Endometrial thickness and risk of breast and endometrial carcinomas in the prostate, lung, colorectal and ovarian cancer screening trial.

Postmenopausal women with higher circulating estrogen levels are at increased risk of developing breast and endometrial carcinomas. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Therefore, the hypothesis that endometrial thickness is a biological marker of excess estrogen stimulation that is associated with risk of breast and endometrial carcinomas was tested. Endometrial thickness was measured in 1,272 postmenopausal women, aged 55-74 years, who underwent transvaginal ultrasound (TVU) screening as part of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Serial endometrial thickness measurements were available for a subset of women at 1 year (n = 1,018), 2 years (n = 869) and 3 years (n = 641) after baseline. The associations between endometrial thickness and breast (n = 91) and endometrial (n = 14) carcinoma were evaluated by estimating relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression with age as the time metric. Models incorporating baseline endometrial thickness and as a time-varying covariate using all measurements were examined. Median follow-up among study participants was 12.5 years (range: 0.3-13.8 years). Compared to baseline endometrial thickness of 1.0-2.99 mm, women with baseline endometrial thickness greater than or equal to 5.0 mm had an increased risk of breast (RR = 2.00, 95% CI = 1.15-3.48) and endometrial (RR = 5.02, 95% CI = 0.96-26.36) carcinomas in models adjusted for menopausal hormone use and BMI. These data suggest that increased endometrial thickness as assessed by TVU was associated with increased risk of breast and endometrial carcinomas.

Paclitaxel and carboplatin for recurrent or persistent cancer of the cervix.

OBJECTIVE: The objective of this study was to evaluate the effectiveness and degree of toxicity of paclitaxel and carboplatin (PC) combination chemotherapy in patients with recurrent or persistent cervical carcinoma. METHODS: Fifteen patients who received PC chemotherapy for recurrent or persistent carcinoma of the cervix at the Magee-Womens Hospital from 1994-1998 were studied retrospectively. Demographic data, pathology, radiation treatment response, site of recurrence, chemotherapy response, survival rates, and toxicities were reviewed. Months of survival were calculated by the method of Kaplan-Meier from the date after initiation of chemotherapy to death or the last date of follow-up. RESULTS: Fifteen patients received PC for recurrence or persistence of disease with a median of six courses of PC (range, four to 26). Fourteen patients (93.3%) had received prior radiation, and one patient had received surgery as the primary therapy. Four (26.7%) of 15 patients had complete response and five (33.3%) had partial response for an overall clinical response rate of 60%. The median survival of all 15 patients treated with PC was 17 months (range, four to 39). Four patients demonstrated progression of disease while two patients had stable disease. Grade 3 or 4 neutropenia occurred in four patients (26.7%) while one patient (6.7%) suffered from sepsis. Three patients (20%) suffered from Grade 2 anemia and four patients (26.7%) patients developed Grade 2 or Grade 3 neuropathy. There was no incidence of nephrotoxicity. CONCLUSIONS: Paclitaxel/carboplatin chemotherapy appears to have promising activity in recurrent or persistent carcinoma of the cervix with an acceptable toxicity profile. Due to patient convenience and tolerance, consideration should be given to carboplatin as an alternative regimen to cisplatin in combination with paclitaxel.

Transvaginal ultrasound measurement of endometrial thickness as a biomarker for estrogen exposure.

OBJECTIVE: In clinical settings, transvaginal ultrasound has been used to evaluate abnormal vaginal bleeding. Because the endometrium responds to estrogens, endometrial thickness may constitute a biomarker of estrogen status in postmenopausal women. This study aimed to validate the transvaginal ultrasonographic measurement of endometrial thickness as an estrogen biomarker in asymptomatic, postmenopausal women by demonstrating an association between endometrial thickness and risk factors known to be associated with estrogen exposure. METHOD: Endometrial thickness was measured in 1,271 women ages 55 to 74 years who underwent transvaginal ultrasound screening as part of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A questionnaire, completed before screening, provided risk factor information, including reproductive and hormone use histories. RESULTS: Endometrial thickness measurements ranged from 1 to 32 mm (median 3.0 mm). The frequencies of thicker endometrium (> or =3.0 mm), according to body mass index (BMI) quartile, were 55.2%, 66.1%, 69.7%, and 76.7% (P < 0.0001). The frequencies of thicker endometrium were 57.8%, 58.3%, and 82.6% among never users, ex-users, and current users of hormone replacement therapy (HRT), respectively (P < 0.0001). Other factors associated with thicker endometrium included age, marital status, history of uterine fibroids, years since menopause, and history of hypertension. Statistically significant associations were not seen in analyses limited to current HRT users (n = 461). In multiple variable analysis (R2 = 0.08), current HRT use (P < 0.0001) and higher BMI (P < 0.0001) were independently associated with thicker endometrium. CONCLUSION: In postmenopausal women, factors reflecting exogenous (current HRT use) and endogenous (BMI) estrogen exposure were associated with increased endometrial thickness as measured during screening transvaginal ultrasound. Practical limitations related to screening transvaginal ultrasound include measurement variability, lack of information regarding type or dose of HRT, and problems of differentiating true endometrial thickening from unrecognized endometrial polyps or fluid accumulations. Constrained by these limitations, these results partially validate a transvaginal ultrasound measurement of endometrial thickness as a potential biomarker related to estrogen status.

Hormone replacement therapy formulations and risk of epithelial ovarian carcinoma.

OBJECTIVE: Hormone replacement therapy (HRT) has been inconsistently linked to ovarian cancer. Estrogen formulations in HRT vary in their effects on estrogen-sensitive target tissues, such as the ovary. The aim of the study is to evaluate the impact of various HRT formulations and their characteristics of use on the risk of epithelial ovarian carcinoma (EOC). METHODS: We assessed the association between the use of HRT and the risk of invasive EOC in women participating in a population-based, case-control study conducted in the Delaware Valley from 1994 to 1998. Cases aged 45 or above at diagnosis (n = 484) were compared to community controls (n = 926) frequency matched by age and area of residence. Information on HRT formulation, timing, and duration were obtained by in-person interview by trained interviewers. HRT formulations were classified as opposed (estrogen + progestin) or unopposed (estrogen alone). They were further categorized according to the estrogen component as either conjugated equine estrogen (CEE), the most common formulation, or non-CEE. Multivariate unconditional logistic regression analyses were used to adjust for age at diagnosis, number of live births, use of oral contraceptives, family history of ovarian carcinoma, and history of tubal ligation. RESULTS: Overall, no association was found between any use of HRT and EOC. Although use of unopposed non-CEE was associated with a significant decrease in risk among hysterectomized women (OR = 0.17, 95% CI = 0.04,0.82), this was not true for women with an intact uterus (OR = 1.14, 95% CI = 0.44,2.98; P for interaction = 0.049). No significant differences in EOC risk were observed for other HRT formulations. CONCLUSIONS: Our results did not suggest any consistent pattern of altered risk for EOC and the overall use of HRT by specific formulations of HRT.