Preoperative breast MRI and mortality in older women with breast cancer.

PURPOSE: The survival benefit from detecting additional breast cancers by preoperative magnetic resonance imaging (MRI) continues to be controversial. METHODS: We followed a cohort of 4454 women diagnosed with non-metastatic breast cancer (stage I-III) from 2/2005-6/2010 in five registries of the breast cancer surveillance consortium (BCSC). BCSC clinical and registry data were linked to Medicare claims and enrollment data. We estimated the cumulative probability of breast cancer-specific and all-cause mortality. We tested the association of preoperative MRI with all-cause mortality using a Cox proportional hazards model. RESULTS: 917 (20.6%) women underwent preoperative MRI. No significant difference in the cumulative probability of breast cancer-specific mortality was found. We observed no significant difference in the hazard of all-cause mortality during the follow-up period after adjusting for sociodemographic and clinical factors among women with MRI (HR 0.90; 95% CI 0.72-1.12) compared to those without MRI. CONCLUSION: Our findings of no breast cancer-specific or all-cause mortality benefit supplement prior results that indicate a lack of improvement in surgical outcomes associated with use of preoperative MRI. In combination with other reports, the results of this analysis highlight the importance of exploring the benefit of preoperative MRI in patient-reported outcomes such as women's decision quality and confidence levels with decisions involving treatment choices.

Mammographic screening detects low-risk tumor biology breast cancers.

Overdiagnosis of breast cancer, i.e. the detection of slow-growing tumors that would never have caused symptoms or death, became more prevalent with the implementation of population-based screening. Only rough estimates have been made of the proportion of patients that are overdiagnosed and identification of those patients is difficult. Therefore, the aim of this study is to evaluate whether tumor biology can help identify patients with screen-detected tumors at such a low risk of recurrence that they are likely to be overdiagnosed. Furthermore, we wish to evaluate the impact of the transition from film-screen mammography (FSM) to the more sensitive full-field digital mammography (FFDM) on the biology of the tumors detected by each screening-modality. All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041) accrued 2007-2011, who participated in the national screening program (biennial screening ages 50-75) were included (n = 1,165). We calculated the proportions of high-, low- and among those the ultralow-risk tumors according to the 70-gene signature for patients with screen-detected (n = 775) and interval (n = 390) cancers for FSM and FFDM. Screen-detected cancers had significantly more often a low-risk tumor biology (68 %) of which 54 % even an ultralow-risk compared to interval cancers (53 % low-, of which 45 % ultralow-risk (p = 0.001) with an OR of 2.33 (p < 0.0001; 95 % CI 1.73-3.15). FFDM detected significantly more high-risk tumors (35 %) compared to FSM (27 %) (p = 0.011). Aside from favorable clinico-pathological factors, screen-detected cancers were also more likely to have a biologically low-risk or even ultralow-risk tumor. Especially for patients with screen-detected cancers the use of tools, such as the 70-gene signature, to differentiate breast cancers by risk of recurrence may minimize overtreatment. The recent transition in screening-modalities led to an increase in the detection of biologically high-risk cancers using FFDM.

Trends in Clinical Breast Density Assessment From the Breast Cancer Surveillance Consortium.

Changes to mammography practice, including revised Breast Imaging Reporting and Data System (BI-RADS) density classification guidelines and implementation of digital breast tomosynthesis (DBT), may impact clinical breast density assessment. We investigated temporal trends in clinical breast density assessment among 2 990 291 digital mammography (DM) screens and 221 063 DBT screens interpreted by 722 radiologists from 144 facilities in the Breast Cancer Surveillance Consortium. After age-standardization, 46.3% (95% CI = 44.1% to 48.6%) of DM screens were assessed as dense (heterogeneously/extremely dense) during the BI-RADS 4th edition era (2005-2013), compared to 46.5% (95% CI = 43.8% to 49.1%) during the 5th edition era (2014-2016) (P = .93 from two-sided generalized score test). Among DBT screens in the BI-RADS 5th edition era, 45.8% (95% CI = 42.0% to 49.7%) were assessed as dense (P = .77 from two-sided generalized score test) compared to 46.5% (95% CI = 43.8% to 49.1%) dense on DM in BI-RADS 5th edition era. Results were similar when examining all four density categories and age subgroups. Clinicians, researchers, and policymakers may reasonably expect stable density distributions across screened populations despite changes to the BI-RADS guidelines and implementation of DBT.

Comparison of risk factors for ductal carcinoma in situ and invasive breast cancer.

BACKGROUND: Ductal carcinoma in situ (DCIS) accounts for approximately 12% of newly diagnosed breast cancers. Knowledge of the factors that predict who will be diagnosed with DCIS is very limited. PURPOSE: The goal of this study was to determine risk factors associated with DCIS and whether these risk factors are similar to those associated with invasive breast cancer. METHODS: We conducted a cross-sectional study of 39,542 women aged 30 years and older who underwent a screening mammographic examination at the University of California San Francisco Mobile Mammography Screening Program from April 1985 through September 1995. A breast cancer risk profile and clinical history were obtained for each woman. Follow-up after abnormal mammography was performed to determine the presence of DCIS or invasive breast cancer by contacting the women's physicians and by linkage to the regional Surveillance, Epidemiology, and End Results cancer registry. Multivariate analysis was performed by the use of polytomous logistic regression. Two-sided statistical tests were used to determine P values. RESULTS: Among women aged 30-49 years, a family history of breast cancer (i.e., at least one affected first degree relative) was associated with an increased risk of DCIS (Odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.1-4.9) and body mass index greater than or equal to 25 kg/m2 was associated with a decreased risk of DCIS (OR = 0.4, 95% CI = 0.2 to 0.9). For each of these factors, there was a trend in the same direction bordering on statistical significance for invasive cancer (ORs = 1.7 [95% CI = 0.9-3.4] and 0.6 [95% CI = 0.3-1.1], respectively). Report of a palpable mass was associated with an increased risk of invasive cancer among women aged 30-49 years (OR = 12.0; 95% CI = 7.1-20.0); there was a trend in the same direction for DCIS (OR = 2.0; 95% CI = 0.8-5.1), but the association was much stronger for invasive disease than for DCIS (OR = 6.0; 95% CI = 2.1-18.0; P = .001). Among women aged 50 years and older, family history of breast cancer and nulliparity or age at birth of first child of 30 years or older increased the risk of both DCIS (ORs = 2.2 [95% CI = 1.0-4.2] and 2.3 [95% CI = 1.3-3.8], respectively) and invasive breast cancer (ORs = 1.5 [95% CI = 1.0-2.2] and 1.6 [95% CI = 1.2-2.1], respectively). Report of a palpable mass was not associated with an increased risk of DCIS among women 50 years and older, but it was strongly associated with an increased risk of invasive cancer (OR = 9.3; 95% CI = 6.0-14.0). Increasing age was associated with an increased risk of both DCIS and invasive cancer among women aged 30-49 years, but the association was stronger for invasive disease; a trend in the same direction bordering on statistical significance was observed for women aged 50 years and older. CONCLUSION: Risk factors for DCIS are similar to those for invasive breast cancer. IMPLICATIONS: More research is needed to better understand the malignant potential of DCIS lesions and factors that predict which lesions will become invasive breast cancer if left untreated.

Chromosomal alterations in ductal carcinomas in situ and their in situ recurrences.

BACKGROUND: Ductal carcinoma in situ (DCIS) recurs in the same breast following breast-conserving surgery in 5%-25% of patients, with the rate influenced by the presence or absence of involved surgical margins, tumor size and nuclear grade, and whether or not radiation therapy was performed. A recurrent lesion arising soon after excision of an initial DCIS may reflect residual disease, whereas in situ tumors arising after longer periods are sometimes considered to be second independent events. The purpose of this study was to determine the clonal relationship between initial DCIS lesions and their recurrences. METHODS: Comparative genomic hybridization (CGH) was used to compare chromosomal alterations in 18 initial DCIS lesions (presenting in the absence of invasive disease) and in their subsequent ipsilateral DCIS recurrences (detected from 16 months to 9.3 years later). RESULTS: Of the 18 tumor pairs, 17 showed a high concordance in their chromosomal alterations (median = 81%; range = 65%-100%), while one case showed no agreement between the paired samples (having two and 20 alterations, respectively). Morphologic characterization of the DCIS pairs showed clear similarities. The mean number of CGH changes was greater in the recurrent tumors than in the initial lesions (10.7 versus 8.8; P =.019). The most common changes in both the initial and the recurrent in situ lesions were gains involving chromosome 17q and losses involving chromosomes 8p and 17p. The degree of concordance was independent of the time interval before recurrence and of the presence of positive surgical margins. CONCLUSIONS: In this study, DCIS recurrences were clonally related to their primary lesions in most cases. This finding is consistent with treatment paradigms requiring wide surgical margins and/or postoperative radiation therapy.

Variability and accuracy in mammographic interpretation using the American College of Radiology Breast Imaging Reporting and Data System.

BACKGROUND: Several studies, which were limited by their small sample size and selection of difficult cases for review, have reported substantial variability among radiologists in interpretation of mammographic examinations. We have determined, in the largest study to date, intraobserver and interobserver agreement in interpreting screening mammography and accuracy of mammography by use of the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS). METHODS: The mammographic examinations were randomly selected on the basis of original mammographic interpretation and cancer outcome from 71,713 screening examinations performed by the Mobile Mammography Screening Program of the University of California, San Francisco, during the period from April 1985 through February 1995. The final sample included 786 abnormal examinations with no cancer detected, 267 abnormal examinations with cancer detected, and 1563 normal examinations. Films were read separately by two radiologists according to BI-RADS. Cancer status was determined by contacting women's physicians and by linkage to the regional Surveillance, Epidemiology, and End Results Program. RESULTS: There was moderate agreement between radiologists in reporting the presence of a finding when cancer was present (kappa = 0.54) and substantial agreement when cancer was not present (kappa = 0.62). Agreement was moderate in assigning one of the five assessment categories but was statistically significantly lower when cancer was present relative to when cancer was not present (kappa = 0.46 versus 0.56; two-sided P = .02). Agreement for reporting the presence of a finding and mammographic assessment was two-fold more likely for examinations with less dense breasts. Agreement was higher on repeat readings by the same radiologists than between radiologists. The sensitivity of mammography was lower with BI-RADS than with the original system for mammographic interpretation, but the positive predictive value of mammography was higher. CONCLUSION: Considerable variability in interpretation of mammographic examinations exists; this variability and the accuracy of mammography are neither improved nor diminished with use of BI-RADS.

Identification of risk factors in hypertensive patients: contribution of randomized controlled trials through an individual patient database.

BACKGROUND: Predicting individual risk is needed to target preventive interventions toward people with the highest probability of benefit over a given time period. We assessed which prognostic factors should be used in predicting risk for hypertensive patients and in searching for treatment modifiers. METHODS AND RESULTS: Data from 24 390 hypertensive participants who constituted the control groups from 8 controlled trials (1726 deaths over 5 years) were analyzed in multivariate survival models. Outcomes were coronary heart disease death, stroke death, and cardiovascular death. We explored systematically the heterogeneity of results between trials. Left ventricular hypertrophy was electrocardiographically confirmed to be a powerful risk factor and should be included in risk scoring. Height, glomerular filtration rate, and serum uric acid deserve further exploration. Body mass index and heart rate were not confirmed as independent cardiovascular risk factors in this population. The association between male sex and coronary heart disease death was significantly stronger in British cohorts. The lack of prognostic value of diastolic blood pressure was explained by an interaction with age, with a positive association before 65 years and a negative association thereafter. Previous antihypertensive treatment was a significant risk factor. CONCLUSIONS: Clinical trials provide valuable information for risk prediction. Carefully exploring the heterogeneity among trials is a way to assess the generalizability of findings. This approach, if systematically performed, should increase the ability to identify risk modifiers and to predict individual therapeutic benefit.

Antimycobacterial therapy for disseminated Mycobacterium avium complex infection in patients with acquired immunodeficiency syndrome.

BACKGROUND--Antimycobacterial therapy for disseminated Mycobacterium avium complex (DMAC) in patients with acquired immunodeficiency syndrome (AIDS) may ameliorate symptoms and decrease bacteremia. However, no studies have demonstrated improved survival in patients with AIDS treated for DMAC. We assessed the effects of treatment of DMAC on the survival of patients with AIDS. METHODS--We retrospectively reviewed records of patients with AIDS and DMAC seen at two San Francisco, Calif, hospitals between January 1, 1988, and January 1, 1990. The treatment group (N = 76) consisted of patients who received 2 weeks or more of antimycobacterial therapy with at least three agents. The untreated group (N = 74) received either no therapy or isoniazid alone. Patients in both groups lived a minimum of 2 weeks after the diagnosis of DMAC. RESULTS--The median survival in the treatment group was 191 days, compared with 80 days in the untreated group. In a multivariate proportional hazards model (N = 145), both treatment of DMAC (relative hazard = 0.34; 95% confidence interval, 0.23 to 0.51) and treatment with zidovudine (relative hazard = 0.54; 95% confidence interval, 0.36 to 0.82) were associated with improved survival. CONCLUSION--Patients with AIDS and DMAC who are treated with antimycobacterial drugs may survive longer than untreated patients. We recommend that a randomized trial be conducted to evaluate the optimal treatment of DMAC.

Mortality among women with ductal carcinoma in situ of the breast in the population-based surveillance, epidemiology and end results program.

BACKGROUND: Over 14% of breast cancers diagnosed in the United States annually are ductal carcinomas in situ (DCIS). There are no published population-based reports of the likelihood of breast cancer death among US women with DCIS. METHODS: We used data from the Surveillance, Epidemiology and End Results program to determine the likelihood of breast cancer death at 5 and 10 years among US women aged 40 and older diagnosed with DCIS from 1978 to 1983 (before screening mammography was common; n = 1525) and from 1984 to 1989 (when screening mammography became common; n = 5547). We also calculated standardized mortality ratios (SMRs) to compare observed deaths from breast cancer, cardiovascular disease, and all causes combined among women with DCIS with deaths expected based on general population mortality rates. RESULTS: Among women diagnosed with DCIS from 1978 to 1983, 1.5% died of breast cancer within 5 years and 3.4% within 10 years. Among women diagnosed from 1984 to 1989, 0.7% died of breast cancer within 5 years and 1.9% within 10 years. Relative to the general population, risk of breast cancer death was greater for women diagnosed from 1978 to 1983 (SMR, 3.4; 95% confidence interval [CI], 2.5-4.5) than for women diagnosed from 1984 to 1989 (10-year SMR, 1.9; 95% CI, 1.5-2.3). Women diagnosed from 1984 to 1989 were significantly less likely than women in the general population to have died of cardiovascular diseases (10-year SMR, 0.6; 95% CI, 0.5-0.7) or of all causes combined (SMR, 0.8; 95% CI, 0.7-0.8). CONCLUSIONS: Among women diagnosed with DCIS, risk of death from breast cancer was low, at least within the 10 years following diagnosis. This may reflect the effectiveness of treatment for DCIS, the "benign" nature of DCIS, or both. At 10 years, women diagnosed from 1984 to 1989 were less likely than women diagnosed from 1978 to 1983 to have died of breast cancer, and their risk of dying of all causes combined was lower than that in the general population.

Beta 2-microglobulin as a predictor of death in HIV-infected women from Kigali, Rwanda.

OBJECTIVE: To determine if beta 2-microglobulin (beta 2M) predicts death among HIV-infected African women. DESIGN: Nested case-control study. SETTING: Kigali, Rwanda. PARTICIPANTS: Two hundred and five seroprevalent women known to be HIV-infected since 1986-1987; 67 of whom died of HIV disease (cases) and 138 were alive (controls) as of November 1991. In addition, 128 women who seroconverted between 1986 and 1991. MAIN OUTCOME MEASURES: HIV serology, clinical signs and symptoms of HIV disease, hematology variables, and beta 2M concentration. RESULTS: beta 2M concentration increased over time (P < 0.001) in the seroprevalent women and seroconvertors. The average rate of beta 2M increase in women who died was 0.5 compared with 0.3 mg/l/year in the vital, seroprevalent women (P = 0.07). The strongest independent predictors of death were the rate of change of beta 2M (mg/l/year) [odds ratio (OR), 3.4; 95% confidence interval (CI), 1.7-6.8] and baseline beta 2M concentration (mg/l) [OR, 1.6; 95% CI, 1.2-2.1]. The rate of death for women with beta 2M concentration > or = 7.0 mg/l and a rate of change of beta 2M > or = 0.4 mg/l/year was 7.3 times higher than for women with beta 2M concentration < 7.0 mg/l and a rate of change of beta 2M of < 0.4 mg/l/year (95% CI, 3.1-17.2). The estimated median time from seroconversion to death assuming a constant rate of change of beta 2M was 10.6 years (95% CI, 9.9-11.2) for this cohort of HIV-infected women. CONCLUSIONS: Elevated beta 2M and a high rate of beta 2M increase were strongly associated with mortality among HIV-infected African women. Based on survival estimates using the rate of change of beta 2M, HIV-infected African women have similar survival compared with HIV-infected adults in the United States.

Efficacy of screening mammography among women aged 40 to 49 years and 50 to 69 years: comparison of relative and absolute benefit.

In randomized controlled trials, screening mammography has been shown to reduce mortality from breast cancer about 25% to 30% among women aged 50 to 69 years after only five to six years from the initiation of screening. Among women aged 40 to 49 years, trials have reported no reduction in breast cancer mortality after seven to nine years from the initiation of screening; after 10 to 14 years there is a 16% reduction in breast cancer mortality. Given that the incidence of breast cancer for women aged 40 to 49 years is lower and the potential benefit from mammography screening smaller and delayed, the absolute number of deaths prevented by screening women aged 40 to 49 years is much less than in screening women aged 50 to 69 years. Because the absolute benefit of screening women aged 40 to 49 years is small and there is concern that the harms are substantial, the focus should be to help these women make informed decisions about screening mammography by educating them of their true risk of breast cancer and the potential benefits and risks of screening.

Outcomes of modern screening mammography.

The University of California, San Francisco, Mobile Mammography Screening Program is a low-cost, community-based breast cancer screening program that offers mammography to women of diverse ethnic backgrounds (36% nonwhite) in six counties in northern California. Analysis of data collected on approximately 34,000 screening examinations from this program shows that the positive predictive value and sensitivity of modern screening mammography to be lower for women aged 40 to 49 years compared to women aged 50 and older. This lower performance is due to the lower prevalence of invasive breast cancer in younger women and possibly to age differences in breast tumor biology. Because of this lower performance, women in their forties may be subjected to more of the negative consequences of screening, which include additional diagnostic evaluations and the associated morbidity and anxiety, the potential for detecting and surgically treating clinically insignificant breast lesions, and the false reassurance resulting from normal mammographic results. Since the evidence is not compelling that the benefits of mammography screening outweigh the known risks for women aged 40 to 49 years, women considering mammography screening should be informed of the risks, potential benefits, and limitations of screening mammography, so that they can make individualized decisions based on their personal risk status and utility for the associated risks and potential benefits of screening.

Is screening mammography effective in elderly women?

PURPOSE: Screening mammography is effective in reducing breast cancer mortality in women between the ages of 50 and 69 years. We sought to determine whether older women who undergo screening mammography have a decreased risk of metastatic breast cancer. SUBJECTS AND METHODS: We studied 690,993 women aged 66 to 79 years who were California Medicare beneficiaries from January 1992 to December 1993, and who chose the fee-for-service plan. Health Care Financing Administration part B billing records were used to determine the use of screening mammography. The extent of breast cancer (in situ, local, regional, or metastatic) was ascertained for the 6,767 women who were diagnosed with the disease in 1993, using data from the California State Cancer Registry. For each type (extent) of breast cancer, the relative risk (RR) and 95% confidence (CI) of developing breast cancer was estimated by dividing the risk of its development in screened women by the risk in women who were not screened. RESULTS: A total of 46% of women had mammography during the 2-year study period. In situ, local, and regional breast cancer were more likely to be detected among women who underwent screening mammography. For example, the relative risk of detecting local breast cancer in screened women was 3.3 (95% CI: 3.1 to 3.5). The risk of detecting metastatic breast cancer, on the other hand, was significantly reduced among women aged 66 to 79 years who underwent screening mammography (RR = 0.57, 95% CI: 0.45 to 0.72). CONCLUSION: Screening mammography is associated with a decreased risk of detecting metastatic breast cancer among elderly women. Public health recommendations need to weigh the benefit of screening elderly women against the cost and potential harm from screening and treating early lesions that may have no effect on mortality.

Should women with familial ovarian cancer undergo prophylactic oophorectomy?

OBJECTIVES: To estimate the lifetime probabilities of ovarian cancer in women from families with hereditary ovarian cancer syndromes and those with a family history of ovarian cancer, and to assess the needs for prevention and surveillance in such women. DATA SOURCES: We searched for studies of familial ovarian cancer published since 1966 and used ovarian cancer incidence data from the Surveillance, Epidemiology, and End Results program of the National Cancer Institute. METHODS: Pooled estimates of relative risk of ovarian cancer among women with a family history of ovarian cancer were derived using statistical methods based on fixed effects. Modified life-table methods were used to estimate the lifetime probability of ovarian cancer. DATA SYNTHESIS: The lifetime probability of ovarian cancer increases from about 1.6% in a 35-year-old woman without a family history of ovarian cancer to about 5% if she has one relative and 7% if she has two relatives with ovarian cancer. The lifetime probability may decrease to about 3-4% if she takes oral contraceptives for 5-9 years. Women from families with hereditary ovarian cancer syndromes may have as high as a 50% lifetime risk of ovarian cancer. CONCLUSIONS: The risk of ovarian cancer in women from families with hereditary ovarian cancer syndromes is sufficiently high to warrant prophylactic oophorectomy. Among women with one relative with ovarian cancer, the lifetime probability of ovarian cancer is not high enough to recommend oophorectomy. However, some women may choose oophorectomy depending on their attitudes concerning risk-taking, surgery, and hormone replacement. Oral contraceptives should be considered as preventive therapy to decrease the risk of ovarian cancer in women with a family history of ovarian cancer.

Hormone replacement therapy and endometrial cancer risk: a meta-analysis.

OBJECTIVE: To assess the association of unopposed estrogen or estrogen plus progestin and the risk of developing endometrial cancer or dying of that disease. DATA SOURCES: A literature search of English-language studies was performed using MEDLINE, a review of bibliographies, and consultations with experts. METHODS OF STUDY SELECTION: We identified 30 studies with adequate controls and risk estimates. DATA EXTRACTION AND SYNTHESIS: Risk estimates were extracted by two authors and summarized using meta-analytic methods. The summary relative risk (RR) was 2.3 for estrogen users compared to nonusers (95% confidence interval [CI] 2.1-2.5), with a much higher RR associated with prolonged duration of use (RR 9.5 for 10 or more years). The summary RR of endometrial cancer remained elevated 5 or more years after discontinuation of unopposed estrogen therapy (RR 2.3). Interrupting estrogen for 5-7 days per month was not associated with lower risk than daily use. Users of unopposed conjugated estrogen had a greater increase in RR of developing endometrial cancer than users of synthetic estrogens. The risk for endometrial cancer death was elevated among unopposed estrogen users (RR 2.7, 95% CI 0.9-8.0). Among estrogen plus progestin users, cohort studies showed a decreased risk of endometrial cancer (RR 0.4), whereas case-control studies showed a small increase (RR 1.8). CONCLUSIONS: Endometrial cancer risk increases substantially with long duration of unopposed estrogen use, and this increased risk persists for several years after discontinuation of estrogen. Although not statistically significant, the risk of death from endometrial cancer among unopposed estrogen users is increased, similar to the increased risk of developing the disease. Data regarding risk for endometrial cancer among estrogen plus progestin users are limited and conflicting.

Antibiotics at the time of induced abortion: the case for universal prophylaxis based on a meta-analysis.

OBJECTIVE: To determine the efficacy of periabortal antibiotics in preventing postabortal upper genital tract infection using data from published trials. DATA SOURCES: We performed a literature search of all studies published from January 1966 to September 1, 1994, using MEDLINE, and we manually searched bibliographies of published articles. MEDLINE search terms included: abortion, infection, prophylaxis, antibiotics, pelvic inflammatory disease (PID), and suction curettage. METHODS OF STUDY SELECTION: Randomized, controlled trials comparing antibiotics with placebo in women undergoing suction curettage abortion before 16 weeks' gestation were identified. TABULATION, INTEGRATION, AND RESULTS: Data were extracted independently by two reviewers, one of whom was blinded to journal, year of publication, authors, and institution. Data from 12 studies were combined using meta-analytic techniques based on a fixed-effects model. The overall summary relative risk (RR) estimate for developing postabortal upper genital tract infection in women receiving antibiotic therapy compared with those receiving placebo was 0.58 (95% confidence interval [CI] 0.47-0.71). Of high-risk women, those with a history of PID had a summary RR estimate of 0.56 (95% CI 0.37-0.84); women with a positive chlamydia culture at abortion had a summary RR estimate of 0.38 (95% CI 0.15-0.92). Of low-risk women, those with no reported history of PID had a summary RR estimate of 0.65 (95% CI 0.47-0.90); in women with a negative chlamydia culture, the summary RR estimate was 0.63 (95% CI 0.42-0.97). The lowest summary RR estimate was among women drawn from populations with a low incidence (5-6%) of postabortal infection (summary RR estimate 0.22, 95% CI 0.11-0.42). The overall 42% decreased risk of infection in women given periabortal antibiotics is similar to the risk reduction demonstrable when only studies published before 1985 are combined (summary RR estimate 0.63, 95% CI 0.44-0.89). CONCLUSION: Our meta-analysis revealed a substantial protective effect of antibiotics in all subgroups of women undergoing therapeutic abortion, even women in low-risk groups. No more placebo-controlled trials should be performed, because women assigned to placebo are exposed to preventable risk. Routine use of periabortal antibiotics in the United States may prevent up to half of all cases of postabortal infections.

Hormone replacement therapy and the risk of epithelial ovarian carcinoma: a meta-analysis.

OBJECTIVE: To determine if use of postmenopausal hormone replacement therapy (HRT) increases the risk of invasive epithelial ovarian carcinoma. DATA SOURCES: English-language articles published from January 1966 to June 1997 examining HRT and ovarian cancer were found by using MEDLINE, searching the bibliographies of relevant articles and by consulting experts. STUDY SELECTION: Of 327 articles identified, nine provided data on the risk of invasive cancer among ever-users of HRT and were selected for inclusion by consensus of two independent reviewers. Studies were included if cases were age-matched to controls or results were age-adjusted and if women with bilateral salpingo-oophorectomy were excluded. TABULATION, INTEGRATION, AND RESULTS: Two independent unblinded reviewers abstracted data regarding risk of developing epithelial ovarian carcinoma and use of HRT. A general variance-based, fixed-effects model was used to calculate summary relative risks. Ever-use of HRT was associated with an increased risk of developing invasive epithelial ovarian carcinoma (odds ratio [OR] 1.15; 95% confidence interval [CI] 1.05, 1.27). Use of HRT for more than 10 years was associated with the greatest risk of ovarian cancer (OR 1.27; 95% CI 1.00, 1.61). CONCLUSION: Prolonged use of hormone therapy by postmenopausal women may be associated with an increased risk of developing epithelial carcinoma of the ovary.

Frequency of cervical smear abnormalities within 3 years of normal cytology.

OBJECTIVE: To compare cervical screening outcomes associated with age and three screening intervals, 1, 2, and 3 years. METHODS: We did a prospective cohort study comprising 128,805 women at community-based clinics throughout the United States who were screened for cervical cancer within 3 years of normal smears through the National Breast and Cervical Cancer Early Detection Program. We determined the incidence of cytologic abnormalities defined as atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (SIL), high-grade SIL, and suggestive of squamous cell cancer. RESULTS: Over the 3 years after normal smear results, the incidence of new smears interpreted as high-grade SIL or suggestive of squamous cell cancer (high-grade SIL or worse) was 66 of 10,000 for women under 30 years old, 22 of 10, 000 for those 30-49 years, 15 of 10,000 for those 50-64 years, and 10 of 10,000 for those over 65 years. Age-adjusted incidence rates of high-grade SIL or worse were similar for women screened at 9-12 months (25 of 10,000), 13-24 months (29 of 10,000), and 25-36 months (33 of 10,000) after normal smears (P =.46). Age-adjusted incidence rates of ASCUS, the most common cytologic abnormality, did not change (P =.36). Incidence of smears interpreted as low-grade SIL increased as time from the normal smear increased (P =.01). CONCLUSIONS: Within 3 years after normal cytology results, cervical smears interpreted as high-grade SIL or worse are uncommon, and the incidence rate is unrelated to the time since last normal smear. Optimal screening strategies for women with recent normal cytology results should be based on comprehensive modeling studies that incorporate the true risks and benefits of repetitive screening.

Selection of patients for laparoscopic pelvic lymphadenectomy prior to radical prostatectomy: a decision analysis.

Indications for laparoscopic pelvic lymphadenectomy prior to radical prostatectomy have not been established. Criteria to predict lymph node metastases were derived from the preoperative evaluations of 164 prostate cancer patients undergoing pelvic lymphadenectomy. Decision analysis was used to determine which criteria would be optimal indicators for laparoscopic pelvic lymphadenectomy prior to intended radical prostatectomy. Besides a digital rectal examination suggesting uncontained tumor, which was the best indication for laparoscopic pelvic lymphadenectomy, the most useful criteria were sonographic tumor volume > or = 3 cc and prostate-specific antigen (PSA) > or = 20 ng/mL. If either parameter was met, the sensitivity for identifying patients with pelvic lymph node metastases was 88 percent and the positive predictive value was 42 percent. When both were met, the sensitivity fell to 47 percent but the positive predictive value increased to 67 percent. A combination of Gleason biopsy score and PSA was the best criterion that was independent of transrectal ultrasonography. Using a PSA > or = 15 ng/mL for tumors with Gleason biopsy score > or = 7 or a PSA > or = 25 ng/mL for tumors with a Gleason biopsy score of 5-6 had a sensitivity of 71 percent and positive predictive value of 48 percent for identifying patients with pelvic lymph node metastases. In selecting patients for laparoscopic pelvic lymphadenectomy prior to radical retropubic prostatectomy, criteria with a positive predictive value greater than 39 percent maximize the utility of laparoscopic pelvic lymphadenectomy. Prior to radical perineal prostatectomy, laparoscopic pelvic lymphadenectomy will identify pelvic lymph node metastases that would otherwise be undetected by prostatectomy alone. The sensitivity of selection criteria, therefore, should be increased, as long as the positive predictive value remains above 20 percent.

Factors associated with women's adherence to mammography screening guidelines.

OBJECTIVE: To examine individual and environmental factors associated with adherence to mammography screening guidelines. DATA SOURCES: A unique data set that combines a national probability sample (1992 National Health Interview Survey); a national probability sample of mammography facility characteristics (1992 National Survey of Mammography Facilities); county-level data on 1990 HMO market share; and county-level data on the supply of primary care providers (1991 Area Resource File). STUDY DESIGN: The design was cross-sectional. DATA EXTRACTION/ANALYSIS: Data sets were linked to create an individual-level sample of women ages 50-74 (weighted n = 2,026). We used multipart, sequential logistic regression models to examine the predictors of having ever had mammography, having had recent mammography, and adherence to guidelines. We categorized women as adherent if they reported a lifetime number of exams appropriate for their age (based on screening every two years) and they reported having had an exam in the past two years. PRINCIPAL FINDINGS: Only 27 percent of women had the age-appropriate number of screening exams (range 16 percent-37 percent), while 59 percent of women had been screened within two years. Women were significantly more likely to adhere to screening guidelines if they reported participating with their doctor in the decision to be screened; were younger; had smaller families, higher education and income, and a recent Pap smear; reported breast problems; and lived in an area with a higher percentage of mammography facilities with reminder systems, no shortage of primary care providers, higher HMO market share, and higher screening charges. CONCLUSIONS: A small percentage of women adhere to screening guidelines, suggesting that adherence needs to become a focus of clinical, programmatic, and policy efforts.