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Quality of Life in Women With Breast Cancer Treated With or Without Chemotherapy

Tiezzi, Maria Fernanda Barbirato da Mata MS; de Andrade, Jurandyr Moreira MD, PhD; Romão, Adriana Peterson Mariano Salata PhD; Tiezzi, Daniel Guimarães MD, PhD; Lerri, Maria Rita MS; Carrara, Hélio Angotti Humberto MD, PhD; Lara, Lúcia Alves Silva MD, PhD

doi: 10.1097/NCC.0000000000000370
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Background: The diagnosis and treatment of breast cancer may negatively affect the quality of life (QOL) of women.

Objectives: The aim of this study is to assess QOL in women with breast cancer who were treated with or without chemotherapy and to identify factors associated with improved or worsening QOL in these women.

Methods: This cross-sectional study enrolled 112 women who were treated with chemotherapy (CTX group, with 85 [75.9%] women) or without chemotherapy (non-CTX group, with 27 [24.1%] women) for breast cancer. The Short-Form Health Survey (SF-36) assessed QOL and the Hospital Anxiety and Depression scale assessed anxiety and depression.

Results: The overall mean SF-36 score was below 50 in all domains. Relative to CTX women, non-CTX women were significantly older (P = .001) and more likely to engage in physical exercise (P = .002). The non-CTX group had higher scores in the Physical Functioning (P = .001) and Role-Physical (P = .0009) domains of the SF-36 relative to the CTX group, and the fluoruracil + epirubicin + cyclophosphamide group had significantly lower scores in the SF-36 domains Physical Functioning (P = .009) and Role-Physical (P = .02).

Conclusion: Chemotherapy treatment for breast cancer worsens QOL in the Physical Functioning and the Role-Physical domains of the SF-36 relative to women treated without chemotherapy.

Implications for Practice: Nurses should assess Physical Functioning and the Role-Physical before treatment, as a woman who was not physically active before breast cancer is not likely to become physically active after treatment. Establishing support groups and providing educational sessions about the disease and its management, supportive care can improve the QOL of this population.

Author Affiliations: Sector of Human Sexuality of the Department of Gynecology and Obstetrics, Ribeirão Preto School of Medicine, São Paulo (Ms Tiezzi, Dr Romão, Ms Lerri, and Dr Lara); and Breast Disease Division, Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, São Paulo University, Brazil (Drs de Andrade, Tiezzi, and Carrara).

The authors have no funding or conflicts of interest to disclose.

Correspondence: Lúcia Alves Silva Lara, MD, PhD, Service of Human Sexuality of the Department of Gynecology and Obstetrics, Ribeirão Preto School of Medicine, São Paulo University, Brazil Av Bandeirantes, 3900, 14049-900 Ribeirão Preto, SP, Brazil (luciaalvess@yahoo.com.br).

Accepted for publication February 2, 2016.

The diagnosis and treatment of breast cancer may negatively affect the physical and emotional well-being of women because of adverse effects of treatment, fear of death, and feelings of social devaluation.1 In addition, treatment of breast cancer may lead to reduced functional capacity, loss of breast sensitivity, and changes in self-image, as well as anxiety, depression, and other psychological and emotional changes.2 Women with breast cancer experience a range of treatments, including radiotherapy, surgery, chemotherapy, and hormone therapy. The type of treatment may affect the degree of physical and psychological distress related to poorer body image and sexual problems experienced by breast cancer patients.3 Indeed, even cancer-free women who experience a loss of physical integrity show abrupt shifts in self-identity and distancing in intimate relationships.4 When treatment involves a mastectomy, the surgical sequelae may negatively impact the physical and psychological functioning of the patient. All of these effects may negatively impact the quality of life (QOL) of breast cancer patients.5

Quality of life has been defined as a “state of complete physical, mental and social well-being, and not merely the absence of disease and infirmity”6 and as “the individual’s perception of their position in life in the context of culture and value systems in which they live, and in relation to their goals, expectations, standards and concerns.”7 It is recommended that instruments for measuring QOL should involve 3 dimensions: physical function, mental status, and ability to engage in normal social interactions.8

Chemotherapy is frequently indicated for the treatment of breast cancer to increase the disease-free survival time. However, this treatment may have short-term and long-term adverse effects.9 Previous research indicated that women who underwent chemotherapy and radiotherapy reported negative effects on general health and sexual function.2,10,11 Neutropenia and anemia are frequent in patients treated with the fluorouracil/epirubicin/cyclophosphamide (FEC) regimen, and docetaxel toxicities give rise to stomatitis and alopecia12 and nausea/vomiting.13 Alopecia is a transitory effect of chemotherapy but has negative effects on self-image and psychosocial well-being and can lead to depression, and many women consider it one of the worst experiences from undergoing treatment for breast cancer.14 Chemotherapy also affects the ovaries, and alkylating agents have cytotoxic effects that decrease the number of primordial follicles and leads to ovarian failure. This impairs the synthesis of sex steroids (estrogen and androgen) and leads to climacteric symptoms such as hot flashes, night sweating, irritability, sleep disorders, weight gain, and urogenital atrophy.15 Patients may experience the toxic effects of chemotherapy after the end of the treatment.11 Thus, evidence from various populations indicates that chemotherapy may decrease the posttreatment QOL of breast cancer patients. A survey of the literature showed that many studies have evaluated the QOL of women undergoing treatment for breast cancer. However, few studies have evaluated the impact of chemotherapy on the QOL of women undergoing treatment for breast cancer, and these limited studies have reported discordant results. A German study showed significant negative impact of adjuvant chemotherapy on QOL in women with breast cancer treated with chemotherapy compared with women treated with radiotherapy and adjuvant hormonal therapy.16 Similarly, a Swedish study showed that chemotherapy treatment is associated with physical and emotional problems such as anxiety, pain, nausea/vomiting, altered body image, increase in fatigue, as well as other side effects measured over time.17 In contrast, Brazilian women treated for breast cancer reported no impairment of QOL as measured by overall 36-item Short-Form Health Survey (SF-36) scores after treatment was completed.18,19

The lack of clear data on this topic hinders the development of interventions to reduce chemotherapy-related symptoms that negatively impact the QOL of women with breast cancer.

After breast cancer treatment is completed, the medical interventions involved, such as chemotherapy, radiotherapy, and surgery, may have sequelae, including hair loss, weight gain, scarring, infertility, premature menopause, physical limitation such as limited ability to walk,20,21 as well as limitation to perform certain body movements,22 body image concerns, and low self-esteem23–27 that can impact QOL. Common concerns in the sexual dimension are related to dyspareunia, decreased sexual desire, alterations in body image, emotional distancing from the partner, and perceived change in the partner’s level of sexual interest.28

In a randomized controlled trial, nursing interventions such as proactive telephone calls as part of disease management programs were considered useful by patients to address specific symptoms related to the chemotherapy or medication concerns.29 A multidisciplinary approach is required to reduce the negative impacts of breast cancer treatment on women. Specific measures that may improve QOL include exercising after treatment30 and during chemotherapy that may either protect against chemotherapy-induced declines in physical and aerobic fitness31 or improve self-esteem, body composition, and lymphedema.32

The objective of this cross-sectional study was to assess the QOL of women with breast cancer who were treated with or without chemotherapy and to identify factors associated with improvement or worsening of QOL in these women.

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Methods

This was a cross-sectional study of a convenience sample of women, aged 40 to 70 years, who underwent treatment for breast cancer 1 to 3 years previously and were followed up at the Mastology Outpatient Clinic of the Gynecology and Obstetrics Department, of Ribeirão Preto Medical School, São Paulo University. A psychologist (M.F.B.M.T.) consecutively invited women while they were waiting for medical visits in the waiting room of the clinics for follow-up from July 2013 to May 2014. All included women were in full remission for 1 to 3 years and had no clinical or radiological signs of cancer. Women were excluded if they used anxiolytics or antidepressants, had benign breast neoplasia or malignant breast neoplasia of nonepithelial origin, developed metastatic disease during the study period, or had evidence of another malignant neoplasia except nonmelanoma skin carcinoma.

A total of 136 eligible women were initially invited to participate. Twenty-four women were excluded (10 refused to participate and 14 dropped out); the final sample consisted of 112 women. The demographic, clinical, and anthropometric data of these women were determined from their medical records. Eighty-five women (75.9%) were treated with chemotherapy, surgery (mastectomy or tumorectomy), and radiotherapy (CTX); the other 27 women (24.1%) were treated with surgery and radiotherapy, with or without hormone therapy, but no chemotherapy (non-CTX). The chemotherapy regimen consisted of FEC, epirubicin + cyclophosphamide (EC), or EC with a taxane; each treatment was given with or without tamoxifen. All participants gave written informed consent and were sent to a private room in the outpatient clinic to answer a semistructured interview and the questionnaire for assessment of QOL and risk of anxiety and depression.

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Interview

The semistructured interview consisted of open questions about clinical and sociodemographic data, including years of education, monthly income, paid employment status, number of children, marital status, duration of relationship, and use of medicines. Women were asked to report any kind of physical exercise (walking, physical resistance training, swimming, etc) they practiced after treatment. Data regarding diagnosis and treatment were obtained from medical records. At the same time, women responded individually to instruments used for psychological assessment.

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Instruments

The Hospital Anxiety and Depression Scale (HADS) was used to assess the risk for depression and anxiety. This scale has 14 items, 7 for measurement of anxiety (HADS-A) and 7 for measurement of depression (HADS-D). There were 4 alternatives (0 to 3) for each item, so the scores of each subscale ranged from 0 to 21. The cut-off point was 8 for a diagnosis of anxiety and 9 for a diagnosis of depression.33

The Medical Outcomes Study SF-36 was used to assess QOL. The SF-36 is a generic questionnaire designed to compare patients with different diseases or patients given different treatments. It is a multidimensional questionnaire composed of 36 items covering 8 scales or components: physical functioning, physical role functioning, bodily pain, general health, vitality, social functioning, emotional role functioning, and mental health. In addition, it yields a final score ranging from 0 to 100, in which 0 corresponds to the worst general health status, and 100, to the best general health status. The reliability and validity of this instrument have been established, with the median reliability coefficients for each of the 8 scales being equal to or greater than 0.80.34 The reliability and validity of the Portuguese language version of the instrument created by Ciconelli et al35 were confirmed by a Cronbach’s α value of .9. The SF-36 considers the perception of individuals regarding their own health status by accounting for the most representative aspects of health and is easy to administer and understand. The final score ranges from 0 to 100, where 0 is the worst score and 100 is the best score. Scores higher than 50 indicate preserved or good QOL.36 The SF-36 is divided into 8 domains: (1) Physical Functioning (10 items), which measures limitations in the execution of minor physical activities such as bathing or getting dressed, to more demanding activities such as lifting or carrying groceries from the store, climbing stairs, or walking a given distance; (2) Role-Physical (4 items), which measures health limitations due to physical problems according to the type and quantity of work performed, including limitations of the usual type of tasks executed, need to reduce the quantity of work, and difficulty in performing tasks; (3) Role-Emotional (3 items), which measures health limitations due to emotional problems and the type and quantity of work executed, including limitations of the usual types of tasks performed, need to reduce the quantity of work, and difficulty in performing tasks; (4) General Health (5 items), which measures the general perception of health, including current health, physical strength, and healthy appearance; (5) Vitality (4 items), which measures the levels of energy and fatigue; (6) Social Functioning (2 items), which measures the quantity and quality of social activities and the impact of physical and emotional problems on social activities; (7) Bodily Pain (3 items), which measures pain in body and pain to perform homework and work out of home; and (viii) Mental Health (5 items), which measures mental health such as anxiety, depression, loss of control in behavioral or emotional terms, and psychological well-being.37,38

The study was approved by the Research Ethics Committee of the University Hospital (protocol HCRP no. 7713/2013) and followed the ethical norms of Resolution 196/96 of the National Health Council regarding investigations with human beings.

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Statistical Analysis

Data were analyzed using SAS version 9.3 software. The nonparametric Mann-Whitney U test was used to compare HADS-D and HADS-A scores, and Fisher exact test was used to compare qualitative variables. Cronbach’s α values were calculated to estimate the internal consistency of the HADS and SF-36. Comparisons between groups according to type of surgical intervention (mastectomy, lumpectomy) and chemotherapy regimen (FEC, EC, and non-CTX) in relation to SF-36 domains were performed using Student t test or the nonparametric Wilcoxon test for independent samples. Average values and standard deviations of each domain of the SF-36, as well as P values, were determined using 1-way analysis of variance, followed by Tukey’s multiple comparison test. The SF-36 domains were considered as dependent variables, and age and the practice of sport were independent variables. The level of significance was set at .05 in all analyses.

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Results

Women in the non-CTX group were significantly older (P = .001), less likely to have undergone mastectomy (P < .001) but more likely to have undergone lumpectomy (P < .001), and engaged in more physical exercise (P = .002). Women in the 2 groups had a similar number of children, years of schooling, family income, history of treatment with tamoxifen, use of alcohol, and use of tobacco. Chemotherapy is not indicated for early-stage breast cancer, so all women in the non-CTX group had early-stage cancers, and all women in the CTX group had stage IIIa/b/c cancers (Table 1).

Table 1

Table 1

The reliability analyses of the SF-36 showed good internal consistency (Cronbach’s α = .83). The overall mean SF-36 score in the entire sample was below the threshold measure in the domains of Physical Functioning (31 [27.7%]), Role-Physical (70 [62.5%]), Bodily Pain (55 [45%]), General Health (20 [17.9%]), Vitality (32 [28.6%]), Social Functioning (34 [30.3%]), Role-Emotional (49 [43.8%]), and Mental Health (18 [16%]).

Patients were assigned to groups according to chemotherapy regimen (CTX: FEC, EC), non-CTX, and type of surgery (mastectomy or lumpectomy). There was no association between type of surgery and any of the SF-36 domains: Physical Functioning (P = .38), Role-Physical (P = .06), Bodily Pain (P = .88), General State of Health (P = .87), Vitality (P = .18), Social Functioning (P = .98), Role-Emotional (P = .78), and Mental health (P = .55).

Table 2 shows the QOL scores of women in the CTX and non-CTX groups in the 8 domains of the SF-36. The non-CTX group had significantly higher scores for Physical Functioning (77.41 vs 60.41; P = .01) and Role-Physical (60.19 vs 28.82; P = .01), but the 2 groups had similar scores in the other 6 domains.

Table 2

Table 2

When comparing subgroups according to chemotherapy regimen, the FEC group had significantly lower scores in the SF-36 domains Physical Functioning (P = .009) and Role-Physical (P = .02) compared with the EC and non-CTX groups. In this analysis, SF-36 domains were considered as dependent variables, and age, tamoxifen, as well as the practice of sport were independent variables. There was no influence of these variables on SF-36 domains (Table 3).

Table 3

Table 3

Table 4 shows the results of the effect of chemotherapy on HADS-A and HADS-D scores and on the 8 domains of the SF-36 in women who were treated with or without chemotherapy. Reliability analyses of the HADS showed good internal consistency (Cronbach’s α = 0.79). There was no significant difference between the CTX and non-CTX groups in the proportion of subjects diagnosed with anxiety and depression on the basis of HADS-A (CTX, 35 patients [41%] vs non-CTX, 11 patients [41%], P = .1) and HADS-D (CTX, 19 patients [22%] vs non-CTX, 10 patients [37%], P = .12). The cut-off point was 8 for a diagnosis of anxiety and 9 for a diagnosis of depression. Women from the CTX group with lower scores in the Physical Functioning and Role-Physical domains were at higher risk of depression and anxiety in relation to women from non-CTX group.

Table 4

Table 4

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Discussion

The present study demonstrated that women who received treatment for breast cancer had diminished scores in all domains of SF-36, especially in the Role-Physical (62.5%), Bodily Pain (45%), and Role-Emotional (43.8%) domains. In addition, among treated women, those who received chemotherapy had lower SF-36 scores in the Physical Functioning and Role-Physical domains than did those who did not receive chemotherapy. Moreover, among women who received chemotherapy, those who were administered the FEC regimen showed significantly lower scores for the Physical Functioning and Role-Physical domains of the SF-36 than those who were administered other drug combinations. In agreement with the SF-36 data, significantly fewer women who received chemotherapy practiced physical exercise after treatment. The differences between these groups in the 2 SF-36 domains persisted even when we controlled for type of surgery. These findings are consistent with previous studies showing that women with breast cancer had lower scores on the SF-36 physical and mental components, regardless of time since diagnosis.39 However, our data are not consistent with the findings of observational studies of Brazilian women treated for breast cancer, which showed no impairment of overall QOL after treatment was completed.18,19 Also, Jordanian breast cancer survivors were found to have QOL that was superior to that of treated women from Western countries.40 However, although the above studies found no impact of breast cancer treatment on posttreatment QOL, they did report symptoms such as dizziness, insomnia, and postmenopausal status,18,19 as well as high rates of anxiety and depression in these women,40 conditions that may negatively influence QOL. Few studies were designed to specifically assess the effects of different treatments on the QOL of women with breast cancer. It should be emphasized that we controlled for several confounding variables, such as type of treatment, sexual relationship, and physical activity. In addition, we excluded women with cancer recurrence, which could affect emotional status,40 and also excluded women taking psychoactive medications, because these might interfere with assessments in the physical and emotional domains of the SF-36.41 Thus, our results indicate that chemotherapy itself may impair certain physical functions and negatively impact the QOL of women with breast cancer. Thus, our results may be used to guide the development of programs and public policies that seek to improve care for these patients.

The observation that women treated with the FEC regimen had worse scores in the Physical Functioning and Role-Physical domains of SF-36 may be related to the cardiac toxicity of this drug combination.42 For example, patients who underwent FEC chemotherapy were found to have a greater than 20% lower left ventricle ejection fraction after compared with before treatment.43

The lower scores in the Physical Functioning domain of the SF-36 among women treated with chemotherapy reflects their limitations in daily activities such as running, lifting heavy objects, climbing stairs, kneeling, walking several blocks, and bathing. These limitations may be associated with changes in the muscles and nerves, which is common in patients who are treated with chemotherapy and hormone therapy.

All women in our chemotherapy group were treated with an FEC regimen, an EC regimen, or an EC + taxane regimen. These drugs, as well aromatase inhibitors and tamoxifen, can lead to structural changes of the muscles and nerves44 that may negatively impact physical activity in women treated for breast cancer. The randomized trial UK Taxotere as Adjuvant Chemotherapy Trial-Quality of Life (TACT-QL)45 provided data about the side effects of the FEC + taxane regimen for treatment of breast cancer. These previous results indicated that women who received this regimen suffered impairment of overall health and QOL (assessed by the European Organization for the Research and Treatment of Cancer) during treatment and over the 6 years of follow-up.45 The results of the present study confirm these previous findings.

As demonstrated here, women treated with chemotherapy engaged in less physical exercise, and this is presumably related to their poor scores on the Physical Functioning and Role-Physical domains of the SF-36. Reduced physical activity after chemotherapy is expected because chemotherapy can lead to fatigue, nausea, and muscle pain because it alters body composition and metabolism.46 This means that women have a reduced capacity to perform daily tasks and difficulty or limitations in performing their jobs. A recent study reported that physical inactivity among women treated for breast cancer is related to reduced health and increased symptoms such as pain, depression, and anxiety.47 However, the physical limitations caused by chemotherapy improve over time and the ability to walk is better after than during chemotherapy.48 Previous studies have not thoroughly examined the motivations or limitations of women regarding physical activity, a practice that clinicians commonly recommend. Nevertheless, there are indications that women who have completed chemotherapy have lower adherence to physical exercise programs.49 Future studies should more thoroughly examine this topic.

Assessment of anxiety and depression in the present sample indicated that more than one-third of the women had anxiety and about one-quarter had depression, with no significant differences between the groups. This result supports the findings of a recent study that compared women with breast cancer after 1 to 3 years of chemotherapy with women given surgery. However, in this previous study, there was no significant difference between groups in QOL, assessed with the Functional Assessment of Cancer Therapy–Breast Cancer.50 It should be pointed out that Functional Assessment of Cancer Therapy–Breast Cancer and SF-36 are complementary instruments used to assess QOL and are based on different constructs.51 In agreement with another recent study, women who had lower scores in the SF-36 domains had increased risk of depression and anxiety.52

Finally, the present study identified important changes in the Physical Functioning and Role-Physical domains of women who were treated with or without chemotherapy for breast cancer. However, caution should be exercised when interpreting our results because of the small size of each subgroup. A larger sample would be needed to accurately evaluate these subgroups to determine the best types of care for these women and to implement the best public policies for this population. This issue notwithstanding, the physical limitations identified in our sample may provide useful information to direct the design of counseling and educational materials aimed at enhancing QOL in this dimension. Health professionals cannot always accurately assess the suffering of women with breast cancer, even when the patients provide apparently precise information.53 Simple measures, such as establishing support groups with women who had the same problem and providing educational sessions about the disease and its management, supportive care based on the woman’s individual experience of distress,54 dietary advice, and physical exercises, can improve the QOL of women with breast cancer. In fact, evidence exists that providing educational sessions about the disease and its management, in conjunction with supportive care based on physical activity and exercise,55 improves the QOL of women with breast cancer. In this sense, a multidisciplinary approach to the treatment of breast cancer is recommended. In implementing such an approach, breast care nurses play an important role through providing practical information on the disease, recognizing the women’s needs, giving advice on changes in life style,56 providing expert advice to patients and their families,57,58 and explaining the importance of an adequate diet, exercise programs, and other activities to improve physical capacity. Exercising during the early stage of breast cancer treatment has been shown to reduce the increase in physical fatigue experienced during cancer treatment.59 In addition, women starting breast cancer treatment who received support from nurses, in particular advice about arm care, were more likely to avoid strenuous arm activity and hence showed lower rates of upper limb edema.60 Moreover, information provision by nurses about the disease and posttreatment status has been found to reduce fear levels and increase adherence to the proposed interventions for rehabilitation.61 Indeed, a lack of such information has been shown to be associated with poor adherence to rehabilitation programs. The challenge for nurses is to create programs to provide comfort and humane care to women undergoing treatment for breast cancer, by offering comprehensive care that includes educational measures aimed at fostering a positive attitude toward the disease and treatment that may reduce physical and emotional impact of this condition. Nurses may provide pretreatment and posttreatment psychoeducational information to patients about the illness and the treatment-related side effects of chemotherapy and changes to their health status.62 Nurses could provide education on care of the vascular access, affected superior member procedures to prevent lymphedema, chemotherapy toxicities, and strategies for follow-up.63

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Limitations

This study has some limitations. First, the mean age of the women who received chemotherapy was significantly lower than that of women who have not received chemotherapy. This may be because breast cancer is often more aggressive in younger women. However, when controlled for age, women who received chemotherapy also had lower scores in physical functioning and physical domains of the SF-36 role. Consistent with this finding, a previous study provided evidence of no significant correlation between age and most domains of health-related QOL in women treated for breast cancer.64 We recommend caution when interpreting the result that women treated with FEC regimen had lower scores in physical functioning and physical function domains of the SF-36 because of the small sample size. A larger sample is recommended for future studies to confirm our findings. Furthermore, the use of a convenience sample, the lack of information if women were physically active before treatment for breast cancer, together with the small sample size of non-CTX, may prevent the generalization of our data.

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Conclusion

Women who received chemotherapy treatment for breast cancer had poorer QOL in the Physical Functioning and Role-Physical domains of the SF-36 relative to women treated without chemotherapy. Among the women in this study, 37% of women had anxiety and 41% had depression, with the risks for anxiety and depression being similar in women who did and did not receive chemotherapy. The adverse effects of chemotherapy on physical aspects imply the need for interventions to minimize such effects. A multidisciplinary approach involving educational measures and rehabilitation is required to improve the physical functioning of these women. Nurses can play an important role in implementing these measures. In particular, nurses can provide comprehensive information on body status after treatment, facilitate communication between patients and doctors, motivate women to participate in rehabilitation programs, and offer counseling to a healthy life.

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Keywords:

Breast cancer; Cancer; Chemotherapy; Quality of life; Radiotherapy

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