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receptors and distinct patterns of breast cancer relapse. Breast Cancer Res Treat. 2003;78:105-118. Survival After Adjuvant Oophorectomy and Tamoxifen in Operable Breast Cancer in Premenopausal Women Love RR, Van Dinh N, Quy TT, et al (Ohio State Univ, Columbus, OH) J Clin Oncol 26:253-257, 2008 Purpose.—Worldwide, approximately 750,000 new cases of breast cancer are diagnosed annually in premenopausal women with limited economic resources. Longer-term survival benefits from adjuvant therapies in such women with operable breast cancer are unknown. Patients and Methods.—From 1993 to 1999, we recruited 709 premenopausal women with operable breast cancer to a multisite randomized clinical trial of adjuvant oophorectomy and tamoxifen for 5 years or observation and this combined hormonal therapy on recurrence. Results.—With a median followup of 7.0 years, disease-free and overall survival were significantly improved with the adjuvant treatment (log-rank P ¼.0003 and .0002, respectively). Five year disease-free survival (DFS) probabilities of 74% and 61% (95% CI for difference, 7% to 21%) and overall survival (OS) rates of 78% and 71% (95% CI for difference, 1% to 21%) were observed in the adjuvant and observation groups. Ten-year DFS probabilities of 62% and 51% (95% CI for difference, 4% to 22%) and OS probabilities of 70% and 52% (95% CI for difference, 6% to 34%) 278 6. Korkola JE, DeVries S, Fridlyand J, et al. Differentiation of lobular versus ductal breast carcinomas between adjuvant and observation groups, respectively, were observed. In the subset of estrogen receptor–positive patients, 5-year DFS probabilities were 83% and 61%, and 10-year DFS probabilities were 66% and 47%, while 5-year OS probabilities were 88% and 74%, and 10-year OS probabilities were 82% and 49% in the adjuvant and observation groups, respectively. Conclusion.—In premenopausal women with operable breast cancer not selected for estrogen receptor status or with estrogen receptor–positive tumors, 5- and 10-year DFS and OS rates are significantly improved following adjuvant oophorectomy and tamoxifen. Love and colleagues made 2 points in their conclusion. First, they stated that ‘‘the survival of adjuvanttreated patients in this trial.supports use of [surgical oophorectomy and tamoxifen] in many circumstances.’’ Probably. However, whereas ovarian function suppression (OFS) by oophorectomy has clear advantages in a resource-poor population, its exact role in the treatment of hormone receptor-positive breast cancer in premenopausal women remains unclear. Adjuvant tamoxifen is now routinely recommended. The benefit of OFS when added to 5 years of tamoxifen is unproven. Previous trials frequently utilized 2 years of tamoxifen.1 The 1 randomized European Cooperative Oncology Group trial addressing the issue in nodenegative breast cancer was under- Breast Diseases: A Year BookÒ Quarterly Vol 19 No 3 2008 by expression microarray analysis. Cancer Res. 2003;63: 7167-7175. powered and did not show a significant benefit.2 Chemotherapy followed by tamoxifen is commonly recommended in high-risk patients, and the advantage of adding OFS to this combination is uncertain. OFS can add significantly to toxicity and should not be added without solid evidence of benefit. The international Suppression of Ovarian Function Trial, which randomly assigns premenopausal women with hormone receptor–positive breast cancer to tamoxifen versus OFS plus tamoxifen versus OFS plus an aromatase inhibitor, remains open to accrual and has the potential to answer the question definitively. The second conclusion Love and colleagues drew was that ‘‘the increase in the hazard function for recurrence between years 5 and 10 supports investigation of intervention and treatment strategies directed to this hazard.’’ Definitely. The risk of recurrence for women with estrogen receptor–positive breast cancer after 5 years of tamoxifen therapy remains substantial. Few data have specifically addressed the issue in premenopausal women. In the study by Love and colleagues, the hazard for recurrence after year 5 appears to increase for women who were treated (despite permanent ovarian function ablation), whereas women not treated appear to have a continued decline in risk. However, the confidence intervals on these estimates are large. Over time, an increasing proportion of the untreated women would naturally undergo menopause, which may have influenced their risk of late relapse. A recent abstract presenting preliminary results of the Adjuvant Tamoxifen, Longer against Shorter (ATLAS) trial suggested that, contrary to previous publication of smaller trials, the recurrence rate was lower among women allocated to continue tamoxifen.3 It would be interesting to see an analysis of outcomes in the premenopausal women from the ATLAS trial. G. F. Fleming, MD P. Francis, MD Quality of life and qualityadjusted survival (Q-TWiST) in patients receiving doseintensive or standard dose chemotherapy for high-risk primary breast cancer Bernhard J, Zahrieh D, Zhang JJ, et al (IBCSG Coordinating Ctr, Bern, Switzerland; IBCSG Statistical Ctr, Dana-Farber Cancer Inst, Boston; Harvard School of Public Health, Boston; et al) Br J Cancer 98:25-33, 2008 Quality of life (QL) is an important consideration when comparing adjuvant therapies for early breast cancer, especially if they differ substantially in toxicity. We evaluated QL and Q-TWiST among patients randomised to adjuvant dose-intensive epirubicin and cyclophosphamide administered with filgrastim and progenitor cell support (DI-EC) or standard-dose anthracycline-based chemotherapy (SD-CT). We estimated the duration of chemotherapy toxicity (TOX), time without disease symptoms and toxicity (TWiST), and time following relapse (REL). Patients scored QL indicators. Mean durations References 1. Cuzick J, on behalf of the LHRHagonists in Early Breast Cancer Group. Use of luteinising-hormonereleasing hormone agonsists as adjuvant treatment in premenopausal patients with hormone-receptorpositive breast cancer: a metaanalysis of individual patient data from randomised adjuvant trials. Lancet. 2007;369:1711-1723. 2. Robert NJ, Wang M, Cella D, et al. Phase III comparison of tamoxifen versus tamoxifen with ovarian for the three transition times were weighted with patient reported utilities to obtain mean Q-TWiST. Patients receiving DI-EC reported worse QL during TOX, especially treatment burden (month 3: P < 0.01), but a faster recovery 3 months following chemotherapy than patients receiving SD-CT, for example, less coping effort (P < 0.01). Average Q-TWiST was 1.8 months longer for patients receiving DI-EC (95% CI, 2.5 to 6.1). Q-TWiST favoured DI-EC for most values of utilities attached to TOX and REL. Despite greater initial toxicity, quality-adjusted survival was similar or better with dose-intensive treatment as compared to standard treatment. Thus, QL considerations should not be prohibitive if future intensive therapies show superior efficacy. On the basis of well-designed randomized controlled trials,1-4 highdose chemotherapy (HDC) with stem cell support has proven to be more toxic and no more efficacious than standard-dose chemotherapy for cases of both high-risk and metastatic breast cancer. This approach of hitting the most serious cases of breast cancer with the most aggressive or intense ablation in premenopausal women with axillary node-negative receptorpositive breast cancer < 3 cm [abstract 16]. Proc Am Soc Clin Oncol. 2003;22:5. 3. Peto R, Davies C, on behalf of the ATLAS Collaboration. ATLAS (Adjuvant Tamoxifen, Longer Against Shorter): international randomized trial of 10 versus 5 years of adjuvant tamoxifen among 11,500 women-preliminary results [abstract 48]. Breast Cancer Res Treat. 2008; 109:585. form of chemotherapy was initially viewed as promising based on the results of single-arm trials demonstrating results that appeared superior to historical outcomes from standard therapy.5 Accrual to randomized trials was difficult due to patients’ and physicians’ preferences, with the majority of patients treated offprotocol or in single-arm studies.6 In this context, 2 recent publications, one by Bernhard and colleagues in the British Journal of Cancer and one by Crump and colleagues1 in the Journal of Clinical Oncology present results that are important both for the clinical information they provide and for their fulfillment of the obligation between researcher and trial participants to analyze and publicize trial results, even when the trial is negative. The article by Crump and colleagues presented the results of a randomized multicenter trial conducted by the National Cancer Institute Clinical Trials Group, in which 386 patients with metastatic breast cancer were treated with induction chemotherapy, and those with a significant response (224) wererandomized to HDC versus standarddose chemotherapy. Although this trial Breast Diseases: A Year BookÒ Quarterly Vol 19 No 3 2008 279