Breast Cancer – Specifics of Gynecological Care and Counseling
Authors:
Vít Weinberger 1; Michal Zikán 2
Authors‘ workplace:
Onkogynekologické centrum, Gynekologicko-porodnická klinika LF MU a FN Brno
1; Onkogynekologické centrum, Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze
2
Published in:
Klin Onkol 2016; 29(Supplementum 3): 7-15
Category:
Review
doi:
https://doi.org/10.14735/amko20163S7
Overview
Background:
This paper summarizes current knowledge about clinically important aspects of gynecological care in female breast cancer patients. Despite the overall positive acceptance of oral contraceptives and hormone replacement drugs, hormone therapy may raise fears of developing breast cancer. Specifics of gynecological care of fertile patients are discussed as these patients face ovarian failure when undergoing oncological treatment of breast cancer. Tamoxifen is used in adjuvant therapy of breast cancer, in metastatic breast cancer or as prophylaxis of breast cancer in high-risk patients.
Aim:
We aim to study the influence of hormonal treatment on breast cancer development in women with and without congenital predisposition. The main risk factors for developing breast cancer are family history, increased density of breast tissue, atypical hyperplasia of the breast and previous radiotherapy to the chest area. All these factors increase the relative risk of cancer more than four times. Contraceptives and hormone replacement therapy show generally less than two-fold or no increase at all (RR 0.96–1.6). We concentrate with safety of hormonal therapy in breast cancer patients after they finish breast cancer treatment in pre- and postmenopausal period. We discuss fertility-sparing methods for preservation of ovarian function due to oncological treatment. Those methods are cryopreservation of embryos, oocytes in metaphase II and ovarian tissue. Simultaneous administration of GnRH agonists may protect ovarian function before gonadotoxic chemotherapy. We describe in detail the effects of tamoxifen on gynecological organs in both pre- and postmenopausal women in relation to the potential risk of developing secondary malignancy. In premenopausal women, tamoxifen has no increased risk of cancer of the uterine body. In postmenopausal patients, the risk after five years of tamoxifen is increased 2–3 times. Transvaginal sonography is not the screening tool for detection of the pathology in the uterine cavity during tamoxifen therapy, and so we only recommend looking for symptoms. Hysteroscopy is the golden standard for the examination of the uterine cavity in symptomatic postmenopausal patients using tamoxifen.
Conclusion:
This paper summarizes the current knowledge in areas where oncological and gynecological cares for breast cancer patients mingle. It should lead to greater understanding and deepening cooperation between clinical oncologists and oncogynecologists for the benefit of our patients.
Key words:
adjuvant hormonal therapy – fertility preservation – GnRH analogs – contraceptives – endometrial hyperplasia – hormone replacement therapy – breast neoplasm – tamoxifen
This work was supported by the Czech Ministry of Health – RVO (FNBr, 65269705).
The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.
The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted:
6. 6. 2016
Accepted:
22. 7. 2016
Sources
1. Dušek L, Mužík J, Kubásek M et al. Epidemiologie zhoubných nádorů v České republice. Masarykova univerzita, Česká republika; 2005, [citováno 15. dubna 2016]. Dostupné z: http: //www.svod.cz.
2. Zikán M. Hereditární syndromy. In: Cibula D, Petruželka L (eds). Onkogynekologie. Praha: Grada 2009: 614.
3. Cummings SR, Tice JA, Bauer S et al. Prevention of breast cancer in postmenopausal women: approaches to estimating and reducing risk. J Natl Cancer Inst 2009; 101 (6): 384–398. doi: 10.1093/jnci/djp018.
4. Medina D, Kittrell FS, Tsimelzon A et al. Inhibition of mammary tumorigenesis by estrogen and progesterone in genetically engineered mice. Ernst Schering Found Symp Proc 2007; 1: 109–126.
5. Dumeaux V, Alsaker E, Lund E. Breast cancer and specific types of oral contraceptives: a large Norwegian cohort study. Int J Cancer 2003; 105 (6): 844–850.
6. Marchbanks PA, McDonald JA, Wilson HG et al. Oral contraceptives and the risk of breast cancer. N Engl J Med 2002; 346 (26): 2025–2032.
7. Rosenberg L, Zhang Y, Coogan PF et al. A case-control study of oral contraceptive use and incident breast cancer. Am J Epidemiol 2009; 169 (4): 473–479. doi: 10.1093/aje/kwn360.
8. Shapiro S. Re: “A case-control study of oral contraceptive use and incident breast cancer.” Am J Epidemiol 2009; 170 (6): 802–803; author reply 803–804. doi: 10.1093/aje/kwp245.
9. Thomas HV, Reeves GK, Key TJ. Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control 1997; 8 (6): 922–928.
10. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 1997; 350 (9084): 1047–1059. doi: 10.1016/S0140-6736 (97) 08233-0.
11. Schairer C, Gail M, Byrne C et al. Estrogen replacement therapy and breast cancer survival in a large screening study. J Natl Cancer Inst 1999; 91 (3): 264–270.
12. Willis B, Calle E, Miracle-McMahill L et al. Estrogen replacement therapy and risk of fatal breast cancer in a prospective cohort of postmenopausal women in the United States. Cancer Causes Control 1996; 7 (4): 449–457.
13. Beral V, Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003; 362 (9382): 419–427.
14. Ruddy KJ, Gelber SI, Tamimi RM et al. Prospective study of fertility concerns and preservation strategies in young women with breast cancer. J Clin Oncol 2014; 32 (11): 1151–1156. doi: 10.1200/JCO.2013.52.8877.
15. Gonçalves V, Sehovic I, Quinn G. Childbearing attitudes and decisions of young breast cancer survivors: a systematic review. Hum Reprod Update 2014; 20 (2): 279–292. doi: 10.1093/humupd/dmt039.
16. 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.
17. Bundred NJ, Kenemans P, Yip CH et al. Tibolone increases bone mineral density but also relapse in breast cancer survivors: LIBERATE trial bone substudy. Breast Cancer Res 2012; 14 (1): R13.
18. Kenemans P, Bundred J, Foidart JM et al. Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol 2009; 10 (2): 135–146. doi: 10.1016/S1470-2045 (08) 70341-3.
19. Ory H, Cole P, MacMahon B et al. Oral contraceptives and reduced risk of benign breast diseases. N Engl J Med 1976; 294 (8): 419–422.
20. Vessey M, Yeates D. Oral contraceptives and benign breast disease: an update of findings in a large cohort study. Contraception 2007; 76 (6): 418–424.
21. LiVolsi VA, Stadel BV, Kelsey JL at al. Fibroadenoma in oral contraceptive users: a histopathologic evaluation of epithelial atypia. Cancer 1979; 44 (5): 1778–1781.
22. Rohan TE, Miller AB. A cohort study of oral contraceptive use and risk of benign breast disease. Int J Cancer 1999; 82 (2): 191–196.
23. Gaffield ME, Culwell KR, Ravi A. Oral contraceptives and family history of breast cancer. Contraception 2009; 80 (4): 372–380. doi: 10.1016/j.contraception.2009.04.010.
24. Lipnick RJ, Buring JE, Hennekens CH et al. Oral contraceptives and breast cancer. A prospective cohort study. JAMA 1986; 255 (1): 58–61.
25. Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 2001; 358 (9291): 1389–1399.
26. Colditz AG, Rosner BA, Speizer FE. Risk factors for breast cancer according to family history of breast cancer. For the Nurses’ Health Study Research Group. J Natl Cancer Inst 1996; 88 (6): 365–371.
27. Grabrick DM, Hartmann LC, Cerhan JR et al. Risk of breast cancer with oral contraceptive use in women with a family history of breast cancer. JAMA 2000; 284 (14): 1791–1798.
28. Silvera SA, Miller AB, Rohan TE. Oral contraceptive use and risk of breast cancer among women with a family history of breast cancer: a prospective cohort study. Cancer Causes Control 2005; 16 (9): 1059–1063.
29. Narod SA. Modifiers of risk of hereditary breast and ovarian cancer. Nat Rev Cancer 2002; 2 (2): 113–123.
30. Cibula D, Zikan M, Dusek L et al. Oral contraceptives and risk of ovarian and breast cancers in BRCA mutation carriers: a meta-analysis. Expert Rev Anticancer Ther 2011; 11 (8): 1197–1207. doi: 10.1586/era.11.38.
31. Rebbeck R, Friebel T, Wagner T et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2005; 23 (31): 7804–7810.
32. Chlebowski RT, Kuller LH, Prentice RL et al. Breast cancer after use of estrogen plus progestin in postmenopausal women. N Engl J Med 2009; 360 (6): 573–587. doi: 10.1056/NEJMoa0807684.
33. Rebbeck TR, Friebel T, Wagner T et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol 2005; 23 (31): 7804–7810.
34. Torino F, Barnabei A, De Vecchis L et al. Chemotherapy-induced ovarian toxicity in patients affected by endocrine-responsive early breast cancer. Crit Rev Oncol Hematol 2014; 89 (1): 27–42. doi: 10.1016/j.critrevonc.2013.07.007.
35. Oktem O, Oktay K. Quantitative assessment of the impact of chemotherapy on ovarian follicle reserve and stromal function. Cancer 2007; 110 (10): 2222–2229.
36. Kalich-Philosoph L, Roness H, Carmely A et al. Cyclophosphamide triggers follicle activation and “burnout”; AS101 prevents follicle loss and preserves fertility. Sci Transl Med 2013; 5 (185): 185ra62. doi: 10.1126/scitranslmed.3005402.
37. Blumenfeld Z, Katz G, Evron A. ‚An ounce of prevention is worth a pound of cure‘: the case for and against GnRH-agonist for fertility preservation. Ann Oncol 2014; 25 (9): 1719–1728. doi: 10.1093/annonc/mdu036.
38. De Vos M, Smitz J, Woodruff TK. Fertility preservation in women with cancer. Lancet 2014; 384 (9950): 1302–1310. doi: 10.1016/S0140-6736 (14) 60834-5.
39. Cardozo ER, Thomson AP, Karmon AE et al. Ovarian stimulation and in-vitro fertilization outcomes of cancer patients undergoing fertility preservation compared to age matched controls: a 17-year experience. J Assist Reprod Genet 2015; 32 (4): 587–596. doi: 10.1007/s10815-015-0428-z.
40. Blumenfeld Z, Patel B, Leiba R et al. Gonadotropin-releasing hormone agonist may minimize premature ovarian failure in young women undergoing autologous stem cell transplantation. Fertil Steril 2012; 98 (5): 1266–1270. doi: 10.1016/j.fertnstert.2012.07.1144.
41. Revelli A, Porcu E, Levi Setti PE et al. Is letrozole needed for controlled ovarian stimulation in patients with estrogen receptor-positive breast cancer? Gynecol Endocrinol 2013; 29 (11): 993–996. doi: 10.3109/ 09513590.2013.819083.
42. Quinn GP, Vadaparampil ST, Bower B et al. Decisions and ethical issues among BRCA carriers and the use of preimplantation genetic diagnosis. Minerva Med 2009; 100 (5): 371–383.
43. Tomasi-Cont N, Lambertini M, Hulsbosch S et al. Strategies for fertility preservation in young early breast cancer patients. Breast 2014; 23 (5): 503–510. doi: 10.1016/j.breast.2014.05.024.
44. Dursun P, Doğan NU, Ayhan A. Oncofertility for gynecologic and non-gynecologic cancers: fertility sparing in young women of reproductive age. Crit Rev Oncol Hematol 2014; 92 (3): 258–267. doi: 10.1016/j.critrevonc.2014.07.001.
45. Dolmans MM, Donnez J, Camboni A et al. IVF outcome in patients with orthotopically transplanted ovarian tissue. Hum Reprod 2009; 24 (11): 2778–2787. doi: 10.1093/humrep/dep289.
46. Dolmans MM, Marinescu C, Saussoy P et al. Reimplantation of cryopreserved ovarian tissue from patients with acute lymphoblastic leukemia is potentially unsafe. Blood 2010; 116 (16): 2908–2914. doi: 10.1182/blood-2010-01-265751.
47. Blumenfeld Z, von Wolff M. GnRH-analogues and oral contraceptives for fertility preservation in women during chemotherapy. Hum Reprod Update 2008; 14 (6): 543–552. doi: 10.1093/humupd/dmn022.
48. Blumenfeld Z. GnRH-agonists in fertility preservation. Curr Opin Endocrinol Diabetes Obes 2008; 15 (6): 523–528. doi: 10.1097/MED.0b013e32831a46e9.
49. Roness H, Gavish Z, Cohen Y et al. Ovarian follicle burnout: a universal phenomenon? Cell Cycle 2013; 12 (20): 3245–3246. doi: 10.4161/cc.26358.
50. Del Mastro L, Levaggi A, Giraudi S et al. Luteinising hormone releasing hormone agonists (LH-RHa) in premenopausal early breast cancer patients: current role and future perspectives. Cancer Treat Rev 2011; 37 (3): 208–211. doi: 10.1016/j.ctrv.2010.07.007.
51. Clowse ME, Behera MA, Anders CK et al. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J Womens Health (Larchmt) 2009; 18 (3): 311–319. doi: 10.1089/jwh.2008.0857.
52. Wong M, O’Neill S, Walsh G et al. Goserelin with chemotherapy to preserve ovarian function in pre-menopausal women with early breast cancer: menstruation and pregnancy outcomes. Ann Oncol 2013; 24 (1): 133–138. doi: 10.1093/annonc/mds250.
53. Edgar AB, Wallace WH. Pregnancy in women who had cancer in childhood. Eur J Cancer 2007; 43 (13): 1890–1894.
54. Wang C, Chen M, Fu F et al. Gonadotropin-releasing hormone analog cotreatment for the preservation of ovarian function during gonadotoxic chemotherapy for breast cancer: a meta-analysis. PLoS One 2013; 8 (6): e66360. doi: 10.1371/journal.pone.0066360.
55. Aebi S, Davidson T, Gruber G et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 (Suppl 5): v9–v14. doi: 10.1093/annonc/mdq159.
56. Cuzick J, Forbes J, Edwards R et al. First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet 2002; 360 (9336): 817–824.
57. Bevers TB, Armstrong DK, Arun B et al. Breast cancer risk reduction. J Natl Compr Canc Netw 2010; 8 (10): 1112–1146.
58. Osborne CK. Tamoxifen in the treatment of breast cancer. N Engl J Med 1998; 339 (22): 1609–1618.
59. Polin SA, Ascher SM. The effect of tamoxifen on the genital tract. Cancer Imaging 2008; 8: 135–145. doi: 10.1102/1470-7330.2008.0020.
60. Neven P, Vergote I. Should tamoxifen users be screened for endometrial lesions? Lancet 1998; 351 (9097): 155–157.
61. Lahti E, Blanco G, Kauppila A et al. Endometrial changes in postmenopausal breast cancer patients receiving tamoxifen. Obstet Gynecol 1993; 81 (5): 660–664.
62. McGonigle KF, Shaw SL, Vasilev SA et al. Abnormalities detected on transvaginal ultrasonography in tamoxifen-treated postmenopausal breast cancer patients may represent endometrial cystic atrophy. Am J Obstet Gynecol 1998; 178 (6): 1145–1150.
63. Cohen I, Bernheim J, Azaria R et al. Malignant endometrial polyps in postmenopausal breast cancer tamoxifen-treated patients. Gynecol Oncol 1999; 75 (1): 136–141.
64. Neven P, De Muylder X, Van Belle Y et al. Longitudinal hysteroscopic follow-up during tamoxifen treatment. Lancet 1998; 351 (9095): 36.
65. Dilts PV Jr, Hopkins MP, Chang AE et al. Rapid growth of leiomyoma in patient receiving tamoxifen. Am J Obstet Gynecol 1992; 166 (1): 167–168.
66. Ramondetta LM, Sherwood JB, Dunton CJ et al. Endometrial cancer in polyps associated with tamoxifen use. Am J Obstet Gynecol 1999; 180 (2): 340–341.
67. Cohen I. Endometrial pathologies associated with postmenopausal tamoxifen treatment. Gynecol Oncol 2004; 94 (2): 256–266.
68. Neven P, Vernaeve H. Guidelines for monitoring patients taking tamoxifen treatment. Drug Saf 2000; 22 (1): 1–11.
69. Cohen I, Rosen DJ, Altaras M et al. Tamoxifen treatment in premenopausal breast cancer patients may be associated with ovarian overstimulation, cystic formations and fibroid overgrowth. Br J Cancer 1994; 69 (3): 620–621.
70. Mourits MJ, De Vries EG, Willemse PH et al. Tamoxifen treatment and gynecologic side effects: a review. Obstet Gynecol 2001; 97 (5): 855–866.
71. Curtis RE, Freedman DM, Sherman ME et al. Risk of malignant mixed mullerian tumors after tamoxifen therapy for breast cancer. J Natl Cancer Inst 2004; 96 (1): 70–74.
72. Braithwaite RS, Chlebowski RT, Lau J et al. Meta-analysis of vascular and neoplastic events associated with tamoxifen. J Gen Intern Med 2003; 18 (11): 937–947.
73. Davies C, Pan H, Godwin J et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet 2013; 381 (9869): 805–816.
74. Gray R. aTTom: long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,934 women with early breast cancer. J Clin Oncol 2013; 31 (Suppl): abstr. 5.
75. Love CD, Muir BB, Scrimgeour JB et al. Investigation of endometrial abnormalities in asymptomatic women treated with tamoxifen and an evaluation of the role of endometrial screening. J Clin Oncol 1999; 17 (7): 2050–2054.
76. Seoud M, Shamseddine A, Khalil A et al. Tamoxifen and endometrial pathologies: a prospective study. Gynecol Oncol 1999; 75 (1): 15–19.
77. Ceci O, Bettocchi S, Nappi L et al. Comparison of hysteroscopic and hysterectomy findings to assess the diagnostic accuracy of office hysteroscopy in tamoxifen-treated patients with breast cancer. J Am Assoc Gynecol Laparosc 2003; 10 (3): 392–395.
78. Guruwadayarhalli B, Jones SE, Srinivasan V. Hysteroscopy in the diagnosis of postmenopausal bleeding. Menopause Int 2007; 13 (3): 132–134.
79. Fung MF, Reid A, Faught W et al. Prospective longitudinal study of ultrasound screening for endometrial abnormalities in women with breast cancer receiving tamoxifen. Gynecol Oncol 2003; 91 (1): 154–159.
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Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2016 Issue Supplementum 3
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