EORTC QLQ-BR45-based assessment of quality of life in breast cancer survivors: A comprehensive study

INTRODUCTION

Breast cancer stands as the most prevalent form of cancer among women globally and represents the leading cause of cancer-related deaths among them.^[1] Annually, approximately 2.3 million new cases of female breast cancer are diagnosed, accounting for 11.7% of all cancer cases, thereby surpassing lung cancer in frequency.^[2] Between 1965 and 1985, India witnessed a notable 50% rise in breast cancer incidence rates. Over the past 26 years, every Indian state has experienced an increase in age-standardized incidence rates of breast cancer in females, marking a 39.1% overall rise.^[3] According to Globocan 2022, the number of new cases of breast cancer is 192020 (13.6%), and the number of deaths due to breast cancer is 98337 (10.7%) in India.^[2]

The number of breast cancer survivors has also risen due to advancements in early detection and treatment. However, the disease and its therapies often result in enduring physical and psychological challenges for survivors.^[1] Common issues following treatment, such as cardiotoxicity from adjuvant therapies, ovarian failure, and concerns over fertility preservation, body image, self-esteem, and sexuality, as well as pain, lymphedema, osteoporosis, and long-term survival, can significantly impact their quality of life (QoL)^[1]. QoL is a complex concept encompassing physical, psychological, social, and spiritual well-being. It serves as a crucial measure of outcomes for breast cancer survivors, reflecting the broader effects of the disease and its treatment on their overall well-being. Numerous studies indicate that breast cancer survivors typically report lower QoL compared to women who have not experienced breast cancer.^[4]

This research paper aims to investigate the factors influencing the QoL among breast cancer survivors in India. While other validated questionnaires, such as the EORTC QLQ BR23, have been utilized in the Indian context, this study marks the first attempt to correlate clinicopathological factors with QoL domains using the QLQ BR45 questionnaire specifically in India. The research will comprehensively explore the physical, psychological, social, and spiritual dimensions of QoL experienced by breast cancer survivors. The outcomes of this study are expected to pinpoint specific areas where targeted interventions can be implemented to enhance the QoL of this population.

The purpose of this research paper is to explore the factors that affect QoL in breast cancer survivors in India. While other validated questionnaires, such as the EORTC QLQ BR23, have been utilized in studies involving the Indian population, a notable gap remains in research investigating the correlation between clinicopathological factors and QoL domains using the QLQ BR45 questionnaire, specifically in India. This study represents the pioneering use of the EORTC QLQ BR45 questionnaire in Western India and is, to our knowledge, the second of its kind in the country.

The study will examine the physical, psychological, social, and spiritual dimensions of QoL in breast cancer survivors. The findings will help identify areas where interventions can be targeted to improve QoL in this population.

MATERIAL AND METHODS

RESULTS

A total of 107 patients treated at our center were approached; out of those, only 40 fulfilled the eligibility criteria for our study. The baseline characteristics of the study participants are presented in [Table 1].

The mean score of Global health status was 58.33 ± 15.38. Among the functional scales, high mean scores (>66.66) were observed for Physical functioning (73.33), Role functioning (78.54), and Cognitive functioning (88.31), whereas low mean scores (<33.33) were noted for Emotional functioning (52.49) and Social functioning (36.63). Among symptom scales, nausea and vomiting, dyspnea, and diarrhoea had a score of zero. Low mean scores (≤33.33) were observed for Insomnia (29.98), Appetite loss (19.98), Constipation (16.67), and financial difficulties (33.33). High mean scores (>66.66) were seen for fatigue (48.88) and Pain (56.67) [Table 2].

Among the QLQ BR45 Functional domains, high scores were seen in the Body Image (93.54±9.33), Future perspective (86.67±25.93), and Sexual functioning scores (90.42±16.40). Among the symptom domains, 'Upset by hair loss' (40±14.9) and 'Arm symptoms' (15.56±18.28) were the highest [Tables 3 and 4]. There are fewer entries in the Sexual Enjoyment and Upset by Hair Loss domains, as there is a provision for “Not applicable(NA)” as an entry for the questionnaire for these two domains.

The mean functional and symptom scores are also displayed in [Figures 1 and 2].

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Figure 1:

Mean QLQ BR45 functional domain scores of breast cancer survivors. There were zero patients falling within the 20–30 score interval for the functional domains displayed.

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Figure 2:

Mean QLQ BR45 symptom domain scores of breast cancer survivors. The 70–80, 80–90, and 90–100 colour bands are not visible because no patients had symptom scores within these higher intervals, resulting in zero-frequency categories that are not rendered in the stacked bar chart.

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The Mann-Whitney test was used to assess whether there were significant differences in mean Functional and symptom scores of patients due to various clinicopathological factors.

DISCUSSION

This study aimed to investigate the long-term impact of breast cancer diagnosis and treatment on patients. Specifically, it focused on assessing the QoL among breast cancer survivors. According to the American Cancer Society (ACS), a long-term cancer survivor is defined as someone who has survived the disease for five years or more.^[7] The mortality rate from breast cancer has dropped as a result of the adoption and utilization of better detection and treatment programs. However, the QoL of survivors has been significantly influenced by the persistent unknown side effects and toxicity of this novel long-term therapy.

Surgery for breast cancer is linked to long-term side effects such as pain, exhaustion, and emotional distress. With little attention paid to the long-term effects of medicines, treatments are adopting more aggressive, multimodal regimens. Systemic therapy has long-term side effects, including fatigue, weight gain, lymphedema, pain, and menopausal symptoms. While women on aromatase inhibitors are more likely to experience bone loss and fractures, anthracycline usage, and adjuvant trastuzumab have been related to an increased risk of heart issues occurring even after the course of treatment has ended. Radiation therapy may increase the risk of secondary sarcomas.^[8,9]

The European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30) is a widely used questionnaire that assesses the QoL of cancer patients. It consists of 30 items that assess five functional domains (physical, role, emotional, cognitive, and social), three symptom domains (fatigue, pain, and nausea/ vomiting), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties).^[10]

The EORTC QoL Group has developed two questionnaires specifically for use in breast cancer patients: EORTC QLQBR23 and EORTC QLQ-BR45. The EORTC QLQ-C30 is a core questionnaire that assesses the QoL of cancer patients.

The EORTC QLQ-BR45 is a breast cancer-specific module that is used in combination with the EORTC QLQ-C30 core questionnaire as an updated version with more dimensions compared to the QLQ BR23 questionnaire.^[6]

Studies on the QoL of cancer patients and survivors are of utmost importance in these current times since we are constantly focused on the search for a better drug, but only in terms of its efficacy in improving survival outcomes. Interestingly, a systematic review by Shrestha et al showed that QoL was preferred over length of life in patients with older age and poorer physical status.^[11] This further underscores the value of baseline and periodic QoL assessments, which might even help us decide the treatment plan for patients instead of empiric treatment for all.

The patients in our study showed high physical, role, and cognitive function scores with modest Global QoL mean scores (58.33 ± 15.38), similar to those observed in another study from India. However, compared to the study by Singh et al., the social(36.63 ± 22.82) and emotional functioning(52.49 ± 25.69) scores were comparatively lower in our study, which can be attributed to the sociodemographic and cultural differences in the populations chosen for the two studies.^[12]

The QLQ-C30 symptom score analysis also reveals that the mean scores achieved in our study are comparable to those reported in similar Indian studies.^[12], The scores revealed the predominant symptoms in breast cancer survivors to be fatigue(MS-48.88) and pain(MS-56.67). Biering et al., in their study of the long-term course of fatigue in breast cancer patients, demonstrated that fatigue was a significant problem affecting approximately 35% of patients, with it peaking in the first six months post-intensive treatment and then gradually decreasing over time, but never returning to pretreatment levels.^[13]

Pain is another significant determinant of QoL, with another study by Kaur et al.^[14] showing that post-mastectomy chronic pain (defined as pain lasting for more than three months) was prevalent in around 41.4% of breast cancer patients, with the most common type of pain being that of pins and needles sensation. The most common site is the mastectomy scar.^[14]

Notably, our study showed lower scores for nausea, vomiting, and dyspnea. Strangely, the mean financial toxicity (FT) score (33.33 ±21.59) was seemingly higher despite being treated at a government setup where most of the treatment was provided for free. This may be due to other out-of-pocket expenses, such as travel, accommodation, and supplementary medications, as well as the long-term and multidisciplinary nature of follow-up care. A systematic review and meta-analysis on the same revealed that rates of FT in breast cancer patients were around 35% and 78% in high-income and Low-middle-income countries, respectively, which suggests that expansion of health care coverage, transportation, and accommodation facilities may be the way to cut down these costs.^[15]

The overall mean scores in the Body image, Future perspectives, and Sexual functioning domains were high (93.5, 86.7, and 90.42, respectively), with more than 90% of the participants achieving scores of 66.7 or higher (high score). However, the overall mean scores in the Sexual Enjoyment and Breast Satisfaction domains were low (60.6 and 63.33, respectively), with only 62% of participants achieving high scores. The mean scores in the Symptom Scale domains were generally low, except for the domain of Upset about hair loss (MS-40). Overall mean symptom scores are lower compared to those reported in the study by Singh et al.^[12]

Our findings are similar to those reported in Global QoL systematic reviews, with the highest Functional domain scores in the QLQ-C30 and breast-specific modules (BR23 and BR45) observed in the Cognitive Functioning and Breast image domains, respectively. Diarrhea had one of the lowest Symptom domain scores in our study, similar to the review.^[16] This indicates that, although the general Global QoL in our study is low, the overall trend of the individual domain scores aligns with the pattern observed in similar studies worldwide.

Limited studies are available assessing QoL in breast cancer survivors in India using the EORTC QLQ BR45 scale. Most existing data are on patients during or after treatment and focus on the general QoL QLQ-C30 domains. Hence, we sought to study and shed light on the factors affecting breast cancer-specific domains, which were assessed using the EORTC QLQ BR45 questionnaire. Kim et al., in their study of breast cancer patients up to 3 years post-treatment, showed that the presence of comorbidities, fatigue, anxiety, and depression was a significant determinant of poor QoL.^[17] Similarly, other Indian studies have also shown that age, general condition, level of education, and disease stage at presentation were determinants of QoL in breast cancer patients.

In our study, we found that older patients (ages greater than 50 years) had significantly better sexual functioning scores compared to their younger counterparts. Morales et al. had shown that endocrine symptoms such as loss of sexual interest, dyspareunia, hot flashes, dry vagina, etc, are more prevalent in younger patients and thereby negatively impact female sexual health.^[18] This can also be seen in the nonsignificant trend of higher endocrine sexual symptoms scores in younger patients in our study. Obesity (BMI≥25) is another major determinant of QoL in breast cancer survivors, with it resulting in both significantly low Body Image perception as well as higher Systemic therapy side effect scores. This has been observed in previous studies, although its effects have been mixed. Ram et al. showed that Obese patients required more frequent dose reductions than their non-obese counterparts.^[19] We also saw a non-significant trend towards higher arm and Breast symptom scores in obese patients.

Pre-menstrual status was associated with higher breast satisfaction in our study, which contrasts with the results of some other studies.^[12] This can be attributed partly to the changes in perception with age, as well as due to the emotional distress, anxiety, depression, etc, induced after menopause due to hormonal changes.

Patients with addictions (Tobacco chewing, smoking, etc) had higher endocrine therapy side effects. There have been studies that have shown that tobacco use is associated with increased estrogen receptor activity.^[20] Patients who had received NACT had lower breast symptom domain scores, which might be due to the tumor bulk decreasing, resulting in better surgical outcomes. This is also evidenced by a non-significant trend toward a better Body Image domain score in patients who received NACT in our study. A higher disease stage at presentation was associated with significantly higher Arm symptom domain scores due to the need for nodal irradiation in these patients.

Lastly, Skin Mucosis symptom scores were higher in those who underwent MRM, had node positivity, or presented at a higher stage. This can be due to treatment intensification in the form of extended radiation fields or Adjuvant chemotherapy in these subsets of patients.

A limitation of our study is its small sample size, which makes it challenging to perform further subset-specific analysis to estimate the contribution of each treatment modality to the QoL changes.

Consideration of the impact of a treatment modality on the QoL of cancer survivors should be incorporated into the decision-making process. If explained to the patient, the factors affecting the QoL would help the patient decide the most suitable treatment for him, considering his financial, physical, cultural, familial, and social situation. This can also help us navigate the “grey” areas in medicine, primarily when no conclusive evidence supports one modality over another.

CONCLUSION

Breast cancer is the most common cancer in women worldwide. While pushing the limits of optimizing the therapeutic efficacy of treatment modalities such as systemic therapy and radiation, we should not lose track of these modalities' impact on patients' QoL. Sociodemographic factors such as age, obesity, menstrual status, and presence of addictions, as well as clinicopathological factors such as stage of disease, nodal involvement, type of surgery, and receipt of NACT, are determinants of QoL in breast cancer survivors.