, physical and daily living, sexuality, health system and information, care and support: GHS – CS: refs 48 and 70 OWB – CS: refs 51 and 71	(Higher) Scores for sexuality: OWB – CS: ref 71	(Higher) Scores in all domains: GHS – CS: ref 70 OWB – CS: ref 51 (Higher) Scores for psychological, physical and daily living: GHS – CS: ref 48 OWB – CS: ref 71 (Higher) Scores for care and support: GHS – CS: ref 48
Others
Complementary and complementary medicine: GHS – CS: refs 21, 22 and 58 OWB – CS: ref 43	Traditional Chinese medication (yes): OWB – CS: ref 43	–	–
Cosmetic appearance: GHS – CS: ref 61 OWB – CS: ref 98	(Better) Subjectively measured cosmetic appearance: GHS – CS: ref 61	–	–
Symptom distress: GHS – CS: ref 54 OWB – CS: ref 75	–	Symptom distress: GHS – CS: ref 54 OWB – CS: ref 75	–
Involvement in decision making: GHS – CS: refs 67 and 72	Involvement in decision making (yes): GHS – CS: refs 67 and 72	–	–
Reflection of own value to decision: GHS – CS: ref 72	Reflection of own value to decision (yes): GHS – CS: ref 72	–	–
Problem obtaining surgery: GHS – CS: ref 72	–	Problem obtaining surgery (yes): GHS – CS: ref 72	–
Problems before surgery: GHS – CS: ref 67	–	Problems before surgery (yes): GHS – CS: ref 67	–
Experience of treatment toxicity: GHS – CS: ref 72	–	Experience of treatment toxicity (yes): GHS – CS: ref 72	–
Hospitalisation with treatment toxicity: GHS – CS: ref 72	–	Hospitalisation with treatment toxicity (yes): GHS – CS: ref 72	–
Time needed to travel from home to hospital: OWB – CS: ref 51	–	(Longer) Time needed to travel from home to hospital: OWB – CS: ref 51	–
Perceived overall medical care: GHS – CS: ref 67	(Better) Perceived overall medical care: GHS – CS: ref 67	–	–
Preoperative quality of life score: GHS – L: ref 47	(Higher) Preoperative quality of life score: GHS – L: ref 47	–	–
Sexual activity/function: OWB – CS: ref 52	(Higher) Frequency of sexual activity: OWB – CS: ref 52 (Higher) Sexual function: OWB – CS: ref 52	–	–
Experiencing menopausal symptoms: OWB – CS: ref 52	–	Experiencing menopausal symptoms: OWB – CS: ref 52	–
Symptom management self-efficacy: GHS – CS: ref 54	Symptom management self-efficacy: GHS – CS: ref 54	–	–
Insurance: OWB – CS: ref 43	–	–	URBMI/NRCMS<UEBMI health insurance<undefined: OWB – CS: ref 43
Optimism: OWB – CS: ref 75	(Higher) Optimism: OWB – CS: ref 75	–
Positive mood: OWB – L: ref 56	Positive mood: OWB – L: ref 56	–	–
Boredom: OWB – L: ref 56	–	(Higher) Levels of boredom: OWB – L: ref 56	–
Appraisal of illness: OWB – CS: ref 75	–	(Higher) Scores for appraisal of illness (ie, more stress): OWB – CS: ref 75
Post-traumatic growth: OWB – CS: ref 74	(Higher) Post-traumatic growth: OWB – CS: ref 74	–	–
Adverse childhood event: OWB – CS: ref 74	–	More adverse childhood event: OWB – CS: ref 74	–
Locus of control: OWB – CS: ref 76	(Higher) Internal locus of control: OWB – CS: ref 76	(Higher) External locus of control: OWB – CS: ref 76 (Higher) Score on powerful others: OWB – CS: ref 77 (Higher) Score on chance: OWB – CS: ref 77	–
Coping mode: OWB – CS: refs 75 and 77	Active emotional coping: OWB – CS: ref 77	–	Affront coping mode>give in coping mode: OWB – CS: ref 75
Empowerment: OWB – CS: ref 95	Empowerment (yes): OWB – CS: ref 95	–	–
Family harmony status: OWB – CS: ref 43	(Good) family harmony status: OWB – CS: ref 43	–	–
Interaction with friends/neighbours: OWB – CS: ref 43	Interaction with friends/neighbours: OWB – CS: ref 43	–	–
Participation in healing club: OWB – CS: ref 43	Participation in healing club: OWB – CS: ref 43	–	–
Participation in peer-patient activities and communication: OWB – CS: ref 43:	Participation in peer-patient activities and communication: OWB – CS: ref 43	–	–
Social support: OWB – CS: refs 43 and 101	(Higher) Score on Perceived Social Support Scale: OWB – CS: ref 43	–	–
Satisfaction with family support: OWB – CS: ref 52	Satisfaction with family support: OWB – CS: ref 52	–	–

BCS, breast-conserving surgery; CS, cross-sectional study; L, longitudinal study; NRCMS, New Rural Cooperative Medical Scheme health insurance; TM, mastectomy; UEBMI, Urban Employee Basic Medical Insurance; URBMI, Urban Resident Basic Medical Insurance.

Age

Park et al found that patients with breast cancer who were of older age had poorer overall well-being and that older age was associated with longer time since surgery.42 In patients who were at least 5-year postdiagnosis, older age was associated with poorer overall well-being in those.43 44 In patients undergoing chemotherapy or radiotherapy, So et al observed that older age was associated with better overall well-being than those aged below 60 years.45 Apart from the study by So et al,45 other studies21 46–48 on this association showed that older age was associated with poorer global health status.

Marital status

Chui et al 21 and Edib et al 48 found that women who were single (as compared with ever married) and unmarried (as compared with currently married and widowed/divorced), respectively, had better global health status. However, Chang et al found that being married as compared with being single/divorced/widowed was associated with better global health status.49 The classification of widowed/divorced, which confers poorer HRQL than married, may have contributed to the difference in findings of Chui et al 21 and Chang et al,49 in addition the proportion of women who were never married (single) is small in both populations (11% unmarried and 17% unmarried/divorced/widowed, respectively).

Income

Edib et al 48 and Huang et al 50 found that higher household income was associated with better global health status, while Chui et al 21 found the opposite. While some reported higher household income to be also associated with better overall well-being, others did not find evidence of associations.44 51 Standard of living for the population is different among the different studies, making it difficult to access if the association seen was a result of the choice of categorisation of household income. Among the six studies21 43 48–50 52 that assessed household income, Chui et al were the only ones who looked at the effect of household income during treatment, in particular during chemotherapy, and found that higher income was associated with poorer global health status.21 Lower income might have been less of a concern in Malaysia, where lower income patients have access to welfare assistance, while patients of higher income are not eligible for. In addition, Edib et al studied survivors in the post-treatment period in Malaysia and found that higher household income was associated with better global health status.48

Other demographic determinants

Shorter time since breast cancer diagnosis,39 41 46–48 50 being of Chinese or Indian ethnicity as compared with Malay ethnicity,21 48 53 lower educational level21 49 and being diagnosed at later calendar year54 were associated with poorer global health status. Shorter time since diagnosis of breast cancer43 55 56 and lower educational level43 57 were associated with poorer overall well-being.

Tumour characteristics

Advanced stage disease was associated with poorer global health status46 48 50 58 and poorer overall well-being.52

Type of surgery

Edib et al observed that women who underwent breast-conserving surgery had better global health status than women who had mastectomy.48 However, Dubashi et al 59 and Huang et al 60 found that patients who had breast-conserving surgery had poorer global health status than those who had mastectomy. This could be due to the higher levels of, pain, breast symptoms and arm symptoms experienced by patients who had breast-conserving surgery as compared with those who had mastectomy.59 60 Furthermore, other studies comparing breast-conserving surgery and mastectomy did not find associations with global health status46 47 61 62 or overall well-being.43 44 55 57 63 64

Radiotherapy

Kao et al 46 and Shi et al 47 found that at 2 years postdiagnosis, women who have had radiotherapy had better global health status as compared with those who did were not treated with radiotherapy; however, Edib et al 48 found contrary results. After adjusting for potential confounders, the association between radiotherapy with poorer global health status was no longer significant.48 Park et al 58 and Hong-Li et al 55 did not find association between having had radiotherapy and global health status or overall well-being.

Hormone therapy

Edib et al 48 found hormone therapy was associated with poorer global health status; however, Kao et al 46 and Shi et al 47 found the opposite. Kao et al 46 and Shi et al 47 obtained information on hormone therapy from medical records. Using the classification of ever or current user of hormone therapy may result in misclassifying those who had discontinued with those on active therapy. Furthermore, patients who suffer adverse events, like hot flushes, are more likely to discontinue hormone therapy, which may result in patients who are on hormone therapy to be incorrectly perceived as having better global health status.65 66 In other studies, hormone therapy was not associated with global health status58 or overall well-being.44 55 64

Other treatment determinants

Ongoing treatment (vs completed treatment),67 having received chemotherapy46 48 or not having delayed chemotherapy21 39 were associated with poorer global health status. Recent (≤30 days) postsurgery (vs presurgery)68 and having received chemotherapy43 64 were associated with poorer overall well-being.

Complementary and alternative medication

The use of complementary and alternative medication in general, including dietary supplements, prayer, exercise and/or self-help techniques, was not associated with overall well-being.21 22 However, the use of traditional Chinese medication,43 empowerment of patients with breast cancer57 and participating in self-help groups57 were independently was associated with better overall well-being.

Lifestyle

Gong et al found that patients who had less healthy behaviour (comparing zero healthy behaviour, 2, or 3 to 1) had lower global health status and overall well-being.69 Patients with breast cancer who did not exercise (vs exercise) or with lower frequency of exercising (vs ≥5 times a week) had lower global health status and overall well-being.69 Furthermore, those who had low vegetable (vs >250 g per day) intake and did not eat fruits daily had lower global health status and overall well-being.69

Unmet needs

Having more unmet needs, especially in the physical and daily living, were associated with poorer global health status48 70 and poorer overall well-being.44 51 So et al 51 found that women who had unmet sexuality needs (measured by SCNS) had poorer overall well-being, while Park et al 71 reported the opposite. Park et al found that higher needs was associated with better overall well-being in 52 women who experienced recurrence of breast cancer, citing that patients who have better sexual functioning are more likely to have more sexuality needs.71 Akechi et al 70 found that unmet sexuality need was associated with poorer global health status, while Edib et al 48 did not find such association.

Others

Lack of involvement in decision making,67 72 lower self-efficacy in symptom management,54 poorer perceived overall medical care67 and having higher Charlson comorbidity index or comorbidities, including diabetes, hypertension and arthritis,46 50 73 were associated with poorer global health status. Adopting a give-in coping mode or believing that they are not in control,74–77 lower perceived social support and lower self-efficiency43 52 57 and poorer perceived overall medical care43 were associated with poorer overall well-being.

Differences in quality of life between patients with breast cancer patients and general population

Two studies both conducted in Korea studied differences in global health status between patients with breast cancer and the general population.67 78 Lee et al found that global health status was not different among patients who had completed treatment for recurrent breast cancer as compared with the general population.67 However, role functioning, cognitive functioning and social functioning were lower, and fatigue levels and financial difficulties were higher in patients treated for recurrence as compared with the general population.67 Lee et al compared patients with breast cancer to the general population at two time points, immediately after diagnosis and 1 year after diagnosis and found that the general population had higher global health status at both time points.78

Discussion

In Asia, patients with breast cancer have poorer HRQL than the general population. Patients with comorbidities, with chemotherapy, lower social support and with more unmet needs have poorer quality of life. However, HRQL improves with time since diagnosis and having healthier behaviour is associated with better HRQL. Within and across the scope of each questionnaire, most associations with poor global health status or overall well-being were concordant. Discordant results in studies were found in the associations of age, marital status, household income, type of surgery, radiotherapy and hormone therapy, and unmet sexuality needs with global health status or overall well-being.

Patients with one or more comorbidities during the time of survey had poorer HRQL. Comorbidity occurs in 20%–30% of patients with breast cancer.79 Comorbidities may be pre-existence or developed after diagnosis; hypertension, arthritis and diabetes are common to patients with breast cancer.14 Studies outside Asia showed similar results; having less co-morbidity was also found to be associated with better HRQL in African-American and Latina breast cancer survivors.80 81 Having pre-existing diabetes was associated with poorer HRQL, in patients with early breast cancer in the USA.82 In addition, patients with pre-existing comorbidities are more likely to have treatment complications, which may lead to poorer HRQL.79

In Asian patients with breast cancer, of all treatments studied, only being on or received chemotherapy was clearly associated with poorer HRQL. This is in agreement with Wöckel et al, who found that patients who received chemotherapy had decreased HRQL, and it was more likely to remain low.83 However, patients on chemotherapy are more likely to be diagnosed with advanced stage disease which was also found to be associated with HRQL. Other treatments, like surgery, are less likely to be associated with advance stage disease, and may be the reason for the null findings. Furthermore, patients with poorer prognosis or who are undergoing chemotherapy are more likely to experience pain, fatigue and potentially other adverse events.84 85

The lack of social support and higher unmet needs were associated with poorer HRQL, in Asian countries. Having a large percentage of unmet needs is not unique to Asia.86 87 Provision of social support should be in-line with the needs of the patient, so as to not adversely impact their HRQL.88 89 In this review, social support, in areas that enable patients to be empowered with higher self-efficacy, was associated with better HRQL. The provision for the educational needs or having access to the service of a breast care nurse may help in reducing unmet needs and provide social support from an institutional effort.89 90

We acknowledge that this systematic review has some limitation. The studies included had varying patient selection criteria, which may be the reason for discordance results in certain determinants. Studies conducted in patients during the treatment period would differ from those conducted after completion of treatment. The choice of statistical analysis varies, with most reporting associations from linear models and some from correlation analysis; thus, we were not able to provide a sense of the level of association. Non-standard methods of measuring determinants were used in some studies, limiting the comparability of the studies. Furthermore, we cannot determine the direction of association from cross-sectional studies; it is possible that some determinant, such as unmet needs and use of CAM, were the result of poorer HRQL. While most of the studies of longitudinal design were of high quality, the majority of the cross-sectional design studies were of moderate or poor quality. Future cross-sectional studies should consider reporting reasons for non-response and include multiple sites if sample size is insufficient.

Conclusion

Patients with breast cancer in Asia have a poorer HRQL than the general population. A shorter time since diagnosis of breast cancer,39 41 43 46–48 50 55 56 having a Chinese or Indian ethnic background as compared with Malay ethnicity,21 48 53 lower educational level21 43 49 57 and advanced stage breast cancer disease46 48 50 52 58 were associated with poorer HRQL. There is some evidence that patients with comorbidities or with chemotherapy are more likely to experience poorer HRQL. The lack of social support and having unmet needs may predict poorer HRQL. Further studies into methods to provide social support in the Asian setting is needed to identify effective ways to improve patients’ HRQL.