Health related quality of life: Impact of surgery and treatment modality in breast cancer

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1 Original Article Health related quality of life: Impact of surgery and treatment modality in breast cancer ABSTRACT Background: Breast cancer is the most common malignancy among women leading to serious sequelae on the health related quality of life (HRQOL). Materials and Methods: This is a cross sectional study. The Arabic version of EORTC QLQ C30 (version 3) and EORTC QLQ BR23 questionnaire was administered to a random sample of 172 Egyptian women with breast cancer. One hundred and nineteen patients had modified radical mastectomy (MRM) and 53 had breast conservative surgery (BCS). Results: The mean age was years (±standard deviation [SD] = 8.54) with a mean period of 4.75 years (±SD 3.33) from surgery. The global health was poor (28.38 ± 11.7, 95% confidence interval [95% CI]: 30.71). Among the functional scales of QLQ C30, social functioning scored the highest (87.91 ± 17.92, 95% CI: 91.64) whereas emotional functioning scored the lowest (59.61 ± 24.96, 95% CI: 64.66). The most distressing symptom on the symptom scales of QLQ C30 was financial impact followed by fatigue and pain (mean: 57.87, 39.43, and 36.44). Using the disease specific tools, it was found that body image and sexual functioning scored the lowest (mean ± and ± 14.89, 95% CI: and 77.55), respectively. On the symptom scale, arm symptoms scored the highest with a mean of ± (95% CI: 37.19). MRM patients had more favorable global health status and body image among the functional scale (P = 0.011, 0.027) due to social and religious issues. The functional scale was better in BCS with significant role function (P = 0.004). In the symptom scale, fatigue, pain, systemic side effects, and arm symptoms were statistically significant better in the BCS (P = 0.004, 0.006, 0.002, and 0.003, respectively). Conclusion: Egyptian breast cancer survivors reported lower overall global QOL. HRQOL is better in BCS in spite of good global health and body image in MRM. KEY WORDS: Breast cancer, Middle East, quality of life, surgery INTRODUCTION Breast cancer is the most common malignancy among women leading to serious sequelae on the health related quality of life (HRQOL). [1,2] The survival of patients has recently improved due to the early stage at diagnosis, a better understanding of tumor biology, and the evolution in adjuvant treatment and clinical trials. Long term survival is expected among early breast cancer patients; however, the QOL may be compromised. Long term consequences including painful and often debilitating lymph edema postsurgery or radiation therapy may be expected. Therefore, breast conservative surgery (BCS) is the treatment of choice for early stage breast cancer with equal or even higher survival when compared to modified radical mastectomy (MRM). [3-5] This has led to increase in the QOL concerns among these patients and experiencing less stress with good compliance to medical care. [6] This is a pilot study in Egypt studying the QOL of breast cancer patients with special attention to the type of surgery as well as cultural and religious impact. MATERIALS AND METHODS This is a cross sectional random study including breast cancer patients attending the follow up This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution NonCommercial ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: reprints@medknow.com Mona Aboul Enien, Noha Ibrahim, Wael Makar, Dalia Darwish, Mohamed Gaber 1 Department of Clinical Oncology, Kasr Al Ainy Center of Clinical Oncology and Nuclear Medicine (NEMROCK), Kasr Al Ainy School of Medicine, Cairo University, 1 Department of Clinical Oncology, Mataria Teaching Hospital, Cairo, Egypt For correspondence: Dr. Dalia Darwish, Department of Clinical Oncology, Kasr Al Ainy Center of Clinical Oncology and Nuclear Medicine (NEMROCK), Kasr Al Ainy School of Medicine, Cairo University, P.O. Box 99, Manial El Roda, Cairo 11553, Egypt. E mail: daliaomard@ kasralainy.edu.eg Access this article online Website: DOI: / PMID: *** Quick Response Code: Cite this article as: Enien MA, Ibrahim N, Makar W, Darwish D, Gaber M. Health-related quality of life: Impact of surgery and treatment modality in breast cancer. J Can Res Ther 2018;14: Journal of Cancer Research and Therapeutics Published by Wolters Kluwer - Medknow 957

2 clinic at Centre of Clinical Oncology. All pathologically proven female with breast cancer above 18 years, >12 months from the diagnosis with no recurrence or distant metastasis, Eastern Cooperative Oncology Group performance status of 0 2, and accepting to take the questionnaire were included. Patients with any psychiatric disease or double malignancy were excluded from the study. A structured questionnaire collecting sociodemographic, clinical, and QOL data were used. This was introduced orally by a physician to the patients as most of them were illiterate. QOL was assessed using the European Organization for Research and Treatment of Cancer QOL Cancer Specific Version (EORTC QLQ C30, version 3.0) translated into Arabic and validated. [7] The EORTC QLQ 30 included 30 questions divided into four domains: Global health, functional scale (physical, role, cognitive, emotional, and social), symptom scale (fatigue, pain, nausea, and vomiting), and six single items assessing additional symptoms (dyspnea, loss of appetite, insomnia, constipation, diarrhea, and financial impact of the disease). The QOL Breast Cancer Specific Version, (EORTC QLQ BR23), [7] translated and validated into Arabic including 23 questions was also used. This included two scales: Functional (body image, sexual function, sexual enjoyment, and future perspective) and symptom scale (systemic side effect, breast symptoms, arm symptoms, and upset by hair loss). Scores for these questions are transformed linearly to range between 0 and 100. For scales evaluating global health and function, a higher score 66.6% represents a higher level of functioning and health where as in the symptom scale it reflects more problems and symptoms. Low scores are 33.3%. Functional scale = 1 (row score 1/range) 100 Global health status and symptom scale = (row score 1/ range) 100 Row score = Estimate of the average items that contribute to the scale (e.g., the physical function contains five items [five questions], so it is divided by 5). Range = Range of score in each item = 3 in most items (scoring from 1 to 4) = 6 in global health status (scoring from 1 to 7). Ethical approval was granted by the Center Research and Ethics Committee. Written consent was obtained from every participant. Statistical analysis The collected data were coded, entered, and analyzed using the statistical package SPSS version 15.0 for Microsoft Windows (2006). Relevant descriptive statistics was computed for all items. A higher score represents a better level of functioning or a worse level of symptoms. The score served as the dependent variable in the study for the purpose of data analyses. Sociodemographic data, cancer and treatment information, represented the independent variables. Data were statistically described regarding means ± standard deviation (±SD) or frequencies (number of cases) and percentage when appropriate. Comparison of the numerical variables between the study groups was performed using Student s t test for independent samples while the equality of means across the categories of each categorical independent variable was tested using parametric tests (ANOVA). For comparing categorical data, Chi square was performed. Fisher s exact test was used instead when the expected frequency is <5. The value of P < 0.05 was considered statistically significant. As recommended by an empirical population based study, [8] for the functional scales and the global QOL, we defined subjects with problematic functioning as those who scored <33.3% while subjects in good condition scored 66.7%. For symptom scales, subjects scoring <33.3% were judged as having less severe symptoms while those scoring 66.7% had more intense symptoms. Multivariate linear regression modeling was used to build a predictive model to assess the significance of predictors of the important QOL scale values. R 2 was computed. A P < 0.05 was considered statistically significant. RESULTS The questionnaire was administered to a random sample of 172 Egyptian women with breast cancer. Among these patients, 119 were subjected to MRM and 53 were subjected to BCS. All questions were answered except those related to sexual and body image as they deem it culturally improper to express sexual desire and affairs. This was illustrated in all unmarried women and 28.46% of the married ones. The characteristics of the sample are presented in Table 1. The mean age of participants was 50, 32 years (±SD 8.54) with a mean period of 4.75 years (±SD 3.33) from surgery (5 and 4.3 years from MRM and BCS, respectively). Patient characteristics tended to be similar except for age, stage, and nodal status (P = 0.06, 0.05, , and 0.001). Women with BCS were younger, had more early stage and no nodal infiltration. Most patients in both groups were married (75%), however divorce was more common in BCS (13.2% vs. 4.2%, P = 0.05). Most of the population were illiterate (54.7%), living in rural areas (69.8%), having no active role in selecting the type of surgery (90.7%) with a period of 2 5 years since surgery (73.8%). Participants had a mean score for global health of ± 11.7 (95% confidence interval [95% CI]: 30.71). Among the functional scales of QLQ C30, social functioning scored the 958 Journal of Cancer Research and Therapeutics - Volume 14 - Issue 5 - July-September 2018

3 Table 1: Demographic characteristics of the study population (n=172) Characteristics n Overall (%) MRM BCS Age < (26.1) 16 (30.2) (39.5) 28 (52.8) > (34.5) 9 (17.0) Education University (5.9) 1 (1.9) 0.2 High school (23.5) 19 (35.8) Primary school (12.6) 8 (15.1) Illiterate (58.0) 25 (47.2) Marital status Married (75.6) 40 (75.5) Widow (20.2) 6 (11.3) Divorced (4.2) 7 (13.2) Living environment Urban (32.8) 13 (24.5) 0.2 Rural (67.2) 40 (75.5) Menstruation before treatment Pre (50.4) 29 (54.7) 0.6 Post (49.6) 24 (45.3) DM Yes (21.0) 8 (25.1) 0.3 No (79.0) 45 (84.9) HTN Yes (30.3) 9 (17.0) 0.06 No (69.7) 44 (83.0) Active role in selecting type of surgery Yes (7.6) 7 (13.2) 0.2 No (92.4) 46 (86.8) Laterality Right (47.9) 28 (52.8) 0.5 Left (52.1) 25 (47.2) Time since surgery (years) 2 and (70.6) 43 (81.1) 0.1 > (29.4) 10 (18.9) Stage I (5.9) 18 (34.0) II (46.2) 26 (49.1) III (47.9) 9 (17.0) Nodes positive N0 (0) (31.9) 36 (67.9) 0.00 N1 (1-3) (28.6) 8 (15.1) N2 (4-9) (21.8) 6 (11.3) N3 (>9) (17.6) 3 (5.7) Nodes removed (5.9) 3 (5.7) (57.1) 31 (58.5) > (37.0) 19 (35.8) ER Positive (86.6) 45 (84.9) 0.7 Negative (13.4) 8 (15.1) PR Positive (84.9) 41 (77.4) 0.2 Negative (15.1) 12 (22.6) HER 2/neu Positive (13.4) 10 (18.9) 0.07 Negative (68.1) 40 (75.5) Not done (18.5) 3 (5.7) Ki 67 Not done (91.6) 45 (84.9) 0.3 Low <14% (3.4) 2 (3.8) High >14% (5.0) 6 (11.3) P Contd... Table 1: Contd... Characteristics n Overall (%) MRM BCS Radiotherapy Yes (89.9) 51 (96.2) 0.1 No (10.1) 2 (3.8) Chemotherapy Yes (90.8) 45 (84.9) 0.2 No (9.2) 8 (15.1) Hormonal therapy Yes (92.4) 45 (84.9) 0.1 No (7.6) 8 (15.1) Lymphedema No (36.1) 27 (50.9) 0.1 After surgery (44.5) 18 (34.0) After the 1 st year (19.3) 8 (15.1) MRM=Modified radical mastectomy, BCS=Breast conservative surgery, HTN=Hypertension, PR=Progesterone receptor, ER=Estrogen receptor, HER 2=Human epidermal growth factor receptor 2, DM=Diabetes mellitus highest ± (95% CI: 91.64) whereas emotional functioning scored the lowest ± (95% CI: 64.66) [Table 2]. The most distressing symptom on the symptom scales of QLQ C30 was a financial impact with a mean of ± (95% CI: 62.24) followed by fatigue ± (95% CI: 43.12) and pain ± (95% CI: 40.21). Using the disease specific tools, it was found that body image and sexual functioning scored the lowest (mean ± and ± [95% CI: and 77.55]), respectively. On the symptom scale, arm symptoms scored the highest with a mean of ± (95% CI: 37.19). In comparison of QOL scale between MRM and BCS, MRM patients had more favorable significant mean global health status and body image among the functional scale (mean: 32.2 vs. 27.2, P = 0.011, mean 76.5 vs. 69.7, P = 0.027, respectively) due to social and religious issues. The functional scale was better in BCS with significant role function (mean: 63.5 vs. 52.3, P = 0.004) [Table 3]. In the symptom scale, fatigue, pain, systemic side effects, and arm symptoms were statistically significantly better in the BCS (P = 0.004, 0.006, 0.002, and 0.003, respectively). Elderly illiterate postmenopausal patients with advanced stage and lymphedema had more unfavorable HRQOL. Regarding the factors associated with QOL scale scores, Global health and functional scale in QLO C30. There were significant differences in the global health means across categories of age (P = 0.002), education (P = 0.002), menopausal status (P = 0.009), comorbidity (P = 0.013), stage of the disease (P = 0.038), human epidermal growth factor receptor 2 (HER 2) positive (0.015), chemotherapy (P = 0.043), lymphedema (P = 0.044), and the type of surgery (P = 0.011). P Journal of Cancer Research and Therapeutics - Volume 14 - Issue 5 - July-September

4 Table 2: Mean score of all items in quality of life questionnaire C30 and quality of life questionnaire BR23 (n=172) QOL items Number of items scoring <33.3) a (%) scoring 66.7) a (%) Mean (SD) 95% CI QLQ C30 Global health status 2 77 (44.8) 1 (0.6) 28.38± Functional scales b Physical functioning 5 2 (1.2) 149 (86.6) 83.37± Role functioning 2 13 (7.6) 107 (62.2) 62.45± Emotional functioning 4 7 (4.1) 98 (57) 59.61± Cognitive functioning 2 10 (5.8) 95 (55.2) 65.56± Social functioning 2 0 (0) 162 (94.2) 87.91± Symptom scales c Fatigue 3 25 (14.5) 46 (26.7) 39.43± Nausea and vomiting (90.7) 0 (0) 5.86± Pain 2 38 (22.1) 42 (24.4) 36.44± Dyspnea 1 99 (57.6) 25 (24.5) 17.58± Sleep disturbance 1 98 (57) 30 (17.4) 21.24± Appetite loss (63.4) 23 (13.4) 13.18± Constipation 1 89 (51.7) 30 (17.4) 21.24± Diarrhea (85.5) 1 (0.6) 5.86± Financial impact 1 4 (2.3) 122 (70.9) 57.87± QLQ BR23 Functional scales b Body image no answer 79 (45.9%) 4 93 (54.1) 69 (40.1) 74.51± Sexual functioning no answer 2 91 (52.9) 67 (39) 74.45± (47.1%) Sexual enjoyment no answer 1 17 (9.9) 14 (8.1) 32.23± (47.1%) Future perspective no answer 1 36 (20.9) 12 (7) 41.75± (45.9%) Symptom scales c Systemic side effect (59.9) 2 (1.2) 28.41± Breast symptoms (91.3) 4 (2.3) 11.53± Arm symptoms 3 72 (41.9) 33 (19.2) 32.35± Upset by hair loss (62.8) 23 (13.4) 15.75± a For functional scales, subjects scoring <33.3% have problems; those scoring 66.7% have good functioning. For symptom scales/symptoms, subjects scoring <33.3% have good functioning; those scoring=66.7% have problems, b For functional scales, higher scores indicate better functioning, c For symptom scales, higher scores indicate worse functioning. QLQ=Quality of life questionnaire, SD=Standard deviation, CI=Confidence interval, QOL=Quality of life Analysis of the results revealed that subjects >55 years, illiterate, postmenopausal, hypertensive, stage III disease, received adjuvant chemotherapy having lymphedema after surgery, and undergone MRM tended to have better global HRQOL. In the functional scale, there were significant differences in the physical, role, and emotional function. The physical function was correlated with age (P = 0.001), education (P = 0.015), menopausal status (P = 0.001), comorbidity (P = 0.001), stage (P = 0.011), and lymphedema (P = 0.044). Analysis of the results revealed that subjects <40 years, university educated, premenopausal, not hypertensive nor diabetic with stage I not complaining of lymphedema tended to have better physical functioning related QOL. The role function was correlated with age (P = 0.008), education (P = 0.041), menopausal status (P = 0.024), comorbidity (P = 0.002), and type of surgery (P = 0.004). Analysis of the results revealed that subjects <40 years, university educated, premenopausal, not hypertensive and undergone BCS tended to have better role functioning related QOL. The emotional function was correlated with age (P = 0.002), marital status (P = 0.003), and menopausal status (P = 0.016). Analysis of the results revealed that subjects >50 years and postmenopausal tended to have better emotional functioning related QOL. The body image was affected by marital status (P = 0.015), hypertension (P = 0.032), lymph node status (P = 0.27), and the type of surgery (P = 0.027). The results revealed that subjects who were widowed, hypertensive with nodal status no. 1, and undergone MRM tended to have better body image related QOL. Sexual function was better in premenopausal (P = 0.046) whereas sexual enjoyment was relevant in postmenopausal (P = 0.037). On the symptom scale, there were significant differences in sleep disturbance, arm symptoms, and lymphedema. Sleep disturbance was significant among categories of marital status (P = 0.028), estrogen receptor (ER) status (P = 0.015), and hormonal treatment (P = 0.038). Divorced women with ER positive and receiving hormonal treatment tended to have more severe symptoms of sleep disturbance related QOL. Arm symptoms were more intensely correlated among categories related to the type of surgery (P = 0.003), time since surgery (P = 0.048), nodal status (P = 0.001), stage (P = 0.001), HER 2 status (P = 0.02), and lymphedema (P = 0.001). These 960 Journal of Cancer Research and Therapeutics - Volume 14 - Issue 5 - July-September 2018

5 Table 3: Comparison of surgical treatment alternatives based on quality of life questionnaire scale scores QLQ C30 and BR23 items Number of items MRM Mean±SD BCS QLQ C30 Global health status ± ± Functional scales Physical functioning ± ± Role functioning ± ± Emotional functioning ± ± Cognitive functioning ± ± Social functioning ± ± Symptom scales Fatigue ± ± Nausea and vomiting ± ± Pain ± ± Dyspnea ± ± Sleep disturbance ± ± Appetite loss ± ± Constipation ± ± Diarrhea 1 4.4± ± Financial impact ± ± QLQ BR23 Functional scales Body image ± ± Sexual functioning ± ± Sexual enjoyment ± ± Future perspective ± ± Symptom scales Systemic side effect ± ± Breast symptoms ± ± Arm symptoms ± ± Upset by hair loss ± ± QLQ=Quality of life questionnaire, SD=Standard deviation, MRM=Modified radical mastectomy, BCS=Breast conservative surgery symptoms were clear in women with MRM, <5 years from surgery, stage III disease, node II III, HER 2 positive, and complaining of lymphedema after the 1 st year of surgery. Upset due to hair loss was observed among categories of marital status (P = and lymphedema (P = 0.043). Divorced women with lymphedema had more severe symptoms. Predictors of QOL explained 21% of the variation in global health (R 2 = 0.21). The predictors which had a significant effect on global health given the other predictors in the model were education (P = 0.002) and chemotherapy (P = 0.014). The same model was built for every domain in QLQ C30 and QLQ BR23 functional scales. The significant predictors in the models were age in the emotional functioning (P = 0.009), hypertension in the physical functioning (P = 0.020), MRM in the role functioning, and body image models (P = and 0.035), respectively. Stage was a significant predictor in the body image functioning model (P = 0.003) whereas chemotherapy was a significant predictor in the global health and cognitive functioning models (P = and 0.050), respectively. Radiotherapy was the most important predictor in the physical and social functioning models (P = and 0.039) whereas lymphedema was the most relevant in the physical functioning model (P = 0.023). P DISCUSSION This is one of the rare studies in Egypt that assess QOL of breast cancer survivors and indicated that Egyptian women with breast cancer have average to good QOL functioning and low to average symptoms experience. The global health score was low. The poorest functions regarding symptoms were fatigue, pain, and arm symptoms. The global health was much lower when compared to other Western and Asian studies (28.38 ± 11.7) such as Bahraini (63.9), South Korea (66.5), the UK (66.8), and India studies (42.24). [8 11] Furthermore, it was the lowest among the Middle East region when compared to their counterparts in Bahrain (63.9), Kuwait (45), and Iran (32). [8,12,13] This may be attributed to the limitation of psychological support among the families and the poor understanding of QOL, thus giving more negative response. This study was similar to other studies in Europe and Asia in showing that the poorest functioning regarding symptoms was fatigue, pain, and arm symptoms. [10,13] QOL may not be limited to mean scores but referred to the population based reference values. [8,14] This was not elicited in all the studies and so comparison is not always applicable. Interpreting the results should be guided by the place culture, the study design, population characteristics as well as the time elapsed from surgery. For example, although the mean score for global health indicated mild good functioning, only 0.6% of participants met the 66.7% criterion for good functioning. This was elicited in 10.9% of a participant in Kuwait and 38.5% in Bahrain. [8,15] Our study group was enrolled at a random selection from the clinic while the Bahraini study by Jassim and Whitford 2013 was from national registry and the Kuwait authors 2008 used a convenient sample. The participants in this study had a higher mean age (50.32) compared to Kuwait (46.6) and Bahrain (48.3), respectively. [8,12] The patients were studied at a higher mean time of 4.75 years from surgery compared to 23 months in the Iranian study by Hadi et al and 12.5 years in the Canadian study by Hsu et al. 2013, whereas the Turkish study by Akca et al completely neglected the time factor. [16 18] Similar to other studies, women showed an average performance on most functional scales except for sexual functioning, enjoyment, and body image which demonstrated poor functioning. [19] Disturbed sexual function may be due to low self esteem, hair loss, abrupt menopause, vaginal dryness partner s difficulty understanding one s feelings, and body image problems. However, one should note that in this study all unmarried subjects 24.42% and 28.46% of married subjects did not respond to the questions of sexual and body image Journal of Cancer Research and Therapeutics - Volume 14 - Issue 5 - July-September

6 as they may deem it culturally improper to express sexual desire or affairs. In our study, global health and emotional functioning were more favorable in participants >50 years, illiterate, postmenopausal, stage III disease, and received adjuvant chemotherapy which is different from other studies which may refer to their age group, traditional, and religious issues. [11] In spite of poor global health and fair emotional functioning in previously mentioned participants, the rest of functional scales and significantly physical functioning and role functioning were more favorable in <50 years, university education, premenopausal, and stage I disease without lymphedema participants as other studies. Fatigue, pain, and arm symptoms were more intense in >50 years, illiterate, postmenopausal stage III with lymphedema participants. This was comparable to other studies. [9,11] When the QOL scales were compared between surgical alternatives, we found that in our study global health, emotional functioning, and body image were more favorable in MRM group than BCS group. This may be explained by that the MRM group had more participant >50 years, illiterate, from rural areas, and were stage III disease having special cultural and religious beliefs. They thought that they should not complain in the questions related to global health and emotional function as they should be grateful to God for his gifts to them even if they were annoyed. This was not consistent with another Egyptian study by Denewer et al in Mansoura University comparing 100 patients with sparing mastectomy and immediate autologous breast reconstruction to another 100 with traditional mastectomy. The body satisfaction scale was higher in the reconstructed group with no difference in the breast impact of the treatment scale. The group with reconstruction had a lower mean age (39 vs years) with a higher level of education and more support from the partner. [20] However, in our study like other literatures, patients who had undergone BCS had more favorable functional scales outcomes relative to MRM in almost all other items. Furthermore, MRM had more intense symptoms relative to BCS patients. [17,19] Breast cancer in Arab countries is affected by religious and cultural issues which are different than Western countries. Improvement of QOL of these patients has improved in the last decade mainly due to increased Arab publications in the breast cancer field. Egypt contributed 35.1% (582) of the publications mainly from Cairo University (8.9%, 149) followed by Saudi Arabia. [21] Limitations The study was limited by the small number of patients, relatively short follow up, and lack of control group. Furthermore, each patient was assessed only once from diagnosis and compared with others at different time interval. CONCLUSION QOL must be integrated in the treatment plan of breast cancer patients. BCS had more favorable functional scales, especially the role functioning while MRM had more intense symptoms, especially arm symptoms. Acknowledgments The questionnaires were used with authorization from the EORTC QOL Study Group., we would like to thank all participants, physicians, and nurses in the Kasr Al Ainy Centre of Clinical Oncology and Nuclear Medicine (NEMROCK), Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. REFERENCES 1. U.S Cancer Statistics Working Group. United States Cancer Statistics Incidence and Mortality Web Based Report. 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