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      Effects of Age on the Detection and Management of Breast Cancer

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          Abstract

          Currently, breast cancer affects approximately 12% of women worldwide. While the incidence of breast cancer rises with age, a younger age at diagnosis is linked to increased mortality. We discuss age related factors affecting breast cancer diagnosis, management and treatment, exploring key concepts and identifying critical areas requiring further research. We examine age as a factor in breast cancer diagnosis and treatment relating it to factors such as genetic status, breast cancer subtype, hormone factors and nodal status. We examine the effects of age as seen through the adoption of population wide breast cancer screening programs. Assessing the incidence rates of each breast cancer subtype, in the context of age, we examine the observed correlations. We explore how age affects patient’s prognosis, exploring the effects of age on stage and subtype incidence. Finally we discuss the future of breast cancer diagnosis and treatment, examining the potential of emerging tests and technologies (such as microRNA) and how novel research findings are being translated into clinically relevant practices.

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          Most cited references101

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          Twenty-Year Follow-up of a Randomized Trial Comparing Total Mastectomy, Lumpectomy, and Lumpectomy plus Irradiation for the Treatment of Invasive Breast Cancer

          Bernard Fisher, Stewart Anderson, John Bryant … (2002)
          New England Journal of Medicine, 347(16), 1233-1241
          Article 0 comments Cited 1150 times – based on 0 reviews     Review now
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            Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial.

            Kathy S. Albain, William Barlow, Steven Shak … (2010)
            The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogen-receptor-positive breast cancer treated with tamoxifen. A low recurrence score predicts little benefit of chemotherapy. For node-positive breast cancer, we investigated whether the recurrence score was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher risks of recurrence. The phase 3 trial SWOG-8814 for postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer showed that chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) before tamoxifen (CAF-T) added survival benefit to treatment with tamoxifen alone. Optional tumour banking yielded specimens for determination of recurrence score by RT-PCR. In this retrospective analysis, we assessed the effect of recurrence score on disease-free survival by treatment group (tamoxifen vs CAF-T) using Cox regression, adjusting for number of positive nodes. There were 367 specimens (40% of the 927 patients in the tamoxifen and CAF-T groups) with sufficient RNA for analysis (tamoxifen, n=148; CAF-T, n=219). The recurrence score was prognostic in the tamoxifen-alone group (p=0.006; hazard ratio [HR] 2.64, 95% CI 1.33-5.27, for a 50-point difference in recurrence score). There was no benefit of CAF in patients with a low recurrence score (score or =31; log-rank p=0.033; HR 0.59, 0.35-1.01), after adjustment for number of positive nodes. The recurrence score by treatment interaction was significant in the first 5 years (p=0.029), with no additional prediction beyond 5 years (p=0.58), although the cumulative benefit remained at 10 years. Results were similar for overall survival and breast-cancer-specific survival. The recurrence score is prognostic for tamoxifen-treated patients with positive nodes and predicts significant benefit of CAF in tumours with a high recurrence score. A low recurrence score identifies women who might not benefit from anthracycline-based chemotherapy, despite positive nodes. National Cancer Institute and Genomic Health. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
            Article 0 comments Cited 382 times – based on 0 reviews     Review now
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              Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium.

              D. Ford, D. Easton, M. Stratton … (1998)
              The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age.
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                Author and article information

                Contributors
                Jonas Cicenas: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Cancers (Basel)
                Journal ID (iso-abbrev): Cancers (Basel)
                Journal ID (publisher-id): cancers
                Title: Cancers
                Publisher: MDPI
                ISSN (Electronic): 2072-6694
                Publication date (Electronic): 22 May 2015
                Publication date Collection: June 2015
                Volume: 7
                Issue: 2
                Pages: 908-929
                Affiliations
                Discipline of Surgery, School of Medicine, National University of Ireland, Galway, Ireland; E-Mails: andrewmcguire@ 123456rcsi.ie (A.M.); carmel.malone@ 123456nuigalway.ie (C.M.); ray.mclaughlin@ 123456hse.ie (R.M.)
                Author notes
                [†]

                These authors contributed equally to this work.

                [‡]

                ORCID: 0000-0002-3155-0334.

                [* ]Authors to whom correspondence should be addressed; E-Mails: james.brown@ 123456nuigalway.ie (J.A.L.B.); michael.kerin@ 123456nuigalway.ie (M.J.K.); Tel.: +353-0-91-524390 (M.J.K.).
                Article
                Publisher ID: cancers-07-00815
                DOI: 10.3390/cancers7020815
                PMC ID: 4491690
                PubMed ID: 26010605
                SO-VID: f0291c41-5915-4443-9539-c6ef6d2e775f
                Copyright © © 2015 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 12 March 2015
                Date accepted : 12 May 2015
                Categories
                Subject: Review

                Keywords: breast cancer,age,subtype,screening,mirna
                Data availability:
                Keywords: breast cancer, age, subtype, screening, mirna

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