Jeffrey D. Blume

Combined Screening With Ultrasound and Mammography vs Mammography Alone in Women at Elevated Risk of Breast Cancer

CONTEXT Screening ultrasound may depict small, node-negative breast cancers not seen on mammography. OBJECTIVE To compare the diagnostic yield, defined as the proportion of women with positive screen test results and positive reference standard, and performance of screening with ultrasound plus mammography vs mammography alone in women at elevated risk of breast cancer. DESIGN, SETTING, AND PARTICIPANTS From April 2004 to February 2006, 2809 women, with at least heterogeneously dense breast tissue in at least 1 quadrant, were recruited from 21 sites to undergo mammographic and physician-performed ultrasonographic examinations in randomized order by a radiologist masked to the other examination results. Reference standard was defined as a combination of pathology and 12-month follow-up and was available for 2637 (96.8%) of the 2725 eligible participants. MAIN OUTCOME MEASURES Diagnostic yield, sensitivity, specificity, and diagnostic accuracy (assessed by the area under the receiver operating characteristic curve) of combined mammography plus ultrasound vs mammography alone and the positive predictive value of biopsy recommendations for mammography plus ultrasound vs mammography alone. RESULTS Forty participants (41 breasts) were diagnosed with cancer: 8 suspicious on both ultrasound and mammography, 12 on ultrasound alone, 12 on mammography alone, and 8 participants (9 breasts) on neither. The diagnostic yield for mammography was 7.6 per 1000 women screened (20 of 2637) and increased to 11.8 per 1000 (31 of 2637) for combined mammography plus ultrasound; the supplemental yield was 4.2 per 1000 women screened (95% confidence interval [CI], 1.1-7.2 per 1000; P = .003 that supplemental yield is 0). The diagnostic accuracy for mammography was 0.78 (95% CI, 0.67-0.87) and increased to 0.91 (95% CI, 0.84-0.96) for mammography plus ultrasound (P = .003 that difference is 0). Of 12 supplemental cancers detected by ultrasound alone, 11 (92%) were invasive with a median size of 10 mm (range, 5-40 mm; mean [SE], 12.6 [3.0] mm) and 8 of the 9 lesions (89%) reported had negative nodes. The positive predictive value of biopsy recommendation after full diagnostic workup was 19 of 84 for mammography (22.6%; 95% CI, 14.2%-33%), 21 of 235 for ultrasound (8.9%, 95% CI, 5.6%-13.3%), and 31 of 276 for combined mammography plus ultrasound (11.2%; 95% CI. 7.8%-15.6%). CONCLUSIONS Adding a single screening ultrasound to mammography will yield an additional 1.1 to 7.2 cancers per 1000 high-risk women, but it will also substantially increase the number of false positives. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00072501.

Screening women at high risk for breast cancer with mammography and magnetic resonance imaging

The authors compared the performance of screening mammography versus magnetic resonance imaging (MRI) in women at genetically high risk for breast cancer.

Locally Advanced Breast Cancer: MR Imaging for Prediction of Response to Neoadjuvant Chemotherapy—Results from ACRIN 6657/I-SPY TRIAL

PURPOSE To compare magnetic resonance (MR) imaging findings and clinical assessment for prediction of pathologic response to neoadjuvant chemotherapy (NACT) in patients with stage II or III breast cancer. MATERIALS AND METHODS The HIPAA-compliant protocol and the informed consent process were approved by the American College of Radiology Institutional Review Board and local-site institutional review boards. Women with invasive breast cancer of 3 cm or greater undergoing NACT with an anthracycline-based regimen, with or without a taxane, were enrolled between May 2002 and March 2006. MR imaging was performed before NACT (first examination), after one cycle of anthracyline-based treatment (second examination), between the anthracycline-based regimen and taxane (third examination), and after all chemotherapy and prior to surgery (fourth examination). MR imaging assessment included measurements of tumor longest diameter and volume and peak signal enhancement ratio. Clinical size was also recorded at each time point. Change in clinical and MR imaging predictor variables were compared for the ability to predict pathologic complete response (pCR) and residual cancer burden (RCB). Univariate and multivariate random-effects logistic regression models were used to characterize the ability of tumor response measurements to predict pathologic outcome, with area under the receiver operating characteristic curve (AUC) used as a summary statistic. RESULTS Data in 216 women (age range, 26-68 years) with two or more imaging time points were analyzed. For prediction of both pCR and RCB, MR imaging size measurements were superior to clinical examination at all time points, with tumor volume change showing the greatest relative benefit at the second MR imaging examination. AUC differences between MR imaging volume and clinical size predictors at the early, mid-, and posttreatment time points, respectively, were 0.14, 0.09, and 0.02 for prediction of pCR and 0.09, 0.07, and 0.05 for prediction of RCB. In multivariate analysis, the AUC for predicting pCR at the second imaging examination increased from 0.70 for volume alone to 0.73 when all four predictor variables were used. Additional predictive value was gained with adjustments for age and race. CONCLUSION MR imaging findings are a stronger predictor of pathologic response to NACT than clinical assessment, with the greatest advantage observed with the use of volumetric measurement of tumor response early in treatment.

Prostate cancer: sextant localization at MR imaging and MR spectroscopic imaging before prostatectomy--results of ACRIN prospective multi-institutional clinicopathologic study.

PURPOSE To determine the incremental benefit of combined endorectal magnetic resonance (MR) imaging and MR spectroscopic imaging, as compared with endorectal MR imaging alone, for sextant localization of peripheral zone (PZ) prostate cancer. MATERIALS AND METHODS This prospective multicenter study, conducted by the American College of Radiology Imaging Network (ACRIN) from February 2004 to June 2005, was institutional review board approved and HIPAA compliant. Research associates were required to follow consent guidelines approved by the Office for Human Research Protection and established by the institutional review boards. One hundred thirty-four patients with biopsy-proved prostate adenocarcinoma and scheduled to undergo radical prostatectomy were recruited at seven institutions. T1-weighted, T2-weighted, and spectroscopic MR sequences were performed at 1.5 T by using a pelvic phased-array coil in combination with an endorectal coil. Eight readers independently rated the likelihood of the presence of PZ cancer in each sextant by using a five-point scale-first on MR images alone and later on combined MR-MR spectroscopic images. Areas under the receiver operating characteristic curve (AUCs) were calculated with sextant as the unit of analysis. The presence or absence of cancer at centralized histopathologic evaluation of prostate specimens was the reference standard. Reader-specific receiver operating characteristic curves for values obtained with MR imaging alone and with combined MR imaging-MR spectroscopic imaging were developed. The AUCs were estimated by using Mann-Whitney statistics and appropriate 95% confidence intervals. RESULTS Complete data were available for 110 patients (mean age, 58 years; range, 45-72 years). MR imaging alone and combined MR imaging-MR spectroscopic imaging had similar accuracy in PZ cancer localization (AUC, 0.60 vs 0.58, respectively; P > .05). AUCs for individual readers were 0.57-0.63 for MR imaging alone and 0.54-0.61 for combined MR imaging-MR spectroscopic imaging. CONCLUSION In patients who undergo radical prostatectomy, the accuracy of combined 1.5-T endorectal MR imaging-MR spectroscopic imaging for sextant localization of PZ prostate cancer is equal to that of MR imaging alone.

Percutaneous radiofrequency ablation of painful osseous metastases: A multicenter American College of Radiology Imaging Network trial

The study was conducted to determine whether radiofrequency ablation (RFA) can safely reduce pain from osseous metastatic disease.

Reasons Women at Elevated Risk of Breast Cancer Refuse Breast MR Imaging Screening: ACRIN 6666

PURPOSE To determine reasons for nonparticipation in a trial of supplemental screening with magnetic resonance (MR) imaging after mammography and ultrasonography (US). MATERIALS AND METHODS Women(n = 2809) at elevated risk of breast cancer were enrolled in the American College of Radiology Imaging Network 6666 US Screening Protocol at 21 institutions. Fourteen institutions met technical and experience requirements for this institutional review board-approved, HIPAA-compliant substudy of supplemental screening with MR imaging. Those women who had completed 0-, 12-, and 24-month screenings with mammography combined with US were considered for a single contrast material-enhanced MR examination within 8 weeks after completing the 24-month mammography-US screening. A total of 1593 women had complete MR substudy registration data: 378 of them were ineligible for the study, and 1215 had analyzable data. Reasons for nonparticipation were determined. Demographic data were compared between study participants and nonparticipants. RESULTS Of 1215 women with analyzable data, 703 (57.9%), with a mean age of 54.8 years, were enrolled in the MR substudy and 512 (42.1%) declined participation. Women with a 25% or greater lifetime risk of breast cancer were more likely to participate (odds ratio, 1.53; 95% confidence interval: 1.10, 2.12). Of 512 nonparticipants, 130 (25.4%) refused owing to claustrophobia; 93 (18.2%), owing to time constraints; 62 (12.1%), owing to financial concerns; 47 (9.2%), because their physician would not provide a referral and/or did not believe MR imaging was indicated; 40 (7.8%), because they were not interested; 39 (7.6%), because they were medically intolerant to MR imaging; 29 (5.7%), because they did not want to undergo intravenous injection; 27 (5.3%), owing to additional biopsy or other procedures that might be required subsequently; 21 (4.1%), owing to MR imaging scheduling constraints; 11 (2.2%), because of the travel required; seven (1.4%), owing to gadolinium-related risks or allergies; and six (1.2%), for unknown reasons. CONCLUSION Of 1215 women with elevated breast cancer risk who could, according to protocol guidelines, undergo breast MR imaging, only 57.9% agreed to participate.

Young maternal age associated with increased risk of postneonatal death

OBJECTIVE To determine whether full‐term, healthy infants born to early adolescent mothers (15 years old and younger) are at higher risk of postneonatal death compared with infants of adult mothers. METHODS We combined the comprehensive 1996 and 1997 United States birth cohorts to compare postneonatal mortality rates among maternal age groups. With postneonatal death as our main outcome measure, we used multivariable logistic regression to model adjusted odds ratios. RESULTS The postneonatal mortality rate for infants born to mothers 15 years old and younger was substantially higher (3.2 per 1000) than that of infants born to mothers 23–29 years old (0.8 per 1000) and remained substantially higher after adjusting for maternal race or ethnicity. Even after adjusting for maternal race or ethnicity, prenatal care utilization, and marital status, infants born to early adolescent mothers had a three‐fold higher risk (odds ratio 3.0, 95% confidence interval 2.5, 3.6) of postneonatal death compared with adult mothers. CONCLUSION Healthy infants born to early adolescent mothers are at increased risk of postneonatal death. Many of these deaths are potentially preventable; therefore, developing targeted postnatal support services specifically designed to address the needs of healthy infants born to adolescent mothers might have a positive effect on the lives of these children.

Evaluation of clinical methods for diagnosing bacterial vaginosis.

OBJECTIVE: To determine whether the current clinical criteria for diagnosing bacterial vaginosis can be simplified by using 2 clinical criteria rather than the standard 3 of 4 criteria (Amsels criteria). METHODS: This was a prospective observational study of 269 women undergoing a vaginal examination in the Womens Primary Care Center, Division of Research, or Colposcopy Clinic at Women & Infants Hospital. All 4 clinical criteria for diagnosing bacterial vaginosis were collected, and Gram stain was used as the gold standard. Sensitivity and specificity were calculated for each individual criterion, combinations of criteria, and a colorimetric pH and amine card. Receiver operating characteristic curve was generated to estimate the preferred pH and percentage of clue cells for diagnosing bacterial vaginosis. RESULTS: The prevalence of bacterial vaginosis in our study population was 38.7%. Vaginal pH was the most sensitive of all the criteria, at 89%, and a positive amine odor was the individual criteria with the highest specificity, at 93%. Similar specificity was seen with combinations of 2 criteria and Amsels criteria. Receiver operating characteristic curve analysis yielded a preferred pH and percentage of clue cells of 5.0 and 20%, respectively. However, a pH of 4.5 or greater improves sensitivity with minimal loss of specificity. CONCLUSION: The clinical criteria for diagnosing bacterial vaginosis can be simplified to 2 clinical criteria without loss of sensitivity and specificity. LEVEL OF EVIDENCE: II-2

Is a previous unplanned pregnancy a risk factor for a subsequent unplanned pregnancy

OBJECTIVE The objective of the study was to determine whether a history of unplanned pregnancy was a risk factor for a subsequent unplanned pregnancy. STUDY DESIGN We analyzed 542 women aged 14-35 years, enrolled in Project PROTECT, a randomized clinical trial to promote dual-method contraception use to prevent sexually transmitted diseases and unplanned pregnancy. Predictors of unplanned pregnancy were assessed by comparing women with and without a history of unplanned pregnancy. RESULTS More than 1 in 5 women (22.5%) experienced an unintended pregnancy. History of an unintended pregnancy was a predictor of unintended pregnancy (adjusted odds ratio, 1.91; 95% confidence interval, 1.09-3.34). Other factors that were significantly associated with unplanned pregnancy included young age and low educational status. CONCLUSIONS Future efforts should focus on bridging the gap between identifying risk factors for unplanned pregnancy and interventions aimed at reducing the incidence in high-risk groups.

Bacterial vaginosis, race, and sexually transmitted infections: does race modify the association?

Background: There are significant racial disparities in the prevalence of sexually transmitted infections (STIs) in the United States. The purpose of this study was to evaluate whether the association of bacterial vaginosis and incident STI is modified by race even after adjustment for sexual practices and other potential confounding variables. Methods: We evaluated the association of bacterial vaginosis (BV) and STI acquisition in a group of 523 women at high risk for unplanned pregnancies and STI. BV was diagnosed by both Gram stain and Amsel criteria. STIs included Chlamydia trachomatis, Neisseria gonorrhoeae, pelvic inflammatory disease, trichomoniasis, syphilis, and HIV. Cox regression estimated the associations and the synergy index assessed whether race modified the association of BV and incident STI. Results: Sixteen percent of participants developed an STI during the 2-year follow-up. Compared with white women without BV at baseline, the adjusted hazard ratios were as follows: white women with BV = 0.59; African American women without BV = 1.96; and African American women with BV = 2.86. The synergy index of 3.38 implies a combined association of BV and African American race with STI in excess of each factor individually. Conclusions: African American race modifies the association of BV and incident STI. Future research should strive to determine the relative contributions of other factors, such as biologic variation, social network or the consequences of socioeconomic position, in this disparity.