Prolactin, its physiological function and role in breast oncogenesis (a review of the literature)


  • V.V. Lihostaieva Bogomolets National Medical University, Kyiv, Ukraine,
  • O.S. Zotov Bogomolets National Medical University, Kyiv, Ukraine,
  • M.V. Braitsara Bogomolets National Medical University, Kyiv, Ukraine,



breast cancer, prolactin, prolactin receptors, hyperprolactinemia, review


Breast cancer is the most frequent cancer among wo­men, impacting 2.1 million individuals each year, and also causes the greatest number of cancer-related deaths among women. Prolactin, known as not only a hormone involved in normal breast development and lactation, but also a cytokine, has been hypothesized to be important in the etiology of breast cancer. The literature review contains the data regarding the physiological role of prolactin, as well as its synthesis, regulation, pathogenesis, and clinical manifestations of hyperprolactinemic states. We have described the results of the relevant epidemiological trials on the role of prolactin in breast oncogenesis, particularly in different molecular types of breast cancer. The publications (reviews, original articles, results of in vitro, in vivo and clinical studies, meta-analyses) used in this work were analyzed using the search databases such as PubMed, MEDLINE, Medscape.

References (National Cancer Registry of Ukraine).

Frantz A.G., Kleinberg D.L. Prolactin: evidence that it is separate from growth hormone in human blood. Science. 1970. 170(3959). 745-747. DOI:10.1126/science.170.3959.745.

Татарчук Т.Ф., Гуньков С.В., Ефименко О.А. Современные подходы к диагностике и лечению гиперпролактинемии. Репродуктивная эндокринология. 2012. № 1. С. 26-44. DOI:

Иловайская И.А., Марова Е.И. Биология пролактина (молекулярные формы пролактина). Акушерство и гинекология. 2000. № 6. С. 3-6.

Щепотин И.Б., Зотов А.С., Костюченко Е.А. Пролактин, его антагонисты и неопластический процесс в молочной железе. Новоутворення. 2007. С. 3-13.

Веропотвелян П.Н., Веропотвелян Н.П., Бондаренко А.А. и др. Влияние пролактина на состояние молочной железы. Медичні аспекти здоров’я жінки. 2011. № 3-1(43). С. 29-37.

Subramani R., Nandy S.B., Pedroza A.D. et al. Role of Growth Hormone in Breast Cancer. Endocrinology. 2017. Vol. 158. Issue 6. P. 1543-1555.

O’Shea J.J., Gadina М., Shreiber R.D. Cytokine Signaling in 2002: New Surprises in JAK/STAT Pathway. Cell. 2002. Vol. 109. Suppl. S. 121-131.

Watson С.J., Burdon T.G. Prolactin Signal Transduction Mechanisms in the Mammary Gland: The Role of the Jak/Stat Pathway. Reviews of reproduction. 1996. 1(1). P. 1-5

Clapp C. et al. Regulation of blood vessels by prolactin and vasoinhibins. Advances in experimental medicine and biology. 2015.Vol. 846. P. 83-95.

Булатов А.А., Мартынов А.В., Смирнова Н.Б. Биохимическая природа пролактина сыворотки крови человека. Биохимия. 1997. Т. 62. № 9. С. 1212-1220.

Ginsburg E., Alexander S., Lieber S. et al. Characterization of ductal and lobular breast carcinomas using novel prolactin receptor isoform specific antibodies. BMC Cancer. 2010. 10. 678. DOI: 10.1186/1471-2407-10-678.

Motamedi B., Rafie-Pour H.A., Khorsavi M.R. et al. Prolactin receptor as a novel prognostic biomarker for triple-negative breast cancer patients. Ann. Diag. Path. 2020. Vol. 46. 15507.

Ben-Jonathan N. et al. Prolactin as an Autocrine/Paracrine Growth Factor in Human Cancer. Trands Endocrinol. Metab. 2002. Vol. 13(6). P. 245-250.

Clevenger C.V. et al. The Role of Prolactin in Mammary Carcinoma. Endocrine Reviews. 2003. Vol. 24. P. 1-27.

Tworoger S.S. et al. A 20-Year Prospective Study of Plasma Prolactin as a Risk Marker of Breast Cancer Development. Prevention and Epidemiology. 2013. Vol. 73(15).

Hachim I.Y. et al. Concomitant Expression of Prolactin Receptor and TGFβ Receptors in Breast Cancer: Association With Less Aggressive Phenotype and Favorable Patient Outcome. International Journal of molecular sciences. 2019. 20(7). 1640.

Hachim I.Y. et al. A favorable role of prolactin in human breast cancer reveals novel pathway-based gene signatures indicative of tumor differentiation and favorable patient outcome. Human Pathology. 2016. Vol. 53. P. 142-152.

Holloran S.M. Reciprocal fine-tuning of progesterone and prolactin-regulated gene expression in breast cancer cells. Molecular and Cellular Endocrinology. 2020. Vol. 511(110859).

Rasmussen L.M. et al. Prolactin and Oestrogen Synergistically Regulate Gene Expression and Proliferation of Breast Cancer Cells. Endocr. Relat. Cancer. 2010. Vol. 17(3). 809-22.

Naderi A. Prolactin-induced protein in breast cancer. Adv. Exp. Med. Biol. 2015. 846. 189-200. DOI: 10.1007/978-3-319-12114-7_8.

Baniwal S.K., Chimge N.O., Jordan V.C. et al. Prolactin-induced protein (PIP) regulates proliferation of luminal A type breast cancer cells in an estrogen-independent manner. PLoS One. 2013. 8(6). e62361. Published 2013 Jun 3. DOI: 10.1371/journal.pone.0062361.

Naderi A., Vanneste M. Prolactin-induced protein is required for cell cycle progression in breast cancer. Neoplasia. 2014. 16(4). 329-342.e14. DOI: 10.1016/j.neo.2014.04.001.

Jablonska K., Grzegrzolka J., Podhorska-Okolow M. et al. Prolactin-induced protein as a potential therapy response marker of adjuvant chemotherapy in breast cancer patients. Am. J. Cancer Res. 2016. Vol. 6(5). P. 878-893.

Goffin V. Prolactin receptor targeting in breast and prostate cancers: New insights into an old challenge. Pharmacol. Ther. 2017. Vol. 179. P. 111-126. DOI: 10.1016/j.pharmthera.2017.05.009.

Jacobson E.M., Hugo E.R., Borcherding D.C. et al. Prolactin in breast and prostate cancer: molecular and genetic perspectives. Discov. Med. 2011. Vol. 11(59). P. 315-324.

Agarwal N., Machiels J.P., Suárez C et al. Phase I Study of the Prolactin Receptor Antagonist LFA102 in Metastatic Breast and Castration-Resistant Prostate Cancer. Oncologist. 2016. Vol. 21(5). P. 535-536. DOI:10.1634/theoncologist.2015-0502.

Kalinina T.S., Kononchuk V.V., Sidorov S.V. et al. Analysis of prolactin receptor expression in breast cancer subtypes. Biomed. Khim. 2020. Vol. 66(1). P. 89-94. DOI: 10.18097/PBMC20206601089.

Hachim I.Y., López-Ozuna V.M., Hachim M.Y. et al. Prolactin hormone exerts anti-tumorigenic effects in HER-2 overexpres­sing breast cancer cells through regulation of stemness. Stem. Cell. Res. 2019. Vol. 40. 101538. DOI: 10.1016/j.scr.2019.101538.

Zhou Y., Zong H., Han L. et al. A novel bispecific antibody targeting CD3 and prolactin receptor (PRLR) against PRLR-expression breast cancer. J. Exp. Clin. Cancer Res. 2020. Vol. 39(1). 87. DOI: 10.1186/s13046-020-01564-4.

Luciano A.A. Clinical presentation of hyperprolactinemia. J. Reprod. Med. 1999. Vol. 44. P. 1085-1090.

Molitch M.E. Prolactinomas. The Pituitary. Ed. S. Melmed. Cambridge MA: Blacwell Sci, 1995. P. 443-477.

Григорян О.Г. и др. Гиперпролактинемия в практике гинеколога: этиология, патогенез, клиника, диагностика, лечение. Проблемы репродукции. 2013. 4. C. 14-20.

Мельниченко Г.А. и др. Гиперпролактинемия у женщин и мужчин. Пособие для врачей. 2007.

Fuh G., Colosi P., Wood W.I. et al. The pole of fat cells in Prolactin synthesis. J. Biol.Chem. 1993. Vol. 268. P. 5376-5381.

Wang M. et al. Plasma prolactin and breast cancer risk: a meta- analysis. Sci. Rep. 2016. Vol. 6. 25998. DOI: 10.1038/srep25998.

Tikk K., Sookthai D., Fortner R. et al. Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study. Breast Cancer Res. 2015. Vol. 17(1). 49. DOI:10.1186/s13058-015-0563-6.

López-Ozuna V., Hachim I., Hachim M. et al. Prolactin Pro-Differentiation Pathway in Triple Negative Breast Cancer: Impact on Prognosis and Potential Therapy. Sci Rep. 2016. 6. 30934.

Tworoger S.S., Eliassen A.H., Sluss P. et al. A prospective study of plasma prolactin concentrations and risk of premenopausal and postmenopausal breast cancer. J. Clin. Oncol. 2007 Apr 20. 25(12). 1482-8. DOI: 10.1200/JCO.2006.07.6356.

Tworoger S.S., Sorensen B., Chubak J. et al. A. Effect of a 12-month randomized clinical trial of exercise on serum prolactin concentrations in postmenopausal women. Cancer Epidemiol. Biomarkers Prev. 2007 May. 16(5). 895-9. DOI: 10.1158/1055-9965.EPI-06-0701.

Faupel-Badger J., Sherman M., Garcia-Closas M. et al. Prolactin serum levels and breast cancer: relationships with risk factors and tumour characteristics among pre- and postmenopausal women in a population-based case-control study from Poland. Br. J. Cancer. 2010. 103. 097-1102.

Hachim I.Y., Hachim M.Y., Lopez V.M. et al. Prolactin Receptor Expression is an Independent Favorable Prognostic Marker in Human Breast Cancer. Applied Immunohistochemistry & Molecular Morphology. 2016 Apr. 24(4). 238-245. DOI: 10.1097/pai.0000000000000178.