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Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers
BACKGROUND: Higher circulating prolactin has been associated with increased breast cancer risk. Prolactin binding to the prolactin receptor (PRLR) can activate the transcription factor STAT5, thus, we examined the association between plasma prolactin and breast cancer risk by tumor expression of PRL...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990334/ https://www.ncbi.nlm.nih.gov/pubmed/36882838 http://dx.doi.org/10.1186/s13058-023-01618-3 |
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author | Hathaway, Cassandra A. Rice, Megan S. Collins, Laura C. Chen, Dilys Frank, David A. Walker, Sarah Clevenger, Charles V. Tamimi, Rulla M. Tworoger, Shelley S. Hankinson, Susan E. |
author_facet | Hathaway, Cassandra A. Rice, Megan S. Collins, Laura C. Chen, Dilys Frank, David A. Walker, Sarah Clevenger, Charles V. Tamimi, Rulla M. Tworoger, Shelley S. Hankinson, Susan E. |
author_sort | Hathaway, Cassandra A. |
collection | PubMed |
description | BACKGROUND: Higher circulating prolactin has been associated with increased breast cancer risk. Prolactin binding to the prolactin receptor (PRLR) can activate the transcription factor STAT5, thus, we examined the association between plasma prolactin and breast cancer risk by tumor expression of PRLR, STAT5, and the upstream kinase JAK2. METHODS: Using data from 745 cases and 2454 matched controls in the Nurses’ Health Study, we conducted polytomous logistic regression to examine the association between prolactin (> 11 ng/mL vs. ≤ 11 ng/mL) measured within 10 years of diagnosis and breast cancer risk by PRLR (nuclear [N], cytoplasmic [C]), phosphorylated STAT5 (pSTAT5; N, C), and phosphorylated JAK2 (pJAK2; C) tumor expression. Analyses were conducted separately in premenopausal (n = 168 cases, 765 controls) and postmenopausal women (n = 577 cases, 1689 controls). RESULTS: In premenopausal women, prolactin levels > 11 ng/mL were positively associated with risk of tumors positive for pSTAT5-N (OR 2.30, 95% CI 1.02–5.22) and pSTAT5-C (OR 1.64, 95% CI 1.01–2.65), but not tumors that were negative for these markers (OR 0.98, 95% CI 0.65–1.46 and OR 0.73, 95% CI 0.43–1.25; p-heterogeneity = 0.06 and 0.02, respectively). This was stronger when tumors were positive for both pSTAT5-N and pSTAT5-C (OR 2.88, 95% CI 1.14–7.25). No association was observed for PRLR or pJAK2 (positive or negative) and breast cancer risk among premenopausal women. Among postmenopausal women, plasma prolactin levels were positively associated with breast cancer risk irrespective of PRLR, pSTAT5, or pJAK2 expression (all p-heterogeneity ≥ 0.21). CONCLUSION: We did not observe clear differences in the association between plasma prolactin and breast cancer risk by tumor expression of PRLR or pJAK2, although associations for premenopausal women were observed for pSTAT5 positive tumors only. While additional studies are needed, this suggests that prolactin may act on human breast tumor development through alternative pathways. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-023-01618-3. |
format | Online Article Text |
id | pubmed-9990334 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-99903342023-03-08 Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers Hathaway, Cassandra A. Rice, Megan S. Collins, Laura C. Chen, Dilys Frank, David A. Walker, Sarah Clevenger, Charles V. Tamimi, Rulla M. Tworoger, Shelley S. Hankinson, Susan E. Breast Cancer Res Research BACKGROUND: Higher circulating prolactin has been associated with increased breast cancer risk. Prolactin binding to the prolactin receptor (PRLR) can activate the transcription factor STAT5, thus, we examined the association between plasma prolactin and breast cancer risk by tumor expression of PRLR, STAT5, and the upstream kinase JAK2. METHODS: Using data from 745 cases and 2454 matched controls in the Nurses’ Health Study, we conducted polytomous logistic regression to examine the association between prolactin (> 11 ng/mL vs. ≤ 11 ng/mL) measured within 10 years of diagnosis and breast cancer risk by PRLR (nuclear [N], cytoplasmic [C]), phosphorylated STAT5 (pSTAT5; N, C), and phosphorylated JAK2 (pJAK2; C) tumor expression. Analyses were conducted separately in premenopausal (n = 168 cases, 765 controls) and postmenopausal women (n = 577 cases, 1689 controls). RESULTS: In premenopausal women, prolactin levels > 11 ng/mL were positively associated with risk of tumors positive for pSTAT5-N (OR 2.30, 95% CI 1.02–5.22) and pSTAT5-C (OR 1.64, 95% CI 1.01–2.65), but not tumors that were negative for these markers (OR 0.98, 95% CI 0.65–1.46 and OR 0.73, 95% CI 0.43–1.25; p-heterogeneity = 0.06 and 0.02, respectively). This was stronger when tumors were positive for both pSTAT5-N and pSTAT5-C (OR 2.88, 95% CI 1.14–7.25). No association was observed for PRLR or pJAK2 (positive or negative) and breast cancer risk among premenopausal women. Among postmenopausal women, plasma prolactin levels were positively associated with breast cancer risk irrespective of PRLR, pSTAT5, or pJAK2 expression (all p-heterogeneity ≥ 0.21). CONCLUSION: We did not observe clear differences in the association between plasma prolactin and breast cancer risk by tumor expression of PRLR or pJAK2, although associations for premenopausal women were observed for pSTAT5 positive tumors only. While additional studies are needed, this suggests that prolactin may act on human breast tumor development through alternative pathways. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-023-01618-3. BioMed Central 2023-03-07 2023 /pmc/articles/PMC9990334/ /pubmed/36882838 http://dx.doi.org/10.1186/s13058-023-01618-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Hathaway, Cassandra A. Rice, Megan S. Collins, Laura C. Chen, Dilys Frank, David A. Walker, Sarah Clevenger, Charles V. Tamimi, Rulla M. Tworoger, Shelley S. Hankinson, Susan E. Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers |
title | Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers |
title_full | Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers |
title_fullStr | Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers |
title_full_unstemmed | Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers |
title_short | Prolactin levels and breast cancer risk by tumor expression of prolactin-related markers |
title_sort | prolactin levels and breast cancer risk by tumor expression of prolactin-related markers |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9990334/ https://www.ncbi.nlm.nih.gov/pubmed/36882838 http://dx.doi.org/10.1186/s13058-023-01618-3 |
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