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Colleoni M.,Italian National Cancer Institute | Colleoni M.,International Breast Cancer Study Group | Munzone E.,Italian National Cancer Institute

Endocrine treatments are key component of the adjuvant strategy for pre-menopausal patients with luminal tumors. Treatment options should be based not only upon the risk of relapse and level of endocrine responsiveness, but also on co-morbidities, preferences of the patient and degree of side effects. Tamoxifen should still be considered as an appropriate endocrine therapy in a large group of premenopausal patients (e.g. lower risk patient, presence of co-morbidities, patient preference). However, the results of the SOFT and TEXT trials, evaluating the value of ovarian function suppression (OFS) as well as the role of adjuvant aromatase inhibitor (AI), raised questions about the use of tamoxifen alone in selected higher risk patient. In the SOFT study, premenopausal patients did not benefit from the addition of OFS, but for those women at sufficient risk of recurrence to deserve adjuvant chemotherapy and who maintained pre-menopausal estradiol, the addition of OFS to tamoxifen reduced the risk of recurrence. Moreover, in the TEXT trial, adjuvant treatment with exemestane plus OFS, as compared with tamoxifen plus OFS, significantly improved disease-free survival, breast cancer-free interval and distant disease-free survival, thus representing a new treatment option. Recent available information on endocrine options for younger patients with luminal tumors support the use of tailored endocrine treatments. Issues specific for younger patients related to pregnancies desire, family planning, safety, quality of life and subjective side effects should be a priority in the therapeutic algorithm. © 2015 Elsevier Ltd. Source

Lee C.K.,University of Sydney | Stockler M.R.,University of Sydney | Stockler M.R.,Sydney Cancer Center | Coates A.S.,University of Sydney | And 5 more authors.
British Journal of Cancer

Background:Baseline health-related quality of life (QL) is associated with survival in advanced breast cancer. We sought to identify patients who were less likely to respond to chemotherapy and at greater risk of toxicity on the basis of their QL.Methods:We used data from three advanced breast cancer trials in which patients (n378) were treated with cyclophosphamide, methotrexate and 5-fluouracil. Patients self-rated their QL using LASA scales for physical well-being (PWB), mood, pain, nausea/vomiting, appetite and overall QL. Multivariable regression models were constructed to compare overall survival (OS), objective tumour response (OTR), adverse events (AEs) and weight loss according to grouped QL scores.Results:Physical well-being, mood, appetite and overall QL were significant univariable predictors of OS. Physical well-being and appetite remained significant after adjustment for baseline biomedical factors. Poor PWB was associated with lower OTR (odds ratio (OR)0.21, 95% confidence interval (CI) 0.09-0.51), higher risk of non-haematological AEs (OR3.26, 95% CI 1.49-7.15) and greater risk of weight loss (OR 2.37, 95% CI 1.12-5.01) compared with good PWB.Conclusion:In women with advanced breast cancer, PWB and appetite are predictors of chemotherapy response and toxicity as well as survival. Quality of life should be a routine clinical assessment to guide patient selection for chemotherapy and for stratification of patients in clinical trials. © 2010 Cancer Research UK All rights reserved. Source

Lee C.K.,University of Sydney | Lord S.J.,University of Sydney | Stockler M.R.,Sydney Cancer Center Royal Prince Alfred and Concord Hospitals | Coates A.S.,International Breast Cancer Study Group | And 2 more authors.
European Journal of Cancer

Purpose: Randomised controlled trials (RCTs) provide optimal evidence to assess the benefits of new treatments. However, clinicians routinely rely on cross-trial comparisons to assess competing treatments when head-to-head randomised comparisons are unavailable. We investigate the validity of cross-trial comparisons using individual patient data (IPD) where patients received the same treatment protocol. We also examine the extent to which statistical adjustment for baseline characteristics can account for inter-trial differences in outcomes. Patients and methods: We used pooled IPD of 378 women with advanced breast cancer assigned to oral cyclophosphamide, intravenous methotrexate and 5-fluorouracil (CMF) in the control arms of three first-line treatment RCTs (ANZ8101, ANZ8614 and ANZ0001) conducted between 1982 and 2001. The Kaplan-Meier method was used to compare progression-free survival (PFS) and overall survival (OS) across trials. Proportional hazard models were constructed to estimate the hazard rates across trials after adjustment for baseline characteristics. Results: The distribution of baseline characteristics varied across trials. There was a statistically significant difference in survival among women treated with CMF in these trials (logrank p = 0.009). The median OS were 17.7, 10.3 and 10.1 months for 0001, 8101 and 8614, respectively. The hazard ratios for survival, adjusted for baseline characteristics differences, were 1.44 (8614) and 1.45 (8101) compared to 0001 (p = 0.03). PFS did not differ across trials (logrank p = 0.38). Conclusions: Caution should be exercised when interpreting results from historical cross-trial comparisons even if the adjustment of baseline prognostic characteristics can be performed. Cross-trial comparisons have some role in hypothesis-generating, identifying and prioritising promising treatments for further investigation; however RCTs are still essential to guide sound clinical practice. © 2009 Elsevier Ltd. All rights reserved. Source

Castellano I.,University of Turin | Allia E.,University of Turin | Accortanzo V.,SantAnna Hospital | Vandone A.M.,Centro Oncologico Subalpino COES | And 9 more authors.
Breast Cancer Research and Treatment

The purpose of this article is to evaluate the prognostic value of androgen receptor (AR) expression in patients with estrogen receptor (ER)-positive breast cancer, treated with endocrine therapy, with or without the addition of chemotherapy. A consecutive series of 953 patients with ER-positive breast cancer, treated between 1998 and 2003, was selected. Repeated immunohistochemistry confirmed the expression of ER in the tumor of 938 patients. AR expression was measured by immunohistochemistry. The Kaplan-Meier method, logrank test and multivariate Cox models were used to explore the impact of AR expression on time to relapse (TTR) and disease specific survival (DSS) in all patients and in subgroups treated with chemo-endocrine therapy or endocrine therapy alone. AR immunoreactivity was assessable in 859 tumors and positive in 609 (70.9%). AR expression was a significant marker of good prognosis for TTR (P = 0.001) and DSS (P < 0.001). This effect was particularly evident in the group of patients receiving chemo-endocrine therapy (TTR (P = 0.015) and DSS (P < 0.001)). Cox models confirmed AR as an independent variable for both TTR (P = 0.003, HR 0.444, 95%CI 0.258-0.765) and DSS (P < 0.001, HR 0.135, 95%CI 0.054-0.337). Thus, we focused on ER-positive luminal B breast cancer that may be selected for chemotherapy because of their more aggressive immunophenotype. In this subset AR expression identified a group of patients with better prognosis for TTR (P = 0.017, HR 0.521, 95%CI 0.306-0.888) and DSS (P = 0.001, HR 0.276, 95% CI 0.130-0.588). AR expression is an independent prognostic factor of better outcome in patients with ER-positive breast cancers. © 2010 Springer Science+Business Media, LLC. Source

Pruneri G.,Italian National Cancer Institute | Pruneri G.,University of Milan | Vingiani A.,Italian National Cancer Institute | Vingiani A.,University of Milan | And 10 more authors.
Annals of Oncology

Background: Although tumor-infiltrating lymphocytes (TILs) have been associated with a favorable prognosis in triplenegative breast cancer (TNBC) patients, this marker is not currently considered robust enough for entering the clinical practice. In the present study, we assessed the clinical validity of the guidelines recently issued by the International TIL Working Group in a large retrospective series of well-annotated TNBC patients. Patients and methods: TILs were evaluated in all the full-face H & E sections from 897 consecutive TNBC (i.e. tumors with >1% of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification) patients diagnosed and treated at the European Institute of Oncology between 1995 and 2010 (median follow-up 8.2 years, range 6 months to 18 years). All mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor, reported as a percentage value and treated as a continuous variable in survival analysis. Results: The median percentage of TILs was 20%, and 21.9% of the cases had =50% (lymphocyte predominant breast cancer, LPBC) TILs. At univariable survival analysis, TILs were a significant predictor of better disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) (P < 0.0001). Multivariable analysis confirmed that each 10% increase in TILs strongly predicted better survival, independent of patients' age, lymph node status, tumor size, histological grade, peritumoral vascular invasion and Ki-67 labeling index. Patients with LPBC had a 10-year survival rate of 71%, 84% and 96% for DFS, DDFS and OS, respectively. Stratified analysis revealed a positive correlation between TILs and OS across all the subgroups analyzed. Conclusion: Our data support the analytical validity of the recently issued TILs evaluation guidelines in the clinical practice. © The Author 2015. Source

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