Medline ® Abstracts for References 7-10
of 'Adjuvant chemotherapy for HER2-negative breast cancer'
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG)
BACKGROUND: Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5 year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects.
METHODS: Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxorubicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modern aromatase inhibitors.
FINDINGS: Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0.0001 for recurrence, 2p<0.00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69,>or =70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0.00001 for recurrence, 2p=0.01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14,000); anthracycline-based versus CMF-based chemotherapy (14,000); about 5 years of tamoxifen versus none (15,000); about 1-2 years of tamoxifen versus none (33,000); and about 5 years versus 1-2 years of tamoxifen (18,000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age<50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial resultscould well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes.
INTERPRETATION: Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
Adjuvant! Breast Cancer Help Files. www.adjuvantonline.com/index.jsp (Accessed on October 14, 2011).
no abstract available
Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer.
Ravdin PM, Siminoff LA, Davis GJ, Mercer MB, Hewlett J, Gerson N, Parker HL
J Clin Oncol. 2001;19(4):980.
PURPOSE: The goal of the computer program Adjuvant! is to allow health professionals and their patients with early breast cancer to make more informed decisions about adjuvant therapy.
METHODS: Actuarial analysis was used to project outcomes of patients with and without adjuvant therapy based on estimates of prognosis largely derived from Surveillance, Epidemiology, and End-Results data and estimates of the efficacy of adjuvant therapy based on the 1998 overviews of randomized trials of adjuvant therapy. These estimates can be refined using the Prognostic Factor Impact Calculator, which uses a Bayesian method to make adjustments based on relative risks conferred and prevalence of positive test results.
RESULTS: From the entries of patient information (age, menopausal status, comorbidity estimate) and tumor staging and characteristics (tumor size, number of positive axillary nodes, estrogen receptor status), baseline prognostic estimates are made. Estimates for the efficacy of endocrine therapy (5 years of tamoxifen) and of polychemotherapy (cyclophosphamide/methotrexate/fluorouracil-like regimens, or anthracycline-based therapy, or therapy based on both an anthracycline and a taxane) can then be used to project outcomes presented in both numerical and graphical formats. Outcomes for overall survival and disease-free survival and the improvement seen in clinical trials, are reasonably modeled by Adjuvant!, although an ideal validation for all patient subsets with all treatment options is not possible. Additional speculative estimates of years of remaining life expectancy and long-term survival curves can also be produced. Help files supply general information about breast cancer. The program's Internet links supply national treatment guidelines, cooperative group trial options, and other related information.
CONCLUSION: The computer program Adjuvant! can play practical and educational roles in clinical settings.
Division of Oncology, University of Texas Health Sciences Center, San Antonio, TX 78284, USA. email@example.com
Decision-making in early breast cancer: guidelines and decision tools.
Baum M, Ravdin PM
Eur J Cancer. 2002;38(6):745.
The meta-analysis of trials of adjuvant systemic therapy for early breast cancer provides robust information on the impact of both cytotoxic chemotherapy and tamoxifen on relapse-free and overall survival to 15 years from diagnosis. These data are described in terms of relative risk reduction and are not meant to be viewed as a prescription for therapy. To translate relative risk reductions into absolute benefits for the individual patient and then trade off the gains against the long-term and short-term side-effects and toxicities is a highly complex process for the clinician, and current guidelines are formatted in such a way that they fail to use current information in a way that allows a quantitative assessment of the benefits and risks of adjuvant therapy. This review article explores current guidelines and describes some aids that may be used to help inform women about their treatment options for early breast cancer.
CRC/UCL Cancer Trials Centre, Stephenson House, 158-160 North Gower Street, London NWI 2ND, UK. firstname.lastname@example.org