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.	馬飛, 徐兵河, 邵志敏. 乳腺癌隨訪及伴隨疾病全方位管理指南. 中華腫瘤雜志, 2019, 41(1): 29-41.
3.	鄭榮壽, 孫可欣, 張思維, 等. 2015年中國惡性腫瘤流行情況分析. 中華腫瘤雜志, 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.	關競紅, 馬淼, 孫強, 等. 絕經前乳腺癌術后輔助治療對月經的影響. 生殖醫學雜志, 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.	中國抗癌協會乳腺癌專業委員會. 中國早期乳腺癌卵巢功能抑制臨床應用專家共識(2018年版). 中國癌癥雜志, 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.	鄧文慧, 杜俊, 楊麗, 等. 孕激素對人乳腺組織雌激素受體、孕激素受體、增殖細胞核抗原、bcl-2及c-myc、c-fos、表皮生長因子受體表達的影響. 中華醫學雜志, 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.	趙越, 阮祥燕, 張泉東, 等. 乳腺癌患者血液中PGRMC1濃度與臨床相關性. 首都醫科大學學報, 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, 楊春, 谷牧青, 等. 受孕激素調節的microRNAs與乳腺癌的關系. 首都醫科大學學報, 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.	黃曉娟, 何桂芳, 尹玉. 雌、孕激素聯合給藥逆轉miR-145對三陰性乳腺癌的抑癌作用. 安徽醫科大學學報, 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.	中華醫學會婦產科學分會婦科內分泌學組. 排卵障礙性異常子宮出血診治指南. 中華婦產科雜志, 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.	中華醫學會婦產科學分會婦科內分泌學組. 異常子宮出血診斷與治療指南. 中華婦產科雜志, 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. 馬飛, 徐兵河, 邵志敏. 乳腺癌隨訪及伴隨疾病全方位管理指南. 中華腫瘤雜志, 2019, 41(1): 29-41.
3. 鄭榮壽, 孫可欣, 張思維, 等. 2015年中國惡性腫瘤流行情況分析. 中華腫瘤雜志, 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. 關競紅, 馬淼, 孫強, 等. 絕經前乳腺癌術后輔助治療對月經的影響. 生殖醫學雜志, 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. 中國抗癌協會乳腺癌專業委員會. 中國早期乳腺癌卵巢功能抑制臨床應用專家共識(2018年版). 中國癌癥雜志, 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. 鄧文慧, 杜俊, 楊麗, 等. 孕激素對人乳腺組織雌激素受體、孕激素受體、增殖細胞核抗原、bcl-2及c-myc、c-fos、表皮生長因子受體表達的影響. 中華醫學雜志, 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. 趙越, 阮祥燕, 張泉東, 等. 乳腺癌患者血液中PGRMC1濃度與臨床相關性. 首都醫科大學學報, 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, 楊春, 谷牧青, 等. 受孕激素調節的microRNAs與乳腺癌的關系. 首都醫科大學學報, 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. 黃曉娟, 何桂芳, 尹玉. 雌、孕激素聯合給藥逆轉miR-145對三陰性乳腺癌的抑癌作用. 安徽醫科大學學報, 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. 中華醫學會婦產科學分會婦科內分泌學組. 排卵障礙性異常子宮出血診治指南. 中華婦產科雜志, 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. 中華醫學會婦產科學分會婦科內分泌學組. 異常子宮出血診斷與治療指南. 中華婦產科雜志, 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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