scholarly journals Machine Learning Methods to Identify Genetic Correlates of Radiation-Associated Contralateral Breast Cancer in the WECARE Study

2019 ◽  
Author(s):  
Sangkyu Lee ◽  
Xiaolin Liang ◽  
Meghan Woods ◽  
Anne S. Reiner ◽  
Duncan Thomas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Contralateral Breast Cancer ◽  
Area Under The Curve ◽  
Contralateral Breast ◽  
Dependent Manner ◽  
Nucleotide Polymorphisms ◽  
Unilateral Breast Cancer ◽  
Validation Data ◽  
Increased Risk

AbstractThe purpose of this study is to identify germline single nucleotide polymorphisms (SNPs) that optimally predict radiation-associated contralateral breast cancer (RCBC) and to provide new biological insights into the carcinogenic process. Fifty-two women with contralateral breast cancer and 153 women with unilateral breast cancer were identified within the Women’s Environmental Cancer and Radiation Epidemiology (WECARE) Study who were at increased risk of RCBC because they were ≤ 40 years of age at first diagnosis of breast cancer and received a scatter radiation dose > 1 Gy to the contralateral breast. A previously reported algorithm, preconditioned random forest regression, was applied to predict the risk of developing RCBC. The resulting model produced an area under the curve of 0.62 (p=0.04) on hold-out validation data. The biological analysis identified the cyclic AMP-mediated signaling and Ephrin-A as significant biological correlates, which were previously shown to influence cell survival after radiation in an ATM-dependent manner. The key connected genes and proteins that are identified in this analysis were previously identified as relevant to breast cancer, radiation response, or both. In summary, machine learning/bioinformatics methods applied to genome-wide genotyping data have great potential to reveal plausible biological correlates associated with the risk of RCBC.

Contralateral breast cancer: annual incidence and risk parameters.

1995 ◽  
Vol 13 (7) ◽  
pp. 1578-1583 ◽  
Author(s):  
P Broët ◽  
A de la Rochefordière ◽  
S M Scholl ◽  
A Fourquet ◽  
V Mosseri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Contralateral Breast Cancer ◽  
Clinical Stage ◽  
Incidence Rates ◽  
Contralateral Breast ◽  
Annual Incidence ◽  
Second Primary ◽  
Unilateral Breast Cancer ◽  
Increased Risk

PURPOSE To screen for factors that might predict the risk of developing metachronous contralateral breast cancer (CBC), taking into account the influence of local or distant recurrence, and to assess the annual incidence of CBC. PATIENTS AND METHODS Of 4,748 women with invasive unilateral breast cancer, clinical stage I to IIIa, treated between 1981 and 1987, 282 metachronous CBCs were diagnosed. Due to competing risks between the occurrence of CBC and other events, several options for multivariate analysis were considered. RESULTS The median follow-up time was 80 months (range, 1 to 158). The cumulative rate of CBC was 4.1% +/- 0.3% at 5 years, and the annual incidence rate of CBC increased slowly, while the risk of local recurrence and metastases decreased after the fourth year. Whichever model we chose, age less than 55 years (relative risk [RR] = 1.40) at the time of diagnosis of the first breast cancer, as well as the presence of lobular type carcinoma (RR = 1.50), was associated with an increased risk of developing a tumor in the contralateral breast. Adjuvant chemotherapy significantly decreased (RR = 0.54) the risk of CBC. CONCLUSION Lobular histology and age less than 55 years are found to increase the risk of CBC, while adjuvant chemotherapy significantly decreased the risk of CBC. The progressive rise in the annual incidence rates of CBC, together with the absence of a link between clinical prognostic factors of the first cancer and CBC, suggested that CBC can be considered as a second primary breast cancer.

Factors leading to the decision for contralateral prophylactic mastectomy in patients with breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1528-1528
Author(s):  
M. Yi ◽  
K. K. Hunt ◽  
B. K. Arun ◽  
I. Bedrosian ◽  
A. M. Gutierrez Barrera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Primary Breast Cancer ◽  
Contralateral Breast Cancer ◽  
Prophylactic Mastectomy ◽  
Contralateral Prophylactic Mastectomy ◽  
Contralateral Breast ◽  
Cancer Center ◽  
Tumor Characteristics ◽  
Increased Risk

1528 Background: Women with breast cancer have an increased risk of developing contralateral breast cancer in their lifetime. Thus increasing numbers of women have been electing to undergo contralateral prophylactic mastectomy (CPM) at the time of their initial breast cancer treatment. The objective of this study was to identify factors that determine the decision for CPM in patients at a major cancer center. Methods: 2,544 women with Stage 0-III unilateral primary breast cancer who underwent surgery to the breast at our institution from January 2000 to August 2006 were identified from a prospectively maintained database. Patient and tumor characteristics were evaluated and comparisons were made between patients who did or did not undergo CPM using logistic regression. Results: Of the 2,544 patients, 1254 (49.3%) underwent total mastectomy for their known cancer; 282 (22.5%) of these patients underwent immediate or delayed CPM. Overall, 171 patients (6.7%) had genetic testing; and the use of testing increased in the latter years of the study (3.% in 2000–2002 vs. 8.2% in 2003–2006, p<.0001). 49 of 171 patients had genetic testing prior to surgery. 10 had a deleterious BRCA1/2 mutation, 9 of whom had a CPM (p=.002). 14 patients without a mutation also had a CPM. Multivariate analysis revealed factors associated with use of CPM were: age younger than 50, white race, family history of breast cancer, higher clinical tumor stage, invasive lobular histology, and use of reconstruction (Table). Conclusions: Both patient and tumor characteristics influence selection of CPM. Although the use of genetic testing is increasing, most women elect to undergo CPM without having genetic testing. Evidence-driven models are needed to better inform women of their absolute risk of contralateral breast cancer as well as competing risk from their primary breast cancer in order to empower them in their active-decision-making. [Table: see text] No significant financial relationships to disclose.

Detection of Malignant lesion in Contralateral Breast in Newly Diagnosed Patients of Unilateral Carcinoma Breast on MRI

2020 ◽  
Vol 10 (2) ◽  
Author(s):  
Ghazala Wahid ◽  
Naila Tamkeen ◽  
Anjum Naz ◽  
Maimoona Afsar ◽  
Amina Ashraf ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Examination ◽  
Bilateral Breast Cancer ◽  
Malignant Lesion ◽  
Contralateral Breast ◽  
Radiology Department ◽  
Newly Diagnosed ◽  
Unilateral Breast Cancer ◽  
Carcinoma Breast ◽  
Increased Risk

Background: Women having unilateral breast cancer have added risk of contralateral breast cancer with an incidence of 1-5% synchronous cancer. There is also increased risk of metachronous cancer in contralateral breast . Female patients with bilateral breast cancer have grave prognosis in comparison to those with unilateral breast cancer. MRI breast is used to assess the multifocality and multicentricity of tumour. Objective: To determine the diagnostic performance of MRI in detecting malignant lesion in contralateral breast in newly diagnosed patients of unilateral carcinoma breast.Material and Methods: In this study total 150 newly diagnosed patients of unilateral breast cancer with normal mammographic and clinical examination of other breast were included. Study was conducted in Radiology department, Hayatabad Medical Complex Peshawar from Jan 2017 to March 2020. MRI scan of normal breast was done on a 1.5 Tesla magnet with multi-channel breast coil. For evaluating the breast lesions, administration of IV contrast and high spatial resolution is necessary .The malignant lesions of breast found on MRI were confirmed histo-pathologically. Results: In 5 out of total 150 women included in study, MRI detected occult breast cancer in the opposite breast in whom clinical examination and mammography was normal (3.3%). 18 women (12.5 %) out of total 150 with positive findings on MRI underwent biopsy, and 5 specimens turned out to be carcinoma (27%). Conclusion: MRI is very useful and helpful to detect occult malignancy in opposite breast which are not detected clinically or by mammography at the time of the initial diagnosis of carcinoma breast.

Tumor Stage Affects Risk and Prognosis of Contralateral Breast Cancer: Results From a Large Swedish-Population–Based Study

2012 ◽  
Vol 30 (28) ◽  
pp. 3478-3485 ◽  
Author(s):  
Voralak Vichapat ◽  
Hans Garmo ◽  
Marit Holmqvist ◽  
Göran Liljegren ◽  
Fredrik Wärnberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Primary Tumor ◽  
Primary Breast Cancer ◽  
Contralateral Breast Cancer ◽  
Cox Regression ◽  
Short Interval ◽  
Contralateral Breast ◽  
Increased Risk

Purpose The number of breast cancer survivors at risk of developing contralateral breast cancer (CBC) is increasing. However, ambiguity remains regarding risk factors and prognosis for women with CBC. Patients and Methods In a cohort of 42,670 women with breast cancer in the Uppsala/Örebro and Stockholm regions in Sweden in 1992 to 2008, we assessed risk factors for and prognosis of metachronous CBC by using survival analysis. Breast cancer–specific survival for women with CBC was evaluated and compared with results for women with unilateral breast cancer (UBC) by using time-dependent Cox-regression modeling. Results An increased risk for CBC was observed among women who had primary breast cancer with ≥ 10 involved lymph nodes compared with node-negative women (adjusted hazard ratio [HR], 1.8; 95% CI, 1.2 to 2.7). The prognosis was poorer in women with CBC than with UBC. The hazard of dying from breast cancer was especially high for women with a short interval time to CBC (adjusted HR, 2.3; 95% CI, 1.8 to 2.8 for CBC diagnosed ≤ 5 years v UBC) and gradually decreased with longer follow-up time but remained higher than the hazard originating from the primary tumor for ≥ 10 years. Conclusion Women with advanced-stage primary breast cancer had an increased risk of developing CBC. CBC is associated with an increased risk of dying from breast cancer throughout a long period of follow-up after the primary tumor. Our findings suggest that the event of CBC marks a new clinical situation in terms of investigations for metastases, treatment considerations, and follow-up strategy.

scholarly journals Genetic Variants in pre-miR-146a, pre-miR-499, pre-miR-125a, pre-miR-605, and pri-miR-182 Are Associated with Breast Cancer Susceptibility in a South American Population

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 427 ◽  
Author(s):  
Sebastián Morales ◽  
Tomas De Mayo ◽  
Felipe Gulppi ◽  
Patricio Gonzalez-Hormazabal ◽  
Valentina Carrasco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
South American ◽  
Dependent Manner ◽  
Nucleotide Polymorphisms ◽  
American Population ◽  
South American Population ◽  
Risk Alleles ◽  
Increased Risk

Breast cancer (BC) is one of the most frequent tumors affecting women worldwide. microRNAs (miRNAs) single-nucleotide polymorphisms (SNPs) likely contribute to BC susceptibility. We evaluated the association of five SNPs with BC risk in non-carriers of the BRCA1/2-mutation from a South American population. The SNPs were genotyped in 440 Chilean BRCA1/2-negative BC cases and 1048 controls. Our data do not support an association between rs2910164:G>C or rs3746444:A>G and BC risk. The rs12975333:G>T is monomorphic in the Chilean population. The pre-miR-605 rs2043556-C allele was associated with a decreased risk of BC, both in patients with a strong family history of BC and in early-onset non-familial BC (Odds ratio (OR) = 0.5 [95% confidence interval (CI) 0.4–0.9] p = 0.006 and OR = 0.6 [95% CI 0.5–0.9] p = 0.02, respectively). The rs4541843-T allele is associated with increased risk of familial BC. This is the first association study on rs4541843 and BC risk. Previously, we showed that the TOX3-rs3803662:C>T was significantly associated with increased risk of familial BC. Given that TOX3 mRNA is a target of miR-182, and that both the TOX3 rs3803662-T and pri-miR-182 rs4541843-T alleles are associated with increased BC risk, we evaluated their combined effect. Risk of familial BC increased in a dose-dependent manner with the number of risk alleles (p-trend = 0.0005), indicating an additive effect.

scholarly journals MRI Evaluation of the Contralateral Breast in Women with Recently Diagnosed Breast Cancer: 2-Year Follow-up

2019 ◽  
Vol 2 (1) ◽  
pp. 50-55
Author(s):  
Nanette D Debruhl ◽  
Su-Ju Lee ◽  
Mary C Mahoney ◽  
Lucy Hanna ◽  
Catherine Tuite ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Contralateral Breast Cancer ◽  
Diagnostic Yield ◽  
Study Participant ◽  
Breast Mri ◽  
Contralateral Breast ◽  
Unilateral Breast Cancer

Abstract Objective The American College of Radiology Imaging Network Trial 6667 showed that MRI can detect cancer in the contralateral breast that is missed by mammography and clinical examination at the time of the initial breast cancer diagnosis, based on 1-year follow-up. This study is a continuation of the trial that evaluates the diagnostic accuracy of MRI for contralateral breast cancer after 2 years of follow-up. Methods In total, 969 women with a diagnosis of unilateral breast cancer and no clinical or imaging abnormalities in the contralateral breast underwent breast MRI. The cancer status of all participants was monitored for 2 years after the initial MRI. Follow-up included documentation of any clinical, imaging, or interventional procedures performed. A study participant was considered positive for cancer if she had a tissue diagnosis of in situ or invasive breast cancer in the contralateral breast within 730 days of her initial MRI. Results Three additional cancers were diagnosed in the study population in the second year of the trial. The diagnostic yield for MRI for the 2-year period was 3% (31/969). After 2 years of follow-up, breast MRI has a sensitivity of 86% and specificity of 88% for detection of contralateral breast cancer. Its negative predictive value was 99%, and its positive predictive value was 22%. These values did not change significantly from the 1-year data. Conclusion A negative contralateral breast MRI has a very high and reliable negative predictive value over 2 years, and, therefore, is helpful in managing and counseling patients during the period of initial diagnosis and early treatment.

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