Tim H. Emory

In vivo quantification of choline compounds in the breast with 1H MR spectroscopy.

This work describes a methodology for quantifying levels of total choline‐containing compounds (tCho) in the breast using in vivo 1H MR spectroscopy (MRS) at high field (4 Tesla). Water is used as an internal reference compound to account for the partial volume of adipose tissue. Peak amplitudes are estimated by fitting one peak at a time over a narrow frequency band to allow measurement of small metabolite resonances in spectra with large lipid peaks. This quantitative method significantly improves previously reported analysis methods by accounting for the variable sensitivity of breast 1H MRS measurements. Using this technique, we detected and quantified a tCho peak in 214 of 500 in vivo spectra. tCho levels were found to be significantly higher in malignancies than in benign abnormalities and normal breast tissues, which suggests that this technique could be used to diagnose suspicious lesions and monitor response to cancer treatments. Magn Reson Med 50:1134–1143, 2003.

Contralateral prophylactic mastectomy for patients with unilateral breast cancer

Patients with unilateral breast cancer are at increased risk of developing a second cancer in the contralateral breast. Some women choose contralateral prophylactic mastectomy (CPM) to prevent cancer in the contralateral breast. Several studies have demonstrated that CPM significantly decreases the occurrence of contralateral breast cancer. However, the effectiveness of CPM at reducing breast cancer mortality is not as clear. Moreover, CPM is not risk free and patients may need to undergo additional surgical procedures, especially if reconstruction is performed. Nevertheless, most patients are satisfied with their decision to undergo CPM. Alternatives to CPM include close surveillance with clinical breast examination, mammography and possibly breast magnetic resonance imaging. Endocrine therapy with tamoxifen or aromatase inhibitors significantly reduces the risk of contralateral breast cancer and may be more acceptable than CPM for some patients. The decision to undergo CPM is complex and many factors likely contribute to its use. Future prospective studies are critically needed to evaluate the decision-making processes leading to CPM.

Microsomal metabolism of arylamides by the rat and guinea pig—I.: Oxidation of N-3-fluorenylacetamide at carbon-atom-9—A major metabolic reaction☆

Abstract The N-hydroxylation of N-3-fluorenylacetamide (3-FAA), an isomer of the carcinogen, N-2-fluorenylacetamide (2-FAA), by hepatic microsomes of untreated and 3-methylcholanthrene (3-MC)-treated guinea pigs was found to be of a similar low order as that previously observed in the rat. Hepatic microsomes of the guinea pig and of the rat converted 3-FAA to N-(9-hydroxy)-3-FAA and to N-(9-oxo)-3-FAA. These new metabolites were separated and identified by high-pressure liquid chromatography (h.p.l.c.). N-(9-hydroxy)-3-FAA was the major product of the hydroxylation of 3-FAA by hepatic microsomes of the rat or guinea pig exceeding the formation of N-(7-hydroxy)-3-FAA, the principal phenolic metabolite of 3-FAA. The amounts of N-(9-oxo)-3-FAA formed were about one-third of the amounts of N-(9-hydroxy)-3-FAA produced. In contrast to the formation of phenolic metabolites, the hydroxylation of 3-FAA to N-(9-hydroxy)-3-FAA was not increased by pretreatment of guinea pigs or rats with 3-MC. Similarly, pretreatment of rats with PB did not enhance the yield of N-(9-hydroxy)-3-FAA. Co inhibited the formation of N-(9-hydroxy)-3-FAA by 80 per cent. These data lead us to conclude that the formation of N-(9-hydroxy)-3-FAA is catalyzed by a microsomal hemoprotein not identical with cytochrome P1-450 or P-450. In contrast to 3-FAA, 2-FAA appeared to be a poor substrate for hydroxylation to the N-(9-hydroxy)-2-FAA. The susceptibility of 3-FAA to hydroxylation at carbon-atom 9 of the fluorene moiety may be rationalized by resonance structures in which carbon-atom 9 is positively charged and acts as a electrophilic center. Similar resonance structures cannot be written for 2-FAA.

Feasibility of single-voxel MRS measurement of apparent diffusion coefficient of water in breast tumors.

We report initial results with single voxel spectroscopy (SVS) using diffusion weighting and localization by adiabatic selective refocusing (LASER) in breast tumors to measure the apparent diffusion coefficient of water (ADCw). This is a quick (30 s) and relatively easy method to implement compared with image‐based diffusion measurements, and is insensitive to lipid signal contamination. The ADCw and concentration of total choline containing compounds [tCho] were evaluated for associations with each other and final pathologic diagnosis in 25 subjects. The average (± SD) ADCw in benign and malignant lesions was 1.96 ± 0.47 mm2/s and 1.26 ± 0.29 × 10−3 mm2/s, respectively, P< 0.001. Receiver operating characteristic curve analysis showed an area under the curve of 0.92. Analysis of the single voxel (SV) ADCw and [tCho] showed significant correlation with a R2 of 0.56, P< 0.001. Compared with more commonly used image‐based methods of measuring water ADC, SV‐ADCw is faster, more robust, insensitive to fat, and potentially easier to implement on standard clinical systems. Magn Reson Med, 2009.

A randomized controlled trial of green tea extract supplementation and mammographic density in postmenopausal women at increased risk of breast cancer

Epidemiologic and animal studies suggest a protective role of green tea against breast cancer. However, the underlying mechanism is not understood. We conducted a randomized, double-blinded, placebo-controlled phase II clinical trial to investigate whether supplementation with green tea extract (GTE) modifies mammographic density (MD), as a potential mechanism, involving 1,075 healthy postmenopausal women. Women assigned to the treatment arm consumed daily 4 decaffeinated GTE capsules containing 1,315 mg total catechins, including 843 mg epigallocatechin-3-gallate (EGCG) for 12 months. A computer-assisted method (Madena) was used to assess MD in digital mammograms at baseline and month 12 time points in 932 completers (462 in GTE and 470 in placebo). GTE supplementation for 12 months did not significantly change percent MD (PMD) or absolute MD in all women. In younger women (50–55 years), GTE supplementation significantly reduced PMD by 4.40% as compared with the placebo with a 1.02% PMD increase from pre- to postintervention (P = 0.05), but had no effect in older women (Pinteraction = 0.07). GTE supplementation did not induce MD change in other subgroups of women stratified by catechol-O-methyltransferase genotype or level of body mass index. In conclusion, 1-year supplementation with a high dose of EGCG did not have a significant effect on MD measures in all women, but reduced PMD in younger women, an age-dependent effect similar to those of tamoxifen. Further investigation of the potential chemopreventive effect of green tea intake on breast cancer risk in younger women is warranted. Cancer Prev Res; 10(12); 710–8. ©2017 AACR.

What is new in breast MRI spectroscopy.

A review of breast spectroscopy and its metabolite imaging – MRS is useful for clinical evaluation in neoadjuvant chemotherapy for the treatment of breast cancer. Why has it not been implemented on all clinical breast MRI scanners? Doing MRI/MRS on smaller breast cancers is difficult and cannot be done on breast cancers less than 6mm × 6mm × 6mm. High field magnets are used in single voxel spectroscopy (laser) for beast quantitative results (3T or 4T). The MRI/MRS latest results from I-SPY I (NIH/ACRIN) are not yet published for the multi-centered trial. Also having to shim the magnet and preset sequences for optimizing MRS has been an issue and requires a MRI physicist to do these studies. Choline measurements on 1.5T magnets that are shimmed well can detect choline within a large tumor (>2–3 cm). However, it is difficult to quantitate the choline with the breast cancer using 1.5T magnets. The results from the first MRS trial at the University of Minnesota Center for Magnetic Resonance Research will be published at the San Antonio Breast Meeting (December 2012). The report will be on 60 MRI/MRS cases and 5 year survival data. MRI/MRS neoadjuvant breast cancer imaging can be evaluated by three MRI methods to get to the RECIST evaluation: (1) L/D – longest diameter; (2) MRS – metabolite imaging and (3) Volume imaging of contrast (3D). All these methods have difficulty with non-mass like tumors. Making objective measurements of changes in breast tumor size can be challenging. The spectrum of breast tumor morphology and appearance on MRI creates difficulty generating accurate objective measurements which is used by oncology RECIST criteria to track tumor response in breast cancer. Depending on morphology and enhancement of an individual lesion an objective LD comparison may be problematic as seen in the following abstract. Inter-observer agreement in assessment of breast cancer response to neoadjuvant chemotherapy on MRI: Qualitative versus quantitative evaluation (11/28/11 RSNA, Chicago, IL). Volume Imaging: MRI tumor volume for predicting response to neoadjuvant chemotherapy in locally advanced breast cancer: findings from ACRIN 6657/calgb 15007 (2009 Asco) Noxla Hilton. Tumor response measured volumetrically by MRI is a stronger and earlier predictor of pathologic response after (NACT) than clinical exam or tumor diameter. Volumetric MRI imaging must use accurate volume (3D) placement of a voxel under MRI guidance. This procedure is not yet automated and must be completed by an experienced MRI radiologist. If the clinical trial shows that the pathologic response is very good (in 1–2 weeks) then this test may not be as sensitive for predicting (NACT) response. (Chemotherapy drugs work extremely well and the tumor decreases gadolinium uptake to zero.)

Intracystic Papillary Carcinoma in a Man With Gynecomastia

Male breast cancer is a rare disease in the male breast whereas gynecomastia is quite common. An elevation of the estrogen-to-androgen ratio increases the risk of both of these diseases. However, a connection between gynecomastia and subsequent breast cancer development is controversial and unclear. Imaging studies including mammography and ultrasound provide valuable information in leading to a correct diagnosis. Traditionally, intracystic papillary carcinoma, also known as encapsulated papillary carcinoma, has been considered a form of ductal carcinoma in situ. Recent immunohistochemical studies, demonstrating an absence of myothelium, in many cases would be more compatible with the diagnosis of invasive malignancy. However, intracystic papillary carcinoma holds a favorable prognosis with local therapy alone. We report a case of intracystic papillary carcinoma in a male patient with long-standing gynecomastia diagnosed eight years prior by mammography. The patient presented with a breast lump on both occasions. Current work-up consisted of both mammography and ultrasound. Ultrasound provided key information revealing a complex mass requiring further evaluation. Ultrasound-guided core needle biopsy revealed intracystic papillary carcinoma with confirmation upon surgical excision.

Use of CT to Reduce Understaging in Prostatic Cancer: Comparison With Conventional Staging Techniques

wereevaluated forstaging purposes withbothCT(18-secscanspeed) andcertain commonly used‘conventional” diagnostic tests,namely: radionuclide bonescanwithcorrelative plainfilms,theprostatic fraction oftheserumacidphosphatase, excretory urogram, andchestradiograph. Allpatientsincluded inthestudyhadhistopathologic proofofdiagnosis. CTcorrectly identifiedextracapsular prostatic cancer spread locally orinpelvic lymphnodes in14%ofpatients withcompletely negative conventional studies. Sensitivity ofextracapsulartumorspreaddetection increased from41%to59%byaddingCTtotheconventionalstudies.CTconfirmed thepresence oftumorspreadandlocalized itin43%ofpatientswithpositive conventional studies. Conventional studies werepositive whentumorspread waspresent in32%ofpatients withnegative CT.CTreduces understagingwhenconventional testsarenegative, localizes andconfirms tumor spread whenconventional testsarepositive, butcannotdemonstrate tumorspreadinsomepatientswhoseconventional testsarepositiveandwhoaresubsequently showntohavetumorspreadhistopathologically.Conventional noninvasive diagnostic techniques used forstaging prostaticcancer often cannot show thefullextent ofthedisease. Forexample, digitalrectal examination hasbeen reported tounderestimate local spread in25%-45%ofcases [i