Constance D. Lehman

American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.

New evidence on breast Magnetic Resonance Imaging (MRI) screening has become available since the American Cancer Society (ACS) last issued guidelines for the early detection of breast cancer in 2003. A guideline panel has reviewed this evidence and developed new recommendations for women at different defined levels of risk. Screening MRI is recommended for women with an approximately 20–25% or greater lifetime risk of breast cancer, including women with a strong family history of breast or ovarian cancer and women who were treated for Hodgkin disease. There are several risk subgroups for which the available data are insufficient to recommend for or against screening, including women with a personal history of breast cancer, carcinoma in situ, atypical hyperplasia, and extremely dense breasts on mammography. Diagnostic uses of MRI were not considered to be within the scope of this review.

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.

Pathologic Complete Response Predicts Recurrence-Free Survival More Effectively by Cancer Subset: Results From the I-SPY 1 TRIAL—CALGB 150007/150012, ACRIN 6657

PURPOSE Neoadjuvant chemotherapy for breast cancer provides critical information about tumor response; how best to leverage this for predicting recurrence-free survival (RFS) is not established. The I-SPY 1 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis) was a multicenter breast cancer study integrating clinical, imaging, and genomic data to evaluate pathologic response, RFS, and their relationship and predictability based on tumor biomarkers. PATIENTS AND METHODS Eligible patients had tumors ≥ 3 cm and received neoadjuvant chemotherapy. We determined associations between pathologic complete response (pCR; defined as the absence of invasive cancer in breast and nodes) and RFS, overall and within receptor subsets. RESULTS In 221 evaluable patients (median tumor size, 6.0 cm; median age, 49 years; 91% classified as poor risk on the basis of the 70-gene prognosis profile), 41% were hormone receptor (HR) negative, and 31% were human epidermal growth factor receptor 2 (HER2) positive. For 190 patients treated without neoadjuvant trastuzumab, pCR was highest for HR-negative/HER2-positive patients (45%) and lowest for HR-positive/HER2-negative patients (9%). Achieving pCR predicted favorable RFS. For 172 patients treated without trastuzumab, the hazard ratio for RFS of pCR versus no pCR was 0.29 (95% CI, 0.07 to 0.82). pCR was more predictive of RFS by multivariate analysis when subtype was taken into account, and point estimates of hazard ratios within the HR-positive/HER2-negative (hazard ratio, 0.00; 95% CI, 0.00 to 0.93), HR-negative/HER2-negative (hazard ratio, 0.25; 95% CI, 0.04 to 0.97), and HER2-positive (hazard ratio, 0.14; 95% CI, 0.01 to 1.0) subtypes are lower. Ki67 further improved the prediction of pCR within subsets. CONCLUSION In this biologically high-risk group, pCR differs by receptor subset. pCR is more highly predictive of RFS within every established receptor subset than overall, demonstrating that the extent of outcome advantage conferred by pCR is specific to tumor biology.

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.

Quantitative Diffusion-Weighted Imaging as an Adjunct to Conventional Breast MRI for Improved Positive Predictive Value

OBJECTIVE The purpose of our study was to investigate whether adding diffusion-weighted imaging (DWI) to dynamic contrast-enhanced MRI (DCE-MRI) could improve the positive predictive value (PPV) of breast MRI. MATERIALS AND METHODS The retrospective study included 70 women with 83 suspicious breast lesions on DCE-MRI (BI-RADS 4 or 5) who underwent subsequent biopsy. DWI was acquired during clinical breast MRI using b = 0 and 600 s/mm(2). Apparent diffusion coefficient (ADC) values were compared for benign and malignant lesions. PPV was calculated for DCE-MRI alone (based on biopsy recommendations) and DCE-MRI plus DWI (adding an ADC threshold) for the same set of lesions. Results were further compared by lesion type (mass, nonmasslike enhancement) and size. RESULTS Of the 83 suspicious lesions, 52 were benign and 31 were malignant (11 ductal carcinoma in situ [DCIS], 20 invasive carcinoma). Both DCIS (mean ADC, 1.31 +/- 0.24 x 10(-3) mm(2)/s) and invasive carcinoma (mean ADC, 1.29 +/- 0.29 x 10(-3) mm(2)/s) exhibited lower mean ADC than benign lesions (1.70 +/- 0.44 x 10(-3) mm(2)/s, p < 0.001). Applying an ADC threshold of 1.81 x 10(-3) mm(2)/s for 100% sensitivity produced a PPV of 47% versus 37% for DCE-MRI alone, which would have avoided biopsy for 33% (17/52) of benign lesions without missing any cancers. DWI increased PPV similarly for masses and nonmasslike enhancement and preferentially improved PPV for smaller (< or = 1 cm) versus larger lesions. CONCLUSION DWI shows potential for improving the PPV of breast MRI for lesions of varied types and sizes. However, considerable overlap in ADC of benign and malignant lesions necessitates validation of these findings in larger studies.

Statement of the Science Concerning Locoregional Treatments After Preoperative Chemotherapy for Breast Cancer: A National Cancer Institute Conference

PURPOSE To review the state of the science with respect to diagnostic imaging and locoregional therapy for patients with breast cancer receiving preoperative chemotherapy. METHODS Published data relevant to clinical staging, monitoring of tumor response, and locoregional therapy for patients with breast cancer treated with preoperative chemotherapy were reviewed. RESULTS High-quality data from prospective randomized trials are limited. Available data suggest that locoregional therapy decisions should be based on both the pretreatment clinical extent of disease and the pathologic extent of the disease after chemotherapy. Accordingly, physical examination and imaging studies that accurately define the initial extent of disease are required before treatment. Sentinel lymph node biopsy can be performed either before or after preoperative chemotherapy for patients with clinical N0 disease. The success of breast conservation after preoperative chemotherapy depends on careful patient selection and achieving negative surgical margins. Adjuvant breast radiation is indicated for all patients treated with breast conservation. For patients treated with mastectomy, chest-wall and regional nodal radiation should be considered for those who present with clinical stage III disease or have histologically positive lymph nodes after preoperative chemotherapy. Additional prospective studies are needed to determine the value of postmastectomy radiation for patients with stage II breast cancer who have negative lymph nodes after chemotherapy. CONCLUSION The increased use of preoperative chemotherapy has raised new questions concerning the optimal methods to stage and monitor disease response to treatment and how to optimize locoregional treatment. The available evidence suggests that a multidisciplinary approach improves outcomes.

Comparative Effectiveness of Digital Versus Film-Screen Mammography in Community Practice in the United States: A Cohort Study

BACKGROUND Few studies have examined the comparative effectiveness of digital versus film-screen mammography in U.S. community practice. OBJECTIVE To determine whether the interpretive performance of digital and film-screen mammography differs. DESIGN Prospective cohort study. SETTING Mammography facilities in the Breast Cancer Surveillance Consortium. PARTICIPANTS 329,261 women aged 40 to 79 years underwent 869 286 mammograms (231 034 digital; 638 252 film-screen). MEASUREMENTS Invasive cancer or ductal carcinoma in situ diagnosed within 12 months of a digital or film-screen examination and calculation of mammography sensitivity, specificity, cancer detection rates, and tumor outcomes. RESULTS Overall, cancer detection rates and tumor characteristics were similar for digital and film-screen mammography, but the sensitivity and specificity of each modality varied by age, tumor characteristics, breast density, and menopausal status. Compared with film-screen mammography, the sensitivity of digital mammography was significantly higher for women aged 60 to 69 years (89.9% vs. 83.0%; P = 0.014) and those with estrogen receptor-negative cancer (78.5% vs. 65.8%; P = 0.016); borderline significantly higher for women aged 40 to 49 years (82.4% vs. 75.6%; P = 0.071), those with extremely dense breasts (83.6% vs. 68.1%; P = 0.051), and pre- or perimenopausal women (87.1% vs. 81.7%; P = 0.057); and borderline significantly lower for women aged 50 to 59 years (80.5% vs. 85.1%; P = 0.097). The specificity of digital and film-screen mammography was similar by decade of age, except for women aged 40 to 49 years (88.0% vs. 89.7%; P < 0.001). LIMITATION Statistical power for subgroup analyses was limited. CONCLUSION Overall, cancer detection with digital or film-screen mammography is similar in U.S. women aged 50 to 79 years undergoing screening mammography. Women aged 40 to 49 years are more likely to have extremely dense breasts and estrogen receptor-negative tumors; if they are offered mammography screening, they may choose to undergo digital mammography to optimize cancer detection. PRIMARY FUNDING SOURCE National Cancer Institute.

ACR Appropriateness Criteria Breast Cancer Screening

Mammography is the recommended method for breast cancer screening of women in the general population. However, mammography alone does not perform as well as mammography plus supplemental screening in high-risk women. Therefore, supplemental screening with MRI or ultrasound is recommended in selected high-risk populations. Screening breast MRI is recommended in women at high risk for breast cancer on the basis of family history or genetic predisposition. Ultrasound is an option for those high-risk women who cannot undergo MRI. Recent literature also supports the use of breast MRI in some women of intermediate risk, and ultrasound may be an option for intermediate-risk women with dense breasts. There is insufficient evidence to support the use of other imaging modalities, such as thermography, breast-specific gamma imaging, positron emission mammography, and optical imaging, for breast cancer screening. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Differential diagnosis of mammographically and clinically occult breast lesions on diffusion‐weighted MRI

To investigate the diagnostic performance of diffusion‐weighted imaging (DWI) for mammographically and clinically occult breast lesions.

Apparent Diffusion Coefficient Values for Discriminating Benign and Malignant Breast MRI Lesions: Effects of Lesion Type and Size

OBJECTIVE The purpose of this study was to determine whether lesion type and size affect discrimination of benign and malignant breast lesions with diffusion-weighted MRI. MATERIALS AND METHODS This study included 91 women with 116 breast lesions identified with dynamic contrast-enhanced MRI. Diffusion-weighted images were acquired during clinical breast MRI at b values of 0 and 600 s/mm(2). Differences in the apparent diffusion coefficients (ADCs) of benign and malignant lesions were compared by lesion type (mass or nonmasslike enhancement) and size (<or= 1 cm or > 1 cm), and receiver operating characteristics analysis was performed to evaluate diagnostic performance based on ADC thresholds. RESULTS Sixteen of 71 masses and 13 of 45 lesions with nonmasslike enhancement were malignant. The mean ADC was significantly lower for malignant than for benign lesions for both masses (mean difference, 0.49 x 10(-3) mm(2)/s; p < 0.001) and lesions with nonmasslike enhancement (mean difference, 0.20 x 10(-3) mm(2)/s; p = 0.02). The area under the receiver operating characteristics curve (AUC) was greater for masses (AUC, 0.80) than for lesions with nonmasslike enhancement (AUC, 0.66). The mean ADC for malignant masses (1.25 x 10(-3) mm(2)/s) was lower than that for malignant lesions with nonmasslike enhancement (1.41 x 10(-3) mm(2)/s; p = 0.07). The median lesion size was 1.1 cm (range, 0.5-8.3 cm); 45 of 71 masses (63%) measured 1 cm or smaller, and 37 of 45 lesions with nonmasslike enhancement (82%) were larger than 1 cm. There was no relation (p > 0.05) between ADC value and lesion size for benign or malignant lesions, and there were no differences in AUC based on lesion size (p > 0.05). CONCLUSION Diffusion-weighted MRI shows promise in differentiation of benign and malignant masses and lesions with nonmasslike enhancement found at breast MRI and is not affected by lesion size. However, ADC measurements may be more useful for discriminating masses than for discriminating lesions with nonmasslike enhancement.