To compare the efficacy of chemoendocrine treatment with that of endocrine treatment (ET) alone for postmenopausal women with highly endocrine responsive breast cancer. In the International Breast ...Cancer Study Group (IBCSG) Trials VII and 12–93, postmenopausal women with node-positive, estrogen receptor (ER)-positive or ER-negative, operable breast cancer were randomized to receive either chemotherapy or endocrine therapy or combined chemoendocrine treatment. Results were analyzed overall in the cohort of 893 patients with endocrine-responsive disease, and according to prospectively defined categories of ER, age and nodal status. STEPP analyses assessed chemotherapy effect. The median follow-up was 13 years. Adding chemotherapy reduced the relative risk of a disease-free survival event by 19% (
P
= 0.02) compared with ET alone. STEPP analyses showed little effect of chemotherapy for tumors with high levels of ER expression (
P
= 0.07), or for the cohort with one positive node (
P
= 0.03). Chemotherapy significantly improves disease-free survival for postmenopausal women with endocrine-responsive breast cancer, but the magnitude of the effect is substantially attenuated if ER levels are high.
Byline: Olivia Pagani (1,2), Karen N. Price (3), Richard D. Gelber (4), Monica Castiglione-Gertsch (5), Stig B. Holmberg (6), Jurij Lindtner (7), Beat Thurlimann (2,8), John Collins (9), Martin F. ...Fey (2,10), Alan S. Coates (11,12), Aron Goldhirsch (13,14) Keywords: Breast cancer; Chemotherapy; Estrogen receptor; Hormonal therapy The current therapeutic strategy in breast cancer is to identify a target, such as estrogen receptor (ER) status, for tailoring treatments. We investigated the patterns of recurrence with respect to ER status for patients treated in two randomized trials with 25 years' median follow-up. In the ER-negative subpopulations most breast cancer events occurred within the first 5--7 years after randomization, while in the ER-positive subpopulations breast cancer events were spread through 10 years. In the ER-positive subpopulation, 1 year endocrine treatment alone significantly prolonged disease-free survival (DFS) with no additional benefit observed by adding 1 year of chemotherapy. In the small ER-negative subpopulation chemo-endocrine therapy had a significantly better DFS than endocrine alone or no treatment. Despite small numbers of patients, "old-fashioned" treatments, and competing causes of treatment failure, the value of ER status as a target for response to adjuvant treatment is evident through prolonged follow-up. Author Affiliation: (1) Oncology Institute of Southern Switzerland, Ospedale Italiano, Viganello, Lugano, Switzerland (2) Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland (3) IBCSG Statistical Center and Frontier Science and Technology Research Foundation, Boston, MA, USA (4) IBCSG Statistical Center, Dana-Farber Cancer Institute and Frontier Science and Technology Research Foundation, Boston, MA, USA (5) IBCSG Coordinating Center, Bern, Switzerland (6) Department of Surgery, Sahlgrenska University Hospital, Goteborg, Sweden (7) The Institute of Oncology, Ljubljana, Slovenia (8) Senology Center of Eastern Switzerland, Kantonsspital, St. Gallen, Switzerland (9) Department of Surgery, The Royal Melbourne Hospital, Melbourne, Australia (10) Department of Medical Oncology, Inselspital, Bern, Switzerland (11) International Breast Cancer Study Group, Bern, Switzerland (12) University of Sydney, Sydney, Australia (13) Department of Medicine, European Institute of Oncology, Milan, Italy (14) Oncology Institute of Southern Switzerland, Bellinzona, Switzerland Article History: Registration Date: 09/12/2008 Received Date: 10/10/2008 Accepted Date: 09/12/2008 Online Date: 10/01/2009
A single-item linear analogue self-assessment scale for mood was compared with a 28-item adjective checklist for emotional well-being. To confirm its concurrent validity and responsiveness to ...treatment and recurrence in patients with breast cancer, emotional well-being was assessed every 3 months for 2 years and at 1 and 6 months after recurrence in 1,169 patients who were premenopausal and 960 patients who were postmenopausal. These patients were enrolled in two International Breast Cancer Study Group randomized clinical trials in operable breast cancer conducted from 1986 to 1993. To assess concurrent validity, Pearson's correlations between the linear analogue self-assessment scale and the adjective checklist were calculated for each time-point within each treatment group and for the two assessments after recurrence. Responsiveness to treatment and recurrence were analyzed using paired t tests and the squared ratio of these t tests, an estimate of relative efficiency. Concurrent validity of the mood linear analogue self-assessment was consistently confirmed across four language groups. Both measures were responsive; out of 24 changes over time, 19 were in the expected direction for the linear analogue self-assessment scale (P ≤ 0.05 for 9 of 19) and 17 for the adjective checklist (P ≤ 0.05 for 10 of 17). The linear analogue self-assessment scale was less but sufficiently efficient for detection of treatment effects, with relative efficiency estimates ranging from 0.16 to 2.45 and a median of 0.66 among the comparisons with relatively stable estimates (|t| ≥ 1.0) and more efficient for recurrence than the adjective checklist. The mood linear analogue self-assessment scale is a valid indicator of emotional well-being in patients with breast cancer in large multicenter, multicultural trials in which comprehensive scales are less feasible. This investigation supports the clinical relevance of linear analogue self-assessment scales as indicators of components of quality of life in cancer clinical trials.
The International Breast Cancer Study Group (formerly the Ludwig Group) has conducted nine clinical trials since 1978 (see the Appendix for participants and authors). Biologic hypotheses related to ...the combined use of chemotherapy and endocrine therapy in women with operable breast cancer were tested. Questions of timing of chemotherapy with respect to tumor surgery and late introduction of chemotherapy were also evaluated. Ongoing and future trials continue in this tradition to investigate combinations of available endocrine therapies and cytotoxic agents.
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