e-ISSN: 2722-3558 Sriwijaya Journal of Surgery [SJS] https://sriwijayasurgery.
Dissecting the Triad of Distress: A Multivariate Analysis of Clinical.
Surgical, and Sociodemographic Determinants of Quality of Life in Indonesian Breast Cancer Patients Undergoing Chemotherapy Muhammad Yufimar Riza Fadilah1*.
Mulawan Umar2.
Theodorus3 1Department of General Surgery.
Dr.
Mohammad Hoesin General Hospital/Faculty of Medicine.
Universitas Sriwijaya.
Palembang.
Indonesia 2Department of Surgical Oncology.
Dr.
Mohammad Hoesin General Hospital.
Palembang.
Indonesia 3Faculty of Medicine.
Universitas Sriwijaya.
Palembang.
Indonesia
ARTICLE
INFO
Keywords:
Axillary dissection Breast cancer Mastectomy Quality of life Surgical oncology *Corresponding author:
Muhammad Yufimar Riza Fadilah E-mail address:
yopirf@gmail.
All authors have reviewed and approved the Anal version of the manuscript.
https://doi.
org/10.
37275/sjs.
ABSTRACT
Introduction: The assessment of health-related quality of life (HRQoL) is a paramount outcome in breast cancer survivorship, yet the interplay of disease-specific, treatment-related, and patient-level factors is not fully understood in Southeast Asian populations.
This study aimed to comprehensively model the predictors of HRQoL and fatigue by simultaneously evaluating clinical, surgical, and sociodemographic variables among Indonesian breast cancer patients.
Methods: A cross-sectional study was conducted with 102 female breast cancer patients undergoing chemotherapy at Dr.
Mohammad Hoesin General Hospital.
Palembang.
Indonesia.
Data on clinical variables (AJCC stage, chemotherapy cycles, treatment inten.
, surgical procedures .
reast and axillary surgery typ.
, and sociodemographic characteristics were collected.
HRQoL was assessed using the validated Indonesian versions of the Functional Assessment of Cancer Therapy-General (FACT-G) and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaires.
Bivariate correlations and a hierarchical multivariate linear regression analysis were performed to identify significant independent predictors of FACIT-F scores.
Results: The cohort was characterized by advanced disease (Stage i/IV: 62.
7%) and aggressive surgical management (Mastectomy: 75.
Axillary Lymph Node Dissection: 68.
6%).
In the multivariate analysis, several factors emerged as significant independent predictors of poorer HRQoL.
These included advanced cancer stage ( = -0.
41, p < 0.
, having undergone a mastectomy versus breast-conserving surgery ( = -0.
28, p = 0.
, having had an axillary lymph node dissection versus sentinel node biopsy ( = -0.
p = 0.
, and a higher number of chemotherapy cycles ( = -0.
19, p = The final model explained a substantial portion of the variance in HRQoL (Adjusted RA = 0.
In contrast, sociodemographic factors including age, income, and education were not significant predictors in the final model .
> 0.
Conclusion: HRQoL in this cohort is not determined by a single factor but by a triad of distress: the biological burden of the disease .
, the physical and psychological morbidity of surgical treatment, and the cumulative toxicity of chemotherapy.
These treatment-related realities powerfully override the influence of sociodemographic characteristics.
These findings mandate a paradigm shift towards an integrated supportive care model that proactively addresses surgical morbidity alongside systemic side effects from the point of diagnosis.
Introduction mortality in women worldwide.
1 The epidemiology of Breast cancer represents a formidable global health breast cancer reveals a concerning trend, with a challenge, standing as the most frequently diagnosed disproportionately escalating incidence and mortality malignancy and a principal cause of cancer-related burden in low- and middle-income countries (LMIC.
, including Indonesia.
2 In 2020 alone, approximately stages is intrinsically linked to a greater systemic 3 million women were newly diagnosed with breast inflammatory response, paraneoplastic syndromes, cancer, a figure that underscores the urgent need for and a heavier symptom load.
6 Concurrently, the effective and holistic oncological care strategies on a intensity and nature of the treatment itself represent global scale.
Over the past several decades, the advent a major source of morbidity.
Beyond the cumulative of multimodal treatmentAia coordinated application of toxicity of chemotherapy, the surgical interventionAi surgery, systemic therapy .
hemotherapy, endocrine often the first and most definitive treatment stepAi therapy, targeted agent.
, and radiation therapyAihas carries its own significant and lasting impact.
The type markedly improved survival rates.
This success has of surgery, ranging from breast-conserving surgery catalyzed a crucial evolution in the philosophy of (BCS) with sentinel lymph node biopsy (SLNB) to a modified radical mastectomy with axillary lymph node traditional endpoint of mere survival to encompass the dissection (ALND), has vastly different implications for comprehensive well-being and health-related quality a patient's physical functioning, body image, and of life (HRQoL) of patients throughout their arduous emotional state.
7 Morbidities such as chronic pain, cancer journey.
lymphedema, and restricted shoulder mobility are Chemotherapy remains a central pillar of systemic treatment for breast cancer, employed across various settings: as neoadjuvant therapy to downstage tumors direct surgical sequelae that can severely compromise HRQoL for years after treatment completion.
Alongside these powerful disease- and treatment- before surgery, as adjuvant therapy to eradicate including age, socioeconomic status, educational attainment, and social support systemsAiare also While its cytotoxic efficacy is indispensable for postulated to modulate a patient's capacity to cope disease post-surgery, palliative capacity to control metastatic variablesAi notoriously associated with a wide spectrum of acute influencing their perceived HRQoL.
8 In many Western and chronic toxicities that can profoundly impair a healthcare systems, where patients often present with patient's HRQoL.
Among these, cancer-related fatigue earlier-stage (CRF) is arguably the most pervasive, distressing, and socioeconomic factors are frequently identified as functionally limiting symptom reported.
CRF is a significant modifiers of patient-reported outcomes.
complex, multidimensional syndrome characterized by However, the relative contribution of these distinct a persistent and debilitating sense of physical, domainsAiclinical, surgical, and sociodemographicAi emotional, and cognitive exhaustion disproportionate to recent activity, which is not ameliorated by rest.
5 Its constrained settings like Indonesia.
In such settings, pathophysiology is intricate, involving a complex patients often present with more advanced disease at interplay of pro-inflammatory cytokines, dysregulation diagnosis due to a combination of factors, including of the hypothalamic-pituitary-adrenal (HPA) axis, low awareness, cultural barriers, and limited access to metabolic disturbances, and direct neurotoxic effects, screening programs, thus facing a greater biological all induced by both the underlying malignancy and its burden from the outset.
Furthermore, the Indonesian healthcare system, largely unified under the national The HRQoL of a breast cancer patient is shaped by health insurance scheme (BPJS Kesehata.
, provides a complex interplay of numerous factors.
Clinical a relatively standardized pathway for core cancer characteristics, such as the anatomical extent of the therapies, which may moderate the influence of personal income on access to treatment.
A higher tumor burden in advanced Understanding which factors are the primary well-being over a two-month period, from June 1st, 2025, to July 31st, 2025.
Ethical approval was obtained from the designing effective, targeted, and resource-appropriate Institutional Review Board and the Ethics Committee supportive care interventions.
If disease stage is the of the Faculty of Medicine.
Universitas Sriwijaya and dominant factor, efforts must be redoubled in public the study was conducted in accordance with the health campaigns for early detection.
If surgical principles of the Declaration of Helsinki.
morbidity is a key independent predictor, then The target population included all female patients resources should be channeled towards rehabilitation, with a histopathologically confirmed diagnosis of physiotherapy, and psychological support for body breast cancer who were undergoing chemotherapy.
image issues.
If chemotherapy toxicity is paramount, total sampling technique was employed, wherein every then aggressive symptom palliation protocols are consecutive patient who met the eligibility criteria during the study period was invited to participate to Therefore, the primary aim of this study was to minimize selection bias.
The inclusion criteria were: .
dissect the complex interplay of predictors affecting Female.
HRQoL in a cohort of Indonesian breast cancer histopathological diagnosis of breast cancer .
ny The novelty of this research lies in its .
Having received at least one cycle of a comprehensive, multi-domain approach, aiming to chemotherapy regimen.
The last chemotherapy simultaneously quantify and compare the predictive administration was within three months of the data power of .
clinical disease characteristics .
, .
surgical treatment morbidity .
ype of breast and independently complete questionnaires in Bahasa axillary surger.
, .
systemic treatment intensity Indonesia.
Provision of written informed consent.
hemotherapy cycle.
, and .
sociodemographic The exclusion criteria were: .
Presence of severe characterized by advanced disease presentation, the patient's HRQoL would be determined by a confluence severe, uncontrolled systemic illnesses, such as of treatment-related morbidities, with the biological congestive heart failure NYHA Class IV or end-stage burden of the disease .
and the physical impact of its treatment .
urgery and chemotherap.
emerging profoundly affect HRQoL.
Inability to complete the as dominant, independent predictors that would questionnaires due to physical incapacitation.
Refusal to provide informed consent.
Ou18 Ability Confirmed self-reporting.
Co-existing .
Based on these criteria, a final sample of 102 patients was enrolled.
The sample size was deemed Methods This study utilized a cross-sectional, descriptive- multivariate regression analyses, calculated a priori to analytical design to investigate the determinants of detect a medium effect size .
A = 0.
with an alpha of HRQoL.
05 and a power of 80% for a model with up to eight Data patients attending the outpatient Surgical Oncology independent variables.
Clinic at Dr.
Mohammad Hoesin General Hospital in Palembang.
South Sumatra.
Indonesia.
Data were gathered using a two-pronged approach:
This a structured review of official medical records and the institution functions as a national tertiary referral administration of validated self-report questionnaires.
hospital and is the primary center for comprehensive A trained research assistant, who was not involved in cancer care in the region, serving a diverse urban and rural patient population.
The study was conducted individuals in the clinic waiting area, provided a detailed explanation of the study's purpose and Fatigue Subscale (FS).
The FS specifically measures procedures, and obtained written informed consent.
the intensity of fatigue and its impact on daily A standardized data extraction form was used to The total FACIT-F score is the sum of the collect information from patients' medical records.
FACT-G and FS scores, ranging from 0 to 160.
For all Clinical data were: .
Cancer Stage: Staging was FACIT instruments, higher scores represent a better based on the American Joint Committee on Cancer outcome .
etter HRQoL and less fatigu.
(AJCC) 8th Edition guidelines and recorded as Stage I.
All data were coded and analyzed using SPSS II, i, or IV.
Chemotherapy Frequency: Recorded as Statistics Version 27.
0 (IBM Corp.
Armonk.
NY).
the total number of chemotherapy cycles the patient Frequencies and percentages were used for categorical had received to date.
Treatment Intent: Categorized Means, standard deviations (SD), and ranges were calculated for continuous variables.
Neoadjuvant .
hemotherapy Adjuvant .
hemotherapy after surger.
, or Palliative .
or Stage IV metastatic diseas.
Surgical data were:
SpearmanAos rank correlation coefficient .
was used .
Type of breast surgery: categorized as breast- to assess the strength and direction of monotonic conserving surgery (BCS) or mastectomy.
Type of relationships between ordinal independent variables axillary surgery: categorized as sentinel lymph node .
tage, income, educatio.
and the primary dependent biopsy (SLNB) or axillary lymph node dissection variables .
otal FACT-G and FACIT-F score.
The (ALND).
Sociodemographic data: collected via a point-biserial correlation was used for dichotomous structured interview.
age: recorded in years and categorized (<40, 40-59, >.
education level: highest statistically significant.
To address the potential influence of the very small Stage I subgroup .
, the school/elementary, middle/high school, universit.
SpearmanAos correlation between cancer stage and FACIT-F score was re-calculated after excluding these .
ategorized self-reported HRQoL p-value <0.
(Low: <1.
5 million IDR.
Medium: 1.
5 million IDR, regression analysis was performed to identify the High: >3.
5 million IDR).
Marital status: categorized as independent predictors of HRQoL, using the total married or not married.
FACIT-F score as the continuous dependent variable.
non-parametric The categorized based on the regional minimum wage HRQoL Variables were entered in blocks to assess their translated and validated Bahasa Indonesia versions of the Functional Assessment of Chronic Illness Therapy sociodemographic variables.
Block 2 contained the (FACIT) measurement system instruments.
Functional primary clinical variable .
ancer stag.
Block 3 Assessment of Cancer Therapy-General (FACT-G, contained surgical variables, and Block 4 contained Version .
is a 27-item core questionnaire that the chemotherapy variable.
This hierarchical approach allows for the assessment of how much additional Physical Well-Being (PWB, 7 item.
Social/Family variance is explained by treatment-related factors after Well-Being (SWB, 7 item.
Emotional Well-Being (EWB, 6 item.
, and Functional Well-Being (FWB, 7 Standardized beta coefficients () were used to Each item is rated on a 5-point Likert scale compare the relative predictive power of each variable.
="Not at all" to 4="Very much").
The total FACT-G Collinearity diagnostics (Variance Inflation Factor.
VIF score ranges from 0 to 108, with higher scores < .
were checked to ensure model stability.
HRQoL Block patient-level indicating better HRQoL.
Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F.
Version .
includes the 27 items of the FACT-G plus a 13-item Results patient population was defined by advanced disease at A total of 102 eligible patients were enrolled.
The The majority of patients had Stage i detailed sociodemographic, clinical, and surgical .
1%) or Stage II .
3%) disease, with a significant characteristics of the cohort are presented in Table 1.
6%) having Stage IV metastatic disease.
The mean age of participants was 48.
7 years (SD A Only 2.
0% were diagnosed at Stage I.
The treatment The cohort was predominantly from lower-to- intent was primarily adjuvant .
7%).
Surgical middle socioeconomic strata, with 78.
4% having management was correspondingly aggressive: 75.
completed high school or less and 78.
5% reporting of patients underwent a mastectomy, and 68.
6% had low-to-medium household incomes.
Clinically, the a full axillary lymph node dissection.
The mean FACIT-F score for the entire cohort was there was distinct separation in the median scores 5 (SD A 21.
, and the mean FACT-G score was 76.
between stages, there was also considerable overlap in (SD A 18.
, indicating a moderate level of HRQoL impairment and fatigue.
As shown in Figure 1, a box- stages, reflecting the inherent variability in patient and-whisker plot of FACIT-F scores stratified by cancer stage revealed a clear negative trend.
While Figure 1.
Distribution of FACIT-F scores by cancer stage.
The plot illustrates a strong negative monotonic relationship, with median HRQoL scores decreasing as cancer stage advances.
The interquartile ranges and whiskers show variability within each stage and some overlap between adjacent stages.
When stratified by key characteristics (Table .
, a ALND consistent dose-response relationship was observed statistically significant lower mean HRQoL scores than between advancing cancer stage and deteriorating those who received breast-conserving surgery and HRQoL.
Patients with Stage IV disease reported SLNB, respectively.
In contrast, variations in mean severely compromised quality of life (Mean FACIT-F:
compared to those with Stage II disease (Mean minimal and showed no discernible pattern.
FACIT-F: 115.
Similarly, patients who underwent The Spearman's correlation analysis (Table .
RA = 0.
02, p = 0.
Model 2, which added cancer confirmed the profound negative impact of disease stage, resulted in a dramatic and significant increase severity and treatment intensity on HRQoL.
A strong, in explanatory power (Adjusted RA = 0.
47, p < 0.
statistically significant negative correlation was found Cancer stage was a powerful predictor ( = -0.
64, p < between cancer stage and both FACIT-F (A = -0.
68, p Model 3, which added the surgical variables < 0.
and FACT-G scores (A = -0.
65, p < 0.
(Mastectomy vs.
BCS.
ALND vs.
SLNB), further sensitivity analysis excluding the two Stage I patients improved the model significantly (Adjusted RA = 0.
showed the correlation remained strong and highly p < 0.
Crucially, both Mastectomy ( = -0.
28, p = significant (A = -0.
66, p < 0.
, confirming the .
and ALND ( = -0.
25, p = 0.
emerged as stability of this finding.
Similarly, chemotherapy significant independent predictors of poorer HRQoL, frequency showed a moderate negative correlation even after controlling for stage.
Model 4, the final with HRQoL (FACIT-F: A = -0.
42, p < 0.
In stark model, added chemotherapy cycles.
This led to a small contrast, none of the sociodemographic variables but significant improvement (Adjusted RA = 0.
58, p < demonstrated a significant correlation with either In this final comprehensive model, four HRQoL measure .
> 0.
05 for al.
To determine the independent contribution of each (Table Model predictors of diminished HRQoL: advanced cancer stage, undergoing a mastectomy, undergoing an ALND, and a higher frequency of chemotherapy.
sociodemographic variables, was not statistically Sociodemographic factors remained non-significant.
significant and explained negligible variance (Adjusted Discussion This measurable insults.
First, cancer stage remained a robust and powerful HRQoL independent predictor of HRQoL, even after controlling Indonesian breast cancer patients by dissecting the for the type of treatment.
This confirms the intrinsic negative impact of the biological burden of advanced The findings provide a Progressing from Stage II to Stage i/IV is not clear and compelling answer: patient well-being in this merely a change in anatomical classification.
it is a cohort is powerfully dictated by a triad of treatment- surrogate for increasing tumor volume, systemic related distressAithe biological burden of the disease, the morbidity of the required surgery, and the systemic release of pro-inflammatory cytokines such cumulative toxicity of chemotherapy.
This confluence as IL-6.
IL-1, and TNF- by tumor cells and the host of factors effectively eclipses the impact of traditional immune response is a well-established mechanism underlying cancer cachexia, anorexia, pain, and, carries profound implications for the design and centrally, cancer-related fatigue.
13 These cytokines act delivery of supportive oncology care in Indonesia and on the central nervous system to induce "sickness similar healthcare settings.
behavior," a syndrome of lethargy, anhedonia, and Our hierarchical regression analysis successfully The social withdrawal that is directly captured by the PWB.
EWB, and SWB subscales of the FACT-G.
Therefore, different facets of the cancer experience.
The final the significant predictive power of stage in our final model demonstrates that a patient's HRQoL is not a monolithic construct determined by "cancer" but is biological hostility of the malignancy itself.
non-removable rather a composite outcome shaped by distinct.
Second, and central to the novelty of this study, is disease, is a source of significant psychological the finding that surgical morbidity is a powerful, distress related to body image, femininity, and self- independent determinant of HRQoL.
After accounting esteem, which directly impacts the Emotional Well- for the effect of stage, undergoing a mastectomy and Being (EWB) domain.
Axillary lymph node dissection, while crucial for regional disease control, carries a associated with a significant and substantial decline high risk of long-term morbidity, most notably in HRQoL scores.
This refutes any simplistic notion 14 This chronic swelling of the arm leads that the patient's experience is solely a function of to pain, recurrent infections, and profound functional their disease stage or chemotherapy.
The surgical impairment, severely impacting both the physical intervention leaves an indelible mark.
A mastectomy, (PWB) and functional well-being (FWB) domains.
The while oncologically necessary for many with advanced independent significance of these surgical variables in our primary treatment, while strong communal and family consequences of treatment are not just "side effects" support systems prevalent in the culture might buffer but core drivers of the patient's overall suffering.
the effect of marital status.
Third, the cumulative toxicity of chemotherapy was The practical implications of these findings are also confirmed as a significant, independent predictor.
They advocate for a clinical strategy that Each additional cycle of cytotoxic agents inflicts moves beyond a stage-centric view to a multi-domain, damage on rapidly dividing healthy cells, leading to morbidity-focused paradigm of supportive care.
Integrated Pre- and Post-Surgical Rehabilitation:
nemia, neutropeni.
, gastrointestinal mucositis, and Given the independent impact of surgery, supportive peripheral neuropathy.
Anemia, in particular, is a care must begin before the operation.
Pre-operative major contributor to fatigue by reducing oxygen- counseling should address body image concerns, and post-operative referral to physiotherapy must be The frequency remained significant even after accounting for stage and surgery highlights the relentless, dose- dependent attrition that systemic therapy exacts on a Management: Resources should be intensely focused on symptom palliation protocols tailored not just to the .
Proactive Symptom chemotherapy regimen but also to the patient's Perhaps the most thought-provoking finding is the HRQoL surgical procedure and disease stage.
Early and concurrent integration of palliative care services, focused on managing pain and fatigue, is essential for bivariate and multivariate analyses.
This finding, observed in the context of a robust model that Assessment: Clinical assessments of patient well- accounts for disease and treatment severity, strongly being should routinely include questions about suggests a threshold or "floor" effect.
When the surgical sequelae .
rm function, body imag.
in combined clinical burdenAifrom advanced disease, addition to chemotherapy side effects.
Relying on performance status alone is insufficient.
chemotherapyAiis .
Holistic sufficiently severe, its profound physiological and The findings of this study must be interpreted in psychological impact may create a level of distress that the context of several limitations.
First, the cross- sectional design allows for the identification of sociodemographic advantages.
The clinical imperative significant associations but precludes any inference of for survival and the severity of symptoms like A longitudinal study would be required to intractable pain, debilitating fatigue, or functional track the trajectory of HRQoL over the course of the limb impairment become the all-consuming aspects of treatment continuum.
Second, this was a single- a patient's existence.
17 In such circumstances, the center study conducted at a tertiary referral hospital, potential benefits of a higher income or educationAi which may limit the generalizability of the findings to such as access to niche supportive therapies or a more other types of hospitals or regions in Indonesia with nuanced understanding of the diseaseAimay become different patient populations and resources.
19 Third, marginal in the face of overwhelming biological and the use of a non-probability, total sampling technique, treatment-induced while pragmatic, may introduce selection bias.
Fourth, standardized care pathway provided by the Indonesian despite our comprehensive model, there are other national health insurance system (BPJS Kesehata.
potential confounding variables not accounted for, may level the playing field regarding access to core therapies, thereby reducing the influence of income on psychological conditions, and the specific level of Furthermore, pre-existing social support, which could also influence HRQoL.
Kim EY.
Shin S.
Chang Y.
Ryu S.
Serum Finally, the very small subgroup of patients with Stage ferritin and iron-related biomarkers in relation I disease .
limited our ability to make robust to breast cancer risk by menopausal status: a statistical comparisons with this group, although a prospective cohort study.
Cancer Epidemiol sensitivity analysis confirmed the stability of our Biomarkers Prev.
primary correlation finding.
Fielder AM.
Kim S.
Ruterbusch JJ.
Martin C.
Gottschlich A.
Schwartz AG, et al.
Prescription Conclusion and self-reported use of endocrine therapy In this cohort of Indonesian breast cancer patients, receptor-positive health-related quality of life is not determined by who the patient is .
, but by what they Research on Cancer Survivors cohort.
Breast are enduring.
A triad of distress, comprising the Cancer Res Treat.
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Swinehart- morbidity of extensive surgical intervention, and the Hord P.
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cumulative toxicity of chemotherapy, collectively and Patient-driven decisions and perceptions of The the Ausafest possible choiceAy: insights from powerful impact of these treatment-related realities patient-provider conversations about how renders the influence of sociodemographic factors statistically insignificant.
This research fundamentally reframes the drivers of patient suffering in this Psychol Health.
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