Abstract
There is consensus that attitudes toward seeking complementary and alternative medicine (CAM) are different between oriental and western patients. A 16-year-old girl who presented with enlarged breast tumours also had a 3-year history of “Si-Wu-Tang” (SWT) intake. Pathology of the resected breast tumour disclosed a giant fibroadenoma with aneuploid status. A cohort study was conducted between two groups of patients with fibroadenomas: SWT intake (+) group and SWT intake (−) group. Patients were told to discontinue SWT intake for 3 months, and this was followed by breast ultrasonographic examination in both groups. The tumour sizes before and after discontinued SWT intake were 2.3±0.11 cm and 1.5±0.12 cm in the SWT (+) group, and 1.7±0.15 cm and 1.6±0.14 cm in SWT (−) group, respectively (p<0.05). It is concluded that this report provides important information for patients with breast tissue diseases and that continuous intake of medicinal herbs is recommended only under the guidance of trained CAM providers.
BACKGROUND
Accumulating evidence suggests that the use of complementary and alternative medicine (CAM) worldwide has increased substantially in the past decade.1 Owing to the fact that hormone replacement treatment increases the risk of breast cancer, many patients use CAM therapies to relieve their postmenopausal discomfort.2 These reports suggest that there are many patients receiving CAM therapies but are not aware of their safety profiles or potential adverse effects. Furthermore, the advantages of CAM therapies on breast tissue diseases such as breast cancer remain controversial.
CASE PRESENTATION
We treated a 16-year-old girl who had a progressively enlarged right breast tumour. An over-the-counter modified herbal pill “Si-Wu-Tang” (SWT) had been given to her by her mother since she was 13 years. SWT, an old Chinese medicinal formula for regulation of menstruation, is composed of Angelicae sinensis, Rehmanniae preparata, Ligusticum chuanxiong Hortorum, and Paeonia lactiflora Pallas; the modified herbal patent medicine is composed of SWT plus Panax ginseng and Eucommia ulmoides Oliver. The frequency was 1 tablet per day except during the menstruation period. A fullness sensation over the breasts was complained of several months after starting this regimen. It was not until 6 months ago that she noticed several masses palpable in both breasts, especially on the right side. Since the masses enlarged rapidly, she was admitted under the tentative diagnosis of giant fibroadenoma or phylloides tumour with malignant potential. Physical examination showed a huge (13 cm) fixed tumour in the right breast and two small nodules in the left breast.
INVESTIGATIONS
Breast ultrasonography showed a large lobulated and homogenous mass with marginal hypervascularity. Fine needle aspiration cytology (right breast tumour) disclosed mammary ductal hyperplasia with atypia.
DIFFERENTIAL DIAGNOSIS
Right breast tumour: R/I herb-related giant fibroadenoma or phylloides tumour with malignant potential.
Left breast tumours: R/I multiple fibroadenomas.
TREATMENT
The patient received wide excision for right breast tumour (265 gm) and pathological diagnosis was fibroadenoma with atypical hyperplasia.
OUTCOME AND FOLLOW-UP
Analysed by DNA flow cytometry, the ploidy status of white blood cells and resected tumour was 2.00 N and 2.42 N, respectively (fig 1). She was discharged uneventfully.
Figure 1.
DNA content of a huge fibroadenoma obtained from a patient taking modified Si-Wu-Tang formula for 3 years. The DNA content of white blood cells (WBC; upper panel), breast tumour (middle panel) and mixed white blood cells and tumour tissue (lower panel) were analysed by DNA flow cytometry. The ploidy status of white blood cells (upper panel) and resected tumour (middle panel) was 2.00 N and 2.42 N, respectively.
DISCUSSION
Previous investigations have shown that the nutritional intake of phytoestrogens seems to reduce the risk of breast cancer or other neoplastic diseases. Isoflavones possess non-hormonal properties that are associated with the inhibition of cancer cell growth through several possible mechanisms. However, the role of isoflavones in breast cancer has become controversial because, in contrast to the possible beneficial effects, some data from in vitro and animal studies suggest that isoflavones may stimulate the growth of oestrogen-sensitive tumours.3,4 Furthermore, phytoestrogens appear to mitigate oestrogenic signalling in the presence of both oestrogen receptor (ER) subtypes, but in late-stage cancer cells lacking ER-beta these phytochemicals contribute to a tumour-promoting transcriptional signature.4 To our knowledge, there are few reports suggesting that SWT has a stimulatory activity on proliferation of human mammary ducts. This case raised our attention enough that it encouraged us to conduct a clinical cohort observation study. Two groups of patients with fibroadenomas were included. They were: (1) SWT (+) group, or patients with a history SWT intake; and (2) SWT (−) group, or patients without a history of SWT intake. After obtaining informed consent, patients with SWT (+) intake were instructed to discontinue SWT intake for 3 months and come back to receive breast ultrasonographic examinations to measure tumour progression. Patients without a history of SWT intake were asked to receive a breast ultrasonographic check up 3 months later. The tumour sizes before and after discontinued SWT intake were 2.3+0.11 cm, 1.5+0.12 cm in the SWT (+) group (n=21), and 1.7+0.15 cm, 1.6+0.14 cm in the SWT (−) group (n=10), respectively (p<0.05, Mann–Whitney U test). Moreover, our recent investigations have demonstrated that repeated administration of SWT and some of its constituents stimulate mammary duct cell growth by modulating HER-2, PI3K/AKT and MAPK signalling, as well as influencing the positive feedback of HER-2 gene expression, indicating possible mitogenic effects of this combination of medicinal herbs.5,6 In fact, SWT, as mentioned in traditional classic literature, is only prescribed to patients 3–5 days after their menstruation. Therefore, the knowledge of how herbal therapies are properly applied is important for patients with breast diseases and continuous CAM usage is highly recommended only under the guidance of trained CAM providers (fig 2).
Figure 2.
Decision making in the treatment of patients with breast diseases who receive complementary and alternative medicine (CAM) therapies.
LEARNING POINTS
Si-Wu-Tang (SWT) is prescribed to patients 3–5 days after menstruation in traditional Chinese medicine (TCM) treatment strategy.
SWT has mitogenic potential on breast duct cells in long-term use. It should not be prescribed indiscriminately for the treatment of gynaecological problems.
For those patients who are taking SWT and have breast lesions discovered, it is important to have a dialogue between his/her family doctor and the TCM doctor.
Acknowledgments
We are in debt to Miss Wu in the Taipei Veterans General Hospital for her excellent technical assistance.
Footnotes
Competing interests: none.
Patient consent: Patient/guardian consent was obtained for publication.
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