【Veterinary Research】Long Disease-Free Intervals Observed in Three Cats With Mammary Carcinoma Following Partial Mastectomy and Daily Huaier Administration

Target Article

About the Journal

The article was published in Open Veterinary Journal, an international peer-reviewed journal covering a broad range of topics in veterinary medicine and animal health. The journal is indexed in PubMed/MEDLINE, Scopus, and Web of Science. The reported 2025 Journal Impact Factor is 1.6, and the journal is classified within Q2 in its relevant category.

 

Study Overview Using the PICO Framework

 

Study Design and Sample Size

 

Detailed Results

Disease-Free Intervals Observed in the Three Cases

No clinically detectable local recurrence or distant metastasis was reported in any of the three cats during their respective observation periods.

The reported DFIs were:

Case 1: 612 days
Case 2: 695 days
Case 3: 557 days

The article cites previous reports describing DFIs of approximately 205–428 days following conservative surgical resection. The DFIs observed in these three cases were numerically longer than the values reported in those historical studies.

However, these values cannot be directly compared without caution because the historical studies differed from the present report in patient population, tumor characteristics, staging, surgical procedures, follow-up methods, and other potentially relevant prognostic factors.

Furthermore, because all three cats underwent surgical resection followed by Huaier administration and no untreated or surgery-only concurrent control group was included, the extent to which Huaier contributed to the observed DFIs cannot be determined.

The findings should therefore be interpreted as descriptive clinical observations rather than evidence that Huaier prolonged DFI.

Clinical Course in Cases With Adverse Histopathological Features

The three cats had heterogeneous pathological characteristics.

Case 1 was a 12-year-old spayed female with Stage II, grade II mammary carcinoma associated with lymphatic and muscular invasion.

Case 2 was a 13-year-old spayed female with Stage II, grade I mammary carcinoma without identified lymphatic invasion.

Case 3 was a 14-year-old spayed female with multiple grade I and grade II mammary lesions, lymphatic invasion, and extensive inguinal lymph node metastasis and was classified as Stage III.

Lymphatic invasion and regional lymph node metastasis have been associated with an unfavorable prognosis in feline mammary carcinoma. In this context, the absence of clinically detectable recurrence or distant metastasis during the 557-day observation period in Case 3 is noteworthy as an individual clinical observation.

Nevertheless, this clinical course cannot be attributed specifically to Huaier administration. Tumor biology, surgical removal of macroscopic disease, individual host factors, and other measured or unmeasured variables may also have contributed to the observed outcome.

Accordingly, this case provides a rationale for further investigation rather than evidence that Huaier suppresses recurrence or metastasis.

Safety and Tolerability Observations During Long-Term Administration

Huaier was administered orally at 1 g/day beginning on postoperative day 2 in all three cats.

Follow-up continued for 557–695 days. During these periods, no clinical signs or hematologic or biochemical abnormalities considered attributable to Huaier administration were reported.

These observations indicate that no identifiable treatment-related adverse events were detected in these three individual cats during the reported follow-up periods.

However, the sample size is too small to establish the overall safety profile of Huaier in cats. Rare adverse events, effects occurring in specific patient populations, and long-term toxicities cannot be adequately evaluated from this case series.

Accordingly, these findings should be interpreted as preliminary observations regarding tolerability rather than evidence of established safety.

 

Potential Clinical Relevance in Veterinary Medicine

Possible Clinical Positioning

Feline mammary carcinoma is generally regarded as a biologically aggressive malignancy. Surgical excision remains the principal treatment, and the extent of surgery is selected according to tumor distribution, disease stage, patient condition, and other clinical considerations. Systemic chemotherapy may also be considered in selected patients, although the magnitude of its clinical benefit may vary according to disease characteristics and the available evidence.

In clinical practice, extensive surgery or systemic chemotherapy may not always be feasible or selected. Advanced age, concurrent disease, anesthetic risk, anticipated adverse effects, and owner preference may influence treatment decisions.

The present case series provides preliminary information regarding the clinical courses of three cats treated with partial mastectomy followed by long-term Huaier administration.

These observations raise the possibility that Huaier could be further investigated as an adjunctive approach in feline mammary carcinoma.

However, the present findings are insufficient to support Huaier as an alternative to established surgical or systemic treatment and should not be interpreted as evidence that standard treatment can be replaced by Huaier administration.

Relationship to Conventional Anticancer Therapy

Cytotoxic agents such as doxorubicin and carboplatin have been used as systemic treatments for feline mammary carcinoma. These agents have pharmacological and clinical characteristics that differ fundamentally from those proposed for Huaier.

Cytotoxic chemotherapy may be associated with adverse effects such as myelosuppression and gastrointestinal toxicity, with the nature and severity of adverse effects varying among agents and individual patients.

In the present case series, no adverse events considered attributable to Huaier were identified. This observation may be relevant when considering long-term administration, but it does not demonstrate that Huaier is safer than conventional chemotherapy because no direct comparative study was performed.

Similarly, there is currently insufficient evidence to conclude that Huaier causes direct tumor regression or has an anticancer effect comparable to that of established cytotoxic agents.

If Huaier has clinically relevant activity in feline mammary carcinoma, its role should currently be regarded as investigational and potentially adjunctive rather than as a substitute for established local or systemic therapy.

Study Limitations and Critical Interpretation

This report has several important limitations.

The most important limitations are the very small sample size of three cats and the absence of a concurrent control group.

As a result, the observed DFIs cannot be causally attributed to Huaier administration, and no reliable estimate of treatment effect can be calculated.

Although previously published DFIs following conservative surgery were cited as historical reference values, comparisons with historical data are particularly susceptible to bias. Differences in tumor size, disease stage, histological grade, lymphatic invasion, metastatic status, surgical margins, surgical technique, imaging methods, follow-up intervals, and patient characteristics may substantially influence clinical outcomes.

The three cases themselves were also heterogeneous with respect to histological grade, lymphatic invasion, lymph node involvement, and disease stage. These factors may independently influence prognosis and make interpretation of the three cats as a single treatment group difficult.

Another limitation concerns the assessment of recurrence and metastatic disease. Follow-up was based on clinical examination and conventional diagnostic imaging. Although these methods are clinically appropriate, microscopic residual disease or subclinical metastatic disease cannot be excluded.

In addition, a relatively long DFI in an individual patient does not necessarily indicate a treatment effect. Variation in the natural biological behavior of feline mammary carcinoma may also contribute to differences in outcome.

For these reasons, the present observations should be regarded as hypothesis-generating rather than confirmatory evidence of efficacy.

Interpretation of Proposed Biological Mechanisms

Experimental studies involving Huaier or Huaier-derived components have described several potential biological effects, including modulation of innate immune signaling, macrophage activity, angiogenesis, inflammatory signaling pathways, and epithelial–mesenchymal transition.

Some studies have implicated pathways involving Toll-like receptor 4 (TLR4), tumor necrosis factor-related signaling, interleukins, and other immune- or tumor-associated signaling mechanisms.

However, much of this evidence is derived from in vitro studies, experimental animal models, and human oncology research.

The biological activity, pharmacokinetics, effective dose, and relevant molecular targets of Huaier in cats with naturally occurring mammary carcinoma have not been sufficiently established.

Accordingly, mechanistic findings obtained from human or experimental models should not be regarded as direct evidence of clinical efficacy in cats.

At present, any proposed relationship between these molecular mechanisms and the relatively long DFIs observed in the three cats remains hypothetical.

Further studies are required to determine whether Huaier has reproducible biological or clinical activity in feline mammary carcinoma.

Ideally, future research should include larger prospective cohorts, clearly defined treatment protocols, standardized staging and follow-up procedures, appropriate control groups, and clinically relevant endpoints such as DFI, progression-free survival, disease-specific survival, and overall survival.

Mini-Glossary for Readers

Huaier

Huaier is a medicinal basidiomycete from which polysaccharide–protein complexes and other biologically active constituents have been isolated. Huaier-derived preparations have been investigated primarily in human and experimental oncology. Their efficacy and mechanisms of action in veterinary cancer patients remain incompletely defined.

Disease-Free Interval (DFI)

The period from treatment until the first detection of tumor recurrence or metastatic disease. In patients in whom recurrence is not observed during follow-up, the reported DFI represents the duration of disease-free observation up to the latest assessment rather than necessarily a completed endpoint.

Epithelial–Mesenchymal Transition (EMT)

A biological process in which epithelial cells acquire characteristics associated with a more migratory and invasive phenotype. EMT has been investigated as one of several mechanisms potentially involved in cancer invasion and metastasis.

Historical Control

Previously reported patient data used as a contextual comparator for a current study. Historical controls may be useful for generating hypotheses but are less reliable than concurrently enrolled control groups because differences in patient characteristics, diagnostic methods, treatment protocols, and study design may introduce substantial bias.

Overall Interpretation

This case series describes three cats with feline mammary carcinoma that remained free of clinically detectable local recurrence and distant metastasis for 557–695 days after partial mastectomy followed by daily Huaier administration.

No adverse events considered attributable to Huaier were identified during the reported follow-up periods.

These observations are clinically noteworthy, particularly because some of the cats had pathological features associated with an unfavorable prognosis.

However, because the report includes only three heterogeneous cases, lacks a concurrent control group, and does not permit statistical assessment of treatment effect, it cannot establish that Huaier prolonged DFI, prevented recurrence or metastasis, or improved survival.

The findings should therefore be regarded as preliminary, hypothesis-generating clinical observations that support further controlled investigation of Huaier in feline mammary carcinoma.

Link to the full article:
https://doi.org/10.5455/OVJ.2026.v16.i6.74