Younger tamoxifen-treated breast cancer patients also had higher risk of endometrial cancer and the risk could be reduced by sequenced aromatase inhibitor use: A population-based study in Taiwan

Chu, Sung‐Chao; Hsieh, Chia‐Jung; Wang, Tso‐Fu; Hong, Mun-Kun; Chu, Tang–Yuan

doi:10.4103/tcmj.tcmj_17_19

Cited by 6 publications

(24 citation statements)

References 21 publications

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“…In previous studies, endometrial biopsy or transvaginal ultrasound was not used to screen asymptomatic women receiving TAM ( 18 , 19 ). Although another previous study reported that there was no significant increase in the incidence of endometrial cancer in young breast cancer patients aged below 40 years, the study did not analyze the presence or absence of benign endometrial symptoms and disease ( 20 ). In our study, the risk of endometrial cancer increased only in young breast cancer survivors with TAM-related endometrial benign disease.…”

Section: Discussionmentioning

confidence: 99%

Risk of Endometrial Cancer and Frequencies of Invasive Endometrial Procedures in Young Breast Cancer Survivors Treated With Tamoxifen: A Nationwide Study

et al. 2021

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BackgroundAlthough the guidelines recommend gynecological assessment and close monitoring for symptoms of endometrial cancer in postmenopausal breast cancer survivors taking tamoxifen (TAM), the risk of endometrial cancer in young breast cancer survivors has not yet been fully assessed. This study aimed to investigate the risk of developing endometrial cancer and the frequencies of gynecological examinations in young breast cancer survivors taking TAM in South Korea.MethodsA nationwide retrospective cohort study was conducted using the Health Insurance Review and Assessment Service claims data. Kaplan–Meier analyses and log-rank tests were used to assess the probability of endometrial cancer, benign endometrial conditions, and the probability of invasive endometrial procedure. To analyze the risk of endometrial cancer and benign endometrial conditions, we used a multivariable Cox proportional hazards regression model.ResultsBetween 2010 and 2015, 60,545 newly diagnosed female breast cancer survivors were included. The total person–years were 256,099 and 140 (0.23%) patients developed endometrial cancer during the study period. In breast cancer survivors aged ≥60 years [hazard ratio (HR), 5.037; 95% confidence interval (CI), 2.185–11.613], 50–59 years (HR, 4.343; 95% CI, 2.122–8.891), and 40–49 years (HR, 2.121; 95% CI, 1.068–4.213), TAM was associated with an increased risk of endometrial cancer. In subjects aged below 40 years, TAM did not significantly increase the risk of endometrial cancer. However, among the TAM subgroups, breast cancer survivors aged below 40 years [1.61 per 1,000 person–years (PY); HR, 12.460; 95% CI, 2.698–57.522] and aged 40–49 years (2.22 per 1,000 PY; HR, 9.667; 95% CI, 4.966–18.819) with TAM-related endometrial diseases showed significantly increased risks of endometrial cancer. Among the TAM subgroup with benign endometrial conditions, the ratios of the frequency of invasive diagnostic procedures to the incidence of endometrial cancer were higher in subjects under 40 than subjects aged 60 or more.ConclusionYoung breast cancer survivors with TAM-related benign endometrial diseases are at a higher risk of developing endometrial cancer. Gynecological surveillance should be tailored to the risk of endometrial cancer in young breast cancer survivors to improve the early detection of endometrial cancer and avoid unnecessary invasive procedures.

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Section: Discussionmentioning

confidence: 99%

Risk of Endometrial Cancer and Frequencies of Invasive Endometrial Procedures in Young Breast Cancer Survivors Treated With Tamoxifen: A Nationwide Study

et al. 2021

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“… 19 Unlike previous Western studies, recent studies conducted in East Asian populations showed contrasting results. A population-based cohort study 20 with a 14-year study period included 39 216 women with nonmetastatic breast cancer in Taiwan. The study found that both older (aged ≥50 years) and younger (aged 40-49 years) patients treated with tamoxifen had a higher risk (HR, 3.74; 95% CI, 1.65-8.48) of endometrial cancer than those who did not use tamoxifen.…”

Section: Discussionmentioning

confidence: 99%

“…The study found that both older (aged ≥50 years) and younger (aged 40-49 years) patients treated with tamoxifen had a higher risk (HR, 3.74; 95% CI, 1.65-8.48) of endometrial cancer than those who did not use tamoxifen. 20 A recent retrospective cohort study 17 using Health Insurance Review and Assessment Service claims data from South Korea included 60 545 women who had new diagnoses of breast cancer between 2010 and 2015. The study found that the use of tamoxifen was associated with an increased risk of endometrial cancer among women aged 40 to 49 years (HR, 2.12; 95% CI, 1.07-4.21).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…17 However, these studies could not assess the menopausal status of women and did not control for some confounding factors in their analyses, such as BMI, although differences in baseline characteristics were observed between the tamoxifen and control groups. 19,20 Tamoxifen is also associated with endometrial hyperplasia and polyp formation. 12 Although these benign diseases are not life-threatening, they might be the most common endometrial pathologies occurring in tamoxifen users.…”

Section: Discussionmentioning

confidence: 99%

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Risk of Endometrial Polyps, Hyperplasia, Carcinoma, and Uterine Cancer After Tamoxifen Treatment in Premenopausal Women With Breast Cancer

et al. 2022

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ImportanceThe association of tamoxifen use with the risk of uterine diseases, such as endometrial cancer, in premenopausal women with breast cancer remains controversial. However, many studies have reported an increased risk of uterine disease among postmenopausal tamoxifen users.ObjectiveTo investigate the association of tamoxifen use with the risk of endometrial cancer and other uterine diseases in premenopausal women with breast cancer.Design, Setting, and ParticipantsA nationwide, population-based, retrospective longitudinal cohort study with an 18-year study period was conducted using data obtained from the Korean National Health Insurance Service. Participants included premenopausal women aged 20 to 50 years with breast cancer diagnoses between January 2003 and December 2018. Data were analyzed from April to December 2021.ExposuresTamoxifen treatment.Main Outcomes and MeasuresThe incidence of uterine diseases, including endometrial cancer, hyperplasia, polyps, and other uterine cancers, was identified in the study cohort using insurance claim codes. The incidence of uterine diseases per 1000 person-years was compared between women receiving tamoxifen and those not treated with adjuvant hormone therapy. Multivariable Cox proportional hazard regression analysis was performed to determine the risk of each uterine disease.ResultsAmong 78 320 female participants with a mean (SD) age of 42.1 (6.1) years, 34 637 (44.2%) were categorized into the tamoxifen group and 43 683 (55.8%) were categorized into the control group. Among tamoxifen users, during the mean (SD) follow-up duration of 6.13 (4.15) years, the incidence of newly diagnosed endometrial polyps was 20.13 cases per 1000 person-years, that of endometrial hyperplasia was 13.49 cases per 1000 person-years, that of endometrial cancer was 2.01 cases per 1000 person-years, and that of other uterine cancers was 0.45 cases per 1000 person-years. The risk of endometrial cancer was higher in the tamoxifen group than in the control group (hazard ratio, 3.77; 95% CI, 3.04-4.66) after adjusting for age, body mass index, history of diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, gonadotropin-releasing hormone agonist treatment, and trastuzumab treatment.Conclusions and RelevanceIn this longitudinal cohort study, premenopausal Korean women with breast cancer who received tamoxifen as adjuvant hormone therapy had a significantly increased risk of endometrial hyperplasia, polyps, carcinoma, and other uterine cancers compared with those who were not treated with adjuvant hormone therapy. These findings suggest that clinicians should consider the risk of uterine disease among tamoxifen users, including premenopausal women.

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Adherence, clinical benefits, and adverse effects of endocrine therapies among women with nonmetastatic breast cancer in developing countries: A systematic review and meta‐analysis

Elshafie,

Trivedi,

Villa‐Zapata

et al. 2024

Cancer

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BackgroundDespite significant advances in breast cancer control and survival with endocrine therapies (ETs), treatment utilization and outcomes in developing countries have not been adequately explored. This review evaluated ET adherence, potential benefits, and harms in populations across developing countries.MethodsA literature search was conducted through August 2023 in five databases: PubMed, Cochrane Library, Web of Science, Global Health, and WHO Global Index Medicus. Retrieved records were screened to identify observational research presenting at least one outcome in women with nonmetastatic breast cancer in developing countries who received ET (tamoxifen or aromatase inhibitors). A random effects model was used to compute the rates of adherence, discontinuation, adverse events (AEs), disease progression, and death.ResultsA total of 104 studies met the inclusion criteria. Risk of bias was low in most studies, and a large portion of the patients involved Asians. The overall heterogeneity between studies was partially attributed to variations in study design or outcome measurement method. Results showed a pooled adherence rate of 75% (95% confidence interval [CI], 67%–81%) and a discontinuation rate of 16% (95% CI, 10%–25%). Treatment side effects and young age consistently emerged as significant predictors of nonadherence. A wide range of AEs was identified in our analysis. The estimated average rates of cancer recurrence and mortality at 5‐years were 16% and 8%, respectively.ConclusionsThe findings of this study underscore suboptimal ET use in developing countries and provide comprehensive insights into treatment experiences in the real‐world setting. Targeted strategies are warranted to enhance adherence and subsequently optimize treatment benefits.

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Younger tamoxifen-treated breast cancer patients also had higher risk of endometrial cancer and the risk could be reduced by sequenced aromatase inhibitor use: A population-based study in Taiwan

Cited by 6 publications

References 21 publications

Risk of Endometrial Cancer and Frequencies of Invasive Endometrial Procedures in Young Breast Cancer Survivors Treated With Tamoxifen: A Nationwide Study

Risk of Endometrial Cancer and Frequencies of Invasive Endometrial Procedures in Young Breast Cancer Survivors Treated With Tamoxifen: A Nationwide Study

Risk of Endometrial Polyps, Hyperplasia, Carcinoma, and Uterine Cancer After Tamoxifen Treatment in Premenopausal Women With Breast Cancer

Adherence, clinical benefits, and adverse effects of endocrine therapies among women with nonmetastatic breast cancer in developing countries: A systematic review and meta‐analysis

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