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Health-related quality of life of postmenopausal Chinese women with hormone receptor-positive early breast cancer during treatment with adjuvant aromatase inhibitors: a prospective, multicenter, non-interventional study

  • Ayong Cao1,
  • Jin Zhang2,
  • Xiaoan Liu3,
  • Weizhu Wu4,
  • Yinhua Liu5,
  • Zhimin Fan6,
  • Anqin Zhang7,
  • Tianning Zhou8,
  • Peifen Fu9,
  • Shu Wang10,
  • Quchang Ouyang11,
  • Jinhai Tang12,
  • Hongchuan Jiang13,
  • Xiaohua Zhang14,
  • Da Pang15,
  • Jianjun He16,
  • Linxiang Shi17,
  • Xianming Wang18,
  • Yuan Sheng19,
  • Dahua Mao20 and
  • Zhimin Shao1Email author
Health and Quality of Life Outcomes201614:51

https://doi.org/10.1186/s12955-016-0446-2

Received: 29 May 2015

Accepted: 9 March 2016

Published: 24 March 2016

Abstract

Background

Estimating quality of life (QoL) in patients with breast cancer is of importance in assessing treatment outcomes. Adjuvant endocrine therapy is widely used for hormone receptor-positive (HR+) early-stage breast cancer (EBC), and evidence suggests that aromatase inhibitors (AIs) may improve QoL for these patients. This study evaluated QoL in postmenopausal Chinese patients with HR+ EBC taking AIs.

Methods

This was a prospective, multicenter, and observational study that had no intent to intervene in the current treatment of recruited patients. Eligible patients were recruited within 7 days of beginning adjuvant treatment with AIs. The Functional Assessment of Cancer Therapy-Breast (FACT-B) scale was used to evaluate the patients’ QoL. Data were collected at baseline and at 6, 12, 18, and 24 months.

Results

From June 2010 to October 2013, a total of 494 patients with HR+ EBC were recruited from 21 centers. There was a 7.51-point increase in the patients’ mean FACT-B trial outcome index (TOI), from 90.69 at baseline to 98.72 at 24 months (P < .0001). The mean TOI scores at baseline, 6, 12, and 18 months were 90.69, 94.36, 97.71, and 96.75, respectively (P < .0001, for all). The mean (FACT-B) emotional well-being subscale scores at baseline, 6, 12, 18, and 24 months were 16.32, 16.55, 17.34 (P < .0001), 17.47 (P < .0001), and 17.85 (P < .0001), respectively, and social well-being scores were 18.61, 19.14 (P < .04), 19.35 (P < .008), 18.32, and 18.40, respectively. In the mixed model, baseline TOI, clinical visits, prior chemotherapies, age group, and axillary lymph-node dissection presented statistically significant effects on the change of FACT-B TOI and FACT-B SWB, whereas only baseline TOI, clinical visits, and prior chemotherapies presented statistically significant effects on the change of FACT-B EWB. FACT-B TOI, being the most pertinent and precise indicator of patient-reported QoL, demonstrated significant changes reflecting clinical benefit of adjuvant AIs endocrine therapy in the QoL of HR + EBC patients.

Conclusions

The study demonstrated significant improvements in the long-term QoL of postmenopausal Chinese patients with HR+ EBC at 6, 12, 18, and 24 months after starting treatment with AIs. The current study indicates improved long-term QoL with AI adjuvant treatment, which will aid clinicians in optimizing treatment to yield effective healthcare outcomes.

Trial registration

Clinicaltrials.gov NCT01144572

Keywords

Quality of lifeProspectiveFunctional Assessment of Cancer Therapy-BreastTrial outcome indexHormone receptor-positive early-stage breast cancer postmenopauseAdjuvantAromatase inhibitorsEarly breast cancer

Background

Breast cancer is the most common cancer in women worldwide, with nearly 1.7 million new cases diagnosed in 2012, representing about 12 % of all new cancer cases and 25 % of all cancers in women [1]. China accounts for nearly 12.2 % of all newly diagnosed breast cancer cases and about 9.6 % of all deaths from breast cancer worldwide [2]. In the past two decades, although the incidence of breast cancer has steadily increased, the death rate from the disease has declined [3]. Moreover, awareness of patients’ quality of life (QoL) during treatment is increasing, making it important for physicians and patients to consider therapeutic efficacy, safety of medical interventions, and QoL when selecting a treatment program. In addition, health-related QoL (HRQoL) is now being considered as an important end point in cancer clinical trials, which could contribute to improved treatment outcomes [4, 5].

Because various studies have consistently demonstrated superior efficacy and safety of the third-generation aromatase inhibitors (AIs) compared with those of tamoxifen alone in postmenopausal women with ER (+) breast cancer [6, 7], AIs are widely administered as standard adjuvant endocrine therapy in this population [8]. Previous researches suggested that treatment of patients with early-stage breast cancer (EBC) with third-generation AIs (e.g., anastrozole, letrozole, and exemestane) may improve their QoL [69]. However, this therapy is associated with persistent side effects and toxicity, which lead to negatively impact the patient’s QoL [10].

The Functional Assessment of Cancer Therapy-Breast (FACT-B), developed by Rush-Presbyterian-St. Luke’s Medical Center, Chicago, United States, is a widely used international scale to assess the QoL of patients with cancer [11, 12]. The use of such internationally consistent and validated scales to evaluate the QoL of Chinese patients will help improve the understanding of breast cancer outcomes. Specifically, they should enable physicians and patients to more clearly understand the long-term effects of AI therapy in breast cancer while making important treatment decisions. To date no nationwide, prospective, multicenter study has been available in China to evaluate the QoL of postmenopausal patients with early-stage breast cancer (EBC) positive (+) for hormone receptors (HR) treated with adjuvant therapy with AIs. It is of vital importance to evaluate the quality of life of Chinese patients using an internationally accepted method, so that the Chinese physicians are better knowledgeable about the effects of AIs on the long-term therapy when making therapeutic decisions. Because QoL studies can further indicate the directions needed for efficient treatment of cancer, the current study was conducted to evaluate the QoL of postmenopausal patients with HR (+) EBC receiving adjuvant treatment with AIs [13, 14].

Methods

Study design

This was the first prospective, multicenter, observational, non-interventional study in Chinese postmenopausal women [HR (+) and EBC] undergoing adjuvant treatment with AIs. There was no intent to intervene in the current treatment of the recruited patients (NCT01144572).

Participants

The following were the screening criteria: postmenopausal women, age ≤70 years, histologically documented HR (+) EBC, currently on adjuvant endocrine therapy with AIs and indications approved by the State Food and Drug Administration (SFDA), or AI adjuvant therapy started within the past 7 days. Women were eligible to be included in the study if they had simple mastectomy, breast-conserving surgery, or axillary lymph node dissection or sampling. Patients were excluded from the analysis if they were disinterested in participating, unable to adhere to the trial requirements for any reason, or were using AIs not approved by the SFDA for initial adjuvant endocrine therapy for EBC. Written informed consent for the data collection was obtained at the clinic visit after eligibility requirements were confirmed by the investigator. At any point during the study, patients could discontinue from the final analysis if it was their own decision, they had discontinued previous AI medication, or they had a documented evidence of disease relapse or progression.

The study was performed in accordance with Declaration of Helsinki and Good Clinical Practice Guidelines, with approval obtained from each center’s independent ethics committee.

Study objective

The primary objective was to evaluate overall QoL in postmenopausal patients with HR(+) EBC during adjuvant treatment with AIs by assessing the change in the trial outcome index (TOI) of the FACT-B questionnaire from baseline to 24 months. The secondary objective was to evaluate the QoL in the same population during adjuvant treatment with AIs by examining FACT-B questionnaire results at several time points (baseline, 6, 12, and 18 months) on three FACT-B measures: TOI, emotional well-being (EWB) subscale scores, and social well-being (SWB) subscale scores. In addition, the factors affecting the QoL of patients with breast cancer were also determined.

Data collection

Data for demography and pathological examination for breast cancer were obtained for all the patients included in the analysis. Demographic parameters recorded were age, ethnic background, height, weight, basal metabolic index, and World Health Organization (WHO) performance status score. Pathological examination for breast cancer included assessment of the primary site, histological type, histological grading, and TNM stage. In addition, data were recorded for status of estrogen and progesterone receptors, history of breast cancer surgery, history of prior chemotherapy or radiotherapy, and use of AIs.

Quality of life assessment

QoL was assessed using the FACT-B questionnaire from baseline to 6, 12, 18, and 24 months. The TOI (sum of the physical well-being, functional well-being, and breast cancer–specific questions in the FACT-B) was regarded as the primary end point. An increase in TOI of more than 5 points from baseline, disease progression, or death was considered a clinically meaningful improvement in QoL. FACT-B instrument uses a 5-point rating scale, including measures for physical, social/family, emotional, and functional well-being. The instrument was used to inquire respondents on how true each statement was for the past 7 days and rate them. Response scales ranged from 0 (not at all) to 4 (very much). A one-on-one discussion was scheduled to collect data on demographic characteristics and QoL.

Statistical methods

The sample size was not formally calculated as this was a cohort study and there was no formal comparison between the groups. It was projected that 500 patients would be enrolled within 3 years given the patient pool capacity in the participating sites. The primary QoL analysis, inclusive of all available questionnaires, was based on the patients who completed the informed consent form (ICF) and had one clinical visit included in the final analysis. The analysis was performed using the MIXED procedure of the SAS statistical software (SAS Institute, Cary, North Carolina, USA), which has the advantage of handling missing data without any imputation of missing values, provided that data are missing at random. Baseline covariates such as TOI score, prior chemotherapy (yes/no), age group, mastectomy (yes/no), and axillary clearance (yes/no) were included in the model regardless of statistical significance. This repeated measures analysis also included time from baseline, as both fixed and random polynomial effects, to allow patient-specific time trends and intercepts (described via random effects) to vary around an overall average trend and intercept (described via the fixed effects). The results of the analyses are presented in terms of adjusted means, associated confidence intervals (CIs), and P values. The mean score change from baseline was calculated for each patient with valid baseline questionnaires.

Results

Patient disposition

From June 2010 to October 2013, a total of 494 patients were enrolled in the study; of these patients, 453 (91.7 %) completed the study and 41 (8.3 %) prematurely discontinued from the study as a result of loss to follow-up (5.1 %), disease relapse/progression (1.2 %), failure to adhere to inclusion/exclusion criteria (0.6 %), voluntarily discontinuation (0.4 %), cessation of AI therapy (0.4 %) and other (0.6 %). Thirty-one patients had at least one protocol violation, majorly because of failure to adhere to inclusion criteria pertaining to postmenopausal women aged ≤70 years (n = 21), starting of AI adjuvant therapy within the past 7 days (n = 7), and unavailability of FACT-B data for clinical visits 2–5 (n = 8). Subsequently, a total of 486 patients (98.4 %) were included for the final analysis (Fig. 1).
Fig. 1

Study flow chart

Demographics and other baseline characteristics

All the 486 patients were of Chinese ethnic origin with a mean age of 57.3 years (range: 27–79 years), including 316 (65 %) women aged ≤60 years and 170 (35 %) women aged >60 years. Other baseline characteristics are listed in Table 1. Most patients had unilateral breast cancer, except three patients who reported bilateral primary breast cancer. More than half (372; 76.5 %) of the patients had estrogen receptor (ER, +)/progesterone receptor (PR, +) breast cancer, 99 (20.4 %) patients had ER(+)/PR(−) breast cancer, and 15 (3.1 %) patients had ER(−)/PR(+) breast cancer.
Table 1

Baseline characteristics

Parameter

(N = 486)

Weight (kg)

N (missing)

486 (0)

 Mean (SD)

59.8 (8.93)

 Median

59.0

 Min ~ max

35,105

Height (cm)

N(missing)

486 (0)

 Mean (SD)

159.4 (4.58)

 Median

160.0

 Min ~ max

143,175

BMI (kg/m2)

N(missing)

486 (0)

 Mean (SD)

23.5 (3.25)

 Median

23.0

 Min ~ max

16,39

WHO Performance Status Score

Activities limited

148 (30.5 %)

 

Normal activities

329 (67.7 %)

Bedridden time ≤ 50 %

9 (1.9 %)

Total

486 (100.0 %)

Primary site

Right breast

240 (49.4 %)

 

Left breast

243 (50.0 %)

Left breast, right breast

3 (0.6 %)

Total

486 (100.0 %)

Histological type

Invasive carcinoma

463 (95.3 %)

 

Carcinoma in-situ

23 (4.7 %)

Total

486 (100.0 %)

Histological grading

Unevaluable(GX)

58 (11.9 %)

 

Poorly differentialted(G3)

84 (17.3 %)

Well differentiated(G1)

56 (11.5 %)

Undifferentiated(G4)

9 (1.9 %)

Moderately differentiated(G2)

279 (57.4 %)

Total

486 (100.0 %)

ER status

Positive

471 (96.9 %)

 

Negative

15 (3.1 %)

Total

486 (100.0 %)

PR status

Positive

387 (79.6 %)

 

Negative

99 (20.4 %)

Total

486 (100.0 %)

ER and PR status

ER positive,PR positive

372 (76.5 %)

 

ER positive,PR negative

99 (20.4 %)

ER negative,PR positive

15 (3.1 %)

Total

486 (100.0 %)

Mastectomy

No

36 (7.4 %)

 

Yes

450 (92.6 %)

Total

486 (100.0 %)

Breast-conserving surgery

No

450 (92.6 %)

 

Yes

36 (7.4 %)

Total

486 (100.0 %)

Axillary lymph node dissection

No

103 (21.2 %)

 

Yes

383 (78.8 %)

Total

486 (100.0 %)

Axillary lymph node sampling

No

312 (64.2 %)

 

Yes

174 (35.8 %)

Total

486 (100.0 %)

Prior chemotherapy

No

227 (46.7 %)

 

Yes

259 (53.3 %)

Total

486 (100.0 %)

Prior radiotherapy

No

432 (88.9 %)

 

Yes

54 (11.1 %)

Total

486 (100.0 %)

A total of 450 (92.6 %) patients had mastectomy, 36 (7.4 %) had breast-conserving surgery, 383 (78.8 %) had axillary lymph-node dissection, and 312 (64.2 %) had undergone axillary lymph-node sampling. Fifteen patients had an unknown AI use status; 426 patients were taking anastrozole, with 416 (97.7 %) treated for more than 2 years. The detailed information is given in Table 2. Among the 486 patients, only 1 patient reported hormone replacement therapy, 152 (31.3 %) patients were found to have major medical conditions other than breast cancer, and 92 (18.9 %) patients had major surgical therapies other than breast cancer surgery.
Table 2

Use of aromatase inhibitors (final analysis set)

  

Final analysis set

 

Treatment duration (months)

(N = 486) n (%)

Anastrozole

<6

1 (0.2)

 

6–12

5 (1.2)

 

12–18

1 (0.2)

 

18–24

3 (0.7)

 

>24

416 (97.7)

 

Total

426 (100)

 

Missing

15

Anastrozole/exemestane

>24

1 (100)

 

Total

1 (100)

Anastrozole/letrozole

>24

5 (100)

 

Total

5 (100)

Exemestane

>24

10 (100)

 

Total

10 (100)

Letrozole

6–12

2 (6.9)

 

>24

27 (93.1)

 

Total

29 (100)

Primary endpoint-change in the FACT-B TOI from baseline to 24 months

A significant improvement was observed on the mean FACT-B TOI from baseline (mean: 90.69) to 24 months (mean: 98.72; P < .0001) (Table 3). In the MIXED model, baseline TOI, visit, prior chemotherapies, age group, and axillary lymph-node dissection presented statistically significant effects on the change of FACT-B TOI; however, mastectomy presented no statistically significant effects on the change of FACT-B TOI (Table 4). Lower boundary of the CI of the least squares (LS) mean (adjusted mean) change from baseline to 24 months in FACT-B TOI was >0, indicative of an increased TOI at 24 months of treatment. Moreover, LS mean change from 6 to 24 months of treatment was −4.48 (P < .0001). The LS mean of changes from baseline in FACT-B TOI with 95 % CIs is given in Table 4.
Table 3

FACT-B TOI at each post-treatment visit and changes from baseline (final analysis set)

  

Final analysis set (N = 486)

Visit

Clinical efficacy

TOI

TOI change from baseline

Baseline

N (missing)

486 (0)

 
 

Mean (SD)

90.69 (19.526)

 
 

Median

89.65

 
 

Min–max

31.3–137.0

 

6 months

N (missing)

480 (6)

480 (6)

 

Mean (SD)

94.36 (18.995)

3.58 (15.312)

 

Median

94.00

1.50

 

Min–max

58.5–141.0

−61.0 to 61.8

 

P value in comparison to baseline

 

<.0001

12 months

N (missing)

483 (3)

483 (3)

 

Mean (SD)

97.71 (20.670)

7.03 (19.241)

 

Median

98.00

3.83

 

Min–max

47.0–140.0

−50.0 to 82.0

 

P value in comparison to baseline

 

<.0001

18 months

N (missing)

447 (39)

447 (39)

 

Mean (SD)

96.75 (22.074)

5.18 (21.378)

 

Median

95.83

4.00

 

Min–max

54.0–142.0

−58.0 to 78.0

 

P value in comparison to baseline

 

<.0001

24 months

N (missing)

436 (50)

436 (50)

 

Mean (SD)

98.72 (22.672)

7.51 (22.476)

 

Median

97.58

6.00

 

Min–max

49.0–140.0

−59.0 to 81.3

 

P value in comparison to baseline

 

<.0001

FACT-B Functional Assessment of Cancer Therapy-Breast, SD standard deviation, TOI trial outcome index

Table 4

LS mean of changes from baseline in FACT-B TOI with 95 % CIs (final analysis set)

  

Final analysis set (N = 486)

  

LS Mean

95 % CI

P value

Visit

6 months

4.04

1.64–6.43

 

12 months

7.10

4.57–9.63

 

18 months

6.54

3.84–9.25

 

24 months

8.51

5.75–11.27

 

6–12 months

−3.06

−4.06 to −2.06

<.0001

 

6–18 months

−2.50

−3.83 to −1.17

.0002

 

6–24 months

−4.48

−5.96 to −2.99

<.0001

 

12–18 months

0.56

−0.59 to 1.70

.3405

 

12–24 months

−1.41

−2.78 to −0.05

.0422

 

18–24 months

−1.97

−2.92 to −1.02

<.0001

Prior chemotherapies

Yes

10.99

8.20–13.77

 

No

2.11

−0.69 to 4.90

 

Yes–No

8.88

6.36–11.40

<.0001

Age group

>60 years

8.04

5.04–11.05

 

≤60 years

5.05

2.44–7.66

 

>60 to ≤60 years

2.99

0.37–5.61

.0256

Mastectomy

Yes

7.63

5.88–9.38

 

No

5.46

0.90–10.03

 

Yes–No

2.17

−2.63 to 6.97

.3752

Axillary lymph-node dissection

Yes

4.77

2.00–7.55

 

No

8.32

5.22–11.43

 

Yes–No

−3.55

−6.68 to −0.41

.0268

CI confidence interval, FACT-B Functional Assessment of Cancer Therapy-Breast, LS least squares, TOI trial outcome index

Secondary end points

Changes in the FACT-B TOI from baseline to 6, 12, and 18 months

The mean FACT-B TOI was 90.69, 94.36, 97.71, and 96.75 at baseline, 6, 12, and 18 months, respectively, contributing to the increases from baseline 3.58, 7.03, and 5.18 at 6, 12, and 18 months, respectively (Table 3). The mean change in FACT-B TOI was significant at all time points as compared with baseline (P < .0001, for all).

Changes in the FACT-B EWB from baseline to 6, 12, 18, and 24 months

The mean FACT-B EWB was 16.32, 16.55, 17.34, 17.47, and 17.85 at baseline, 6, 12, 18, and 24 months, respectively, contributing to the mean increases from baseline 0.18, 1.03, 0.90, and 1.36 at 6, 12, 18, and 24 months, respectively (Table 5). The mean change in FACT-B EWB was significant at 12, 18, and 24 months as compared with baseline (P < .0001, for all).
Table 5

FACT-B EWB scores at each post-treatment visit and changes from baseline (final analysis set)

  

Final analysis set (N = 486)

Visit

Clinical efficacy

Total score

Change from baseline in total score

Baseline

N (missing)

486 (0)

 
 

Mean (SD)

16.32 (4.497)

 
 

Median

17.00

 
 

Min–max

2.0–24.0

 

6 months

N (missing)

480 (6)

480 (6)

 

Mean (SD)

16.55 (4.318)

0.18 (3.741)

 

Median

17.00

0.00

 

Min–max

6.0–24.0

−13.0 to 12.0

 

P value in comparison to baseline

 

0.2846

12 months

N (missing)

483 (3)

483 (3)

 

Mean (SD)

17.34 (4.083)

1.03 (4.314)

 

Median

17.00

1.00

 

Min–max

6.0–24.0

−11.0 to 17.0

 

P value in comparison to baseline

 

<.0001

18 months

N (missing)

447 (39)

447 (39)

 

Mean (SD)

17.47 (4.215)

0.90 (4.600)

 

Median

18.00

1.00

 

Min–max

0.0–24.0

−12.0 to 17.0

 

P value in comparison to baseline

 

<.0001

24 months

N (missing)

436 (50)

436 (50)

 

Mean (SD)

17.85 (4.163)

1.36 (5.027)

 

Median

18.00

1.00

 

Min–max

0.0–24.0

−14.0 to 16.0

 

P value in comparison to baseline

 

<.0001

EWB emotional well-being, FACT-B Functional Assessment of Cancer Therapy-Breast, SD standard deviation

In the MIXED model, baseline TOI, clinical visit, and prior chemotherapies had statistically significant effects on the change in FACT-B TOI, whereas age group, mastectomy, and axillary lymph-node dissection had no statistically significant effects on the change in FACT-B EWB (Table 6). In the MIXED model including baseline TOI, clinical visit, prior chemotherapies, age group, mastectomy, and axillary lymph-node dissection, the lower boundaries of the CIs of the LS mean (adjusted mean) changes from baseline to 12, 18, and 24 months in FACT-B EWB were all >0, indicating increased scores at 12, 18, and 24 months of treatment. The changes from 6 months of treatment to 12, 18, and 24 months of treatment are detailed in Table 6.
Table 6

LS mean of changes from baseline in FACT-B EWB score with 95 % CIs (final analysis set)

  

Final analysis set (N = 486)

  

LS mean

95 % CI

P value

Follow-up

6 months

−0.00

−0.53 to 0.53

 

12 months

0.76

0.22–1.30

 

18 months

0.92

0.36–1.48

 

24 months

1.29

0.71–1.86

 

6–12 months

−0.76

−1.04 to −0.48

<.0001

 

6–18 months

−0.92

−1.26 to −0.58

<.0001

 

6–24 months

−1.29

−1.65 to −0.93

<.0001

 

12–18 months

−0.16

−0.46 to 0.14

.2895

 

12–24 months

−0.53

−0.88 to −0.18

.0033

 

18–24 months

−0.37

−0.67 to −0.07

.0172

Prior chemotherapies

Yes

1.54

0.96–2.12

 

No

−0.06

−0.64 to 0.53

 

Yes–No

1.60

1.05–2.14

<.0001

Age group

>60 years

1.01

0.38–1.64

 

≤60 years

0.47

−0.07–1.01

 

>60 years – ≤60 years

0.54

−0.03 to 1.10

.0613

Mastectomy

Yes

1.20

0.85–1.55

 

No

0.29

−0.68 to 1.25

 

Yes–No

0.91

−0.12 to 1.94

.0823

Axillary lymph-node dissection

Yes

0.48

−0.10 to 1.06

 

No

1.01

0.36–1.65

 

Yes–No

−0.53

−1.20–0.14

.1233

CI confidence interval, EWB emotional well-being, FACT-B Functional Assessment of Cancer Therapy-Breast, LS least squares

Changes in the FACT-B SWB from baseline to 6, 12, 18, and 24 months

The mean FACT-B SWB was 18.61, 19.14, 19.35, 18.32, and 18.40 at baseline, 6, 12, 18, and 24 months, respectively, contributing to the mean changes from baseline 0.54, 0.75, −0.45, and −0.19 at 6, 12, 18, and 24 months, respectively. The mean change in FACT-B SWB was significant at 6 months (P < .0435) and 12 months (P < .0086) as compared with the baseline value (Table 7). In the MIXED model, baseline TOI, clinical visit, prior chemotherapies, age group, and axillary lymph-node dissection presented statistically significant effects on the FACT-B SWB, whereas mastectomy presented no statistically significant effects on the FACT-B SWB. The LS means of changes from baseline in the FACT-B SWB score with 95 % CI are presented in Table 8.
Table 7

FACT-B SWB scores at each post-treatment visit and changes from baseline (final analysis set)

  

Final analysis set (N = 486)

Visit

Clinical efficacy

Total score

Change from baseline in total score

Baseline

N (missing)

486 (0)

 
 

Mean (SD)

18.61 (6.732)

 
 

Median

19.30

 
 

Min–max

0.0–28.0

 

6 months

N (missing)

480 (6)

480 (6)

 

Mean (SD)

19.14 (6.068)

0.54 (5.872)

 

Median

19.83

0.00

 

Min–max

0.0–28.0

−24.5 to 28.0

 

P value in comparison to baseline

 

.0435

12 months

N (missing)

483 (3)

483 (3)

 

Mean (SD)

19.35 (6.531)

0.75 (6.245)

 

Median

20.00

0.00

 

Min–max

0.0–28.0

−21.3 to 28.0

 

P value in comparison to baseline

 

.0086

18 months

N (missing)

447 (39)

447 (39)

 

Mean (SD)

18.32 (6.900)

−0.45 (6.605)

 

Median

19.00

0.00

 

Min–max

0.0–28.0

−20.0 to 28.0

 

P value in comparison to baseline

 

0.1523

24 months

N (missing)

436 (50)

436 (50)

 

Mean (SD)

18.40 (7.422)

−0.19 (6.961)

 

Median

19.83

0.00

 

Min–max

1.0–28.0

−21.0 to 28.0

 

P value in comparison to baseline

 

0.5677

FACT-B Functional Assessment of Cancer Therapy-Breast, SD standard deviation, SWB social well-being

Table 8

LS mean of changes from baseline in FACT-B SWB score with 95 % CIs (final analysis set)

  

Final analysis set (N = 486)

  

LS mean

95 % CI

P value

Follow-up

6 months

0.85

0.07–1.63

 

12 months

1.02

0.23–1.80

 

18 months

0.13

−0.69 to 0.95

 

24 months

0.22

−0.62 to 1.07

 

6–12 months

−0.16

−0.63 to 0.30

.4849

 

6–18 months

0.72

0.21–1.23

.0057

 

6– 24 months

0.63

0.05–1.20

.0323

 

12–18 months

0.89

0.49–1.28

<.0001

 

12–24 months

0.79

0.27–1.31

.0029

 

18–24 months

−0.09

−0.51 to 0.32

.6622

Prior chemotherapies

Yes

1.75

0.90–2.61

-

 

No

−0.64

−1.49 to 0.21

-

 

Yes–No

2.40

1.60-3.19

<.0001

Age group

>60 years

1.30

0.39–2.22

 

≤60 years

−0.19

−0.99 to 0.60

 

>60 to ≤60 years

1.50

0.68–2.32

.0004

Mastectomy

Yes

0.72

0.21–1.24

 

No

0.39

−1.02 to 1.79

 

Yes–No

0.33

−1.16 to 1.83

.6596

Axillary lymph-node dissection

Yes

0.06

−0.78 to 0.90

 

No

1.05

0.10–2.00

 

Yes–No

−0.99

−1.97 to −0.01

.0482

Discussion

This first prospective, multicenter, observational, and non-interventional study in Chinese postmenopausal women with HR (+) breast cancer or HR+ EBC undergoing adjuvant treatment with AIs demonstrated significant improvements in the long-term QoL when evaluated at 6, 12, 18, and 24 months post-AI treatment. The study will provide insight to the concerns of the survivors and convey the information to clinical decision-makers who can use it to create patient-centered solutions.

Shen et al. [15] conducted a clinical controlled study in 522 patients to investigate the QoL of Chinese women with breast cancer by using the FACT-B scale. Regression analysis demonstrated that there was a significant increase in FACT-B TOI of the patients >50 years of age, with low-stage cancer, and with high education and income. This was a cross-sectional, single-center observational study in Chinese patients that provided valuable information about factors affecting the QoL of Chinese women with breast cancer. However, dynamic changes on the long-term QoL were not assessed.

Mixed results have been obtained from previous studies conducted on the HRQoL outcomes following AI therapy. Some studies have suggested that treatment with AIs may improve QoL, whereas others have indicated no increased benefit in HRQoL with AI compared with tamoxifen [16]. Fallowfield et al. first published results from a longitudinal follow-up of the impact of 5 years of adjuvant AI (anastrozole) and tamoxifen (alone/combination) treatment on HRQoL in a subgroup of 1105 patients (ATAC) [12]. Improvement in TOI was comparable in both the treatment groups over the 5-year recommended adjuvant treatment period [11, 12].

A 5-point increase in the FACT-B TOI is considered as a significant clinical benefit [17, 18]. The results of our current analysis are in line with those of the above-mentioned studies and demonstrated a significant increase of more than 5 points from baseline (mean: 90.69) to 24 months (mean: 98.72; P < .0001), thereby indicating significant clinical benefit of adjuvant AIs endocrine therapy in the QoL of patients with breast cancer.

Kwan et al. [19] demonstrated that the improvement of FACT-B TOI score in elderly patients (>60 years of age) was better than that in young patients. In addition, ATAC study demonstrated improvement of FACT-B TOI score in patients with previous chemotherapy than in those with no previous chemotherapy [12]. Our findings are in line with these two studies. The findings showed significant effects of all of these factors, except for mastectomy, on the changes in FACT-B TOI scores. Further exploratory analysis also showed that the TOI for the previous chemotherapy patient group >60 years of age without axillary lymph-node dissection was significantly improved from the baseline value. Additionally, effects of baseline score, follow-up, and prior chemotherapy on changes in FACT-B EWB subscale scores were significant, whereas the effects of age group, mastectomy, and axillary lymph-node dissection were not significant. We prospectively set the two subscales of FACT-B, i.e. EWB and SWB as secondary endpoints. We considered that EWB and SWB are more important to women compared with other subscales for the breast cancer, as they serve as an individual resource for dealing with illness and attuning to uncertainties related with chronic illness. It can also affect a woman’s self-esteem or may have psychological impact as a result of breast cancer. There were significant effects of baseline score, follow-up, previous chemotherapy, age group, and axillary lymph-node dissection on changes in FACT-B SWB subscale scores, but mastectomy had no significant effect. Although studies have analyzed the HRQoL outcomes following AI treatment, a definitive comprehensive conclusion on long-term HRQoL is still lacking in China. Several unresolved issues still prevent clinicians from designing an optimal endocrine therapy for postmenopausal women with EBC. Thus, the current study provides reinforcement to the previous findings and indicates improved long-term QoL with AI treatment. This will aid clinicians in optimizing treatment to yield effective healthcare outcomes.

Our results were different from those of ATAC and the Intergroup Exemestane Study (IES) substudy, which may be probably because of the following factors: (1) culture background: after treatment, American women with breast cancer were more likely to feel a loss of personal image, intimacy, and sex life than East Asian women [20, 21]; (2) study population: although the patients in ATAC, IES, and this study were menopausal women, there was no clear definition of “menopause” in the relevant published literature; therefore, it cannot be confirmed whether the definition was consistent with that in NCCN-Breast Cancer Version 2013 ( having previous bilateral oophorectomy; ≥60 years of age; <60 years of age having experienced amenorrhea for more than 12 months with no chemotherapy, tamoxifen, toremifene, or ovariectomy and follicle-stimulating hormone (FSH) and estradiol within menopausal range; <60 years of age having taken tamoxifen or toremifene, and FSH and plasma estradiol within menopausal range). Women ≤60 years of age accounted for only 33.7 % in the IES study, whereas women ≤60 years of age accounted for 65.0 % in this study.

Finally, the inherent limitations of this study should not be neglected. The study had neither a control or a standard group nor a blinding design. It is well known that a standard endocrine therapy for breast cancer would continue for at least 5 years; however, in the current study, all but 1 patient received the initial hormonal therapy at baseline and the follow-up was only for 2 years. Therefore, the effect of endocrine therapy on 3- to 5-year long-term QoL remains unknown. The aforementioned limitations indicate that this study only recognizes the significant improvements in the long-term QoL (6, 12, 18, and 24 months) of postmenopausal Chinese patients with HR+ EBC after starting treatment with AIs and does not provide a robust association between improvement of QoL scores ande treatment with AIs. Generally, observational studies have the benefit of assessing multiple aspects of lifestyle and better represent the results; however, potential limitation of selection bias and reporting of scores may have confounded the overall results in this study. We also did not assess the side effects of the treatment by aromatase inhibitors in this population. We had not systematically recorded the safety profile during the study execution and retrospective safety recall would have bias. Taken together, our study results showed the dynamic change of FACT-B, which will guide the physicians to communicate with the HR+ EBC patients about the QOL when receiving adjuvant AIs. Also, the improved QoL will increase patient compliance during the study treatment.

Conclusions

The present study demonstrated significant improvements in the long-term QoL of postmenopausal patients with EBC at 6, 12, 18, and 24 months after starting treatment with AIs compared with baseline values. Based on results from the MIXED model (for data collection at 6, 12, and 18 months), we found significant effects of baseline score, follow-up, previous chemotherapy, age group, and axillary lymph-node dissection on changes in FACT-B TOI score and SWB scores, as well as significant effects of baseline score, follow-up, and previous chemotherapy on changes in FACT-B EWB scores. However, there were no significant effects of mastectomy on changes in TOI, SWB, or EWB scores. Further comparative work should be undertaken to strengthen the findings from this study.

Abbreviations

AI: 

Aromatase inhibitor

ATAC: 

Arimidex, Tamoxifen, Alone or in Combination (trial)

BCS: 

Breast Cancer Subscale

CI: 

Confidence interval

EBC: 

Early-age breast cancer

ER+: 

Estrogen receptor-positive

ES: 

Endocrine subscale

EWB: 

Emotional well-being

FACT-B: 

Functional Assessment of Cancer Therapy-Breast

FACT-G: 

Functional Assessment of Cancer Therapy-General

FSH: 

Follicle-stimulating hormone

HR+: 

Hormone receptor-positive

HRQoL: 

Health-related QoL

ICF: 

Informed consent form

IES: 

Intergroup Exemestane Study

ITT: 

Intent to treat

LS: 

Least squares

NCCN: 

National Comprehensive Cancer Network

PR+: 

Progesterone receptor-positive

QoL: 

Quality of life

SD: 

Standard deviation

SFDA: 

State Food and Drug Administration

SWB: 

Social well-being

TOI: 

Trial outcome index

TNM: 

Cancer classification system based on tumour (T), lymph node (N) and metastase (M)

WHO: 

World Health Organization

Declarations

Acknowledgments

The authors would like to thank Dr. Amit Bhat and Mrs. Nishi Gupta (Indegene Lifesystems Pvt. Ltd., Bangalore, India), and Dr. Simon Vass (Complete Medical Communications) for providing medical writing support and technical assistance in the preparation of this manuscript, funded by AstraZeneca. We also thank all the authors for their dedication to the study.

Funding

The study was supported by the AstraZeneca Pharmaceutical Company.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
(2)
Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
(3)
Department of Breast Surgery, Jiangsu Province Hospital, Nanjing, China
(4)
Department of Oncology Surgery, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo, China
(5)
Breast Disease Center, Peking University First Hospital, Beijing, China
(6)
Department of Breast Surgery, First Hospital of Jilin University, Changchun, China
(7)
Breast Disease Center, Guangdong Women and Children’s Hospital and Health Institute, Guangzhou, China
(8)
Department of Breast Disease, Yunnan Tumor Hospital, Kunming, China
(9)
Breast Disease Center, First Affiliated Hospital of Medicine College of Zhejiang University, Hangzhou, China
(10)
Breast Disease Center, Peking University People’s Hospital, Beijing, China
(11)
Medical Oncology Center, Hunan Tumor Hospital, Changsha, China
(12)
Department of General Surgery, Jiangsu Cancer Hospital, Nanjing, China
(13)
Department of General Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
(14)
Department of Oncology Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, China
(15)
Department of Breast Surgery, The Tumor Hospital of Harbin Medical University, Harbin, China
(16)
Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an, China
(17)
Department of Breast and Thyroid Surgery, Shanghai Tenth People’s Hospital, Shanghai, China
(18)
Department of Breast and Thyroid Surgery, Shenzhen Second Hospital, Shenzhen, China
(19)
Department of Breast Surgery, Shanghai Changhai Hospital, Shanghai, China
(20)
Department of Breast Surgery, The Affiliated Hospital of Guiyang Medical College, Guiyang, China

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Copyright

© Cao et al. 2016

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