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      Tamoxifen-associated Endometrial Cancer after Treatment in Young Premenopausal Women with Breast Cancer: A Case Report

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          Abstract

          Background:

          Tamoxifen has been successfully administered as adjunctive therapy for breast cancer. However, the effect of tamoxifen as an estrogen agonist and antagonist can cause pathological changes in the uterus. The agonist effect may stimulate endometrial proliferation leading to endometrial polyps, hyperplasia, and, rarely, endometrial cancer.

          Objective:

          We present the case of tamoxifen-treated breast cancer case to better understand one of the most serious consequences, endometrial cancer.

          Case presentation:

          A 37-year-old woman came to our centre with complaints of abnormal vaginal bleeding. She has diagnosed with grade I infiltrative ductal carcinoma in 2018, with primary complaints of right breast mass and axillary lymphadenopathy. During this period, adjuvant chemotherapy was given tamoxifen 20 mg once daily. There were no complaints or relapses at a six-month follow-up over three years. In the fourth year, the patient complained of vaginal bleeding. A vaginal biopsy was performed, and the results showed low-grade endometrioid-type endometrial carcinoma. Total hysterectomy and bilateral salpingo-oophorectomy were performed with the resultant mass of up to half of the myometrial lining with metastatic negative parallax lymph nodes.

          Conclusion:

          Following tamoxifen therapy, endometrial cancer is more likely to occur in patients. Patients who experience irregular vaginal hemorrhage should have hysteroscopy or uterine ultrasound performed, and if the cause is unknown, a biopsy should be performed.

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          Most cited references9

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          Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials.

          The optimal ways of using aromatase inhibitors or tamoxifen as endocrine treatment for early breast cancer remains uncertain.
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            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

            Summary Background For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. Methods In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12 894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. Findings Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality reduction 2·8%). Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status. Among all 12 894 women, mortality without recurrence from causes other than breast cancer was little affected (691 deaths without recurrence in 6454 women allocated to continue versus 679 deaths in 6440 controls; RR 0·99 [0·89–1·10]; p=0·84). For the incidence (hospitalisation or death) rates of specific diseases, RRs were as follows: pulmonary embolus 1·87 (95% CI 1·13–3·07, p=0·01 [including 0·2% mortality in both treatment groups]), stroke 1·06 (0·83–1·36), ischaemic heart disease 0·76 (0·60–0·95, p=0·02), and endometrial cancer 1·74 (1·30–2·34, p=0·0002). The cumulative risk of endometrial cancer during years 5–14 was 3·1% (mortality 0·4%) for women allocated to continue versus 1·6% (mortality 0·2%) for controls (absolute mortality increase 0·2%). Interpretation For women with ER-positive disease, continuing tamoxifen to 10 years rather than stopping at 5 years produces a further reduction in recurrence and mortality, particularly after year 10. These results, taken together with results from previous trials of 5 years of tamoxifen treatment versus none, suggest that 10 years of tamoxifen treatment can approximately halve breast cancer mortality during the second decade after diagnosis. Funding Cancer Research UK, UK Medical Research Council, AstraZeneca UK, US Army, EU-Biomed.
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              Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data

              Summary Background Tamoxifen and raloxifene reduce the risk of breast cancer in women at elevated risk of disease, but the duration of the effect is unknown. We assessed the effectiveness of selective oestrogen receptor modulators (SERMs) on breast cancer incidence. Methods We did a meta-analysis with individual participant data from nine prevention trials comparing four selective oestrogen receptor modulators (SERMs; tamoxifen, raloxifene, arzoxifene, and lasofoxifene) with placebo, or in one study with tamoxifen. Our primary endpoint was incidence of all breast cancer (including ductal carcinoma in situ) during a 10 year follow-up period. Analysis was by intention to treat. Results We analysed data for 83 399 women with 306 617 women-years of follow-up. Median follow-up was 65 months (IQR 54–93). Overall, we noted a 38% reduction (hazard ratio [HR] 0·62, 95% CI 0·56–0·69) in breast cancer incidence, and 42 women would need to be treated to prevent one breast cancer event in the first 10 years of follow-up. The reduction was larger in the first 5 years of follow-up than in years 5–10 (42%, HR 0·58, 0·51–0·66; p<0·0001 vs 25%, 0·75, 0·61–0·93; p=0·007), but we noted no heterogeneity between time periods. Thromboembolic events were significantly increased with all SERMs (odds ratio 1·73, 95% CI 1·47–2·05; p<0·0001). We recorded a significant reduction of 34% in vertebral fractures (0·66, 0·59–0·73), but only a small effect for non-vertebral fractures (0·93, 0·87–0·99). Interpretation For all SERMs, incidence of invasive oestrogen (ER)-positive breast cancer was reduced both during treatment and for at least 5 years after completion. Similar to other preventive interventions, careful consideration of risks and benefits is needed to identify women who are most likely to benefit from these drugs. Funding Cancer Research UK.
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                Author and article information

                Journal
                Acta Inform Med
                Acta Inform Med
                Acta Informatica Medica
                Academy of Medical sciences (Bosnia and Herzegovina )
                0353-8109
                1986-5988
                2023
                : 32
                : 1
                : 85-87
                Affiliations
                [1 ]Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
                [2 ]Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
                [3 ]Division of Oncology, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
                [4 ]Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia
                [5 ]Department of Surgical Pathology, Columbia Asia General Hospital Medan, Medan, Indonesia
                Author notes
                Corresponding author: Prof. Dedy Hermansyah, M.D., Ph.D. Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Universitas Sumatera Utara. Medan, Indonesia. Address: Jl. Dr.Mansyur, No,5, Medan, Sumatera Utara, Indonesia. Contact: dedi.hermansyah@ 123456usu.ac.id ; ORCID ID: https://orcid.org/0000-0002-5980-2556.
                Article
                AIM-32-85
                10.5455/aim.2024.32.85-87
                10997177
                38585594
                924a7751-1790-4a38-a2fc-f0c1df480cf8
                © 2024 Dedy Hermansyah, Muhammad Al Anas, Muhammad Rizki Yaznil, Arvitamuriany Triyanthi Lubis, Ricky Alianto

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 November 2023
                : 19 December 2023
                Categories
                Case Report

                Bioinformatics & Computational biology
                endometrial cancer,tamoxifen,premenopausal,cancer treatment

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