Jennifer D. Brooks

Background Parenchymal Enhancement at Breast MR Imaging and Breast Cancer Risk

PURPOSE To examine the relationships between breast cancer and both amount of fibroglandular tissue (FGT) and level of background parenchymal enhancement (BPE) at magnetic resonance (MR) imaging. MATERIALS AND METHODS A waiver of authorization was granted by the institutional review board for this retrospective HIPAA-compliant study. Among 1275 women who underwent breast MR imaging screening between December 2002 and February 2008, 39 breast carcinoma cases were identified. Two comparisons were performed: In one comparison, two normal controls--those of the women with negative (benign) findings at breast MR imaging--were matched to each breast cancer case on the basis of age and date of MR imaging. In the second comparison, one false-positive control--that of a woman with suspicious but nonmalignant findings at MR imaging--was similarly matched to each breast cancer case. Two readers independently rated the level of MR imaging-depicted BPE and the amount of MR imaging-depicted FGT by using a categorical scale: BPE was categorized as minimal, mild, moderate, or marked, and FGT was categorized as fatty, scattered, heterogeneously dense, or dense. RESULTS Compared with the odds ratio (OR) for a normal control, the OR for breast cancer increased significantly with increasing BPE: The ORs for moderate or marked BPE versus minimal or mild BPE were 10.1 (95% confidence interval [CI]: 2.9, 35.3; P < .001) and 3.3 (95% CI: 1.3, 8.3; P = .006) for readers 1 and 2, respectively. Similar odds were seen when the false-positive controls were compared with the breast cancer cases: The ORs for moderate or marked BPE versus minimal or mild BPE were 5.1 (95% CI: 1.4, 19.1; P = .005) and 3.7 (95% CI: 1.2, 11.2; P = .013) for readers 1 and 2, respectively. The breast cancer odds also increased with increasing FGT, but the BPE findings remained significant after adjustment for FGT. CONCLUSION Increased BPE is strongly predictive of breast cancer odds.

Mammalian lignans and genistein decrease the activities of aromatase and 17β-hydroxysteroid dehydrogenase in MCF-7 cells

Estrogen plays a major role in breast cancer development and progression. Breast tissue and cell lines contain the necessary enzymes for estrogen synthesis, including aromatase and 17beta-hydroxysteroid dehydrogenase (17beta-HSD). These enzymes can influence tissue exposure to estrogen and therefore have become targets for breast cancer treatment and prevention. This study determined whether the isoflavone genistein (GEN) and the mammalian lignans enterolactone (EL) and enterodiol (ED) would inhibit the activity of aromatase and 17beta-HSD type 1 in MCF-7 cancer cells, thereby decreasing the amount of estradiol (E2) produced and consequently cell proliferation. Results showed that 10 microM EL, ED and GEN significantly decreased the amount of estrone (E1) produced via the aromatase pathway by 37%, 81% and 70%, respectively. Regarding 17beta-HSD type 1, 50 microM EL and GEN maximally inhibited E2 production by 84% and 59%, respectively. The reduction in E1 and E2 production by EL and the reduction in E2 production by GEN were significantly related to a reduction in MCF-7 cell proliferation. 4-Hydroxyandrostene-3,17-dione (50 microM) did not inhibit aromatase but inhibited the conversion of E1 to E2 by 78%, suggesting that it is a 17beta-HSD type 1 inhibitor. In conclusion, modulation of local E2 synthesis is one potential mechanism through which ED, EL and GEN may protect against breast cancer.

Risk of Asynchronous Contralateral Breast Cancer in Noncarriers of BRCA1 and BRCA2 Mutations With a Family History of Breast Cancer: A Report From the Women's Environmental Cancer and Radiation Epidemiology Study

PURPOSE To fully characterize the risk of contralateral breast cancer (CBC) in patients with breast cancer with a family history who test negative for BRCA1 and BRCA2 mutations. PATIENTS AND METHODS From our population-based case-control study comparing women with CBC to women with unilateral breast cancer (UBC), we selected women who tested negative for BRCA1 and BRCA2 mutations (594 patients with CBC/1,119 control patients with UBC). Rate ratios (RRs) and 95% CIs were estimated to examine the association between family history of breast cancer and risk of asynchronous CBC. Age- and family history-specific 10-year cumulative absolute risks of CBC were estimated. RESULTS Family history of breast cancer was associated with increased CBC risk; risk was highest among young women (< 45 years) with first-degree relatives affected at young ages (< 45 years; RR, 2.5; 95% CI, 1.1 to 5.3) or women with first-degree relatives with bilateral disease (RR, 3.6; 95% CI, 2.0 to 6.4). Women diagnosed with UBC before age 55 years with a first-degree family history of CBC had a 10-year risk of CBC of 15.6%. CONCLUSION Young women with breast cancer who have a family history of breast cancer and who test negative for deleterious mutations in BRCA1 and BRCA2 are at significantly greater risk of CBC than other breast cancer survivors. This risk varies with diagnosis age, family history of CBC, and degree of relationship to an affected relative. Women with a first-degree family history of bilateral disease have risks of CBC similar to mutation carriers. This has important implications for the clinical management of patients with breast cancer with family history of the disease.

Impact of Tamoxifen on Amount of Fibroglandular Tissue, Background Parenchymal Enhancement, and Cysts on Breast Magnetic Resonance Imaging

Abstract:  The objective of this study was to evaluate the impact of tamoxifen treatment on amount of fibroglandular tissue (FGT), background parenchymal enhancement (BPE), and cysts on breast MRI. Retrospective search identified 96 women with breast cancer who had a breast MRI both before and during adjuvant tamoxifen therapy between 2002 and 2008. After exclusion of all irradiated breasts, 88 women were eligible. Two readers blinded to tamoxifen treatment status independently rated level of BPE, amount of FGT, and cysts using a 4‐point categorical scale: BPE––Minimal, Mild, Moderate, Marked; FGT––Fatty, Scattered, Heterogeneously Dense (HD), Dense; Cysts––Minimal, Mild, Moderate, Marked. A consensus interpretation was reached in cases of disagreement. During tamoxifen, there was a significant shift from higher to lower degree BPE, cysts, and FGT compared with before tamoxifen. BPE, cysts and FGT decreased in 68% (60/88), 38% (33/88), and 40% (35/88) of women during tamoxifen (p < 0.001 for all measures). After the exclusion of all cases with minimal BPE, cysts, or FGT on the pre‐tamoxifen MRI, the percentage of women demonstrating a decrease in these factors increased to 81% (60/74), 77% (33/43), and 41% (35/86), respectively. Exclusion of patients treated with chemotherapy did not substantially change these results. The percentage of women with decreases in FGT and cysts increased with greater duration on tamoxifen, whereas decreases in BPE were detected early in treatment (<90 days) and did not change substantially with longer duration on tamoxifen. A significant association exists between treatment with tamoxifen and decreases in BPE, cysts, and FGT on breast MRI.

Effect of Aromatase Inhibitors on Background Parenchymal Enhancement and Amount of Fibroglandular Tissue at Breast MR Imaging

PURPOSE To evaluate whether treatment with an aromatase inhibitor (AI) influences background parenchymal enhancement (BPE) or amount of fibroglandular tissue (FGT) at breast magnetic resonance (MR) imaging in postmenopausal women with prior history of breast cancer. MATERIALS AND METHODS A waiver of authorization and patient consent was granted by the institutional review board for this HIPAA-compliant retrospective study. Postmenopausal women with breast cancer and MR imaging findings of the contralateral unaffected breast, before and during 6-12 months of AI treatment (anastrozole, letrozole, or exemestane), between August 1999 and June 2010 were retrospectively identified (n = 149). Two readers performed blinded side-by-side comparison of BPE and MR imaging-depicted FGT before and during treatment. BPE and FGT were classified as the same or greater on one of the two MR studies and by using categorical scales: minimal, mild, moderate, or marked for BPE and fatty, scattered, heterogeneously dense, or dense for FGT. Consensus was reached in cases of disagreement. The sign test was used to conduct a side-by-side comparison of BPE and FGT before and during AI treatment. RESULTS A decrease in BPE occurred in 33.9% (37 of 109) of women during anastrozole treatment, while an increase occurred in only one (P < .0001); 28 of 37 decreases resulted in a category change of BPE. A decrease in MR imaging-depicted FGT occurred in 5.5% (six of 109) of women, while no increases occurred (P = .031). During letrozole treatment, a decrease in BPE occurred in 46% (15 of 33), while an increase occurred in one woman (P = .0003); a decrease in FGT occurred in only one woman, and no increases occurred. Similar results were seen when women also undergoing chemotherapy were excluded. Only seven women were treated with exemestane. CONCLUSION Treatment with 6-12 months of anastrozole or letrozole was associated with decreases in BPE, which occurred in a greater proportion of women than decreases in FGT.

Safety and efficacy of radioactive seed localization with I-125 prior to lumpectomy and/or excisional biopsy

PURPOSE To evaluate the safety and efficacy of pre-operative I-125 radioactive seed localization (RSL) as an alternative to wire localization (WL). METHODS A waiver was granted by the institutional review board for this HIPAA compliant study. Review of 356 consecutive single site nonpalpable mammographic and ultrasound guided I-125 RSLs done between November 2011 and April 2012 was conducted. Preoperative mammograms and specimen radiographs were reviewed for seed-target distance, lesion location, and target/seed removal. During a brief surgical training period, 35 of 356 women had both RSL and wire localization (WL) of the same lesion. Chi-square and single sample t-tests were used to compare margin status and duration of procedures. RESULTS Of the 356 RSLs, 303 (85.1%) were performed ≥ 1 day before surgery. Mammographic guidance was used in 330 (93%) and ultrasound in 26 (7%). Mean seed to target distance was 1mm (range 0-20mm); all targeted lesions were retrieved. In 31 women in whom mammographic guidance was used for both RSL and WL, median procedure time was not significantly different (RSL 9.0 min; WL 7.0 min; p=0.91), and median seed migration distance was <1mm (range 0-15 mm). No difference was detected between margin status with RSL alone versus WL (p=0.40 and p=0.65 for positive and <1mm margins, respectively). Two adverse events occurred requiring an additional wire/surgery. CONCLUSION RSL ≥ 1 day before surgery is a safe effective procedure for pre-operative localization, with few adverse events and surgical outcomes comparable to those achieved with wire localization.

The increasing burden of phlebotomy in the development of anaemia and need for blood transfusion amongst trauma patients

BACKGROUND Diagnostic laboratory tests are an integral part of the management of trauma patients, however, may be responsible for significant iatrogenic blood loss. The purpose of this study was to examine how phlebotomy practises have changed over time, and to assess the impact of these practises on patient outcomes. METHODS A continuous series of injured patients admitted to a level I trauma centre (March-April 2004) was compared to the same period in 2009. All diagnostic tests and blood volumes withdrawn for each patient were tabulated. Primary outcomes were in-hospital mortality and length of stay (LOS); secondary outcomes were development of anaemia (Hgb<9 g/dl) and need for blood transfusion. A cost analysis was performed to determine the financial impact of the blood tests ordered. RESULTS The 360 patients in 2009 and 384 patients in 2004 demonstrated no significant differences in demographics or clinical data. When outcomes were compared, there were no significant differences in hospital LOS, ICU LOS or mortality. From 2004 to 2009, the mean number of laboratory tests per patient increased significantly (21.2±32.5 to 28.5±44.4, p=0.003). The total blood volumes drawn during the hospital stay also increased significantly (144.4±191.2 ml to 187.3±265.1 ml, p=0.025). For ICU patients (329.7±351.0 ml to 435.9±346.3 ml, p=0.048). There was a 25% increase in costs due to laboratory blood tests over the study period. For ICU patients, a 36% increase in costs was observed. CONCLUSIONS From 2004 to 2009, there was a significant increase in the utilisation of diagnostic laboratory tests in the management of the injured patient with no demonstrable improvements in mortality or LOS. Further prospective evaluation of these results is warranted.

Variants in activators and downstream targets of ATM, radiation exposure, and contralateral breast cancer risk in the WECARE study.

Ionizing radiation (IR) is a breast carcinogen that induces DNA double‐strand breaks (DSBs), and variation in genes involved in the DNA DSB response has been implicated in radiation‐induced breast cancer. The Womens Environmental, Cancer, and Radiation Epidemiology (WECARE) study is a population‐based study of cases with contralateral breast cancer (CBC) and matched controls with unilateral breast cancer. The location‐specific radiation dose received by the contralateral breast was estimated from radiotherapy records and mathematical models. One hundred fifty‐two SNPs in six genes (CHEK2, MRE11A, MDC1, NBN, RAD50, TP53BP1) involved in the DNA DSBs response were genotyped. No variants or haplotypes were associated with CBC risk (649 cases and 1,284 controls) and no variants were found to interact with radiation dose. Carriers of a RAD50 haplotype exposed to ≥1 gray (Gy) had an increased risk of CBC compared with unexposed carriers (Rate ratios [RR] = 4.31 [95% confidence intervals [CI] 1.93–9.62]); with an excess relative risk (ERR) per Gy = 2.13 [95% CI 0.61–5.33]). Although the results of this study were largely null, carriers of a haplotype in RAD50 treated with radiation had a greater CBC risk than unexposed carriers. This suggests that carriers of this haplotype may be susceptible to the DNA‐damaging effects of radiation therapy associated with radiation‐induced breast cancer. Hum Mutat 33:158–164, 2012.

Breast Cancers Detected at Screening MR Imaging and Mammography in Patients at High Risk: Method of Detection Reflects Tumor Histopathologic Results

Purpose To compare the clinical, imaging, and histopathologic features of breast cancers detected at screening magnetic resonance (MR) imaging, screening mammography, and those detected between screening examinations (interval cancers) in women at high risk. Materials and Methods This retrospective institutional review board-approved, HIPAA-compliant review of 7519 women at high risk for breast cancer who underwent screening with MR imaging and mammography between January 2005 and December 2010 was performed to determine the number of screening-detected and interval cancers diagnosed. The need for informed consent was waived. Medical records were reviewed for age, risk factors (family or personal history of breast cancer, BRCA mutation status, history of high-risk lesion or mantle radiation), tumor histopathologic results, and time between diagnosis of interval cancer and most recent screening examination. The χ(2) test and logistic regression methods were used to compare the features of screening MR imaging, screening mammography, and interval cancers. The Wilcoxon signed-rank test was used to calculate P values. Results A total of 18 064 screening MR imaging examinations and 26 866 screening mammographic examinations were performed. Two hundred twenty-two cancers were diagnosed in 219 women, 167 (75%) at MR imaging, 43 (19%) at mammography, and 12 (5%) interval cancers. Median age at diagnosis was 52 years. No risk factors were associated with screening MR imaging, screening mammography, or interval cancer (P > .06). Cancers found at screening MR imaging were more likely to be invasive cancer (118 of 167 [71%]; P < .0001). Of the 43 cancers found at screening mammography, 38 (88%) manifested as calcifications and 28 (65%) were ductal carcinoma in situ. Interval cancers were associated with nodal involvement (P = .005) and the triple-negative subtype (P = .03). Conclusion In women at high risk for breast cancer who underwent screening with mammography and MR imaging, invasive cancers were more likely to be detected at MR imaging, whereas most cancers detected at screening mammography were ductal carcinoma in situ. Interval cancers were found infrequently and were more likely to be node positive and of the triple-negative subtype. (©) RSNA, 2016.

The Impact of Bilateral Salpingo-Oophorectomy on Breast MRI Background Parenchymal Enhancement and Fibroglandular Tissue

ObjectiveThe objective of this study was to evaluate the effect of bilateral salpingo-oophorectomy (BSO) on background parenchymal enhancement (BPE) and the amount of fibroglandular tissue (FGT) seen on breast MRI.MethodsRetrospective review identified 21 BRCA mutation carriers who underwent breast MRI before and after elective BSO. After exclusion of patients placed on postoperative hormone replacement therapy, there were 18 eligible patients. Blinded to surgical status, three independent readers used categorical scales to rate BPE (minimal, mild, moderate, marked) and the amount of FGT (fatty, scattered, heterogeneously dense, dense) on pre- and post-BSO MRI examinations. The sign test was used to assess for changes in the categorical ratings of BPE and FGT.ResultsSignificant proportions of women demonstrated decreases in BPE and in the amount of FGT following oophorectomy (P = 0.004 and 0.02, respectively.) BPE decreases were larger and seen earlier than FGT changes. There was no significant relationship between age/body mass index and changes in BPE and FGT.ConclusionsBPE and the amount of FGT seen on breast MRI are significantly decreased by oophorectomy; BPE decreases to a greater extent and earlier than FGT.Key Points• Background parenchymal enhancement significantly decreases at breast MRI following oophorectomy.• Fibroglandular tissue significantly decreases on breast MRI following oophorectomy.• Decrease in background parenchymal enhancement is greater than in fibroglandular tissue.• Decrease in background parenchymal enhancement occurs earlier than in fibroglandular tissue.