Risk of Leukemia after Chemotherapy and Radiation Treatment for Breast Cancer

Curtis, Rochelle E.; Boice, John D.; Stovall, Marilyn; Bernstein, Leslie; Greenberg, Raymond S.; Flannery, John; Schwartz, Ann G.; Weyer, Peter J.; Moloney, William C.; Hoover, Robert N.

doi:10.1056/nejm199206253262605

Cited by 411 publications

(232 citation statements)

References 18 publications

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“…24 In other studies, relative risks in the order of 2.0-2.4 have been observed following radiotherapy. 32,33 This indicates that approximately 50% of such AMLs are directly radiation induced, whereas another 50% are cases of de novo AML. Hence, cases 29, 52 and 148, as well as case R treated with methotrexate þ prednisone without a confirmed leukemogenic potential, could all be suspected to represent de novo leukemias.…”

Section: Discussionmentioning

confidence: 99%

NPM1 mutations in therapy-related acute myeloid leukemia with uncharacteristic features

2008

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Frameshift mutations of the nucleophosmin gene (NPM1) were recently reported as a frequently occurring abnormality in patients with de novo acute myeloid leukemia (AML). To evaluate the frequency of NPM1 mutations in patients with therapy-related myelodysplasia (t-MDS) and therapy-related AML (t-AML), and their possible association to type of previous therapy and to other gene mutations, 140 patients with t-MDS or t-AML were analyzed for mutations of NPM1. NPM1 mutations were observed in 7 of 51 patients presenting as overt t-AML, as compared to only 3 of 89 patients presenting as t-MDS (P ¼ 0.037). The mutations were not related to any specific type of previous therapy, but they were significantly associated with a normal karyotype and mutations of FLT3 (P ¼ 0.0002 for both comparisons). Only 1 of 10 patients with NPM1 mutations presented chromosome aberrations characteristic of therapyrelated disease, and 7qÀ/À7, the most frequent abnormalities of t-MDS/t-AML, were not observed (P ¼ 0.002). This raises the question whether some of the cases presenting NPM1 mutations were in fact cases of de novo leukemia. The close association to class I mutations and the inverse association to class II mutations suggest mutations of NPM1 as representing a class II mutation-like abnormality in AML. Leukemia (2008) 22, 951-955;

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Section: Discussionmentioning

confidence: 99%

NPM1 mutations in therapy-related acute myeloid leukemia with uncharacteristic features

2008

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“…Bone Marrow Transplantation (2003) 32, 1153-1157. doi:10.1038/sj.bmt.1704291 Keywords: high-dose chemotherapy; adjuvant therapy; breast cancer; mitoxantrone; secondary AML Secondary myelodysplasia (MDS) or acute myeloid leukemia (AML) in breast cancer patients is a rare but wellknown long-term complication of prior chemotherapy or radiation therapy as adjuvant therapy. [1][2][3] Specific risk factors are the combinations of chemotherapy and radiation therapy, the cumulative dose of alkylating agents and the duration of therapy. 2 Two different types of treatmentrelated leukemia can be distinguished.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] Specific risk factors are the combinations of chemotherapy and radiation therapy, the cumulative dose of alkylating agents and the duration of therapy. 2 Two different types of treatmentrelated leukemia can be distinguished. The first type results from prior therapy with alkylating agents or radiation therapy, and occurs after a latency period of 5-7 years.…”

Section: Discussionmentioning

confidence: 99%

Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patients

Kröger

Damon

Zander

et al. 2003

Bone Marrow Transplant

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Summary:The incidence of secondary myelodysplasia/acute myeloid leukemia (AML) was retrospectively assessed in an international joint study in 305 node-positive breast cancer patients, who received mitoxantrone-based high-dose chemotherapy (HDCT) followed by autologous stem cell support as adjuvant therapy. The median age of the patients was 57 years (range 22-67). In all, 268 patients received peripheral blood stem cells, and 47 patients received autologous bone marrow. After a median followup of 57 months (range 10-125), three cases of secondary AML (sAML) were observed, resulting in a cumulative incidence of 0.94%. One case of sAML developed 18 months after HDCT (FAB M3) The karyotype was translocation 15;17 and, after induction therapy, the patient underwent autologous stem cell transplantation, and is in complete remission (CR) of both breast cancer and AML. The second patient developed AML (FAB M4eo with inversion 16) 5 months after HDCT. This patient achieved CR after induction therapy, but died of infectious complication. A third patient developed AML (FAB M4) 6 months after HDCT. She achieved CR after induction therapy, but relapsed and expired 28 months after diagnosis of AML. sAML after mitoxantrone-based HDCT is a possible, but rare complication in breast cancer patients. Bone Marrow Transplantation (2003) 32, 1153-1157. doi:10.1038/sj.bmt.1704291 Keywords: high-dose chemotherapy; adjuvant therapy; breast cancer; mitoxantrone; secondary AML Secondary myelodysplasia (MDS) or acute myeloid leukemia (AML) in breast cancer patients is a rare but wellknown long-term complication of prior chemotherapy or radiation therapy as adjuvant therapy. 1-3 Specific risk factors are the combinations of chemotherapy and radiation therapy, the cumulative dose of alkylating agents and the duration of therapy. 2 Two different types of treatmentrelated leukemia can be distinguished. The first type results from prior therapy with alkylating agents or radiation therapy, and occurs after a latency period of 5-7 years. This type of AML is often preceded by a preleukemic period of MDS. Nearly 90% of the patients with alkylating agentrelated MDS or AML show clonal chromosome aberrations including monosomy or deletions on chromosomes 5 and/or 7 or complex aberrations involving chromosomes 3, 12, 17, and 21. 4 The second type of therapy-related leukemia is induced by topoisomerase II-targeted drugs like etoposide, anthracyclines or, recently, anthracenediones. [5][6][7] This type of AML usually occurs after a median of 2 years and is not preceded by a myelodysplastic syndrome. According to the French-American-British (FAB) classification, more frequently, M4 or M5 subtype is observed and cytogenetic analysis showed a high frequency of rearrangements of the chromosome band as 11q23, translocation (t)(8;21), t(15;17), inversion 16 (inv(16)) or t(8;16), as in de novo AML. 5,8 Recently, several studies indicated that adjuvant chemotherapy consisting of the anthracenedione mitoxantrone, a topoisomerase II-targeted drug, may induce sec...

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“…11 Our results suggest that almost all of the excess leukaemia cases occurring in cancer patients who had received radiotherapy are in breast cancer survivors. The elevated risks of acute nonlymphocytic leukaemia following breast cancer has been ascribed primarily to alkylating agent chemotherapy, with radiotherapy possibly adding to this risk, [12][13][14] and some studies have suggested that adjuvant radiotherapy without chemotherapy may also confer a small increased risk of leukaemia, with risks rising in relation to increasing bone marrow dose. 12,15 We have no information on the joint distribution of chemotherapy and radiotherapy from the SEER study, so the possibility of confounding by chemotherapy must be considered.…”

Section: Risk Due To Radiotherapymentioning

confidence: 99%

The cancer burden in the United Kingdom in 2007 due to radiotherapy

Maddams

Dm²,

Darby

2011

Intl Journal of Cancer

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The number of long-term cancer survivors in the general population of the UK is substantial and increasing rapidly. Many cancer survivors have been treated with radiotherapy but the likely number of radiotherapy-related second cancers has not previously been estimated. We used estimates of the numbers of cancer survivors in the UK at the beginning of 2007, in conjunction with estimates of the relative risk of a second primary cancer associated with previous radiotherapy from the United States Surveillance Epidemiology and End Results (SEER) programme, to estimate the numbers of incident cancers in the UK in 2007 that were associated with radiotherapy for a previous cancer and that may have been caused by it. We estimated that 1,346 cases of cancer, or about 0.45% of the 298,000 new cancers registered in the UK in 2007, were associated with radiotherapy for a previous cancer. The largest numbers of radiotherapy-related second cancers were lung cancer (23.7% of the total), oesophageal cancer (13.3%), and female breast cancer (10.6%); 54% of radiotherapy-related second cancers were in individuals aged 75 or over. The highest percentages of second cancers related to radiotherapy were among survivors of Hodgkin's disease and cancers of the oral cavity and pharynx and cervix uteri; over 15% of second cancers among these survivors were associated with radiotherapy for the first cancer. These calculations, which involve a number of assumptions and approximations, provide a reasonable, if conservative, estimate of the fraction of incident cancers in the UK that are attributable to past radiation therapy.Around 3% of the UK population are cancer survivors, with the total number now around two million and increasing by 3% per annum. 1 The increasing trend is partly the consequence of an ageing population but also the result of the successful use of several types of therapy, including radiotherapy. For many cancers, treatment with radiotherapy involves some incidental irradiation of the surrounding normal tissues, thus increasing the risk of a radiation-induced second cancer. Up until now, estimates of the radiation exposure of the UK population have not included exposure from radiotherapy, 2,3 and the total number of cancers in the UK population associated with past radiation exposure from radiotherapy has not previously been assessed.The largest study evaluating the risk of second cancers is the follow-up of more than two million cancer cases registered within the United States Surveillance Epidemiology and End Results (SEER) programme from 1973-2000, 390,000 of whom had survived 10 years or more. 4 That study provides, for several cancer sites, the risk of developing a second primary cancer at varying intervals after diagnosis of the initial cancer in individuals who have, and who have not, received radiotherapy. We used the SEER data, in conjunction with estimates of the numbers of survivors of different cancers in the UK at the beginning of 2007, to estimate the number of incident cancers in the UK during 2007 that wer...

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Risk of Leukemia after Chemotherapy and Radiation Treatment for Breast Cancer

Cited by 411 publications

References 18 publications

NPM1 mutations in therapy-related acute myeloid leukemia with uncharacteristic features

NPM1 mutations in therapy-related acute myeloid leukemia with uncharacteristic features

Secondary acute leukemia following mitoxantrone-based high-dose chemotherapy for primary breast cancer patients

The cancer burden in the United Kingdom in 2007 due to radiotherapy

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