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Continuing Outcomes Relevant to Evista: Breast Cancer Incidence in Postmenopausal Osteoporotic Women in a Randomized Trial of Raloxifene
Prognostic Analysis of Early Lymphocyte Recovery in Patients With Advanced Breast Cancer Receiving High-Dose Chemotherapy With an Autologous Hematopoietic Progenitor Cell Transplant
Phase II Study of Feasibility of Dose-Dense FEC Followed by Alternating Weekly Taxanes in High-Risk, Four or More Node-Positive Breast Cancer
Nieto Y, Shpall EJ, McNiece IK, et al
Clin Cancer Res 10:5754-5761, 2004
Clin Cancer Res 10:5076-5086, 2004
This study by Dang and colleagues assessed the feasibility of 6 cycles of dose-dense fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by 18 weeks of alternating weekly docetaxel and paclitaxel for patients with high-risk node-positive breast cancer. Excessive toxicity led to the study’s being stopped early after 17 women (39%) had completed the planned treatment. This trial was important in its application of dose-dense principles to regimens other than doxorubicin, cyclophosphamide, and paclitaxel. The pneumonitis experienced during the FEC portion of the study has not been previously identified and merits additional investigation, as the etiology is unclear. Working hypotheses as to the cause of FEC– associated pneumonitis include chemical pneumonitis related to FEC; the every-2-weeks schedule; and the addition of granulocytecolony stimulating factor. Also of note, 2 of the 17 patients (12%) who completed the planned alternating taxane portion of the trial experienced clinically significant pericardial effusions. Results of the GONO-MIG1 study, presented in abstract form at the San Antonio Breast Symposium in 2003, showed that accelerated FEC was not associated with an improvement in survival over that of standard FEC (although the epirubicin dose was different in the 2 groups).1 Neither pneumonitis nor pericardial effusion were reported. The optimal schedule of anthracyclines and taxanes for adjuvant therapy continues to be investigated in studies such as the 1199 and 0221 trials of the Eastern Cooperative Oncology Group. The role of alternating taxanes, if any, is still unclear, but the toxicity related to effusions seen in this trial is a cautionary tale. D. Shafer, MD L. J. Goldstein, MD
This report from Nieto and colleagues demonstrated that the absolute lymphocyte count at day 15 after peripheral blood stem cell transplantation correlated with freedom from relapse and overall survival rates in patients with metastatic breast cancer. This finding did not correlate with stem cell yields of the transplanted graft and remained an independent predictor of outcome in multivariate analyses. Moreover, this finding was not observed in patients who received bone marrow or CD34-selected stem cell transplants, suggesting that lymphocytes infused with the stem cell graft were responsible for the effect. This paper raises the provocative thesis that recovering immune effector cells may mediate an antitumor effect on malignant cells remaining after the transplant. Previous studies have demonstrated that tumor-mediated immune suppression may be temporarily suspended soon after the transplant, offering a window for immune intervention. This study also raises the question as to whether efforts to enhance tumor-specific immunity after a transplant could be effective in augmenting cytoreduction and potentially in increasing curative outcomes. D. E. Avigan, MD
Continuing Outcomes Relevant to Evista: Breast Cancer Incidence in Postmenopausal Osteoporotic Women in a Randomized Trial of Raloxifene Martino S, Cauley JA, Barrett-Connor E, et al J Natl Cancer Inst 96:1751-1761, 2004 The Continuing Outcomes Relevant to Evista (CORE) trial is a continuation of the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, a 3-arm comparison of placebo vs the selective estrogen-receptor modulator raloxifene at either 60 mg or 120 mg per day for postmenopausal women with osteoporosis. Although the MORE trial included participants who were not at increased risk of breast cancer, the results at 4 years demonstrated a 72% decrease in the incidence of invasive breast cancer among women who received raloxifene. The CORE trial has a complex design in which a subset of the MORE participants were allowed to continue or restart their assigned therapy (either raloxifene or placebo) for up to 4 additional years. The results demonstrated a significant reduction in invasive breast cancer that continued beyond the initial 4 years of raloxifene treatment and identified no new safety concerns. The CORE results are reassuring and strongly suggest that raloxifene is an effective therapy for breast cancer risk reduction; however, it would be premature to use raloxifene for that indication until the results of the National Surgical Adjuvant Breast and Bowel Project’s Study of Tamoxifen and Raloxifene (STAR) are analyzed. That trial is a breast cancer prevention study involving more than 19,000 postmenopausal women at high risk of developing breast cancer, and the results should be available in early 2006. D. L. Wickerham, MD
278 278
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Breast Diseases: A Year Book Quarterly Vol 16 No 3 2005
Dang CT, D’Andrea GM, Moynahan ME, et al
Reference 1. Venturini M, Aitini E, Del Mastro L, et al: Phase III adjuvant trial comparing standard versus accelerated FEC regimen in early breast cancer patients. Results from GONO–MIG1 study (abstract 12). Breast Cancer Res Treat 82:S9, 2003. Also available at http://www.abstracts2view.com/bcs03/view.php ?nu=BCS3L_251. Accessed June 2, 2005.
Disease-Free Survival Advantage of Weekly Epirubicin Plus Tamoxifen Versus Tamoxifen Alone as Adjuvant Treatment of Operable, Node-Positive, Elderly Breast Cancer Patients: 6-Year Follow-up Results of the French Adjuvant Study Group 08 Trial Fargeot P, Bonneterre J, Roché H, et al J Clin Oncol 22:4622-4630, 2004 The title of this paper implies that women older than 65 years treated with chemotherapy (epirubicin) plus tamoxifen had better diseasefree survival than did women treated with tamoxifen alone.
Phase II Study of Feasibility of Dose-Dense FEC Followed by Alternating Weekly Taxanes in High-Risk, Four or More Node-Positive Breast Cancer
Nieto Y, Shpall EJ, McNiece IK, et al
Clin Cancer Res 10:5754-5761, 2004
Clin Cancer Res 10:5076-5086, 2004
This study by Dang and colleagues assessed the feasibility of 6 cycles of dose-dense fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by 18 weeks of alternating weekly docetaxel and paclitaxel for patients with high-risk node-positive breast cancer. Excessive toxicity led to the study’s being stopped early after 17 women (39%) had completed the planned treatment. This trial was important in its application of dose-dense principles to regimens other than doxorubicin, cyclophosphamide, and paclitaxel. The pneumonitis experienced during the FEC portion of the study has not been previously identified and merits additional investigation, as the etiology is unclear. Working hypotheses as to the cause of FEC– associated pneumonitis include chemical pneumonitis related to FEC; the every-2-weeks schedule; and the addition of granulocytecolony stimulating factor. Also of note, 2 of the 17 patients (12%) who completed the planned alternating taxane portion of the trial experienced clinically significant pericardial effusions. Results of the GONO-MIG1 study, presented in abstract form at the San Antonio Breast Symposium in 2003, showed that accelerated FEC was not associated with an improvement in survival over that of standard FEC (although the epirubicin dose was different in the 2 groups).1 Neither pneumonitis nor pericardial effusion were reported. The optimal schedule of anthracyclines and taxanes for adjuvant therapy continues to be investigated in studies such as the 1199 and 0221 trials of the Eastern Cooperative Oncology Group. The role of alternating taxanes, if any, is still unclear, but the toxicity related to effusions seen in this trial is a cautionary tale. D. Shafer, MD L. J. Goldstein, MD
This report from Nieto and colleagues demonstrated that the absolute lymphocyte count at day 15 after peripheral blood stem cell transplantation correlated with freedom from relapse and overall survival rates in patients with metastatic breast cancer. This finding did not correlate with stem cell yields of the transplanted graft and remained an independent predictor of outcome in multivariate analyses. Moreover, this finding was not observed in patients who received bone marrow or CD34-selected stem cell transplants, suggesting that lymphocytes infused with the stem cell graft were responsible for the effect. This paper raises the provocative thesis that recovering immune effector cells may mediate an antitumor effect on malignant cells remaining after the transplant. Previous studies have demonstrated that tumor-mediated immune suppression may be temporarily suspended soon after the transplant, offering a window for immune intervention. This study also raises the question as to whether efforts to enhance tumor-specific immunity after a transplant could be effective in augmenting cytoreduction and potentially in increasing curative outcomes. D. E. Avigan, MD
Continuing Outcomes Relevant to Evista: Breast Cancer Incidence in Postmenopausal Osteoporotic Women in a Randomized Trial of Raloxifene Martino S, Cauley JA, Barrett-Connor E, et al J Natl Cancer Inst 96:1751-1761, 2004 The Continuing Outcomes Relevant to Evista (CORE) trial is a continuation of the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, a 3-arm comparison of placebo vs the selective estrogen-receptor modulator raloxifene at either 60 mg or 120 mg per day for postmenopausal women with osteoporosis. Although the MORE trial included participants who were not at increased risk of breast cancer, the results at 4 years demonstrated a 72% decrease in the incidence of invasive breast cancer among women who received raloxifene. The CORE trial has a complex design in which a subset of the MORE participants were allowed to continue or restart their assigned therapy (either raloxifene or placebo) for up to 4 additional years. The results demonstrated a significant reduction in invasive breast cancer that continued beyond the initial 4 years of raloxifene treatment and identified no new safety concerns. The CORE results are reassuring and strongly suggest that raloxifene is an effective therapy for breast cancer risk reduction; however, it would be premature to use raloxifene for that indication until the results of the National Surgical Adjuvant Breast and Bowel Project’s Study of Tamoxifen and Raloxifene (STAR) are analyzed. That trial is a breast cancer prevention study involving more than 19,000 postmenopausal women at high risk of developing breast cancer, and the results should be available in early 2006. D. L. Wickerham, MD
278 278
®
Breast Diseases: A Year Book Quarterly Vol 16 No 3 2005
Dang CT, D’Andrea GM, Moynahan ME, et al
Reference 1. Venturini M, Aitini E, Del Mastro L, et al: Phase III adjuvant trial comparing standard versus accelerated FEC regimen in early breast cancer patients. Results from GONO–MIG1 study (abstract 12). Breast Cancer Res Treat 82:S9, 2003. Also available at http://www.abstracts2view.com/bcs03/view.php ?nu=BCS3L_251. Accessed June 2, 2005.
Disease-Free Survival Advantage of Weekly Epirubicin Plus Tamoxifen Versus Tamoxifen Alone as Adjuvant Treatment of Operable, Node-Positive, Elderly Breast Cancer Patients: 6-Year Follow-up Results of the French Adjuvant Study Group 08 Trial Fargeot P, Bonneterre J, Roché H, et al J Clin Oncol 22:4622-4630, 2004 The title of this paper implies that women older than 65 years treated with chemotherapy (epirubicin) plus tamoxifen had better diseasefree survival than did women treated with tamoxifen alone.