A randomized, prospective study of endometrial resection to prevent recurrent endometrial polyps in women with breast cancer receiving tamoxifen.

STUDY OBJECTIVE: To assess the role of endometrial resection in preventing recurrence of tamoxifen-associated endometrial polyps in women with breast cancer. DESIGN: Randomized, prospective study (Canadian Task Force classification I). SETTING: Tertiary university-affiliated medical center. PATIENTS: Twenty consecutive women (age range 43-61 yrs). INTERVENTIONS: Hysteroscopic removal of tamoxifen-associated endometrial polyps with or without simultaneous resection of the endometrium. MEASUREMENTS AND MAIN RESULTS: Patients were randomized to undergo (10 women) or not undergo (10) concomitant endometrial resection. They were followed for at least 18 months (range 18-24 mo), including transvaginal ultrasonography every 6 months and hysteroscopy when endometrial irregularity was noted. The main outcome variable was recurrence of endometrial polyps; occurrence of uterine bleeding was also noted. In women who underwent endometrial resection, only one had a 1 x 1-cm endometrial polyp diagnosed and removed during follow-up. Seven women remained amenorrheic, and three experienced spotting for a few days every month. In the control group, six women had recurrent endometrial polyps requiring hysteroscopic removal (two-tail Fisher's exact test p <0.06). CONCLUSION: Recurrence of endometrial polyps, one of the most common problems in patients with breast cancer receiving long-term treatment with tamoxifen, may be reduced by performing endometrial resection at the time of hysteroscopic removal of polyps. The possible risk of occult endometrial cancer is yet to be determined. (J Am Assoc Gynecol Laparosc 6(3):285-288, 1999)     

他莫昔芬对乳腺癌患者子宫内膜影响的前瞻性临床病理研究

目的:前瞻性研究他莫昔芬对乳腺癌患者子宫内膜的影响。方法:对2005年1月~2008年10月于温州医学院附属第二医院乳腺外科手术的155例乳腺癌患者进行随访,以阴道B超、宫腔镜及子宫内膜活检评价服用他莫昔芬前后子宫内膜情况。结果:可评价患者共135例,其中绝经前46例,绝经后89例。服用他莫昔芬后,未绝经组36例(78.26%)出现异常阴道流血,9例(19.56%)出现子宫内膜病变,绝经组22例(24.72%)发生异常阴道流血,出现子宫内膜病变29例(32.60%),其中术前绝经组18例(18/59,30.51%),化疗后绝经组11例(11/30,36.67%)。阴道B超对绝经后子宫内膜病变诊断的灵敏度为52.3%,特异度为90.2%,宫腔镜诊断相应的灵敏度为81.8%,特异度为100%。结论:他莫昔芬导致绝经后妇女子宫内膜病变发生增加,对绝经前妇女的影响还不确定。阴道B超可作为初步检测手段,宫腔镜检查可提高诊断的准确率。     

Baseline endometrial assessment before tamoxifen for breast cancer in asymptomatic menopausal women

OBJECTIVE: The aim of this study is to estimate the prevalence of endometrial pathology before the start of tamoxifen therapy in menopausal breast cancer patients. METHODS: Ninety-one gynecologically asymptomatic patients, suffering from estrogen receptor-positive breast cancer and scheduled for adjuvant tamoxifen, underwent pretreatment endometrial assessment. In all patients, a transvaginal ultrasonography was carried out; a double-layered endometrial stripe measuring above 4 mm was considered as abnormal. In these patients, outpatient hysteroscopy and endometrial biopsy were performed. Pathologic findings were considered the reference test in estimating the prevalence of endometrial morbidity. RESULTS: In 34 patients (37.3%) a thickened endometrium was an indication for hysteroscopic and pathologic assessment. Endometrial polyps, simple hyperplasias, and complex atypical hyperplasias were found in 10 (10.9%), 4 (4.3%), and 3 (3.2%) patients, respectively, leading to an overall prevalence of baseline endometrial morbidity of 18.6%. Established individual risk factors for development of endometrial pathology, such as body mass index, age at menarche and menopause, and parity, did not significantly differ in patients with and without endometrial abnormalities. Only patients' age (63.8 +/- 8.6 and 52.2 +/- 11.8; P = 0.03) and endometrial thickness (10.5 +/- 3.5 and 3.9 +/- 3.0; P > 0.001) were significant predictive factors of endometrial pathology. CONCLUSIONS: Menopausal women with estrogen receptor-positive breast cancer appear to have high risk of baseline subclinical endometrial abnormalities; therefore, an endometrial assessment, before the start of tamoxifen therapy, is always recommended in such patients.     

A randomized prospective study of the use of endometrial ablation for prevention of recurrent endometrial polyps in breast cancer patients receiving tamoxifen

Objective: To assess the roles of endometrial ablation in prevention of recurrence of tamoxifen-associated endometrial polyps in breast cancer patients.Design: A randomized prospective study of tamoxifen-treated patients who underwent hysteroscopic removal of endometrial polyps with or without simultaneous resection of the endometrium.Materials and Methods: Twenty consecutive women (aged 43–61 years) undergoing hysteroscopic removal of tamoxifen-associated endometrial polyps were randomized via a computer-generated random table to undergo or not to undergo concomitant endometrial ablation. All patients had undergone endometrial sampling prior to the procedure. The patients were followed for at least 18 months (range 18–24 months). The follow-up included transvaginal ultrasonography every 6 months and hysteroscopy when endometrial irregularity was noted. The main outcome variable was recurrence of endometrial polyps while the occurrence of uterine bleeding was noted.Results: In the 10 study group women, who underwent endometrial ablation, only 1 patient had a 1 × 1 cm endometrial polyp diagnosed and removed during the follow-up period. Seven of the study women remained amenorrheic, and 3 experienced spotting a few days every month. In the control group, a recurrent endometrial polyp, necessitating hysteroscopic removal, was diagnosed postoperatively in 6 women (two-tailed Fisher’s Exact test; P < .06).Conclusion: Recurrence of endometrial polyps, one of the most common problems in breast cancer patients receiving long-term treatment with tamoxifen, can be significantly reduced by performing endometrial ablation at the time of hysteroscopic removal of the polyp. The possible risk of occult endometrial cancer is yet to be determined.     

Uterine abnormalities in non menopausal women who received tamoxifen for breast cancer adjuvant therapy

OBJECTIVE: To elaborate a strategy of endometrial follow-up for premenopausal women treated with Tamoxifen as adjuvant hormonal treatment of breast cancer. PATIENTS AND METHODS: Retrospective study of 152 premenopausal patients treated with Tamoxifen in Nantes Comprehensive Cancer Center for a breast cancer from January 2003 to December 2005. Vaginal sonography was used in the follow-up of 70 of them. RESULTS: Endometrial hypertrophy was found in 26 patients. Sonohysterography and hysteroscopy allowed to find 11 polyps and three hyperplasias in the 19 women who were investigated. In our study, endometrial pathology was found in 20% of premenopausal women treated with Tamoxifen (polyps or hyperplasia). Uterine bleeding was found in half patient of this group. DISCUSSION AND CONCLUSION: Vaginal sonography monitoring could be proposed to premenopausal women treated with Tamoxifen among whom endometrial pathology is usual.     

Hysteroscopically targeted biopsies compared with blind samplings in endometrial assessment of menopausal women taking tamoxifen for breast cancer

STUDY OBJECTIVE: To determine the validity of tissue sampling accomplished by hysteroscopically targeted or blind biopsies in the assessment of endometrial morbidity associated with tamoxifen treatment. DESIGN: Retrospective, unrandomized study (Canadian Task Force classification II-2). SETTING: Public hospital. PATIENTS: One hundred seventy-six menopausal women who had an endometrial stripe of more than 4 mm on transvaginal ultrasonography. INTERVENTION: Review of histopathologic reports of patients undergoing hysteroscopy followed by targeted (94 samplings) or blind (82 samplings) endometrial biopsies. MEASUREMENTS AND MAIN RESULTS: Histopathology was considered the reference test to assess endometrial morbidity, and correlates with hysteroscopic findings were made to evaluate the validity of the two sampling procedures. Overall, in 23 women (13.0%) tissue samples were insufficient for pathologic evaluation. Functional or atrophic endometrium and cystic atrophy were found in 51 (28.8%) and 37 patients (21.0%), respectively. Polyps, hyperplasias, and carcinomas were found in 38 (21.5%), 19 (10.7%), and 6 (3.3%), respectively. Blind biopsies failed to detect 5 of 5 polyps and 33 of 37 cystic atrophies, and in 34.1% of cases provided insufficient tissue for diagnosis; however, no hyperplasias or carcinomas were undetected. All specimens collected under vision were pathologically evaluable; 34 of 38 hysteroscopic reports of cystic atrophy were confirmed, and neither endometrial polyps nor hyperplasias and carcinomas were undetected. In distinguishing between normal and abnormal endometrium, hysteroscopy showed sensitivity and negative predictive value of 100% regardless of sampling modality. We found better specificity (80.0% vs 68.9%) and positive predictive value (68.9% vs 43.7%) for hysteroscopic diagnosis when tissue was collected under vision compared with blind sampling. CONCLUSION: In women taking tamoxifen, endometrial evaluation performed by blind sampling is safe in excluding hyperplasias or carcinomas. For complete understanding of tamoxifen-associated morbidity, hysteroscopy with sampling under vision has better diagnostic compliance.     

High-grade endometrial stromal sarcoma after tamoxifen therapy for breast cancer

A case of high-grade endometrial stromal sarcoma, confined into an intrauterine polypoid growth, in a woman with a history of breast cancer who was treated with adjuvant tamoxifen. Based on the findings, a high-grade endometrial stromal sarcoma was diagnosed. The patient underwent a total hysterectomy and bilateral salpingo-oophorectomy with multiple omental biopsies. Pathological examination on multiple uterine sections showed the absence of residual tumor cells in the uterus. The endometrium showed patterns of glandular cystic hyperplasia. After 14 months of follow-up, the patient is well and free of disease. In deciding if tamoxifen therapy is warranted, all potentially life-threatening adverse events associated with tamoxifen should be considered, including endometrial adenocarcinoma or uterine sarcoma.     

Histopathologic behavior of endometrial hyperplasia during tamoxifen therapy for breast cancer

OBJECTIVE: The purpose of the present study is to prospectively evaluate the effects of tamoxifen on the pathological behavior of endometrial hyperplasias without atypia, diagnosed before the start of adjuvant endocrine therapy, in menopausal patients suffering from breast cancer. METHODS: Twenty-six patients suffering from estrogen-receptor positive breast cancer and candidate to receive adjuvant tamoxifen, were found to be affected by endometrial hyperplasias before the start of endocrine therapy. All women showed a baseline endometrial stripe, measured by transvaginal ultrasonography, thicker than 4 mm and the diagnosis of endometrial hyperplasia was made by hysteroscopy and endometrial biopsy. Two patients showing complex atypical hyperplasia underwent vaginal hysterectomy, whereas the remaining 24 patients, suffering from endometrial hyperplasia without atypia, were followed on a yearly basis during the period of tamoxifen intake, by hysteroscopy and endometrial biopsy. RESULTS: Baseline histopathology showed simple and complex hyperplasia in 20 and in 4 patients, respectively. The median follow-up period was 38 months; in particular, all patients underwent endometrial assessment after 12 months, while 22, 16, 10 and 4 patients were followed-up after 24, 36, 48 and 60 months of tamoxifen therapy, respectively. Progression from complex hyperplasia to complex atypical hyperplasia (1 patient) and from complex and simple hyperplasia to adenocarcinomas (2 patients) was found within 24 months of tamoxifen intake in 3 patients (12.5%). In 2 patients (8.3%), a progression from simple to complex hyperplasia was detected within 36 months of tamoxifen treatment. In 13 patients (54.1%), stable histology of simple or complex hyperplasia was found, whereas 6 patients (25.0%), with focal hyperplasia harbored in an endometrial polyp, showed a normalization of endometrial histology after polyp resection. CONCLUSIONS: Endometrial hyperplasias without atypia diagnosed before endocrine therapy for breast cancer in menopausal patients show an early and high progression-rate to atypical lesions under tamoxifen influence.     

Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients

Abstract. Nishimura N, Hachisuga T, Saito T, Kawarabayashi T. Subsequent endometrial carcinoma with adjuvant tamoxifen treatment in Japanese breast cancer patients.
This study aimed to detail the clinicopathologic features of endometrial carcinomas that developed in Japanese patients receiving adjuvant tamoxifen treatment for breast cancer patients. Ten endometrial carcinomas in tamoxifen-treated breast cancer patients were collected from two medical centers. The endometrial carcinomas included two stage Ia, four stage Ib, two stage Ic and two stage IIIc. Three tumors were Grade 1, six were Grade 2, and one was Grade 3. The tumor was limited to the endometrium in two cases. Myometrial invasion was limited to the inner half of the myometrium in five cases and involved the outer half in three. A mild degree of lymphovascular space invasion was identified in five cases. Deep cervical invasion was recognized in one case. The cell types comprised nine endometrioid adenocarcinomas and one serous carcinoma. Five of eight postmenopausal endometrial carcinomas were associated with polypoid endometrial lesions composed of cystically dilated atrophic and proliferative glands widely separated by fibrotic stroma. Two patients with retroperitoneal lymph node metastases died of endometrial cancer. One patient developed a contralateral breast cancer during tamoxifen treatment. No patient died of breast cancer. We did not demonstrate a higher frequency of either high-grade tumors or unfavorable histologic subtypes in tamoxifen-treated Japanese breast cancer patients.     

Sonographic, hysteroscopic, and histologic evaluation of the endometrium in postmenopausal women with breast cancer receiving tamoxifen

STUDY OBJECTIVE: To evaluate the estrogenic effects of tamoxifen on the endometrium in postmenopausal women with breast cancer. DESIGN: Consecutive study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: Thirty-three women. Interventions. All patients underwent transvaginal sonography (TVS) and color flow Doppler of endometrial vessels, hysteroscopy, and, if necessary, endometrial biopsy or other operative hysteroscopic procedures. MEASUREMENTS AND MAIN RESULTS: In four women the endometrium was thin on TVS and atrophic at hysteroscopic assessment. In 29 women with thick endometrium on TVS, hysteroscopy and endometrial biopsy showed atrophy (11 patients), hyperplasia (5), polyps (11), and well-differentiated adenocarcinoma (2). The two endometrial cancers were present in women with uterine bleeding. In women with positive histologic findings, the endometrium was significantly thicker (p = 0.04) and duration of tamoxifen therapy longer than in those with negative findings, although this was not statistically significant (p = 0.067). CONCLUSION: We believe regular assessment of the endometrium by TVS should be performed in postmenopausal patients at the start of the tamoxifen therapy, and hysteroscopy in women with a thick endometrium or postmenopausal bleeding. We believe that patients with thin endometrium on TVS at the beginning of tamoxifen therapy, who have no abnormal uterine bleeding should be screened with these examinations for 2 years.     

Recurrent endometrial polyps in postmenopausal breast cancer patients on tamoxifen

OBJECTIVES: Endometrial polyps are the most common endometrial pathology described in association with postmenopausal tamoxifen exposure, with an incidence of up to 10.7% of malignancy. Some women tend to develop recurrent polyps. However, no one has yet described any risk factors for the development of recurrent endometrial polyps in postmenopausal breast cancer tamoxifen-treated patients. METHODS: We compared various clinical features of 64 postmenopausal breast cancer tamoxifen-treated patients with a primary endometrial polyp (Group I), with those of 27 similar patients with recurrent polyps (Group 2). RESULTS: Previous exposure to hormone replacement therapy was significantly more common and duration of tamoxifen treatment, up to the diagnosis of primary endometrial polyp, was significantly shorter in Group II patients (P = 0.0217 and P = 0.0148, respectively). Logistic regression analysis revealed that the combination of shorter tamoxifen exposure before the diagnosis of primary polyp, lower parity, lower menopausal age at the diagnosis of primary polyp, and higher years of tamoxifen treatment was found to increase significantly the risk of developing recurrent endometrial polyps. Any additional year of tamoxifen treatment may increase by fivefold the risk of developing recurrent polyps. There was no significant difference in ultrasonographic endometrial thickness measured before resection of the primary polyps in both groups and before the resection of recurrent polyps in Group II. CONCLUSIONS: Previous use of HRT, shorter duration of tamoxifen exposure, and additional years of tamoxifen treatment may significantly increase the risk of developing recurrent endometrial polyps in postmenopausal breast cancer tamoxifen-treated patients.     

绝经后乳腺癌患者服用他莫昔芬发生子宫内膜息肉危险因素的探讨

目的:探讨绝经后因乳腺癌服用他莫昔芬(TAM)与子宫内膜息肉发生的相关性。方法:随诊了46例绝经后服用TAM超过6个月的妇女,其中22例经宫腔镜手术及内膜病理证实为内膜息肉(A组),24例宫腔镜检查未发现息肉(B组)。比较2组服用TAM的时间、剂量,经阴道超声波(TVS)检查的结果,并分析与子宫内膜癌相关的危险因素。结果:息肉组妇女的体重明显重于非息肉组(P=0.013),且比非息肉组服用TAM的时间长,TAM的累计剂量增加(P值均为0.002)。经阴道超声波检查示息肉组子宫内膜增厚或者宫内异常回声的发生率明显高于非息肉组(P=0.019)。结论:肥胖,长期服用TAM超过2年或累计剂量超过15g是绝经后妇女服用TAM发生子宫内膜息肉的高危因素。TVS提示内膜增厚或者宫内异常回声有诊断价值,可作为预测内膜息肉发生的指标。     

Clinicopathologic study of 56 patients with endometrial cancer during or after adjuvant tamoxifen use for their breast cancers

OBJECTIVES: The aim of this study was to describe the clinicopathologic features and prognosis of endometrial cancer patients diagnosed during or after tamoxifen treatment for breast cancer. METHODS: Fifty-six tamoxifen-related endometrial cancers were identified from 10 hospitals in Japan. Past users were defined as endometrial cancer patients diagnosed more than 12 months after the cessation of tamoxifen treatment for breast cancer. All other users were classified as recent users. RESULTS: Age at diagnosis of the endometrial cancer ranged from 29 to 81 years. Sixteen (29%) and 19 (34%) patients were nulliparous and overweight, respectively. When the patients were divided into two groups: 30 recent and 26 past users, the distribution of various clinical characteristics, except for age at the time of diagnosis for endometrial cancer and the interval between the diagnoses of two cancers, was similar for two groups. The daily dose, duration and cumulative dose also showed no significant difference between the two groups. Past users had histopathologically more invasive tumors showing prognostically more unfavorable subtypes than recent users. The background lesions including endometrial polyps and diffuse cystic changes were similar for the two groups. The cumulative 3-year survival was significantly worse for past users than for recent users (74.8% and 96.4%, respectively, P < 0.04). In multivariate analysis including recentness of tamoxifen use and age at diagnosis of endometrial cancer, the significance of past user disappeared. CONCLUSIONS: Past users had a worse prognosis of endometrial cancer with more invasive histologic features than recent users, probably because they included more elderly patients.     

Endometrial metastasis from breast cancer in a patient receiving tamoxifen therapy

Tamoxifen (TAM) is known to be associated with several types of endometrial pathologies, e.g. hyperplasias, polyps and endometrial carcinomas, sometimes of special histologic type. Here we report a rare case of endometrial metastasis from a breast carcinoma (ductal carcinoma) discovered during TAM therapy. This occurrence does not suggest that TAM treatment causes endometrial metastases of breast cancer. However, clinicians should be aware of this possibility and provide patients receiving TAM therapy with close gynecologic follow-up using liberal indications for endometrial biopsies.