Higher Incidence Of Endometrial Cancer Research Articles

P-317 Risk of endometrial polyps and hyperplasia after tamoxifen treatment in women with breast cancer: a population-based study in Taiwan

Abstract Study question This study aimed to examine the association between tamoxifen treatment and incident risks of uterine disease among breast cancer patients in Taiwan. Summary answer We found tamoxifen treatment group may have greater risk of endometrial polyps and hyperplasia than unexposured group after adjusting for age and body mass index. What is known already In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) breast cancer treatment trail reported that the women continue tamoxifen up to 10 years, compared with 5 years may reduce breast cancer recurrence and mortality rate. However, tamoxifen use has been reported to be associated with the cumulative risk of subsequently endometrial cancer during 5–14 years was 3.1%. Specifically, several Western studies have showed that the high incidence of endometrial cancer in breast cancer survivors with tamoxifen treatment. Study design, size, duration We conducted a retrospective cohort study using population-based data from Taiwan Cancer Registry and the National Health Insurance Research Database (NHIRD), and the National Population Registry Data set from 2011 to 2020. Participants/materials, setting, methods A total 138,934 newly diagnosed breast cancer female patients with age greater than 18 years old were included. We further used a 1-to-1 propensity score matching to generate comparable exposure and un-exposure groups. Cox proportional hazard regression models were used to examine the research question. All statistical analysis was performed using SAS version 9.4, and p-values < 0.05 were considered statistically significant Main results and the role of chance Incidence rate ratio (IRR) to compare incidence rate of uterine disease between tamoxifen treatment groups and unexposed group, adjusting for age and BMI. Our results showed that IRR were 1.36, 0.33, 3.73, 0.63, endometrial polyps, endometrial carcinoma, endometrial hyperplasia and uterine carcinosarcoma, respectively. This study found possible correlations between tamoxifen exposure with endometrial polyps and hyperplasia among breast cancer. During the 10-year study period, tamoxifen group did not significantly increase the risk of endometrial cancer in breast cancer survivors at aged 40 and over. Limitations, reasons for caution Our cohort study with 10-year period is its short study period, Tamoxifen group did not significantly increase the risk of endometrial cancer. Wider implications of the findings This cohort study found higher endometrial polyps and hyperplasia incidence rates among women with breast cancer who received tamoxifen women than those not treated with tamoxifen. Results of this study suggest that clinicians should consider the risk of uterine disease among tamoxifen use and counsel patients accordingly. Trial registration number KMUHIRB-G(II)20200217

Intratumoral environment of premenopausal endometrial cancers in South Texas Hispanic patients

Objective: There is a high incidence of endometrial cancer (EC) in young Hispanic women residing in south Texas. EC is a devastating disease in young women who desire childbearing. Medical management with progestin therapy is rarely effective. Recent evidence has shown that cancers have a unique intratumoral environment that allows them to make their own growth factors. In this study we sought to characterize the intratumoral environment of EC in a cohort of premenopausal patients.

Gynecological Cancer as a Second Malignancy in Patients With Breast Cancer.

The aim of this study was to determine the incidence and risk factors for gynecological cancer as second malignancy (SM) after treatment of breast cancer (BC). Between January 1985 and December 2007, a total of 2756 patients with BC were analyzed for gynecological cancers as an SM. Analysis was carried out for patient-, disease-, and treatment-related characteristics. The Cox proportional hazards regression model was used to estimate the relative risk of gynecologic malignancies. The median age at BC diagnosis was 49 years and median follow-up of 14 years. In total, 25 cases of gynecological cancer were noted with an incidence of 0.9%. We observed 9 ovarian and endometrium (0.3%) as well as 7 uterine cervix (0.25%) cancers. Family history of BC was the most significant risk factor for SM (relative risk, 7.4; 95% confidence interval, 3.03-18.28; P<0.001). Women with a family history of BC had a higher incidence of endometrial (12%) and ovarian (16%) cancer compared with those who have no family history (0.1%, P = 0.003). Statistically significant higher incidence of endometrial cancer was seen in patients undergoing hormonal therapy (0.4%) as compared with those who are not undergoing hormonal therapy (0.1%, P = 0.001). Most of the endometrial (88.9%) and cervical (71%) cancers were detected at an early stage but ovarian cancers (66.6%) in advanced stage. Chemotherapy and radiotherapy did not increase the risk of gynecological SM. Women with BC are at risk of developing a second primary gynecological malignancy particularly of endometrium and ovary. Family history of BC was a high risk factor for gynecologic SM. These patients should be followed up for its early detection.

Coexisting endometrial cancer in patients with a preoperative diagnosis of atypical endometrial hyperplasia.

To investigate the possibility of coexisting endometrial cancer (EC) in patients with atypical endometrial hyperplasia (AEH). Forty-six consecutive women who underwent hysterectomy for AEH were analyzed. Final histopathological evaluation of hysterectomy specimens revealed EC in 11 patients (23.9%). Preoperative diagnosis of AEH was established by pipelle biopsy in eight patients and curettage was performed in the remaining patients. Of the patients with pipelle biopsy, two had a diagnosis of EC (25%), whereas nine women who underwent curettage, were further diagnosed as having EC (23.7%) (P > 0.05). Four (13.3%) of 30 women who had frozen sections at hysterectomy, were diagnosed with EC. Diagnosis of EC was missed in two patients (50%) at frozen section. In contrast, seven of 16 women (43.7%) who did not have frozen section, had EC. A relatively high incidence of EC is seen in patients with a diagnosis of AEH. Diagnostic results of pipelle biopsy and curettage were comparable. Frozen sections of hysterectomy specimens does not guarantee to exclude the possibility of EC, especially in patients with no myometrial invasion.

The CAG repeats in exon 1 of the androgen receptor gene are significantly longer in endometrial cancer patients

Human androgen receptor (AR) gene contains polymorphic CAG repeats in the N-terminal domain that influence transcription efficiency. The CAG repeats encode a poly-glutamine tract, which has a length that is inversely and linearly related to AR activity. It has been observed that longer CAG repeats impose a lower transactivation activity on AR and have a decreased binding affinity for androgens. Androgens have an anti-proliferative effect on endometrial cells. We hypothesize that the length of CAG repeats on the AR gene can predict higher incidence of endometrial cancer. To test this hypothesis, the genetic distributions of CAG repeats on AR gene polymorphisms were investigated in endometrial cancer patients and healthy controls. Genotyping and a χ 2 test revealed that the distribution of CAG repeats was significantly different between the endometrial cancer patients and normal healthy controls ( P<0.001). The endometrial cancer patients had longer alleles than normal healthy controls. The longer CAG repeats in the AR gene may cause a decrease of transactivation function in the receptor, weaken an anti-proliferative effect on uterine endometrial cells, and promote carcinogenesis of the uterine endometrial cells. The findings suggest that the CAG repeats in the AR gene may be important in the carcinogenesis of uterine endometrial cells.

The effects of tamoxifen on proliferation and steroid receptor expression in postmenopausal endometrium.

To study the effects of tamoxifen on the proliferation index and oestrogen receptor (ER) and progesterone receptor (PR) expression in postmenopausal endometrium. A total of 125 endometrial specimens of postmenopausal women, comprising benign endometria from tamoxifen users (n = 35) and non-users (n = 24), and endometrial cancer from tamoxifen users (n = 15) and non-users (n = 51), were immunohistochemically examined using MIB-1, anti-ER, and anti-PR antibodies in endometrial epithelium and stroma. In benign endometrium the mean MIB-1 index in the epithelium was higher in tamoxifen users than in non-users (mean, 13% (SD, 13%) v mean, 2% (SD, 2%); p < 0.05), whereas in endometrial cancer the MIB-1 index was higher, but similar in tamoxifen users and non-users (mean, 32% (SD, 24%) and mean, 35% (SD, 18%)). The expression of ER was comparably high in benign epithelium from tamoxifen users and non-users (97% and 92%, respectively), but in endometrial cancer it was lower in tamoxifen users (60% and 88%; p < 0.05). The expression of PR in stromal cells was higher in tamoxifen users, both in benign (84% v 54%) and in malignant endometrium (33% v 10%; p < 0.05). The proliferation index (as measured by MIB-1) in benign endometrial epithelium is higher in tamoxifen users than in non-users, and this might play a role in the reported higher incidence of endometrial cancer in postmenopausal tamoxifen users. The increased expression of PR in stroma from tamoxifen users with both benign and malignant endometrium demonstrates an additional oestrogenic effect of tamoxifen on the endometrial stroma.

Endometrial Cancer in Elderly Women: A Histologic and Steroid Receptor Study

Background: Information on steroid receptor content in endometrial tissue of aging women is limited and somewhat controversial. The high incidence of endometrial cancer (EC) and the implication of hormone replacement therapy (HRT) in this group prompted the investigation of steroid receptors and endometrial cancer histology in the elderly. Objective: Review of histologic characteristics correlated with estrogen and progesterone receptors (ER and PR) status in EC in women over 75 years of age in order to determine the prevalence of a more aggressive endometrial neoplasm arising in late postmenopausal atrophic endometrium of elderly patients. Methods: Histologic slides and deeper sections stained immunohistologically for ER/PR from 54 cases of EC in women aged 75–95 years were reviewed. The histologic characteristics and degree of differentiation were correlated with the steroid receptor status, evaluated on a scale of 0–3. Benign endometrial tissue from women of the same group was used as controls. Results: The 57.4% endometrioid adenocarcinomas were mostly moderately and poorly differentiated. The nonendometrioid carcinomas were anaplastic, papillary, clear cell, squamous cell, mixed müllerian and nongestational choriocarcinoma. The staining intensity for ER/PR decreased with the degree of dedifferentiation being weak or absent in nonendometrioid tumors. Conclusion: Elderly patients have less differentiated EC displaying histologically nonendometrioid patterns (‘alienation’) with no differential loss of receptors in cancer. ER/PR are partly preserved in endometrioid tumors and controls. We conclude that differential loss of receptor capacity is not a factor in pathogenesis of this age-related cancer.

Operative hysteroscopy procedure on an unsuspected mixed Müllerian tumour of the uterus

In the past few years hysteroscopy has become a useful method, improving the specificity of the diagnosis of intrauterine lesions. Today, operative hysteroscopy is commonly performed for the evaluation and treatment of benign intrauterine lesions, including postmenopausal bleeding. We present a case of rapid peritoneal and liver dissemination after operative hysteroscopy on an unsuspected mixed Müllerian tumour of the uterus. We suggest that irrigation of the endometrial cavity during the operative hysteroscopic procedure may disseminate the disease and may change the prognosis. Our case report should lead to a cautious evaluation of the indications for and limitations of the operative hysteroscopy procedure, in view of the high incidence of endometrial cancer in postmenopausal women.

Accumulation of Ethinylestradiol in Blood and Endometrium of Women Taking Oral Contraceptives: The Sequential Therapy

A radioimmunoassay to quantitate ethinylestradiol (EE-2) in both plasma and endometrium is described. In 29 women under sequential oral contraceptive therapy (chlormadinone acetate, 2 mg, plus mestranol, 80 microgram) for 6 to 84 months, a single blood sample and a single endometrial sample were simultaneously obtained on different days of the pseudomenstrual cycle. In 24 women under 40 years of age the mean plasma EE-2 concentrations were similar during the first (989 +/- 94 pg/ml) and the second half of the cycle (1053 +/- 186 pg/ml) (P greater than 0.05). A similar finding was observed with regard to mean endometrial EE-2 concentrations (3.55 +/- 2.1 and 5.89 +/- 1.7 microgram/gm of wet tissue, respectively). On the other hand, five women over 40 years of age had plasma EE-2 concentrations similar to those of the previous group, but the mean endometrial EE-2 concentrations was 0.9 +/- 0.6 microgram/gm of wet tissue (P less than 0.05). Although plasma follicle-stimulating hormone and luteinizing hormone did not show midcycle peak values, complete suppression of both gonadotropins was not observed. These results show that endometrium has a great ability to concentrate EE-2, and this ability seems to be greater in women below age 40 than above. Whether or not this observation might be related to the known higher incidence of endometrial cancer in women less than 40 years old who have been under chronic sequential oral contraceptive therapy cannot be disclosed from this limited number of determinations.