Use of ultrasound and MRI to stage the axilla for breast cancer before and after neoadjuvant chemotherapy prior to targeted sentinel lymphadenectomy.

PURPOSE: Prior data from this Center demonstrated that for patients who had biopsy-proven axillary metastases, were ycN0 after neoadjuvant chemotherapy (NAC), and had a wire-directed (targeted) sentinel lymphadenectomy (WD-SLND), 60% were node negative. The hypothesis of this study was that results of axillary imaging either before or after NAC would be predictive of final pathologic status after WD-SLND. METHODS: For patients treated with NAC between 2015 and 2023, ultrasound and MRI images of the axilla were retrospectively reviewed by radiologists specializing in breast imaging, who were blinded to the surgical and pathology results. RESULTS: Of 113 patients who fit the clinical criteria, 66 (58%) were ypN0 at WD-SLND and 34 (30%) had a pathologic complete response to NAC. There was no correlation between the number of abnormal lymph nodes on pre-NAC ultrasound or MRI imaging and the final pathologic status of the lymph nodes. The positive predictive value (PPV) of abnormal post-NAC axillary imaging was 48% for ultrasound and 53% for MRI. The negative predictive value (NPV) for normal post-NAC axillary imaging was 67% for ultrasound and 68% for MRI. CONCLUSION: The results of axillary imaging were not adequate to identify lymph nodes after NAC that were persistently pathologically node positive or those which had become pathologically node negative.

Imaging of Benign and Malignant Breast Lesions Using Contrast-Enhanced Ultrasound: A Pictorial Essay.

ABSTRACT: Contrast-enhanced ultrasound is a promising noninvasive imaging technique for evaluating benign and malignant breast lesions, as contrast provides information about perfusion and microvasculature. Contrast-enhanced ultrasound is currently off-label use in the breast in the United States, but its clinical and investigational use in breast imaging is gaining popularity. It is important for radiologists to be familiar with the imaging appearances of benign and malignant breast masses using contrast-enhanced ultrasound. This pictorial essay illustrates enhancement patterns of various breast masses from our own experience. Pathologies include subtypes of invasive breast cancer, fibroadenomas, papillary lesions, fibrocystic change, and inflammatory processes. Contrast-enhanced ultrasound pitfalls and limitations are discussed.

Accuracy of contrast-enhanced spectral mammography compared with MRI for invasive breast cancers: Prospective study in population of predominantly underrepresented minorities.

OBJECTIVES: This prospective study compares contrast-enhanced spectral mammography (CESM) with contrast-enhanced breast MRI in assessing the extent of newly diagnosed breast cancer in a multiethnic cohort. METHODS: This study includes 41 patients with invasive breast cancer detected by mammography or conventional ultrasound imaging from May 2017 to March 2020. CESM and MRI scans were performed prior to any treatment. Results are compared with each other and to histopathology. Detection of the malignant lesion was assessed by sensitivity, specificity, PPV, NPV. Consistency of malignant tumor size measurement was compared between modalities using Intraclass Correlation Coefficient (ICC). RESULTS: In a multiethnic cohort with over 65% Hispanic and African-American women, the sensitivity of detecting malignant lesions for CESM is 93.1% (77.23%, 99.15%) and MRI is 96.55% (82.24%, 99.91%). The PPV for CESM 96.43% (81.65%, 99.91%) is better compared to MRI 82.35% (65.47%, 93.24%). CESM is as effective as MRI in evaluating index cancers and multifocal/multicentric/contralateral disease. CESM has greater specificity and PPV since MRI tends to overcall benign lesions. There is a good agreement of tumor size between CESM to surgery and MRI to surgery with ICC of 0.85 (95% CI 0.69, 0.93) and 0.87 (95% CI 0.74, 0.94), respectively. There is good agreement of malignancy detection between CESM and MRI with Kappa of 0.74 (95% CI 0.52, 0.95). CONCLUSIONS: CESM is an effective imaging modality for evaluating the extent of disease in newly diagnosed invasive breast cancers and a good alternative to MRI in a multiethnic population.

Breast MRI during Neoadjuvant Chemotherapy: Lack of Background Parenchymal Enhancement Suppression and Inferior Treatment Response.

Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response. Materials and Methods A retrospective review was performed for women with menopausal status data who were treated for breast cancer by one of 10 drug arms (standard NAC with or without experimental agents) between May 2010 and November 2016 in the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2 TRIAL (NCT01042379). Patients underwent MRI at four points: before treatment (T0), early treatment (T1), interregimen (T2), and before surgery (T3). BPE was quantitatively measured by using automated fibroglandular tissue segmentation. To test the hypothesis effectively, a subset of examinations with BPE with high-quality segmentation was selected. BPE change from T0 was defined as suppressed or nonsuppressed for each point. The Fisher exact test and the Z tests of proportions with Yates continuity correction were used to examine the relationship between BPE suppression and pathologic complete response (pCR) in hormone receptor (HR)-positive and HR-negative cohorts. Results A total of 3528 MRI scans from 882 patients (mean age, 48 years ± 10 [standard deviation]) were reviewed and the subset of patients with high-quality BPE segmentation was determined (T1, 433 patients; T2, 396 patients; T3, 380 patients). In the HR-positive cohort, an association between lack of BPE suppression and lower pCR rate was detected at T2 (nonsuppressed vs suppressed, 11.8% [six of 51] vs 28.9% [50 of 173]; difference, 17.1% [95% CI: 4.7, 29.5]; P = .02) and T3 (nonsuppressed vs suppressed, 5.3% [two of 38] vs 27.4% [48 of 175]; difference, 22.2% [95% CI: 10.9, 33.5]; P = .003). In the HR-negative cohort, patients with nonsuppressed BPE had lower estimated pCR rate at all points, but the P values for the association were all greater than .05. Conclusions In hormone receptor-positive breast cancer, lack of background parenchymal enhancement suppression may indicate inferior treatment response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.

Factors associated with MRI detection of occult lesions in newly diagnosed breast cancers.

BACKGROUND: The use of preoperative magnetic resonance imaging (MRI) for newly diagnosed breast cancer remains controversial. We examined factors associated with detection of occult multicentric, multifocal, and contralateral malignant lesions only seen by MRI. METHODS: We performed a retrospective analysis of consecutive patients undergoing preoperative MRI for breast cancer. Clinicopathologic data were assessed regarding the findings of multifocality, multicentricity, and the presence of contralateral lesions. We analyzed the association of factors with these findings on MRI. RESULTS: Of 857 patients undergoing MRI, 770 patients met inclusion criteria. Mean age was 54.7 years. Biopsy-proven detection rates by MRI for multifocal, multicentric, and contralateral cancers were 6.2% (48 of 770), 1.9% (15 of 770) and 3.1% (24 of 770), respectively. African American race and heterogeneously or extremely dense mammographic density were associated with multifocal cancers on MRI. Larger lesion size and mammographic density were associated with multicentric cancers. Invasive lobular carcinoma (ILC) and progesterone receptor (PR)-positivity were associated with contralateral cancers. CONCLUSIONS: African American race, heterogeneously or extremely dense mammographic density, ILC, and PR-positivity were associated with additional biopsy-proven cancers based on MRI. These factors should be considered when assessing the clinical utility of preoperative breast MRI.

Contrast-Enhanced Ultrasound Imaging of Breast Masses: Adjunct Tool to Decrease the Number of False-Positive Biopsy Results.

OBJECTIVES: This pilot study evaluated use of contrast-enhanced ultrasound (CEUS) to reduce the number of benign breast masses recommended for biopsy. METHODS: This prospective study included 131 consenting women, from October 2016 to June 2017, with American College of Radiology Breast Imaging Reporting and Data System category 4a, 4b, and 4c masses detected by mammography, conventional ultrasound (US), or both. Contrast-enhanced US examinations (using intravenous injection of perflutren lipid microspheres or sulfur hexafluoride lipid-type A microspheres) were performed before biopsy. Qualitative and quantitative CEUS parameters were compared with reference standard histopathologic results from biopsy of 131 masses. RESULTS: There were 109 benign, 6 high-risk, and 16 malignant masses, with a median size of 12 mm (range, 4 to 48 mm) on conventional US imaging. Of 131 masses, 93 (71%) enhanced on CEUS imaging, including 73 of 109 (67%) benign, 6 of 6 (100%) high-risk, and 14 of 16 (87.5%) malignant. Thirty-eight lesions did not enhance, including 36 of 109 (33%) benign and 2 of 16 (12.5%) malignant. Prediction models using recursive petitioning revealed that CEUS may reduce 31% (95% confidence interval, 23%, 40%) of benign biopsies for masses that are: nonenhancing with circumscribed margins or enhancing with an oval shape and homogeneous enhancement. Quantitative parameters indicated that benign masses had the longest time to peak (P = .078), highest time-to-peak ratio of mass to background (P = .036), lowest peak intensity (P = .021), and smallest difference in peak intensity between the mass and background (P = .079) compared to high-risk and malignant lesions. CONCLUSIONS: Contrast-enhanced US may be a valuable modality that can be used to predict benign pathologic results of breast masses, thereby reducing the number of biopsies.

Accuracy of Contrast-Enhanced Ultrasound Compared With Magnetic Resonance Imaging in Assessing the Tumor Response After Neoadjuvant Chemotherapy for Breast Cancer.

OBJECTIVES: This pilot study compared contrast enhanced ultrasound (US) with contrast-enhanced magnetic resonance imaging (MRI) in assessing the treatment response in patients with breast cancer receiving preoperative neoadjuvant chemotherapy (NAC). METHODS: This prospective Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study included 30 patients, from January 2014 to October 2015, with invasive breast cancer detected by mammography, conventional US imaging, or both and scheduled for NAC. Informed consent was obtained. Contrast-enhanced US (perflutren lipid microspheres, 10 µL/kg) and MRI (gadopentetate dimeglumine, 0.1 mmol/kg) scans were performed at baseline before starting NAC and after completing NAC before surgery. Results of the imaging techniques were compared with each other and with histopathologic findings obtained at surgery using the Spearman correlation. Tumor size and enhancement parameters were compared for 15 patients with contrast-enhanced US, MRI, and surgical pathologic findings. RESULTS: The median tumor size at baseline was 3.1 cm on both contrast-enhanced US and MRI scans. The Spearman correlation showed strong agreement in tumor size at baseline between contrast-enhanced US and MRI (r = 0.88; P < .001) but less agreement in tumor size after NAC (r = 0.66; P = .004). Trends suggested that contrast-enhanced US (r = 0.75; P < .001) had a better correlation than MRI (r = 0.42; P = .095) with tumor size at surgery. Contrast-enhanced US was as effective as MRI in predicting a complete pathologic response (4 patients; 75.0% accuracy for both) and a non-complete pathologic response (11 patients; 72.7% accuracy for both). CONCLUSIONS: Contrast enhanced US is a valuable imaging modality for assessing the treatment response in patients receiving NAC and had a comparable correlation as MRI with breast cancer size at surgery.

High-frequency ultrasound imaging for breast cancer biopsy guidance.

Image-guided core needle biopsy is the current gold standard for breast cancer diagnosis. Microcalcifications, an important radiographic finding on mammography suggestive of early breast cancer such as ductal carcinoma in situ, are usually biopsied under stereotactic guidance. This procedure, however, is uncomfortable for patients and requires the use of ionizing radiation. It would be preferable to biopsy microcalcifications under ultrasound guidance since it is a faster procedure, more comfortable for the patient, and requires no radiation. However, microcalcifications cannot reliably be detected with the current standard ultrasound imaging systems. This study is motivated by the clinical need for real-time high-resolution ultrasound imaging of microcalcifications, so that biopsies can be accurately performed under ultrasound guidance. We have investigated how high-frequency ultrasound imaging can enable visualization of microstructures in ex vivo breast tissue biopsy samples. We generated B-mode images of breast tissue and applied the Nakagami filtering technique to help refine image output so that microcalcifications could be better assessed during ultrasound-guided core biopsies. We describe the preliminary clinical results of high-frequency ultrasound imaging of ex vivo breast biopsy tissue with microcalcifications and without Nakagami filtering and the correlation of these images with the pathology examination by hematoxylin and eosin stain and whole slide digital scanning.

A Phase II Study of 3'-Deoxy-3'-18F-Fluorothymidine PET in the Assessment of Early Response of Breast Cancer to Neoadjuvant Chemotherapy: Results from ACRIN 6688.

UNLABELLED: Our objective was to determine whether early change in standardized uptake values (SUVs) of 3'deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) using PET with CT could predict pathologic complete response (pCR) of primary breast cancer to neoadjuvant chemotherapy (NAC). The key secondary objective was to correlate SUV with the proliferation marker Ki-67 at baseline and after NAC. METHODS: This prospective, multicenter phase II study did not specify the therapeutic regimen, thus, NAC varied among centers. All evaluable patients underwent (18)F-FLT PET/CT at baseline (FLT1) and after 1 cycle of NAC (FLT2); 43 patients were imaged at FLT1, FLT2, and after NAC completion (FLT3). The percentage change in maximum SUV (%ΔSUVmax) between FLT1 and FLT2 and FLT3 was calculated for the primary tumors. The predictive value of ΔSUVmax for pCR was determined using receiver-operating-characteristic curve analysis. The correlation between SUVmax and Ki-67 was also assessed. RESULTS: Fifty-one of 90 recruited patients (median age, 54 y; stage IIA-IIIC) met the eligibility criteria for the primary objective analysis, with an additional 22 patients totaling 73 patients for secondary analyses. A pCR in the primary breast cancer was achieved in 9 of 51 patients. NAC resulted in a significant reduction in %SUVmax (mean Δ, 39%; 95% confidence interval, 31-46). There was a marginal difference in %ΔSUVmax_FLT1-FLT2 between pCR and no-pCR patient groups (Wilcoxon 1-sided P = 0.050). The area under the curve for ΔSUVmax in the prediction of pCR was 0.68 (90% confidence interval, 0.50-0.83; Delong 1-sided P = 0.05), with slightly better predictive value for percentage mean SUV (P = 0.02) and similar prediction for peak SUV (P = 0.04). There was a weak correlation with pretherapy SUVmax and Ki-67 (r = 0.29, P = 0.04), but the correlation between SUVmax and Ki-67 after completion of NAC was stronger (r = 0.68, P < 0.0001). CONCLUSION: (18)F-FLT PET imaging of breast cancer after 1 cycle of NAC weakly predicted pCR in the setting of variable NAC regimens. Posttherapy (18)F-FLT uptake correlated with Ki-67 on surgical specimens. These results suggest some efficacy of (18)F-FLT as an indicator of early therapeutic response of breast cancer to NAC and support future multicenter studies to test (18)F-FLT PET in a more uniformly treated patient population.

Modified Bi-Rads Scoring of Breast Imaging Findings Improves Clinical Judgment.

In contrast with the reporting requirements currently mandated under the Federal Mammography Quality Standards Act (MQSA), we propose a modification of the Breast Imaging Reporting and Data System (Bi-Rads) in which a concluding assessment category is assigned, not to the examination as a whole, but to every potentially malignant abnormality observed. This modification improves communication between the radiologist and the attending clinician, thereby facilitating clinical judgment leading to appropriate management. In patients with breast cancer eligible for breast conserving therapy, application of this modification brings to attention the necessity for such patients to undergo pretreatment biopsies of all secondary, synchronous ipsilateral lesions scored Bi-Rads 3-5. All contralateral secondary lesions scored Bi-Rads 3-5 also require pretreatment biopsies. The application of this modification of the MSQA demonstrates the necessity to alter current recommendations ("short-interval follow-up") for secondary, synchronous Bi-Rads 3 ("probably benign") image-detected abnormalities prior to treatment of the index malignancy.

Double-Blind Randomized 12-Month Soy Intervention Had No Effects on Breast MRI Fibroglandular Tissue Density or Mammographic Density.

Soy supplementation by patients with breast cancer remains controversial. No controlled intervention studies have investigated the effects of soy supplementation on mammographic density in patients with breast cancer. We conducted a double-blind, randomized, placebo-controlled intervention study in previously treated patients with breast cancer (n = 66) and high-risk women (n = 29). We obtained digital mammograms and breast MRI scans at baseline and after 12 months of daily soy (50 mg isoflavones per day; n = 46) or placebo (n = 49) tablet supplementation. The total breast area (MA) and the area of mammographic density (MD) on the mammogram were measured using a validated computer-assisted method, and mammographic density percent (MD% = 100 × MD/MA) was determined. A well-tested computer algorithm was used to quantitatively measure the total breast volume (TBV) and fibroglandular tissue volume (FGV) on the breast MRI, and the FGV percent (FGV% = 100 × FGV/TBV) was calculated. On the basis of plasma soy isoflavone levels, compliance was excellent. Small decreases in MD% measured by the ratios of month 12 to baseline levels were seen in the soy (0.95) and the placebo (0.87) groups; these changes did not differ between the treatments (P = 0.38). Small decreases in FGV% were also found in both the soy (0.90) and the placebo (0.92) groups; these changes also did not differ between the treatments (P = 0.48). Results were comparable in patients with breast cancer and high-risk women. We found no evidence that soy supplementation would decrease mammographic density and that MRI might be more sensitive to changes in density than mammography.

The role of axillary ultrasound in the detection of metastases from primary breast cancers.

BACKGROUND: The value of diagnostic axillary ultrasound (AUS) in the preoperative evaluation of lymph nodes for breast cancer patients has yet to be completely clarified. METHODS: Results of AUS were reviewed for all patients with invasive cancers who were clinically node negative (cN0) and had subsequent axillary lymphadenectomy. Patients with positive ultrasound-guided node core biopsies bypassed sentinel lymph node biopsy (SLNB) and had axillary lymph node dissection, whereas those with sonographically normal nodes or benign/nondiagnostic biopsy results had SLNB. RESULTS: Of 128 cN0 patients with invasive cancer, 23 (18%) had abnormal axillary AUS. Of 18 core biopsies, 12 (67%) were malignant. SLNB was positive in 19 of 110 (17%) patients. ALND was performed in 32 (25%) patients. For determining axillary metastases, AUS sensitivity was 16 of 31 (52%), specificity was 90 of 97 (93%), the positive predictive value was 16 of 23 (69%), and the negative predictive value was 90 of 105 (86%). CONCLUSIONS: AUS examination was a valuable method for evaluating the axilla in newly diagnosed cN0 breast cancer patients.

Lowering oral contraceptive norethindrone dose increases estrogen and progesterone receptor levels with no reduction in proliferation of breast epithelium: a randomized trial.

BACKGROUND: This study was conducted to compare breast epithelial-cell proliferation and estrogen and progesterone receptor levels in women taking one of two oral contraceptives (OCs) containing the same dose of estrogen but different doses of the progestin norethindrone (NET). STUDY DESIGN: Thirty-three women were randomly assigned 1:1 to one of two OCs with 35-mcg ethinylestradiol (EE2) but different doses of NET - 1 or 0.4 mg. At the end of the active pill phase of the third OC cycle, a breast biopsy was performed and the percentages of epithelial cells of the terminal duct lobular units were measured for Ki67 (MIB1), progesterone receptors A and B (PRA and PRB, respectively), and estrogen receptor α (ERα). RESULTS: The biopsies from 27 women had sufficient epithelium for analysis. The percentages of cells positive for PRA, PRB and ERα were approximately double with the lower progestin dose (PRA: p=.041; PRB: p=.030; ERα: p=.056). The Ki67 percentage was not reduced with the lower progestin dose (12.5% for 0.4-mg NET vs. 7.8% for 1.0-mg NET). CONCLUSIONS: The increase in PRA-, PRB- and ERα-positive cells with the 60% lower progestin dose OC appears likely to account for its failure to decrease breast-cell proliferation. This breast-cell proliferation result is contrary to that predicted from the results of lowering the medroxyprogesterone acetate dose in menopausal hormone therapy.

Breast epithelial cell proliferation is markedly increased with short-term high levels of endogenous estrogen secondary to controlled ovarian hyperstimulation.

Oocyte donors have high serum estradiol (E2) levels similar to the serum levels seen in the first trimester of pregnancy. We report in this article our studies comparing cell proliferation, Ki67 (MIB1), and estrogen and progesterone receptor levels (ERα, PRA, and PRB) in the breast terminal duct lobular units of oocyte donors, women in early pregnancy, and in normally cycling women. Breast tissue and blood samples were obtained from 10 oocyte donors, and 30 pregnant women at 5-18 weeks of gestation. Breast tissue samples were also obtained from 26 normally cycling women. In the oocyte donors: peak E2 (mean ~15,300 pmol/l) was reached on the day before oocyte (and tissue) donation; peak progesterone (P4; mean 36.3 nmol/l) was reached on the day of donation; Ki67 was positively associated with level of E2, and the mean Ki67 was 7.0% significantly greater than the mean 1.8% of cycling women. In the pregnant women: mean E2 rose from ~2,000 pmol/l at 5 weeks of gestation to ~27,000 pmol/l at 18 weeks; mean P4 did not change from ~40 nmol/l until around gestational week 11 when it increased to ~80 nmol/l; mean Ki67 was 15.4% and did not vary with gestational age or E2. Oocyte donors have greatly increased levels of E2 and of breast-cell proliferation, both comparable in the majority of donors to the levels seen in the first trimester of pregnancy. Whether their short durations of greatly increased E2 levels are associated with any long-term beneficial effects on the breast, as occurring in rodent models, is not known.

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.

Granulomatous lobular mastitis: imaging, diagnosis, and treatment.

OBJECTIVE: Granulomatous lobular mastitis is a rare chronic inflammatory disease that has clinical and radiologic findings similar to those of breast cancer. We performed a retrospective analysis of clinical, imaging, and treatment findings in 54 women diagnosed with granulomatous lobular mastitis between January 2000 and April 2008. CONCLUSION: The imaging findings of granulomatous lobular mastitis overlap with those of malignancy. The most common presentation is a focal asymmetric density on mammography and an irregular hypoechoic mass with tubular extensions on ultrasound. Core biopsy is typically diagnostic. Once the diagnosis is established by tissue sampling, corticosteroids are the first line of treatment.

Progesterone and estrogen receptors in pregnant and premenopausal non-pregnant normal human breast.

We report here our studies of nuclear staining for the progesterone and estrogen receptors (PRA, PRB, ERalpha) and cell proliferation (MIB1) in the breast terminal duct lobular unit epithelium of 26 naturally cycling premenopausal women and 30 pregnant women (median 8.1 weeks gestation). Square root transformations of the PRA, PRB and ERalpha values, and a logarithmic transformation of the MIB1 values, were made to achieve more normal distributions of the values. PRA expression decreased from a mean of 17.8% of epithelial cells in cycling subjects to 6.2% in pregnant subjects (P = 0.013). MIB1 expression increased from 1.7% in cycling subjects to 16.0% in pregnant subjects (P < 0.001). PRB and ERalpha expression was slightly lower in pregnant subjects but the differences were not statistically significant. Sixteen of the non-pregnant subjects were nulliparous and ten were parous so that we had limited power to detect changes associated with parity. PRA was statistically significantly lower in parous women than in nulliparous women (32.2% in nulliparous women vs. 10.2%; P = 0.014). PRB (23.5 vs. 12.9%), ERalpha (14.4 vs. 8.6%) and MIB1 (2.2 vs. 1.2%) were also lower in parous women, but the differences were not statistically significant. The marked decreases in PRA in pregnancy and in parous women has also been found in the rat. A reduction in PRA expression may be a useful marker of the reduction in risk with pregnancy and may be of use in evaluating the effect of any chemoprevention regimen aimed at mimicking pregnancy. Short-term changes in PRA expression while the chemoprevention is being administered may be a more useful marker.

Differentiation of cancerous lesions in excised human breast specimens using multiband attenuation profiles from ultrasonic transmission tomography.

OBJECTIVE: This study examines the tissue differentiation capability of the recently developed high-resolution ultrasonic transmission tomography (HUTT) system in the context of differentiating between benign and malignant tissue types in mastectomy specimens. METHODS: Eight mastectomy patients provided breast specimens with benign and malignant lesions. The specimens were scanned by the HUTT system with a pair of either 8- or 4-MHz transducers. Multiband HUTT images over the frequency range from 2 to 10 MHz provide characteristic profiles of frequency-dependent attenuation, termed "multiband profiles," at individual pixels. These features are classified through a novel algorithm of "segment-wise classification" that identifies the disjoint segments of various tissue types and subsequently classifies them into respective diagnostic categories using a measure of proximity to the respective multiband profile templates that have been previously obtained from reference data. RESULTS: We preformed intraspecimen and interspecimen analyses of 108 slices from 8 mastectomy specimens for which "ground truth" was provided by pathology reports. The average performance indices for 2-way classification (malignant versus nonmalignant tissue) in these intraspecimen (interspecimen) specimen studies were found to be sensitivity of 81.9% (89.6%), specificity of 92.9% (92.1%), and accuracy of 89.2% (89.4%), whereas the indices for the 3-way classification were moderately lower. CONCLUSIONS: The results have shown the potential of the HUTT technology for reliable differentiation of cancerous lesions from benign changes and normal tissue in mastectomy specimens using frequency-dependent ultrasound attenuation profiles.

Greatly increased occurrence of breast cancers in areas of mammographically dense tissue.

INTRODUCTION: Mammographic density is a strong, independent risk factor for breast cancer. A critical unanswered question is whether cancers tend to arise in mammographically dense tissue (i.e. are densities directly related to risk or are they simply a marker of risk). This question cannot be addressed by studying invasive tumors because they manifest as densities and cannot be confidently differentiated from the densities representing fibrous and glandular tissue. We addressed this question by studying ductal carcinoma in situ (DCIS), as revealed by microcalcifications. METHOD: We studied the cranio-caudal and the mediolateral-oblique mammograms of 28 breasts with a solitary DCIS lesion. Two experienced radiologists independently judged whether the DCIS occurred in a mammographically dense area, and determined the density of different areas of the mammograms. RESULTS: It was not possible to determine whether the DCIS was or was not in a dense area for six of the tumors. Of the remaining 22 lesions, 21 occurred in dense tissue (test for difference from expected taken as the percentage of density of the 'mammographic quadrant' containing DCIS; P < 0.0001). A preponderance of DCIS (17 out of 28) occurred in the mammographic quadrant with the highest percentage density. CONCLUSION: DCIS occurs overwhelmingly in the mammographically dense areas of the breast, and pre-DCIS mammograms showed that this relationship was not brought about by the presence of the DCIS. This strongly suggests that some aspect of stromal tissue comprising the mammographically dense tissue directly influences the carcinogenic process in the local breast glandular tissue.