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Frontiers in Cancer Control and Society ·

Volume 4 - 2026 | https://doi.org/10.3389/fcacs.2026.1677567

Retrospective observational study of Kampo medicines for suppressing the side effects of endocrine therapy in the treatment of breast cancer: a pilot study

  • Shin Takayama1,2*corresponding author
  • Atsuhiko Furuta3
  • Haruhiko Shindo3
  • Ryutaro Arita1,2
  • Kaolu Sato3
  • Tadashi Ishii1,2
  1. 1Department of Kampo and Integrative Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
  2. 2Department of Education and Support for Regional Medicine, Department of Kampo Medicine, Tohoku University Hospital, Sendai, Japan
  3. 3Department of Breast Surgery, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Miyagi, Japan
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Abstract

Long-term endocrine therapy for breast cancer often causes menopause-like symptoms, affecting quality of life. Although Japanese traditional (Kampo) medicine is utilized for relief, research remains limited. This retrospective observational study aimed to evaluate the efficacy of Kampo medicines in managing endocrine therapy-related side effects in breast cancer patients. Data from breast cancer patients receiving endocrine therapy treated with Kampo medicines at Japanese Red Cross Ishinomaki Hospital between July 2017 to June 2024 were analyzed. Symptom severity was measured using a Numerical Rating Scale (NRS; 0–10). Kampo medicine, administered by a specialist, was tailored to individual symptoms and physical findings. Multivariate analysis was performed to examine the association between symptom relief. Symptom progression was analyzed using Kaplan-Meier curves, and outcomes were compared using the log-rank test. Fifty-three patients (median age: 54) were enrolled. Vasomotor, motor/sensory, and psychiatric symptoms accounted for 90% of complaints. After 6 months, 75% of patients reported NRS scores of 3 or less (enabling them to perform daily activities without difficulty). Keishibukuryogan (KBG) or keishibukuryogankayokuinin (KBGY) were the most prescribed (41.5%). Multivariate analysis indicated KBG/KBGY was significantly associated with symptom relief (Hazard Ratio 4.18; 95% CI 1.03–16.92; p = 0.046). Patients prescribed KBG/KBGY experienced significantly faster overall symptom improvement than those on other Kampo medicines (p = 0.022). Kampo medicines are effective in alleviating side effects in breast cancer patients undergoing endocrine therapy. KBG/KBGY has shown promise in reducing overall symptoms.

Keywords

1 Introduction

Breast cancer is the leading cause of cancer among women in Japan, and most cases occur during their working years (1). The Ministry of Health, Labor, and Welfare of Japan focuses on employment support for cancer survivors in the 4th Basic Plan for the Promotion of Cancer Control (2). The number of patients with breast cancer reached 94,400 in 2021, or one in every nine women. Although advances in treatment have improved the 10-year survival rate to 79.3%, long-term endocrine therapy that suppresses sex hormones for up to 10 years causes menopausal-like symptoms as a side effect, and decreases quality of life (QOL) and labor productivity (3). There is still no well-established treatment for these side effects. Some Kampo medicines have been used for menopausal symptoms and are based on insurance reimbursement. They are also employed to manage hot flashes, a common side effect of hormone therapy. However, the frequency of their use and associated symptom relief have not been fully clarified (4).

We previously reported cases at the Japanese Breast Cancer Society Annual Meetings (2018 and 2024) where patients experienced an improvement in side effect symptoms and successfully returned to work following Kampo medicine treatment. We believe that showing evidence of the usefulness of Kampo medicines for side effects will improve the rate of return to work and continuity of work with improvements in QOL, and there may be a benefit in the hope that cancer survivors will return to work in society.

The aim of this study is to clarify the time course of symptoms treated with Kampo medicine during endocrine therapy for breast cancer, with a view to identifying Kampo medicines that could be used to alleviate these side effects.

2 Methods

2.1 Study design

Retrospective observational study.

2.2 Participants

Patients with breast cancer undergoing endocrine therapy at Japanese Red Cross Ishinomaki Hospital (Miyagi, Japan). The patients were referred to the Kampo Support Clinic to control the side effects of endocrine therapy. Patients with severe liver dysfunction, renal failure or uncontrolled diabetes mellitus were excluded.

2.3 Setting

Kampo treatment was performed by a Kampo specialist from the Japanese Society of Oriental Medicine, and Kampo medicine was selected based on the symptoms and conditions at the Kampo support clinic for breast cancer in Japanese Red Cross Ishinomaki Hospital.

In the prescription of Kampo medicines, keishibukuryogan (KBG) or keishibukuryogankayokuinin (KBGY) is mainly prescribed for hot flashes with blood stasis pattern[™], kamishoyosan (KSS) for irritation with blood stasis pattern[™], rokumigan (RJG) for hot flashes and night sweats with kidney deficiency pattern[™], tokishakuyakusan (TSS) for blood deficiency pattern[™] with fluid retention pattern[™], boiogito (BOT) for joint stiffness or pain with fluid retention pattern[™], and goerisan (GRS) for fluid retention pattern[™]. The other Kampo medicines were prescribed based on the patients' conditions. The composition and indication of Kampo medicines mainly prescribed for post-menopausal symptoms are listed in Table 1.

Table 1. Composition and indication of Kampo medicines mainly prescribed for post-menopausal symptoms.

Name of Kampo medicine (product name)Composition (g)Indication
Keishibukuryogan (KBG) (TJ-25)JP cinnamon bark (3.0) JP peony root (3.0) JP peach kernel (3.0) JP poria sclerotium (3.0) JP moutan bark (3.0)Patients with solid constitution who have ruddy face and generally solid abdomen with resistance in the lower abdomen Inflammation in the uterus and its adnexa, endometritis, menstrual irregularity, dysmenorrhea, leukorrhea, climacteric disturbance (headache, dizziness, feeling of hot flashes, shoulder stiffness, etc.), oversensitivity to cold, peritonitis, contusion, hemorrhoid and orchitis
Keishibukuryogankayokuinin (KBGY) (TJ-125)JP cinnamon bark (4.0) JP peony root (4.0) JP peach kernel (4.0) JP poria sclerotium (4.0) JP moutan bark (4.0) JP coix seed (10.0)Patients with a comparatively strong constitution who sometimes complain of lower abdominal pain, shoulder stiffness, dull headache, dizziness, cold feet with feeling of flashes, etc. Menstrual irregularity, automatic imbalance syndrome peculiar to women resembling climacteric disturbance, acne, spots, and roughness of the hands and feet
Kamishoyosan (KSS) (TJ-24)JP bupleurum root (3.0) JP peony root (3.0) JP atractylodes lancea rhizome (3.0) JP Japanese angelica root (3.0) JP poria sclerotium (3.0) JP gardenia fruit (2.0) JP moutan bark (2.0) JP glycyrrhiza (1.5) JP ginger (1.0) JP mentha herb (1.0)Women with delicate constitution who are easily fatigued and are apt to have stiffness shoulder, psychoneurotic symptoms including anxiety, and sometimes tendency to constipation Oversensitivity to cold, delicate constitution, menstrual irregularity, dysmenorrhea, climacteric disturbance and automatic imbalance syndrome peculiar to women resembling climacteric disturbance
Rokumigan (RJG) (TJ-87)JP rehmannia root (5.0) JP cornus fruit (3.0) JP dioscorea rhizome (3.0) JP alisma rhizome (3.0) JP poria sclerotium (3.0) JP moutan bark (3.0)Patients with decreased urine volume or polyuria sometimes having dry mouth who are easily fatigued Dysuria, frequent urination, edema and pruritus
Tokishakuyakusan (TSS) (TJ-23)JP peony root (4.0) JP atractylodes lancea rhizome (4.0) JP alisma rhizome (4.0) JP poria sclerotium (4.0) JP cnidium rhizome (3.0) JP Japanese angelica root (3.0)Patients who have generally weak muscles and are easily fatigued and whose waist and lower limbs are susceptible to cold Anemia, malaise, climacteric disturbance (dull headache, headache, dizziness, shoulder stiffness, etc.), menstrual irregularity, dysmenorrhea, infertility, palpitation pounding, chronic nephritis, diseases during pregnancy (edema, habitual abortion, hemorrhoids, abdominal pain), beriberi, hemiplegia and valvular diseases of the heart
Boiogito (BOT) (TJ-20)JP astragalus root (5.0) JP sinomenium stem (5.0) JP atractylodes lancea rhizome (3.0) JP jujube (3.0) JP glycyrrhiza (1.5) JP ginger (1.0)Patients with a white-complexion, soft muscles, and a flabby constitution who are easily fatigued, perspire profusely, do not excrete enough urine, and develop edema in the lower limbs and swelling and pain of the knee joint Nephritis, nephrosis, nephropathy of pregnancy, hydrocele testis, obesity, arthritis, carbuncle, furuncle, myositis, edema, dermatosis, hyperhidrosis, and menstrual irregularity
Goreisan (GRS) (TJ-17)JP alisma rhizome (4.0) JP atractylodes lancea rhizome (3.0) JP polyporus sclerotium (3.0) JP poria sclerotium (3.0) JP cinnamon bark (1.5)Patients with oral dryness and decreased urine volume Edema, nephrosis, alcoholic hangover, acute gastrointestinal catarrh, diarrhea, nausea, vomiting, dizziness, water retention in the stomach, headache, uremia, heat-stroke, and diabetes mellitus

JP, the Japanese pharmacopeia.

All of Kampo medicines are manufactured by (Tsumura and Co, Tokyo, Japan).

This table is referred and modified from STORK: http://mpdb.nibiohn.go.jp/stork/.

2.4 Data extraction

We retrospectively collected information from medical records regarding patients' backgrounds, clinical stage of breast cancer, anti-cancer treatment, comorbidities, and their treatment. Symptoms associated with breast cancer and hormone therapy were evaluated on every symptom in every visit with Numerical Rating Scale [NRS: symptom severity from 0 (no symptom) to 10 (worst symptom)]. We also collected data on Kampo medicine prescriptions. Adverse event was collected on each visit. The data extraction was performed at first visit, 3, 6, and 12 months from July 2017 to June 2024. Blood samples were examined at the first visit and 12 months after for safety assessment.

2.5 Statistical analysis

An NRS score of 3 or less (defined as a level permitting daily activities without difficulty) was considered an improvement. Kaplan-Meier analysis and the log-rank test were used to compare the time taken for symptoms to improve to an NRS score of 3 or less between the following groups: patients treated with and without KBG/KBGY, and those treated with and without Bupleurum Root-containing prescriptions. To adjust for potential confounding biases in the evaluation of KBG/KBGY, a multivariable Cox proportional hazards model was performed. Since missing data further reduced the effective sample size for this analysis, multiple imputation was implemented. Due to the limited sample size, the explanatory variables in this multivariable analysis were restricted to age, body mass index, and blood pressure, in addition to the presence of KBG/KBGY. Data were presented as medians, ranges, and percentages, as appropriate. Continuous variables were described by means and standard deviations. Statistical significance was set at p < 0.05. Given the exploratory nature of this study, all p-values are nominal and unadjusted for multiple comparisons. The statistical analysis was conducted by Data Seed Inc. using R version 4.2.3 (R Foundation for Statistical Computing, Vienna, Austria).

2.6 Ethical approval

This study was approved by the Ethics Committee of Japanese Red Cross Ishinomaki Hospital (approval no. is 22-19). The ethics committee waived the requirement for written informed consent because the study was conducted using an opt-out procedure via public disclosure.

3 Results

Table 2 shows the characteristics of the patients enrolled in this study. Fifty-three female patients (median age: 54 years) were included in the study. The clinical stages were 0 (9.4%), I (32.1%), II (39.6%), III (17.0%), and IV (1.9%). The most frequent comorbidity was hypertension (22.6%), followed by dyslipidemia (7.5%), depression (3.8%), and diabetes mellitus (3.8%). The most frequently prescribed medications were angiotensin receptor blockers (11.3%), statins (7.5%), calcium blockers (7.5%), diuretics (3.8%), dipeptidyl peptidase-4 inhibitor (3.8%), and antidepressants (3.8%). The treatments for primary breast cancer included breast-conserving surgery (49.1%), total mastectomy (50.9%), and lymph node dissection (45.3%). Chemotherapy and radiation were administered to 58.5 and 62.3% of patients, respectively. Endocrine therapy was administered to estrogen and/or progesterone receptor-positive patients with tamoxifen (75.5%) and anastrozole (24.5%).

Table 2. Characteristics of the patients enrolled in this study.

Patients' characteristicsAge and body mass index
Age (years old): median with range54 (37, 77)
Body mass index: median with range22.6 (18.7, 42.5)
Clinical stage (%)
09.4
I32.1
II39.6
III17.0
IV1.9
Treatment for primary breast cancer
Surgery (%)
Breast-conserving surgery49.1
Total mastectomy50.9
Lymph node dissection45.3
Chemotherapy with anti-cancer drugs (%)58.5
Radiation (%)62.3
Endocrine therapy (%)
Tamoxifen75.5
Anastrozole24.5
Comorbidities (%)
Hypertension22.6
Dyslipidemia7.5
Depression3.8
Diabetes mellitus3.8
Cerebrovascular disease1.9
Rheumatoid arthritis1.9
Reflex esophagitis1.9
Osteoporosis1.9
Myoma uteri1.9
Fatty liver1.9
Asthma1.9
Medication for comorbidities (%)
Angiotensin receptor blocker11.3
Statin7.5
Calcium blocker7.5
Diuretics3.8
DPP-4 inhibitor3.8
Antidepressant3.8
Anti-platelet drug3.8
Metformin1.9
SGLT2 inhibitor1.9
Anti-histamine1.9
Anti-anxiety drugs1.9
Antiepileptic drug1.9
Theophylline1.9
Others3.8

DPP-4, dipeptidyl peptidase-4; SGLT2, sodium glucose cotransporter 2.

Of the 139 total complaints reported, the three main categories were vasomotor ataxia including hot flashes, uncontrolled sweating, and palpitation (32.4%); psychiatric symptoms including irritation, anxiety, and depression (32.4%); and motor and sensory organ symptoms including joint stiffness, joint pain, muscle stiffness, muscle pain, and sensory disturbance (24.5%). Together, these categories accounted for approximately 90% of the total complaints.

Kampo medicines prescribed for the symptoms are listed in Table 3. Among the Kampo medicines prescribed, KBG/KBGY was used in 41.5% of the cases.

Table 3. The list of Kampo medicines prescribed for the symptoms.

Kampo medicines*53 (n)*100 (%)
Keishibukuryogan/keishibukuryogankayokuinin (KBG/KBGY)2241.5
Kamishoyosan (KSS)815.1
Rokumigan (RJG)713.2
Tokishakuyakusan (TSS)611.3
Boiogito (BOT)47.5
Goreisan (GRS)47.5
Others2649.0

Prescriptions for Kampo medicines may be duplicated for each case.

Others include yokukansan, daisaikoto, hangekobokuto, juzentaihoto, ninjin'yoeito, kamikihito, keishikaryukotsuboreito, saikokaryukotsuboreito, mashiningan, and so on.

Figure 1 illustrates the course of symptom relief following Kampo treatment. Due to missing values, the survival time analysis was conducted on 43 subjects. In terms of the course of symptoms, approximately 75% of patients had an NRS score of 3 or less (improvement) 6 months after the start of Kampo medicine treatment.

Time until the NRS falls below three for any one of the several symptoms.
Figure 1. Time until the NRS falls below three for any one of the several symptoms.

Table 4 shows the results of a multivariate analysis examining the association between symptom relief. Age, body mass index and blood pressure were not associated with symptom relief. However, KBG/KBGY was associated with symptom relief, with a 95% confidence interval of 1.03–16.92 (p = 0.046) and a hazard ratio of 4.18 in the multivariate analysis.

Table 4. Association between KBG/KBGY prescription and symptom relief.

ModelHazard ratio (95% CI)**p-Value**
Univariate3.66 (1.15–11.69)0.029
Multivariable*4.18 (1.03–16.92)0.046

CI, confidence interval. *Adjusted for age, body mass index, and systolic blood pressure using multiple imputation.

Additional analysis of overall symptoms showed that patients prescribed KBG/KBGY were alleviated significantly faster than those of patients prescribed other Kampo medicines (p = 0.022, log-rank test; Figure 2). Conversely, 18.6% of patients (8 out of 43, excluding those for whom data were missing) used prescriptions containing Bupleurum root. However, these prescriptions did not demonstrate a significant improvement in symptoms (Figure 3).

Comparison of time to overall symptom improvement between with and without KBG/KBGY.
Figure 2. Comparison of time to overall symptom improvement between with and without KBG/KBGY.
Comparison of time to overall symptom improvement between with and without Bupleurum Root-containing prescriptions.
Figure 3. Comparison of time to overall symptom improvement between with and without Bupleurum Root-containing prescriptions.

Table 5 shows the blood sampling data before and after Kampo treatment. The safety analysis of blood data revealed significant changes in albumin, alkaline phosphatase and high-density lipoprotein levels before and after Kampo treatment. In the clinical setting, no adverse events related to Kampo medicine treatment were observed.

Table 5. Data on blood sampling before and after Kampo treatment.

VariableBefore (mean ±SD)After (mean ±SD)**p-Value**
Total protein (g/dl)6.9 ± 0.46.9 ± 0.40.45
Albumin (g/dl)4.3 ± 0.44.2 ± 0.30.04
AST (U/L)23.6 ± 8.527.2 ± 16.60.16
ALT (U/L)22.6 ± 13.324.7 ± 17.80.46
ALP (U/L)204.8 ± 63.8177.4 ± 74.60.01
γ-GTP (U/L)27.5 ± 22.231.5 ± 44.70.51
LDH (U/L)175.3 ± 31.9180.0 ± 47.00.42
T-Cho (mg/dl)189.6 ± 37.7186.2 ± 33.30.87
TG (mg/dl)165.2 ± 120.4140.3 ± 75.90.06
HDL (mg/dl)60.1 ± 18.261.8 ± 16.20.02
LDL (mg/dl)106.7 ± 34.3107.9 ± 35.40.79
Sodium (mEq/L)141.5 ± 1.8138.9 ± 19.30.33
Potassium (mEq/L)4.1 ± 0.44.2 ± 0.40.39
CEA (ng/ml)2.3 ± 1.45.5 ± 16.70.36
CA15-3 (U/ml)11.3 ± 4.923.1 ± 49.80.16
White blood cell (× 103/μl)4.9 ± 1.314.8 ± 68.00.29
Lymphocyte (%)25.2 ± 5.015.2 ± 4.50.33
Hemoglobin (g/dl)12.8 ± 1.113.0 ± 0.90.24
Platelet (× 104/μl)23.6 ± 5.423.7 ± 6.00.94

AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; γ-GTP, gamma-glutamyltransferase; LDH, lactate dehydrogenase; T-Cho, total cholesterol; TG, triglyceride; HDL, high-density lipoprotein; LDL, low-density lipoprotein; CEA, carcinoembryonic antigen; CA15-3, cancer antigen 15-3.

4 Discussion

The present study reveals the time course of the support provided by Kampo medicine for side effects during endocrine therapy for breast cancer. The three main complaints were vasomotor ataxia, psychiatric symptoms and symptoms affecting the motor and sensory organs. Several Kampo medicines were prescribed to treat these symptoms. Three-quarters of patients experienced sufficient improvement in their symptoms to enable them to live their daily lives without difficulty 6 months after starting Kampo medicine treatment. Symptom relief was not related to age, body mass index or blood pressure; however, it was related to KBG/KBGY prescriptions. Conversely, Bupleurum Root-containing prescriptions did not demonstrate significant symptom relief, indicating the potential of KBG/KBGY to alleviate side effects of the endocrine therapy in breast cancer patients. Although some significant differences were observed in blood sampling data before and after Kampo treatment, these were not clinically meaningful, suggesting that Kampo medicine could be used safely.

The selection of Kampo formulas in this study was strictly guided by the traditional “Sho” (pattern diagnosis), ensuring that treatment was tailored to each patient's constitution and symptomatic profile rather than applying a uniform therapy. Specifically, KBG/KBGY was selected for patients presenting with blood stasis[™], a pattern characterized by microcirculatory disturbances with vasomotor dysregulation often manifested as palpable lower abdominal resistance or tenderness. The finding that KBG/KBGY was the most frequent and effective prescription suggests that blood stasis is a predominant pathological mechanism underlying the side effects of endocrine therapy. This implies that targeting blood stasis[™] is crucial for alleviating this cluster of symptoms. In contrast, Bupleurum root-containing formulas were used for patients exhibiting qi stagnation[™], such as anxiety or irritability. The superior overall symptom relief observed in patients treated with the KBG/KBGY prescription indicates that addressing the somatic dysregulation associated with blood stasis[™] may be more critical than focusing solely on psychological symptoms in this context.

The pathophysiological mechanisms of hot flashes during endocrine therapy for breast cancer are unclear, but suppression of the estrogen effect is considered to play a role (5). There is still no widely accepted treatment for these side effects. However, hormone replacement therapy is not recommended for the purpose of reducing hot flashes caused by endocrine therapy because of disease progression (6). Tamoxifen and aromatase inhibitors can also cause hot flashes. Serotonin and norepinephrine may also cause hot flashes. A selective serotonin reuptake inhibitor (SSRI) is one of the options for treating hot flashes (7); however, caution is required regarding drug interactions between SSRIs and tamoxifen (8). Other relations between hot flashes and calcitonin gene-related peptide (CGRP) have been reported (9). CGRP could act both centrally, on the thermoregulatory center of the hypothalamus, and peripherally, causing vasodilation and sweating (10). Nevertheless, there has never been any development of CGRP normalization with new drugs for these side effects.

In the present study, KBG/KBGY was the most commonly prescribed Kampo medicine. It has been reported that KBG improves hot flash symptoms in females, as assessed by a visual analog scale (11). Furthermore, Ushiroyama et al. (12) reported that administering KBG decreased blood flow under the jaw, where the symptoms of hot flashes appear in the upper body, and increased blood flow in the lower extremities in postmenopausal women experiencing these flashes. Concerning the hormonal metabolism of hot flashes, Saruwatari et al. (13) demonstrates that KBG inhibits cytochrome P450 1A2 activity, which plays a key role in estrogen metabolism. KBG has more pharmacological mechanisms as follows (14): protective effect on vascular function by anti-oxidative effect (15); effect on female hormones, such as suppressing estradiol secretion and concentrations (16, 17), acting as an LH-RH antagonist and/or a weak anti-estrogen (18), without estrogenic activity (19); and effect on hot flash by normalizing CGRP release (20–22).

KSS, a prescription containing Bupleurum root, is another frequently used Kampo medicine for treating premenstrual and postmenstrual syndromes, as well as dysphoric disorders (23). It has been reported to reduce the serum concentrations of interleukin (IL)-6, macrophage inflammatory protein-1β, and IL-8 in women with hot flashes (24).

BOT has been used for the pain or stiffness of osteoarthritis of the knee. Additional effect of BOT on osteoarthritis of the knee with joint effusion is to improve staircase climbing up and down ability, physical function, and amount of joint fluid have been reported in clinical study (25). Basic research showed that BOT administration may reduce articular cartilage degeneration, osteoclast differentiation and proliferation in the osteoarthritis of the knee (26).

GRS has been used to control fluid retention, such as edema, because it increases the expression of vascular endothelial growth factor receptor-3 in lymphatic vessels (27), regulates aquaporin-3 expression (28), and inhibits aquaporin-4 function (29). Additionally, it exerts effects that enhance phagocytic activity, increase mRNA levels of IL-12 and interferon-γ, and decrease mRNA levels of tumor necrosis factor-α (30). The combination of regular administration and temporary use of Kampo medicines enhances their anti-inflammatory effects and relieves the symptoms (31).

Long-term endocrine therapy that suppresses sex hormones for up to 10 years, causes menopausal-like symptoms as a side effect, decreasing the QOL and labor productivity of breast cancer patients. Support with Kampo medicines for menopausal symptoms may be an alternative treatment option. This study may contribute to the body of evidence on supporting quality of life and labor productivity.

More than 86% of the doctors in Japan prescribe Kampo medicines (32). Numerous clinical studies of Kampo medicine have been reported (33), and medical societies have incorporated Kampo medicine into their clinical practice guidelines (34). Widely used Kampo medicines, such as hangekobokuto, yokukansan, ninjin'yoeito, and rikkunshito, are used to treat several diseases and conditions, including cancer treatment (35–44). Kampo medicines are also widely prescribed by the Japanese health insurance system for women's healthcare (45).

Among the limitations of this study is its single-arm design. The analyses were limited to factor analysis and associations with symptom relief. The small sample size also resulted in the limited number of explanatory variables in the multivariate analysis. Further studies involving control groups and larger samples are required to confirm the effects of the treatment. To address these limitations and confirm study results, a further study is being conducted which includes a control group and a sample size of 160 (46).

5 Conclusions

Patients undergoing endocrine therapy for breast cancer treated with Kampo medicines show improvement in symptoms after 6 months of treatment. In particular, KBG/KBGY prescriptions may reduce overall symptoms. The present study is preliminary due to the single-arm study design and small sample size. Further studies involving control groups and larger sample sizes are required to confirm the effects of the treatment.

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Footnotes

Edited by: Elena Amaricai, Victor Babes University of Medicine and Pharmacy, Romania

Reviewed by: Eun Hye Kim, Gachon University, Republic of Korea

Angel Justiz-Vaillant, The University of the West Indies St. Augustine, Trinidad and Tobago

Dongwoo Nam, Kyung Hee University, Republic of Korea

Statements

Conflict of interest

ST, RA, and TI belong to the Department of Kampo and Integrative Medicine at Tohoku University Graduate School of Medicine, which offers a joint research course with Tsumura and Co.

The remaining author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

The author(s) declared that financial support was received for this work and/or its publication. This study was funded by the Department of Kampo and Integrative Medicine, Tohoku University Graduate School of Medicine and Tsumura and Co.

Data availability

The datasets presented in this article are not readily available because the data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions. Requests to access the datasets should be directed to shin.takayama.c4@tohoku.ac.jp.

Ethics approval

The studies involving humans were approved by Japanese Red Cross Ishinomaki Hospital (approval no. 22-19). The studies were conducted in accordance with the local legislation and institutional requirements. The Ethics Committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants' legal guardians/next of kin due to the retrospective nature of the study.

Author contributions

ST: Methodology, Conceptualization, Investigation, Project administration, Writing – original draft, Writing – review & editing. AF: Methodology, Conceptualization, Investigation, Supervision, Project administration, Formal analysis, Resources, Writing – review & editing. HS: Data curation, Supervision, Investigation, Conceptualization, Methodology, Resources, Writing – review & editing, Formal analysis, Project administration. RA: Conceptualization, Writing – review & editing, Formal analysis, Methodology, Data curation. KS: Writing – review & editing, Data curation, Investigation, Resources, Conceptualization, Project administration, Supervision, Methodology. TI: Methodology, Conceptualization, Supervision, Writing – review & editing, Visualization, Validation.

Acknowledgements

We would like to thank Editage for their English editing. We would also like to thank Mr. Hiroki Yoshida for his help with data cleaning and statistical analysis.

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Citation

Takayama, S., et al. (2026). Retrospective observational study of Kampo medicines for suppressing the side effects of endocrine therapy in the treatment of breast cancer: a pilot study. Frontiers in Cancer Control and Society, Volume 4. https://doi.org/
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4 - 2026

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Copyright © 2026 Takayama, Furuta, Shindo, Arita, Sato and Ishii.

License: https://creativecommons.org/licenses/by/4.0/

*Correspondence: Shin Takayama

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