https://orcid.org/0000-0003-2714-623X
Endometrial cancer (EC) is one of the top 10 most frequently diagnosed cancers in women, with 417,000 new diagnoses made globally in 2020 [Citation1]. North America and Europe are among the geographic areas with the highest EC rates [Citation2]. According to calculations made on the Surveillance, Epidemiology, and End Results (SEER), the cumulative prevalence of EC at stage I occurs in 14% and 41% below 50 or 60 years of age, respectively. In the last decades (1992–2019), EC incidence has been progressively increasing, from 2.6 to 4.0/100,000 of individuals below 50 years of age, and from 20.1 to 24.1/100,000 among those between 50 and 59 years of age; but cancer-specific mortality has remained low. Although the number of women affected by EC during the premenopause or in the early postmenopausal stage has increased, their 18 year-survival rate is 95.9% (95% CI: 95.5–96.3%). The standard surgical management of early-stage low-grade EC includes total hysterectomy with bilateral salpingo-oophorectomy. However, the clinical management of these women and their quality of life is becoming more and more a necessity.
Ovarian conservation can be offered to premenopausal women to maintain a physiological hormonal milieu, even if adjuvant radiotherapy can still lead to premature ovarian failure [Citation3]. In some cases, the ovaries can be the location of synchronous ovarian micro-metastasis (0.4%–0.8%), macro-metastases (4.2%), ovarian cancer (3.0%–5.0%), or metachronous ovarian cancer (1.2%) [Citation3]. Despite this, overall survival of these patients does not seem to be compromised, due to adequately performed rescue treatments [Citation4]. In a meta-analysis of 7 retrospective studies, ovarian conservation proved to be safe and did not increase EC recurrence [Citation5]. Sparing of the ovaries is useful to avoid short- and long-term sequelae of induced hypoestrogenism, such as menopausal symptoms, sexual disturbances, reduced quality of life, osteoporosis, and cardiovascular diseases [Citation3]. Nevertheless, in premenopausal women ovary conservation is only around 9.5% in the US, and 8.7% in Japan [Citation4].
Hormone therapy reduces menopausal symptoms, sexual disturbances, bone loss, the risk of fractures at any skeletal site, and when started within 10 years since menopause onset, or before 60 years of age, it reduces the risk of cardiovascular disease [Citation6,Citation7]. These benefits, in addition to cognitive improvement, are more pronounced when hormone therapy is performed in women with an early or premature menopause, or ovariectomy induced menopause [Citation6,Citation7].
Women surviving EC share the same symptoms and risks as women without the disease [Citation8–10], and cardiovascular mortality is the major cause of death in this population [Citation11]. A recent multicentric retrospective cohort has revealed that hormone therapy induces a better disease-free survival than ovarian conservation in a cohort of Japanese women surviving EC [Citation4]. Despite this, hormone therapy use is 8.8% in Japan and 9.9% in the US [Citation4].
The association between the use of hormone therapy and the increased risk of EC recurrence, is still not clear. There is no evidence in vivo that after surgery, estrogens stimulate the growth of residual microscopic cancer cells [Citation12,Citation13], or that adjuvant therapy adds any type of benefit [Citation14]. Metastatic EC cells have decreased hormone receptor expression [Citation15], and it cannot be excluded that cancer progression may depend on alternative oncogenic pathways and not on estrogen exposure [Citation13,Citation16]. A recent meta-analysis has evaluated the risks associated to the use of hormone therapy in survivors of EC stage I or stage II [Citation12]. Most evidence is of poor quality, but according to survival analysis, hormone therapy did not increase the risk of EC recurrence (HR 0.90, 95% CI: 0.28–2.87) [Citation12]. This same pattern of outcomes was seen in a subgroup analysis by tumor stage, timing, duration of therapy, or whether only estrogens or estrogens plus progestins were used. As an exception, Afro-American women showed an increased risk of EC recurrence associated with hormone therapy (HR 7.58, 95% CI: 1.96–29.31) [Citation12]. Afro-descendant women have some dissimilarities from their Caucasian counterparts, in endogenous estrogen levels or in the prevalence of hormone-sensitive tumors [Citation17]. In these women EC may respond differently to hormone therapy. Still, this observation derives from a single study, and should be interpreted with caution.
Overall, studies indicate that women surviving early-stage low-grade EC can receive hormone therapy to treat their menopausal symptoms and to prevent the long-term consequences of prolonged hypoestrogenism. This treatment should be performed with only estrogens, because progestins are known to have negative impact on the breast [Citation6,Citation7] and, as data indicate, their addition does not change the risk of EC recurrence [Citation12].
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Ethics approval and consent to participate
The present editorial is exempt from ethical approval since it only uses anonymous data which has already been published or openly available in the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program at http://seer.cancer.gov/
Consent to publish
Not applicable.
Availability of data and materials
All data were extracted from previously published studies or openly available data-sets, thus they are publicly available.
Competing interests
The authors declare that they have no potential conflicts of interest relevant to this editorial.
Contribution to authorship
Drafting the article or revising it critically for important intellectual content (AC, AL). Both authors have read and approved the final manuscript.
Academic Unit of Obstetrics and Gynecology, IRCCS- San Martino Hospital of Genova, Genova, Italy;Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Infant Health (DiNOGMI), University of Genova, Genova, Italy
[email protected] Ambrogio P. Londero
Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Infant Health (DiNOGMI), University of Genova, Genova, Italy
Acknowledgements
The authors would like to thank our staff collaborating in article collection, selection, reading and in paper writing and reviewing.
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References
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