Breast cancer screening: Biology of tumors detected by analog and digital mammography.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 587-587
Author(s):  
Caroline Drukker ◽  
Marjanka Schmidt ◽  
Emiel J. Rutgers ◽  
Fatima Cardoso ◽  
Karla Kerlikowske ◽  
...  

587 Background: Population-based screening might be associated with a higher likelihood of a (ultra)low risk tumor assessed by the 70-gene signature (MammaPrint) (ultralow defined as indexscore >0.6, no distant metastasis observed at 5 years in the original 78 patients). The aim of this study is to determine the proportion of biologically (ultra)low risk tumors among the screen-detected tumors and to evaluate the impact of the analog versus digital screening technique. Methods: All Dutch breast cancer patients enrolled in the MINDACT trial (EORTC-10041), who were invited for the Dutch screening program (biennial, age 50-75), were included (n=1409). The proportions of 70-gene signature high, low and ultralow risk were calculated for patients with screen-detected (n=775), interval (n=390), and symptomatic, non-screening (n=244) carcinomas, taking into account analog vs. digital technology. Co-variants such as age, tumor size, grade, histological type, ER, HER2 and nodal status were included in the analyses. Results: Among the screen-detected tumors, 31.5% had a high risk, 31.2% a low risk and 37.3% an ultralow risk 70-gene signature result, compared to 47.4%, 28.5% and 24.1% among the interval carcinomas, respectively (p=0.001). Among the screen-detected carcinomas, 40.6% were detected using analog (n=315) and 59.4% using digital mammography (n=459). When using digital imaging a shift was seen among the screen-detected tumors in the proportions of high risk tumors from 27% to 35% and ultralow risk from 42% to 34%, low risk proportions remained the same (31%)(p=0.011). No such difference was seen for other tumor characteristics. Conclusions: Screen-detection was found to be associated with a higher likelihood of a biologically low risk tumor. The transition from analog to digital mammography resulted in a smaller proportion of ultralow risk and a larger proportion of high risk tumors among the screen-detected carcinomas.

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengdi Chen ◽  
Deyue Liu ◽  
Weilin Chen ◽  
Weiguo Chen ◽  
Kunwei Shen ◽  
...  

BackgroundThe 21-gene assay recurrence score (RS) provides additional information on recurrence risk of breast cancer patients and prediction of chemotherapy benefit. Previous studies that examined the contribution of the individual genes and gene modules of RS were conducted mostly in postmenopausal patients. We aimed to evaluate the gene modules of RS in patients of different ages.MethodsA total of 1,078 estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients diagnosed between January 2009 and March 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were included. All patients were divided into three subgroups: Group A, ≤40 years and premenopausal (n = 97); Group B, >40 years and premenopausal (n = 284); Group C, postmenopausal (n = 697). The estrogen, proliferation, invasion, and HER2 module scores from RS were used to characterize the respective molecular features. Spearman correlation and analysis of the variance tests were conducted for RS and its constituent modules.ResultsIn patients >40 years, RS had a strong negative correlation with its estrogen module (ρ = −0.76 and −0.79 in Groups B and C) and a weak positive correlation with its invasion module (ρ = 0.29 and 0.25 in Groups B and C). The proliferation module mostly contributed to the variance in young patients (37.3%) while the ER module contributed most in old patients (54.1% and 53.4% in Groups B and C). In the genetic high-risk (RS >25) group, the proliferation module was the leading driver in all patients (ρ = 0.38, 0.53, and 0.52 in Groups A, B, and C) while the estrogen module had a weaker correlation with RS. The impact of ER module on RS was stronger in clinical low-risk patients while the effect of the proliferation module was stronger in clinical high-risk patients. The association between the RS and estrogen module was weaker among younger patients, especially in genetic low-risk patients.ConclusionsRS was primarily driven by the estrogen module regardless of age, but the proliferation module had a stronger impact on RS in younger patients. The impact of modules varied in patients with different genetic and clinical risks.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11008-11008 ◽  
Author(s):  
N. Ben-Baruch ◽  
A. Hammerman ◽  
S. Klang ◽  
N. Liebermann

11008 Background: The Oncotype DX™ Recurrence Score (RS) assay predicts distant recurrence risk and benefit of chemotherapy (CT) in N-, ER+ breast cancer patients (pts). In February 2006, Clalit Health Services in Israel (CHS) was the first public health insurer to reimburse the assay outside the USA. Methods: CHS requires a pre-authorization form with data on biological parameters and specification of treatment (Rx) recommendation (1) before knowledge of RS and (2) the Rx planned according to each of 3 possible RS risk levels. For the first 200 reimbursed assays, we compared: (1) the Rx offered without RS knowledge, (2) the Rx the patient actually received after RS, and (3) the planned Rx stated on the form to be given according to the RS. Results: 200 pts. Median age: 57 yrs (34–81). RS: Low risk (RS<18), 37.5%; Intermediate (int) risk (RS 18–30), 44.5%; High risk (RS≥31), 18%. In 20 pts, Rx recommendations before RS were not specified. Before the RS, CT was offered in 106/180 (59%) and hormonal therapy (HT) in 74/180 (41%). In 71/180 pts (39%) the actual Rx changed from the recommendation before RS - CT to HT in 62 pts (low risk: 37, int risk: 21, high risk: 4) and HT to CT in 9 pts (int risk: 4, high risk: 5). Suggested therapy by RS was not specified in 19 pts. In 30/181 (17%) actual Rx differed from planned - CT to HT in 20 pts (int risk: 17, high risk: 3) and HT to CT in 10 pts (low risk: 4, int risk: 6). Conclusions: RS changed the treatment decision in a significant proportion of pts (39%), mostly from CT to HT. In 58% of pts originally offered CT, knowledge of RS changed the Rx to HT. 12% of pts originally offered HT were treated with CT. Rx decisions in intermediate RS are sometimes not obvious. In 26% of intermediate RS, final Rx differed from original plan; in these cases, patients’ preferences might have had a major impact on decision making. No significant financial relationships to disclose.


2020 ◽  
Author(s):  
Jianing Tang ◽  
Gaosong Wu

Abstract Background Metabolic change is the hallmark of cancer. Even in the presence of oxygen, cancer cells reprogram their glucose metabolism to enhance glycolysis and reduce oxidative phosphorylation. In the present study, we aimed to develop a glycolysis-related gene signature to predict the prognosis of breast cancer patients.Methods Gene expression profiles and clinical data of breast cancer patients were obtained from the GEO database. Univariate, Lasso-penalized, and multivariate Cox analysis were performed to construct the glycolysis-related gene signature.Results A four-gene based signature (ALDH2, PRKACB, STMN1 and ZNF292) was developed to separate patients into high-risk and low-risk groups. Kaplan-Meier survival analysis demonstrated that patients in low-risk group had significantly better prognosis than those in the high-risk group. Time-dependent ROC analysis demonstrated that the glycolysis-related gene signature had excellent prognostic accuracy. We further confirmed the expression of the four prognostic genes in breast cancer and paracancerous tissues samples using qRT-PCR analysis. Expression level of PRKACB was higher in paracancerous tissues, while STMN1 and ZNF292 were overexpressed in tumor samples. No difference was found in ALDH2 expression. The same results were observed in the IHC data from the human protein atlas. Global proteome data of 105 TCGA breast cancer samples obtained from the Clinical Proteomic Tumor Analysis Consortium were used to evaluate the prognostic value of their protein levels. Consistently, high expression of PRKACB protein level was associated with better prognosis, while high ZNF292 and STMN1 protein expression levels indicated poor prognosis.Conclusions The glycolysis-related gene signature might provide an effective prognostic predictor and a new view for individual treatment of breast cancer patients.


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 47-47
Author(s):  
B. Nguyen ◽  
K. B. Deck ◽  
R. Sinha ◽  
D. Kerlin ◽  
J. Barone ◽  
...  

47 Background: MammaPrint (MP) is a powerful predictor of disease outcome in early stage breast cancer. In addition, TargetPrint (TP), a microarray-based test that measures the mRNA expression level of ER, PR and HER2 and an 80 gene expression Molecular Subtyping profile BluePrint (BP) were developed. In the present study, MP, BP and TP were measured in a prospective U.S. breast cancer patient cohort. Methods: MP results were evaluated in fresh tumor samples from 127 breast cancer patients (T1-4N0-2; median age 62 [39-97 yr]) collected by core needle biopsy or from a surgical specimen between July 2008 and January 2011. We compared treatment advice as recommended by NCCN guidelines and classification according to MP. In addition, we compared IHC/FISH ER, PR and HER2 assessments with TP. The MP and BP results were used to subtype the patients into molecular subgroups. Results: For the group of patients (n=59) for which NCCN recommends the use of a multi-gene signature for determining chemotherapy treatment recommendations, 42 patients were classified as High Risk and 17 as Low Risk by MP. Comparison of TP with IHC/FISH indicated a concordance of 98% for ER, 94% for PR, and 98% for HER2. For a subgroup of 53 patients combined MP and BP results were available; 18 patients were Luminal-type/MP Low Risk, 27 patients were Luminal-type/MP High risk, 1 patient was Her2-type/MP Low Risk, 1 patient was Her2-type/MP High Risk and 6 patients were Basal-type/MP High Risk. Conclusions: Adding the multi-gene signature MammaPrint, as well as BluePrint and TargetPrint provides additional information for treatment guidance. By combining MammaPrint with the BluePrint molecular subtyping profile, specific groups of patients can be recognized that are at high risk of recurrence and that would possibly benefit from specific treatment. This study shows that TargetPrint provides high quality second opinion for local IHC/FISH assessment.


Author(s):  
Satish Sankaran ◽  
Jyoti Bajpai Dikshit ◽  
Chandra Prakash SV ◽  
SE Mallikarjuna ◽  
SP Somashekhar ◽  
...  

AbstractCanAssist Breast (CAB) has thus far been validated on a retrospective cohort of 1123 patients who are mostly Indians. Distant metastasis–free survival (DMFS) of more than 95% was observed with significant separation (P < 0.0001) between low-risk and high-risk groups. In this study, we demonstrate the usefulness of CAB in guiding physicians to assess risk of cancer recurrence and to make informed treatment decisions for patients. Of more than 500 patients who have undergone CAB test, detailed analysis of 455 patients who were treated based on CAB-based risk predictions by more than 140 doctors across India is presented here. Majority of patients tested had node negative, T2, and grade 2 disease. Age and luminal subtypes did not affect the performance of CAB. On comparison with Adjuvant! Online (AOL), CAB categorized twice the number of patients into low risk indicating potential of overtreatment by AOL-based risk categorization. We assessed the impact of CAB testing on treatment decisions for 254 patients and observed that 92% low-risk patients were not given chemotherapy. Overall, we observed that 88% patients were either given or not given chemotherapy based on whether they were stratified as high risk or low risk for distant recurrence respectively. Based on these results, we conclude that CAB has been accepted by physicians to make treatment planning and provides a cost-effective alternative to other similar multigene prognostic tests currently available.


2021 ◽  
Author(s):  
juanjuan Qiu ◽  
Li Xu ◽  
Yu Wang ◽  
Jia Zhang ◽  
Jiqiao Yang ◽  
...  

Abstract Background Although the results of gene testing can guide early breast cancer patients with HR+, HER2- to decide whether they need chemotherapy, there are still many patients worldwide whose problems cannot be solved well by genetic testing. Methods 144 735 patients with HR+, HER2-, pT1-3N0-1 breast cancer from the Surveillance, Epidemiology, and End Results database were included from 2010 to 2015. They were divided into chemotherapy (n = 38 392) and no chemotherapy (n = 106 343) group, and after propensity score matching, 23 297 pairs of patients were left. Overall survival (OS) and breast cancer-specific survival (BCSS) were tested by Kaplan–Meier plot and log-rank test and Cox proportional hazards regression model was used to identify independent prognostic factors. A nomogram was constructed and validated by C-index and calibrate curves. Patients were divided into high- or low-risk group according to their nomogram score using X-tile. Results Patients receiving chemotherapy had better OS before and after matching (p < 0.05) but BCSS was not significantly different between patients with and without chemotherapy after matching: hazard ratio (HR) 1.005 (95%CI 0.897, 1.126). Independent prognostic factors were included to construct the nomogram to predict BCSS of patients without chemotherapy. Patients in the high-risk group (score > 238) can get better OS HR 0.583 (0.507, 0.671) and BCSS HR 0.791 (0.663, 0.944) from chemotherapy but the low-risk group (score ≤ 238) cannot. Conclusion The well-validated nomogram and a risk stratification model was built. Patients in the high-risk group should receive chemotherapy while patients in low-risk group may be exempt from chemotherapy.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 542-542
Author(s):  
Martin Filipits ◽  
Peter Christian Dubsky ◽  
Margaretha Rudas ◽  
Jan C. Brase ◽  
Ralf Kronenwett ◽  
...  

542 Background: Many ER-positive, HER2-negative breast cancer patients are treated by adjuvant chemotherapy according to current clinical guidelines. We retrospectively assessed whether the combined gene expression/ clinicopathological EndoPredict-clin (EPclin) score improved the accuracy of risk classification in addition to considering clinical guidelines. Methods: Three clinical breast cancer guidelines (National Comprehensive Cancer Center Network (NCCN), German S3 and St. Gallen 2011), and the EPclin score - assessed by quantitative RT-PCR in formalin-fixed paraffin-embedded tissue - were used to assign risk groups in 1,702 ER-positive, HER2-negative breast cancer patients from two randomized phase III trials (Austrian Breast and Colorectal Cancer Study Group 6 and 8) treated with endocrine therapy only. Results: Although all analyzed clinical guidelines identified a low-risk group with improved metastasis-free survival, the overwhelming majority of all patients (81-94%) were classified as intermediate / high risk. In contrast to that, the EPclin classified only 37% of all patients as high risk and that stratification resulted in the best separation between low and high risk groups (p < 0.001, HR = 5.11 (3.48-7.51). Consequently, the majority of all patients deemed intermediate / high risk by the clinical guidelines was re-classified as low risk by the EPclin score. Kaplan Meier analyses demonstrated that the re-classified subgroups (47 to 57% of all patients) had an excellent 10-year metastasis-free survival of 95% comparable to the clinical assigned low-risk groups although encompassing a higher proportion of the trial patients. Conclusions: The EPclin score predicted distant recurrence more accurately than all three clinical guidelines and is especially useful to reclassify patients considered as intermediate / high risk by the guidelines. The data suggests that the EPclin score provides clinically useful prognostic information beyond common clinical guidelines and can be used to accurately identify the clinically relevant group of patients who are adequately and sufficiently treated with adjuvant endocrine therapy alone.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3599-3599
Author(s):  
David Mansouri ◽  
Donald C. Mcmillan ◽  
Emilia M Crighton ◽  
Paul G Horgan

3599 Background: Population-based FOBt colorectal cancer screening has been shown to reduce cancer specific mortality and is used across the UK. Despite evidence that socioeconomic deprivation is associated with increased incidence of colorectal cancer, uptake of screening may be lower in those who are more deprived. The aim of this study was to assess the impact of deprivation on the screening process. Methods: A prospectively maintained database, encompassing the first screening round in a single geographical area, was analysed with deprivation categories calculated from the Scottish Index of Multiple Deprivation 2009. Results: Overall, 395,698 individuals were invited to screening, 204,812(52%) participated and 6,094(3%) tested positive. 32% of screened individuals were in the most deprived quintile. Of the positive tests, 5,457(95%) agreed to be pre-assessed for colonoscopy. 839(16%) did not proceed to colonoscopy following pre-assessment. Of the 4,618 that attended for colonoscopy, cancer was detected in 7%. Colonoscopy results were not recorded in 1,035(22%) cases. Lower uptake of screening was seen in males, those that were younger and those who were more deprived (p<0.001). Higher levels of deprivation were also associated with not proceeding to colonoscopy following pre-assessment (p<0.001). Higher positivity rates were seen in males, those that were older and more deprived (p<0.001). Despite higher positivity rates in the more deprived individuals (4% most deprived vs 2% least deprived, p<0.001), the positive predictive value of detecting cancer in those attending for colonoscopy was lower in those who were more deprived (6% most deprived vs 8% least deprived, p=0.040). Conclusions: Socioeconomic deprivation has a significant effect throughout the FOBt screening process. Individuals who are more deprived are less likely to participate in screening, less likely to complete the screening process and less likely to have cancer identified as a result of a positive test. This study adds further weight to existing evidence that individuals who are more deprived are less likely to engage in population-based FOBt colorectal cancer screening. Novel strategies to improve this are required.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 555-555
Author(s):  
Dennis Sgroi ◽  
Yi Zhang ◽  
Catherine A. Schnabel

555 Background: Identification of N+ breast cancer patients with a limited risk of recurrence improves selection of those for which chemotherapy and/or extended endocrine therapy (EET) may be most appropriate to reduce overtreatment. BCIN+ integrates gene expression with tumor size and grade, and is highly prognostic for overall (0-10yr) and late (5-10yr) distant recurrence (DR) in N1 patients. Clinical Treatment Score post-5-years (CTS5) is a prognostic model based on clinicopathological factors (nodes, age, tumor size and grade) and significantly prognostic for late DR. The current analysis compares BCIN+ and CTS5 for risk of late DR in N1 patients. Methods: 349 women with HR+, N1 disease and recurrence-free for ≥5 years were included. BCIN+ results were determined blinded to clinical outcome. CTS5 was calculated as previously described (Dowsett et al, JCO 2018; 36:1941). Kaplan-Meier analysis and Cox proportional hazards regression for late DR (5-15y) were evaluated. Results: 64% of patients were > 50 years old, 34% with tumors > 2cm, 79% received adjuvant chemotherapy and 64% received up to 5 years of ET. BCIN+ stratified 23% of patients as low-risk with 1.3% risk for late DR vs those classified as high-risk with 16.1% [HR 12.4 (1.7-90.4), p = 0.0014]. CTS5 classified patients into 3 risk groups: 29% of patients as low-risk (4.2% DR), 37% as intermediate-risk (10.6% DR), and 34% as high-risk (22.1% DR) [HR intermediate vs. low: 2.3 (0.7-7.0), p = 0.16; high vs. low: 5.3 (1.8-15.5), p = 0.002]. In a subset of patients who completed 5 years of ET (N = 223), BCIN+ identified 22% of patients as low-risk with a late DR rate of 2.1%, while CTS5 identified 29% and 37% of patients as low- and intermediate-risk with late DR rates of 5.2% and 10.3%, respectively. Conclusions: BCIN+ classified N1 patients into binary risk groups and identified 20% patients with limited risk of late DR ( < 2%) that may be advised to forego EET and its attendant toxicities/side effects. In comparison, CTS5 classified patients into 3 risk groups, with low- and intermediate-risk of late DR of 4-5% and 10%, wherein the risk-benefit profile for extension of endocrine therapy is less clear.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13671-e13671
Author(s):  
Chen Tian ◽  
Lili Fu ◽  
Jiyu Wei ◽  
Pengfei Yin ◽  
Henghui Zhang

e13671 Background: A 70-gene prognosis-signature, known as MammaPrint (MP), is validated as a good predictor of recurrence in patients with ER+/HER2- early stage breast cancer in Europe and America. Previous studies on Japanese and Korean breast cancer patients showed that the proportion of MP Low-Risk tumours is significantly lower than the percentage which reported in previous studies. Here we use MammaPrint to determine the gene profiles of breast cancer tumours from Chinese patients and investigate the test’s potential clinical applications. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumour samples or fresh tumour samples from 594 eligible breast cancer patients were collected from 97 hospitals in China. Tumor RNAs were isolated from samples and analyzed using RNA sequencing technology. Clinical risk was categorized based on the Adjuvant! algorithm as used in the MINDACT trial. Concordance between risk predicted by the MammaPrint and clinical characteristics were evaluated. We also analyzed the clinical-pathology features of patients and compared them to previous studies. Results: Overall, 315 patients were categorized as clinical high risk (182 were MP Low-Risk and 133 MP High-Risk), while 279 patients were categorized as clinical low risk (203 were MP Low-Risk and 76 MP High-Risk). The concordance rate between risk predicted by the MammaPrint and clinical characteristics was 56.57%. Among the clinical-pathology features, age, ER/PR/HER2 status, tumour grade and tumour size were significantly related to the genomic risk (p = 0.009, 0.003, < 0.001, 0.001, < 0.001, and 0.007 respectively). Conclusions: The proportion of MP Low-Risk tumours was 64.81%, which is similar to previous validated studies in Europe and America. Of the patients that were clinical high risk, 58% was categorized as MP Low-Risk, and this group of patients may have limited benefit from chemotherapy. Our results indicate that MammaPrint is applicable to Chinese patients and has potential value in clinical practice to avoid over-treatment.


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