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      Impact of race and tumor subtype on second malignancy risk in women with breast cancer

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          Abstract

          Purpose

          Women with breast cancer are at increased risk of second malignancy (SM). However, the impact of race and the hormone receptor (HR) status of the primary breast tumor on risk of SM are not known. The purpose of this study is to analyze the incidence of SM in women with a history of breast cancer according to race and HR status.

          Methods

          In the surveillance, epidemiology, and end results database, multiple primary standardized incidence ratio sessions were used to compare the incidence of SM in women with a history breast cancer to the cancer incidence in the general population. Analyses of SM by age, race, and hormone-receptor status were performed using the absolute excess risk (AER) and observed/expected (O/E) ratio.

          Results

          Younger black women (under the age of 50) were at greater risk of SM with an AER = 76.03 (O/E = 2.3, 95 % CI = 12.19–2.4) compared to younger white women who had an AER = 38.59 (O/E = 1.55, 95 % CI = 1.53–1.58). Older black women (50 years and older) had at an increased risk of SM with an AER = 42.26 (O/E = 1.3, 95 % CI = 1.26–1.34) compared to older white women who had an AER = 11.56 (O/E = 1.07, 95 % CI = 1.06–1.08). Second breast malignancy is the predominant SM in both black and white women. Women with hormone-receptor (HR)-negative breast cancer had higher risk of SMs with an AER = 43.53 (O/E = 1.41, 95 % CI = 1.38– 0.145–3.31) compared to women with HR-positive disease with an AER = 21.43 (O/E = 1.17, 95 % CI = 1.16–0.1.18). In HR-negative women, younger black women had an AER = 96.46 (O/E = 2.99, 95 % CI = 2.70–3.31), younger white women had an AER = 66 (O/E = 2.25, 95 % CI = 2.13–2.36), older black women had an AER = 58.58 (O/E = 1.45, 95 % CI = 1.34–1.57), and older white women had an AER = 20.88 (O/E = 1.14, 95 % CI = 1.11–1.18).

          Conclusions

          Black breast cancer survivors and women with HR-negative breast cancer are at increased risk of SM, which deserves further evaluation to understand the biological and clinical basis for this increased risk.

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          Most cited references12

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          Differences in breast cancer stage at diagnosis and cancer-specific survival by race and ethnicity in the United States.

          Women with early-stage breast cancers are expected to have excellent survival rates. It is important to identify factors that predict diagnosis of early-stage breast cancers.
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            Genomic scars as biomarkers of homologous recombination deficiency and drug response in breast and ovarian cancers

            Poly (ADP-ribose) polymerase (PARP) inhibitors and platinum-based chemotherapies have been found to be particularly effective in tumors that harbor deleterious germline or somatic mutations in the BRCA1 or BRCA2 genes, the products of which contribute to the conservative homologous recombination repair of DNA double-strand breaks. Nonetheless, several setbacks in clinical trial settings have highlighted some of the issues surrounding the investigation of PARP inhibitors, especially the identification of patients who stand to benefit from such drugs. One potential approach to finding this patient subpopulation is to examine the tumor DNA for evidence of a homologous recombination defect. However, although the genomes of many breast and ovarian cancers are replete with aberrations, the presence of numerous factors able to shape the genomic landscape means that only some of the observed DNA abnormalities are the outcome of a cancer cell’s inability to faithfully repair DNA double-strand breaks. Consequently, recently developed methods for comprehensively capturing the diverse ways in which homologous recombination deficiencies may arise beyond BRCA1/2 mutation have used DNA microarray and sequencing data to account for potentially confounding features in the genome. Scores capturing telomeric allelic imbalance, loss of heterozygosity (LOH) and large scale transition score, as well as the total number of coding mutations are measures that summarize the total burden of certain forms of genomic abnormality. By contrast, other studies have comprehensively catalogued different types of mutational pattern and their relative contributions to a given tumor sample. Although at least one study to explore the use of the LOH scar in a prospective clinical trial of a PARP inhibitor in ovarian cancer is under way, limitations that result in a relatively low positive predictive value for these biomarkers remain. Tumors whose genome has undergone one or more events that restore high-fidelity homologous recombination are likely to be misclassified as double-strand break repair-deficient and thereby sensitive to PARP inhibitors and DNA damaging chemotherapies as a result of prior repair deficiency and its genomic scarring. Therefore, we propose that integration of a genomic scar-based biomarker with a marker of resistance in a high genomic scarring burden context may improve the performance of any companion diagnostic for PARP inhibitors.
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              A perfect storm: How tumor biology, genomics, and health care delivery patterns collide to create a racial survival disparity in breast cancer and proposed interventions for change.

              It is well known that there is a significant racial divide in breast cancer incidence and mortality rates. African American women are less likely to be diagnosed with breast cancer than white women but are more likely to die from it. This review explores the factors that may contribute to the racial survival disparity. Consideration is paid to what is known about the role of differences in tumor biology, genomics, cancer screening, and quality of cancer care. It is argued that it is the collision of 2 forces, tumor biology and genomics, with patterns of care that leads to the breast cancer mortality gap. The delays, misuse, and underuse of treatment for African American patients are of increased significance when these patients are presenting with more aggressive forms of breast cancer. In the current climate of health care reform ushered in by the Affordable Care Act, this article also evaluates interventions to close the disparity gap. Prior interventions have been too narrowly focused on the patient rather than addressing the system and improving care across the continuum of breast cancer evaluation and treatment. Lastly, areas of future investigation and policy initiatives aimed at reducing the racial survival disparity in breast cancer are discussed.
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                Author and article information

                Contributors
                Nicholas.s.diab@vanderbilt.edu
                Gary.Clark@arraybiopharma.com
                Lucy.Langer@usoncology.com
                yxwang6@texaschildrens.org
                Barbara.hamlington@usoncology.com
                Laura.Brzeskiewicz@usoncology.com
                Joyce.O'Shaughnessy@usoncology.com
                sami.diab@usoncology.com
                Jabbousk@cinj.rutgers.edu
                Journal
                Springerplus
                Springerplus
                SpringerPlus
                Springer International Publishing (Cham )
                2193-1801
                6 January 2016
                6 January 2016
                2016
                : 5
                : 14
                Affiliations
                [ ]Vanderbilt University, Nashville, TN USA
                [ ]Array BioPharma, Inc., Boulder, CO USA
                [ ]Genetic Risk Evaluation and Testing Program, Compass Oncology, Portland, OR USA
                [ ]Texas Children Hospital, Houston, TX USA
                [ ]Genetic Risk Evaluation and Testing Program, Rocky Mountain Cancer Centers, Denver, CO USA
                [ ]Baylor Charles A. Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX USA
                [ ]Rutgers Cancer Institute of New Jersey Rutgers, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ USA
                Article
                1657
                10.1186/s40064-015-1657-4
                4703603
                26759753
                1a7cb323-e028-48b6-ad3e-50c5e18d0eeb
                © Diab et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 18 December 2015
                : 22 December 2015
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