Treating Breast Cancer Metastases to the Lung and Brain?
Treating Breast Cancer Metastases to the Lung and Brain?
A 37-year-old woman underwent a right mastectomy and axillary clearance for a T3N1M0, grade 2, ER-positive, PR-negative, metaplastic breast carcinoma. She underwent 6 cycles of 5-fluorouracil/doxorubicin/cyclophosphamide (FAC) and radiotherapy to the chest wall and supraclavicular area, and was maintained on tamoxifen 20 mg daily. Fifteen months later, multiple nodules were detected in each lung on chest x-ray, and further work-up revealed multiple brain metastases. What would you recommend at this time?
Prof. Mehmet Koc
This is a case of a 37-year-old woman who, 15 months after treatment of a breast carcinoma, relapsed in the lungs and in the brain. The initial treatment was optimal; she had an early relapse with a poor prognosis (ie, brain metastases) but is not symptomatic.
First, we would propose immediate radiation therapy in order to preclude the patient from becoming symptomatic, even if such a treatment will not have an impact on the overall survival.
Second, tamoxifen should be stopped. We would suggest chemotherapy rather than hormonal therapy since the relapse occurred while the patient was on tamoxifen, the viscera are poorly hormone-sensitive, and the tumor is very fast-growing. The question remains, however, as to which chemotherapy regimen is best. With regard to high-dose chemotherapy, there are no clinical trials comparing high- vs standard-dose chemotherapy that showed a benefit with the higher dose.
If the relapse was observed less than 1 year after the end of adjuvant chemotherapy, it can be concluded that the tumor was anthracycline-resistant and, accordingly, a nonanthracycline regimen should be proposed. For such a case, it has been shown that docetaxel was better than vinblastine/mitomycin, even in terms of overall survival.
If, however, the relapse occurs more than 15 months after the end of chemotherapy, several alternatives are possible. Depending on the total initial dose of doxorubicin, a FAC-like regimen may be appropriate. However, if the initial dose was 60 mg/m, the remaining acceptable dose would be too small for this regimen to be proposed. If the total anthracycline dose was lower, a half-dose (50 mg/m) epirubicin in 5-fluorouracil/epirubicin/cyclophosphamide (FEC 50) could be proposed.
A polychemotherapy approach combining taxanes and anthracyclines could be another alternative. To our knowledge, 4 studies with paclitaxel and 3 studies with docetaxel have been published, at least in abstract form. Although the overall as well as the complete response rates were slightly higher with the combinations, the time to progression was similar, and the overall survival was longer only in 1 study in the taxane-containing arm. Conversely, tolerability was poorer when a taxane was added, yielding higher rates of febrile neutropenia in the docetaxel arms. These combination regimens should therefore be proposed only in symptomatic patients in whom a rapid response is important.
In this patient, however, given that she is asymptomatic, based on the above, we would favor a regimen of docetaxel monochemotherapy.
A 37-year-old woman underwent a right mastectomy and axillary clearance for a T3N1M0, grade 2, ER-positive, PR-negative, metaplastic breast carcinoma. She underwent 6 cycles of 5-fluorouracil/doxorubicin/cyclophosphamide (FAC) and radiotherapy to the chest wall and supraclavicular area, and was maintained on tamoxifen 20 mg daily. Fifteen months later, multiple nodules were detected in each lung on chest x-ray, and further work-up revealed multiple brain metastases. What would you recommend at this time?
Prof. Mehmet Koc
This is a case of a 37-year-old woman who, 15 months after treatment of a breast carcinoma, relapsed in the lungs and in the brain. The initial treatment was optimal; she had an early relapse with a poor prognosis (ie, brain metastases) but is not symptomatic.
First, we would propose immediate radiation therapy in order to preclude the patient from becoming symptomatic, even if such a treatment will not have an impact on the overall survival.
Second, tamoxifen should be stopped. We would suggest chemotherapy rather than hormonal therapy since the relapse occurred while the patient was on tamoxifen, the viscera are poorly hormone-sensitive, and the tumor is very fast-growing. The question remains, however, as to which chemotherapy regimen is best. With regard to high-dose chemotherapy, there are no clinical trials comparing high- vs standard-dose chemotherapy that showed a benefit with the higher dose.
If the relapse was observed less than 1 year after the end of adjuvant chemotherapy, it can be concluded that the tumor was anthracycline-resistant and, accordingly, a nonanthracycline regimen should be proposed. For such a case, it has been shown that docetaxel was better than vinblastine/mitomycin, even in terms of overall survival.
If, however, the relapse occurs more than 15 months after the end of chemotherapy, several alternatives are possible. Depending on the total initial dose of doxorubicin, a FAC-like regimen may be appropriate. However, if the initial dose was 60 mg/m, the remaining acceptable dose would be too small for this regimen to be proposed. If the total anthracycline dose was lower, a half-dose (50 mg/m) epirubicin in 5-fluorouracil/epirubicin/cyclophosphamide (FEC 50) could be proposed.
A polychemotherapy approach combining taxanes and anthracyclines could be another alternative. To our knowledge, 4 studies with paclitaxel and 3 studies with docetaxel have been published, at least in abstract form. Although the overall as well as the complete response rates were slightly higher with the combinations, the time to progression was similar, and the overall survival was longer only in 1 study in the taxane-containing arm. Conversely, tolerability was poorer when a taxane was added, yielding higher rates of febrile neutropenia in the docetaxel arms. These combination regimens should therefore be proposed only in symptomatic patients in whom a rapid response is important.
In this patient, however, given that she is asymptomatic, based on the above, we would favor a regimen of docetaxel monochemotherapy.
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