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      Incidence of Acute Myeloid Leukemia after Breast Cancer

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          Abstract

          Breast cancer is the most frequent cancer among women and the leading cause of death among middle-aged women. Early detection by mammography screening and improvement of therapeutic options have increased breast cancer survival rates, with the consequence that late side effects of cancer treatment become increasingly important. In particular, patients treated with adjuvant chemotherapy regimens, commonly including alkylating agents and anthracyclines, are at increased risk of developing leukemia, further enhanced by the use of radiotherapy. In the last few years also the use of growth factors seems to increase the risk of secondary leukemia. The purpose of this review is to update epidemiology of therapy-related myeloid neoplasms occurring in breast cancer patients.

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          Most cited references34

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          Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series.

          Therapy-related myelodysplasia and myeloid leukemia (t-MDS/t-AML) is a distinctive clinical syndrome occurring after exposure to chemotherapy (CT) or radiotherapy (RT). We report findings on 306 consecutive patients referred to our institution with morphologic review and cytogenetic analyses. Since 1972, 141 males and 165 females with a median age of 51 years (range, 3-83 years) at primary diagnosis and 58 years (range, 6-86 years) at secondary diagnosis were analyzed. Patients had been administered various cytotoxic agents, including alkylating agents (240 patients, 78%) and topoisomerase 2 inhibitors (115 patients, 39%). One hundred twenty-one (40%) had undergone CT alone, 43 (14%) had undergone RT alone, and 139 (45%) had undergone both modalities. At diagnosis of t-MDS/t-AML, 282 (92%) had clonal abnormalities involving chromosome 5 (n = 63), chromosome 7 (n = 85), chromosomes 5 and 7 (n = 66), recurring balanced rearrangements (n = 31), other clonal abnormalities (n = 39), or normal karyotype (n = 24). Abnormalities of chromosome 5, 7, or both accounted for 76% of all cases with an abnormal karyotype. Seventeen patients acquired t-MDS/t-AML after autologous stem cell transplantation, but no unique pattern of cytogenetic abnormalities was observed. Shorter latency was observed for patients with balanced rearrangements (median, 28 vs 67 months; P <.0001). Patients with acute leukemia were more likely to have balanced rearrangement than those with myelodysplasia (28% vs 4%; P <.0001). Median survival time after diagnosis of t-MDS/t-AML was 8 months; survival at 5 years was less than 10%. These data confirm and extend previous associations between clinical, morphologic, and cytogenetic findings in t-MDS/t-AML.
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            Docetaxel With Cyclophosphamide Is Associated With an Overall Survival Benefit Compared With Doxorubicin and Cyclophosphamide: 7-Year Follow-Up of US Oncology Research Trial 9735.

            We previously reported that four cycles of docetaxel/cyclophosphamide (TC) produced superior disease-free survival (DFS) compared with four cycles of doxorubicin/cyclophosphamide (AC) in early breast cancer. Older women are under-represented in adjuvant chemotherapy trials. In our trial 16% of patients were > or = 65 years. We now report 7-year results for DFS and overall survival (OS) as well as the impact of age, hormone receptor status, and HER2 status on outcome and toxicity. Patients were randomly assigned to receive either four cycles of standard-dose AC (60/600 mg/m(2); n = 510), or TC (75/600 mg/m(2); n = 506), administered by intravenous infusion every 3 weeks. The median age in women younger than 65, was 50 years (range, 27 to 64) and for women > or = 65 was 69 years (range, 65 to 77). Baseline characteristics in the two age subgroups were generally well matched, except that older women tended to have more lymph node involvement. At a median of 7 years follow-up, the difference in DFS between TC and AC was significant (81% TC v 75% AC; P = .033; hazard ratio [HR], 0.74; 95% CI 0.56 to 0.98) as was OS (87% TC v 82% AC; P = .032; HR, 0.69; 95% CI, 0.50 to 0.97). TC was superior in older patients as well as younger patients. There was no interaction of hormone-receptor status or HER-2 status and treatment. Older women experienced more febrile neutropenia with TC and more anemia with AC. With longer follow-up, four cycles of TC was superior to standard AC (DFS and OS) and was a tolerable regimen in both older and younger patients.
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              Long-term toxic effects of adjuvant chemotherapy in breast cancer.

              Breast cancer is the most common malignant tumor affecting women. Adjuvant systemic therapies have been shown to have a significant impact on reducing the risk for breast cancer recurrence and overall mortality. Chemotherapy remains an important and frequently used treatment option in the adjuvant setting, and the associated short-term adverse events are very well described. However, there is insufficient information regarding the long-term sequelae of most chemotherapeutic agents. In this review, we describe different potential long-term adverse events associated with adjuvant chemotherapy in breast cancer, with a particular focus on long-term cardiac toxicity, secondary leukemia, cognitive function, and neurotoxicity. In addition, we discuss the effect of adjuvant chemotherapy on fertility and sexual function of young breast cancer patients. These adverse events are frequently overshadowed by the well-demonstrated clinical efficacy and/or reassuring short-term safety profiles of the different chemotherapy regimens commonly used today. We believe that a proper understanding and appreciation of these adverse events will enable us to refine our strategies for managing breast cancer. The fact that adjuvant chemotherapy is often given to patients who might not really need it urges us to consider the whole spectrum of chemotherapy risks versus benefits to maximize benefit without compromising quality of life.
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                Author and article information

                Journal
                Mediterr J Hematol Infect Dis
                Mediterranean Journal of Hematology and Infectious Diseases
                Mediterranean Journal of Hematology and Infectious Diseases
                Università Cattolica del Sacro Cuore
                2035-3006
                2011
                22 December 2011
                : 3
                : 1
                : e2011069
                Affiliations
                Hematology Institute, Catholic University, Rome, Italy
                Author notes
                Correspondence to: Caterina Giovanna Valentini, MD. Istituto di Ematologia, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy. Tel : +39-0630154180, Fax +39-063051343. E-mail: giovannavalentini@ 123456libero.it
                Article
                mjhid-3-1-e2011069
                10.4084/MJHID.2011.069
                3248346
                22220266
                6fb23a82-f768-4be9-9572-53619d94f60d
                Copyright @ 2011

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 December 2011
                : 17 December 2011
                Categories
                Review Articles

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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