Long-Term Toxicity of Adjuvant Chemotherapy in Breast Cancer
Long-Term Toxicity 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.
Chemotherapy in the adjuvant setting has contributed to significant progress in the management of breast cancer. During the past few decades, we have witnessed a paradigm shift, moving from classic CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) to anthracycline-based regimens, to the subsequent incorporation of taxanes, administration of dose-dense regimens, and, most recently, the use of biological agents. Both earlier diagnosis of the disease and novel chemotherapy strategies have resulted in a considerable improvement in breast cancer survival. However, given the curative intent of adjuvant therapies, it is vital to address issues related to long-term toxic effects that could affect the overall quality of patient survival.
The primary objectives of chemotherapy adjuvant trials have been predominantly focused on breast cancer outcome and short-term patient safety. Little attention has been given to the long-term side-effects of these drugs. This is of paramount importance as long-term effects could considerably compromise patients' quality of life (QoL). Also, a better understanding of the whole spectrum of chemotherapy adverse events—both short and long term—would enable us to refine our use of such therapy, in terms of both scheduling and individual patients' risks and preferences.
In this review, we focus on the long-term toxic effects associated with chemotherapy regimens commonly given in the adjuvant setting. We shed light on different adverse events, discussing their magnitude, clinical implications, and possible management strategies. The long-term toxic effects related to endocrine and targeted agents are not covered in this review.
Abstract and Introduction
Abstract
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.
Introduction
Chemotherapy in the adjuvant setting has contributed to significant progress in the management of breast cancer. During the past few decades, we have witnessed a paradigm shift, moving from classic CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) to anthracycline-based regimens, to the subsequent incorporation of taxanes, administration of dose-dense regimens, and, most recently, the use of biological agents. Both earlier diagnosis of the disease and novel chemotherapy strategies have resulted in a considerable improvement in breast cancer survival. However, given the curative intent of adjuvant therapies, it is vital to address issues related to long-term toxic effects that could affect the overall quality of patient survival.
The primary objectives of chemotherapy adjuvant trials have been predominantly focused on breast cancer outcome and short-term patient safety. Little attention has been given to the long-term side-effects of these drugs. This is of paramount importance as long-term effects could considerably compromise patients' quality of life (QoL). Also, a better understanding of the whole spectrum of chemotherapy adverse events—both short and long term—would enable us to refine our use of such therapy, in terms of both scheduling and individual patients' risks and preferences.
In this review, we focus on the long-term toxic effects associated with chemotherapy regimens commonly given in the adjuvant setting. We shed light on different adverse events, discussing their magnitude, clinical implications, and possible management strategies. The long-term toxic effects related to endocrine and targeted agents are not covered in this review.
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