Security of progesterone drugs in breast cancer survivors_West China Medical Journal

Authors：

SUN Fangcan ,  HAN Bing

Department of Obstetrics and Gynecology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P. R. China;

Corresponding author：

HAN Bing, Email: hanbing@suda.edu.cn

Keywords：

Progesterone; Breast cancer; Abnormal uterine bleeding; Menstruation; Hormone receptor

DOI：

10.7507/1002-0179.201912109

Video：

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Breast cancer is one of the most common malignant tumors in women. The systematic therapy of breast cancer may affect the endometrium and ovarian function, such as abnormal endometrial hyperplasia and abnormal uterine bleeding caused by ovulation disorders. If we do not consider the patients suffering from breast cancer, we can use progesterone drugs to stop bleeding, regulate menstruation, and protect the endometrium. But there is no consistent conclusion on the safety of progesterone drugs in breast cancer patients. This article reviews the security of progesterone drugs in breast cancer survivors from the perspective of basic and clinical research. At present, whether the use of progesterone drugs in breast cancer survivors increases the risk of disease may be related to the type, dosage, and method of use of progesterone drugs. At the same time, it is also related to the type of breast cancer the patient has. Based on the available data, it is safe to use natural progesterone or dydrogesterone for the short term in patients with breast cancer. More studies are needed to evaluate other approaches.

Citation： SUN Fangcan, HAN Bing. Security of progesterone drugs in breast cancer survivors. West China Medical Journal, 2020, 35(10): 1273-1278. doi: 10.7507/1002-0179.201912109 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	马飞, 徐兵河, 邵志敏. 乳腺癌随访及伴随疾病全方位管理指南. 中华肿瘤杂志, 2019, 41(1): 29-41.
3.	郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析. 中华肿瘤杂志, 2019, 41(1): 19-28.
4.	Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China. Lancet Oncol, 2014, 15(7): e279-e289.
5.	Waks AG, Winer EP. Breast cancer treatment: a review. JAMA, 2019, 321(3): 288-300.
6.	Waks AG, Winer EP. Breast cancer treatment. JAMA, 2019, 321(3): 316.
7.	Liem GS, Mo FK, Pang E, et al. Chemotherapy-related amenorrhea and menopause in young Chinese breast cancer patients: analysis on incidence, risk factors and serum hormone profiles. PLoS One, 2015, 10(10): e0140842.
8.	Kim HA, Ahn SH, Nam SJ, et al. The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress. BMC Cancer, 2016, 16(1): 319.
9.	Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet, 2011, 378(9793): 771-784.
10.	Bracken-Clarke DB, Lucas MW, Higgins MJ. Extended adjuvant endocrine therapy in hormone receptor-positive early breast cancer. Breast Care (Basel), 2017, 12(3): 138-144.
11.	Committee Opinion. 601:Tamoxifen and uterine cancer. Obstet Gynecol, 2014, 123(6): 1394-1397.
12.	关竞红, 马淼, 孙强, 等. 绝经前乳腺癌术后辅助治疗对月经的影响. 生殖医学杂志, 2017, 26(2): 106-111.
13.	Taponeco F, Curcio C, Fasciani A, et al. Indication of hysteroscopy in tamoxifen treated breast cancer patients. J Exp Clin Cancer Res, 2002, 21(1): 37-43.
14.	Runowicz CD, Costantino JP, Wickerham DL, et al. Gynecologic conditions in participants in the NSABP breast cancer prevention study of tamoxifen and raloxifene (STAR). Am J Obstet Gynecol, 2011, 205(6): 535.e1-535.e5.
15.	中国抗癌协会乳腺癌专业委员会. 中国早期乳腺癌卵巢功能抑制临床应用专家共识(2018年版). 中国癌症杂志, 2018, 28(11): 871-880.
16.	Rice MS, Tamimi RM, Bertrand KA, et al. Does mammographic density mediate risk factor associations with breast cancer? An analysis by tumor characteristics. Breast Cancer Res Treat, 2018, 170(1): 129-141.
17.	Endogenous Hormones and Breast Cancer Collaborative Group, Key TJ, Appleby PN, et al. Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies. Lancet Oncol, 2013, 14(10): 1009-1019.
18.	Gompel A, Plu-Bureau G. Progesterone, progestins and the breast in menopause treatment. Climacteric, 2018, 21(4): 326-332.
19.	邓文慧, 杜俊, 杨丽, 等. 孕激素对人乳腺组织雌激素受体、孕激素受体、增殖细胞核抗原、bcl-2及c-myc、c-fos、表皮生长因子受体表达的影响. 中华医学杂志, 2018, 98(35): 2827-2831.
20.	Mohammed H, Russell IA, Stark R, et al. Progesterone receptor modulates ERα action in breast cancer. Nature, 2015, 523(7560): 313-317.
21.	Piette P. The history of natural progesterone, the never-ending story. Climacteric, 2018, 21(4): 308-314.
22.	赵越, 阮祥燕, 张泉东, 等. 乳腺癌患者血液中PGRMC1浓度与临床相关性. 首都医科大学学报, 2018, 39(4): 486-493.
23.	Neubauer H, Chen R, Schneck H, et al. New insight on a possible mechanism of progestogens in terms of breast cancer risk. Horm Mol Biol Clin Investig, 2011, 6(1): 185-192.
24.	Ruan X, Neubauer H, Yang Y, et al. Progestogens and membrane-initiated effects on the proliferation of human breast cancer cells. Climacteric, 2012, 15(5): 467-472.
25.	王利娟, 杨春, 谷牧青, 等. 受孕激素调节的microRNAs与乳腺癌的关系. 首都医科大学学报, 2017, 38(4): 521-525.
26.	Finlay-Schultz J, Cittelly DM, Hendricks P, et al. Progesterone downregulation of miR-141 contributes to expansion of stem-like breast cancer cells through maintenance of progesterone receptor and Stat5a. Oncogene, 2015, 34(28): 3676-3687.
27.	黄晓娟, 何桂芳, 尹玉. 雌、孕激素联合给药逆转miR-145对三阴性乳腺癌的抑癌作用. 安徽医科大学学报, 2018, 53(1): 20-24.
28.	Wang Y, Lewin N, Qaoud Y, et al. The oncologic impact of hormone replacement therapy in premenopausal breast cancer survivors: a systematic review. Breast, 2018, 40(40): 123-130.
29.	Holmberg L, Iversen OE, Rudenstam CM, et al. Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J Natl Cancer Inst, 2008, 100(7): 475-482.
30.	Holmberg L, Anderson H, HABITS steering and data monitoring committees. HABITS (hormonal replacement therapy after breast cancer--is it safe?), a randomised comparison: trial stopped. Lancet, 2004, 363(9407): 453-455.
31.	Fahlén M, Fornander T, Johansson H, et al. Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial. Eur J Cancer, 2013, 49(1): 52-59.
32.	Angioli R, Luvero D, Armento G, et al. Hormone replacement therapy in cancer survivors: Utopia?. Crit Rev Oncol Hematol, 2018, 124: 51-60.
33.	Brewster AM, Do KA, Thompson PA, et al. Relationship between epidemiologic risk factors and breast cancer recurrence. J Clin Oncol, 2007, 25(28): 4438-4444.
34.	中华医学会妇产科学分会妇科内分泌学组. 排卵障碍性异常子宫出血诊治指南. 中华妇产科杂志, 2018, 53(12): 801-807.
35.	Stute P, Wildt L, Neulen J. The impact of micronized progesterone on breast cancer risk: a systematic review. Climacteric, 2018, 21(2): 111-122.
36.	Eden J. The endometrial and breast safety of menopausal hormone therapy containing micronised progesterone: a short review. Aust N Z J Obstet Gynaecol, 2017, 57(1): 12-15.
37.	中华医学会妇产科学分会妇科内分泌学组. 异常子宫出血诊断与治疗指南. 中华妇产科杂志, 2014, 49(11): 801-806.
38.	Bakkum-Gamez JN, Laughlin SK, Jensen JR, et al. Challenges in the gynecologic care of premenopausal women with breast cancer. Mayo Clin Proc, 2011, 86(3): 229-240.
39.	Wong AW, Chan SS, Yeo W, et al. Prophylactic use of levonorgestrel-releasing intrauterine system in women with breast cancer treated with tamoxifen: a randomized controlled trial. Obstet Gynecol, 2013, 121(5): 943-950.
40.	Dominick S, Hickey M, Chin J, et al. Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen. Cochrane Database Syst Rev, 2015(12): CD007245.
41.	Royal College of Obstetricians and Gynaecologists, British Society for Gynaecological Endoscopy. Management of endometrial hyperplasia: RCOG/BSGE green-top guideline No. 67. (2006-02-26)[2019-12-01]. https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg67/.
42.	Vaz-Luis I, Partridge AH. Exogenous reproductive hormone use in breast cancer survivors and previvors. Nat Rev Clin Oncol, 2018, 15(4): 249-261.
43.	Van Heertum K, Liu J. Differential effects of progestogens used for menopausal hormone therapy. Clin Obstet Gynecol, 2018, 61(3): 454-462.
44.	Stute P, Neulen J, Wildt L. The impact of micronized progesterone on the endometrium: a systematic review. Climacteric, 2016, 19(4): 316-328.
45.	Briki R, Cherif O, Bannour B, et al. Uncommon metastases of invasive lobular breast cancer to the endometrium: a report of two cases and review of the literature. Pan Afr Med J, 2018, 30: 268.
46.	Abdalla AS, Lazarevska A, Omer MM, et al. Metastatic breast cancer to the cervix presenting with abnormal vaginal bleeding during chemotherapy: a case report and literature review. Chirurgia (Bucur), 2018, 113(4): 564-570.
47.	Razia S, Nakayama K, Tsukao M, et al. Metastasis of breast cancer to an endometrial polyp, the cervix and a leiomyoma: a case report and review of the literature. Oncol Lett, 2017, 14(4): 4585-4592.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. 马飞, 徐兵河, 邵志敏. 乳腺癌随访及伴随疾病全方位管理指南. 中华肿瘤杂志, 2019, 41(1): 29-41.
3. 郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析. 中华肿瘤杂志, 2019, 41(1): 19-28.
4. Fan L, Strasser-Weippl K, Li JJ, et al. Breast cancer in China. Lancet Oncol, 2014, 15(7): e279-e289.
5. Waks AG, Winer EP. Breast cancer treatment: a review. JAMA, 2019, 321(3): 288-300.
6. Waks AG, Winer EP. Breast cancer treatment. JAMA, 2019, 321(3): 316.
7. Liem GS, Mo FK, Pang E, et al. Chemotherapy-related amenorrhea and menopause in young Chinese breast cancer patients: analysis on incidence, risk factors and serum hormone profiles. PLoS One, 2015, 10(10): e0140842.
8. Kim HA, Ahn SH, Nam SJ, et al. The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress. BMC Cancer, 2016, 16(1): 319.
9. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Godwin J, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet, 2011, 378(9793): 771-784.
10. Bracken-Clarke DB, Lucas MW, Higgins MJ. Extended adjuvant endocrine therapy in hormone receptor-positive early breast cancer. Breast Care (Basel), 2017, 12(3): 138-144.
11. Committee Opinion. 601:Tamoxifen and uterine cancer. Obstet Gynecol, 2014, 123(6): 1394-1397.
12. 关竞红, 马淼, 孙强, 等. 绝经前乳腺癌术后辅助治疗对月经的影响. 生殖医学杂志, 2017, 26(2): 106-111.
13. Taponeco F, Curcio C, Fasciani A, et al. Indication of hysteroscopy in tamoxifen treated breast cancer patients. J Exp Clin Cancer Res, 2002, 21(1): 37-43.
14. Runowicz CD, Costantino JP, Wickerham DL, et al. Gynecologic conditions in participants in the NSABP breast cancer prevention study of tamoxifen and raloxifene (STAR). Am J Obstet Gynecol, 2011, 205(6): 535.e1-535.e5.
15. 中国抗癌协会乳腺癌专业委员会. 中国早期乳腺癌卵巢功能抑制临床应用专家共识(2018年版). 中国癌症杂志, 2018, 28(11): 871-880.
16. Rice MS, Tamimi RM, Bertrand KA, et al. Does mammographic density mediate risk factor associations with breast cancer? An analysis by tumor characteristics. Breast Cancer Res Treat, 2018, 170(1): 129-141.
17. Endogenous Hormones and Breast Cancer Collaborative Group, Key TJ, Appleby PN, et al. Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies. Lancet Oncol, 2013, 14(10): 1009-1019.
18. Gompel A, Plu-Bureau G. Progesterone, progestins and the breast in menopause treatment. Climacteric, 2018, 21(4): 326-332.
19. 邓文慧, 杜俊, 杨丽, 等. 孕激素对人乳腺组织雌激素受体、孕激素受体、增殖细胞核抗原、bcl-2及c-myc、c-fos、表皮生长因子受体表达的影响. 中华医学杂志, 2018, 98(35): 2827-2831.
20. Mohammed H, Russell IA, Stark R, et al. Progesterone receptor modulates ERα action in breast cancer. Nature, 2015, 523(7560): 313-317.
21. Piette P. The history of natural progesterone, the never-ending story. Climacteric, 2018, 21(4): 308-314.
22. 赵越, 阮祥燕, 张泉东, 等. 乳腺癌患者血液中PGRMC1浓度与临床相关性. 首都医科大学学报, 2018, 39(4): 486-493.
23. Neubauer H, Chen R, Schneck H, et al. New insight on a possible mechanism of progestogens in terms of breast cancer risk. Horm Mol Biol Clin Investig, 2011, 6(1): 185-192.
24. Ruan X, Neubauer H, Yang Y, et al. Progestogens and membrane-initiated effects on the proliferation of human breast cancer cells. Climacteric, 2012, 15(5): 467-472.
25. 王利娟, 杨春, 谷牧青, 等. 受孕激素调节的microRNAs与乳腺癌的关系. 首都医科大学学报, 2017, 38(4): 521-525.
26. Finlay-Schultz J, Cittelly DM, Hendricks P, et al. Progesterone downregulation of miR-141 contributes to expansion of stem-like breast cancer cells through maintenance of progesterone receptor and Stat5a. Oncogene, 2015, 34(28): 3676-3687.
27. 黄晓娟, 何桂芳, 尹玉. 雌、孕激素联合给药逆转miR-145对三阴性乳腺癌的抑癌作用. 安徽医科大学学报, 2018, 53(1): 20-24.
28. Wang Y, Lewin N, Qaoud Y, et al. The oncologic impact of hormone replacement therapy in premenopausal breast cancer survivors: a systematic review. Breast, 2018, 40(40): 123-130.
29. Holmberg L, Iversen OE, Rudenstam CM, et al. Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. J Natl Cancer Inst, 2008, 100(7): 475-482.
30. Holmberg L, Anderson H, HABITS steering and data monitoring committees. HABITS (hormonal replacement therapy after breast cancer--is it safe?), a randomised comparison: trial stopped. Lancet, 2004, 363(9407): 453-455.
31. Fahlén M, Fornander T, Johansson H, et al. Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial. Eur J Cancer, 2013, 49(1): 52-59.
32. Angioli R, Luvero D, Armento G, et al. Hormone replacement therapy in cancer survivors: Utopia?. Crit Rev Oncol Hematol, 2018, 124: 51-60.
33. Brewster AM, Do KA, Thompson PA, et al. Relationship between epidemiologic risk factors and breast cancer recurrence. J Clin Oncol, 2007, 25(28): 4438-4444.
34. 中华医学会妇产科学分会妇科内分泌学组. 排卵障碍性异常子宫出血诊治指南. 中华妇产科杂志, 2018, 53(12): 801-807.
35. Stute P, Wildt L, Neulen J. The impact of micronized progesterone on breast cancer risk: a systematic review. Climacteric, 2018, 21(2): 111-122.
36. Eden J. The endometrial and breast safety of menopausal hormone therapy containing micronised progesterone: a short review. Aust N Z J Obstet Gynaecol, 2017, 57(1): 12-15.
37. 中华医学会妇产科学分会妇科内分泌学组. 异常子宫出血诊断与治疗指南. 中华妇产科杂志, 2014, 49(11): 801-806.
38. Bakkum-Gamez JN, Laughlin SK, Jensen JR, et al. Challenges in the gynecologic care of premenopausal women with breast cancer. Mayo Clin Proc, 2011, 86(3): 229-240.
39. Wong AW, Chan SS, Yeo W, et al. Prophylactic use of levonorgestrel-releasing intrauterine system in women with breast cancer treated with tamoxifen: a randomized controlled trial. Obstet Gynecol, 2013, 121(5): 943-950.
40. Dominick S, Hickey M, Chin J, et al. Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen. Cochrane Database Syst Rev, 2015(12): CD007245.
41. Royal College of Obstetricians and Gynaecologists, British Society for Gynaecological Endoscopy. Management of endometrial hyperplasia: RCOG/BSGE green-top guideline No. 67. (2006-02-26)[2019-12-01]. https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg67/.
42. Vaz-Luis I, Partridge AH. Exogenous reproductive hormone use in breast cancer survivors and previvors. Nat Rev Clin Oncol, 2018, 15(4): 249-261.
43. Van Heertum K, Liu J. Differential effects of progestogens used for menopausal hormone therapy. Clin Obstet Gynecol, 2018, 61(3): 454-462.
44. Stute P, Neulen J, Wildt L. The impact of micronized progesterone on the endometrium: a systematic review. Climacteric, 2016, 19(4): 316-328.
45. Briki R, Cherif O, Bannour B, et al. Uncommon metastases of invasive lobular breast cancer to the endometrium: a report of two cases and review of the literature. Pan Afr Med J, 2018, 30: 268.
46. Abdalla AS, Lazarevska A, Omer MM, et al. Metastatic breast cancer to the cervix presenting with abnormal vaginal bleeding during chemotherapy: a case report and literature review. Chirurgia (Bucur), 2018, 113(4): 564-570.
47. Razia S, Nakayama K, Tsukao M, et al. Metastasis of breast cancer to an endometrial polyp, the cervix and a leiomyoma: a case report and review of the literature. Oncol Lett, 2017, 14(4): 4585-4592.

West China Medical Journal

Security of progesterone drugs in breast cancer survivors

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