Study design and participants

This prospective cohort included patients newly diagnosed with histologically confirmed breast cancer without prior treatment at Samsung Medical Center (SMC) in November 2018. The BIG-S study included survivors aged > 20 years without secondary cancer, metastasis, or recurrence.

The study was approved by the Institutional Review Board of the SMC (SMC-2019-08-009-020). We strictly adhered to the ethical guidelines outlined in the latest version of the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice.

MeasurementClinical information

Clinical information, including pregnancy, birth history, body mass index, year of diagnosis, Eastern Cooperative Oncology Group Performance Status score, comorbidities, pathological stage based on the American Joint Committee on Cancer staging manual, subtype, breast cancer susceptibility gene 1 and/or 2, and treatment modalities, was regularly updated by a trained data manager.

In terms of pathologic data, two experienced pathologists reviewed and determined the primary tumor characteristics based on size, axillary nodal status, and receptor status including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) using immunohistochemical (IHC) staining. ER positivity (ER+) and PR positivity (PR+) were defined as Allred scores of 3–8 based on IHC staining with antibodies against ER (Immunotech, Marseille, France) and PR (Novocastra, Newcastle upon Tyne, UK), respectively. HER2 status was evaluated using appropriate antibodies (Dako, Carpinteria, CA, USA) and/or silver in situ hybridization (SISH). Additionally, HER2 grades 0 and 1+ indicate negative results, whereas grade 3+ indicates positive results. Grade 2+ was equivocal and further confirmed using FISH. SISH was used to confirm HER2 amplification in patients with 2+ staining. Triple-negative breast cancer was defined as breast cancer with negative ER (ER−), PR (PR−), and HER2 expression (Table 1). Pathological data, including IHC results, were collected at the time of recurrence or distant metastasis.

Table 1 Overview of collected variableBody composition

At each visits, we used bioelectrical impedance analysis to determine body composition using a multifrequency bioelectrical impedance device according to the manufacturer’s instructions (InBody 720; InBody Co., Ltd., Seoul, Korea).

Health-related quality of life, physical, psychological, social, and cognitive function, as well as symptoms

In patient-reported outcome, we followed by recommendation from International Consortium for Health Outcomes Measurement (ICHOM) [13]. To collect the Patient Reported Outcome (PRO), we used a digital platform with the mobile phones of the patients.

The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) was used to measure physical, emotional, cognitive, and social functioning; ability to work; and overall well-being [14]. Breast cancer-specific functions such as body image, sexual functioning, future perspective, systemic therapy side effects, arm and breast symptoms, and upset by hair loss were measured using the Breast Cancer-Specific Module (BR23) [14]. We used FACT-Cognitive to estimate cognitive function, which was constructed of 37 questions. The sub-items included 20 questions on perceived cognitive impairment, 9 on perceived cognitive function, 4 on other people’s views, and 4 on the impact on quality of life. The tool uses a 5-point scale ranging from 0 (never or not at all) to 4 (many times a day or very much so),” with the total score from each subscale summed to represent the overall cognitive function, with higher scores indicating better cognitive function.

The EORTC QLQ C30 includes cancer-related symptoms such as fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Breast cancer-specific symptoms such as side effects of systemic therapy, arm and breast symptoms, and upset by hair loss were measured using the Breast Cancer-Specific Module (BR23).

The Menopause Rating Scale (MRS) was used to measure menopausal symptoms. The MRS includes 11 items in three dimensions: somatic-vegetative, psychological, and urogenital. Composite scores (range: 0–44) were calculated by adding the scores of the items from the respective dimensions.

Healthy behavior

We used the Centers for Disease Control and Prevention and developed an 11-question dietary checklist using the Healthy Eating Index, based on the 10 items of the Healthy Eating Index.

Physical activity was measured using the Physical Activity International Physical Activity Questionnaire developed by the International Consensus Organization to comprehensively and objectively assess health-related physical activity and usual physical activity—the questionnaire was surveyed using the Short Last 7 Days Self-Administered Form.

Financial difficulty

We used the Functional Assessment of Chronic Illness Therapy (FACIT) -COmprehensive Score for Financial Toxicity (COST) to assess financial toxicity, a 12-item questionnaire [15]. The COST-K is a valid and reliable instrument to measure financial toxicity in disease-free breast cancer survivors [16].

Insurance status was defined based on whether the individuals had private insurance. Private insurance status.

Spiritual well-being and adaptation to cancer

Spiritual well-being was evaluated using three questions from the Spiritual Well-Being Domain of the Korean version of the QoL of Cancer Survivors questionnaire [17]. From these, we selected four questions related to spiritual health. The Mini-Mental Adjustment to Cancer Scale (Mini-MAC) was used to capture how a person responded to a cancer diagnosis. It consists of 29 items on five scales: helpless/hopeless, anxious preoccupation, fighting spirit, cognitive avoidance, and fatalism.

The severity of the fear of cancer recurrence was assessed using the 9-item Korean version of the Fear of Cancer Recurrence Inventory-Short Form. Each item is rated on a 5-point scale ranging from 0 (“not at all” to 4 “very much ”) [18].

Depression was assessed using the Patient Health Questionnaire 9 (PHQ9), a standardized instrument for measuring depressive symptoms. Higher PHQ9 scores reflect greater severity of depression, with a score of 5 or above (score range: 0–27) indicating the presence of depressive symptoms [19].

Health care utilization

Healthcare utilization information was identified using the electronic medical records (EMR) of all patients. We have plant-to-link cohort data from Korea’s National Health Insurance and Health Insurance Review and Assessment Service databases. These provide a unique opportunity to examine healthcare utilization, long-term outcomes, and broader societal impacts, offering insights that are often absent in other studies due to fragmented healthcare systems.

Clinical outcomes

Survival and recurrence information were updated regularly by trained data managers using EMR for all patients. For recurrence monitoring, tumor marker tests and imaging such as CT and bone scan were performed every 6–12 months. If necessary, a PET-CT scan was performed to determine recurrence. If suspicious findings of recurrence were observed on imaging, a biopsy was performed for diagnostic confirmation. The recurrence date was defined as the day when clinicians confirmed recurrence according to the imaging or pathological results and is described in the chart. We also used official death certificates obtained from the Ministry of Strategy and Finance of South Korea to confirm the vital status.

Disease-free survival was defined as the period from the date of treatment initiation until recurrence or death, whichever occurred first. Patients who survived without recurrence at the time of the final analysis were evaluated at the last tumor assessment date. Overall survival was defined as the period from the start of treatment to the date of death. Patients who survived at the time of the final analysis were assessed at the time of their last survival.

Statistical analyses

Cohort data are represented using descriptive analysis, displaying the mean (standard deviation) and number (percentage) of continuous and categorical variables. By combining the questionnaires and EMR information of patients with breast cancer who participated in the study, we will identify the survival period of the target group (survivors immediately after the end of treatment, 6 months, and 1, 2, 3, and 4 years after the end of treatment) and perform descriptive analyses such as frequency analysis and mean analysis by the target group.

Statistical significance was set at p <.05, and two-tailed tests were used for all calculations. Statistical analyses were performed using R 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria).