Endocrine therapy, which has a standard duration of 5 years, is a well-known and effective treatment for endocrine-sensitive breast cancer. Classic drugs such as tamoxifen and aromatase inhibitors block the body's ability to produce hormones or prevent hormones from reaching breast cancer cells, decreasing the 15-year breast cancer mortality rates by approximately 30% and 40%, respectively.1

Although endocrine therapy significantly extends the overall and disease-free survival of women with breast cancer, it is associated with multiple side effects that increase patients’ symptom burden. Berkowitz et al2 conducted a large survey of participants in online breast cancer communities who received endocrine therapy and found that 91.2% of the respondents reported side effects and approximately one-third discontinued therapy early. Additionally, Kadakia et al3 found that worsening symptoms in the musculoskeletal, cognitive, mood, and weight/body image clusters were associated with an increased risk for early medication discontinuation in aromatase inhibitor–treated postmenopausal women with early-stage breast cancer. Zhu et al4 created a symptom map of endocrine therapy for breast cancer in which five key symptoms associated with endocrine therapy were identified, including joint/muscle pain, hot flashes, low sexual interest/desire, joint/muscle stiffness, and fatigue/lack of energy. Cella et al5 summarized patient-reported side effects and management associated with adjuvant endocrine therapies in clinical trials, including gynecologic symptoms, bone loss and osteoporosis, arthralgia, hot flashes, sexual dysfunction and vaginal dryness, and cognitive dysfunction. Moreover, with the accumulating evidence of adjuvant endocrine treatment extended beyond 5 years, an emergency need for the management of endocrine therapy–related side effects is rising.1,6

Increasing evidence suggests that endocrine therapy–associated symptoms may affect patients’ quality of life. The mind–body observational cohort study directly examined the impact of adjuvant endocrine therapy on quality of life and symptoms, which showed impaired health-related quality of life by using physical health scores among patients receiving endocrine therapy.7 Sitlinger et al8 found that a higher symptom burden was associated with lower function in women receiving adjuvant endocrine therapy for breast cancer as well. In addition, Martino et al9 found that postmenopausal women receiving aromatase inhibitor treatment for early breast cancer had higher anxious and depressive symptoms and lower perceived quality of life compared with healthy postmenopausal women. Additionally, Olufade et al10 and Laroche et al11 evaluated quality of life among breast cancer patients during aromatase inhibitor treatment, focusing particularly on the impact of pain. They found that musculoskeletal pain adversely affected both mental and physical dimensions of quality of life.

To better manage multiple symptoms related to endocrine therapy and effectively improve the quality of life of breast cancer patients, the research focus shifted from a single symptom to symptom clusters. For instance, Li et al12 identified seven symptom clusters, including four stable symptom clusters (ie, musculoskeletal, vasomotor, urinary, and sexual) and three relatively stable symptom clusters (ie, psychological, neurocognitive, and weight) during the first 18 months of adjuvant endocrine therapy; however, the impact of these symptom clusters on quality of life was not examined in this study. In addition, Wen et al13 identified three symptom clusters (ie, disease-related, treatment-related-psychological and gastrointestinal) and found that the more severe the disease symptom cluster, the more severe was the treatment-related psychological symptom cluster and the worse physical health will be. However, the symptom assessment tool used in this study was not specific to breast cancer patients receiving endocrine therapy, which may not reflect the overall symptom experience.

To verify the associations between symptom clusters and quality of life, endocrine therapy–specific scales were used in this study to investigate symptoms of breast cancer patients, identify core symptom clusters, and explore the impact of these symptom clusters on quality of life. Our study may contribute to developing intervention strategies for better symptom management and improving patients’ quality of life.