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Journal of Assisted Reproduction and Genetics
Published in: Journal of Assisted Reproduction and Genetics 4/2020

01-04-2020 | Fertility | Fertility Preservation

Outcomes of ovarian stimulation and fertility preservation in breast cancer patients with different hormonal receptor profiles

Authors: Jacques Balayla, Togas Tulandi, William Buckett, Hananel Holzer, Naama Steiner, Guy Shrem, Alexander Volodarsky-Perel

Published in: Journal of Assisted Reproduction and Genetics | Issue 4/2020

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Abstract

Purpose

To evaluate fertility preservation outcomes in breast cancer women with different hormonal receptor profiles before oncological treatment.

Methods

The study population included women with a diagnosis of breast cancer who underwent fertility preservation from 2009 until 2018 at a university-affiliated tertiary hospital. Stimulation parameters and fertility preservation outcomes were compared among the following receptor-specific profile groups: (1) estrogen receptor positive (ER+) versus estrogen receptor negative (ER−), (2) triple-negative breast cancer (TNBC) versus estrogen and progesterone receptor positive (ER+/PR+), and (3) TNBC versus non-TNBC. Primary outcome was the total number of mature oocytes. Secondary outcomes included the number of retrieved oocytes, the peak estradiol level, and the number of follicles > 14 mm on the final oocyte maturation trigger day.

Results

A total of 155 cycles were included in the final analysis. These were divided into the exposure groups of ER+ (n = 97), ER− (n = 58), ER+/PR+ (n = 85), TNBC (n = 57), and non-TNBC (n = 98). Cycle outcomes revealed similar number of retrieved oocytes and follicles > 14 mm on the trigger day. Women with TNBC had significantly lower number of mature oocytes compared with those with ER + PR+ (7 (5–11) versus 9 (7–15); p = 0.02) and non-TNBC (7 (5–11) versus 9 (7–16); p = 0.01) status. Triple-negative breast cancer profile was associated with a significant reduction in the chance of developing over 10 mature oocytes (OR 0.41; 95% CI 0.19–0.92).

Conclusion

Among the different hormonal receptor profiles in breast cancer, the TNBC subtype has a negative effect on fertility preservation outcomes.
Literature
1.
Singletary SE, Allred C, Ashley P, Bassett LW, Berry D, Bland KI, et al. Revision of the American joint committee on cancer staging system for breast cancer. J Clin Oncol. 2002;20:3628–36.PubMed
2.
Blows FM, Driver KE, Schmidt MK, Broeks A, Van Leeuwen FE, Wesseling J, et al. Subtyping of breast cancer by immunohistochemistry to investigate a relationship between subtype and short and long term survival: a collaborative analysis of data for 10,159 cases from 12 studies. PLoS Med. 2010;7:e1000279.PubMedPubMedCentral
3.
Allred D, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11:155–68.PubMed
4.
Allemani C, Sant M, Berrino F, Aareleid T, Chaplain G, Coebergh JW, et al. Prognostic value of morphology and hormone receptor status in breast cancer – a population-based study. Br J Cancer. 2004;91:1263–8.PubMedPubMedCentral
5.
Osborne CK, Yochmowitz MG, Knight WA III, McGuire WL. The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer. 1980;46:2884–8.PubMed
6.
Onitilo AA, Engel JM, Greenlee RT, Mukesh BN. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res. 2009;7:4–13.PubMedPubMedCentral
7.
Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13:4429–34.PubMed
8.
Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, Couture J, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor–positive tumors. N Engl J Med. 1989;320:479–84.PubMed
9.
Badowska-Kozakiewicz AM, Patera J, Sobol M, Przybylski J. The role of oestrogen and progesterone receptors in breast cancer – immunohistochemical evaluation of oestrogen and progesterone receptor expression in invasive breast cancer in women. Contemp Oncol. 2015;19:220–5.
10.
McCormack VA, Joffe M, van den Berg E, Broeze N, Silva Idos S, Romieu I, et al. Breast cancer receptor status and stage at diagnosis in over 1,200 consecutive public hospital patients in Soweto, South Africa: a case series. Breast Cancer Res. 2013;15:R84.PubMedPubMedCentral
11.
Chen L, Li CI, Tang MT, Porter P, Hill DA, Wiggins CL, et al. Reproductive factors and risk of luminal, HER2-overexpressing and triple negative breast cancer among multiethnic women. Cancer Epidemiol Biomark Prev. 2016;25:1297–304.
12.
Dawood S, Broglio K, Gong Y, Yang WT, Cristofanilli M, Kau SW, et al. Prognostic significance of HER-2 status in women with inflammatory breast cancer. Cancer. 2008;112:1905–11.PubMed
13.
Hickey M, Peate M, Saunders C, Friedlander M. Breast cancer in young women and its impact on reproductive function. Hum Reprod Update. 2009;15:323–39.PubMedPubMedCentral
14.
Oktem O, Oktay K. Fertility preservation for breast cancer patients. Semin Reprod Med. 2009;27:486–92.PubMed
15.
Ethics Committee of the American Society for Reproductive Medicine. Fertility preservation and reproduction in patients facing gonadotoxic therapies: an Ethics Committee opinion. Fertil Steril. 2018;110:380–6.
16.
Stoop D, Cobo A, Silber S. Fertility preservation for age-related fertility decline. Lancet. 2014;384:1311–9.PubMed
17.
Quinn GP, Vadaparampil ST, Lee J-H, Jacobsen PB, Bepler G, Lancaster J, et al. Physician referral for fertility preservation in oncology patients: a national study of practice behaviors. J Clin Oncol. 2009;27:5952–7.PubMed
18.
Oktay K, Harvey BE, Partridge AH, Quinn GP, Reinecke J, Taylor HS, et al. Fertility preservation in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018;36:1994–2001.PubMed
19.
Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge AH, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31:2500–10.PubMedPubMedCentral
20.
Decanter C, Robin G, Mailliez A, Sigala J, Morschhauser F, Ramdane N, et al. Prospective assessment of follicular growth and the oocyte cohort after ovarian stimulation for fertility preservation in 90 cancer patients versus 180 matched controls. Reprod BioMed Online. 2018;36:543–51.PubMed
21.
Anderson RA, Brewster DH, Wood R, Nowell S, Fischbacher C, Kelsey TW, et al. The impact of cancer on subsequent chance of pregnancy: a population-based analysis. Hum Reprod. 2018;33:1281–90.PubMedPubMedCentral
22.
Friedler S, Koc O, Gidoni Y, Raziel A, Ron-El R. Ovarian response to stimulation for fertility preservation in women with malignant disease: a systematic review and meta-analysis. Fertil Steril. 2012;97:125–33.PubMed
23.
Domingo J, Guillen V, Ayllon Y, Martinez M, Munoz E, Pellicer A, et al. Ovarian response to controlled ovarian hyperstimulation in cancer patients is diminished even before oncological treatment. Fertil Steril. 2012;97:930–4.PubMed
24.
Tulandi T, Holzer H. Effects of malignancies on the gonadal function. Fertil Steril. 2012;98:813–5.PubMed
25.
Volodarsky-Perel A, Cohen Y, Arab S, Son WY, Suarthana E, Dahan MH, et al. Effects of cancer stage and grade on fertility preservation outcome and ovarian stimulation response. Hum Reprod. 2019;34:530–8.PubMed
26.
Oktay K, Kim JY, Barad D, Babayev SN. Association of BRCA1 mutations with occult primary ovarian insufficiency: a possible explanation for the link between infertility and breast/ovarian cancer risks. J Clin Oncol. 2010;28:240–4.PubMed
27.
Cakmak H, Katz A, Cedars MI, Rosen MP. Effective method for emergency fertility preservation: random-start controlled ovarian stimulation. Fertil Steril. 2013;100:1673–80.PubMed
28.
Escudero E, Bosch E, Crespo J, Simón C, Remohí J, Pellicer A. Comparison of two different starting multiple dose gonadotropin-releasing hormone antagonist protocols in a selected group of in vitro fertilization–embryo transfer patients. Fertil Steril. 2004;81:562–6.PubMed
29.
Oktay K, Buyuk E, Libertella N, Akar M, Rosenwaks Z. Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J Clin Oncol. 2005;23:4347–53.PubMed
30.
Creux H, Monnier P, Son W-Y, Tulandi T, Buckett W. Immature oocyte retrieval and in vitro oocyte maturation at different phases of the menstrual cycle in women with cancer who require urgent gonadotoxic treatment. Fertil Steril. 2017;107:198–204.PubMed
31.
Chian RC, Gilbert L, Huang JY, Demirtas E, Holzer H, Benjamin A, et al. Live birth after vitrification of in vitro matured human oocytes. Fertil Steril. 2009;91:372–6.PubMed
32.
33.
Cottam D, Rees R. Regulation of matrix metalloproteinases - their role in tumor invasion and metastasis. Int J Oncol. 1993;2:861–72.PubMed
34.
Dranoff G. Cytokines in cancer pathogenesis and cancer therapy. Nat Rev Cancer. 2004;4:11–22.PubMed
35.
Blumenfeld Z, Avivi I, Eckman A, Epelbaum R, Rowe JM, Dann EJ. Gonadotropin-releasing hormone agonist decreases chemotherapy-induced gonadotoxicity and premature ovarian failure in young female patients with Hodgkin lymphoma. Fertil Steril. 2008;89:166–73.PubMed
36.
Bedaiwy MA, Abou-Setta AM, Desai N, Hurd W, Starks D, El-Nashar SA, et al. Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: a systematic review and meta-analysis. Fertil Steril. 2011;95:906–14.PubMed
37.
Smith MF, Ricke WA, Bakke LJ, Dow MP, Smith GW. Ovarian tissue remodeling: role of matrix metalloproteinases and their inhibitors. Mol Cell Endocrinol. 2002;191:45–56.PubMed
38.
Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med. 2010;363:1938–48.PubMed
39.
Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, 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;381:805–16.PubMedPubMedCentral
40.
Bardin A, Boulle N, Lazennec G, Vignon F, Pujol P. Loss of ERβ expression as a common step in estrogen-dependent tumor progression. Endocr Relat Cancer. 2004;11:537–51.PubMedPubMedCentral
41.
Early Breast Cancer Trialists’ Collaborative Group (EBCTC). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.
42.
Lara-Medina F, Pérez-Sánchez V, Saavedra-Pérez D, Blake-Cerda M, Arce C, Motola-Kuba D, et al. Triple-negative breast cancer in Hispanic patients: high prevalence, poor prognosis, and association with menopausal status, body mass index, and parity. Cancer. 2011;117:3658–69.PubMed
43.
Lee A, Djamgoz MBA. Triple negative breast cancer: emerging therapeutic modalities and novel combination therapies. Cancer Treat Rev. 2018;62:110–22.PubMed
44.
Boyle P. Triple-negative breast cancer: epidemiological considerations and recommendations. Ann Oncol. 2012;23:vi7–12.PubMed
45.
Cleator S, Heller W, Coombes RC. Triple-negative breast cancer: therapeutic options. Lancet Oncol. 2007;8:235–44.PubMed
46.
Jamnongjit M, Gill A, Hammes SR. Epidermal growth factor receptor signaling is required for normal ovarian steroidogenesis and oocyte maturation. Proc Natl Acad Sci U S A. 2005;102:16257–62.PubMedPubMedCentral
47.
Jayaprakasan K, Chan Y, Islam R, Haoula Z, Hopkisson J, Coomarasamy A, et al. Prediction of in vitro fertilization outcome at different antral follicle count thresholds in a prospective cohort of 1,012 women. Fertil Steril. 2012;98:657–63.PubMed
48.
Drakopoulos P, Blockeel C, Stoop D, Camus M, de Vos M, Tournaye H, et al. Conventional ovarian stimulation and single embryo transfer for IVF/ICSI. How many oocytes do we need to maximize cumulative live birth rates after utilization of all fresh and frozen embryos? Hum Reprod. 2016;31:370–6.PubMed
49.
Sunkara SK, Rittenberg V, Raine-Fenning N, Bhattacharya S, Zamora J, Coomarasamy A. Association between the number of eggs and live birth in IVF treatment: an analysis of 400 135 treatment cycles. Hum Reprod. 2011;26:1768–74.PubMed
50.
Alvarez RM, Ramanathan P. Fertility preservation in female oncology patients: the influence of the type of cancer on ovarian stimulation response. Hum Reprod. 2018;33:2051–9.PubMed
51.
Lefebvre T, Mirallie S, Leperlier F, Reignier A, Barriere P, Freour T. Ovarian reserve and response to stimulation in women undergoing fertility preservation according to malignancy type. Reprod BioMed Online. 2018;37:201–7.PubMed
52.
Young S, Pilarski RT, Donenberg T, Shapiro C, Hammond LS, Miller J, et al. The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer. 2009;9:86.PubMedPubMedCentral
53.
Greenup R, Buchanan A, Lorizio W, Rhoads K, Chan S, Leedom T, et al. Prevalence of BRCA mutations among women with triple-negative breast cancer (TNBC) in a genetic counseling cohort. Ann Surg Oncol. 2013;20:3254–8.PubMed
54.
Cobo A, García-Velasco J, Domingo J, Pellicer A, Remohí J. Elective and onco-fertility preservation: factors related to IVF outcomes. Hum Reprod. 2018;33:2222–31.PubMed
55.
Cobo A, García-Velasco JA, Coello A, Domingo J, Pellicer A, Remohí J. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril. 2016;105:755–64.PubMed
56.
Sedgwick P. Multiple significance tests: the Bonferroni correction. BMJ. 2012;344:e509.
Metadata
Title
Outcomes of ovarian stimulation and fertility preservation in breast cancer patients with different hormonal receptor profiles
Authors
Jacques Balayla
Togas Tulandi
William Buckett
Hananel Holzer
Naama Steiner
Guy Shrem
Alexander Volodarsky-Perel
Publication date
01-04-2020
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 4/2020
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-020-01730-9

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