Chemotherapy-Induced Amenorrhea With Adjuvant Treatment
Background: The majority of women diagnosed with early-stage breast cancer have an excellent long-term prognosis, but many will undergo temporary or permanent chemotherapy-induced amenorrhea.
Methods: While breast cancer is more common in older women, about 1 in 200 women under the age of 40 is at risk to develop breast cancer. Many of these women benefit from chemotherapy but are afraid to risk the opportunity to bear children. The authors review the current studies on the impact of adjuvant chemotherapy on amenorrhea and fertility in women with breast cancer.
Results: The likelihood of amenorrhea is based on the specific adjuvant chemotherapy regimen administered and the age of the patient. Future childbirth is a viable option for women treated for breast cancer at an early stage. While the use of tamoxifen as a hormonal therapy in premenopausal breast cancer is now the standard of care, no conclusive data confirm the benefit of GnRH agonists in adjuvant therapy after treatment with chemotherapy followed by tamoxifen.
Conclusions: As more women over the age of 35 consider pregnancy, fertility issues are becoming important areas of investigation for the adjuvant treatment of breast cancer. Whether chemotherapy-induced amenorrhea has a prognostic effect remains unclear, and further studies are warranted.
Approximately one third of new cases of invasive breast cancer predicted to occur in the United States in 2003 will occur in women under 50 years of age. With improved education and increased screening, it is likely that more women will be diagnosed with early-stage breast cancer at younger ages than ever before. Fortunately, most breast cancers are diagnosed at an early stage. Most national guidelines of early-stage invasive breast cancer recommend treatment with adjuvant cytotoxic chemotherapy and hormone therapy with estrogen receptor-positive (ER+) tumors. The exception to these guidelines refers to cases in which the tumors are small. Thus, the majority of young women diagnosed with early-stage breast cancer will undergo adjuvant chemotherapy. Long-term survival is likely when breast cancer is diagnosed at an early stage, especially after adjuvant therapy. Temporary or permanent menopause is a consequence that specifically affects young women diagnosed with breast cancer and treated with adjuvant chemotherapy. In addition, premature ovarian failure has been associated with increased morbidity and mortality.
According to the US Census Bureau of Statistics, the average age of onset of menopause in American women is between 50 and 52 years. The median age of women who develop amenorrhea following adjuvant chemotherapy varies from 38 to 46 years. The likelihood of permanent chemotherapy-induced menopause is directly related to age. Women older than age 40 have a higher incidence of amenorrhea than women younger than age 40. The incidence rate of amenorrhea varies from 21% to 71% in younger women, whereas in women older than 40, the rate ranges from 49% to 100%. Thus, as more women with breast cancer survive the disease, treatment-related morbidity and long-term sequelae related to chemotherapy-induced amenorrhea will assume greater importance. Therefore, future trials will require more attention to reporting the incidence of chemotherapy-induced amenorrhea and will consider prevention and treatment strategies for the symptoms and long-term side affects of menopause.
Another important aspect of therapy decisions in the young premenopausal woman undergoing adjuvant chemotherapy is the preservation of fertility ( Table 1 ). At present, there are no conclusive data suggesting that deleterious effects from subsequent pregnancy will occur in women with a prior history of breast cancer. Therefore, in a population with a high likelihood of long-term survival, interventions to preserve fertility should be considered. In addition, in the absence of clearly documented benefits of premature ovarian failure with regard to disease-free survival (DFS), the preservation of ovarian function may improve all-cause survival by decreasing the risks of heart disease and osteoporosis. Over the last 2 decades, the median age at first live birth has steadily increased ( Table 2 ). The number of children born to women over 30 years of age has doubled and now comprises 30% of all live births. In 1999, in the United States alone, more than 500,000 babies were born to women over 35 years of age and many to women over age 40. According to the US Census Bureau, the birth rate in women over age 40 is projected to increase by 7% over the next 10 years. The likelihood of successful conception decreases over age 34 in nulliparous women, and this may be due to selection bias rather than biologic reasons. The infertility rate of parous women remains at 5% or less up to the age of
44. These findings suggest that the preservation of fertility even in women over the age of 35 years is important. Major strides have been made in reproductive medicine that allow many women to become pregnant even when subfertile or when fertility chances are waning due to older age. However, most reproductive interventions are either not possible or exceedingly difficult after menopause. The rate of premature ovarian failure (ie, menopause under the age of 40) has been estimated at 1% and is often familial. Early menopause (ie, menopause between 41-44 years) is estimated to occur in approximately 5% of women. While breast cancer is more common in older women, about 1 in 200 women under the age of 40 is at risk to develop breast cancer. Many of these women benefit from chemotherapy but are afraid to risk the opportunity to bear children.
Background: The majority of women diagnosed with early-stage breast cancer have an excellent long-term prognosis, but many will undergo temporary or permanent chemotherapy-induced amenorrhea.
Methods: While breast cancer is more common in older women, about 1 in 200 women under the age of 40 is at risk to develop breast cancer. Many of these women benefit from chemotherapy but are afraid to risk the opportunity to bear children. The authors review the current studies on the impact of adjuvant chemotherapy on amenorrhea and fertility in women with breast cancer.
Results: The likelihood of amenorrhea is based on the specific adjuvant chemotherapy regimen administered and the age of the patient. Future childbirth is a viable option for women treated for breast cancer at an early stage. While the use of tamoxifen as a hormonal therapy in premenopausal breast cancer is now the standard of care, no conclusive data confirm the benefit of GnRH agonists in adjuvant therapy after treatment with chemotherapy followed by tamoxifen.
Conclusions: As more women over the age of 35 consider pregnancy, fertility issues are becoming important areas of investigation for the adjuvant treatment of breast cancer. Whether chemotherapy-induced amenorrhea has a prognostic effect remains unclear, and further studies are warranted.
Approximately one third of new cases of invasive breast cancer predicted to occur in the United States in 2003 will occur in women under 50 years of age. With improved education and increased screening, it is likely that more women will be diagnosed with early-stage breast cancer at younger ages than ever before. Fortunately, most breast cancers are diagnosed at an early stage. Most national guidelines of early-stage invasive breast cancer recommend treatment with adjuvant cytotoxic chemotherapy and hormone therapy with estrogen receptor-positive (ER+) tumors. The exception to these guidelines refers to cases in which the tumors are small. Thus, the majority of young women diagnosed with early-stage breast cancer will undergo adjuvant chemotherapy. Long-term survival is likely when breast cancer is diagnosed at an early stage, especially after adjuvant therapy. Temporary or permanent menopause is a consequence that specifically affects young women diagnosed with breast cancer and treated with adjuvant chemotherapy. In addition, premature ovarian failure has been associated with increased morbidity and mortality.
According to the US Census Bureau of Statistics, the average age of onset of menopause in American women is between 50 and 52 years. The median age of women who develop amenorrhea following adjuvant chemotherapy varies from 38 to 46 years. The likelihood of permanent chemotherapy-induced menopause is directly related to age. Women older than age 40 have a higher incidence of amenorrhea than women younger than age 40. The incidence rate of amenorrhea varies from 21% to 71% in younger women, whereas in women older than 40, the rate ranges from 49% to 100%. Thus, as more women with breast cancer survive the disease, treatment-related morbidity and long-term sequelae related to chemotherapy-induced amenorrhea will assume greater importance. Therefore, future trials will require more attention to reporting the incidence of chemotherapy-induced amenorrhea and will consider prevention and treatment strategies for the symptoms and long-term side affects of menopause.
Another important aspect of therapy decisions in the young premenopausal woman undergoing adjuvant chemotherapy is the preservation of fertility ( Table 1 ). At present, there are no conclusive data suggesting that deleterious effects from subsequent pregnancy will occur in women with a prior history of breast cancer. Therefore, in a population with a high likelihood of long-term survival, interventions to preserve fertility should be considered. In addition, in the absence of clearly documented benefits of premature ovarian failure with regard to disease-free survival (DFS), the preservation of ovarian function may improve all-cause survival by decreasing the risks of heart disease and osteoporosis. Over the last 2 decades, the median age at first live birth has steadily increased ( Table 2 ). The number of children born to women over 30 years of age has doubled and now comprises 30% of all live births. In 1999, in the United States alone, more than 500,000 babies were born to women over 35 years of age and many to women over age 40. According to the US Census Bureau, the birth rate in women over age 40 is projected to increase by 7% over the next 10 years. The likelihood of successful conception decreases over age 34 in nulliparous women, and this may be due to selection bias rather than biologic reasons. The infertility rate of parous women remains at 5% or less up to the age of
44. These findings suggest that the preservation of fertility even in women over the age of 35 years is important. Major strides have been made in reproductive medicine that allow many women to become pregnant even when subfertile or when fertility chances are waning due to older age. However, most reproductive interventions are either not possible or exceedingly difficult after menopause. The rate of premature ovarian failure (ie, menopause under the age of 40) has been estimated at 1% and is often familial. Early menopause (ie, menopause between 41-44 years) is estimated to occur in approximately 5% of women. While breast cancer is more common in older women, about 1 in 200 women under the age of 40 is at risk to develop breast cancer. Many of these women benefit from chemotherapy but are afraid to risk the opportunity to bear children.
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