Abstract
Objective
To compare the patient-reported outcomes (PROs) and quality of life in patients with HR+/HER2- early breast cancer (EBC) treated with Ribociclib (RIB) and Abemaciclib (ABE) as adjuvant therapy.
Methods
A multicenter, retrospective cohort study was conducted in Chinese patients receiving RIB or ABE as adjuvant therapy for HR+/HER2- EBC. PRO data were collected via an electronic questionnaire. The questionnaire was based on the PRO scale for breast cancer patients in China (NCC-BC-A scale), EQ-5D-5 L and safety information of CDK4/6 inhibitors, including six dimensions of physiological function, psychological status, social support, treatment related symptoms, economic dimension and overall self-evaluation. The higher score of the questionnaire, the better quality of life.
Results
Between Mar 15, and May 12, 2025, 197 patients completed the survey, including 94 patients who received RIB and 103 patients who received ABE. Overall, 195 patients (99%) were female and two (1%) were male. No difference was observed in baseline characteristics such as age, employment status, medical insurance, and concomitant treatment. The total score of the PRO in RIB group was higher than that in ABE group (187.14 ± 17.57 versus(vs.) 180.66 ± 22.26, p = 0.024). In therapeutic domain, the score was significantly higher in RIB group (34.81 ± 5.29 vs. 32.77 ± 5.51, p = 0.009). Patients in RIB group were less affected by the treatment-related symptoms of diarrhea (3.88 ± 0.53 vs. 2.31 ± 1.33, p < 0.001), fatigue (2.29 ± 0.91 vs. 2.00 ± 1.02, p = 0.038) and alopecia (2.94 ± 1.39 vs. 2.49 ± 1.24, p = 0.018). The overall health status score of RIB group was higher (6.67 ± 1.27 vs. 5.83 ± 1.45, p < 0.001).
Conclusion
HR+HER2- EBC patients who received RIB had a better PRO score than those who received ABE. Patients in RIB group experienced less treatment-related adverse reactions, especially diarrhea, fatigue, and alopecia, and had a lower rate of discontinuation/reduction due to adverse events, a better self-evaluation of their overall health status.
Supplementary Information
The online version contains supplementary material available at 10.1186/s12885-026-15983-7.
Keywords: CDK4/6 inhibitors, Early breast cancer, HR+/HER2-, Patient-reported outcomes, RIB, ABE
Introduction
Breast cancer (BC) is recognized as a major global public health issue posing a serious threat to women’s health, with its disease burden remaining persistently high. According to GLOBOCAN data released by the International Agency for Research on Cancer (IARC), BC has consistently ranked as the most frequently diagnosed cancer and one of the leading causes of cancer-related mortality among women worldwide [1]. The situation is particularly severe in China. The latest report on the burden of malignant tumors in China released by the National Cancer Center in 2024 has revealed that in 2022, there were 357,200 newly diagnosed female BC cases and 75,000 deaths in China, corresponding to a crude incidence rate of 51.71 per 100,000 and a crude mortality rate of 10.86 per 100,000 [2]. Notably, due to the widespread implementation of screening programs and advancements in diagnostic techniques, over 90% of Chinese BC patients are diagnosed at an early stage [3]. Although early diagnosis has significantly improved overall prognosis, the risk of recurrence and metastasis remains a core challenge affecting long-term survival and quality of life.
Among molecular subtypes of BC, hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) is identified as the most prevalent subtype, accounting for approximately 70% of all BC cases [4]. Adjuvant endocrine therapy (AET) is established as one of the standard postoperative treatment regimens for early-stage patients with this subtype, aimed at reducing recurrence risk by blocking the estrogen signaling pathway [5]. However, clinical practice has demonstrated that recurrence or metastasis ultimately occurs in a subset of patients despite the receipt of standardized endocrine therapy [6]. Previous studies have revealed that HR+/HER2- early breast cancer (EBC) patients experience a short-term (< 5 years) local or distant recurrence rate of approximately 20–30%, with the recurrence risk peaking within the first 2–3 years of AET initiation. Furthermore, even for patients who remain recurrence-free beyond 5 years, the recurrence risk continues to accumulate over the subsequent 20 years [7]. This persistent recurrence risk underscores the necessity for effective intervention strategies in the HR+/HER2- EBC population. Consequently, authoritative guidelines and consensus statements have recommended that adjuvant intensification strategies should be considered in addition to standard multimodal treatments (surgery, radiotherapy, chemotherapy, and endocrine therapy) for eligible HR+/HER2- EBC patients [8, 9].
In recent years, breakthrough advances in targeted therapies have introduced revolutionary new options for adjuvant intensification. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors function by specifically inhibiting CDK4/6 kinase activity, thereby suppressing retinoblastoma (Rb) protein phosphorylation, arresting cell cycle progression from the G1 to S phase, and effectively inhibiting tumor cell proliferation [10]. These agents have demonstrated significant efficacy in the treatment of early HR+/HER2- BC. Pivotal phase III randomized controlled trials (RCTs), such as the NATALEE [11] and MonarchE [12] studies, have provided compelling evidence-based support. These trials consistently confirmed that the addition of CDK4/6 inhibitors (Ribociclib (RIB) and Abemaciclib (ABE)) to standard adjuvant endocrine therapy significantly improved invasive disease-free survival (IDFS) in high-risk HR+/HER2- EBC patients, substantially reducing the risk of invasive disease recurrence or death. These findings have laid a solid scientific foundation for the clinical application of CDK4/6 inhibitors in the adjuvant setting for EBC. However, the prolonged administration of adjuvant CDK4/6 inhibitors presents novel challenges. Ensuring therapeutic efficacy while effectively managing treatment-related adverse events, minimizing negative impacts on patient quality of life, and maintaining treatment adherence has emerged as the central challenge in optimizing long-term management for patients with HR+/HER2- early breast cancer. Concomitant with the profound shift towards a “patient-centered” model in modern healthcare, the evaluation systems in clinical research are continuously evolving. Overall survival (OS) is regarded as the standard endpoint for assessing the efficacy of anti-cancer therapies [13]. However, patients’ subjective experiences and quality of life (QoL) throughout the treatment course are increasingly being accorded equal importance [14, 15]. Patient-reported outcomes (PROs), derived directly from patients’ reports of their own health status, symptoms, quality of life, and treatment perceptions, play a critical role in evaluating drug efficacy, adverse events, and QoL in cancer patients. PROs have emerged as one of the key indicators for measuring treatment effects [16]. Through the systematic collection and analysis of PRO data, clinicians are enabled to gain deeper insights into treatment tolerability, identify underreported adverse events, and assess the interference of treatment with patients’ daily lives. Consequently, PROs provide crucial evidence to support the selection of more individualized treatment options that offer an optimal balance between efficacy and QoL. Therefore, PROs have become an indispensable component in evaluating the comprehensive value of cancer therapies. PROs not only provide a critical dimension for evaluating treatment effectiveness, but their data hold indispensable value for guiding clinical decision-making, optimizing adverse event management strategies, and enhancing patient treatment experience and adherence.
Therefore, a real-world, multicenter, retrospective cohort study was designed and conducted. This study aims to utilize PRO data from HR+/HER2- EBC patients receiving adjuvant therapy with either RIB or ABE to comprehensively evaluate and compare the safety profiles and multidimensional impact on QoL of these two CDK4/6 inhibitors in real-world practice. It is anticipated that this research will provide clinicians with more comprehensive evidence integrating efficacy and QoL outcomes to guide the selection of adjuvant CDK4/6 inhibitors, thereby facilitating truly individualized precision medicine and ultimately improving patients’ long-term survival quality and treatment experience.
Patients and methods
Study design and patients
This study is a multi-center, retrospective cohort study. BC PRO questionnaire survey was conducted in 5 tertiary hospitals including the Affiliated Tumor Hospital of Shandong First Medical University. According to the inclusion and exclusion criteria, eligible patients with early breast cancer were screened and invited to fill out the relevant questionnaire. The study protocol received ethical approval from the Medical Ethics Committee of the Cancer Hospital Affiliated to Shandong First Medical University (the lead center; Approval Number: SDTHEC202503003). The ethical approval from this lead center was acknowledged and administratively filed by each of the other participating centers, in compliance with the regulations governing multi-center clinical research.
The primary inclusion criterion is that patients must have been diagnosed with HR+/HER2- early breast cancer by a specialized hospital involved in the research, having initially received adjuvant therapy with RIB or ABE within the past year, and possessing an ECOG (Eastern Cooperative Oncology Group) performance status score of 0–1. All enrolled patients were required to sign the informed consent, willing to cooperate with the clinical research related treatment and follow-up, and had good compliance. The above standards are designed to maximize the comparability of the two groups at the clinical characteristic level.
Exclusion criteria were as follows: patients who failed to provide informed consent; patients were unable to complete the questionnaire independently or under the guidance of researchers.
Assessment procedures
From March to May 2025, data were collected by electronic questionnaire during outpatient or inpatient stay. The questionnaire was a self-made scale referring to the PRO scale for breast cancer patients in China (the NCC-BC-A scale) [17] and the EuroQol-five dimensions-five levels questionnaire (EQ-5D-5 L) [18], in which the symptom subscale items are customized according to the safety of CDK4/6 inhibitors, to evaluate the quality of life and treatment experience of patients.
The questionnaire included a section on basic patient information and a PRO scale. The demographic information, medical insurance and breast cancer diagnosis and treatment history of the patients were collected in the basic information section. Basic demographic information included age, gender, marital status, education, and employment status. History of breast cancer included the time of diagnosis, previous or ongoing treatment regimen, and the use of CDK4/6 inhibitors.
We have determined that the PRO scale includes six dimensions of items: (1) physiological functional domain (2), psychological domain (3), social support domain (4), therapeutic domain, including the symptom subscale (5), economic dimension, and (6) self-evaluation domain of overall health status. Unless otherwise specified, respondents were asked to rate each item on a Likert 5-point scale (0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, 4 = very much, and reverse-item with reverse scoring). Regarding the self-evaluation items of physical condition, the scale ranges from 0 to 100, with 0 signifying the worst conceivable health status and 100 denoting the best health state. Summed the scores of all items for each dimension. The higher score, the better quality of life. A small sample of HR+/HER2- early breast cancer patients was presurveyed using this questionnaire. The scale demonstrated good reliability and validity, with a Cronbach’s α coefficient of 0.734 and a validity coefficient of 0.729 (Figure S1).
In this study, all items of the PRO scale required patients to evaluate their symptoms or problems based on the previous week. By specifying a clear and short recall period of the past week, the design aimed to minimize recall bias associated with long-term memory.
Statistical methods
All statistical analyses were performed using R software. Continuous variables at baseline were presented as mean ± standard deviation (SD), while categorical variables were expressed as frequencies and percentages. Scores of each domain of the PRO scales were also summarized as mean ± SD. Treatment-related characteristics between the two groups, including treatment duration, treatment discontinuation, reasons for discontinuation, dose reduction, and reasons for dose reduction, were described using counts and percentages. The normality of continuous variables was assessed using the Shapiro–Wilk test. Independent-samples t tests were applied for variables with a normal distribution, whereas the Mann–Whitney U test was used for non-normally distributed variables. Categorical variables were compared using the Pearson chi-square test, and Fisher’s exact test was applied when the expected frequency in any cell was less than 5. All statistical tests were two-sided, and a p value < 0.05 was considered statistically significant. Given the exploratory nature of the adverse reaction analyses, no formal correction for multiple comparisons was applied.
Results
Study population characteristics
Between March 15, 2025, and May 12, 2025, a total of 275 patients who had received treatment within the past year were enrolled in this study, of whom 70% (197/275) completed the PRO questionnaire assessment. Of these, 94 patients were treated with RIB and 103 patients were treated with ABE. The mean ages of the patients were 52.7 ± 11.0 years and 51.2 ± 10.8 years, respectively. Overall, 195 patients (99%) were female and 2 patients (1%) were male.
No statistically significant differences (p > 0.05) were observed between the RIB and ABE groups regarding demographic characteristics or baseline disease information, including age, gender, marital status, education level, employment status, and medical insurance, except for timing of diagnosis (p < 0.001). The demographic and baseline clinical characteristics of all enrolled HR+/HER2- early breast cancer patients are summarized in Table 1.
Table 1.
Characteristics of patients participating
| Category | RIB(n = 94) | ABE(n = 103) | t-value | p-value |
|---|---|---|---|---|
| Age, mean (SD), y | 52.7 ± 11.0 | 51.2 ± 10.8 | -0.984 | 0.326 |
| Gender, n (%) | 1.000 | |||
| Female | 93(98.9%) | 102(99.0%) | ||
| Male | 1(1.1%) | 1(1.00%) | ||
| Marital status, n (%) | 0.107 | |||
| Married | 90(95.7%) | 100(97.1%) | ||
| Divorced | 1(1.06%) | 1(0.971%) | ||
| Widowed | 3(3.19%) | 0(0.00%) | ||
| Unmarried | 0(0.00%) | 2(1.94%) | ||
| Education, n (%) | 0.248 | |||
| Primary school | 9(9.57%) | 12(11.7%) | ||
| Junior high school | 29(30.9%) | 26(25.2%) | ||
| Senior high school | 47(50%) | 50(48.5%) | ||
| Undergraduate | 9(9.57%) | 12(11.7%) | ||
| Graduate student or above | 0(0%) | 3(2.91%) | ||
| Employment status, n (%) | 0.685 | |||
| Full-time employed | 8(8.5%) | 8(7.8%) | ||
| Part-time employed | 2(2.1%) | 4(3.9%) | ||
| Unemployed | 11(11.7%) | 11(10.7%) | ||
| Retirement | 6(6.4%) | 14(14.6%) | ||
| Medical insurance, n (%) | 1.000 | |||
| No insurance | 1(1.1%) | 1(1.0%) | ||
| UEBMI | 40(42.6%) | 53(51.5%) | ||
| BMIUR | 5(5.3%) | 3(2.9%) | ||
| Flexible employed Insurance | 1(1.1%) | 1(1.0%) | ||
| NCMS | 48(51.1%) | 47(45.6%) | ||
| Insurance for medical care | 3(3.2%) | 7(6.8%) | ||
| Business Insurance | 0(0.0%)) | 1(1.0%) | ||
| Timing of Diagnosis, n (%) | 19.358 | < 0.001 | ||
| 2024 | 51(54.3%) | 25(24.3%) | ||
| 2023 | 33(35.1%) | 54(52.4%) | ||
| Received or receiving treatment, n (%) | 1.782 | 0.410 | ||
| Chemotherapy | 82(87.2%) | 95(92.2%) | ||
| Endocrine therapy | 85(90.4%) | 87(84.5%) | ||
| Other (Radiotherapy) | 6(6.4%) | 12(11.7%) |
RIB Ribociclib, ABE Abemaciclib, SD standard deviation, UEBMI Urban Employee Basic Medical Insurance, BMIUR Basic Medical Insurance for Urban and Rural Residents, NCMS New Rural Co-operative Medical Insurance
The PRO scale
The composite PRO score was significantly higher in the RIB group (187.14 ± 17.57) compared to the ABE group (180.66 ± 22.26; t = 2.276, p = 0.024). Within the therapeutic domain subscale, a significantly higher score was also recorded for the RIB group (34.81 ± 5.29) versus the ABE group (32.77 ± 5.51; t = 2.653, p = 0.009). The composite scores and scores for all dimensions are presented in Table 2.
Table 2.
PRO total score and each dimension score
| Category | Number of items | Total score | RIB(n = 94) | ABE(n = 103) | t-value | p-value |
|---|---|---|---|---|---|---|
| Physiological functional domain | 8 | 32 | 25.34 ± 2.47 | 24.76 ± 3.23 | 1.432 | 0.154 |
| Psychological domain | 4 | 16 | 12.85 ± 2.11 | 12.27 ± 2.42 | 1.793 | 0.075 |
| Social support domain | 7 | 28 | 21.54 ± 2.79 | 21.95 ± 2.76 | -1.034 | 0.302 |
| Therapeutic domain | 11 | 44 | 34.81 ± 5.29 | 32.77 ± 5.51 | 2.653 | 0.009 |
| Economic dimension | 1 | 4 | 2.13 ± 1.19 | 2.01 ± 1.25 | 0.678 | 0.499 |
| Self-evaluation domain | 4 | 112 | 90.47 ± 11.92 | 86.90 ± 14.69 | 1.878 | 0.062 |
| Total | 35 | 236 | 187.14 ± 17.57 | 180.66 ± 22.26 | 2.276 | 0.024 |
RIB Ribociclib, ABE Abemaciclib
Functional subscales
No significant differences were found in the scores for the physiological functional domain (RIB: 25.34 ± 2.47 vs. ABE: 24.76 ± 3.23), psychological dimension (RIB: 12.85 ± 2.11 vs. ABE: 12.27 ± 2.42), or Social support domain (RIB: 21.54 ± 2.79 vs. ABE: 21.95 ± 2.76) between the two groups. However, within the physical dimension, the score for the “daily activities” item was significantly higher in the RIB group (3.95 ± 0.23) compared to the ABE group (3.79 ± 0.65; t = 2.349, p = 0.020). Scores for all other sub-items within these dimensions showed no significant differences (Table 3).
Table 3.
Scores of each subscale
| Category | Number of items | Total score | RIB(n = 94) | ABE(n = 103) | t-value | p-value |
|---|---|---|---|---|---|---|
| Physiological functional domain | 8 | 32 | 25.34 ± 2.47 | 24.76 ± 3.23 | 1.432 | 0.154 |
| Ability to move around | 1 | 4 | 3.93 ± 0.26 | 3.86 ± 0.44 | 1.193 | 0.235 |
| Self-care | 1 | 4 | 3.94 ± 0.29 | 3.86 ± 0.58 | 1.124 | 0.263 |
| Daily Activities | 1 | 4 | 3.95 ± 0.23 | 3.79 ± 0.65 | 2.349 | 0.020 |
| Pain/Discomfort | 1 | 4 | 3.31 ± 0.64 | 3.28 ± 0.60 | 0.304 | 0.761 |
| Sleep problems | 1 | 4 | 3.29 ± 0.88 | 3.03 ± 0.98 | 1.948 | 0.053 |
| Hypomnesis | 2 | 8 | 6.55 ± 1.43 | 6.43 ± 1.67 | 0.572 | 0.568 |
| Harmonious sexual life | 1 | 4 | 0.38 ± 1.18 | 0.50 ± 1.33 | -0.679 | 0.498 |
| Psychological domain | 4 | 16 | 12.85 ± 2.11 | 12.27 ± 2.42 | 1.793 | 0.075 |
| Mental attitude towards disease | 3 | 12 | 9.47 ± 1.88 | 8.92 ± 2.25 | 1.851 | 0.066 |
| Anxiety/Depression | 1 | 4 | 3.38 ± 0.78 | 3.35 ± 0.65 | 0.326 | 0.745 |
| Social support domain | 7 | 28 | 21.54 ± 2.79 | 21.95 ± 2.76 | -1.034 | 0.302 |
| Family/Friend support | 5 | 20 | 17.37 ± 2.53 | 17.80 ± 1.81 | -1.343 | 0.181 |
| Social activities | 2 | 8 | 4.17 ± 1.40 | 4.16 ± 1.62 | 0.069 | 0.945 |
RIB Ribociclib, ABE Abemaciclib
Therapeutic domain
Treatment was received for more than one cycle by 98.5% of the surveyed patients. Details regarding treatment status at the time of the survey are provided in Table 4. Discontinuation of medication was reported for 14 patients in the RIB group and 16 patients in the ABE group. Side effects of long-term treatment were the primary reason for discontinuation in both groups, with a higher proportion of ABE discontinuations attributed to adverse events (AEs) (50.0%) compared to RIB (28.6%). Dose reduction was experienced by 9 patients (9.6%) in the RIB group and 30 patients (29.1%) in the ABE group. The dose reduction rate was significantly lower in the RIB group (p < 0.001). The main reasons cited for dose reduction were adverse drug reactions and Doctor’s advice (Table 4).
Table 4.
Summary of treatment
| Category | RIB(n = 94) | ABE(n = 103) | χ²-value | p-value |
|---|---|---|---|---|
| Duration of medication, n (%) | < 0.001 | |||
| Within 1 month | 2(2.1%) | 1(1%) | ||
| 1–6 months | 42(44.7%) | 8(7.8%) | ||
| More than 6 months | 50(53.2%) | 94(91.3%) | ||
| Discontinuation of medication, n (%) | 0.000 | 1.000 | ||
| Yes | 14(14.9%) | 16(15.5%) | ||
| No | 80(85.1%) | 87(84.5%) | ||
| Reasons for discontinuation*, n (%) | 0.535 | |||
| Adverse events | 4 (28.6%) | 8 (50%) | ||
| Financial difficulties | 2 (14.3%) | 1 (6.2%) | ||
| Insufficient medical resources or inconvenient access to medical services | 1 (7.1%) | 1 (6.2%) | ||
| Personal choice | 4 (28.6%) | 1 (6.2%) | ||
| Others | 5 (35.7%) | 5 (31.2%) | ||
| Dose reduction, n (%) | 10.633 | 0.001 | ||
| Yes | 9(9.6%) | 30(29.1%) | ||
| No | 85(90.4%) | 73(70.9%) | ||
| Reasons for reduction*, n (%) | 0.0624 | |||
| Doctor’s advice | 5 (55.6%) | 21 (70%) | ||
| Adverse drug reactions | 2 (22.2%) | 21 (70%) | ||
| Financial difficulties | 2 (22.2%) | 2 (6.7%) | ||
| Personal choice | 2 (22.2%) | 6 (20%) | ||
| Others | 2 (22.2%) | 1 (3.3%) |
RIB Ribociclib, ABE Abemaciclib
* Multiple-choice question
Analysis of the treatment dimension confirmed the significant difference favoring RIB (34.81 ± 5.29 vs. 32.77 ± 5.51; t = 2.653, p = 0.009). Within this dimension, significantly higher scores (indicating less severe symptoms) were observed in the RIB group for fatigue perception (2.29 ± 0.91 vs. 2.00 ± 1.02; t = 2.088, p = 0.038), diarrhea perception (3.88 ± 0.53 vs. 2.31 ± 1.33; t = 11.096, p < 0.001), and alopecia perception (2.94 ± 1.39 vs. 2.49 ± 1.24; t = 2.397, p = 0.018), suggesting more severe experiences of these AEs in the ABE group. Conversely, a significantly lower score (indicating more severe symptoms) was observed in the RIB group for the swelling or peeling in hands and feet (3.10 ± 1.16 vs. 3.46 ± 0.92; t = -2.412, p = 0.017) (Table 5).
Table 5.
Adverse reaction feeling score
| Category | Number of items | Total score | RIB(n = 94) | ABE(n = 103) | t-value | p-value |
|---|---|---|---|---|---|---|
| discomfortableness | 1 | 4 | 2.49 ± 0.90 | 2.41 ± 0.95 | 0.617 | 0.538 |
| Decreased immunity | 1 | 4 | 2.70 ± 0.88 | 2.52 ± 1.01 | 1.323 | 0.187 |
| Fatigue | 1 | 4 | 2.29 ± 0.91 | 2.00 ± 1.02 | 2.088 | 0.038 |
| Dizzy | 1 | 4 | 3.47 ± 0.83 | 3.49 ± 0.93 | -0.139 | 0.890 |
| Diarrhea | 1 | 4 | 3.88 ± 0.53 | 2.31 ± 1.33 | 11.096 | < 0.001 |
| Constipation | 1 | 4 | 3.56 ± 0.85 | 3.61 ± 0.67 | -0.435 | 0.664 |
| Nausea | 1 | 4 | 3.64 ± 0.80 | 3.61 ± 0.77 | 0.238 | 0.812 |
| Reduced food intake | 1 | 4 | 3.56 ± 0.81 | 3.52 ± 0.80 | 0.344 | 0.731 |
| Alopecia | 1 | 4 | 2.94 ± 1.39 | 2.49 ± 1.24 | 2.397 | 0.018 |
| Swelling or peeling in hands and feet | 1 | 4 | 3.10 ± 1.16 | 3.46 ± 0.92 | -2.412 | 0.017 |
| Not sensitive to heat and cold, numbness or slow reaction in hands and feet | 1 | 4 | 3.18 ± 1.08 | 3.35 ± 0.89 | -1.190 | 0.236 |
RIB Ribociclib, ABE Abemaciclib, 0 None, 4 Severe
Economic dimension
No significant difference was found in the economic dimension score between the RIB group (2.13 ± 1.19) and the ABE group (2.01 ± 1.25) (Table 3).
Overall health status
Regarding the overall self-evaluation dimension score, no significant difference was observed between the RIB group (90.47 ± 11.92) and the ABE group (86.90 ± 14.69). However, significantly higher scores were observed for the item assessing overall health status in patients treated with RIB (6.67 ± 1.27) compared to those treated with ABE (5.83 ± 1.45; t = 4.306, p < 0.001) (Table 6).
Table 6.
The overall self-evaluation dimension and each item score
| Category | Number of items | Total score | RIB(n = 94) | ABE(n = 103) | t-value | p-value |
|---|---|---|---|---|---|---|
| Self-evaluation domain | 4 | 112 | 90.47 ± 11.92 | 86.90 ± 14.69 | 1.878 | 0.062 |
| Treatment Satisfaction | 1 | 4 | 3.15 ± 0.80 | 3.05 ± 0.82 | 0.867 | 0.387 |
| Overall health status | 2 | 8 | 6.67 ± 1.27 | 5.83 ± 1.45 | 4.306 | < 0.001 |
| Physical status | 1 | 100 | 80.65 ± 10.79 | 78.02 ± 13.51 | 1.516 | 0.131 |
RIB Ribociclib, ABE Abemaciclib
Discussion
Precision molecular subtyping of breast cancer based on biomarkers such as ER, PR, and HER2 has been established as the cornerstone of individualized treatment strategies [19]. With prolonged patient survival, increasing attention has been directed toward treatment-related adverse effects and their impact on health-related quality of life, rendering patient-reported outcomes a central measure for evaluating treatment experience and quality of life [16, 17]. In advanced BC, endocrine therapy combined with CDK4/6 inhibitors, such as RIB and ABE, has been demonstrated not only to significantly prolong progression-free survival (PFS) and overall survival (OS), but also to preserve or even improve patients’ quality of life [20, 21]. In the EBC setting, the NATALEE [11] and MonarchE [12] trials further extended the application of CDK4/6 inhibitors to the adjuvant setting, with both studies showing that adjuvant RIB or ABE improved invasive disease–free survival in high-risk patients while maintaining overall quality of life. However, substantial differences existed in the design of the enrolled populations between the two trials [22]. In real-world clinical practice, RIB is applicable to a broader population of patients with EBC [23], suggesting that its benefits may extend to a wider range of EBC patients.
It is noteworthy that both studies recently reported HRQoL outcomes. NATALEE utilized a comprehensive PRO battery (EORTC QLQ-C30, EORTC QLQ-BR23, EQ-5D-5 L VAS, HADS) to assess PROs during RIB adjuvant treatment [24]. MonarchE employed FACT-B, FACT-ES, and FACIT-F scales to evaluate HRQoL and expected treatment-related symptoms during the 2-year ABE treatment period and a subsequent 1-year follow-up [25]. Consistent conclusions were drawn from both studies: although a transient increase in symptom burden related to AEs was observed early in treatment, overall HRQoL was maintained throughout the treatment cycle, and symptom burden demonstrated a declining trend over time. However, due to the utilization of different PRO assessment toolkits, direct comparison of the PRO data reported by these studies is precluded, limiting the precise evaluation of the combined efficacy-QoL benefit across trials.
In this study, a locally developed, BC-specific PRO questionnaire was employed for the first time within a Chinese HR+/HER2- EBC population to systematically evaluate the impact of RIB versus ABE adjuvant therapy on patient QoL and treatment experience. This questionnaire was innovatively developed by integrating core domains from the Chinese NCC-BC-A scale, the utility assessment of EQ-5D-5 L, and incorporating specific items addressing AE experiences and treatment burden, tailored to the characteristics of EBC treatment and the known safety profiles of CDK4/6 inhibitors. It was demonstrated that the composite PRO score was significantly better in the RIB group compared to the ABE group. Specifically, comparable scores between the two groups were observed across five core dimensions: physical functioning, psychological status, social support, economic concerns, and overall self-rated health status. Although significant differences were observed in the long-term use of CDK4 / 6 inhibitors between the two groups, most patients used CDK4 / 6 inhibitors more than the first three cycles, which is the highest stage of adverse events [26]. This confirms that our safety and efficacy assessments adequately capture the highest-risk AE window.
Notably, the key divergence lay in the treatment dimension of AE perception: RIB-treated patients reported significantly milder AE symptom intensity, particularly fatigue, diarrhea, and alopecia. This observation is consistent with findings from the NATALEE [11] and MonarchE [12] trials, in which high rates of fatigue (40.85%, 1140/2791) and diarrhea (83.55%, 2332/2791) were reported among patients receiving ABE, whereas the incidence of fatigue among patients treated with RIB was only 22.3% (564/2525), and diarrhea was not listed among the common adverse events. Furthermore, results from the MonarchE study results [27, 28] indicated that during the early treatment phase (3–6 months), most patients in the ABE group perceived their treatment experience as “a little” or “somewhat” problematic, and fatigue was identified as a relatively common symptom in 31.3% of patients in both the adjuvant and metastatic settings. More critically, this study further revealed that AEs such as diarrhea not only affected patient experience but also directly contributed to a higher rate of treatment discontinuation or dose reduction in the ABE group. Given that premature treatment discontinuation has been associated with worsening QoL, this represents a significant clinical consideration. In summary, these real-world data suggest that patients receiving RIB adjuvant therapy exhibit advantages in overall PRO scores, particularly regarding tolerance to treatment-related AEs, and experience a lower risk of treatment modification due to AEs, potentially offering a superior treatment persistence experience.
The PRO differences between CDK4/6 inhibitors identified in this study carry direct implications for patient management: The higher risk of diarrhea and treatment discontinuation rate observed in the ABE group necessitates the implementation of intensified preventive management, including comprehensive pre-treatment education, predefined anti-diarrheal protocols, and proactive early monitoring to ensure completion of the full treatment course. Although superior tolerability was noted in the RIB group, standard adverse event education and monitoring remain essential to ensure safe and sustained medication use. More importantly, patient-reported adverse event experiences should be incorporated into individualized drug selection decisions. Collaborative evaluation by clinicians and patients is required to assess individual sensitivity to specific symptoms (e.g., diarrhea), lifestyle demands, and concerns regarding treatment interruption. For instance, RIB may be associated with a more favorable treatment experience for patients with poor diarrhea tolerance or high adherence requirements, as supported by this study. The integration of PROs into shared decision-making processes represents a key practice for optimizing management and improving adherence.
However, several limitations inherent in this study must be acknowledged. First, several limitations related to baseline data should be considered. Baseline PRO assessments were not available, which limited our ability to perform fully adjusted comparisons of symptom burden between treatment groups. Although the same PRO assessment tool was used in both groups in this study, the lack of baseline data means that the statistical comparisons of PRO scores between the RIB and ABE groups should be interpreted with caution. The results presented are therefore primarily descriptive, reflecting symptom experiences during treatment rather than providing definitive evidence of differences in drug tolerability. In addition, owing to the retrospective design, certain pathological variables (such as tumor grade, Ki‑67 index, and quantitative ER/PgR status) were not consistently available and therefore could not be systematically incorporated into baseline comparisons. To mitigate this issue, we applied uniform clinical inclusion criteria—including early‑stage disease, ECOG performance status 0–1, and initiation of adjuvant therapy within one year—to enhance baseline comparability; nevertheless, these unavoidable data limitations may have constrained a more comprehensive assessment of baseline equivalence. Future prospective studies with systematic collection of pathological characteristics and baseline as well as longitudinal PRO measurements would allow more refined adjustment and validation of the present findings. Second, potential limitations related to the PRO assessment tool should be acknowledged. Although a self-developed questionnaire was used in this study, its construction was theory-driven rather than arbitrary. The instrument was developed with reference to the NCC-BC-A scale validated for Chinese patients (developed by Ma et al.) and the EQ-5D-5 L framework proposed by Herdman et al., and was further tailored to capture adverse event–related symptoms relevant to the safety profile of CDK4/6 inhibitors. Importantly, preliminary psychometric evaluation of the questionnaire has been completed. Nevertheless, it should be acknowledged that this instrument has not yet undergone large-scale, multicenter validation to fully establish its psychometric properties across broader populations, which may have influenced the precision of the findings. Future studies with prospective designs and larger samples are warranted to further validate and refine this PRO instrument. Third, Adverse events were assessed via patient-reported severity scores rather than clinician-graded CTCAE criteria. While this directly reflects the symptomatic burden experienced by patients, it precludes a direct comparison with standard oncologic toxicity grades, an important dimension for clinical interpretation that should be incorporated in future prospective studies. Fourth, the response rate to the PRO questionnaire was only 71.64% (197/275), which may have introduced a degree of response bias. Although no significant differences in major baseline characteristics were observed between responders and non-responders in our analyses, bias due to unmeasured factors cannot be fully excluded. Therefore, the findings of this study should be interpreted with caution, particularly when generalizing the results to broader patient populations. Future studies could improve response rates through more proactive follow-up strategies and conduct targeted analyses of non-responders to further assess and control for such bias.
Conclusions
This study, by collecting real-world treatment experience data from Chinese HR+/HER2- EBC patients, provides the first localized evidence on the impact of CDK4/6 inhibitors (RIB and ABE) on patient QoL during the adjuvant treatment phase. It was demonstrated that patients receiving RIB adjuvant therapy achieved significantly better composite PRO scores than those receiving ABE. Specifically, RIB-treated patients reported lower perceived intensity of treatment-related adverse events (such as fatigue, diarrhea, and alopecia), superior tolerance, and a reduced risk of treatment interruption or dose reduction due to AEs. Consequently, RIB may offer patients a more sustainable treatment experience and enhanced QoL protection. These findings provide crucial supplementary evidence for clinical decision-making. When selecting a CDK4/6 inhibitor based on the efficacy established in NATALEE and MonarchE, an integrated consideration of efficacy, patient experience, and individual factors is required to achieve the goal of precision medicine.
Supplementary Information
Supplementary Material 1: Figure S1. Reliability and Validity of the Questionnaire. The dashed line represents the prespecified acceptability threshold (≥0.70). The bar chart shows the coefficient values for Construct validity (0.729) and Cronbach’s α (0.734), both of which exceed this threshold, indicating good internal validity and reliability of the scale.
Authors’ contributions
Binbin Cong: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Supervision, Validation, Visualization, Writing - original draft.Chuanqiang Hou: Data curation.Changping Shan: Data curation.Shenyou Sun: Data curation.Shanping Sun: Data curation.Chongsheng Xia: Data curation.Yongsheng Wang: Data curation, Formal analysis, Validation, Writing - review & editing.
Funding
Supported by Collaborative Academic Innovation Project of Shandong Cancer Hospital (GF003).
Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
This study was approved by the Medical Ethics Committee of Shandong First Medical University Affiliated Cancer Hospital (Ethics No. SDC202503003), and written informed consent was obtained from all participants prior to enrollment. This study was conducted in accordance with the principles of the Declaration of Helsinki (https://www.wma.net/policies-post/wma-declaration-of-helsinki/).
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Supplementary Material 1: Figure S1. Reliability and Validity of the Questionnaire. The dashed line represents the prespecified acceptability threshold (≥0.70). The bar chart shows the coefficient values for Construct validity (0.729) and Cronbach’s α (0.734), both of which exceed this threshold, indicating good internal validity and reliability of the scale.
Data Availability Statement
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.