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Cognitive Function of Older Patients Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Prospective Longitudinal Study
International Breast Cancer Study Group, which includes the North American Intergroup and the Breast International Group. In this trial, premenopausal women with hormone receptor-positive tumors who remain premenopausal after chemotherapy (or who never get chemotherapy) are ran-
domized to 5 years of tamoxifen, OAS plus tamoxifen, or OAS plus exemestane. The results of this trial will provide patients and physicians with data needed to make decisions about OAS. G. F. Fleming, MD P. Francis, MD
Reference 1. Early Breast Cancer Trialists’ Collaborative Group (EBCTG): Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 365:16871717, 2005.
ANNOTATED BIBLIOGRAPHY Cognitive Function of Older Patients Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Prospective Longitudinal Study Hurria A, Rosen C, Hudis C, et al J Am Geriatr Soc 54:925-931, 2006 Hurria and colleagues prospectively evaluated cognitive functioning among 28 women, aged 65 years and older, before and 6 months after adjuvant chemotherapy for breast cancer. The authors found that 25% of the women experienced declines in 2 or more domains of cognitive function during this period. Encouragingly, these cognitive declines were not associated with worsened functional status, although the numbers were limited. This is an important study because it focuses on older women, who may be more vulnerable than younger patients to cognitive changes over time and may experience greater declines with adjuvant chemotherapy. The investigators should be applauded for researching this increasingly important cancer survivorship issue in the largest and growing although understudied population of survivors of breast cancer. Ongoing and future longitudinal studies, including baseline pre-chemotherapy assessments and studies in control populations, should help to elucidate further risk factors associated with cognitive dysfunction, effects on functional status and quality of life, and areas for potential intervention. A. H. Partridge, MD, MPH
Randomized Phase II Trial of Letrozole and Letrozole Plus Low-Dose Metronomic Oral Cyclophosphamide as Primary Systemic Treatment in Elderly Breast Cancer Patients Bottini A, Generali D, Brizzi MP, et al J Clin Oncol 24:3623-3628, 2006 Bottini and colleagues conducted a randomized study comparing neoadjuvant aromatase inhibitor therapy with letrozole versus letrozole plus low-dose metronomic cyclophosphamide and demonstrated equivalent rates of response and greater rates of change in Ki67 and vascular endothelial growth factor staining with the combination regimen. This study is of interest for several reasons. First, it is notable because it focused on elderly patients (the median age was 79 years),
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Breast Diseases: A Year Book Quarterly Vol 18 No 1 2007
who represent an understudied group in clinical trials. The elderly women were willing to participate in a randomized study and tolerated treatment handily. Second, this study used neoadjuvant endocrine therapy, which is a strategy still of limited interest in the United States. Six months of endocrine therapy was highly effective, causing responses in nearly 80% of patients. The pathologic complete response rate was low at 3% to 4%, a consistent finding in preoperative endocrine trials. Third, the study added metronomic chemotherapy, a strategy that uses low, repeated doses of chemotherapy to target the vasculature and supporting elements of the tumor. All told, the study demonstrated that metronomic chemotherapy did not interfere with endocrine treatment with an aromatase inhibitor, and there was the suggestion in biomarker assays that the chemotherapy element may contribute to anti-tumor efficacy. The study should give impetus to clinical investigations centering on the use of nonstandard chemotherapy regimens—in particular, low-dose, repetitive regimens that lack acute side effects—as a novel strategy for targeting breast cancers. The study also provided assurance that it is safe to pair such treatments with chronic use of endocrine agents. H. J. Burstein, MD, PhD
Adjuvant Aromatase Inhibitors for Early Breast Cancer After Chemotherapy-Induced Amenorrhoea: Caution and Suggested Guidelines Smith IE, Dowsett M, Yap YS, et al J Clin Oncol 24:2444-2447, 2006 The authors described their experience treating women who had become amenorrheic after chemotherapy. In women over 40 years of age, 27% resumed ovarian function after initiation of therapy with an aromatase inhibitor (AI). This finding highlights concerns regarding the use of AIs in peri-menopausal women and the need for a clear definition of menopause in women for whom AIs are considered a treatment option. Ongoing research is focusing on the role of AIs in combination with ovarian suppression in the treatment of premenopausal women and defining their role in the treatment of perimenopausal women. M. Naughton, MD M. J. Ellis, MB, BChir, PhD, FRCP
domized to 5 years of tamoxifen, OAS plus tamoxifen, or OAS plus exemestane. The results of this trial will provide patients and physicians with data needed to make decisions about OAS. G. F. Fleming, MD P. Francis, MD
Reference 1. Early Breast Cancer Trialists’ Collaborative Group (EBCTG): Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 365:16871717, 2005.
ANNOTATED BIBLIOGRAPHY Cognitive Function of Older Patients Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Prospective Longitudinal Study Hurria A, Rosen C, Hudis C, et al J Am Geriatr Soc 54:925-931, 2006 Hurria and colleagues prospectively evaluated cognitive functioning among 28 women, aged 65 years and older, before and 6 months after adjuvant chemotherapy for breast cancer. The authors found that 25% of the women experienced declines in 2 or more domains of cognitive function during this period. Encouragingly, these cognitive declines were not associated with worsened functional status, although the numbers were limited. This is an important study because it focuses on older women, who may be more vulnerable than younger patients to cognitive changes over time and may experience greater declines with adjuvant chemotherapy. The investigators should be applauded for researching this increasingly important cancer survivorship issue in the largest and growing although understudied population of survivors of breast cancer. Ongoing and future longitudinal studies, including baseline pre-chemotherapy assessments and studies in control populations, should help to elucidate further risk factors associated with cognitive dysfunction, effects on functional status and quality of life, and areas for potential intervention. A. H. Partridge, MD, MPH
Randomized Phase II Trial of Letrozole and Letrozole Plus Low-Dose Metronomic Oral Cyclophosphamide as Primary Systemic Treatment in Elderly Breast Cancer Patients Bottini A, Generali D, Brizzi MP, et al J Clin Oncol 24:3623-3628, 2006 Bottini and colleagues conducted a randomized study comparing neoadjuvant aromatase inhibitor therapy with letrozole versus letrozole plus low-dose metronomic cyclophosphamide and demonstrated equivalent rates of response and greater rates of change in Ki67 and vascular endothelial growth factor staining with the combination regimen. This study is of interest for several reasons. First, it is notable because it focused on elderly patients (the median age was 79 years),
100 100
®
Breast Diseases: A Year Book Quarterly Vol 18 No 1 2007
who represent an understudied group in clinical trials. The elderly women were willing to participate in a randomized study and tolerated treatment handily. Second, this study used neoadjuvant endocrine therapy, which is a strategy still of limited interest in the United States. Six months of endocrine therapy was highly effective, causing responses in nearly 80% of patients. The pathologic complete response rate was low at 3% to 4%, a consistent finding in preoperative endocrine trials. Third, the study added metronomic chemotherapy, a strategy that uses low, repeated doses of chemotherapy to target the vasculature and supporting elements of the tumor. All told, the study demonstrated that metronomic chemotherapy did not interfere with endocrine treatment with an aromatase inhibitor, and there was the suggestion in biomarker assays that the chemotherapy element may contribute to anti-tumor efficacy. The study should give impetus to clinical investigations centering on the use of nonstandard chemotherapy regimens—in particular, low-dose, repetitive regimens that lack acute side effects—as a novel strategy for targeting breast cancers. The study also provided assurance that it is safe to pair such treatments with chronic use of endocrine agents. H. J. Burstein, MD, PhD
Adjuvant Aromatase Inhibitors for Early Breast Cancer After Chemotherapy-Induced Amenorrhoea: Caution and Suggested Guidelines Smith IE, Dowsett M, Yap YS, et al J Clin Oncol 24:2444-2447, 2006 The authors described their experience treating women who had become amenorrheic after chemotherapy. In women over 40 years of age, 27% resumed ovarian function after initiation of therapy with an aromatase inhibitor (AI). This finding highlights concerns regarding the use of AIs in peri-menopausal women and the need for a clear definition of menopause in women for whom AIs are considered a treatment option. Ongoing research is focusing on the role of AIs in combination with ovarian suppression in the treatment of premenopausal women and defining their role in the treatment of perimenopausal women. M. Naughton, MD M. J. Ellis, MB, BChir, PhD, FRCP