HER2 and Responsiveness of Breast Cancer to Adjuvant Chemotherapy
Kathleen I. Pritchard, M.D., Lois E. Shepherd, M.D., Frances P. O'Malley, M.D., Irene L. Andrulis, Ph.D., Dongsheng Tu, Ph.D., Vivien H. Bramwell, M.B., B.S., Mark N. Levine, M.D., for the National Cancer Institute of Canada Clinical Trials Group
Background Amplification of the human epidermal growth factorreceptor type 2 (HER2, also called HER2/neu) gene and overexpressionof its product in breast-cancer cells may be associated withresponsiveness to anthracycline-containing chemotherapy regimens.
Methods In the randomized, controlled Mammary.5 trial, we studied639 formalin-fixed paraffin-embedded specimens obtained from710 premenopausal women with node-positive breast cancer whohad received either cyclophosphamide, epirubicin, and fluorouracil(CEF) or cyclophosphamide, methotrexate, and fluorouracil (CMF)as adjuvant chemotherapy. HER2 amplification or overexpressionwas evaluated with the use of fluorescence in situ hybridization,immunohistochemical analysis, and polymerase-chain-reactionanalysis.
Results Amplification of HER2 was associated with a poor prognosisregardless of the type of treatment. In patients whose tumorsshowed amplification of HER2, CEF was superior to CMF when assessedon the basis of relapse-free survival (hazard ratio, 0.52; 95percent confidence interval, 0.34 to 0.80; P=0.003) and overallsurvival (hazard ratio, 0.65; 95 percent confidence interval,0.42 to 1.02; P=0.06). For women whose tumors lacked amplificationof HER2, CEF did not improve relapse-free survival (hazard ratiofor relapse, 0.91; 95 percent confidence interval, 0.71 to 1.18;P=0.49) or overall survival (hazard ratio for death, 1.06; 95percent confidence interval, 0.83 to 1.44; P=0.68). The adjustedhazard ratio for the interaction between treatment and HER2amplification was 1.96 for relapse-free survival (95 percentconfidence interval, 1.15 to 3.36; P=0.01) and 2.04 for overallsurvival (95 percent confidence interval, 1.14 to 3.65; P=0.02).
Conclusions Amplification of HER2 in breast-cancer cells isassociated with clinical responsiveness to anthracycline-containingchemotherapy. (cancer.gov number, NCI-V90-0027.)
In the 1980s, trials of adjuvant chemotherapy for breast cancerthat compared regimens containing an anthracycline (epirubicinor doxorubicin) with a combination of cyclophosphamide, methotrexate,and fluorouracil (CMF) yielded inconsistent results.1,2,3 Morethan a decade later, the safety and efficacy of an intensiveregimen of cyclophosphamide, epirubicin, and fluorouracil (CEF)as adjuvant therapy for breast cancer were demonstrated.4 Inthe National Cancer Institute of Canada Clinical Trials Group(NCIC CTG) Mammary.5 (MA.5) randomized trial involving premenopausalwomen with node-positive breast cancer, CEF was shown to besuperior to CMF5 and remained superior in terms of relapse-freesurvival and overall survival after a median follow-up of 10years.6 As compared with CMF, however, CEF was associated withincreased rates of alopecia, nausea, vomiting, stomatitis, andneutropenia and febrile neutropenia; a temporary reduction inthe quality of life; and an increase in the risk of congestiveheart failure (1.1 percent) and acute leukemia (1.4 percent).5,6Treatment with CEF is also considerably more expensive thanCMF therapy.
It has been suggested that amplification of the gene for humanepidermal growth factor receptor type 2 (HER2, also referredto as HER2/neu), overexpression of its product, or both in breast-cancercells not only predicts responsiveness to trastuzumab7,8 butalso identifies patients whose tumors will not respond to CMF9,10,11,12,13and who could benefit from high-dose chemotherapy14,15,16,17,18,19or from anthracycline-containing regimens.20,21,22,23,24,25,26,27,28,29To pursue this suggestion, we studied formalin-fixed, paraffin-embeddedspecimens from all patients enrolled in the MA.5 trial to determinewhether amplification of HER2, overexpression of HER2, or bothin breast-cancer cells identifies women who could benefit fromCEF, as compared with CMF.
Methods
Patients
We conducted a study involving premenopausal women, describedpreviously,5,6 with histologically confirmed axillary-node–positivebreast cancer who had undergone a modified radical mastectomyor lumpectomy plus axillary dissection. The MA.5 trial protocolwas approved by the institutional review board at each participatingcenter, and written informed consent was obtained from eachwoman before randomization.
Treatment Regimens
As described previously,5,6 the CMF regimen consisted of sixcycles of oral cyclophosphamide (Cytoxan, Bristol-Myers Squibb)at a dose of 100 mg per square meter of body-surface area ondays 1 through 14, 40 mg of methotrexate (Wyeth [formerly Lederle])per square meter intravenously on days 1 and 8, and 600 mg offluorouracil (Efudex, Valeant Pharm) per square meter intravenouslyon days 1 and 8. The CEF regimen consisted of six cycles oforal cyclophosphamide at a dose of 75 mg per square meter ondays 1 through 14, 60 mg of epirubicin (Pharmorubicin, Pfizer)per square meter intravenously on days 1 and 8, and 500 mg offluorouracil per square meter intravenously on days 1 and 8.During CEF therapy, the women also received antibiotic prophylaxiswith trimethoprim–sulfamethoxazole (Septra, Glaxo Wellcome)at a dose of two tablets orally twice daily or, for those whocould not tolerate trimethoprim–sulfamethoxazole, norfloxacin(Norflox, Merck) at a dose of 400 mg orally twice daily or ciprofloxacin(Cipro, Bayer) at a dose of 500 mg orally twice daily. Endocrinetherapy was not to be used after the completion of chemotherapy.
Outcomes
The primary outcomes for the MA.5 study were relapse-free survivaland overall survival. They have been defined previously.5,6
Specimen Collection
As part of supporting documentation for the MA.5 trial, theNCIC CTG collected diagnostic pathology reports for each woman.For the current analysis, pathologists were asked to submita representative formalin-fixed, paraffin-embedded block oftumor tissue from each woman, or if tumor blocks were unavailable,20 4-µm unstained sections, to the central office of theNCIC CTG. Paraffin blocks were stored at room temperature, andunstained sections were kept at 4°C. Samples were identifiedonly by an identification number assigned to each patient atrandomization. A stained section of each tumor sample was preparedfrom blocks or slides to confirm the diagnosis and identifyrepresentative tumor areas for microdissection and DNA extractionfor analysis by the polymerase chain reaction (PCR). An adjacent10-µm section was also obtained for PCR analysis. Further4-µm sections were obtained for immunohistochemical analysisand fluorescence in situ hybridization (FISH). Assay resultswere reported to the NCIC CTG central office, where the statisticalanalysis was performed.
Measurement of HER2 Expression
Expression of the HER2 protein was measured by immunohistochemicalanalysis with the CB11 antibody (Novocastra) and the TAB 250antibody (Zymed), as previously described.30 Only complete membranestaining of invasive tumor cells was considered in the results.The proportion of cells with complete membrane staining wasassessed with the use of the Allred semiquantitative scoringsystem.31 A score of five or greater on the immunohistochemicalanalysis was considered to be positive for overexpression ofthe HER2 protein on the basis of previous technical validationof this cutoff point.30
FISH
Representative sections of tumor were hybridized with the useof a HER-2 DNA probe kit (PathVysion, Vysis), as previouslydescribed.32 A staining-intensity ratio of HER2 to chromosome17 (assessed with the use of the centromere enumeration probecep 17) of 2 or more was considered to indicate amplification,in accordance with the manufacturer's recommendations.
PCR
PCR analysis for amplification of HER2 was performed as describedby O'Malley et al.30 A relative increase in the number of genecopies of two or more was considered to indicate amplification.
Statistical Analysis
Kaplan–Meier estimates of survival according to the presenceor absence of amplification of HER2 or overexpression of HER2or according to the treatment regimen were compared with theuse of a log-rank test. We use the phrase "amplification ofHER2" throughout to refer to the results of FISH and PCR andthe term "overexpression" to refer to the results of the immunohistochemicalanalysis. We used the Cox proportional-hazards model with asingle covariate to obtain the hazard ratios for relapse ordeath and associated 95 percent confidence intervals for thecomparison between the two groups. We used the Cox model, withtreatment, amplification status, and their interaction as covariates,to assess the interaction between treatment and amplificationstatus. Multivariable analyses were performed with the use ofthe Cox model and were adjusted for age (50 years vs. <50years), number of positive lymph nodes (<3 vs. 4), estrogen-receptorlevel (10 vs. <10 fmol per milligram), type of surgery (totalvs. partial mastectomy), and tumor size (T1, T2, or T3, accordingto the tumor–node–metastasis staging system). Thekappa statistic and associated 95 percent confidence intervalswere used to measure agreement among the four assays of HER2(with a value >0.80 indicating near-perfect agreement, valuesof 0.61 to 0.80 substantial agreement, values of 0.41 to 0.60moderate agreement, values of 0.21 to 0.40 fair agreement, values>0 to 0.20 slight agreement, and values of 0 no agreementor a random association).33
Drs. Shepherd and Tu, of the NCIC CTG central office, were responsiblefor study coordination, collection and management of the data,statistical analyses, and administrative activities. Most ofthe study funding was provided by the NCIC, the Canadian CancerSociety, and the Canadian Breast Cancer Research Alliance. Pharmacia(now Pfizer) provided epirubicin, and Vysis provided FISH kitsat a reduced price.
Results
The outcome data reported here are based on the data set fromthe MA.5 trial, which was updated on April 5, 2002,34 and publishedin 2005.6 All women who were alive were followed for a minimumof 9 years and a median of 10 years. Among the 710 women inthe study, 363 had a recurrence of breast cancer and 284 died.
Tissue samples were available from 639 of 710 eligible women(90 percent) in the MA.5 trial. Immunohistochemical analysiswith the use of the CB11 antibody was successful in 634 tumorsamples (89 percent), immunohistochemical analysis with theuse of the TAB 250 antibody was successful in 632 samples (89percent), and the results of FISH were interpretable for 628samples (89 percent). Amplification of HER2 was assayed by PCRin 624 tumors (88 percent). On FISH, 163 of 628 tumors werefound to have HER2 amplification (26 percent). On immunohistochemicalanalysis, overexpression of the HER2 protein was found in 124of 634 tumors analyzed with the CB11 antibody (20 percent) andin 116 of 632 tumors analyzed with the TAB 250 antibody (18percent). PCR analysis detected amplification of HER2/neu in195 of 624 tumors (31 percent).
Results with the two antibodies, CB11 and TAB 250, were in substantialagreement (kappa statistic, 0.80; 95 percent confidence interval,0.75 to 0.86) (Table 1). There was also substantial agreementbetween the results of FISH and those of the immunohistochemicalanalyses with the CB11 antibody (kappa statistic, 0.76; 95 percentconfidence interval, 0.70 to 0.82) and the TAB 250 antibody(kappa statistic, 0.66; 95 percent confidence interval, 0.59to 0.73) and between FISH and the PCR analysis (kappa statistic,0.60; 95 percent confidence interval, 0.53 to 0.67) (Table 1).Kappa statistics for other analyses showed moderate agreement(Table 1).
Table 1. Results of Assays of HER2 Amplification on FISH and PCR and HER2 Overexpression on Immunohistochemical Analysis with the TAB 250 and CB11 Antibodies.
Associations between the results of analyses of amplificationor overexpression of HER2 and relapse-free survival and overallsurvival were assessed with each of the four assay methods.The results of FISH are presented in detail, because this methodis the gold standard for measurement of HER2 status.35,36Table 2shows the baseline characteristics of the patients for whomFISH-based measurements were available. The distribution ofthe characteristics in this subgroup was similar to that amongall 710 eligible patients who underwent randomization in theMA.5 study.6 There was no significant difference between womenwith HER2 amplification and those without amplification, exceptfor a shift toward younger age among those whose tumors exhibitedHER2 amplification on FISH.
Table 2. Baseline Characteristics of Women for Whom FISH Data Were Available.
As compared with women without HER2 amplification, women withHER2 amplification had a decreased likelihood of both relapse-freesurvival (hazard ratio for relapse, 1.31; 95 percent confidenceinterval, 1.03 to 1.67; P=0.03) and overall survival (hazardratio for death, 1.62; 95 percent confidence interval, 1.24to 2.11; P<0.001) (Figure 1). After adjustment for age, nodalstatus, estrogen-receptor status, type of surgery, and tumorsize, the likelihood of relapse-free survival remained loweramong women with HER2 amplification than among women withoutHER2 amplification (hazard ratio for relapse, 1.24; 95 percentconfidence interval, 0.96 to 1.60; P=0.09), as did the likelihoodof overall survival (hazard ratio for death, 1.53; 95 percentconfidence interval, 1.15 to 2.02; P=0.003).
Figure 1. Relapse-free Survival (Panel A) and Overall Survival (Panel B) among Women with Breast Cancer, According to HER2 Amplification Status on FISH.
Among the women whose tumors showed HER2 amplification, adjuvantchemotherapy with CEF was superior to that with CMF in termsof both relapse-free survival (hazard ratio for relapse, 0.52;95 percent confidence interval, 0.34 to 0.80; P=0.003) and overallsurvival (hazard ratio for death, 0.65; 95 percent confidenceinterval, 0.42 to 1.02; P=0.06) (Figure 2). By contrast, amongthose whose tumors did not show amplification of HER2, therewas no significant difference between adjuvant chemotherapywith CEF and that with CMF in terms of relapse-free survival(hazard ratio for relapse, 0.91; 95 percent confidence interval,0.71 to 1.18; P=0.49) or overall survival (hazard ratio fordeath, 1.06; 95 percent confidence interval, 0.83 to 1.44; P=0.68)(Figure 3). Unadjusted hazard ratios for the interaction betweentreatment and amplification status were 1.79 (95 percent confidenceinterval, 1.08 to 2.96; P=0.02) for relapse-free survival and1.66 (95 percent confidence interval, 0.97 to 2.85; P=0.07)for overall survival. The hazard ratio for the interaction betweentreatment and amplification status, after adjustment for age,nodal status, estrogen-receptor levels, type of surgery, andtumor size, was 1.96 (95 percent confidence interval, 1.15 to3.36; P=0.01) for relapse-free survival and 2.04 (95 percentconfidence interval, 1.14 to 3.65; P=0.02) for overall survival.
Figure 2. Relapse-free Survival (Panel A) and Overall Survival (Panel B) According to the Type of Adjuvant Chemotherapy in Women with HER2 Amplification on FISH.
Figure 3. Relapse-free Survival (Panel A) and Overall Survival (Panel B) According to Type of Adjuvant Chemotherapy in Women without HER2 Amplification on FISH.
Similar analyses were performed with the amplification of HER2obtained by PCR analysis and measurements of the overexpressionof HER2 performed by immunohistochemical analysis with CB11and TAB 250 antibodies. For each of these methods, the adjustedhazard ratio for the interaction between treatment and amplificationstatus was significant for relapse-free survival. Adjusted hazardratios for the interaction reached significance for overallsurvival in the FISH analysis and in the immunohistochemicalanalysis with the use of the CB11 antibody but not with theuse of the TAB 250 antibody or in the PCR analysis (Table 3).
Table 3. Hazard Ratios for Interaction between Treatments and Amplification of HER2 or Overexpression of HER2.
Discussion
Previous analyses have suggested that women with node-positivebreast cancer who receive adjuvant chemotherapy with CEF, ascompared with CMF, have an increase in relapse-free survivalof approximately 30 percent and in overall survival of 18 percent.5,6Our correlative analysis indicated that the increase in benefitattributable to CEF is confined almost completely to women whosetumors exhibit amplification or overexpression of HER2.
Other investigators have examined the effect of HER2 amplificationor overexpression on outcome in trials comparing regimens thatcontained an anthracycline with those that did not contain ananthracycline.20,21,22,23,24,25,26,27,28,29,37 Although mostof these trials suggested a trend toward greater benefit withthe anthracycline-containing regimen in women whose tumors overexpressHER2 or amplify HER2, tests for interaction were significantin only one study, the National Surgical Adjuvant Breast andBowel Project protocol B-11 trial,22 in which a regimen of melphalanand fluorouracil was compared with a regimen of melphalan, doxorubicin,and fluorouracil. In that trial, more than 90 percent of thetumors were tested for HER2 status, whereas in the other studies,tumor specimens were evaluated in no more than 60 percent ofthe patients.20,21,23,24,25,26,27,28,29 Most of these otherstudies lacked the statistical power to detect predictive interactions,unless the interactions were extremely strong.
Pegram et al.38 investigated whether HER2 overexpression orHER2 amplification conferred a sensitivity to doxorubicin infour breast-cancer cell lines that were transfected with theHER2 gene and then exposed to doxorubicin. No alteration inchemosensitivity was observed in any of the lines. An in vitrostudy of breast-cancer cells obtained from 140 patients whohad not undergone chemotherapy showed no association betweenHER2 overexpression or HER2 amplification and resistance toCMF or fluorouracil, epirubicin, and cyclophosphamide and nopreferential benefit of the latter regimen in tumors positivefor HER2.39 These findings argue against a direct role of HER2amplification or HER2 overexpression in the sensitivity of breastcancer to anthracyclines.
The association between HER2 overexpression and HER2 amplificationand sensitivity to anthracycline may be related to topoisomeraseII. There is evidence40 that amplification of the topoisomeraseII gene (TOP2A) is associated with sensitivity of metastaticbreast cancer to anthracyclines. Anthracyclines are topoisomeraseinhibitors, and TOP2A is close to the HER2 gene on chromosome17. Jarvinen et al.41 have shown, however, that HER2 and TOP2Aare not on the same amplicon and that when HER2 is amplified,TOP2A is deleted as often as it is amplified. Nevertheless,changes in topoisomerase II, at the level of the gene or theprotein, may increase sensitivity to anthracyclines, suggestingthat measurement of topoisomerase II in the tumor could be usefulin selecting treatment for a woman with breast cancer. A numberof groups are exploring this hypothesis.42 Three recent reportsof randomized trials have suggested that deletion or amplificationof TOP2A is indicative of a poor outcome and predictive of agreater differential response to anthracycline-containing regimens.37,43,44In two of the three studies, all tumors had amplified HER2,43,44but in the other trial comparing CMF and CEF, which was verysimilar to the MA.5 trial, HER2 was not predictive of a differentialresponse to CEF even in a univariate analysis, whereas deletionor amplification of TOP2A seemed to be predictive of a differentialresponse.37
We believe that our analysis of the association between HER2amplification or overexpression and responsiveness to CEF, ascompared with CMF, is particularly robust, for several reasons.We proposed this analysis before we began collecting tumor specimens;our a priori hypothesis was that women whose tumors exhibitedamplification or overexpression of HER2 would benefit more fromCEF than from CMF. We were able to collect tumor specimens from90 percent of the eligible patients and to measure HER2 amplificationor overexpression of the HER2 protein with the use of all fourof the proposed methods in 88 percent or more of the tumor samplesobtained from these patients.
In conclusion, whether it plays a direct or indirect role, HER2amplification or overexpression in breast cancer is associatedwith a larger benefit from CEF than from CMF. Patients whosetumors do not amplify or overexpress HER2 receive virtuallyno benefit from CEF, as compared with CMF. These data suggestthat patients whose tumors do not exhibit amplification or overexpressionof HER2 could be treated with the less toxic regimen of CMF,whereas those with tumors that show amplified HER2 or overexpressedHER2 should receive dose-intensive anthracycline-containingregimens such as CEF.
Supported by grants from the Canadian Breast Cancer ResearchAlliance (10032, to Dr. Pritchard) and the Canadian Cancer Society(015469, through the National Cancer Institute of Canada).
Presented as a preliminary analysis at the 38th Annual Meetingof the American Society of Clinical Oncology, Orlando, Fla.,May 18–21, 2002.
Dr. Pritchard reports having received consulting fees and speakingfees from Pharmacia (Pfizer). No other potential conflict ofinterest relevant to this article was reported.
We are indebted to Rosemary Mueller, director of the CytogeneticsLaboratory, Capital Health, University of Alberta Hospital,Edmonton; to Eleanor Latta, M.D., for assistance with FISH andimmunohistochemical readings for all specimens; to Tania Molinaroand Suzanna Tjan for technical assistance; to Elizabeth Ramageand Charlene Wainwright for assistance in the preparation ofthe manuscript; to Vysis for providing FISH kits at a reducedprice; and to Pfizer for providing epirubicin.
Source Information
From the Toronto Sunnybrook Regional Cancer Centre and the University of Toronto, Toronto (K.I.P.); Queen's University, Kingston, Ont. (L.E.S., D.T.); the Department of Pathology and Laboratory Medicine, Mount Sinai Hospital and University of Toronto, Toronto (F.P.O., I.L.A.); the Department of Molecular and Medical Genetics, University of Toronto, and the Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto (I.L.A.); the Department of Oncology, University of Calgary, and Tom Baker Cancer Centre, Calgary, Alta. (V.H.B.); and the Departments of Clinical Epidemiology and Biostatistics and Medicine, McMaster University, Hamilton, Ont. (M.N.L.) — all in Canada.
Address reprint requests to Dr. Pritchard at Clinical Trials and Epidemiology, Toronto Sunnybrook Regional Cancer Centre, University of Toronto, 2075 Bayview Ave., Toronto, ON M4N 3M5, Canada, or at kathy.pritchard{at}sunnybrook.ca.
References
Fisher B, Brown AM, Dimitrov NV, et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 1990;8:1483-1496. [Abstract]
Moliterni A, Bonadonna G, Valagussa P, Ferrari L, Zambetti M. Cyclophosphamide, methotrexate and fluorouracil with and without doxorubicin in the adjuvant treatment of resectable breast cancer with one to three positive axillary nodes. J Clin Oncol 1991;9:1124-1130. [Abstract]
Carpenter JT, Velez-Garcia E, Aron BS, et al. Five-year results of a randomized comparison of cyclophosphamide, doxorubicin (Adriamycin) and fluorouracil (CAF) vs cyclophosphamide, methotrexate and fluorouracil (CMF) for node positive breast cancer. Proc Am Soc Clin Oncol 1994;13:A68.
Levine MN, Bramwell V, Pritchard K, et al. A pilot study of intensive cyclophosphamide, epirubicin and fluorouracil in patients with axillary node positive or locally advanced breast cancer. Eur J Cancer 1992;29:37-43.
Levine MN, Bramwell VH, Pritchard KI, et al. A randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methrotrexate, and fluorouracil in premenopausal women with node positive breast cancer. J Clin Oncol 1998;16:2651-2658. [Abstract]
Levine MN, Pritchard KI, Bramwell VH, Shepherd L, Tu D, Paul N. A randomized trial comparing cyclophosphamide, epirubicin, and fluorouracil with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer: update of National Cancer Institute of Canada Clinical Trials Group Trial MA5. J Clin Oncol 2005;23:5166-5170. [Free Full Text]
Vogel CL, Cobleigh MA, Tripathy D, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002;20:719-726. [Free Full Text]
Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 2001;344:783-792. [Free Full Text]
Gusterson BA, Gelber RD, Goldhirsch A, et al. Prognostic importance of c-erbB-2 expression in breast cancer. J Clin Oncol 1992;10:1049-1056. [Abstract]
Ludwig Breast Cancer Study Group. Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer. N Engl J Med 1989;320:491-496. [Abstract]
Ludwig Breast Cancer Study Group. Combination adjuvant chemotherapy for node-positive breast cancer: inadequacy of a single perioperative cycle. N Engl J Med 1988;319:677-683. [Abstract]
Allred DC, Clark GM, Tandon AK, et al. Her-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma. J Clin Oncol 1992;10:599-605. [Free Full Text]
Mansour EG, Gray R, Shatila AH, et al. Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer: an intergroup study. N Engl J Med 1989;320:485-490. [Abstract]
Thor AD, Berry DA, Budman DR, et al. erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. J Natl Cancer Inst 1998;90:1346-1360. [Free Full Text]
Wood WC, Budman DR, Korzun AH, et al. Dose and dose intensity of adjuvant chemotherapy for stage II, node-positive breast carcinoma. N Engl J Med 1994;330:1253-1259. [Erratum, N Engl J Med 1994;331:139.] [Free Full Text]
Arnould L, Fargeot P, Bonneterre J, Fumoleau P, Kerbrat P, Voigt J. Epirubicin dose response effect in node positive breast cancer patients is independent of HER2 overexpression: 10-year retrospective analysis of French Adjuvant Study Group 05 trial. Breast Cancer Res Treat 2003;76:A538-A538.
Bonneterre J, Roche H, Kerbrat P, Bremond A, Fumoleau P, Namer M. 10-Year update of benefit/risk ratio after adjuvant chemotherapy (CT) in node positive (N+), early breast cancer (EBC) patients (pts). Proc Am Soc Clin Oncol 2003;22:A93.
Del Mastro L, Bruzzi P, Venturini M, Cavazzini G, Contu A, Gallo L. HER2 expression and efficacy of dose-dense anthracycline containing adjuvant chemotherapy in early breast cancer patients. J Clin Oncol 2004;22:Suppl:A571-A571. [CrossRef]
Rodenhuis S, Bontenbal M, Beex L, et al. High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer. N Engl J Med 2003;349:7-16. [Free Full Text]
Di Leo A, Larsimont D, Gancberg D, et al. Her-2 and topo-isomerase IIalpha as predictive markers in a population of node-positive breast cancer patients randomly treated with adjuvant CMF or epirubicin plus cyclophosphamide. Ann Oncol 2001;12:1081-1089. [Free Full Text]
Di Leo A, Gancberg D, Larsimont D, et al. HER-2 amplification and topoisomerase IIalpha gene aberrations as predictive markers in node-positive breast cancer patients randomly treated either with an anthracycline-based therapy or with cyclophosphamide, methotrexate, and 5-fluorouracil. Clin Cancer Res 2002;8:1107-1116. [Free Full Text]
Paik S, Bryant J, Park C, et al. erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst 1998;90:1361-1370. [Free Full Text]
Paik S, Bryant J, Tan-Chiu E, et al. HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-15. J Natl Cancer Inst 2000;92:1991-1998. [Free Full Text]
Clahsen PC, van de Velde CJH, Duval C, et al. p53 Protein accumulation and response to adjuvant chemotherapy in premenopausal women with node-negative early breast cancer. J Clin Oncol 1998;16:470-479. [Abstract]
Ravdin PM, Green S, Albain K, et al. Initial report of the SWOG biological correlative study of c-erbB-2 expression as a predictor of outcome in a trial comparing adjuvant CAF T with tamoxifen (T) alone. Proc Am Soc Clin Oncol 1998;17:97A.
Di Leo A, Larsimont D, Beauduin M, et al. CMF or anthracycline-based adjuvant chemotherapy for node-positive breast cancer patients: 4-year results of a Belgian randomized clinical trial with predictive markers analysis. Proc Am Soc Clin Oncol 1999;18: 69A.
Moliterni A, Menard S, Valagussa P, Biganzoli E, Boracchi P, Balsari A. HER2 overexpression and doxorubicin in adjuvant chemotherapy for resectable breast cancer. J Clin Oncol 2003;21:458-462. [Free Full Text]
De Laurentiis M, Caputo F, Massarelli E, et al. HER2 expression and anthracycline effect: results from the Naples GUN 3 randomized trial. Proc Am Soc Clin Oncol 2001;20:A133.
De Placido S, Perrone F, Carlomagno C, et al. CMF vs alternating CMF/EV in the adjuvant treatment of operable breast cancer: a single centre randomised clinical trial (Naples GUN-3 study). Br J Cancer 1995;71:1283-1287. [Web of Science][Medline]
O'Malley FP, Parkes R, Latta E, et al. Comparison of HER2/neu status assessed by quantitative polymerase chain reaction and immunohistochemistry. Am J Clin Pathol 2001;115:504-511. [Free Full Text]
Allred DC, Clark GM, Elledge R, et al. Association of p53 protein expression with tumor cell proliferation rate and clinical outcome in node-negative breast cancer. J Natl Cancer Inst 1993;85:200-206. [Free Full Text]
Latta EK, Tjan S, Parkes RK, O'Malley FP. The role of HER2/neu overexpression/amplification in the progression of ductal carcinoma in situ to invasive carcinoma of the breast. Mod Pathol 2002;15:1318-1325. [CrossRef][Web of Science][Medline]
Landis JR, Koch GG. A one-way components of variance model for categorical data. Biometrics 1977;33:671-679. [CrossRef][Web of Science]
Pritchard KI, O'Malley FA, Andrulis I, et al. Prognostic and predictive value of HER2/neu in a randomized trial comparing CMF to CEF in premenopausal women with axillary lymph node positive breast cancer (NCIC CTG MA.5). Proc Am Soc Clin Oncol 2002;21:42A.
Dressler LG, Berry DA, Broadwater G, et al. Comparison of HER2 status by fluorescence in situ hybridization and immunohistochemistry to predict benefit from dose escalation of adjuvant doxorubicin-based therapy in node-positive breast cancer patients. J Clin Oncol 2005;23:4287-4297. [Free Full Text]
Press MF, Sauter G, Bernstein L, et al. Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trials. Clin Cancer Res 2005;11:6598-6607. [Free Full Text]
Knoop AS, Knudsen H, Balslev E, et al. Retrospective analysis of topoisomerase IIa amplifications and deletions as predictive markers in primary breast cancer patients randomly assigned to cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide, epirubicin, and fluorouracil: Danish Breast Cancer Cooperative Group. J Clin Oncol 2005;23:7483-7490. [Free Full Text]
Pegram MD, Finn RS, Arzoo K, Beryt M, Pietras RJ, Slamon DJ. The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells. Oncogene 1997;15:537-547. [CrossRef][Web of Science][Medline]
Konecny G, Fritz M, Untch M, et al. HER-2/neu overexpression and in vitro chemosensitivity to CMF and FEC in primary breast cancer. Breast Cancer Res Treat 2001;69:53-63. [CrossRef][Web of Science][Medline]
Isola JJ, Tanner M, Holli K, Joensuu H. Amplification of topoisomerase IIalpha is a strong predictor of response to epirubicin-based chemotherapy in HER-2/neu positive metastatic breast cancer. Breast Cancer Res Treat 2000;64:31-31.
Jarvinen TA, Tanner M, Barlund M, Borg A, Isola J. Characterization of topoisomerase II alpha gene amplification and deletion in breast cancer. Genes Chromosomes Cancer 1999;26:142-150. [CrossRef][Web of Science][Medline]
Mueller RE, Parkes RK, Andrulis I, O'Malley FP. Amplification of the TOP2A gene does not predict high levels of topoisomerase II alpha protein in human breast tumor samples. Genes Chromosomes Cancer 2004;39:288-297. [CrossRef][Web of Science][Medline]
Press MF, Mass RD, Zhou J-Y, et al. Association of topoisomerase II-alpha (TOP2A) gene amplification with responsiveness to anthracycline-containing chemotherapy among women with metastatic breast cancer entered in the Herceptin H0648g pivotal clinical trial. Proc Am Soc Clin Oncol 2005;23:847.
Slamon DJ. Update on HER-2 directed therapy. Session 1, 28th San Antonio Breast Cancer Symposium, San Antonio, Tex., December 6–11, 2005. (Accessed April 21, 2006, at http://www.sabcs.org.)
Anthracyclines in Early Breast Cancer
Wilson K. S., Pritchard K. I., Bramwell V. H., Levine M. N., the National Cancer Institute of Canada Clinical Trials Group , Piccart-Gebhart M. J.
Extract |
Full Text |
PDF
N Engl J Med 2006;
355:845-846, Aug 24, 2006.
Correspondence
This article has been cited by other articles:
Pritchard, K. I., O'malley, F., Shepherd, L., Levine, M. N., Tu, D., Bramwell, V., Andrulis, I., Chia, S.
(2009). Response. JNCI J Natl Cancer Inst
0: djp403v1-2
[Full Text]
Robson, D., Verma, S.
(2009). Anthracyclines in Early-Stage Breast Cancer: Is It the End of an Era?. The Oncologist
14: 950-958
[Abstract][Full Text]
Tubbs, R., Barlow, W. E., Budd, G. T., Swain, E., Porter, P., Gown, A., Yeh, I-T., Sledge, G., Shapiro, C., Ingle, J., Haskell, C., Albain, K. S., Livingston, R., Hayes, D. F.
(2009). Outcome of Patients With Early-Stage Breast Cancer Treated With Doxorubicin-Based Adjuvant Chemotherapy As a Function of HER2 and TOP2A Status. JCO
27: 3881-3886
[Abstract][Full Text]
Pritchard, K. I.
(2009). Are HER2 and TOP2A Useful As Prognostic or Predictive Biomarkers for Anthracycline-Based Adjuvant Chemotherapy for Breast Cancer?. JCO
27: 3875-3876
[Full Text]
Gong, Y., Sweet, W., Duh, Y.-J., Greenfield, L., Tarco, E., Trivedi, S., Symmans, W. F., Isola, J., Sneige, N.
(2009). Performance of Chromogenic In Situ Hybridization on Testing HER2 Status in Breast Carcinomas With Chromosome 17 Polysomy and Equivocal (2+) HercepTest Results: A Study of Two Institutions Using the Conventional and New ASCO/CAP Scoring Criteria. Am J Clin Pathol
132: 228-236
[Abstract][Full Text]
Harris, L. N., Broadwater, G., Abu-Khalaf, M., Cowan, D., Thor, A. D., Budman, D., Cirrincione, C. T., Berry, D. A., Winer, E. P., Hudis, C. A., Hayes, D. F., Friedman, P., Ellis, M., Dressler, L.
(2009). Topoisomerase II{alpha} Amplification Does Not Predict Benefit From Dose-Intense Cyclophosphamide, Doxorubicin, and Fluorouracil Therapy in HER2-Amplified Early Breast Cancer: Results of CALGB 8541/150013. JCO
27: 3430-3436
[Abstract][Full Text]
Esteva, F. J., Hortobagyi, G. N.
(2009). Topoisomerase II{alpha} Amplification and Anthracycline-Based Chemotherapy: The Jury Is Still Out. JCO
27: 3416-3417
[Full Text]
Liu, Y.-H., Xu, F.-P., Rao, J.-Y., Zhuang, H.-G., Luo, X.-L., Li, L., Luo, D.-L., Zhang, F., Xu, J.
(2009). Justification of the Change From 10% to 30% for the Immunohistochemical HER2 Scoring Criterion in Breast Cancer. Am J Clin Pathol
132: 74-79
[Abstract][Full Text]
O'Malley, F. P., Chia, S., Tu, D., Shepherd, L. E., Levine, M. N., Bramwell, V. H., Andrulis, I. L., Pritchard, K. I.
(2009). Topoisomerase II Alpha and Responsiveness of Breast Cancer to Adjuvant Chemotherapy. JNCI J Natl Cancer Inst
101: 644-650
[Abstract][Full Text]
Slamon, D. J., Press, M. F.
(2009). Alterations in the TOP2A and HER2 Genes: Association With Adjuvant Anthracycline Sensitivity in Human Breast Cancers. JNCI J Natl Cancer Inst
101: 615-618
[Full Text]
Gong, Y., Sweet, W., Duh, Y.-J., Greenfield, L., Fang, Y., Zhao, J., Tarco, E., Symmans, W. F., Isola, J., Sneige, N.
(2009). Chromogenic In Situ Hybridization Is a Reliable Method for Detecting HER2 Gene Status in Breast Cancer: A Multicenter Study Using Conventional Scoring Criteria and the New ASCO/CAP Recommendations. Am J Clin Pathol
131: 490-497
[Abstract][Full Text]
Magnifico, A., Albano, L., Campaner, S., Delia, D., Castiglioni, F., Gasparini, P., Sozzi, G., Fontanella, E., Menard, S., Tagliabue, E.
(2009). Tumor-Initiating Cells of HER2-Positive Carcinoma Cell Lines Express the Highest Oncoprotein Levels and Are Sensitive to Trastuzumab. Clin. Cancer Res.
15: 2010-2021
[Abstract][Full Text]
de Azambuja, E., Paesmans, M., Beauduin, M., Vindevoghel, A., Cornez, N., Finet, C., Ries, F., Closon-Dejardin, M. T., Kerger, J., Gobert, P., Focan, C., Tagnon, A., Dolci, S., Nogaret, J. M., di Leo, A., Piccart-Gebhart, M. J.
(2009). Long-Term Benefit of High-Dose Epirubicin in Adjuvant Chemotherapy for Node-Positive Breast Cancer: 15-Year Efficacy Results of the Belgian Multicentre Study. JCO
27: 720-725
[Abstract][Full Text]
Cortes, J., Di Cosimo, S., Climent, M. A., Cortes-Funes, H., Lluch, A., Gascon, P., Mayordomo, J. I., Gil, M., Benavides, M., Cirera, L., Ojeda, B., Rodriguez, C. A., Trigo, J. M., Vazquez, J., Regueiro, P., Dorado, J. F., Baselga, J., on behalf of the Spanish Breast Cancer Cooperative,
(2009). Nonpegylated Liposomal Doxorubicin (TLC-D99), Paclitaxel, and Trastuzumab in HER-2-Overexpressing Breast Cancer: A Multicenter Phase I/II Study. Clin. Cancer Res.
15: 307-314
[Abstract][Full Text]
Hartmann, O., Spyratos, F., Harbeck, N., Dietrich, D., Fassbender, A., Schmitt, M., Eppenberger-Castori, S., Vuaroqueaux, V., Lerebours, F., Welzel, K., Maier, S., Plum, A., Niemann, S., Foekens, J. A., Lesche, R., Martens, J. W.M.
(2009). DNA Methylation Markers Predict Outcome in Node-Positive, Estrogen Receptor-Positive Breast Cancer with Adjuvant Anthracycline-Based Chemotherapy. Clin. Cancer Res.
15: 315-323
[Abstract][Full Text]
Morris, P. G., McArthur, H. L., Dang, C. T., Hudis, C. A.
(2009). Selection of Appropriate Patients for Anthracycline Therapy. Am Soc Clin Oncol Ed Book
2009: 11-18
[Abstract][Full Text]
Sturgeon, C. M., Duffy, M. J., Stenman, U.-H., Lilja, H., Brunner, N., Chan, D. W., Babaian, R., Bast, R. C. Jr., Dowell, B., Esteva, F. J., Haglund, C., Harbeck, N., Hayes, D. F., Holten-Andersen, M., Klee, G. G., Lamerz, R., Looijenga, L. H., Molina, R., Nielsen, H. J., Rittenhouse, H., Semjonow, A., Shih, I.-M., Sibley, P., Soletormos, G., Stephan, C., Sokoll, L., Hoffman, B. R., Diamandis, E. P.
(2008). National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for Use of Tumor Markers in Testicular, Prostate, Colorectal, Breast, and Ovarian Cancers. Clin. Chem.
54: e11-e79
[Abstract][Full Text]
Bartlett, J. M.S., Munro, A., Cameron, D. A., Thomas, J., Prescott, R., Twelves, C. J.
(2008). Type 1 Receptor Tyrosine Kinase Profiles Identify Patients With Enhanced Benefit From Anthracyclines in the BR9601 Adjuvant Breast Cancer Chemotherapy Trial. JCO
26: 5027-5035
[Abstract][Full Text]
Rayson, D., Richel, D., Chia, S., Jackisch, C., van der Vegt, S., Suter, T.
(2008). Anthracycline-trastuzumab regimens for HER2/neu-overexpressing breast cancer: current experience and future strategies. Ann Oncol
19: 1530-1539
[Abstract][Full Text]
Gee, M. S., Upadhyay, R., Bergquist, H., Alencar, H., Reynolds, F., Maricevich, M., Weissleder, R., Josephson, L., Mahmood, U.
(2008). Human Breast Cancer Tumor Models: Molecular Imaging of Drug Susceptibility and Dosing during HER2/neu-targeted Therapy. Radiology
248: 925-935
[Abstract][Full Text]
Holmes, J. P., Benavides, L. C., Gates, J. D., Carmichael, M. G., Hueman, M. T., Mittendorf, E. A., Murray, J. L., Amin, A., Craig, D., von Hofe, E., Ponniah, S., Peoples, G. E.
(2008). Results of the First Phase I Clinical Trial of the Novel Ii-Key Hybrid Preventive HER-2/neu Peptide (AE37) Vaccine. JCO
26: 3426-3433
[Abstract][Full Text]
Walker, R A, Bartlett, J M S, Dowsett, M, Ellis, I O, Hanby, A M, Jasani, B, Miller, K, Pinder, S E
(2008). HER2 testing in the UK: further update to recommendations. J. Clin. Pathol.
61: 818-824
[Abstract][Full Text]
Martin, M., Rodriguez-Lescure, A., Ruiz, A., Alba, E., Calvo, L., Ruiz-Borrego, M., Munarriz, B., Rodriguez, C. A., Crespo, C., de Alava, E., Lopez Garcia-Asenjo, J. A., Guitian, M. D., Almenar, S., Gonzalez-Palacios, J. F., Vera, F., Palacios, J., Ramos, M., Gracia Marco, J. M., Lluch, A., Alvarez, I., Segui, M. A., Mayordomo, J. I., Anton, A., Baena, J. M., Plazaola, A., Modolell, A., Pelegri, A., Mel, J. R., Aranda, E., Adrover, E., Alvarez, J. V., Garcia Puche, J. L., Sanchez-Rovira, P., Gonzalez, S., Lopez-Vega, J. M., On behalf of the GEICAM 9906 Study Investigators,
(2008). Randomized Phase 3 Trial of Fluorouracil, Epirubicin, and Cyclophosphamide Alone or Followed by Paclitaxel for Early Breast Cancer. JNCI J Natl Cancer Inst
100: 805-814
[Abstract][Full Text]
Pritchard, K. I., Trudeau, M., Messersmith, H., Elavathil, L., O'Malley, F., Dhesy-Thind, B.
(2008). In Reply. JCO
26: 2596-2597
[Full Text]
DiGiovanna, M. P., Stern, D. F., Edgerton, S., Broadwater, G., Dressler, L. G., Budman, D. R., Henderson, I. C., Norton, L., Liu, E. T., Muss, H. B., Berry, D. A., Hayes, D. F., Thor, A. D.
(2008). Influence of Activation State of ErbB-2 (HER-2) on Response to Adjuvant Cyclophosphamide, Doxorubicin, and Fluorouracil for Stage II, Node-Positive Breast Cancer: Study 8541 From the Cancer and Leukemia Group B. JCO
26: 2364-2372
[Abstract][Full Text]
Pusztai, L.
(2008). Current Status of Prognostic Profiling in Breast Cancer. The Oncologist
13: 350-360
[Abstract][Full Text]
Kyndi, M., Sorensen, F. B., Knudsen, H., Overgaard, M., Nielsen, H. M., Overgaard, J.
(2008). Estrogen Receptor, Progesterone Receptor, HER-2, and Response to Postmastectomy Radiotherapy in High-Risk Breast Cancer: The Danish Breast Cancer Cooperative Group. JCO
26: 1419-1426
[Abstract][Full Text]
Liedtke, C., Mazouni, C., Hess, K. R., Andre, F., Tordai, A., Mejia, J. A., Symmans, W. F., Gonzalez-Angulo, A. M., Hennessy, B., Green, M., Cristofanilli, M., Hortobagyi, G. N., Pusztai, L.
(2008). Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer. JCO
26: 1275-1281
[Abstract][Full Text]
Chen, S.-C., Chang, H.-K., Lin, Y.-C., Hsueh, S., Cheung, Y.-C., Leung, W.-M., Tsai, C.-S., Lo, Y.-F., Tsai, H.-P., Shen, S.-C., Chen, M.-F.
(2008). High Pathologic Complete Response in HER 2-positive Locally Advanced Breast Cancer after Primary Systemic Chemotherapy with Weekly Docetaxel and Epirubicin. Jpn J Clin Oncol
0: hym172v1-7
[Abstract][Full Text]
Pritchard, K. I., Messersmith, H., Elavathil, L., Trudeau, M., O'Malley, F., Dhesy-Thind, B.
(2008). HER-2 and Topoisomerase II As Predictors of Response to Chemotherapy. JCO
26: 736-744
[Abstract][Full Text]
Peoples, G. E., Holmes, J. P., Hueman, M. T., Mittendorf, E. A., Amin, A., Khoo, S., Dehqanzada, Z. A., Gurney, J. M., Woll, M. M., Ryan, G. B., Storrer, C. E., Craig, D., Ioannides, C. G., Ponniah, S.
(2008). Combined Clinical Trial Results of a HER2/neu (E75) Vaccine for the Prevention of Recurrence in High-Risk Breast Cancer Patients: U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clin. Cancer Res.
14: 797-803
[Abstract][Full Text]
Gennari, A., Sormani, M. P., Pronzato, P., Puntoni, M., Colozza, M., Pfeffer, U., Bruzzi, P.
(2008). HER2 Status and Efficacy of Adjuvant Anthracyclines in Early Breast Cancer: A Pooled Analysis of Randomized Trials. JNCI J Natl Cancer Inst
100: 14-20
[Abstract][Full Text]
Di Leo, A., Licitra, S., Claudino, W., Biganzoli, L.
(2008). Molecular Predictors of Response to Anthracyclines. Am Soc Clin Oncol Ed Book
2008: 3-7
[Abstract][Full Text]
Hofmann, M, Stoss, O, Gaiser, T, Kneitz, H, Heinmoller, P, Gutjahr, T, Kaufmann, M, Henkel, T, Ruschoff, J
(2008). Central HER2 IHC and FISH analysis in a trastuzumab (Herceptin) phase II monotherapy study: assessment of test sensitivity and impact of chromosome 17 polysomy. J. Clin. Pathol.
61: 89-94
[Abstract][Full Text]
Harris, L., Fritsche, H., Mennel, R., Norton, L., Ravdin, P., Taube, S., Somerfield, M. R., Hayes, D. F., Bast, R. C. Jr
(2007). American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer. JCO
25: 5287-5312
[Abstract][Full Text]
Winer, E. P., Harris, J. R., Smith, B. L., D'Alessandro, H. A., Brachtel, E. F.
(2007). Case 32-2007 -- A 62-Year-Old Woman with a Second Breast Cancer. NEJM
357: 1640-1648
[Full Text]
Hayes, D. F., Thor, A. D., Dressler, L. G., Weaver, D., Edgerton, S., Cowan, D., Broadwater, G., Goldstein, L. J., Martino, S., Ingle, J. N., Henderson, I. C., Norton, L., Winer, E. P., Hudis, C. A., Ellis, M. J., Berry, D. A., the Cancer and Leukemia Group B (CALGB) Investiga,
(2007). HER2 and Response to Paclitaxel in Node-Positive Breast Cancer. NEJM
357: 1496-1506
[Abstract][Full Text]
Jones, S. E.
(2007). In Reply. JCO
25: 4327-4327
[Full Text]
Conforti, R, Boulet, T, Tomasic, G, Taranchon, E, Arriagada, R, Spielmann, M, Ducourtieux, M, Soria, J., Tursz, T, Delaloge, S, Michiels, S, Andre, F
(2007). 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
[Abstract][Full Text]
Lonning, P., Knappskog, S, Staalesen, V, Chrisanthar, R, Lillehaug, J.
(2007). Breast cancer prognostication and prediction in the postgenomic era. Ann Oncol
18: 1293-1306
[Abstract][Full Text]
Pruthi, S., Brandt, K. R., Degnim, A. C., Goetz, M. P., Perez, E. A., Reynolds, C. A., Schomberg, P. J., Dy, G. K., Ingle, J. N.
(2007). A Multidisciplinary Approach to the Management of Breast Cancer, Part 1: Prevention and Diagnosis. Mayo Clin Proc.
82: 999-1012
[Abstract][Full Text]
Goldhirsch, A., Wood, W. C., Gelber, R. D., Coates, A. S., Thurlimann, B., Senn, H. -J., Panel Members,
(2007). Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol
18: 1133-1144
[Abstract][Full Text]
Henry, N. L., Hayes, D. F.
(2007). Can Biology Trump Anatomy? Do All Node-Positive Patients With Breast Cancer Need Chemotherapy?. JCO
25: 2501-2503
[Full Text]
Liberato, N. L., Marchetti, M., Barosi, G.
(2007). Cost Effectiveness of Adjuvant Trastuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. JCO
25: 625-633
[Abstract][Full Text]
Wolff, A. C., Hammond, M. E. H., Schwartz, J. N., Hagerty, K. L., Allred, D. C., Cote, R. J., Dowsett, M., Fitzgibbons, P. L., Hanna, W. M., Langer, A., McShane, L. M., Paik, S., Pegram, M. D., Perez, E. A., Press, M. F., Rhodes, A., Sturgeon, C., Taube, S. E., Tubbs, R., Vance, G. H., van de Vijver, M., Wheeler, T. M., Hayes, D. F.
(2007). American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. JCO
25: 118-145
[Abstract][Full Text]
Levine, M. N., Whelan, T.
(2006). Adjuvant Chemotherapy for Breast Cancer -- 30 Years Later. NEJM
355: 1920-1922
[Full Text]
Baselga, J., Perez, E. A., Pienkowski, T., Bell, R.
(2006). Adjuvant Trastuzumab: A Milestone in the Treatment of HER-2-Positive Early Breast Cancer. The Oncologist
11: 4-12
[Abstract][Full Text]
Wilson, K. S., Pritchard, K. I., Bramwell, V. H., Levine, M. N., the National Cancer Institute of Canada Clinical T, , Piccart-Gebhart, M. J.
(2006). Anthracyclines in Early Breast Cancer. NEJM
355: 845-846
[Full Text]
Perez, E. A., Suman, V. J., Davidson, N. E., Martino, S., Kaufman, P. A., Lingle, W. L., Flynn, P. J., Ingle, J. N., Visscher, D., Jenkins, R. B.
(2006). HER2 Testing by Local, Central, and Reference Laboratories in Specimens From the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial. JCO
24: 3032-3038
[Abstract][Full Text]
(2006). Is Tailoring of Chemotherapy in HER2-Positive Breast Cancer Feasible?. JWatch Women's Health
2006: 9-9
[Full Text]
Piccart-Gebhart, M. J.
(2006). Anthracyclines and the Tailoring of Treatment for Early Breast Cancer. NEJM
354: 2177-2179
[Full Text]
50 years vs. <50 years), number of positive lymph nodes (<3 vs. 
. There is evidence40 that amplification of the topoisomerase II
Previous
