Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?
Triple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead...
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/11/2506 |
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| author | Mark van Barele Bernadette A. M. Heemskerk-Gerritsen Yvonne V. Louwers Mijntje B. Vastbinder John W. M. Martens Maartje J. Hooning Agnes Jager |
| author_facet | Mark van Barele Bernadette A. M. Heemskerk-Gerritsen Yvonne V. Louwers Mijntje B. Vastbinder John W. M. Martens Maartje J. Hooning Agnes Jager |
| author_sort | Mark van Barele |
| collection | DOAJ |
| description | Triple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead to premature ovarian insufficiency (POI) and can severely impact quality of life. Hormone replacement therapy (HRT) is contraindicated for patients with a history of hormone-sensitive breast cancer, but the data on safety for TNBC patients is inconclusive, with a few randomized trials showing increased risk-ratios with wide confidence intervals for recurrence after HRT. Here, we review the literature on alternative pathways from the classical ER/PR. We find that for both estrogens and progestogens, potential alternatives exist for exerting their effects on TNBC, ranging from receptor conversion, to alternative receptors capable of binding estrogens, as well as paracrine pathways, such as RANK/RANKL, which can cause progestogens to indirectly stimulate growth and metastasis of TNBC. Finally, HRT may also influence other hormones, such as androgens, and their effects on TNBCs expressing androgen receptors (AR). Concluding, the assumption that TNBC is completely hormone-insensitive is incorrect. However, the direction of the effects of the alternative pathways is not always clear, and will need to be investigated further. |
| first_indexed | 2024-03-10T11:12:06Z |
| format | Article |
| id | doaj.art-49ca03de68ef4d3da3fcdd8852263fe0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T11:12:06Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-49ca03de68ef4d3da3fcdd8852263fe02023-11-21T20:40:27ZengMDPI AGCancers2072-66942021-05-011311250610.3390/cancers13112506Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?Mark van Barele0Bernadette A. M. Heemskerk-Gerritsen1Yvonne V. Louwers2Mijntje B. Vastbinder3John W. M. Martens4Maartje J. Hooning5Agnes Jager6Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre, Dr. Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre, Dr. Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsDepartment of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Dr. Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsDepartment of Internal Medicine, Ijsselland Hospital, Prins Constantijnweg 2, 2906 ZC Capelle aan den IJssel, The NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre, Dr. Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre, Dr. Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsDepartment of Medical Oncology, Erasmus MC Cancer Institute, University Medical Centre, Dr. Molewaterplein 40, 3015 GD Rotterdam, The NetherlandsTriple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead to premature ovarian insufficiency (POI) and can severely impact quality of life. Hormone replacement therapy (HRT) is contraindicated for patients with a history of hormone-sensitive breast cancer, but the data on safety for TNBC patients is inconclusive, with a few randomized trials showing increased risk-ratios with wide confidence intervals for recurrence after HRT. Here, we review the literature on alternative pathways from the classical ER/PR. We find that for both estrogens and progestogens, potential alternatives exist for exerting their effects on TNBC, ranging from receptor conversion, to alternative receptors capable of binding estrogens, as well as paracrine pathways, such as RANK/RANKL, which can cause progestogens to indirectly stimulate growth and metastasis of TNBC. Finally, HRT may also influence other hormones, such as androgens, and their effects on TNBCs expressing androgen receptors (AR). Concluding, the assumption that TNBC is completely hormone-insensitive is incorrect. However, the direction of the effects of the alternative pathways is not always clear, and will need to be investigated further.https://www.mdpi.com/2072-6694/13/11/2506triple-negativehormone-receptor negative breast cancerERβRANK/RANKLGPERAR |
| spellingShingle | Mark van Barele Bernadette A. M. Heemskerk-Gerritsen Yvonne V. Louwers Mijntje B. Vastbinder John W. M. Martens Maartje J. Hooning Agnes Jager Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm? Cancers triple-negative hormone-receptor negative breast cancer ERβ RANK/RANKL GPER AR |
| title | Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm? |
| title_full | Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm? |
| title_fullStr | Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm? |
| title_full_unstemmed | Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm? |
| title_short | Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm? |
| title_sort | estrogens and progestogens in triple negative breast cancer do they harm |
| topic | triple-negative hormone-receptor negative breast cancer ERβ RANK/RANKL GPER AR |
| url | https://www.mdpi.com/2072-6694/13/11/2506 |
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