Increased risk of acute myeloid leukaemia after treatment for breast cancer

doi:10.1016/j.breast.2005.11.007

The Breast

Volume 15, Issue 5, October 2006, Pages 614-619

https://doi.org/10.1016/j.breast.2005.11.007 Get rights and content

Summary

This study evaluates the risk of acute myeloid leukaemia (AML) in patients treated for breast cancer.

We included all 6360 breast cancer patients that were recorded at the Geneva Cancer Registry between 1970 and 1999. Patients were followed for AML occurrence until December 2000. We calculated standardized incidence ratios of AML and identified factors modifying the risk of AML by multivariate Cox analysis.

Twelve (0.2%) patients developed AML. In general, patients treated for breast cancer had a 3.5-fold (95% confidence interval (CI): 1.8–6.0) increased risk of developing AML compared with the general population. In particular, patients who were older than 70 years at breast cancer diagnosis and those treated with radiotherapy (with or without chemotherapy) had a significantly increased risk of developing AML.

This population-based study confirms that radiotherapy increases the risk of AML. Due to the relatively low number of women treated with chemotherapy without radiotherapy and due to the infrequency of the disease, the question of whether chemotherapy alone increases this risk of AML cannot yet be answered.

Introduction

In Switzerland, as well as in most developed countries, breast cancer is a major public-health concern. It 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.¹ As a consequence, late side effects of breast cancer treatment become ever more important.

Patients who have been treated for breast cancer are at increased risk of developing leukaemia.2, 3 This increased risk has been reported to be strongly related to the use of radiotherapy, in combination with chemotherapy.2, 4 However, there is an ongoing debate concerning the importance of chemotherapeutic agents as supplementary risk factors. Randomized trials and population-based studies show conflicting results on this issue.5, 6

In particular, the role of mitoxantrone in acute myeloid leukaemia (AML) occurrence has been widely debated over recent years. The results of a population-based study by Chaplain et al. suggest that a dose-dependent relationship exists between mitoxantrone and the development of AML.⁷ The population-based Geneva Cancer Registry, Switzerland, recently estimated the proportion of breast cancer patients treated with mitoxantrone. Among all breast cancer patients treated with chemotherapy in 1982, none received mitoxantrone. In 1996, this proportion increased to 29% (data not published). This survey also showed that mitoxantrone was exclusively prescribed in the private sector and never in public hospitals.

The purpose of the current population-based study was to evaluate the risk of AML in patients treated for breast cancer in Geneva. In addition, we examined which factors modified the risk of AML.

Section snippets

Materials and methods

Data were derived from the Geneva Cancer Registry's dataset, which includes information regarding all incident cases of malignant neoplasms occurring in the canton (approximately 420,000 inhabitants). The registration is based on several sources of information and is highly accurate, as attested by its low percentage (<1%) of cases recorded from death certificates only.⁸ Individual clinical files from the university hospitals are systematically consulted and inquiry forms are regularly sent out

Results

Between January 1970 and December 1999, 6360 women were diagnosed with breast cancer. The median follow-up period of these women was 6.6 years. Between July 1970 and December 2000, 12 women developed AML, six developed chronic lymphocytic leukaemia, three had acute lymphoid leukaemia, three had chronic myeloid leukaemia, one had myelomonocytic leukaemia and one had lymphoblastic leukaemia. Compared with the general population, breast cancer patients were at a 3.5-fold increased risk (95%

Discussion

This study shows that patients treated for breast cancer have an increased risk of developing AML compared with the general female population. This risk was particularly high for patients who underwent radiotherapy (HR 4.0; 95% CI: 1.4–11.8) and radiotherapy plus chemotherapy (HR 7.2; 95% CI: 1.4–36.3). Although the relative risk of developing AML is high in patients treated for breast cancer, the absolute number of patients developing this highly fatal condition is fortunately low.

This study

Conclusion

Radiotherapy with or without chemotherapy for the treatment of breast cancer increases the risk of developing AML. The question of whether chemotherapy alone increases this risk of AML remains to be explored. Physicians should be aware of the potential long-term hematological complications of radiotherapy and/or chemotherapy for primary breast cancer.

Acknowledgements

The authors thank Stina Blagojevic for her technical help and editorial assistance.

H.M. Verkooijen was financially supported by a PROSPER grant from the Swiss National Science Foundation.

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ORIGINAL ARTICLEIncreased risk of acute myeloid leukaemia after treatment for breast cancer

Summary

Introduction

Section snippets

Materials and methods

Results

Discussion

Conclusion

Acknowledgements

Ann Oncol

Lancet

Ann Oncol

Effect of NHS breast screening programme on mortality from breast cancer in England and Wales, 1990–8: comparison of observed with predicted mortality

BMJ

Risk of leukemia after chemotherapy and radiation treatment for breast cancer

N Engl J Med

Increased risk of second cancers following breast cancer: role of the initial treatment

Breast Cancer Res Treat

Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the National Surgical Adjuvant Breast and Bowel Project Experience

J Clin Oncol

ORIGINAL ARTICLE
Increased risk of acute myeloid leukaemia after treatment for breast cancer