Granulomatous mastitis (GLM), also known as idiopathic granulomatous mastitis and granulomatous mastitis, is an inflammation in which macrophages and neutrophils infiltrate the breast lobules to form necrotic granulomatous lesions, which was first described by Kessler et al. (1). The typical clinical manifestations of this disease include breast pain, breast mass, nipple depression, nipple overflow, axillary lymph node enlargement, nonlactating breast abscess, fistula, etc. (2, 3). There was no obvious specificity in the clinical manifestations of GLM. Thus, GLM is easily confused with inflammatory breast cancer, and the diagnosis of GLM mainly requires histopathological examination (4–6).

Because the etiology and pathology of GLM are unclear, there is no unified treatment plan to treat GLM. At present, the reported treatment includes surgical treatment and conservative treatments. Although the healing time of surgical treatment is short, the wound complications and recurrence rate are relatively high, which makes surgeons carefully choose this treatment (7, 8). Conservative treatments mainly include antibiotic treatment, steroid treatment, and traditional Chinese medicine (TCM) treatment. The effect of the antibiotic treatment is poor (9). Steroid therapy can cause complications, and serious side effects limit its long-term use (10). TCM treatment, used as a supplementary treatment for evidence-based diseases, has a significant therapeutic effect on inflammatory diseases (11, 12). Additionally, the therapeutic effect of TCM on GLM was recognized (13). A previous study suggested that the 9-month cure rate of TCM was 63%, which was equivalent to that of the TCM surgical treatment (68%) (14). Although the curative effect of TCM was apparent, the treatment time was relatively long. At present, although GLM is a benign lesion, there is no ideal treatment. This disease is difficult to cure, has a high recurrence rate, and causes a tremendous psychological burden to patients (15). Therefore, the present trial intends to study whether TCM combined with surgical treatment can improve the outcome of GLM using the propensity score matching method.

GLM, which is a chronic inflammatory benign disease, has a higher incidence among Han Chinese women, and its incidence accounts for approximately 3.5% of benign breast diseases in women (16). GLM tends to occur in women of childbearing age, and most patients have a history of pregnancy and breastfeeding (17). In this study, all patients were married women of childbearing age, had an average age of 32 years (21-47 years), and had a history of pregnancy. Moreover, approximately 88% of the patients had a history of breastfeeding. These results are consistent with previous reports. In addition, the average time between the onset of the patient and the last postpartum period was 42 months, and 11.8% of the patients had a history of acute mastitis.

The etiology and pathogenesis of granulomatous lobular mastitis is not yet fully understood. Some researchers believe that the pathogenesis of GLM is due to ductal epithelial damage, which transfers luminal secretions to lobular connective tissue, causing local inflammation of the connective tissue, which in turn allows macrophages and lymphocytes to migrate to this area, causing local granulomatous inflammation (18). The factors that ultimately induce ductal epithelial injury include pregnancy, breastfeeding, history of trauma, hyperprolactinemia, and obesity (18). In this study, 21.6% of patients had high prolactin, 30.1% of patients had breast trauma before the onset, 8.3% of patients had oral contraceptives, 43.1% of patients had inverted nipples, and the average BMI index of these cases was ≥23.9. The results of this study consistent with that of previous studies, suggest that pregnancy, breastfeeding, trauma history, obesity and other factors are risk factors for GLM (18).

There is no clear consensus on the treatment of GLM. At present, the most reported treatments are drug treatment and surgical treatment. Grover et al. believed that steroids or immunomodulatory drugs are used as conventional treatments, and surgical resection is widely adopted as the last treatment for refractory cases (19). Zhou et al. also suggested that drug treatment was recommended as a priority (20). If the patient has a relapse or the drug is not effective, surgery will be used for treatment. However, other researchers believe that the therapeutic effect of immunomodulatory (steroid) therapy is usually poor (21). Therefore, surgical treatment is still one of the main ways to treat GLM abroad. For surgical treatment, Zhang et al. believed that appropriate acute inflammation control methods should be used before surgery, and appropriate surgical methods should be selected after the inflammation has been controlled (13). This strategy has a better therapeutic effect than the traditional extensive resection; i.e., its cosmetic effect is good, the recovery time is short, and the prognosis is better. Wang et al. found that surgery after steroid treatment has a faster curative effect and a lower recurrence rate than steroid treatment alone (22). Zhang et al. found that TCM YangHe decoction combined with surgical treatment had a higher cure rate and a lower recurrence rate than surgical treatment alone (23). Zuo et al. also believed that the treatment of GLM with integrated traditional Chinese and Western medicine could improve the aesthetics of both breasts, thus it is worthy of clinical recommendation (24). A recent review reveals that the effectiveness of TCM plus surgery in the treatment of GLM is similar to that of surgical operation, but TCM plus surgery can significantly improve the satisfaction of patients with breast shape (25). Therefore, the consensus of experts on diagnosis and treatment of granulomatous lobular mastitis in traditional Chinese Medicine was initiated by the China Association of Chinese Medicine (CACM) (26). Although Chinese medicine has a clear curative effect, the treatment time of traditional Chinese medicine is long, and most patients suffer from long-term dressing changes. Therefore, traditional Chinese medicine combined with surgery was used to treat GLM. In the early stage of the disease, TCM was used to reduce the mass and limit the inflammation, and finally the appropriate operation was performed to reduce the damage to the breast shape. Finally, the purpose of shortening the course of treatment and reducing the pain caused by dressing changes was achieved.

Traditional Chinese medicine doctors believes that granulomatous lobular mastitis belongs to the category of “acne breast carbuncle”. There is no clear name of GLM in ancient books. According to its special clinical manifestations and pathogenesis, Professors Gu Bohua and Lu Deming of Shanghai School of Gu’s Surgery proposed the name “acne breast carbuncle” in 1980 (27). They believe that GLM first has nipple deformity or duct dilation and subsequently stagnation of liver qi, failure to follow blood, stagnation of qi and blood stasis, agglomeration into masses, long-term depression, and heat stagnation because of emotional discomfort, which result in meat rot and abscess. Eventually, it becomes a fistula after ulceration. In this study, TCM combined with surgery was used to treat GLM, and Chinese medicines such as Radix Bupleuri, Curcumae Radix, Radix Salviae, and Herba Taraxaci were given to soothe the liver, clear heat, promote blood circulation and remove blood stasis. The local lesions were excised and sutured approximately 4.7 months after the oral administration of TCM. The results of the study suggest that the TCM-surgery group had a significantly lower purulent lesion rate than the TCM group. This result indicates that the use of surgical treatment at the appropriate time can significantly reduce local suppuration, which shortens the course of treatment and reduces pain. The cure rates at 3 months, 6 months and 9 months in the TCM-surgery group were significantly better than those in the TCM group. Moreover, the total treatment course of TCM with surgery was significantly shorter than that of TCM. During the treatment period, there were 3 patients with wound effusion in the traditional Chinese medicine combined with the operation group after surgery. After symptomatic extraction of the effusion and Chinese medicine treatment, the wound healed after an average delay of 2 weeks. There were no obvious adverse reactions in the traditional Chinese medicine group. Therefore, Chinese medicine combined with surgery to treat GLM is worth recommending in clinical practice.

The present study has some limitations. First, this investigation was a retrospective cohort study, and there may be research bias. Second, the sample size in this study was relatively small, and the conclusions of this study must be verified by further multi-center clinical trials with larger sample sizes. Third, the follow-up time of this study was not sufficiently long, and longer clinical follow-up is required for these patients.

In summary, Chinese medicine combined with surgical treatment can increase the cure rate of GLM, shorten the course of treatment, and reduce the rate of suppuration of local lesions. Therefore, this treatment strategy is worthy of clinical recommendation and is expected to become a comprehensive treatment for GLM.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

The studies involving human participants were reviewed and approved by the clinical trial ethics committee in Longhua Hospital of Shanghai University of Traditional Chinese Medicine. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

SL and ZS designed the research. CW and RS performed the research. CW and RS contributed analytic tools. CW and RS wrote the paper. SL and ZS reviewed the paper. All authors contributed to the article and approved the submitted version.

This study was supported by grants from the Shanghai Municipal Health Commission (Grant Number ZY3-LCPT-2-1002), and Shanghai Municipal Science and Technology Commission (Grant Number 20Z21900300), as well as Shanghai Hospital Development Center (No. SHDC2020CR1050B).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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