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Journal of Clinical Oncology, Vol 26, No 16 (June 1), 2008: pp. 2636-2643 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.14.9146 Estrogen Receptor Expression and Efficacy of Docetaxel-Containing Adjuvant Chemotherapy in Patients With Node-Positive Breast Cancer: Results From a Pooled Analysis
From the Department of Breast Medical Oncology and the Division of Quantitative Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Breast Cancer Unit, Department of Medical Oncology and Translational Research Unit, UPRES EA03535, Université Paris Sud, Institut Gustave Roussy, Villejuif; Department of Medical Oncology, Institut Claudius Regault, Toulouse; Department of Pathology, Center Claude Perrin, Clermont-Ferrand, France; Department of Oncology, Hospital Universitario San Carlos, Madrid, Spain; and Department of Oncology, University of Alberta, Edmonton, Alberta, Canada Corresponding author: Lajos Pusztai, MD, DPhil, Department of Breast Medical Oncology, Unit 1354, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston TX 77030-1439; e-mail: lpusztai{at}mdanderson.org
Purpose Several adjuvant chemotherapy trials suggested that cytotoxic treatment is less effective in patients with estrogen receptor (ER) –positive breast cancers. The aim of the present study was to assess the efficacy of adjuvant docetaxel and anthracycline therapy according to ER expression in two randomized clinical trials. Patients and Methods Pooled data from two randomized trials, BCIRG001 and PACS01, were examined. Hazard ratios for recurrence and survival were estimated by Cox proportional hazards models and were adjusted for clinical variables. Interaction between docetaxel and ER expression was tested. Results ER status was available for 3,329 patients (95% of all randomly assigned patients), of whom 75% (n = 2,493) were ER positive. Docetaxel therapy was associated with a 30% reduction in the risk of death (hazard ratio [HR] = 0.70; 95% CI, 0.54 to 0.91) in ER-positive patients and a 31% reduction (HR = 0.69; 95% CI, 0.52 to 0.94) in ER-negative patients. Docetaxel therapy was associated with a 21% reduction in the risk of recurrence (HR = 0.79; 95% CI, 0.66 to 0.93) in ER-positive patients and a 31% reduction (HR = 0.69; 95% CI, 0.54 to 0.97) in ER-negative patients. The interaction between docetaxel therapy and ER status was not statistically significant for either overall survival (P = .87) or disease-free survival (P = .30). ER expression was also not predictive for docetaxel efficacy when it was analyzed as a semi-continuous variable based on percent of positive cells by immunohistochemistry (test for heterogeneity, P = .56 and .86 for overall survival and disease-free survival, respectively). Conclusion In the pooled analysis of these two trials, docetaxel did not have a statistically significantly different effect on the risk of recurrence or death in ER-positive and ER-negative patients.
The use of adjuvant chemotherapy improves survival in early-stage breast cancer, and several combination chemotherapy regimens are effective.1 Anthracycline-containing regimens followed, preceded by, or combined with a taxane (docetaxel or paclitaxel) are considered to be the most efficacious adjuvant chemotherapies. However, not all patients benefit equally from all regimens. Subset analysis of several randomized adjuvant chemotherapy trials suggests that patients with estrogen receptor (ER) –positive disease derive less benefit from anthracycline- and paclitaxel-based chemotherapy regimens than do ER-negative cancers.2,3 For example, analysis of the Cancer and Leukemia Group B 9344 trial that evaluated the efficacy of doxorubicin/cyclophosphamide chemotherapy with or without paclitaxel showed that the reduction in the risk of death resulting from inclusion of paclitaxel was 24% (95% CI, 10% to 37%) in the ER-negative compared with 11% (95% CI, –8% to 26%) the ER-positive patients.3 Greater chemotherapy sensitivity of ER-negative cancers relative to ER-positive disease was also observed in several neoadjuvant studies that used mostly anthracycline or anthracycline/paclitaxel combination chemotherapies.4 However, it is also increasingly clear that a subset of patients with ER-positive cancers (eg, high grade, HER-2 amplified) are highly sensitive to chemotherapy and could derive substantial benefit from adjuvant chemotherapy.5,6 Novel molecular diagnostic tests are now available to aid the identification of these individuals.7,8 Two published randomized trials, BCRIG 001 and PACS01, evaluated the inclusion of docetaxel in adjuvant chemotherapy but failed to observe a significant interaction between hormone receptor expression and efficacy of chemotherapy.9,10 This may be due to several reasons. By some unrecognized selection bias, these studies could have accrued a disproportionally high number of individuals with ER-positive, chemotherapy-sensitive tumors as compared with other trials. It may be that docetaxel has higher activity than other drugs in ER-positive disease. It is also important to consider that these studies individually were not powered to assess interaction between hormone receptor status and chemotherapy efficacy and might thereby fail to detect modest interactions. The goal of the current analysis was to examine pooled data from the BCIRG 001 and PACS01 studies to assess interaction between estrogen receptor status and docetaxel efficacy. The current combined analysis provides a large sample size to detect interactions, examines ER status both as a dichotomous (positive v negative) and continuous variable (percent of positive cells on immunohistochemistry [IHC]), and reports overall survival (OS) results in addition to disease-free survival (DFS) as end points.
Patients Data from the BCIRG001 and PACS01 trials were used in this analysis because we could obtain individual patient data from these trials. The previously locked and reported data were used and no update was performed. These two trials evaluated the efficacy of docetaxel in patients with axillary node-positive breast cancer, and primary efficacy results have already been reported.9,10 Data from the BCIRG001 trial were provided by Sanofi-aventis (Paris, France), and data from the PACS01 trial were provided by the French Federation of Cancer Centers (Paris, France). Other docetaxel-containing adjuvant chemotherapy trials have been reported, including the Breast International Group 2-98,11 US Oncology doxorubicin and cyclophosphamide versus doxorubicin and docetaxel trial,12 Eastern Cooperative Oncology Group 2197,13 National Surgical Adjuvant Breast and Bowel Project (NSABP) B27,14 TAXIT216,15 and E1199.16 Individual patient data from these studies were not available to us for analysis.
Hormone Receptor Status Determination In the second part of the analysis, we examined ER expression as a categoric variable based on percent of ER-positive tumor cells assessed by IHC. For this second part of the analysis, the percent of ER-positive cells was determined centrally in both trials. Percent of ER-positive cells could be determined in 1,190 tumors from PACS01 trial (60%) and 1,285 tumors from BCIRG001 trial (85%). Four IHC classes were constructed for this analysis: ER negative (no tumor cell stained), ER weakly positive (0% to 20% ER-positive cells), ER moderately positive (20% to 80% ER-positive cells), and ER strongly positive (> 80% ER-positive cells).
Treatments
Statistical Analysis The primary objective of this study was to assess the effect of docetaxel by ER status. Trials were not stratified based on ER status. OS was measured from the date of random assignment to the date of death from any cause. DFS was measured from the date of random assignment to the date of death, locoregional relapse, or metastatic relapse. Each study was considered individually as well as in combination. The absolute benefit of docetaxel by ER status was determined by the Kaplan-Meier method. Hazard ratios (HRs) for docetaxel treatment for each study overall as well as by ER status were estimated with Cox proportional hazards models that adjusted for age, T stage, and the number of positive lymph nodes. The two studies were then pooled and HRs for docetaxel treatment were estimated with Cox proportional hazards models that included terms for docetaxel, ER status, study, age, T stage, and the number of positive lymph nodes. We tested for an interaction between docetaxel and ER status with the likelihood ratio test. When ER expression was considered as a continuous variable, the test for heterogeneity was used to assess differences between relative risk reductions across ER categories. Analyses were conducted using SAS 9.1 (SAS Institute, Cary, NC) and S-Plus 7.0 (Insightful Corp, Seattle, WA). P values less than .05 were considered statistically significant.
Patient Characteristics Of the 3,490 patients included in the two trials, ER status was available for 3,329 patients (95%). Clinical characteristics of all patients included in this combined analysis are listed in Table 1. The median age was 49 years (range, 23 to 70 years), the median number of involved lymph nodes was three (range, one to 40 nodes), and 2,493 tumors (75%) with known ER status were ER positive. When the two trials were considered separately, ER was expressed in 1,021 (76%) and 1,472 (74%) tumors in the BCIRG001 and PACS01 trials, respectively.
Docetaxel Efficacy The median follow-up duration among patients still alive was 4.6 years (range, 0 to 5.8 years) in the BCRIG001 trial and 5.0 years (range, 0.7 to 7.0 years) in the PACS01 trial. In BCIRG001, the 5-year DFS was 76% (95% CI, 72% to 79%) in patients treated with docetaxel and 68% (95% CI, 65% to 72%) in patients not treated with docetaxel. In PACS01, the 5-year DFS was 77% (95% CI, 75% to 80%) and 71% (95% CI, 68% to 74%) in patients treated or not treated with docetaxel, respectively. The adjusted HRs for recurrence associated with docetaxel were 0.68 (95% CI, 0.55 to 0.84) and 0.80 (95% CI, 0.67 to 0.96) in the BCIRG001 and PACS01 studies, respectively. The 5-year OS rates were 87% (95% CI, 85% to 90%) and 81% (95% CI, 77% to 84%) for patients treated or not treated with docetaxel, respectively, in the BCIRG001 study. In the PACS01 study, 5-year OS was 91% (95% CI, 89% to 93%) and 87% (95% CI, 84% to 89%) in patients treated or not treated with docetaxel, respectively. The adjusted HRs for death associated with docetaxel treatment were 0.65 (95% CI, 0.49 to 0.86) and 0.74 (95% CI, 0.57 to 0.97) in the BCIRG001 and PACS01 studies, respectively.
Docetaxel Efficacy According to ER Status As Reported in the Case Report Forms
The relative and absolute reductions in the risk of death associated with docetaxel therapy according to ER status are listed in Table 3 and Figure 3. When the two studies were pooled, the relative reduction in the risk of death was 31% (HR = 0.69; 95% CI, 0.52 to 0.94) for ER-negative and 30% (HR = 0.70; 95% CI, 0.54 to 0.91) for ER-positive patients (HR for docetaxel/ER interaction = 1.0; 95% CI, 0.7 to 1.54; P = .86). This translated into a 7% and 4% absolute gain in 5-year OS in patients with ER-negative and ER-positive disease, respectively, when docetaxel was included in their adjuvant chemotherapy.
Next, we examined the impact of PR expression on docetaxel efficacy. The HRs for recurrence associated with docetaxel were 0.74 (95% CI, 0.61 to 0.90), 0.90 (95% CI, 0.65 to 1.26), 0.50 (95% CI, 0.21 to 1.14), and 0.69 (95% CI, 0.54 to 0.88) in ER-positive/PR-positive patients (n = 2,013), ER-positive/PR-negative patients (n = 467), ER-negative/PR-positive patients (n = 109), and ER-negative/PR-negative patients (n = 726), respectively. The HRs for death associated with docetaxel were 0.64 (95% CI, 0.47 to 0.88), 0.84 (95% CI, 0.52 to 1.36), 0.76 (95% CI, 0.22 to 2.59), and 0.66 (95% CI, 0.48 to 0.90) for ER-positive/PR-positive, ER-positive/PR-negative, ER-negative/PR-positive, and ER-negative/PR-negative women, respectively. We next evaluated the efficacy of docetaxel therapy according to menopausal and ER status. Sixty-one percent and 39% of women with known menopausal status (n = 3,208) were pre- and postmenopausal, respectively. The HRs for recurrence with docetaxel were 0.80 (95% CI, 0.63 to 1.00), 0.78 (95% CI, 0.59 to 1.03), 0.81 (95% CI, 0.59 to 1.12), and 0.53 (95% CI, 0.36 to 0.78) in ER-positive/premenopausal, ER-positive/postmenopausal, ER-negative/premenopausal, and ER-negative/postmenopausal women, respectively. The HRs for death associated with docetaxel were 0.71 (95% CI, 0.49 to 1.02), 0.73 (95% CI, 0.48 to 1.12), 0.78 (95% CI, 0.52 to 1.19), and 0.62 (95% CI, 0.38 to 1.01) in ER-positive/premenopausal, ER-positive/postmenopausal, ER-negative/premenopausal, and ER-negative/postmenopausal women, respectively. These results show that risk reduction was observed in all ER and menopausal categories. In the present analysis, ER expression was a strong overall prognostic predictor (HR for death = 0.37; 95% CI, 0.29 to 0.48; HR for recurrence = 0.52; 95% CI, 0.43 to 0.63). This indicates that ER-positive patients (most of whom received adjuvant tamoxifen therapy) had a better prognosis than did ER-negative patients.
Docetaxel Efficacy According to the Level of ER Expression
In the pooled analysis of these two studies, there was no statistically significant interaction between docetaxel efficacy and ER status or semi-quantitative ER expression levels measured by IHC. A lesser reduction in the risk of recurrence was observed for ER-positive patients (HR = 0.88) as compared with ER-negative patients in the PACS01 trial (HR = 0.72), but not in the BCIRG001 trial (HR = 0.69 and 0.68 for ER-positive and ER-negative patients, respectively). There was a small numerical difference that favored ER-negative patients for greater reduction in the risk of recurrence provided by docetaxel as compared with patients with ER-positive tumors (Table 2). The chemotherapy sensitivity of various subsets of breast cancer can be directly examined in preoperative studies. The NSABP B27 trial compared pathologic complete response (pCR) rates after four courses of preoperative doxorubicin/cyclophosphamide (AC) or four courses of AC followed by four courses of docetaxel.14,17 Inclusion of docetaxel increased the absolute pCR rates by 9% both in patients with ER-positive (P < .001) and ER-negative disease (P = .0024).17 The pCR rates in the preoperative AC/docetaxel arm were 22% and 14% in the ER-negative and ER-positive patients, respectively. These results support our finding that docetaxel can have similar efficacy against ER-negative and ER-positive cancers. The NSABP B27 study also showed no significant difference in HRs for DFS and OS by inclusion of docetaxel among ER-negative and ER-positive patients.14 In contrast to these observations, results from other adjuvant studies that evaluated anthracyclines or anthracycline plus taxane-containing chemotherapy regimens reported significantly higher benefit from chemotherapy among ER-negative cancers compared with ER-positive tumors.2,3 Several preoperative clinical trials that used paclitaxel and anthracycline combinations showed higher pCR rates in ER-negative cancers compared with ER-positive tumors.18,19 In one study, pCR rates after 6 months of sequential paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide preoperative chemotherapy were 22% and 48% for ER-positive and ER-negative patients, respectively.18 Two other randomized neoadjuvant studies, GEPARTRIO and ABCSG-14, which both used anthracycline and docetaxel combination chemotherapies, also reported significantly higher pCR rates in the ER-negative cancers as compared with ER-positive tumors.20,21 These seemingly contradictory results may be explained by the molecular heterogeneity of ER-positive breast cancer. The proportion of chemotherapy-sensitive patients is higher among ER-negative tumors, but a fraction of ER-positive cancers is also highly sensitive to chemotherapy. This is born out by preoperative studies that consistently report pCRs among the ER-positive tumors that range from 5% to 25%, depending on the treatment and the study population.14,18,22 Novel molecular diagnostic tests including Oncotype DX (Genomic Health Inc, Redwood, CA) can help identify chemotherapy-sensitive cancers among the ER-positive tumors. In one neoadjuvant study that used sequential paclitaxel plus anthracycline chemotherapy, all pCRs occurred in patients with high Oncotype DX recurrence scores.23 Retrospective analysis of samples from the NSABP B20 trial indicated that patients with ER-positive cancers with a high Oncotype DX recurrence score benefited substantially from adjuvant chemotherapy. The absolute risk of distant recurrence at 10 years was reduced by 28% compared with no chemotherapy, whereas no significant benefit from chemotherapy was seen among the low recurrence score group.24 Because of this chemotherapy-sensitive subset, when all ER-positive patients were considered together, the benefit from chemotherapy was modest but remained significant.25 These observations, together with the current study, suggest that survival in adjuvant studies that include both ER-positive and ER-negative patients is determined by a complex interplay between the subtle difference in efficacy of the chemotherapy regimens under study, the proportion of chemotherapy-sensitive tumors among ER-positive patients, the efficacy of adjuvant endocrine therapy, and the baseline risk of recurrence of patients. Under these circumstances, it is not surprising that individual studies may yield conflicting results on the interaction between chemotherapy effects and ER status. Random assignment may balance the distribution of various subtypes of breast cancers in treatment arms, but competing parallel clinical trials may bias the entire accrual process. For example, if patients with HER-2–positive/ER-positive tumors or patients with high-grade/ER-positive tumors are preferentially accrued to another parallel trial, chemotherapy effect may be difficult to detect among the ER-positive tumors because the whole study becomes depleted of chemotherapy-sensitive subpopulations of ER-positive disease.22,26 In such studies, the small effects of a moderately effective chemotherapy regimen may not be readily detectable in the ER-positive population compared with the ER-negative tumors. It is impossible to decipher retrospectively which of these or other possible confounding effects influence the outcome of a particular study. Unfortunately, HER-2, proliferative index, or Oncotype DX results were not available for us for this analysis, and we could not explore what molecular subsets of ER-positive cancers derived the most benefit from docetaxel chemotherapy. In summary, in this pooled retrospective analysis of PACS01 and BCIRG001 studies, docetaxel improved DFS and OS both in ER-negative and ER-positive breast cancer. When the two studies were pooled, the magnitudes of risk reduction by docetaxel were not significantly different according to ER expression. Nevertheless, because ER expression was a strong prognostic parameter, the absolute gains in 5-year DFS and OS were lower in ER-positive as compared with ER-negative disease. The present study could not explore the predictive values of HER-2 amplification, proliferative activity, or Oncotype Dx scores. Our results in the context of the broader literature highlight the need to conduct future adjuvant studies in a more molecularly tailored manner that recognizes the substantial differences in chemotherapy sensitivity among ER-positive cancers.
Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Henri Roche, Sanofi-aventis (C); Miguel Martin, Sanofi-aventis (C); John R. Mackey, Sanofi-aventis (C) Stock Ownership: None Honoraria: Miguel Martin, Sanofi-aventis; John R. Mackey, Sanofi-aventis Research Funding: None Expert Testimony: None Other Remuneration: None
Conception and design: Fabrice Andre, Gabriel N. Hortobagyi, Lajos Pusztai Administrative support: Gabriel N. Hortobagyi Provision of study materials or patients: Henri Roche, Miguel Martin, John R. Mackey, Frederique Penault-Llorca Collection and assembly of data: Kristine Broglio, Henri Roche, Miguel Martin, John R. Mackey, Frederique Penault-Llorca Data analysis and interpretation: Fabrice Andre, Kristine Broglio, Henri Roche, Miguel Martin, John R. Mackey, Frederique Penault-Llorca, Gabriel N. Hortobagyi, Lajos Pusztai Manuscript writing: Fabrice Andre, Lajos Pusztai Final approval of manuscript: Fabrice Andre, Kristine Broglio, Henri Roche, Miguel Martin, John R. Mackey, Frederique Penault-Llorca, Gabriel N. Hortobagyi, Lajos Pusztai
We thank Jean-Pierre Bizzari, MD, Toufik Bendahmane, and Sanofi-aventis staff.
F.A. was supported by a Career Development Award from American Society of Clinical Oncology and fellowship from Ligue Nationale contre le cancer, Lilly Foundation. Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
1. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG): Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: An overview of the randomised trials. Lancet 365:1687-1717, 2005[CrossRef][Medline] 2. Conforti R, Boulet T, Tomasic G, et al: Breast cancer molecular subclassification and estrogen receptor expression to predict efficacy of adjuvant anthracyclines-based chemotherapy: A biomarker study from two randomized trials. Ann Oncol 18:1477-1483, 2007 3. Berry DA, Cirrincione C, Henderson IC, et al: Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA 295:1658-1667, 2006 4. Rouzier R, Pusztai L, Delaloge S, et al: Nomograms to predict pathologic complete response and metastasis-free survival after preoperative chemotherapy for breast cancer. J Clin Oncol 23:8331-8339, 2005 5. Albain K, Barlow W, O'Malley F, et al: Concurrent versus sequential chemohormonal therapy versus T alone for postmenopausal, node-positive, estrogen and/or progesterone receptor-positive breast cancer: Mature outcomes and new biologic correlates on phase III intergroup trial 0100. San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-11, 2004 (abstr 37) 6. Hayes DF, Thor AD, Dressler LG, et al: HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med 357:1496-1506, 2007 7. Paik S, Shak S, Tang G, et al: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351:2817-2826, 2004 8. Symmans WF, Hatzis C, Sotiriou C, et al: Ability of a 200-gene endocrine sensitivity index (SET) to predict survival for patients who receive adjuvant endocrine therapy or for untreated patients. San Antonio Breast Cancer Symposium, San Antonio, TX, 2007 (abstr 25) 9. Martin M, Pienkowski T, Mackey J, et al: Breast Cancer International Research Group 001 Investigators: Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 352:2302-2313, 2005 10. Roché H, Fumoleau P, Spielmann M, et al: Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: The FNCLCC PACS 01 Trial. J Clin Oncol 24:5664-5671, 2006 11. Crown JP, Francis P, Di Leo A, et al: Docetaxel (T) given concurrently with or sequentially to anthracycline-based (A) adjuvant therapy (adjRx) for patients (pts) with node positive (N+) breast cancer (BrCa), in comparison with non-T adjRx: First results of the BIG 2-98 Trial at 5 years median follow-up (MFU). J Clin Oncol 24:7s, 2006 (suppl, abstr LBA519) 12. Jones SE, Savin MA, Holmes FA, et al: Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 24:5381-5387, 2006 13. Goldstein L, O'Neill A, Sparano J, et al: E2197: Phase III AT (doxorubicin/docetaxel) vs. AC (doxorubicin/cyclophosphamide) in the adjuvant treatment of node positive and high risk node negative breast cancer. J Clin Oncol 23:7s, 2005 (suppl, abstr 512) 14. Bear HD, Anderson S, Smith RE, et al: Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 24:2019-2027, 2006 15. Bianco AR, De Matteis A, Manzione L, et al: Sequential epirubicin-docetaxel-CMF as adjuvant therapy of early breast cancer: Results of the Taxit216 multicenter phase III trial. J Clin Oncol 24:8s, 2006 (suppl, abstr LBA520)[CrossRef] 16. Sparano JA, Wang M, Martino S: Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in operable breast cancer: Results of Intergroup Trial E1199. J Clin Oncol 25:6s, 2007 (suppl, abstr 516)[CrossRef] 17. Bear HD, Anderson S, Brown A, et al: National Surgical Adjuvant Breast and Bowel Project Protocol B-27: The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide—Preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 21:4165-4174, 2003 18. Green MC, Buzdar AU, Smith T, et al: Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel once every 3 weeks. J Clin Oncol 23:5983-5992, 2005 19. Mazouni C, Kau SW, Frye D, et al: Inclusion of taxanes, particularly weekly paclitaxel, in preoperative chemotherapy improves pathologic complete response rate in estrogen receptor-positive breast cancers. Ann Oncol 18:874-880, 2007 20. von Minckwitz G, Blohmer JU, Raab G, et al: German Breast Group: In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer—The GEPARTRIO pilot study. Ann Oncol 16:56-63, 2005 21. Steger GG, Galid A, Gnant M, et al: Pathologic complete response with six compared with three cycles of neoadjuvant epirubicin plus docetaxel and granulocyte colony-stimulating factor in operable breast cancer: Results of ABCSG-14. J Clin Oncol 25:2012-2018, 2007 22. Andre F, Mazouni C, Liedtke C, et al: HER2 expression and efficacy of preoperative paclitaxel/FAC chemotherapy in breast cancer. Breast Cancer Res Treat 108:183-190, 2008[CrossRef][Medline] 23. Gianni L, Zambetti M, Clark K, et al: Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol 23:7265-7277, 2005 24. Paik S, Tang G, Shak S, et al: Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 24:3726-3734, 2006 25. Fisher B, Dignam J, Wolmark N, et al: Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst 89:1673-1682, 1997 26. Burstein HJ, Winer EP: HER2 or not HER2: That is the question. J Clin Oncol 23:3656-3659, 2005 Submitted October 27, 2007; accepted February 25, 2008.
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
