Global tissue stiffness on breast MR elastography: High-risk dense breast patients have higher stiffness compared to average-risk dense breast patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10541-10541
Author(s):  
Bhavika K. Patel ◽  
Kay Pepin ◽  
Kathy R Brandt ◽  
Gina L. Mazza ◽  
Barbara A. Pockaj ◽  
...  

10541 Background: Biomechanical tissue properties may vary in the breasts of patients at elevated risk for breast cancer. We aim to quantify in vivo biomechanical tissue properties in various breast densities and in both normal risk and high risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association of biomechanical properties of the breast with cancer risk. Methods: In this IRB–approved prospective single-institution study, we recruited two groups of women differing by breast cancer risk to undergo a 3.0 T dynamic contrast enhanced MRI/MRE of the breast. Low-average risk women were defined as having no personal or significant family history of breast cancer, no prior high risk breast biopsies and a negative mammography within 12 months. High-risk breast cancer patients were recruited from those patients who underwent standard of care breast MR. Within each breast density group (non-dense versus dense), two-sample t-tests were used to compare breast stiffness, elasticity, and viscosity across risk groups (low-average vs high). Results: There were 50 low-average risk and 86 high-risk patients recruited to the study. The risk groups were similar on age (mean age = 55.6 and 53.6 years), density (68% vs. 64% dense breasts) and menopausal status (66.0% vs. 69.8%). Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high risk patients ( N = 55) compared to low-average risk patients ( N = 34; all p < 0.001). In the multivariate logistic regression model, breast stiffness remained a significant predictor of risk status (OR=4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, MRI BPE, age, and menopausal status. Similar results were seen for breast elasticity (OR=4.88, 95% CI [2.08, 11.43]) and viscosity (OR=11.49, 95% CI [1.15, 114.89]). Conclusions: Structurally-based, quantitative biomarker of tissue stiffness obtained from global 3D breast MRE is associated with differences in breast cancer risk in dense breasts. As such, tissue stiffness could provide a novel prognostic marker to help identify the subset of high-risk women with dense breasts who would benefit from increased surveillance.[Table: see text]

2021 ◽  
Author(s):  
Bhavika Patel ◽  
Kay Pepin ◽  
Kathy Brandt ◽  
Gina Mazza ◽  
Barbara Pockaj ◽  
...  

Abstract Purpose:Quantify in vivo biomechanical tissue properties in various breast densities and in normal risk and high risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association between breast biomechanical properties and cancer risk.Methods: Patients with normal risk or high risk of breast cancer underent 3.0 T breast MR imaging and elastography. Breast parenchymal enhancement (BPE), density (from most recent mammogram), stiffness, elasticity, and viscosity were recorded. Within each breast density group (non-dense versus dense), stiffness, elasticity, and viscosity were compared across risk groups (normal versus high). A multivariable logistic regression model was used to evaluate whether the MRE parameters (separately for stiffness, elasticity, and viscosity) predicted risk status after controlling for clinical factors.Results: 50 normal risk and 86 high risk patients were included. Risk groups were similar on age, density, and menopausal status. Among patients with dense breasts, mean stiffness, elasticity, and viscosity were significantly higher in high risk patients (N = 55) compared to normal risk patients (N = 34; all p < 0.001). Stiffness remained a significant predictor of risk status (OR=4.26, 95% CI [1.96, 9.25]) even after controlling for breast density, BPE, age, and menopausal status. Similar results were seen for elasticity and viscosity.Conclusion: A structurally-based, quantitative biomarker of tissue stiffness obtained from MRE is associated with differences in breast cancer risk in dense breasts. Tissue stiffness could provide a novel prognostic marker to help identify high risk women with dense breasts who would benefit from increased surveillance and/or risk reduction measures.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1508-1508
Author(s):  
D. Euhus ◽  
D. Bu ◽  
S. Milchgrub ◽  
A. M. Leitch ◽  
C. M. Lewis

1508 Background: Tumor suppressor gene (TSG) methylation is identified in nearly all breast cancers, but rarely in histologically normal breast tissue from wonen unaffected with breast cancer. Its occurrence in high risk preneoplasia and in benign breast tissue adjacent to breast cancer suggests that it may represent a high risk field change that could be exploited for cell-based breast cancer risk stratification. Methods: TSG methylation was measured by quantitative methylation-specific real time PCR in 53 breast tumor fine needle aspiration (FNA) biopsies, 84 cellular random periareolar FNAs (RP-FNA) ipsilateral or contralateral to these cancers, 36 cellular RP- FNAs from unaffected women at high risk for breast cancer by the Gail model, and 95 cellular RP-FNAs from unaffected women at lower risk by the Gail model. Results: The breast tumors showed a high frequency of TSG methylation: RASSF1A 80%, HIN-1 65%, Cyclin D2 60%, RAR-β2 53%, and APC 47%. In general, RP-FNA samples from cancer patients and Gail high risk patients showed a greater frequency of methylation than samples from Gail lower risk patients: RASSF1A 43% vs. 21%, P = 0.001, HIN-1 32% vs. 20%, P = 0.05; Cyclin D2 18% vs. 9%, P = 0.10; RAR-β2 21% vs. 18%, P = 0.68; and APC 25% vs. 16%, P = 0.17. Twelve of 215 RP-FNA samples (5%) showed very high levels of methylation (>10% methylation for two or more genes). Only two of these samples were from women classified as lower risk by the Gail model. Methylation frequencies were entirely independent of cell yields but the frequency of RASSF1A methylation increased with increasing Masood scores (P = 0.05). Methylation of RASSF1A in one breast was highly predictive of RASSF1A methylation in the opposite breast (P < 0.0001). Conclusions: TSG methylation appears to be a breast cancer risk-associated field change that can be quantified in RP-FNA samples. RASSF1A methylation occurs frequently in benign breast epithelium, provides reasonable discrimination between high and lower risk breasts (O.R. = 2.0), is related to cytological atypia, and may be an early marker of a methylator phenotype. Quantification of TSG methylation in RP-FNA samples may provide a valuable surrogate endpoint biomarker for Phase II prevention trials. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12535-e12535
Author(s):  
Yoshihiko Kamada ◽  
Seiko Tsuchiya ◽  
Naoko Takigami ◽  
Kentaro Tamaki ◽  
Kanou Uehara ◽  
...  

e12535 Background: Oncotype Dx is becoming the standard assay for chemotherapy decision making for estrogen receptor positive / HER2 negative early breast cancer. Issues concerning the choice of therapy for the intermediate risk patients are currently being addressed. We are using a 95-gene classifier developed by Osaka University and Sysmex Corporation (Curebest 95 GC Breast) which divides patients into "low" and "high" risk groups, which obviates this issue. In this study, we analyzed the histopathological characteristics of low and high risk patients by the 95-gene classifier that would be classified as intermediate risk by 21-gene-recurrence score (21RS). Methods: Fresh tissue samples collected at surgery was sent for 95-GC analysis. Cel-files containing the gene expression data of each sample was uploaded to Recurrence Online (recurrenceonline.com) and the 21-RS was obtained. Histopathological analysis of the tumor specimens including the pathological tumor size, degree of tumor infiltrating lymphocytes ("TIL"s) (0, 1+, 2+, 3+), nuclear pleomorphism (NP score 1, 2, 3), and number of mitoses (M score 1, 2, 3) was done. The age of the patient and the Ki-67 percentage of the preoperative biopsy specimen was also noted. Results: There were a total of 38 cases. The cases with a matching 21RS and 95GC "Low" (Group L-L) was 10, a matching "High" (Group H-H) was 15, 21RS "Intermediate / 95GC "Low" (Group I-L) was 4, 21RS "Intermediate / 95GC "High" (Group I-H) was 7, and discordant 21RS "High" / 95GC "Low" (Group H-L) was 2, respectively. There was no age related differences (average 53.3 y.o.). There was a significant difference between the L-L and H-H groups in all categories (i.e. pT 14.5 mm v.s. 30.0 mm / p = 0.0262, NP score average 2.1 v.s. 2.5 / p = 0.287, M score average 1.2 v.s 2.4 / p < 0.001, TILs average 0.4+ v.s. 1.2+ /p = 0.0413, Ki67 25.0% v.s. 33.2%). The trend was the same between the I-L and I-H group with the exception of the mitosis score, which showed an inverse trend of a high of 2.25 in the I-L v.s. low of 1.43 in the I-H group (p = 0.9522). The H-L group had high NP score (average 3.0), low M score (average 1.0), and high TILs (average 2+). Conclusions: The 95-gene classifier might be more sensitive compared to 21RS in picking up histio-morphological information, and also may be able to differentiate the type of immune response of TILs. We are planning further immunohistological evaluation.


2017 ◽  
Vol 59 (9) ◽  
pp. 1045-1050 ◽  
Author(s):  
Hee Jung Moon ◽  
Min Jung Kim ◽  
Jung Hyun Yoon ◽  
Eun-Kyung Kim

Background Women at high risk for breast cancer and women at average risk have different pretest probabilities. Probably benign lesions on screening ultrasound (US) should be assessed and managed differently for these two risk groups. Purpose To evaluate the effectiveness of short-term follow-up for probably benign lesions on screening US in women at average risk for breast cancer with dense breasts. Material and Methods A total of 445 women at average risk for breast cancer with probably benign lesions on screening US, dense breasts, and negative or benign mammography results were included. Women were classified into the six-month group (n = 345) or 12-month group (n = 100) according to when the first follow-up was performed (3–9 months or 9–15 months). The cancer detection rate, frequencies of newly developed lesions and progressed lesions, and biopsy rate were compared. Results There were no malignancies from three to 15 months. Three cancers newly developed after 15 months. One was a 3-mm ductal carcinoma in situ and two were 10-mm and 18-mm invasive ductal carcinoma without lymph node metastasis. The frequency of newly developed lesions and progressed lesions and biopsy rate were not significantly different between the six-month and 12-month groups ( P = 0.320, 0.621, and >0.999). Conclusion A follow-up at 12 months can be considered for probably benign lesions on screening US in women at average risk for breast cancer with dense breasts. However, a large series prospective study is needed before clinical application.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12509-e12509
Author(s):  
Lei Lei ◽  
Han-Ching Chan ◽  
Wang Xiao Jia ◽  
Tzu-Pin Lu ◽  
Skye Hung-Chun Cheng

e12509 Background: Dutch clinical risk criteria (low-risk definition: age > 35 years and (grade 1 with tumor ≤3cm, grade 2 with tumor ≤2cm, or grade 3 with tumor ≤1cm) have been used to stratify the benefit of MammaPrint and Oncotype DX for the decision-making regarding adjuvant chemotherapy for early-stage luminal breast cancer. We propose that the criteria could help to identify low-risk patients who could barely benefit from multi-gene testing. Methods: Breast cancer patients from Taiwan Cancer Database initially treated with primary surgeries between 2008 and 2012 who met the following criteria: (1) pathologic node-negative, (2) hormone receptor-positive, (3) HER2-negative, (4) undergone hormonal therapy, and (5) a minimum follow-up time of 5-year if free from any event, were enrolled in this study. Out of the total 2679 eligible patients, 1074 (40.1%) patients received adjuvant chemotherapy in addition to endocrine therapy. The study endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Kaplan-Meier statistics estimated the difference between clinical outcomes in low- and high-risk groups. Results: The median follow-up time of BSCC and OS was 5.9 years (range, 0-7 years) and 5.8 years (range, 0-7 years), respectively. There were statistical significances of 5-year BCSS (n = 2679) and 5-year OS (n = 2636) between low-risk and high-risk groups (in both endpoints, P < 0.0001). According to the Dutch criteria, low-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 99.0% vs. 99.2% and a 5-year OS of 98.4% vs. 97.4%, respectively. High-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 97.7% vs. 98.1% and a 5-year OS of 96.4% vs. 95.3%, respectively. Conclusions: The benefit of chemotherapy in low-risk patients classified by Dutch criteria might be very small since the breast cancer mortality was less than 1% with a minimum of 5-year follow-up. Dutch criteria cannot identify high-risk patients who would benefit from chemotherapy. We assumed that multi-gene testing in low-risk patients would not be cost-effective.


2019 ◽  
Vol 1 (1) ◽  
pp. 32-36 ◽  
Author(s):  
Tisha Singer ◽  
Ana P Lourenco ◽  
Grayson L Baird ◽  
Martha B Mainiero

Abstract Objective To evaluate radiologists’ supplemental screening recommendations for women with dense breasts, at average, intermediate, or high risk of breast cancer, and to determine if there are differences between their recommendations for their patients, their friends and family, and themselves. Methods This is an anonymous survey of Society of Breast Imaging (SBI) members. Demographics, knowledge of breast density as a risk factor, and recommendations for screening with digital breast tomosynthesis (DBT), ultrasound (US), and magnetic resonance imaging (MRI) in women with dense breasts, at average, intermediate, or high- risk of breast cancer were assessed. The likelihood of their recommending the screening test for their patients, their family and friends, and themselves was assessed on a Likert scale from 0 to 4 (0 = “not at all likely” to 4 = “extremely likely”). Results There were 295 responses: 67% were women, and breast imaging comprised 95% of their practice. Among participants, 53% correctly answered the question on relative risk of breast cancer when comparing extremely dense versus fatty breasts, and 57% when comparing heterogeneously dense versus scattered breasts. US is recommended at a relatively low rate (1.0–1.4 on the 0–4 scale), regardless of risk. DBT is recommended at a relatively high rate (2.5–3.0 on the 0–4 scale), regardless of risk status. MR is recommended mainly for those at high risk (3.6 on the 0–4 scale). Radiologists were more likely to recommend additional imaging for themselves than for their patients and their family and friends. Conclusion For women with dense breasts, radiologists are “somewhat likely” to recommend US and “likely” to “very likely” to recommend DBT regardless of risk group. They are “very likely” to recommend MRI for high-risk groups.


2001 ◽  
Vol 19 (4) ◽  
pp. 924-930 ◽  
Author(s):  
C.T.M. Brekelmans ◽  
C. Seynaeve ◽  
C.C.M. Bartels ◽  
M.M.A. Tilanus-Linthorst ◽  
E.J. Meijers-Heijboer ◽  
...  

PURPOSE: Women with a high breast cancer risk due to a familial predisposition may choose between preventive surgery and regular surveillance. The effectiveness of surveillance in high-risk women and especially BRCA1/2 mutation carriers is unknown. We present first results from a single large family cancer clinic. PATIENTS AND METHODS: Women with breast cancer risk over 15% were examined by physical examination every 6 months and mammography every year. Detection rates and screening parameters were calculated for the total group and separately for different age and genetic risk groups. RESULTS: At least one examination was performed in 1,198 women: 449 moderate and 621 high-risk women and 128 BRCA1/2 mutation carriers. Within a median follow-up of 3 years, 35 breast cancers were detected (four ductal carcinoma-in-situ; 31 invasive tumors); the average detection rate was 9.7 per 1,000. Detection rates (95% confidence interval) for moderate and high-risk women and BRCA1/2 carriers were 3.3 (1.1 to 8.6), 8.4 (5.4 to 13.2), and 33 (17 to 63) per 1,000 person-years, respectively. The ratio of observed cases versus breast cancers expected in an average-risk population of comparable age was 2.7, 7.0 and 23.7 respectively. Overall, node negativity was 65%; 34% of primary tumors were less than 10 mm; sensitivity was 74%. Results with respect to tumor stage and sensitivity were less favorable in BRCA1/2 carriers and in women under the age of 40. CONCLUSION: It is possible to identify young women at high risk for breast cancer. The number of cancers detected was significantly greater than expected in an age-matched average-risk population and related to the risk category. Overall, screening parameters were comparable to population screening data, with less favorable results in the youngest age group (< 40) and BRCA1/2 carriers.


2019 ◽  
Author(s):  
Helen Cappuccino ◽  
Ermelinda Bonaccio

The fundamental tasks facing surgeons evaluating patients’ breasts are to rule out malignancy, ameliorate breast symptoms, and manage premalignant breast conditions and risk factors to minimize a patient’s chances of developing cancer. Woman presenting to a surgeon should receive thorough and appropriate breast evaluation, breast cancer risk assessment, and treatment, which minimizes risks going forward. In this review, we focus on screening recommendations for (both average and high-risk) patients for breast cancer, Breast Imaging, Reporting and Data System categories, the performance of a thorough breast history and physical examination. We also discuss various breasts imaging modalities and their strengths and weaknesses. We review breast density as a confounding factor and increased risk factor, and the grading of breast density. Finally, different ways of performing breast biopsies are discussed as well as the evaluation of risk for breast cancer with interventions for enhanced screening and risk reduction. This review contains 12 figures, 7 tables, and 35 references.  Key Words: BI-RADs, breast cancer risk factors, breast cancer risk reduction, breast core biopsy, breast screening, enhanced screening, BRCA, chemoprevention, mammography


2019 ◽  
Vol 26 (1) ◽  
pp. 107327481986279 ◽  
Author(s):  
Van Chu Nguyen ◽  
Tien Quang Nguyen ◽  
Thi Ngoc Ha Vu ◽  
Thi Huyen Phung ◽  
Thi Phuong Hoa Nguyen ◽  
...  

Breast cancer is a heterogeneous disease with different tumor subtypes. Identifying risk categories will help make better treatment decisions. Hence, this study aimed to predict the survival outcomes of invasive breast cancer in Vietnam, using St Gallen 2007 classification. This study was conducted on 501 patients with breast cancer who had surgical operations, but had not received neoadjuvant chemotherapy, from 2011 to 2013. The clinicopathological characteristics were recorded. Immunohistochemistry staining was performed on ER, PR, HER2/neu, and Ki67 markers. For HER2/neu(2+), fluorescence in situ hybridization was used as the test. All patients with breast cancer were stratified according to 2007 St Gallen categories. Kaplan-Meier and log-rank models were used to analyze survival rates. There were 3.8% cases classified as low risk (LR), 72.1% as intermediate risk (IR1: 60.1% and IR2: 12.0%), and 24.1% as high risk (HR1: 11.8% and HR2: 12.3%). Patients who were LR had the best prognosis, with a 5-year overall survival (OS) rate of 100%. Intermediate-risk patients were at 92.3%. High-risk patients had the worst prognosis, with a 5-year OS proportion of 69.3% ( P < .05). For disease-free survival (DFS), risk categories were categorized as LR: 100%, IR: 90.3%, and HR: 69.3% ( P < .05). Three main risk categories of breast cancer had a distinct OS and DFS. These findings suggest that the 2007 St Gallen risk category could be used to stratify patients with breast cancer into different risk groups in Vietnam.


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