Ask the Experts - Chemotherapy-Related Amenorrhea?
Ask the Experts - Chemotherapy-Related Amenorrhea?
A 31-year-old woman presented with stage II breast cancer with more than 4 positive nodes. She received postoperative doxorubicin/cyclophosphamide and paclitaxel plus radiotherapy. After the last dose of paclitaxel, she complained of prolonged menstrual periods. I know there is no role for ovarian ablation in this case, and I am reluctant to start her on oral contraceptives because of her breast cancer. Would tamoxifen be appropriate? Do you have any other suggestions?
Treatment-related amenorrhea is a common side effect of adjuvant chemotherapy among premenopausal women. It arises as a consequence of direct toxicity to the ovary and reflects ovarian failure with resulting infertility and menopausal symptoms. Amenorrhea may be permanent or temporary. As with natural menopause, chemotherapy-related amenorrhea is characterized by hypergonadotropic hypogonadism; laboratory tests will reveal diminished levels of estrogen with elevated circulating levels of FSH and LH. The risk of developing amenorrhea is a function of age (older women are at greater risk) and of the particular treatment regimen. In general, the greater the cumulative dose of chemotherapy, particularly alkylator-type therapy, the higher the risk of amenorrhea. For women under age 40 receiving doxorubicin/cyclophosphamide chemotherapy, the incidence of prolonged amenorrhea is approximately 15%. It is not known what impact the addition of taxane-based therapy will have on the rate of amenorrhea.
Women with irregular periods after chemotherapy may resume normal menses, or may progress toward menopause. There are no predictive factors; only time will tell. Patients with temporary amenorrhea or irregular periods may still become pregnant. Therefore, they should be advised to use appropriate forms of birth control if they do not wish to become pregnant. Because the safety of oral contraceptives has not been evaluated in women with personal histories of breast cancer, and because of concerns regarding estrogen exposure in women with tumors that may be hormonally sensitive, oral contraceptives are usually not offered to breast cancer patients. Tamoxifen will not necessarily help regulate menstrual periods, nor is it a form of birth control. Tamoxifen would only be standard of care for this patient if her tumor is estrogen receptor-positive and/or progesterone-receptor (ER/PR)-positive.
The importance of ovarian suppression as part of adjuvant therapy for breast cancer remains controversial. Retrospective studies have suggested that women receiving cyclophosphamide, methotrexate, and fluorouracil (CMF)-based adjuvant chemotherapy regimens who experience amenorrhea have a better outcome compared with those on other regimens. Other randomized trials have suggested that ovarian ablation may be equivalent to adjuvant CMF chemotherapy for premenopausal women with hormone-sensitive breast cancer. In current practice, it is not clear how these observations relate to women with ER/PR-positive tumors receiving tamoxifen, or to women receiving anthracycline and/or taxane-based treatments.
Ovarian suppression as therapy in addition to tamoxifen and chemotherapy for premenopausal women with early-stage breast cancer is an important question that needs to be studied in a large, prospective trial. Studies that compare tamoxifen vs tamoxifen plus ovarian ablation among women with ER/PR-positive tumors have been proposed and will hopefully be under way soon.
A 31-year-old woman presented with stage II breast cancer with more than 4 positive nodes. She received postoperative doxorubicin/cyclophosphamide and paclitaxel plus radiotherapy. After the last dose of paclitaxel, she complained of prolonged menstrual periods. I know there is no role for ovarian ablation in this case, and I am reluctant to start her on oral contraceptives because of her breast cancer. Would tamoxifen be appropriate? Do you have any other suggestions?
Treatment-related amenorrhea is a common side effect of adjuvant chemotherapy among premenopausal women. It arises as a consequence of direct toxicity to the ovary and reflects ovarian failure with resulting infertility and menopausal symptoms. Amenorrhea may be permanent or temporary. As with natural menopause, chemotherapy-related amenorrhea is characterized by hypergonadotropic hypogonadism; laboratory tests will reveal diminished levels of estrogen with elevated circulating levels of FSH and LH. The risk of developing amenorrhea is a function of age (older women are at greater risk) and of the particular treatment regimen. In general, the greater the cumulative dose of chemotherapy, particularly alkylator-type therapy, the higher the risk of amenorrhea. For women under age 40 receiving doxorubicin/cyclophosphamide chemotherapy, the incidence of prolonged amenorrhea is approximately 15%. It is not known what impact the addition of taxane-based therapy will have on the rate of amenorrhea.
Women with irregular periods after chemotherapy may resume normal menses, or may progress toward menopause. There are no predictive factors; only time will tell. Patients with temporary amenorrhea or irregular periods may still become pregnant. Therefore, they should be advised to use appropriate forms of birth control if they do not wish to become pregnant. Because the safety of oral contraceptives has not been evaluated in women with personal histories of breast cancer, and because of concerns regarding estrogen exposure in women with tumors that may be hormonally sensitive, oral contraceptives are usually not offered to breast cancer patients. Tamoxifen will not necessarily help regulate menstrual periods, nor is it a form of birth control. Tamoxifen would only be standard of care for this patient if her tumor is estrogen receptor-positive and/or progesterone-receptor (ER/PR)-positive.
The importance of ovarian suppression as part of adjuvant therapy for breast cancer remains controversial. Retrospective studies have suggested that women receiving cyclophosphamide, methotrexate, and fluorouracil (CMF)-based adjuvant chemotherapy regimens who experience amenorrhea have a better outcome compared with those on other regimens. Other randomized trials have suggested that ovarian ablation may be equivalent to adjuvant CMF chemotherapy for premenopausal women with hormone-sensitive breast cancer. In current practice, it is not clear how these observations relate to women with ER/PR-positive tumors receiving tamoxifen, or to women receiving anthracycline and/or taxane-based treatments.
Ovarian suppression as therapy in addition to tamoxifen and chemotherapy for premenopausal women with early-stage breast cancer is an important question that needs to be studied in a large, prospective trial. Studies that compare tamoxifen vs tamoxifen plus ovarian ablation among women with ER/PR-positive tumors have been proposed and will hopefully be under way soon.
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