|
Advertisement |
|
|
||
 |
|
|||||
|
|||||
|
 |
||||||
|
||||||
|
||||||
|
Journal of Clinical Oncology, Vol 23, No 36 (December 20), 2005: pp. 9304-9311 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.02.5023 Outcome After Pathologic Complete Eradication of Cytologically Proven Breast Cancer Axillary Node Metastases Following Primary ChemotherapyFrom the Department of Breast Medical Oncology, Department of Surgical Oncology, Department of Pathology, Department of Diagnostic Radiology, and Department of Biostatistics at The University of Texas M.D. Anderson Cancer Center, Houston, TX. Address reprint requests to Bryan Hennessy, MD, Department of Breast Medical Oncology, Unit 424, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: bhennessy{at}mdanderson.org
PURPOSE: Pathologic complete remission (pCR) of primary breast tumors after primary chemotherapy (PCT) is associated with higher relapse-free survival (RFS) and overall survival (OS) rates. The purpose of this study was to determine long-term outcome in patients achieving pCR of cytologically proven axillary lymph node (ALN) metastases. METHODS: Patients with cytologically documented ALN metastases were treated in five prospective PCT trials. After surgery, patients were subdivided into those with and without residual ALN carcinoma. Survival was calculated by the Kaplan-Meier method. RESULTS: Of 925 patients treated, 403 patients had cytologically confirmed ALN metastases. Eighty-nine patients (22%) achieved ALN pCR after PCT. Compared with the group without ALN pCR, 5-year OS and RFS were improved in patients achieving ALN pCR (93% [95% CI, 87.5 to 98.5] and 87% [95% CI, 79.7 to 94.3] v 72% [95% CI, 66.5 to 77.5] and 60% [95% CI, 54.1 to 65.9], respectively; P < .0001). Residual primary tumor did not affect outcome of those with ALN pCR. Combination anthracycline/taxane-based PCT resulted in significantly more ALN pCRs, although outcome after ALN pCR was not improved by taxanes. We constructed a nomogram demonstrating that patients who do not benefit from neoadjuvant anthracyclines are unlikely to benefit from subsequent taxanes. CONCLUSION: ALN pCR is associated with an excellent prognosis, even with a residual primary tumor, pointing to biologic differences between primary and metastatic cells. ALN pCR represents an early surrogate marker of long-term outcome. Response to initial PCT has important potential as a guide to subsequent therapy.
Cancer cells are characterized by aberrant proliferation, prolonged survival, and capacity to invade/metastasize. Axillary lymph node (ALN) metastases is the most important prognostic factor in breast cancer. Pathologic complete response (pCR) of axillary metastases may thus affect the long-term course of high-risk breast cancer and provide an early surrogate marker of relapse-free survival (RFS) and overall survival (OS). Primary or neoadjuvant systemic chemotherapy is the standard treatment for patients with locally advanced breast cancer and large, operable breast cancer, who desire breast-conserving surgery; it is also being assessed in patients with earlier-stage disease, and other types of cancer.1-12 The long-term outcome in patients with pCR of cytologically confirmed ALN metastases after primary chemotherapy is unknown. Randomized studies, including the National Surgical Adjuvant Breast and Bowel Project (NSABP) B18 trial, have not shown a survival advantage for patients with operable breast cancer treated with primary compared with postoperative chemotherapy. Nevertheless, patients with pCR of the breast primary have a significantly better outcome than do those with residual disease.11-13 Primary chemotherapy has several advantages over adjuvant chemotherapy.12 From a purely theoretical standpoint, studies of outcome in patients who receive primary chemotherapy allow an accurate assessment of the response of the tumor to chemotherapy in individual patients. In addition to pCR, the number of postchemotherapy metastatic ALNs is prognostic.14-16 ALN metastases are a good biologic model for studying how metastases respond to primary chemotherapy and for studying phenotypic differences in nodal cells associated with increased propensity for distant metastases. Our group has, as far as we know, the largest number of patients with stages II and III breast cancer and cytologically proven ALN metastases before primary systemic chemotherapy.17 In the current study, we determined the long-term outcome of these patients.
Between 1989 and 2001, 925 patients with stages II/III breast cancer (2002 American Joint Committee on Cancer classification18) were treated in five prospective institutional review board-approved trials of anthracycline- or anthracycline/taxane-based primary chemotherapy. Patients gave written informed consent and were registered prospectively. Of the 925 patients, 632 patients had a clinically suspicious axilla; after needle sampling, 403 patients had cytologically documented ALN metastases. Patients were examined by a multidisciplinary team to assess the clinical stage of disease at presentation and response after four chemotherapy cycles. Staging included history and physical examination, CBC, blood chemistries, electrocardiography, chest radiology, abdominal computed tomography or ultrasonography, bone scan, bilateral mammography, and breast/regional lymph node ultrasonography. Patients were entered, prospectively, into the protocol database and data added with follow-up. Complete medical records of all patients were available for review at the time of this analysis. Details of the five primary chemotherapy protocols are presented in Table 1. Most patients underwent a subsequent segmental mastectomy with ALN dissection (n = 116) or a modified radical mastectomy (n = 253). Four patients underwent a sentinel lymph node biopsy. Ten patients had axillary dissection alone, because negative margins had been found at prior primary tumor excision (n = 3) or because no primary tumor was detectable at diagnosis (n = 7). Patients with progressive disease after primary chemotherapy (n = 20) received preoperative radiation treatment (50 to 60 Gy) followed by modified radical mastectomy.
The ALN dissection specimens were assessed completely to identify all lymph nodes. Lymph nodes that appeared to show no residual carcinoma were submitted in toto for histologic evaluation. The blocks were processed by routine methods and only one representative hematoxylin- and eosin-stained section obtained. Immunohistochemistry for keratin was performed when suspicious cells were identified. A histologic response was considered a pCR when there was no evidence of residual tumor in the ALNs. Breast pCR was defined as absence of invasive disease in the breast, but ductal/lobular carcinoma-in-situ was allowed. Immunohistochemistry for estrogen (ER) and progesterone receptor was performed with the avidin-biotin peroxidase complex method using 6F11 and 1A6 antibodies (Novocastra Laboratories Ltd, Newcastle upon Tyne, United Kingdom), respectively.19 Postoperative radiotherapy was delivered to the chest wall, internal mammary, and supraclavicular/high ALNs. Locoregional radiotherapy was instituted within 6 weeks of chemotherapy completion. Tamoxifen was started after chemotherapy in those with hormone receptor-positive tumors.
Data were analyzed with Splus 6.1 (Insightful Corp, Seattle, WA) and SAS 8 (SAS, Cary, NC). OS was calculated from the date of diagnosis and RFS from the chemotherapy start date by the Kaplan-Meier method.20 The log-rank statistic was used for univariate comparisons of survival end points.21 All comparisons were two-tailed. Cox proportional hazards models were fit for OS and RFS and included variables identified a priori as being associated with survival or ALN status. Other variables not identified a priori were entered into the model one at a time and assessed for statistical significance. All pair-wise interactions were tested. The fit of the model and the proportional hazards assumption were assessed visually with residual plots. The relationship between ER status and tumor response and the relationship between residual positive ALNs and tumor response were assessed with The logistic regression model was used to construct a nomogram to predict individual patient probability of axillary conversion. Continuous variables were fit for age, ER status, grade, chemotherapy regimen, and T stage using restricted cubic splines to relax the linearity assumptions. The nomogram was internally validated by bootstrapping with 200 resamples as a means of calculating a relatively unbiased measure of its ability to discriminate between patients as quantified by the area under the receiver operator characteristic curve. Subsequently, the predicted probability of axillary conversion was compared with the actual achievement of axillary conversion, again using 200 bootstrap resamples to decrease overfit bias.
Table 2 presents initial patient and tumor characteristics of 403 patients with cytologically documented ALN metastases. Twenty-two percent of these patients (n = 89) had an axillary pCR after primary chemotherapy. The patient group that achieved ALN pCR more often had ER-negative and high-grade tumors. Sixty-one patients (69%) with ALN pCR also achieved a primary tumor pCR. In the group with residual ALN disease after chemotherapy, there were only 14 patients (4%) who had a primary tumor pCR.
The outcome of those patients who achieved ALN pCR with primary chemotherapy was compared with that of the patient group with residual disease in the ALNs. Median follow-up was 64 months (range, 15 to 178 months). The 5-year OS and RFS rates were significantly better in patients with axillary pCR (93% [95% CI, 87.5 to 98.5] and 87% [95% CI, 79.7 to 94.3] v 72% [95% CI, 66.5 to 77.5] and 60% [95% CI, 54.1 to 65.9], respectively; P < .0001; Fig 1A and 1B; Table 3). In terms of only locoregional recurrences, there were four events (4%) among patients with axillary pCR compared with 28 events (9%; P = .17) in the other group. In patients with residual axillary metastases, the 5-year OS rates in those with one to three (n = 166), four to nine (n = 112), and 10 or more (n = 36) positive ALNs were 74% (95% CI, 66.4 to 81.6), 74% (95% CI, 65.4 to 82.6), and 56% (95% CI, 38.2 to 73.8), respectively (P = .09). The corresponding 5-year RFS rates were 68% (95% CI, 60.2 to 75.8), 56% (95% CI, 46.4 to 65.6), and 43% (95% CI, 26.5 to 59.5; P = .02).
Influence of Hormone Receptor Status on pCR Rates and Outcome Thirty-one percent of those with ER-negative tumors (28% in those aged younger than 50 years and 35% in older patients) and 12% of those with ER-positive tumors (11% in those aged younger than 50 years and 12% in older patients) achieved an ALN pCR (P < .001). In those achieving ALN pCR, ER status was not associated with a survival difference. However, in patients with residual ALN carcinoma, those with ER-positive tumors had significantly better 5-year OS (84% [95% CI, 77.7 to 90.3] v 53% [95% CI, 42.8 to 63.2]; P < .001) and RFS rates (68% [95% CI, 60.5 to 75.5] v 46% [95% CI, 36 to 56]; P < .001).
Residual Disease in the Breast
Taxanes We grouped together those patients from the five clinical protocols treated with primary anthracyclines only (protocols 1 to 3; n = 226) and those given anthracycline/taxane-based primary chemotherapy (protocols 4 to 5; n = 144). Patients treated on protocols 1 to 3 did not receive taxanes after surgery. The remaining 33 patients were treated on protocol 3 with primary paclitaxel only and were excluded from this comparison. Forty-four patients (19%) and 42 patients (29%) treated with primary anthracycline-based or anthracycline/taxane-based therapy achieved ALN pCR, respectively (P = .03). The increase in pCR rate was probably because of the addition of a taxane, although patients in protocol 5 had eight cycles of primary chemotherapy. Although those patients achieving ALN pCR with anthracycline-based chemotherapy had more stage III tumors at diagnosis (34 v 14), 5-year RFS and OS rates were not significantly different between the two groups (Fig 2A and 2B). The benefit of primary chemotherapy may, thus, be related to pCR achievement rather than to the specific drugs per se. However, it should be noted that patient numbers are small and that this analysis is not powered to detect small differences. Interpretation is further limited by the imbalance in the number of primary chemotherapy cycles administered to the two groups.
Patients With Residual ALN Metastases Among all 314 patients with residual ALN disease at surgery after primary chemotherapy, therapy effect (defined as areas of necrosis, fibrosis, hyalinization, vacuolization, and/or cystic degeneration noted by the pathologist within the tumor) was present within the residual tumors of 42% of these patients and was associated with improved 5-year RFS (68.9% [95% CI 60.9 to 78.1] v 54.1% [95% CI 46.9 to 62.5]; P = .025) and OS rates (79.4% [95% CI 72.2 to 87.4] v 66.7% [95% CI 59.5 to 74.8]; P = .05). The location of therapy effect (breast and/or lymph nodes) did not further stratify patients. Therapy effect was more commonly seen in patients with only one metastatic ALN (54% v 39%; P = .03); surprisingly, ER status was not associated with therapy effect. When the size of the largest residual nodal metastatic deposit was categorized as  0.1 cm, 0.1 to 1 cm, and more than 1 cm, we found no trend toward lower OS or RFS rates with increasing size. This was also true when the analysis was confined to 68 patients with one involved ALN.
Multivariable Analysis
Nomogram
Primary systemic chemotherapy completely clears cytologically confirmed ALN metastases in 22% of patients with stages II/III breast cancer. Our data exclude patients with clinically suspicious axillary findings in whom cytology was negative or nondiagnostic. The rate of ALN negativity after primary chemotherapy in patients with clinically suspicious ALNs varies from 25% to 38%.11,14,22 Significantly more patients achieved ALN pCR when taxanes were used in addition to anthracyclines, consistent with the NSABP B27 study.23 In this study, the absolute difference in the proportion of patients with negative nodes after anthracycline-based and anthracycline/taxane-based primary chemotherapy was 8% (50% v 58%). However, in neither of the NSABP studies were clinically suspicious ALNs cytologically sampled before treatment. As in NSABP B18, in those with residual ALN carcinoma after primary chemotherapy, we found that the size of persistent ALN deposits is not associated with outcome. ALN pCR is associated with an excellent prognosis despite an excess of aggressive features (ie, high-grade and ER-negativity) in these tumors. Earlier studies have established that pCR occurs more frequently in these tumors.11,13,24 However, some groups have elected to define pCR as no residual disease in the breast only (eg, NSABP).11,23 Our data suggest not only that the axillary content must be considered in the evaluation of prognosis, but also that it is the dominant determinant of prognosis after primary chemotherapy, in agreement with the results of a smaller French study.25 Primary tumor pCR has prognostic importance possibly because most such patients also achieve ALN pCR. Although the number of patients at risk at 10 years was low in those with residual ALN disease in our study, it seems that these patients continue to suffer relapse after 5 years. However, no patients who achieved ALN pCR suffered relapse after 5 years. Thus, if this is confirmed, ALN pCR has potential to become an early surrogate marker for long-term outcome. Currently, it takes many years and large trials to determine the benefit of experimental adjuvant agents. We recommend that if early surrogate markers of outcome are examined after primary chemotherapy, they should include ALN pCR; using pCR in the breast only is inadequate as an early surrogate marker. Because 22% of patients achieve ALN pCR after primary chemotherapy, axillary dissection, currently the standard approach, might not be necessary in certain patients with ALN-positive breast cancer treated with primary chemotherapy. Sentinel lymph node biopsy may be an alternative in patients with a clinically negative axilla after primary chemotherapy.26-29 We and others are prospectively assessing sentinel lymph node biopsy in patients with ALN-positive breast cancer treated in current primary chemotherapy protocols. Our results suggest that the presence of residual disease in the breast in those achieving ALN pCR does not result in an inferior outcome, perhaps because residual tumor cells in the breast do not have metastatic capability. Further, genetic changes in primary tumor cells, leading to acquisition of a metastatic phenotype, may be associated with changed chemotherapy sensitivity. In addition, because we observed, albeit in a small number of patients, that those achieving ALN pCR with anthracycline-based treatment did just as well as patients achieving ALN pCR with anthracycline/taxane-based therapy, it is possible that as many as 19% of patients with ALN-positive breast cancer are overtreated by adding a taxane (this is the proportion of patients achieving ALN pCR with anthracyclines alone); NSABP B27 provides support for this observation.30 Thus, it may be possible to spare patients unnecessary chemotherapy (taxanes) by determining those who will achieve pCR with initial anthracyclines; although, this is certainly not feasible at present. Gene- and protein-based novel technologies may assist us in this regard. An alternative approach may be to determine which patients with a complete clinical ALN response after primary anthracycline-based treatment have a pCR. Currently, axillary ultrasonography, contrast enhanced magnetic resonance imaging, and positron emission tomography are potentially interesting in this regard.31-33 It is also clear from our data, NSABP B27, and the Scottish neoadjuvant trial that patients not benefiting from primary anthracyclines are unlikely to benefit from subsequent taxanes.34 With new technologies such as gene and protein array, we may explain the behavior of these tumors and identify new potential therapeutic targets.35-38 In patients with breast cancer treated with adjuvant chemotherapy, relative risk reductions for breast cancer subtypes defined by age and ER-status are relatively stable for patients with differing T and N stages of disease.39 Our ALN pCR rates are similar to these relative risk reductions, except in patients aged younger than 50 years with ER-positive tumors in whom ALN pCR rates underrepresent chemotherapy benefit as they do not take into account ovarian function effects. Admittedly, this may be coincidental. However, we believe that it is important. Relative risk reduction equates to the proportion of patients destined to relapse in the absence of a therapy, who benefit from the addition of the therapy. The similarity between the relative risk reductions and pCR rates suggests that chemotherapy has similar activity in terms of pCR rates against breast tumors for which surgery alone will be curative and against those breast tumors that are destined to relapse with surgery alone. Thus, the absolute proportion of patients who benefit from adjuvant chemotherapy reflects not the proportion who would have achieved a pCR with primary chemotherapy but only that proportion of patients who would have relapsed without chemotherapy. This would explain why pCR rates do not equate to absolute risk reductions; some patients achieving pCR with primary chemotherapy are not destined to relapse, if treated with only surgery. For example, in NSABP B27, to predict the absolute increment in RFS rates with primary docetaxel, it may be approximated by 13%, the increase in the pCR rate with docetaxel, of 33%, the approximate proportion of patients who relapse, if treated with surgery and anthracyclines alone. Although taxanes increase pCR rates by 13%, we suggest that this may behave more like a relative than an absolute risk reduction, according to our theory that adding docetaxel will result in pCR in 13% of the 67% of patients destined to be cured with surgery/anthracyclines alone, who, thus, do not benefit, and 13% of the 33% of patients destined to relapse with only surgery/anthracyclines, who, thus, do benefit. Because the absolute benefit is small, a sufficiently large number of patients is required to demonstrate benefit with taxanes. In summary, ALN pCR is an excellent prognostic factor, even with residual breast disease. ALN pCR after primary therapy has potential to become an early surrogate marker of long-term benefit with experimental adjuvant treatments. Further, the use of conventional primary chemotherapy may allow us to determine the biologic features that predict if particular patients will benefit from standard adjuvant chemotherapy. Our study, along other neoadjuvant trials, suggests that we should begin to look at the response to the initial primary therapy regimen as having potential as a guide to subsequent therapy.
The authors indicated no potential conflicts of interest.
Authors' disclosures of potential conflicts of interest are found at the end of this article.
1. Bacci G, Picci P, Ferrari S, et al: Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities: Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin. Cancer 72:3227-3238, 1993[CrossRef][Medline] 2. Spaulding MB, Fischer SG, Wolf GT: Tumor response, toxicity, and survival after neoadjuvant organ-preserving chemotherapy for advanced laryngeal carcinoma. J Clin Oncol 12:1592-1599, 1994 3. Sugarbaker DJ, Herndon J, Kohman LJ, et al: Results of cancer and leukemia group B protocol 8935: A multiinstitutional phase II trimodality trial for stage IIIA (N2) non-small-cell lung cancer—Cancer and Leukemia Group B Thoracic Surgery Group. J Thorac Cardiovasc Surg 109:473-483, 1995 4. Jablonka S, Furmanik F, Jablonka A, et al: Principles of induction chemotherapy for non-small cell lung cancer. Lung Cancer 34:S151-S153, 2001 (suppl 2)[CrossRef][Medline] 5. Herr HW, Bajorin DF, Scher HI: Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer: Ten-year outcome. J Clin Oncol 16:1298-1301, 1998 6. Swisher SG, Holmes EC, Hunt KK, et al: The role of neoadjuvant therapy in surgically resectable esophageal cancer. Arch Surg 131:819-824, 1996 7. Delena M, Zucali R, Viganotti G, et al: Combined chemotherapy–radiotherapy approach in locally advanced (T3b-T4) breast cancer. Cancer Chemother Pharmacol 1:53-59, 1978[Medline] 8. Hortobagyi GN, Blumenschein GR, Spanos W, et al: Multimodal treatment of locoregionally advanced breast cancer. Cancer 51:763-768, 1983[CrossRef][Medline] 9. Lippman ME, Sorace RA, Bagley CS, et al: Treatment of locally advanced breast cancer using primary induction chemotherapy with hormonal synchronization followed by radiation therapy with or without debulking surgery. NCI Monogr 156-159, 1986 10. Scholl SM, Fourquet A, Asselain B, et al: Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: Preliminary results of a randomised trial: S6. Eur J Cancer 30A:645-652, 1994[CrossRef] 11. Fisher B, Bryant J, Wolmark N, et al: Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16:2672-2685, 1998[Abstract] 12. Mamounas EP: Overview of National Surgical Adjuvant Breast Project neoadjuvant chemotherapy studies. Semin Oncol 25:31-35, 1998[Medline] 13. Kuerer HM, Newman LA, Smith TL, et al: Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 17:460-469, 1999 14. McCready DR, Hortobagyi GN, Kau SW, et al: The prognostic significance of lymph node metastases after preoperative chemotherapy for locally advanced breast cancer. Arch Surg 124:21-25, 1989 15. Botti C, Vici P, Lopez M, et al: Prognostic value of lymph node metastases after neoadjuvant chemotherapy for large-sized operable carcinoma of the breast. J Am Coll Surg 181:202-208, 1995[Medline] 16. Kuerer HM, Newman LA, Buzdar AU, et al: Residual metastatic ALNs following neoadjuvant chemotherapy predicts disease-free survival in locally advanced breast cancer patients. Am J Surg 176:502-509, 1998[CrossRef][Medline] 17. Kuerer HM, Sahin AA, Hunt KK, et al: Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg 230:72-78, 1999[CrossRef][Medline] 18. American Joint Committee on Cancer (AJCC) Cancer Staging Handbook (ed 6). New York, NY, Springer-Verlag, 2002 19. Hsu SM, Raine L, Fanger H: Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577-580, 1981[Abstract] 20. Kaplan EL, Meier P: Nonparametric estimation from incomplete observations. J Am Stat Assoc 185:1457-1481, 1958 21. Mantel N: Evaluation of survival data and two row rank order statistics arising in its consideration. Cancer Chemother Rep 50:163-170, 1966[Medline] 22. Schwartz GF, Birchansky CA, Komarnicky LT, et al: Induction chemotherapy followed by breast conservation for locally advanced carcinoma of the breast. Cancer 73:362-369, 1994[CrossRef][Medline] 23. Bear HD, Anderson S, Brown A, et al: 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 24. Fisher ER, Wang J, Bryant J, et al: Pathobiology of preoperative chemotherapy: Findings from the National Surgical Adjuvant Breast and Bowel (NSABP) protocol B-18. Cancer 95:681-695, 2002[CrossRef][Medline] 25. Rouzier R, Extra JM, Klijanienko J, et al: Incidence and prognostic significance of complete axillary downstaging after primary chemotherapy in breast cancer patients with T1 to T3 tumors and cytologically proven axillary metastatic lymph nodes. J Clin Oncol 20:1304-1310, 2002 26. Shimazu K, Tamaki Y, Taguchi T, et al: Sentinel lymph node biopsy using periareolar injection of radiocolloid for patients with neoadjuvant chemotherapy-treated breast carcinoma. Cancer 100:2555-2561, 2004[CrossRef][Medline] 27. Trocha SD, Giuliano AE: Sentinel node in the era of neoadjuvant therapy and locally advanced breast cancer. Surg Oncol 12:271-276, 2003[CrossRef][Medline] 28. Breslin TM, Cohen L, Sahin A, et al: Sentinel lymph node biopsy is accurate after neoadjuvant chemotherapy for breast cancer. J Clin Oncol 18:3480-3486, 2000 29. Mamaonas EP, Brown A, Smith R, et al: Accuracy of sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: Updated results from NSABP B-27. Proc Am Soc Clin Oncol 20, 2002 (abstr 140) 30. Bear HD, Anderson S, Brown A, et al: A randomized trial comparing preoperative (preop) doxorubicin/cyclophosphamide (AC) to preop AC followed by preop docetaxel (T) and to preop AC followed by postoperative (postop) T in patients (pts) with operable carcinoma of the breast: Results of NSABP B-27. Presented at the 27th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-11, 2004 (abstr 26) 31. Kuerer HM, Newman LA, Fornage BD, et al: Role of ALN dissection after tumor downstaging with induction chemotherapy for locally advanced breast cancer. Ann Surg Oncol 5:673-680, 1998[CrossRef][Medline] 32. Martincich L, Montemurro F, De Rosa G, et al: Monitoring response to primary chemotherapy in breast cancer using dynamic contrast-enhanced magnetic resonance imaging. Breast Cancer Res Treat 83:67-76, 2004[CrossRef][Medline] 33. Biersack HJ, Bender H, Palmedo H: FDG-PET in monitoring therapy of breast cancer. Eur J Nucl Med Mol Imaging 31:S112-S117, 2004 (suppl 1)[CrossRef][Medline] 34. Hutcheon AW, Heys SD, Sarkar TK: Neoadjuvant docetaxel in locally advanced breast cancer. Breast Cancer Res Treat 79:S19-S24, 2003 (suppl 1)[CrossRef][Medline] 35. Sorlie T, Perou CM, Tibshirani R, et al: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98:10869-10874, 2001 36. Ayers M, Symmans WF, Stec J, et al: Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. J Clin Oncol 22:2284-2293, 2004 37. Chang JC, Wooten EC, Tsimelzon A, et al: Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer. Lancet 362:362-369, 2003[CrossRef][Medline] 38. Gianni L, Zambetti M, Clark K, et al: Gene expression profiles of paraffin-embedded core biopsy tissue predict response to chemotherapy in patients with locally advanced breast cancer. J Clin Oncol 23:7265-7277, 2005 39. Early Breast Cancer Trialists' Collaborative Group: 2000 analysis overview results. Presented at the fifth meeting of the Early Breast Cancer Trialists' Collaborative Group, Oxford, UK, September 21-23, 2000 Submitted April 25, 2005; accepted September 28, 2005.
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||||||||||
|
|||||||||||
|
|
Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
|
TOP
ABSTRACT
INTRODUCTION
2 tests. The statistical significance level (P) was taken as a measure of the strength of evidence against the null hypothesis, and P 
