scholarly journals Increased incidence of myelodysplastic syndrome and acute myeloid leukemia following breast cancer treatment with radiation alone or combined with chemotherapy: a registry cohort analysis 1990-2005

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Henry G Kaplan ◽  
Judith A Malmgren ◽  
Mary K Atwood
Keyword(s):  
Breast Cancer ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Cancer Treatment ◽  
Myeloid Leukemia ◽  
Cohort Analysis ◽  
Breast Cancer Treatment ◽  
Acute Myeloid

Risk of Acute Myeloid Leukemia and Myelodysplastic Syndrome in Trials of Adjuvant Epirubicin for Early Breast Cancer: Correlation With Doses of Epirubicin and Cyclophosphamide

2005 ◽  
Vol 23 (18) ◽  
pp. 4179-4191 ◽  
Author(s):  
Claudio Praga ◽  
Jonas Bergh ◽  
Judith Bliss ◽  
Jacques Bonneterre ◽  
Bruno Cesana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Early Breast Cancer ◽  
Myeloid Leukemia ◽  
Lower Probability ◽  
Cumulative Probability ◽  
Secondary Leukemia ◽  
Acute Myeloid

Purpose We reviewed follow-up of patients treated in 19 randomized trials of adjuvant epirubicin in early breast cancer to determine incidence, risk, and risk factors for subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Patients and Methods The patients (N = 9,796) were observed from the start of adjuvant treatment (53,080 patient-years). Cases of AML or MDS (AML/MDS) were reported, with disease characteristics. Incidence and cumulative risk were compared for possible risk factors, for assigned regimens, and for administered cumulative doses of epirubicin and cyclophosphamide. Results In 7,110 patients treated with epirubicin-containing regimens (92% of whom also received cyclophosphamide), 8-year cumulative probability of AML/MDS was 0.55% (95% CI, 0.33% to 0.78%). The risk of developing AML/MDS increased in relation to planned epirubicin dose per cycle, planned epirubicin dose-intensity, and administered cumulative doses of epirubicin and cyclophosphamide. Patients with administered cumulative doses of both epirubicin and cyclophosphamide not exceeding those used in standard regimens (≤ 720 mg/m2 and ≤ 6,300 mg/m2, respectively) had an 8-year cumulative probability of developing AML/MDS of 0.37% (95% CI, 0.13% to 0.61%) compared with 4.97% (95% CI, 2.06% to 7.87%) for patients administered higher cumulative doses of both epirubicin and cyclophosphamide. Conclusion Patients treated with standard cumulative doses of adjuvant epirubicin (≤ 720 mg/m2) and cyclophosphamide (≤ 6,300 mg/m2) for early breast cancer have a lower probability of secondary leukemia than patients treated with higher cumulative doses. Increased risk of secondary leukemia must be considered when assessing the potential benefit to risk ratio of higher than standard doses.

Acute Myeloid Leukemia and Myelodysplastic Syndrome After Doxorubicin-Cyclophosphamide Adjuvant Therapy for Operable Breast Cancer: The National Surgical Adjuvant Breast and Bowel Project Experience

2003 ◽  
Vol 21 (7) ◽  
pp. 1195-1204 ◽  
Author(s):  
Roy E. Smith ◽  
John Bryant ◽  
Arthur DeCillis ◽  
Stewart Anderson
Keyword(s):  
Breast Cancer ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Cumulative Incidence ◽  
Myeloid Leukemia ◽  
Incidence Rates ◽  
Breast Radiotherapy ◽  
Increased Risk ◽  
Breast Cancer Relapse ◽  
Acute Myeloid

Purpose: We reviewed data from all adjuvant NSABP breast cancer trials that tested regimens containing both doxorubicin (A) and cyclophosphamide (C) to characterize the incidence of subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Materials and Methods: Six complete NSABP trials have investigated AC regimens (B-15, B-16, B-18, B-22, B-23, and B-25). Six distinct AC regimens have been tested and are distinguished by differences in cyclophosphamide intensity and cumulative dose and by the presence or absence of mandated prophylactic support with growth factor and ciprofloxacin. In all regimens, A was given at 60 mg/m2 q 21 days × 4. C was given as follows: 600 mg/m2 q 21 days × 4 (“standard AC”); 1,200 mg2 q 21 days × 2; 1,200 mg/m2 q 21 days × 4; 2,400 mg/m2 q 21 days × 2; and 2,400 mg/m2 q 21 days × 4. Occurrence of AML/MDS was summarized by incidence per 1,000 patient-years at risk and by cumulative incidence. Rates were compared across regimens, by age, and by treatment with or without breast radiotherapy. Results: The incidence of AML/MDS was sharply elevated in the more intense regimens. In patients receiving two or four cycles of C at 2,400 mg/m2 with granulocyte colony-stimulating factor (G-CSF) support, cumulative incidence of AML/MDS at 5 years was 1.01% (95% confidence interval [CI], 0.63% to 1.62%), compared with 0.21% (95% CI, 0.11% to 0.41%) for patients treated with standard AC. Patients who received breast radiotherapy experienced more secondary AML/MDS than those who did not (RR = 2.38, P= .006), and the data indicated that G-CSF does may possibly also be independently correlated with increased risk. Conclusion: AC regimens employing intensified doses of cyclophosphamide requiring G-CSF support were characterized by increased rates of subsequent AML/MDS, although the incidence of AML/MDS was small relative to that of breast cancer relapse. Breast radiotherapy appeared to be associated with an increased risk of AML/MDS.

No Association of BRCA Mutations with Therapy-Related Myelodysplastic Syndrome or Acute Myeloid Leukemia in Patients Treated for Breast or Ovarian Cancer

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4259-4259
Author(s):  
Aaron S. Mansfield ◽  
Mark A Lewis ◽  
Mrinal M. Patnaik ◽  
Noralane M Lindor ◽  
Matthew P Goetz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Dna Repair ◽  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Myeloid Leukemia ◽  
Brca Mutation ◽  
Seer Database ◽  
Brca Mutations ◽  
Acute Myeloid

Abstract Abstract 4259 Background: Patients with defective DNA repair mechanisms are at higher risk for developing cancer. BRCA1 and BRCA2 are proteins that coordinate DNA repair by homologous-recombination. Mutations in BRCA1 and BRCA2 are associated with an increased risk of cancers, namely breast, ovarian, and pancreatic, thus making these patients more likely to receive chemo- or radiation therapy. Additionally, secondary malignancies can be an unfortunate consequence of treatment with chemo- or radiation therapy. Although tumors with defective DNA repair mechanisms may be more susceptible to therapy, we hypothesized that patients with BRCA mutations that underwent chemotherapy or radiotherapy for treatment of breast or ovarian cancer would be at a higher risk of developing therapy- related myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML). Methods: We accessed patient data from our institution maintained by the Mayo Clinic Life Sciences System using the Data Discovery and Query Builder. We searched for patients whose notes and diagnoses included the terms BRCA, and breast or ovarian cancer, and myelodysplastic syndrome or acute myeloid leukemia. We searched our records from 1/1/1995–7/15/2011. We cross-referenced our findings to a database of patients who were diagnosed with a BRCA mutation through our department of medical genetics. Secondly, we searched the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database for female patients who developed AML after the diagnosis or breast or ovarian cancer from the years 1973–2008 using ratio and multiple primaries standardized incidence ratios sessions. Results: We identified 220 patients with a BRCA mutation, of which 73 received chemotherapy. There were two patients with BRCA mutations that developed t-AML following treatment for breast cancer, and one patient with a BRCA mutation who developed t-AML following treatment for ovarian cancer (Table 1). Manual data extraction from the list of patients with BRCA mutations diagnosed at our institution only identified one of these patients, as two obtained their testing through another institution. We did not identify any patients with BRCA mutations who developed t-MDS following treatment for breast or ovarian cancer. The latency between diagnosis of the primary cancer and the diagnosis or t-AML was 24 months for two patients, and 22 years for the other. From our search of the SEER database we found 649 patients who developed AML after a diagnosis of breast cancer, and 98 patients who developed AML after a diagnosis of ovarian cancer. These patients represented 0.1% and 0.2% of evaluable breast and ovarian cases respectively. The latency from time of diagnosis of the primary cancer to that of AML was 58 months (29–113 interquartile range) for breast cancer and 47 months (29–91) for ovarian cancer. The observed number of patients with AML following the diagnosis of breast or ovarian cancer was 1.68 and 4.74 times higher than that expected of the general population, respectively (both p<0.05). We were not able to stratify patients based on the presence of a BRCA mutation due to the limitations of the database. Conclusions: We identified three patients with confirmed BRCA mutations and t-AML at our institution. Although this does not represent a strong association, patients at risk for BRCA mutations do not always undergo testing. Thus, our results may not fully represent whether there is an association with BRCA mutations and t-MDS or t-AML. Using the SEER database, we confirmed that patients who were diagnosed with breast or ovarian cancer subsequently had a higher incidence of AML than the general population, although we were not able to test if patients with BRCA mutations are at higher risk of t-MDS or t-AML. Disclosures: No relevant conflicts of interest to declare.

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