Breast Cancer Onset in Twins and Women With Bilateral Disease

Purpose Little is known of the onset of breast cancer in high-risk populations. We investigated the risk of breast cancer in twin sisters and in the contralateral breast taking family history into consideration. Patients and Methods We analyzed a Scandinavian population-based cohort of 2,499 female twin pairs, in which at least one had a diagnosis of breast cancer and estimated the risk of breast cancer in the sister. Using a total of 11 million individuals in Sweden with complete family links, we identified 93,448 women with breast cancer and estimated the risk of a bilateral breast cancer. Results The incidence of breast cancer in twin sisters of breast cancer patients was 0.64% per year and 0.42% per year in mono- and dizygotic twin sisters, respectively. In comparison, the risk of familial (affected first-degree relative) and nonfamilial bilateral breast cancer was 1.03% per year and 0.68% per year, respectively. Contrary to the risk of unilateral disease, the risk of cancer in the nonaffected twin and the opposite breast was not affected by age or time since first event. The relative risk of familial bilateral cancer was 52% higher (incidence rate ratio [IRR] = 1.52; 95% CI, 1.42 to 1.64) and the relative risk in the dizygotic twin sister was 25% lower (IRR = 0.75; 95% CI, 0.61 to 0.91) compared with the risk of nonfamilial bilateral cancer. Conclusion The elevated risk of breast cancer in high-risk groups is little affected by age and time since diagnosis. Our findings suggest that susceptible groups of women might have already aggregated genetic prerequisites for breast cancer.

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CanAssist Breast Impacting Clinical Treatment Decisions in Early-Stage HR+ Breast Cancer Patients: Indian Scenario

Indian Journal of Surgical Oncology ◽

10.1007/s13193-019-01014-4 ◽

2019 ◽

Cited By ~ 2

Author(s):

Satish Sankaran ◽

Jyoti Bajpai Dikshit ◽

Chandra Prakash SV ◽

SE Mallikarjuna ◽

SP Somashekhar ◽

...

Keyword(s):

High Risk ◽

Early Stage ◽

Risk Groups ◽

Treatment Decisions ◽

Low Risk ◽

Not Given ◽

Breast Cancer Patients ◽

Number Of Patients ◽

Risk Of Cancer ◽

The Impact

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.

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Breast Subtypes and Prognosis of Breast Cancer Patients With Initial Bone Metastasis: A Population-Based Study

Frontiers in Oncology ◽

10.3389/fonc.2020.580112 ◽

2020 ◽

Vol 10 ◽

Author(s):

Deyue Liu ◽

Jiayi Wu ◽

Caijin Lin ◽

Lisa Andriani ◽

Shuning Ding ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Metastatic Breast Cancer ◽

Bone Metastasis ◽

Cancer Patients ◽

Metastatic Breast ◽

Risk Groups ◽

Population Based ◽

Breast Cancer Patients

BackgroundMetastatic breast cancer (MBC) is a highly heterogeneous disease and bone is one of the most common metastatic sites. This retrospective study was conducted to investigate the clinical features, prognostic factors and benefits of surgery of breast cancer patients with initial bone metastases.MethodsFrom 2010 to 2015, 6,860 breast cancer patients diagnosed with initial bone metastasis were analyzed from Surveillance, Epidemiology, and End Results (SEER) database. Univariate and Multivariable analysis were used to identify prognostic factors. A nomogram was performed based on the factors selected from cox regression result. Survival curves were plotted according to different subtypes, metastatic burdens and risk groups differentiated by nomogram.ResultsHormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) positive patients showed the best outcome compared to other subtypes. Patients of younger age (<60 years old), white race, lower grade, lower T stage (<=T2), not combining visceral metastasis tended to have better outcome. About 37% (2,249) patients received surgery of primary tumor. Patients of all subtypes could benefit from surgery. Patients of bone-only metastases (BOM), bone and liver metastases, bone and lung metastases also showed superior survival time if surgery was performed. However, patients of bone and brain metastasis could not benefit from surgery (p = 0.05). The C-index of nomogram was 0.66. Cutoff values of nomogram point were identified as 87 and 157 points, which divided all patients into low-, intermediate- and high-risk groups. Patients of all groups showed better overall survival when receiving surgery.ConclusionOur study has provided population-based prognostic analysis in patients with initial bone metastatic breast cancer and constructed a predicting nomogram with good accuracy. The finding of potential benefit of surgery to overall survival will cast some lights on the treatment tactics of this group of patients.

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Impact of the EndoPredict-clin score on risk stratification in ER-positive, HER2-negative breast cancer after considering clinical guidelines.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.542 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 542-542

Author(s):

Martin Filipits ◽

Peter Christian Dubsky ◽

Margaretha Rudas ◽

Jan C. Brase ◽

Ralf Kronenwett ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cancer Patients ◽

Endocrine Therapy ◽

Clinical Guidelines ◽

Risk Groups ◽

Low Risk ◽

Breast Cancer Patients ◽

Free Survival ◽

Er Positive

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.

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Comparative performance of Breast Cancer Index (BCIN+) and CTS5 in hormone receptor-positive (HR+) lymph node-positive (N+) breast cancer patients with one to three positive nodes (N1).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.555 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 555-555

Author(s):

Dennis Sgroi ◽

Yi Zhang ◽

Catherine A. Schnabel

Keyword(s):

Breast Cancer ◽

High Risk ◽

Cancer Patients ◽

Endocrine Therapy ◽

Tumor Size ◽

Risk Groups ◽

Cox Proportional Hazards ◽

Low Risk ◽

Intermediate Risk ◽

Breast Cancer Patients

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.

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Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients

BMC Cancer ◽

10.1186/s12885-021-08341-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ding Wang ◽

Guodong Wei ◽

Ju Ma ◽

Shuai Cheng ◽

Longyuan Jia ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

High Risk ◽

Cancer Patients ◽

Roc Curves ◽

Risk Groups ◽

Gene Signature ◽

Breast Cancer Patients ◽

Prognostic Signature ◽

Kaplan Meier

Abstract Background Breast cancer (BRCA) is a malignant tumor with high morbidity and mortality, which is a threat to women’s health worldwide. Ferroptosis is closely related to the occurrence and development of breast cancer. Here, we aimed to establish a ferroptosis-related prognostic gene signature for predicting patients’ survival. Methods Gene expression profile and corresponding clinical information of patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis model was utilized to construct a multigene signature. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, Genomes (KEGG) pathway and single-sample gene set enrichment analysis (ssGSEA) were performed for patients between the high-risk and low-risk groups divided by the median value of risk score. Results We constructed a prognostic signature consisted of nine ferroptosis-related genes (ALOX15, CISD1, CS, GCLC, GPX4, SLC7A11, EMC2, G6PD and ACSF2). The Kaplan-Meier curves validated the fine predictive accuracy of the prognostic signature (p < 0.001). The area under the curve (AUC) of the ROC curves manifested that the ferroptosis-related signature had moderate predictive power. GO and KEGG functional analysis revealed that immune-related responses were largely enriched, and immune cells, including activated dendritic cells (aDCs), dendritic cells (DCs), T-helper 1 (Th1), were higher in high-risk groups (p < 0.001). Oppositely, type I IFN response and type II IFN response were lower in high-risk groups (p < 0.001). Conclusion Our study indicated that the ferroptosis-related prognostic signature gene could serve as a novel biomarker for predicting breast cancer patients’ prognosis. Furthermore, we found that immunotherapy might play a vital role in therapeutic schedule based on the level and difference of immune-related cells and pathways in different risk groups for breast cancer patients.

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Familial breast cancer in Spain: A retrospective study of family history and clinical/pathologic characteristics from the GEICAM “El Álamo III” project.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e12513 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e12513-e12513

Author(s):

Ivan Marquez-Rodas ◽

Marina Pollán ◽

Ana Lluch ◽

Teresa Ramon y Cajal ◽

Angel Guerrero-Zotano ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Retrospective Study ◽

Family History ◽

High Risk ◽

Age Of Onset ◽

Bilateral Breast Cancer ◽

Population Based ◽

International Consensus ◽

Study Characteristics

e12513 Background: Family history (FH) of breast cancer (BC), ovarian cancer (OC), and individual features (IF), like early age of onset, bilateral BC, coexistence of BC and OC, and triple negative BC (TNBC) younger than 50 years, are suspicion criteria of hereditary BC. Although it is assumed in the literature that 15-30% of BC cases can be familial BC (FBC), only 5-10% of BC are hereditary, explained by a germline mutation in BRCA1 or 2. Moreover, there is no international consensus to define FBC (e.g. number of relatives affected, age of onset), in contrast with, e.g. Lynch syndrome and Amsterdam/Bethesda criteria, in order to offer genetic counseling. In Spain, there are not population-based studies analyzing the real percentage of BC with familial and/or individual high risk features. Methods: A retrospective study based on 10,641 Spanish BC patients diagnosed from 1998-2001, collected in the “El Álamo III project”, was conducted. Specific data regarding FBC were analyzed: IF (age of onset, bilateral breast cancer, ovarian cancer and TNBC; and FH features (first and second degree relatives with BC and /or OC). Results: The Table summarizes the results. Conclusions: 21% of BC patients in Spain diagnosed from 1998 to 2001 have at least one relative with BC and/or OC. In addition, 2.8 % of patients with no FH of BC/OC fulfill high risk criteria. However, several study characteristics, such as 18% patients with no FH recorded, and lack of data regarding age of affected relatives, limit the interpretation of these results, being necessary to improve the family data collection in further “El Álamo” project studies. [Table: see text]

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Recurrence risk stratification by Dutch clinical risk criteria for early-stage luminal breast cancer patients in Taiwan: A population-based analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12509 ◽

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

Keyword(s):

Breast Cancer ◽

High Risk ◽

Adjuvant Chemotherapy ◽

Early Stage ◽

Risk Groups ◽

Low Risk ◽

Luminal Breast Cancer ◽

Breast Cancer Patients ◽

Risk Patients

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.

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Computational metabolism modeling predicts risk of distant relapse-free survival in breast cancer patients

Future Oncology ◽

10.2217/fon-2018-0698 ◽

2019 ◽

Vol 15 (30) ◽

pp. 3483-3490 ◽

Cited By ~ 1

Author(s):

Lucía Trilla-Fuertes ◽

Angelo Gámez-Pozo ◽

Mariana Díaz-Almirón ◽

Guillermo Prado-Vázquez ◽

Andrea Zapater-Moros ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Flux Balance Analysis ◽

Risk Groups ◽

Prognostic Models ◽

Breast Cancer Patients ◽

Proteomics Data ◽

Cancer Subtypes ◽

Flux Balance ◽

Balance Analysis

Aim: Differences in metabolism among breast cancer subtypes suggest that metabolism plays an important role in this disease. Flux balance analysis is used to explore these differences as well as drug response. Materials & methods: Proteomics data from breast tumors were obtained by mass-spectrometry. Flux balance analysis was performed to study metabolic networks. Flux activities from metabolic pathways were calculated and used to build prognostic models. Results: Flux activities of vitamin A, tetrahydrobiopterin and β-alanine metabolism pathways split our population into low- and high-risk patients. Additionally, flux activities of glycolysis and glutamate metabolism split triple negative tumors into low- and high-risk groups. Conclusion: Flux activities summarize flux balance analysis data and can be associated with prognosis in cancer.

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Computational metabolism modeling predicts risk of distant relapse-free survival in breast cancer patients

10.1101/468595 ◽

2018 ◽

Author(s):

Lucía Trilla-Fuertes ◽

Angelo Gámez-Pozo ◽

Mariana Díaz-Almirón ◽

Guillermo Prado-Vázquez ◽

Andrea Zapater-Moros ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Flux Balance Analysis ◽

Risk Groups ◽

Prognostic Models ◽

Breast Cancer Patients ◽

Proteomics Data ◽

Cancer Subtypes ◽

Flux Balance ◽

Balance Analysis

AbstractAims:Differences in metabolism among breast cancer subtypes suggest that metabolism plays an important role in this disease. Flux Balance Analysis is used to explore these differences as well as drug response.Materials & Methods:Proteomics data from breast tumors were obtained by mass-spectrometry. Flux Balance Analysis was performed to study metabolic networks. Flux activities from metabolic pathways were calculated and used to build prognostic models.Results:Flux activities of vitamin A, tetrahydrobiopterin and beta-alanine metabolism pathways split our population into low- and high-risk patients. Additionally, flux activities of glycolysis and glutamate metabolism split triple negative tumors into low- and high-risk groups.Conclusions:Flux activities summarize Flux Balance Analysis data and can be associated with prognosis in cancer.

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

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.587 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 587-587

Author(s):

Caroline Drukker ◽

Marjanka Schmidt ◽

Emiel J. Rutgers ◽

Fatima Cardoso ◽

Karla Kerlikowske ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Digital Mammography ◽

Screening Program ◽

Gene Signature ◽

Population Based ◽

Low Risk ◽

Breast Cancer Patients ◽

Background Population ◽

The Impact

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.

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