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Blocking Estrogen Synthesis Leads to Different Hormonal Responses in Canine and Human Triple Negative Inflammatory
Sara Caceres1, Beatriz Monsalve1, Angela Alonso-Diez2
1Department of Animal Physiology, Veterinary Medicine School, Complutense University of Madrid (UCM), 28040 Madrid, Spain.
Abstract:
Blocking estrogen synthesis by inhibitors of estrogen synthesis is a widely used therapy against estrogen receptor-positive tumors. However, these therapies are less effective in negative expression tumors. Therefore, this study determined the effectiveness of anti-aromatase and anti-sulfatase therapies in canine and human inflammatory breast cancer. Cell cultures and xenografts from IPC-366 and SUM149 were treated with different doses of letrozole (anti-aromatase) and STX-64 (anti-sulfatase), in order to observe their effectiveness in terms of cell proliferation, tumor progression, and the appearance of metastases and hormonal profiles. The results revealed that both treatments are effective in vitro since they reduce cell proliferation and decrease the secreted estrogen levels. In xenograft mice, while treatment with letrozole reduces tumor progression by 30-40%, STX-64 increases tumor progression by 20%. The hormonal results obtained determined that STX-64 produced an increase in circulating and intratumoral levels of estradiol, which led to an increase in tumor progression. However, letrozole was able to block estrogen synthesis by decreasing the levels of circulating and intratumoral estrogen and thus slowing down tumor progression. In conclusion, letrozole can be an effective treatment for canine and human inflammatory breast cancer. The knowledge of the hormonal profile of breast tumors reflects useful information on the effectiveness of different endocrine treatments.
Insights
Letrozole effectively inhibits estrogen synthesis, slowing tumor progression in canine and human inflammatory breast cancer. STX-64, however, increased tumor progression by elevating estrogen levels.
Area of Science:
- Oncology
- Endocrinology
- Comparative Pathology
Background:
- Estrogen synthesis inhibitors are key in treating estrogen receptor-positive tumors.
- Therapies targeting estrogen synthesis show limited efficacy in estrogen receptor-negative tumors.
- Inflammatory breast cancer (IBC) presents unique therapeutic challenges.
Purpose of the Study:
- To evaluate the efficacy of anti-aromatase (letrozole) and anti-sulfatase (STX-64) therapies in canine and human inflammatory breast cancer models.
- To assess the impact of these therapies on cell proliferation, tumor progression, metastasis, and hormonal profiles.
- To determine the effectiveness of targeting different estrogen synthesis pathways in IBC.
Main Methods:
- In vitro studies using IPC-366 and SUM149 cell cultures treated with letrozole and STX-64.
- In vivo studies using xenograft mouse models implanted with IPC-366 and SUM149 cells.
- Monitoring of cell proliferation, tumor volume, metastasis, and serum/intratumoral estrogen levels.
Main Results:
- Both letrozole and STX-64 reduced cell proliferation and estrogen levels in vitro.
- Letrozole treatment decreased tumor progression by 30-40% in xenografts.
- STX-64 treatment paradoxically increased tumor progression by 20% due to elevated estradiol levels.
Conclusions:
- Letrozole demonstrates significant efficacy in slowing tumor progression in both canine and human IBC models.
- STX-64's effectiveness is limited, potentially due to increased estradiol, highlighting pathway-specific responses.
- Hormonal profiling is crucial for predicting the effectiveness of endocrine treatments in breast cancer.
