Introduction: As the numbers of young patients diagnosed with early-stage endometrial carcinoma continue to rise, the question regarding fertility-preserving therapeutic options will increasingly gain significance in the future. Case Presentation: Here, we present the case of a 21-year-old patient diagnosed with symptomatic atypical endometrial hyperplasia. After 4 months of treatment with medroxyprogesterone acetate, a follow-up dilatation and curettage revealed early-stage, well-differentiated endometrioid endometrial carcinoma. Despite national guidelines recommending hysterectomy, the nulliparous patient expressed a desire to preserve her fertility. Subsequently, she underwent polyendocrine therapy with letrozole, everolimus, metformin, and Zoladex. Forty-three months after diagnosis, the patient successfully gave birth to a healthy child, and there have been no indications of recurrence thus far. Discussion: This case suggests that triple endocrine therapy may be an option for selected patients with early endometrial cancer and a desire for fertility-sparing therapy.

1.
Leitlinienprogramm Onkologie: Endometriumkarzinom. [cited 2023 Mar 14]. Available from: https://www.leitlinienprogramm-onkologie.de/leitlinien/endometriumkarzinom/.
2.
Moore
K
,
Brewer
MA
.
Endometrial cancer: is this a new disease
.
Am Soc Clin Oncol Educ Book
.
2017 May
37
435
42
.
3.
Soliman
PT
,
Oh
JC
,
Schmeler
KM
,
Sun
CC
,
Slomovitz
BM
,
Gershenson
DM
et al
.
Risk factors for young premenopausal women with endometrial cancer
.
Obstet Gynecol
.
2005 Mar
105
3
575
80
.
4.
Gallup
DG
,
Stock
RJ
.
Adenocarcinoma of the endometrium in women 40 years of age or younger
.
Obstet Gynecol
.
1984
[cited 2023 Mar 14];
64
3
417
20
.
5.
Wise
MR
,
Jordan
V
,
Lagas
A
,
Showell
M
,
Wong
N
,
Lensen
S
et al
.
Obesity and endometrial hyperplasia and cancer in premenopausal women: a systematic review
.
Am J Obstet Gynecol
.
2016 Jun
214
6
689.e1
17
.
6.
Schmid
D
,
Behrens
G
,
Keimling
M
,
Jochem
C
,
Ricci
C
,
Leitzmann
M
.
A systematic review and meta-analysis of physical activity and endometrial cancer risk
.
Eur J Epidemiol
.
2015 May
30
5
397
412
.
7.
Krebs - Datenbankabfrage. [cited 2021 Mar 27]. Available from: https://www.krebsdaten.de/Krebs/SiteGlobals/Forms/Datenbankabfrage/datenbankabfrage_stufe2_form.html.
8.
Uterine Cancer: Cancer Stat Facts. [cited 2021 Mar 28]. Available from: https://seer.cancer.gov/statfacts/html/corp.html.
9.
BiB – fakten – Durchschnittliches Alter der Mütter bei Geburt des 1. Kindes in der bestehenden Ehe in Deutschland, West- und Ostdeutschland (1960-2019). [cited 2021 Mar 27]. Available from: https://www.bib.bund.de/DE/Fakten/Fakt/F20-Alter-Muetter-bei-Erstgeburt-Deutschland-West-Ost-ab-1960.html.
10.
Tomao
F
,
Peccatori
F
,
Del Pup
L
,
Franchi
D
,
Zanagnolo
V
,
Panici
PB
et al
.
Special issues in fertility preservation for gynecologic malignancies
.
Crit Rev Oncol Hematol
.
2016 Jan
97
206
19
.
11.
Concin
N
,
Matias-Guiu
X
,
Vergote
I
,
Cibula
D
,
Mirza
MR
,
Marnitz
S
et al
.
ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma
.
Int J Gynecol Cancer
.
2021 Jan
31
1
12
39
.
12.
Duska
LR
,
Garrett
A
,
Rueda
BR
,
Haas
J
,
Chang
Y
,
Fuller
AF
.
Endometrial cancer in women 40 years old or younger
.
Gynecol Oncol
.
2001
;
83
(
2
):
388
93
.
13.
Lewin
SN
,
Herzog
TJ
,
Barrena Medel
NI
,
Deutsch
I
,
Burke
WM
,
Sun
X
et al
.
Comparative performance of the 2009 international federation of gynecology and obstetrics’ staging system for uterine corpus cancer
.
Obstet Gynecol
.
2010
;
116
(
5
):
1141
9
.
14.
Chen
M
,
Jin
Y
,
Li
Y
,
Bi
Y
,
Shan
Y
,
Pan
L
.
Oncologic and reproductive outcomes after fertility-sparing management with oral progestin for women with complex endometrial hyperplasia and endometrial cancer
.
Int J Gynaecol Obstet
.
2016 Jan
132
1
34
8
.
15.
Park
JY
,
Kim
DY
,
Kim
JH
,
Kim
YM
,
Kim
KR
,
Kim
YT
et al
.
Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002)
.
Eur J Cancer
.
2013
;
49
(
4
):
868
74
.
16.
Ushijima
K
,
Yahata
H
,
Yoshikawa
H
,
Konishi
I
,
Yasugi
T
,
Saito
T
et al
.
Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women
.
J Clin Oncol
.
2007 Jul
25
19
2798
803
.
17.
Gallos
ID
,
Yap
J
,
Rajkhowa
M
,
Luesley
DM
,
Coomarasamy
A
,
Gupta
JK
.
Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis
.
Am J Obstet Gynecol
.
2012
207
4
266.e1
12
.
18.
İşçi Bostanci
E
,
Durmuş
Y
,
Duru Çöteli
AS
,
Kayikçioğlu
F
,
Boran
N
.
Outcomes of the conservative management of the patients with endometrial intraepithelial neoplasia/endometrial cancer: wait or treat! Turkish
.
J Med Sci
.
2021
;
51
(
4
):
2066
72
.
19.
Peiretti
M
,
Congiu
F
,
Ricciardi
E
,
Maniglio
P
,
Mais
V
,
Angioni
S
.
Conservative treatment for well-differentiated endometrial cancer: when and why it should be considered in young women
.
Ecancermedicalscience
.
2019 Jan
13
892
.
20.
Hirata
T
,
Kondo
E
,
Magawa
S
,
Kubo-Kaneda
M
,
Nii
M
,
Yoshida
K
et al
.
Safety and efficacy of levonorgestrel-releasing intrauterine device in the treatment of atypical endometrial hyperplasia and early endometrial cancer
.
J Obstet Gynaecol Res
.
2022 Dec
48
12
3219
25
.
21.
Lago
V
,
Marina
T
,
Laseca Modrego
M
,
Gil-Ibañez
B
,
Rodriguez
JR
,
Domingo
J
et al
.
Fertility sparing treatment in patients with endometrial cancer (FERT-ENC): a multicentric retrospective study from the Spanish Investigational Network Gynecologic Oncology Group (SPAIN-GOG)
.
Arch Gynecol Obstet
.
2022 Sep
306
3
821
8
.
22.
Yu
X
,
Mao
W
,
Zhai
Y
,
Tong
C
,
Liu
M
,
Ma
L
et al
.
Anti-tumor activity of metformin: from metabolic and epigenetic perspectives
.
Oncotarget
.
2017
;
8
(
3
):
5619
28
.
23.
Lee
TY
,
Martinez-Outschoorn
UE
,
Schilder
RJ
,
Kim
CH
,
Richard
SD
,
Rosenblum
NG
et al
.
Metformin as a therapeutic target in endometrial cancers
.
Front Oncol
.
2018 Aug
8
341
.
24.
Xie
Y
,
Wang
YL
,
Yu
L
,
Hu
Q
,
Ji
L
,
Zhang
Y
et al
.
Metformin promotes progesterone receptor expression via inhibition of mammalian target of rapamycin (mTOR) in endometrial cancer cells
.
J Steroid Biochem Mol Biol
.
2011 Sep
126
3–5
113
20
.
25.
Jiang
Y
,
Chen
X
,
Wei
Y
,
Feng
Y
,
Zheng
W
,
Zhang
Z
.
Metformin sensitizes endometrial cancer cells to progestin by targeting TET1 to downregulate glyoxalase I expression
.
Biomed Pharmacother
.
2019 May
113
108712
.
26.
Meireles
CG
,
Pereira
SA
,
Valadares
LP
,
Rêgo
DF
,
Simeoni
LA
,
Guerra
ENS
et al
.
Effects of metformin on endometrial cancer: systematic review and meta-analysis
.
Gynecol Oncol
.
2017 Oct
147
1
167
80
.
27.
Tang
YL
,
Zhu
LY
,
Li
Y
,
Yu
J
,
Wang
J
,
Zeng
XX
et al
.
Metformin use is associated with reduced incidence and improved survival of endometrial cancer: a meta-analysis
.
BioMed Res Int
.
2017
;
2017
:
5905384
.
28.
Yang
BY
,
Gulinazi
Y
,
Du
Y
,
Ning
CC
,
Cheng
YL
,
Shan
WW
et al
.
Metformin plus megestrol acetate compared with megestrol acetate alone as fertility-sparing treatment in patients with atypical endometrial hyperplasia and well-differentiated endometrial cancer: a randomised controlled trial
.
BJOG Int J Obstet Gynaecol
.
2020 Jun
127
7
848
57
.
29.
Slomovitz
BM
,
Jiang
Y
,
Yates
MS
,
Soliman
PT
,
Johnston
T
,
Nowakowski
M
et al
.
Phase II study of everolimus and letrozole in patients with recurrent endometrial carcinoma
.
J Clin Oncol
.
2015 Mar
33
8
930
6
.
30.
Slomovitz
BM
,
Filiaci
VL
,
Walker
JL
,
Taub
MC
,
Finkelstein
KA
,
Moroney
JW
et al
.
A randomized phase II trial of everolimus and letrozole or hormonal therapy in women with advanced, persistent or recurrent endometrial carcinoma: a GOG Foundation study
.
Gynecol Oncol
.
2022 Mar
164
3
481
91
.
31.
Zou
Z
,
Tao
T
,
Li
H
,
Zhu
X
.
MTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges
.
Cell Biosci
.
2020 Mar
10
1
31
.
32.
Salvesen
HB
,
Carter
SL
,
Mannelqvist
M
,
Dutt
A
,
Getz
G
,
Stefansson
IM
et al
.
Integrated genomic profiling of endometrial carcinoma associates aggressive tumors with indicators of PI3 kinase activation
.
Proc Natl Acad Sci USA
.
2009 Mar
106
12
4834
9
.
33.
Slomovitz
BM
,
Lu
KH
,
Johnston
T
,
Coleman
RL
,
Munsell
M
,
Broaddus
RR
et al
.
A phase 2 study of the oral mammalian target of rapamycin inhibitor, everolimus, in patients with recurrent endometrial carcinoma
.
Cancer
.
2010 Dec
116
23
5415
9
.
34.
Colombo
N
,
McMeekin
DS
,
Schwartz
PE
,
Sessa
C
,
Gehrig
PA
,
Holloway
R
et al
.
Ridaforolimus as a single agent in advanced endometrial cancer: results of a single-arm, phase 2 trial
.
Br J Cancer
.
2013 Mar
108
5
1021
6
.
35.
Mackay
H
,
Welch
S
,
Tsao
MS
,
Biagi
JJ
,
Elit
L
,
Ghatage
P
et al
.
Phase II study of oral ridaforolimus in patients with metastatic and/or locally advanced recurrent endometrial cancer: NCIC CTG IND 192
.
J Clin Oncol
.
2011 May
29
15_Suppl l
5013
.
36.
Oza
AM
,
Poveda
A
,
Clamp
AR
,
Pignata
S
,
Scambia
G
,
Del Campo
JM
et al
.
A randomized phase II (RP2) trial of ridaforolimus (R) compared with progestin (P) or chemotheraphy (C) in female adult patients with advanced endometrial carcinoma
.
J Clin Oncol
.
2011 May
29
15_Suppl
5009
.
37.
Oza
AM
,
Pignata
S
,
Poveda
A
,
McCormack
M
,
Clamp
A
,
Schwartz
B
et al
.
Randomized phase II trial of ridaforolimus in advanced endometrial carcinoma
.
J Clin Oncol
.
2015 Nov
33
31
3576
82
.
38.
Bae-Jump
VL
,
Zhou
C
,
Boggess
JF
,
Whang
YE
,
Barroilhet
L
,
Gehrig
PA
.
Rapamycin inhibits cell proliferation in type i and type II endometrial carcinomas: a search for biomarkers of sensitivity to treatment
.
Gynecol Oncol
.
2010 Dec
119
3
579
85
.
39.
Bokhman
JV
.
Two pathogenetic types of endometrial carcinoma
.
Gynecol Oncol
.
1983
;
15
(
1
):
10
7
.
40.
Cheung
LWT
,
Hennessy
BT
,
Li
J
,
Yu
S
,
Myers
AP
,
Djordjevic
B
et al
.
High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability
.
Cancer Discov
.
2011 Jun
1
2
170
85
.
41.
Baselga
J
,
Campone
M
,
Piccart
M
,
Burris
HA
,
Rugo
HS
,
Sahmoud
T
et al
.
Everolimus in postmenopausal hormone-receptor – positive advanced breast cancer
.
N Engl J Med
.
2012 Feb
366
6
520
9
.
42.
Soliman
PT
,
Westin
SN
,
Iglesias
DA
,
Fellman
BM
,
Yuan
Y
,
Zhang
Q
et al
.
Everolimus, letrozole, and metformin in women with advanced or recurrent endometrioid endometrial cancer: a multi-center, single arm, phase II study
.
Clin Cancer Res
.
2020 Feb
26
3
581
7
.
43.
Richards
S
,
Aziz
N
,
Bale
S
,
Bick
D
,
Das
S
,
Gastier-Foster
J
et al
.
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology
.
Genet Med
.
2015 May
17
5
405
24
.
44.
TruSight Rapid Capture | Prepare target sequencing libraries quickly. [cited 2021 Mar 20]. Available from: https://www.illumina.com/products/by-type/clinical-research-products/trusight-rapid-capture.html.
45.
Frumovitz
M
,
Singh
DK
,
Meyer
L
,
Smith
DH
,
Wertheim
I
,
Resnik
E
et al
.
Predictors of final histology in patients with endometrial cancer
.
Gynecol Oncol
.
2004
;
95
(
3
):
463
8
.
46.
Mirza
MR
,
Bjørge
L
,
Marmé
F
,
DePont Christensen
R
,
Gil-Martin
M
,
Auranen
A
et al
.
LBA28 A randomised double-blind placebo-controlled phase II trial of palbociclib combined with letrozole (L) in patients (pts) with oestrogen receptor-positive (ER+) advanced/recurrent endometrial cancer (EC): NSGO-PALEO/ENGOT-EN3 trial
.
Ann Oncol
.
2020 Sep
31
S1160
.
47.
Zhang
X
,
Chen
D
,
Zhao
X
,
Wang
C
,
He
Y
,
Chen
Y
et al
.
Application of molecular classification to guiding fertility-sparing therapy for patients with endometrial cancer or endometrial intraepithelial neoplasia
.
Pathol Res Pract
.
2023 Jan
241
154278
.
48.
Chung
YS
,
Woo
HY
,
Lee
JY
,
Park
E
,
Nam
EJ
,
Kim
S
et al
.
Mismatch repair status influences response to fertility-sparing treatment of endometrial cancer
.
Am J Obstet Gynecol
.
2021 Apr
224
4
370.e1
13
.
You do not currently have access to this content.