Increased Risk of Acute Leukemia After Adjuvant Chemotherapy for Breast Cancer: A Population-Based Study

Chaplain, Gilles; Milan, Chantal; Sgro, C; Carli, Paule‐Marie; Bonithon‐Kopp, Claire

doi:10.1200/jco.2000.18.15.2836

Cited by 102 publications

(56 citation statements)

References 18 publications

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“…The risk was approximately the same during 1-9 and 101 years of follow-up, which corresponds well with previous observations that leukaemia may present within a few years after the breast cancer diagnosis. 28 The observation of approximately the same risk before and after 1975, however, is not compatible with the fact that chemotherapy has been given to a larger proportion of breast cancer patients during later periods. Hormonal therapy with tamoxifen has been used to treat estrogen-receptor positive breast cancer during the past, that is, more than 20 years.…”

Section: Discussionmentioning

confidence: 94%

Risk of second cancer among women with breast cancer

Mellemkjær

Friis

Olsen

et al. 2005

Intl Journal of Cancer

212

250

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A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population-based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943-2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI 5 1.24-1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR 5

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Section: Discussionmentioning

confidence: 94%

Risk of second cancer among women with breast cancer

Mellemkjær

Friis

Olsen

et al. 2005

Intl Journal of Cancer

212

250

View full text Add to dashboard Cite

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“…In that study, a dose-dependent effect was seen for mitoxantrone and the incidence of leukemia was lower in patients treated with anthracyclines than in those treated with mitoxantrone 413 mg/m 2 . 15 In a smaller study, a standardized incidence ratio of 38 for breast cancer patients treated adjuvant with a combination of mitoxantrone, 5-fluorouracil, and cyclophosphamide was reported. 10 The high incidence of AML with an incidence ratio of 339 in the study by Andersson et al 24 was ascribed to prednimustine, a known leukemogenic alkylating agent, but a synergistic or additive effect of mitoxantrone cannot be excluded.…”

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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“…A dose-dependent increase in the risk of leukemia was observed in females treated with mitoxantrone (31). A large case-control study demonstrated that the risk of AML̸MDS was increased following topoisomerase-II inhibitor-based chemotherapy, with the risk of leukemia being higher for mitoxantrone-based compared to anthracycline-based chemotherapy (23).…”

Section: Risks Following Chemotherapy Leukemia and Mds Patt Et Almentioning

confidence: 99%

Second malignancies after breast cancer: The impact of adjuvant therapy

Dong

Chen

2014

Molecular and Clinical Oncology

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Abstract. Second malignant neoplasms (SMNs) are potentially life-threatening late sequelae of the adjuvant therapy for breast cancer (BC). The increased risk of SMNs is associated with adjuvant chemotherapy (development of secondary acute myeloid leukemia and myelodysplastic syndrome) and hormonal therapy (risk of uterine cancer secondary to tamoxifen treatment). Previous studies have demonstrated an increased risk of SMNs associated with alkylating agents, topoisomerase-II inhibitors, granulocyte-stimulating factors and estrogen receptor modulators. Furthermore, analytical investigations have demonstrated that BC patients may be at an increased risk of leukemia following chemotherapy. In addition, correlations between an increased dose of hormonal therapy and solid tumor risk have been identified. Considering the ongoing alterations in the treatment of BC, with respect to lowering the daily as well as the cumulative dose of chemotherapeutic agents, it is anticipated that leukemias will have a considerably lower impact on BC survivors in the future. However, diligent follow-up is required to accurately evaluate the long-term risks associated with chemotherapy.

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Increased Risk of Acute Leukemia After Adjuvant Chemotherapy for Breast Cancer: A Population-Based Study

Cited by 102 publications

References 18 publications

Risk of second cancer among women with breast cancer

Risk of second cancer among women with breast cancer

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

Second malignancies after breast cancer: The impact of adjuvant therapy

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