Visual abstract

Introduction

Adjuvant chemotherapy for breast cancer (BC) aims to eradicate residual cancer cells, reduce recurrence, and improve long-term survival [1]. Over the past 3 decades, chemotherapy has substantially increased the number of disease-free individuals (18%) and overall survival rates (25%) in people with BC as compared with those BC patients not receiving chemotherapy [2,3]. However, these benefits of chemotherapy are typically accompanied with adverse effects including nausea, vomiting, myelosuppression, ovarian failure, alopecia, and peripheral neuropathy, and these side effects can diminish patients’ quality of life [4].

Integrative medicine (IM) treatment is employed to mitigate these toxicities and support immune function. It has been reported that chemotherapy-induced nausea, vomiting, and neuropathy have been alleviated by IM treatment [5–7].

The Korean Medicine Clinical Practice Guideline (KMCPG) for BC supportive care [8] issued in 2021, provides evidence-based recommendations for managing a wide range of symptoms arising from surgery, radiation therapy, endocrine therapy, and chemotherapy. Building on this guideline, a clinical pathway (CP) for IM treatment in non-invasive BC was developed in 2022 [9]. However, existing guidelines and pathways often focus on broad symptoms across the entire BC treatment continuum and lack the specific, detailed guidance clinicians need in particular settings. Take neutropenia (low concentration of neutrophils in the blood) for example, it is one of the most critical chemotherapy-induced side effects, and heightens the risk of severe infections, causes dose reductions, and treatment delays, thereby compromising treatment outcomes [10]. As chemotherapy treatment in Korea increasingly shifts to outpatient settings (such as infusion centers), timely identification, and management of side effects is challenging [11]. In fact, in a study carried out in Canada, 53% of BC patients had at least 1 Emergency Department visit due to chemotherapy-induced toxicities, with 13.4% needing hospital admission [12]. To address chemotherapy-induced toxicities and potential Emergency Department admissions, an IM Inpatient Care Program framework was developed in this study. It was designed to systematically manage chemotherapy-induced adverse effects in BC patients to establish standardized clinical practices in Korea.

This short communication introduces an outline of the IM Inpatient Care Program for breast cancer patient’s post-chemotherapy, and highlights its role in improving supportive care whilst addressing the limitations of existing management approaches.

Materials and Methods

1. Objectives of the inpatient IM care program framework

An IM Inpatient Care Program framework model, specifically for post-chemotherapy BC patients, was developed by reviewing the KMCPG for supportive care of people with BC [8] and a previously established CP [8,9]. The program was structured for healthcare professionals to systematically monitor and manage chemotherapy-related side effects, alleviate patients’ psychological burden (by enhancing access to IM treatment), and facilitate standardization of treatment protocols. The framework is intended for BC patients admitted for inpatient KM treatment within 1 week of chemotherapy administration.

2. Review of existing CPGs and CPs

The KMCPG for supportive care of people with BC [8] provides evidence-based recommendations for various diagnostic tests and KM treatments based on patients’ symptoms, alongside an assessment of the strength of evidence for each recommendation. Additionally, the guideline suggests questionnaire-based assessments to evaluate symptom severity and treatment effectiveness.

Three authors manually reviewed the KMCPG to extract the key components relevant to the development of an IM Inpatient Care Program framework, and referred to the inpatient care plan outlined in the CP [8,9]. However, existing CPGs and CPs encompass a broad spectrum of symptoms associated with different BC treatments including surgery, chemotherapy, radiation therapy, and endocrine therapy. To develop a framework specifically addressing chemotherapy-induced adverse effects additional guidelines were referred to [13,14] that focused on the management of chemotherapy-related toxicities and post-discharge care. These sources helped refine the IM Inpatient Care Program framework to ensure its applicability to the needs of chemotherapy patients.

3. Development of the IM Inpatient Care Program framework

To align the framework with real-world clinical practice, this study was also based on the analysis of hospital data from BC patients who had been admitted for IM treatment following chemotherapy [13,14]. This analysis focused on the diagnostic test results, examinations, and treatments administered during hospitalization. Additionally, the assessment of the current treatment process was employed to identify areas for improvement. Based on these findings, the IM Inpatient Care Program framework was developed.

As this study was based on a literature review and did not involve human participants, Institutional Review Board approval was not required.

Results

1. IM Inpatient Care Program model for BC patients’ post-chemotherapy

The inpatient care process encompassed examination, diagnosis, and treatment from admission to discharge (Figure 1). The program was structured to provide comprehensive monitoring, early intervention for chemotherapy-induced side effects, and systematic KM-based supportive care.

1.1. Observation and monitoring

Vital signs including blood pressure, pulse rate, respiration rate, and body temperature were measured 2 to 3 times per day throughout the inpatient period. In patients who had undergone BC surgery, blood pressure was measured on the unaffected side (to prevent complications such as lymphedema).

1.2. Examinations

During hospitalization, patients underwent routine diagnostic tests including blood tests, electrocardiograms, and radiographical imaging. If abnormal hematological findings were detected, patients were referred to the Department of Hemato-Oncology for further evaluation. Blood tests were performed on Days 3 and 4 of hospitalization to assess the patient’s condition and they were monitored for potential adverse events. Since chemotherapy-induced neutropenia typically develops 7 to 14 days post-chemotherapy [13], an additional blood test was scheduled on the 7^th day post-chemotherapy (or post-discharge) for continued monitoring.

1.3. Diet and activity management

A high-protein diet was provided to ensure sufficient nutrient and calorie intake. Physical activity was generally unrestricted, except in cases of severe weakness or dizziness where limited activity was recommended based on the patient’s condition.

1.4. KM treatment

The KMCPG for supportive care in BC [8] outlines treatment recommendations for symptoms such as fatigue, general weakness, pain, depression, anxiety, nausea, vomiting, hot flashes, and quality of life. In the inpatient care setting, particular emphasis is placed on managing peripheral neuropathy, insomnia, constipation, and diarrhea which are frequently observed post-chemotherapy [13]. KM treatments including herbal prescriptions, acupuncture, and moxibustion are tailored to patients’ individual symptoms, with treatment regimens adjusted accordingly by KM physicians.

1.5. Symptom assessment

Ten key symptom domains were assessed throughout hospitalization, aligning with the treatment targets: fatigue and general weakness, pain, depression, anxiety, nausea and vomiting, quality of life, peripheral neuropathy, insomnia, constipation, and diarrhea. The corresponding assessment tools and questionnaires used for these evaluations are detailed in Supplementary Table 1.

1.6. Referral system

Referrals were made for both inpatient and outpatient follow-up examinations based on clinical findings. Patients were referred to the appropriate medical department if significant abnormalities were detected. Specifically, referrals to the Department of Hemato-Oncology were initiated under the following conditions previously described [13,14]: (1) absolute neutrophil count < 1,000/mm³: (2) body temperature ≥ 38°C; (3) persistent vomiting; and (4) inability to eat for more than 24 hours.

1.7. Patient education

Comprehensive patient education was provided through-out the inpatient stay: (1) ward orientation and safety protocols; (2) explanations of the KM treatments and roles in supportive care; (3) dietary and lifestyle recommendations; and (4) infection control measures. Upon discharge, patients received post-discharge management instructions including self-monitoring strategies and criteria for Emergency Room visits to ensure continuity of care and timely intervention when necessary.

Discussion

The treatment goals of chemotherapy are to shrink cancer before surgery, inhibit the micrometastasis of BC cells after surgery (to prevent relapse), or palliate symptoms and improve the quality of life of patients with metastatic BC [15]. In a review of 123 randomized controlled trials on chemotherapy regimens in early BC, meta-analyses of long-term patient outcomes showed that chemotherapy reduced BC-related deaths by 36% compared with BC patients not receiving chemotherapy [16]. In a real-world population study of the impact of adjuvant chemotherapy on BC survival, the risks of death, and distant metastasis was reduced by 25%, and 18%, respectively [3]. However, chemotherapy may cause various side effects including myelosuppression, nausea and vomiting, peripheral neuropathy, cardiac toxicity, and ovarian failure [4].

In Korea, KM treatment for chemotherapy-induced side effects is provided as an inpatient of KM hospitals. In a study of BC patients admitted to a KM hospital due to the side effects of chemotherapy (n = 6) improvement was observed following KM treatment [17]. In another study, the characteristics and treatments used for KM hospital BC inpatients were analyzed and Gwakhyangjunggisan-gami was the most administered prescription, and acupuncture, moxibustion, and cupping were performed in all inpatients (n = 21) [18]. With a growing demand for treatment to minimize chemotherapy-induced side effects and improve quality of life, the importance of systematic and standardized evidence-based CPG has emerged.

A CP was developed for “fatigue and general weakness,” “BC pain,” “chemotherapy-induced nausea and vomiting,” and “improvement of quality of life” domains [8]. However, challenges were encountered when applying it in real-world KM hospital settings.

Analysis of BC patients visiting KM hospitals showed many cases sought inpatient treatment for chemotherapy-induced side effects including peripheral neuropathy and nausea and vomiting. Neutropenia management was necessary, in some cases, given the risk of invasive infection, septic shock, and death. Therefore, empirical antibiotic therapy and use of granulocyte colony-stimulating factor may be required [19]. In clinical practice, some cases necessitate active observation and treatment of chemotherapy-induced side effects with conventional medicine. Therefore, the IM Inpatient Care Program model for post-chemotherapy care in BC patients was developed to establish IM treatment standards and improve satisfaction among patients and healthcare professionals. This model was developed using the KMCPG for supportive care in BC [8], CP model in IM for the treatment of non-invasive BC [9], and additional guidelines on the management of chemotherapy-induced side effects [13,14].

The IM Inpatient Care Program in this study included assessments and treatments for various chemotherapy-induced side effects observed in clinical practice: “fatigue and general weakness,” “pain,” “depression,” “anxiety,” “nausea and vomiting,” “quality of life,” “peripheral neuropathy,” “insomnia,” “constipation,” and “diarrhea.”

In the KMCPG [8], herbal medicine is recommended for all symptoms except nausea and vomiting, (Grade B recommendation and a moderate level of evidence). For “nausea and vomiting,” acupuncture is recommended (Grade

B recommendation and moderate level of evidence). Concurrent acupuncture and antiemetic medications significantly reduced emesis in BC patients undergoing chemotherapy, and acupuncture is strongly recommended for treating chemotherapy-induced nausea and vomiting [5,6].

Previous studies have analyzed the effectiveness of KM treatment for chemotherapy-induced peripheral neuropathy and other chemotherapy-induced side effects such as constipation, and diarrhea [7,20–23]. Furthermore, acupuncture has been effective in relieving chemotherapy-induced peripheral neuropathy symptoms [7]. Electroacupuncture at GV20, EX-HN1, GV24, PC6, SP6, and KI3, and auricular acupressure at the heart, Shenmen, and sympathetic acupoints, has been effective in chemotherapy-related insomnia [20]. Auricular acupressure has also been effective in treating constipation in BC [21], and in leukemia patients undergoing chemotherapy [22]. In addition, Chinese herbal medicine such as Xiaoaiping has shown significant efficacy in the treatment of chemotherapy-induced diarrhea in BC patients compared with controls [23].

Many studies have demonstrated the effectiveness of KM treatment, but patients often complain about the cost burden of herbal medicine. To reduce costs and increase accessibility, powdered herbal extraction may be considered. Rikkunshito (Yukgunja-tang) has been effective in reducing antiemetic use for cisplatin-induced nausea and vomiting [24], and improving appetite, nausea and vomiting, and quality of life in advanced esophageal cancer patients [25]. Hangeshashinto (Banhasasim-tang) is used in Japan to treat chemotherapy-induced diarrhea and oral ulcerative mucositis [26,27].

The proposed IM Inpatient Care Program model in this study included testing for and the management of neutropenia which is a serious chemotherapy-induced side effect. In a study of Emergency Room visits due to chemotherapy-induced side effects in cancer patients (n = 294), 50.7% involved neutropenia [28]. Patients with neutropenia are highly vulnerable to infections [29], so the proposed IM Inpatient Care Program model included information on assessment and treatment of neutropenia. (Neutropenia is defined as an absolute neutrophil count < 500/mm³, or < 1,000/mm³, expected to drop to < 500/mm³ within 2–3 days, requiring prophylactic antibiotics [29]). Education on dietary restrictions [30] and infection prevention rules were provided during the period of inpatient care and at discharge. Lim et al [28] reported that 50.3% of cancer patients visited the Emergency Room within 10 days of chemotherapy administration, and 64.6% were hospitalized for ≤ 7 days. In this current study, the time from chemotherapy administration to KM hospital admission was set to ≤ 7 days with an inpatient care duration of 7 days (considering that stays are typically less than a week).

In an Australian study, approximately 84% of BC patients (n = 243) experienced side effects after chemotherapy [31], which affects patient quality of life and treatment outcomes. The proposed IM Inpatient Care Program model in this study aimed to systematically manage symptoms, increase satisfaction amongst patients and healthcare professionals, and given the rising medical costs for BC patients in Korea [32], is expected to reduce treatment duration (and thus costs), and increase accessibility to KM treatment.

This study proposed a KM hospital-based IM Inpatient Care Program model for BC Patients post-chemotherapy designed to allow referrals to other departments as needed. However, it does not comprehensively cover various clinical settings in different types of hospital. In the future, applications of the model in clinical studies can analyze treatment effects, satisfaction levels, and medical costs which may lead to reviews and improvements by specialists across different types of hospital. Future steps also include the evaluation of potential challenges in real-world implementation, modifications, and formation of an advisory committee to review and refine the model for broader clinical adoption. This could help develop a more systematic inpatient care program that reflects real-world clinical needs.

Conclusion

An IM Inpatient Care Program model, based on a com-prehensive consideration of general clinical practices and related guidelines, was developed for use in a KM hospital to anticipate the side effects that may occur after chemotherapy in patients with BC. With ongoing improvements and modifications, we anticipate that this program will contribute to standardized treatment for cancer patients receiving IM treatment, whereby costs and time burdens are reduced whilst enhancing patient and healthcare professional satisfaction.

Supplementary Materials

Article information

Author Contributions

Conceptualization: JBJ and DSH. Formal investigation: EBK. Data analysis: EBK, JBJ, and DSH. Writing original draft: EBK. Writing - review and editing: JBJ and DSH.

Conflicts of Interest

The authors declare that there are no conflicts of interest

Funding

None

Ethical Statement

This research did not involve any human or animal subjects and therefore did not require ethics approval. No personal or sensitive data were collected. All relevant guidelines for responsible research were adhered to throughout the study.

Figure 1

Inpatient program model for post-chemotherapy care of breast cancer patients.

References

• [1] Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365(9472):1687−717.ArticlePubMed
• [2] Bonadonna G, Moliterni A, Zambetti M, Daidone MG, Pilotti S, Gianni L, et al. 30 years’ follow up of randomised studies of adjuvant CMF in operable breast cancer: cohort study. BMJ 2005;330(7485):217. ArticlePubMedPMC
• [3] Rossi L, Stevens D, Pierga JY, Lerebours F, Reyal F, Robain M, et al. Impact of adjuvant chemotherapy on breast cancer survival: a real-world population. PLoS One 2015;10(7):e0132853. ArticlePubMedPMC
• [4] Shapiro CL, Recht A. Side effects of adjuvant treatment of breast cancer. N Engl J Med 2001;344(26):1997−2008.ArticlePubMed
• [5] Shen J, Wenger N, Glaspy J, Hays RD, Albert PS, Choi C, et al. Electroacupuncture for control of myeloablative chemotherapy-induced emesis: a randomized controlled trial. JAMA 2000;284(21):2755−61.ArticlePubMed
• [6] Naeim A, Dy SM, Lorenz KA, Sanati H, Walling A, Asch SM. Evidence-based recommendations for cancer nausea and vomiting. J Clin Oncol 2008;26(23):3903−10.ArticlePubMed
• [7] Lu W, Giobbie-Hurder A, Freedman RA, Shin IH, Lin NU, Partridge AH, et al. Acupuncture for chemotherapy-induced peripheral neuropathy in breast cancer survivors: a randomized controlled pilot trial. Oncologist 2020;25(4):310−8.ArticlePubMedPMCPDF
• [8] The Society of Korean Medicine Obstetrics and Gynecology. Korean medicine clinical practice guidelines for supportive care in breast cancer. Seoul (Korea), National Institute of the Korean Medicine Development, 2021.
• [9] Cho S, Ko S-G, Park S. Development of clinical pathway model in integrative Korean medicine: treatment of non-invasive breast cancer. J Soc Prevent Korean Med 2022;26(1):11−23. [in Korean] https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART003075679Article
• [10] Crawford J, Dale DC, Lyman GH. Chemotherapy-induced neutropenia. Cancer 2004;100(2):228−37.ArticlePubMed
• [11] Korea Hospital Newspaper [Internet]. Development of Guidelines for Managing Chemotherapy Side Effects in Cancer Patients in Korea: Seoul (Korea); Korea Hospital Newspaper: 2021 Available from: http://www.khanews.com/news/articleView.html?idxno=214636. [in Korean]
• [12] Pittman NM, Hopman WM, Mates M. Emergency room visits and hospital admission rates after curative chemotherapy for breast cancer. J Oncol Pract 2015;11(2):120−5.ArticlePubMed
• [13] Korean Oncology Nursing Society Korean Cancer Study Group. Guidelines on the management of chemotherapy-induced side effects. Goyang (Korea), National Cancer Center, 2021. [in Korean]
• [14] Kang J, Kang H, Kwak J, Park J, Sun W, Song Y, et al. Primary care manual for post-discarge cancer patients. Goyang (Korea), National Cancer Center, 2020. [in Korean]
• [15] Lee A, Moon BI. Chemotherapy in breast cancer. Ewha Med J 2014;37(2):75−82. [in Korean]Article
• [16] Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 2012;379(9814):432−44.ArticlePubMedPMC
• [17] Kim G, Hwang Y, Park N, Park S, Lee J, Lee C, et al. Six cases of breast cancer patients treated with Korean medical hospitalization for chemotherapy adverse effects. J Korean Obstet Gynecol 2020;33(2):124−44. [in Korean]Article
• [18] Kang S-J, Kim S-K, Yang G-J, Hong K-K, Cho HB. Analysis of the patients and treatment of korean medicine hospital after chemotherapy in patients with breast cancer. J Korean Obstet Gynecol 2020;33(2):77−89. [in Korean]Article
• [19] Jung MK. Optimal management of chemotherapy-related adverse events. Korean J Pancreas Biliary Tract 2020;25(1):46−54. [in Korean]ArticlePDF
• [20] Zhang J, Qin Z, So TH, Chang TY, Yang S, Chen H, et al. Acupuncture for chemotherapy-associated insomnia in breast cancer patients: an assessor-participant blinded, randomized, sham-controlled trial. Breast Cancer Res 2023;25(1):49. ArticlePubMedPMCPDF
• [21] Shin J, Park H. Effects of auricular acupressure on constipation in patients with breast cancer receiving chemotherapy: a randomized control trial. West J Nurs Res 2018;40(1):67−83.ArticlePubMedPDF
• [22] Jing X, Liu J, Wang C, Ji M, Chen X, Mei Y, et al. Auricular acupressure is an alternative in treating constipation in leukemia patients undergoing chemotherapy: a systematic review and meta-analysis. Complement Ther Clin Pract 2018;31:282−9.ArticlePubMed
• [23] Li S, So T-h, Tang G, Tan H-Y, Wang N, Ng BFL, et al. Chinese herbal medicine for reducing chemotherapy-associated side-effects in breast cancer patients: a systematic review and meta-analysis. Front Oncol 2020;10:599073. ArticlePubMedPMC
• [24] Jo T, Shigemi D, Konishi T, Yamana H, Michihata N, Kumazawa R, et al. Antiemetic effect of Rikkunshito, a Japanese Kampo herbal medicine, on Cisplatin-induced nausea and vomiting: a nationwide database study in Japan. Intern Med 2024;63(7):919−27.ArticlePubMedPMC
• [25] Seike J, Sawada T, Kawakita N, Yamamoto Y, Yuasa Y, Yamai H, et al. A new candidate supporting drug, rikkunshito, for the QOL in advanced esophageal cancer patients with chemotherapy using docetaxel/5-FU/. CDDP Int J Surg Oncol 2011;2011:715623. PubMed
• [26] Ohnishi S, Takeda H. Herbal medicines for the treatment of cancer chemotherapy-induced side effects. Front Pharmacol 2015;6:14. ArticlePubMedPMC
• [27] Miyano K, Eto M, Hitomi S, Matsumoto T, Hasegawa S, Hirano A, et al. The Japanese herbal medicine Hangeshashinto enhances oral keratinocyte migration to facilitate healing of chemotherapy-induced oral ulcerative mucositis. Sci Rep 2020;10(1):625. ArticlePubMedPMCPDF
• [28] Lim SJ, Yi M. Study on cancer patients who visited an emergency department with the side effects of chemotherapy. J Korean Clin Nurs Res 2014;20(1):75−89. [in Korean]
• [29] Lee D-G, Kim S-H, Kim SY, Kim C-J, Min C-K, Park WB, et al. Evidence-based guidelines for empirical therapy of neutropenic fever in Korea. Korean J Intern Med 2011;26(2):220−52.ArticlePubMedPMC
• [30] Jeon O, Yim S, Jeong I, Yun E, Kim M, Park Y. Survey on dietary restrictions for neutropenic patients. J Korean Oncol Nurs 2010;10(2):210−7. [in Korean]ArticlePDF
• [31] Pearce A, Haas M, Viney R, Pearson SA, Haywood P, Brown C, et al. Incidence and severity of self-reported chemotherapy side effects in routine care: a prospective cohort study. PLoS One 2017;12(10):e0184360. ArticlePubMedPMC
• [32] Byun J, Lee E. Medical cost trends of breast cancer in Korea. Policy Trends 2020;14(6):57−68. [in Korean] https://repository.hira.or.kr/handle/2019.oak/2516

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References

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