Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials
TL;DR: Recurrence RRs favoured aromatase inhibitors during periods when treatments differed, but not significantly thereafter, and 10-year breast cancer mortality was lower with switching to arom atase inhibitors than with remaining on tamoxifen, and there were fewer recurrences in these trials.
About: This article is published in The Lancet.The article was published on 2015-10-03 and is currently open access. It has received 987 citations till now. The article focuses on the topics: Aromatase inhibitor & Letrozole.
Citations
More filters
TL;DR: This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer as well as distinct risk profiles and treatment strategies.
Abstract: Importance Breast cancer will be diagnosed in 12% of women in the United States over the course of their lifetimes and more than 250 000 new cases of breast cancer were diagnosed in the United States in 2017. This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer. Observations Breast cancer is categorized into 3 major subtypes based on the presence or absence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2 (ERBB2; formerlyHER2): hormone receptor positive/ERBB2 negative (70% of patients),ERBB2positive (15%-20%), and triple-negative (tumors lacking all 3 standard molecular markers; 15%). More than 90% of breast cancers are not metastatic at the time of diagnosis. For people presenting without metastatic disease, therapeutic goals are tumor eradication and preventing recurrence. Triple-negative breast cancer is more likely to recur than the other 2 subtypes, with 85% 5-year breast cancer–specific survival for stage I triple-negative tumors vs 94% to 99% for hormone receptor positive andERBB2positive. Systemic therapy for nonmetastatic breast cancer is determined by subtype: patients with hormone receptor–positive tumors receive endocrine therapy, and a minority receive chemotherapy as well; patients withERBB2-positive tumors receiveERBB2-targeted antibody or small-molecule inhibitor therapy combined with chemotherapy; and patients with triple-negative tumors receive chemotherapy alone. Local therapy for all patients with nonmetastatic breast cancer consists of surgical resection, with consideration of postoperative radiation if lumpectomy is performed. Increasingly, some systemic therapy is delivered before surgery. Tailoring postoperative treatment based on preoperative treatment response is under investigation. Metastatic breast cancer is treated according to subtype, with goals of prolonging life and palliating symptoms. Median overall survival for metastatic triple-negative breast cancer is approximately 1 year vs approximately 5 years for the other 2 subtypes. Conclusions and Relevance Breast cancer consists of 3 major tumor subtypes categorized according to estrogen or progesterone receptor expression andERBB2gene amplification. The 3 subtypes have distinct risk profiles and treatment strategies. Optimal therapy for each patient depends on tumor subtype, anatomic cancer stage, and patient preferences.
2,310 citations
TL;DR: After 5 years of adjuvant endocrine therapy, breast‐cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years, with risks ranging from 10 to 41%, depending on TN status and tumor grade.
Abstract: BackgroundThe administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)–positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment. MethodsIn this meta-analysis of the results of 88 trials involving 62,923 women with ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy, we used Kaplan–Meier and Cox regression analyses, stratified according to trial and treatment, to assess the associations of tumor diameter and nodal status (TN), tumor grade, and other factors with patients’ outcomes during the period from 5 to 20 years. ResultsBreast-cancer recurrences occurred at a steady rate throughout the study period from 5 to 20 years. The risk of distant recurrence w...
929 citations
TL;DR: The combination of P with H and standard chemotherapy resulted in low rates of symptomatic LVSD, and the tolerability of H and P with chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer was assessed.
849 citations
Harvard University1, Medical University of Vienna2, Institut Jules Bordet3, University of St. Gallen4, Kantonsspital St. Gallen5, Institut Gustave Roussy6, Memorial Sloan Kettering Cancer Center7, Karolinska Institutet8, University of Bordeaux9, University of North Carolina at Chapel Hill10, Queen Mary University of London11, Charité12, Marmara University13, Mount Sinai Hospital, Toronto14, Ludwig Maximilian University of Munich15, University of Michigan16, National Taiwan University17, University of Ulm18, National Institutes of Health19, Gdańsk Medical University20, Sahlgrenska University Hospital21, Baylor College of Medicine22, University of Toronto23, Netherlands Cancer Institute24, Paracelsus Private Medical University of Salzburg25, Fudan University26, The Royal Marsden NHS Foundation Trust27, Kyoto University28, Institute of Cancer Research29, University of Milan30, McMaster University31
TL;DR: The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer, and recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence.
777 citations
TL;DR: Evidence-based medicine progressed to recognise limitations of evidence alone, and has increasingly stressed the need to combine critical appraisal of the evidence with patient's values and preferences through shared decision making.
557 citations
References
More filters
TL;DR: The 10-year and 15-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival are reported and it is found that the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.
6,309 citations
TL;DR: The absolute risk reductions produced by tamoxifen depend on the absolute breast cancer risks (after any chemotherapy) without tamox ifen, so all-cause mortality was substantially reduced.
2,347 citations
TL;DR: Exemestane therapy after two to three years ofTamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxIFen treatment.
Abstract: background Tamoxifen, taken for five years, is the standard adjuvant treatment for postmenopausal women with primary, estrogen-receptor–positive breast cancer. Despite this treatment, however, some patients have a relapse. methods We conducted a double-blind, randomized trial to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The primary end point was disease-free survival. results Of the 4742 patients enrolled, 2362 were randomly assigned to switch to exemestane, and 2380 to continue to receive tamoxifen. After a median follow-up of 30.6 months, 449 first events (local or metastatic recurrence, contralateral breast cancer, or death) were reported — 183 in the exemestane group and 266 in the tamoxifen group. The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 (95 percent confidence interval, 0.56 to 0.82; P<0.001 by the log-rank test), representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent (95 percent confidence interval, 2.6 to 6.8) at three years after randomization. Overall survival was not significantly different in the two groups, with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group. Severe toxic effects of exemestane were rare. Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group (P=0.04). conclusions Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment.
1,731 citations
Clinical Trial Service Unit1, Glasgow Caledonian University2, Institut Gustave Roussy3, All India Institute of Medical Sciences4, Cairo University5, Monash University6, Queen's University Belfast7, University of Newcastle8, Tehran University of Medical Sciences9, Kaohsiung Medical University10, Tel Aviv Sourasky Medical Center11, Tata Memorial Hospital12, Charles University in Prague13, Cancer Institute14
TL;DR: Treatment allocation seemed to have no effect on breast cancer outcome among 1248 women with ER-negative disease, and an intermediate effect among 4800 women with unknown ER status, and a further reduction in recurrence and mortality, particularly after year 10.
1,637 citations
TL;DR: In postmenopausal women, treatment with tamoxifen is associated with preservation of the bone mineral density of the lumbar spine, and whether this favorable effect on bone mineraldensity is accompanied by a decrease in the risk of fractures remains to be determined.
Abstract: Background and Methods. Tamoxifen, a synthetic antiestrogen, increases disease-free and overall survival when used as adjuvant therapy for primary breast cancer. Because it is given for long periods, it is important to know whether tamoxifen affects the skeleton, particularly since it is used extensively in postmenopausal women who are at risk for osteoporosis. Using photon absorptiometry, we studied the effects of tamoxifen on the bone mineral density of the lumbar spine and radius and on biochemical measures of bone metabolism in 140 postmenopausal women with axillary-node—negative breast cancer, in a two-year randomized, double-blind, placebo-controlled trial. Results. In the women given tamoxifen, the mean bone mineral density of the lumbar spine increased by 0.61 percent per year, whereas in those given placebo it decreased by 1.00 percent per year (P<0.001). Radial bone mineral density decreased to the same extent in both groups. In a subgroup randomly selected from each group, serum osteoc...
1,120 citations