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Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?
Mark van Barele1, Bernadette A M Heemskerk-Gerritsen1, Yvonne V Louwers2
1Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Cancers
|June 2, 2021
Summary
Triple-negative breast cancer (TNBC) is not entirely hormone-insensitive. Alternative pathways influence TNBC, challenging the assumption of hormone insensitivity and requiring further research into hormone replacement therapy safety.
Area of Science:
- Oncology
- Endocrinology
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) disproportionately affects younger women and lacks estrogen and progesterone receptors, leading to its classification as hormone-insensitive.
- Standard chemotherapy for premenopausal TNBC patients can cause premature ovarian insufficiency (POI), significantly impacting quality of life.
- Hormone replacement therapy (HRT) is generally contraindicated in hormone-sensitive breast cancer, but its safety in TNBC patients remains inconclusive, with some studies suggesting potential recurrence risks.
Purpose of the Study:
- To review the literature on alternative hormonal pathways influencing triple-negative breast cancer (TNBC).
- To evaluate the potential impact of hormone replacement therapy (HRT) on TNBC given its complex hormonal interactions.
- To challenge the established notion of TNBC hormone insensitivity.
Main Methods:
- Literature review of studies investigating non-classical estrogen and progestogen pathways in TNBC.
- Analysis of research on alternative receptors, receptor conversion, and paracrine signaling in TNBC.
- Examination of the influence of HRT on androgens and androgen receptors (AR) in TNBC.
Main Results:
- Estrogens and progestogens can affect TNBC through alternative pathways, including receptor conversion and alternative receptors.
- Paracrine pathways, such as RANK/RANKL, can mediate indirect growth and metastatic stimulation of TNBC by progestogens.
- Hormone replacement therapy may influence androgens and their receptors in TNBC, suggesting complex hormonal interplay.
Conclusions:
- The assumption that triple-negative breast cancer (TNBC) is completely hormone-insensitive is inaccurate.
- Alternative hormonal pathways exist that can influence TNBC growth and metastasis.
- Further investigation is required to clarify the direction and implications of these alternative pathways and the safety of HRT in TNBC patients.
