Molecular breast imaging: advantages and limitations of a scintimammographic technique in patients with small breast tumors

Preliminary studies from our laboratory showed that molecular breast imaging (MBI) can reliably detect tumors <2 cm in diameter. This study extends our work to a larger patient population and examines the technical factors that influence the ability of MBI to detect small breast tumors. Following injection of 740 MBq Tc-99m sestamibi, MBI was performed on 100 patients scheduled for biopsy of a lesion suspicious for malignancy that measured <2 cm on mammography or sonography. Using a small field of view gamma camera, patients were imaged in the standard mammographic views using light pain-free compression. Subjective discomfort, breast thickness, the amount of breast tissue in the detector field of view, and breast counts per unit area were measured and recorded. Follow-up was obtained in 99 patients; 53 patients had 67 malignant tumors confirmed at surgery. Of these, 57 of 67 were detected by MBI (sensitivity 85%). Sensitivity was 29%, 86%, and 97% for tumors <5, 6-10, and > or =11 mm in diameter, respectively. In seven patients, MBI identified eight additional mammographically occult tumors. Of 47 patients with no evidence of cancer at biopsy or surgery, there were 36 true negative and 11 false positive scans on MBI. MBI has potential for the regular detection of malignant breast tumors less than 2 cm in diameter. Work in progress to optimize the imaging parameters and technique may further improve sensitivity and specificity.     

Quantification of Radio-tracer Uptake in Axillary Lymph Nodes using Breast Specific Gamma Imaging (BSGI): Benign Radio-tracer Extravasation versus Uptake Secondary to Breast Cancer

Abstract:  To develop a means of quantifying axillary radio-tracer uptake in patients undergoing breast specific gamma imaging. This may help differentiate uptake secondary to extravasation of the radio-tracer at the injection from increased uptake as a result of breast cancer metastatic to lymph nodes. A retrospective analysis of patients who had undergone breast specific gamma imaging was performed. Scans from 26 patients showing increased axillary uptake of radio-tracer were identified from 939 patients reviewed. Eighteen of these patients had increased axillary uptake ipsilateral to the side of tracer injection in the absence of breast cancer on that side. Of these 18 cases, eight patients had pathologic proven axillary metastatic disease with increased axillary uptake contralateral to the side of tracer injection. The maximum signal intensity for each region of increased radio-tracer uptake was measured using the net maximum uptake per region of interest and the two groups of patients were compared. Statistical significance was determined using a two-tailed p-value and 95% confidence intervals were considered statistically significant. The calculated means of the "net maximum uptake per region of interest" in the subjects with increased radio-tracer uptake secondary to radio-tracer extravasation and metastatic breast cancer were 177.89 and 117.25, respectively. Comparison of the means yielded a two-tailed p-value of 0.0498, which is statistically significant. There is a statistically significant greater intensity of axillary radio-tracer uptake when the uptake occurs secondary to extravasation when compared with metastases to axillary lymph nodes.     

Comparative Diagnostic Utility of Low‐Dose Breast‐Specific Gamma Imaging to Current Clinical Standard

To retrospectively compare low‐dose (7–10 mCi) to high‐dose (15–30 mCi) breast‐specific gamma imaging (BSGI) in the detection of breast cancer. A retrospective review of 223 consecutive women who underwent BSGI exam between February 2011 and August 2013 with subsequent pathologic analysis was performed. Women were divided into low‐dose and high‐dose groups. The results of BSGI and pathology were compared, and the sensitivity, positive predictive value (PPV), and negative predictive value (NPV) were determined. A subgroup analysis was performed to evaluate specificity using benign follow‐up imaging to establish true‐negative results. There were 223 women who met inclusion criteria with 109 patients with 153 lesions in the low‐dose group and 114 patients with 145 lesions in the high‐dose group. Pathologic correlation demonstrates sensitivities of 97.6% (95% CI = 90.9–99.6%) and 94.6% (95% CI = 84.2–98.6%; p = 0.093), PPVs of 62.1% (95% CI = 53.2–70.3%) and 50.5% (95% CI = 40.6–60.3%, p = 0.089), and NPVs of 90.5% (95% CI = 68.2–98.3%) and 92.5% (95% CI = 78.5–98.0%, p = 0.781) in the low‐dose and high‐dose groups, respectively. Subgroup analysis included 72 patients with 98 lesions in the low‐dose group and 116 patients with 132 lesions in the high‐dose group, with a specificity of 53.7% (95% CI = 39.7–67.1%) and 66.3% (95% CI = 56.2–75.2%%, p = 0.143), respectively. Low‐dose BSGI demonstrated high sensitivity and NPV in the detection of breast cancer comparable to the current standard dose BSGI, with moderate specificity and PPV in a limited subgroup analysis, which was associated with a substantial number of false‐positives.     

Breast conserving therapy with accelerated partial breast versus external beam whole breast irradiation: comparison of imaging sequela and complications in a matched population

Our purpose was to evaluate and compare the imaging sequela and complications of accelerated partial breast irradiation (APBI) with those occurring in patients treated with standard external beam therapy. Patient selection included those who met the criteria for possible ABPI: age 45 or older; cancer stage T1N0M0 or ductal carcinoma in situ 3 cm or less, and negative surgical margins. One hundred and ninety seven had complete records and films available for review. Ninety-seven (49%) were treated with APBI (MammoSite) and 100(51%) were treated with external beam. Image findings for APBI versus external beam were: distortion 90(93%) versus 83(83%), seroma 67(69%) versus 7(7%), skin edema 52(54%) versus 47(47%), increased stroma 75(77%) versus 66(66%), calcifications 10(10%) versus 6(6%), and fat necrosis 12(12%) versus 6(6%). For APBI, skin and stromal edema was more commonly focal. At imaging, the seroma rate was statistically and significantly different between the two treatment modes (p < 0.0001). For patients treated with APBI, seroma formation was not related to balloon size and only weakly related to lumpectomy cavity size. The complication rate was significantly higher for those treated with APBI (36 versus 20%) and the types and treatment of complications differed. There were three recurrences among the APBI group and none among those treated with external beam radiation.     

Scientific Impact Recognition Award: Molecular breast imaging: a review of the Mayo Clinic experience

Background

Molecular breast imaging (MBI) depicts functional uptake of targeted radiotracers in the breast using dedicated gamma cameras.

Methods

MBI studies were performed under several institutional protocols evaluating the use of MBI in screening and diagnosis.

Results

By using a single-head system, sensitivity for breast cancer detection was 85% (57 of 67) overall and 29% for tumors 5 mm or less in diameter. Sensitivity improved to 91% (117 of 128) overall and 69% for tumors 5 mm or less using a dual-head system. In 650 high-risk patients undergoing breast cancer screening, MBI detected 7 cancers, 5 of which were missed on mammography. In 24 of 149 (16%) breast cancer patients MBI detected additional disease not seen on mammography. The sensitivity of MBI was 88% (83 of 94) for invasive ductal carcinoma, 79% (23 of 29) for invasive lobular carcinoma, and 89% (25 of 28) for ductal carcinoma in situ.

Conclusions

MBI can detect invasive ductal carcinoma, ductal carcinoma in situ, and invasive lobular carcinoma. It has a promising role in evaluating the extent of disease and multifocal disease in the breast for surgical treatment planning.     

Effectiveness of Breast-Specific Gamma Imaging (BSGI) for Breast Cancer in Korea: A Comparative Study

Abstract: Despite the fact that mammography has been the golden standard in breast cancer detection for several decades, its sensitivity decreases for women with dense breast tissue, which happens to be common in Korea. As an alternative, breast ultrasonography can be effective diagnostic modalities that complement the defect of mammography. Recently, breast‐specific gamma imaging (BSGI) has been introduced as a new diagnostic modality for breast cancer. This study was designed to analyze the effectiveness of BSGI in particular. In a retrospective study, 471 patients underwent BSGI, breast ultrasonography, and mammography simultaneously during the period between February 2009 and March 2010. The indications of BSGI were as follows: (a) patient who was diagnosed with malignancy prior to surgery, (b) patient who is under follow up after cancer surgery, (c) patient with lesions which cannot be evaluated by breast ultrasonography or mammography, (d) patient with multiple benign lesions, and (e) patient with suspicious lesion who refuses biopsy. Among these patients, 121 patients underwent biopsy, whereas others were followed up with imaging studies. We compared the BSGI results with those of mammography, breast ultrasonography, and pathology. The mean age of the patients was 49.63 ± 10.43 years. There were 107 patients with 110 malignant lesions and 364 patients with benign lesions. Total 474 lesions were evaluated. The sensitivities of BSGI, mammography, and breast ultrasonography were 94.45%, 93.64%, and 98.18%, respectively, whereas the specificities of BSGI, mammography, and breast ultrasonography were 90.93%, 90.66%, and 87.09%, respectively. The sensitivity and specificity of BSGI for axillary lymph node (LN) status were 44.7 4% and 87.88%, respectively. BSGI is a good complementary imaging modality with high sensitivity and high specificity for breast cancer detection. However, it has low efficacy for the evaluation for axillary LN status.     

Breast-specific gamma imaging with 99mTc-Sestamibi and magnetic resonance imaging in the diagnosis of breast cancer--a comparative study

The purpose of this study was to compare the sensitivity and specificity of breast-specific gamma imaging (BSGI) using a high-resolution breast-specific gamma camera and magnetic resonance imaging (MRI) in patients with indeterminate breast findings. Twenty-three women with an indeterminate breast finding that required BSGI and MRI as deemed necessary by the interpreting radiologist or referring physician were included. MRI was performed on a GE 1.5T scanner and BSGI was performed on a Dilon high-resolution breast-specific gamma camera. All imaging findings were correlated with pathologic diagnosis. Thirty-three indeterminate lesions were evaluated in the study. There were a total of nine pathologically confirmed cancers. There was no statistically significant difference in sensitivity of cancer detection between BSGI and MRI. BSGI demonstrated a greater specificity than MRI, 71% and 25%, respectively. BSGI has equal sensitivity and greater specificity than MRI for the detection of breast cancer.     

Breast‐Specific Gamma Imaging Influences Surgical Management in Patients with Breast Cancer

Breast‐specific gamma imaging (BSGI) is a physiologic breast imaging modality that provides more sensitive detection of breast lesions than mammography or ultrasound, and appears to have greater specificity than breast MRI. The purpose of this study was to evaluate how often BSGI changed surgical management in patients with breast cancer. Charts were reviewed from 218 consecutive eligible patients who had preoperative evaluation with BSGI or MRI before surgery for breast cancer from January 2008 to May 2010. Patients who were initially considered eligible for breast‐conserving therapy (BCT) were evaluated to determine how many ultimately had mastectomies. Patients who underwent mastectomy because of personal choice or ineligibility for BCT were excluded. Management was changed to mastectomy in 11.9% of those who had BSGI and 28.9% of those who had MRI. Review of pathology demonstrated that all patients who underwent mastectomies were not candidates for breast conservation. 15.4% of patients who underwent BCT based on BSGI findings required a single re‐excision due to positive surgical margins. 14.4% required mastectomy. In the MRI group, 18.8% required a single re‐excision, and 6.3% required mastectomy. Evaluation with BSGI changed management to mastectomy in a substantial proportion of patients believed to be eligible for BCT following standard imaging. BSGI is effective in evaluation of extent of disease in patients with breast cancer, and is comparable to MRI in terms of its influence on surgical management.     

The role of circulating extracellular vesicles in breast cancer classification and molecular subtyping

Currently, tumor biopsies are used for breast cancer molecular subtyping. Biopsies are associated with various pathological changes and are thought to contribute to the dissemination of tumor cells. Extracellular vesicles shed by tumor cells into circulation exhibit the molecular signature of the parent cells. Herein, we show that proteomic analysis of circulating EV can discriminate BC patients from healthy subjects and indicate stage of the disease. Also, we performed a correlation between the BC molecular subtype using plasma EV and immunohistochemistry of tumor biopsies. Circulating EV may represent a useful, non‐invasive tool to study the molecular makeup of BC tumors.     

胃泌素释放肽受体分子影像探针用于乳腺癌诊疗研究进展

分子影像探针因其能精准靶向肿瘤而成为国内外研究热点之一,其中纳米颗粒和肿瘤靶向肽在肿瘤成像与药物递送治疗肿瘤中具有重要作用。胃泌素释放肽受体(GRPR)在乳腺癌中呈高表达,研制自组装分子探针靶向乳腺癌细胞,可通过X线、MRI、PET/CT等成像方式诊断乳腺癌,亦可用于放射治疗、化学治疗及光热治疗等。本文就基于GRPR的分子影像探针用于乳腺癌诊疗进展进行综述。     

In situ analysis of breast cancer progression in murine models using a macroscopic fluorescence imaging system

BACKGROUND AND OBJECTIVE: The goal of this study was to use an inexpensive macroscopic imaging system to monitor tumor progression in mouse models in real-time with minimal intervention. STUDY DESIGN/MATERIALS AND METHODS: Illumination is provided via a xenon arc lamp and a fiber optic probe which delivers white light or quasi-monochromatic excitation via specific bandpass filters. Fluorescence emission from SCID and nude mice following mammary fat pad injection of red fluorescence protein (RFP)-expressing human breast cancer cell lines was recorded and quantified using a single lens reflex (SLR) digital camera. RESULTS: This simple system enabled the verification of successful tumor take and temporal quantification of tumor progression in mouse models. CONCLUSION: The macroscopic fluorescence imaging system represents an inexpensive and portable tool to facilitate non-invasive in situ cancer detection with the potential to monitor fluorescent tumor formation and investigation of the efficacy of potential cancer therapeutics.     

Treatment of early breast cancer, a long-term follow-up study: the GOCS experience

Most cases of breast cancer are diagnosed at early stage of disease; therefore, treatment is oriented to increase the disease-free interval (DFI) and overall survival (OS). The prognosis, in comparison with other malignancies, has improved in the last decades as a result of mammographic screening. The aim of the study was to report the incidence of local and distant recurrence, DFI and OS in patients (pts) with stage I and stage II breast cancer over a period of 26 years divided into three groups. From January 1978 to December 2004, 927 women with early breast cancer (EBC) were included, 350 were stage I and 577 Stage II (AJCC 2002). Patients were divided according to the year of diagnosis into three periods of 10 years: Group A (1978-1987) 135 pts, Group B (1988-1997) 412 pts, and Group C (1998-2004) 380 pts. DFI was analyzed from the date of initial diagnosis to the date of local or distant recurrence. OS was estimated from the date of initial diagnosis to the last follow-up or date of death. Median age was 51 years (28-92). Conservative surgery was performed in 69% of pts, adjuvant radiation therapy in 78%, adjuvant chemotherapy in 29%, and adjuvant hormone therapy in 18%. The median follow-up was 8.4 years (0.3-30). The mean tumor size in Group A was 2.7 cm, in Group B 2.2 cm, and in Group C 1.94 cm (p = 0.0001). The percentage of pts with stage I increased from 13% in Group A to 38% in Group B and to 47% in Group C (p = 0.0001). Local recurrence was documented in 5% of all pts, whereas 28% developed metastatic disease. The DFI and OS showed a statistically significant difference among the three groups (p = 0.005). DFI rate at 5, 10, 15, 20, and 25 years was 71%, 67%, 65%, 65%, and 64%, respectively. OS at 5, 10, 15, 20, and 25 years was 82%, 62%, 49%, 39%, and 28%, respectively. Factors that had an effect in OS demonstrated by the multivariate regression analysis were: Tumor size, ER status, and nodal involvement (p < 0.001). Clinical outcomes in EBC in our experience are similar to those reported in international literature. The DFI and OS showed a statistically significant difference among the three groups. This group of pts continues to have a good prognosis as shown by the OS rate at 5, 10, 15, 20, and 25 years, although a high percentage of pts still to have recurrence and die from breast cancer after 5, 10, 15, 20, and 25 years of follow-up.     

Evaluation of Malignant Breast Lesions in the Diagnostic Setting with Cone Beam Breast Computed Tomography (Breast CT): Feasibility Study

To investigate the feasibility of noncontrast and contrast‐enhanced cone beam breast Computed Tomography (CT) in demonstrating malignant breast lesions in the diagnostic setting. This Institutional Review Board approved, Health Information Portability and Accountability Act compliant, prospective study enrolled BI‐RADS four and five patients from 2008 to 2010. Eighty‐seven subjects had noncontrast breast CT, 42 had contrast‐enhanced breast CT (CE‐breast CT) with 70 pathologically confirmed cancer diagnoses. All 70 comprise the study cohort for noncontrast breast CT, and 23 who had CE‐breast CT comprise the cohort for CE‐breast CT. All had diagnostic work‐up. Patient age, breast density, lesion size and characteristics, biopsy method, and core pathology were recorded. A Fisher's exact test was used to detect a difference in detectability. For agreement in size measurement between the imaging modalities, a paired t‐test was employed. Reported p‐values were based on 2‐sided tests. Two one‐sided tests were calculated to determine equivalence within ±0.3 cm at a 90% significance level. Noncontrast breast CT identified 67 of 70 malignant lesions, detected by diagnostic work‐up. CE‐breast CT identified 23 of 23 index malignant lesions and in addition, found three malignant lesions in three cases not previously detected. Noncontrast breast CT demonstrated the index lesion in 67 of 70 cases and CE‐breast CT demonstrated the index lesion in all 23 cases. An additional three new malignant lesions not seen with conventional diagnostic work‐up were detected. In this preliminary study, breast CT with or without contrast was shown to be accurate at identifying malignant breast lesions in the diagnostic setting.     

Real-world application of breast-specific gamma imaging, initial experience at a community breast center and its potential impact on clinical care

BACKGROUND: Breast-specific gamma imaging (BSGI) has brought scintimammography back to the forefront by using a dedicated small field-of-view system designed to detect and localize lesions down to 2 mm. Initial studies have reported sensitivity equaling that of magnetic resonance imaging, but with improved specificity. We reviewed our initial experience to evaluate the impact of this technology at our community breast center. METHODS: We performed a retrospective review of the initial 176 patients who underwent BSGI. RESULTS: A total of 128 patients underwent BSGI because of suspicious imaging, abnormal physical examination, or high risk with dense breasts. BSGI was positive in 12 of 107 patients with breast imaging reporting and data system (BI-RADS) 1, 2, or 3. Two of these were cancer. Of the 21 patients with BI-RADS 4, 18 were BSGI negative (11 with benign biopsy, 7 observed), and 3 were BSGI positive with 2 being cancer. Forty-eight patients with a new diagnosis of cancer obtained BSGI for further work-up. It was positive at a new location in 6 cases: 2 cases were new cancers in the contralateral breast, 1 was in the ipsilateral breast, and the remaining 3 had benign pathology. Of the 176 initial patients, clinical management was changed significantly in 14.2%, with another 6.3% in whom a negative BSGI could have prevented a biopsy. CONCLUSIONS: BSGI has played an important role in our clinical management of breast patients with complex breast tissue. BSGI is also a good adjunctive imaging tool in the work-up of newly diagnosed breast cancer patients.     

Magnetic resonance imaging patterns of tumor regression in breast cancer patients after neo‐adjuvant chemotherapy,and an analysis of the influencing factors

The objective of this study was to analyze the patterns of breast tumor shrinkage in patients after neo‐adjuvant chemotherapy (NAC) based on magnetic resonance imaging (MRI), and to evaluate the influential factors. Preoperative breast dynamic contrast‐enhanced MRI was performed on 88 patients before NAC, every 2 weeks during their chemotherapy treatment, and the week before their surgery. The MRI enhancement pattern of the primary tumors was classified into one of four categories based on BI‐RADS‐MRI: type I (postcontrast mass image), II (multiple small masses image), III (postcontrast mass image with peripheral non‐mass enhancement image), and IV (nonmass enhancement image). Multivariate regression and χ² test analyses were employed to establish significant associations. Two kinds of tumor regression patterns were observed: concentric shrinkage was observed in 39 lesions of 88 patients (44.3%), and nests or dendritic shrinkage was observed for the other 49 lesions (55.7%). ER+/HER2?, HER2+, and type I lesions were observed in 23 (62.2%), 21 (63.6%), and 29 (60.0%) patients, respectively, out of 49 nest or dendritic shrinkage pattern lesions. Triple negative breast cancer lesions, and type II, III, and IV lesions were observed in 13 (72.2%), 9 (81.8%), 10 (62.5%), and 10 (76.9%) patients, respectively, out of 39 lesions with a concentric shrinkage pattern. Molecular subtypes (χ²=7.171, P<.05) and the MRI schedule of enhancement (χ²=11.244, P<.05) were significantly associated with the tumor regression patterns. Multivariate analysis showed molecular subtypes (P<.05) and MRI pattern enhancement (P<.05) were significant predictive factors. Molecular subtypes and the MRI enhancement patterns of the primary tumors were significant predictive factors for tumor regression patterns of breast cancer after NAC.     

Clinical utility of breast-specific gamma imaging for evaluating disease extent in the newly diagnosed breast cancer patient

Background

Breast-specific gamma imaging (BSGI) is a functional imaging modality that has comparable sensitivity but superior specificity compared with magnetic resonance imaging, yielding fewer false-positive results and thereby improving clinical management of the newly diagnosed breast cancer patient.

Methods

A retrospective review was performed from 2 community-based breast imaging centers of newly diagnosed breast cancer patients in whom BSGI was performed as part of the imaging work-up.

Results

A total of 138 patients (69 invasive ductal carcinoma, 20 invasive lobular carcinoma, 32 ductal carcinoma in situ, and 17 mixtures of invasive ductal carcinoma, invasive lobular carcinoma, or ductal carcinoma in situ and other) were reviewed. Twenty-five patients (18.1%) had a positive BSGI study at a site remote from their known cancer or more extensive disease than detected from previous imaging. Fifteen patients (10.9%) were positive for a synchronous or more extensive malignancy in the same or contralateral breast. Five patients had benign findings on pathology, 5 benign on ultrasound follow-up (false-positive rate, 7.2%). Findings converted 7 patients to mastectomy, 1 patient to neoadjuvant chemotherapy, and 7 patients were found to have previously undetected contralateral cancer. The positive predictive value for BSGI was 92.9%.

Conclusions

BSGI detected additional or more extensive malignancy in the same or contralateral breast in 10.9% of newly diagnosed breast cancer patients. Only 7.2% incurred an additional work-up. BSGI provides accurate evaluation of remaining breast tissue in newly diagnosed breast cancer patients with few false-positive readings.