Publications (47)554 Total impact
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Article: Radiofrequency ablation as a substitute for surgery in elderly patients with nonresected breast cancer: pilot study with long-term outcomes.
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ABSTRACT: To determine the efficacy and tolerance of ultrasonography (US)-guided percutaneous radiofrequency (RF) ablation with endocrine therapy in elderly patients with breast cancer who decline or are not candidates for surgery. Internal ethics committee approval was obtained, and patients gave informed written consent. Women older than 70 years with breast carcinoma, who had undergone neoadjuvant endocrine therapy within the past 6 months, underwent US-guided RF ablation while under local anesthesia and sedation. Only tumors measuring 3 cm or smaller and situated at least 1 cm from the skin, nipple, and chest wall were selected. Multitine electrodes were used. Endocrine therapy was continued for a total of 5 years, and breast irradiation was not performed. Clinical follow-up included US, mammography, and dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging every 2 months for 6 months and then every 6 months until 5 years. Primary end points were RF ablation efficacy at 1 year on the basis of DCE MR imaging follow-up and procedural tolerance. The secondary end point was delayed local efficacy at the end of endocrine therapy (5 years) on the basis of DCE MR imaging follow-up. Twenty-one women were treated from December 2004 to April 2010 (median age, 79 years; age range, 70-88 years). Efficacy was demonstrated at 1 year, with only one patient presenting with a local relapse. No general complications were noted. Skin burn occurred in four patients, with spontaneous healing after a maximum of 2 months. Ten patients were followed up for 5 years, with three additional patients presenting with cancer recurrence outside the ablation zone at 30, 48, and 60 months-including two with lobular carcinoma. Four patients died during the full follow-up, two of breast cancer-related causes and two of unrelated causes. RF ablation in elderly patients with nonresected breast cancer is well tolerated and efficient at 1-year follow-up. The technique is not recommended for lobular carcinoma.Radiology 06/2012; 264(2):597-605. · 5.73 Impact Factor -
Article: Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.
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ABSTRACT: Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median follow-up. BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years. Treatment has ended for all patients and detailed safety results for adverse events that occurred during the 5 years of treatment have been reported elsewhere. Follow-up is continuing for those enrolled in the four-arm option. BIG 1-98 is registered at clinicaltrials.govNCT00004205. 8010 patients were included in the trial, with a median follow-up of 8·1 years (range 0-12·4). 2459 were randomly assigned to monotherapy with tamoxifen for 5 years and 2463 to monotherapy with letrozole for 5 years. In the four-arm option of the trial, 1546 were randomly assigned to letrozole for 5 years, 1548 to tamoxifen for 5 years, 1540 to letrozole for 2 years followed by tamoxifen for 3 years, and 1548 to tamoxifen for 2 years followed by letrozole for 3 years. At a median follow-up of 8·7 years from randomisation (range 0-12·4), letrozole monotherapy was significantly better than tamoxifen, whether by IPCW or intention-to-treat analysis (IPCW disease-free survival HR 0·82 [95% CI 0·74-0·92], overall survival HR 0·79 [0·69-0·90], DRFI HR 0·79 [0·68-0·92], BCFI HR 0·80 [0·70-0·92]; intention-to-treat disease-free survival HR 0·86 [0·78-0·96], overall survival HR 0·87 [0·77-0·999], DRFI HR 0·86 [0·74-0·998], BCFI HR 0·86 [0·76-0·98]). At a median follow-up of 8·0 years from randomisation (range 0-11·2) for the comparison of the sequential groups with letrozole monotherapy, there were no statistically significant differences in any of the four endpoints for either sequence. 8-year intention-to-treat estimates (each with SE ≤1·1%) for letrozole monotherapy, letrozole followed by tamoxifen, and tamoxifen followed by letrozole were 78·6%, 77·8%, 77·3% for disease-free survival; 87·5%, 87·7%, 85·9% for overall survival; 89·9%, 88·7%, 88·1% for DRFI; and 86·1%, 85·3%, 84·3% for BCFI. For postmenopausal women with endocrine-responsive early breast cancer, a reduction in breast cancer recurrence and mortality is obtained by letrozole monotherapy when compared with tamoxifen montherapy. Sequential treatments involving tamoxifen and letrozole do not improve outcome compared with letrozole monotherapy, but might be useful strategies when considering an individual patient's risk of recurrence and treatment tolerability. Novartis, United States National Cancer Institute, International Breast Cancer Study Group.The lancet oncology 11/2011; 12(12):1101-8. · 14.47 Impact Factor -
Article: [Medical treatments of endocrine-sensitive Her-2 negative breast cancers: a review].
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ABSTRACT: New molecular classification is one of the cornerstones of current and future progress in research and patient care for breast carcinoma. For the larger hormone-receptor positive and Her-2 negative subgroup, which concerns 75% of the patients, endocrine therapy and chemotherapy may be considered. Looking toward new-targeted therapies, this paper reviews the current use of these two treatment modalities in adjuvant, neoadjuvant and metastatic settings of this disease.Bulletin du cancer 06/2011; 98(6):655-70. · 0.67 Impact Factor -
Article: TP53 status for prediction of sensitivity to taxane versus non-taxane neoadjuvant chemotherapy in breast cancer (EORTC 10994/BIG 1-00): a randomised phase 3 trial.
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ABSTRACT: TP53 has a crucial role in the DNA damage response. We therefore tested the hypothesis that taxanes confer a greater advantage than do anthracyclines on breast cancers with mutated TP53 than in those with wild-type TP53. In an open-label, phase 3 study, women (age <71 years) with locally advanced, inflammatory, or large operable breast cancers were randomly assigned in a 1:1 ratio to either a standard anthracycline regimen (six cycles of intravenous fluorouracil 500 mg/m², epirubicin 100 mg/m², and cyclophosphamide 500 mg/m² every 21 days [FEC100], or fluorouracil 600 mg/m², epirubicin 75 mg/m², cyclophosphamide 900 mg/m² [tailored FEC] starting on day 1 and then every 21 days) or a taxane-based regimen (three cycles of docetaxel 100 mg/m², intravenously infused over 1 h on day 1 every 21 days, followed by three cycles of intravenous epirubicin 90 mg/m² and docetaxel 75 mg/m² on day 1 every 21 days [T-ET]) at 42 centres in Europe. Randomisation was by use of a minimisation method that stratified patients by institution and initial tumour stage. The primary endpoint was progression-free survival (PFS) according to TP53 status. Analysis was by intention to treat. This is the final analysis of this trial. The study is registered with ClinicalTrials.gov, number NCT00017095. 928 patients were enrolled in the FEC group and 928 in the T-ET group. TP53 status was not assessable for 183 (20%) patients in the FEC group and 204 (22%) patients in the T-ET group mainly because of low tumour-cell content in the biopsy. 361 primary endpoint events were recorded in the FEC group and 314 in the T-ET group. In patients with TP53-mutated tumours, 5-year PFS was 59·5% (95% CI 53·4-65·1) in the T-ET group (n=326) and 55·3% (49·2-60·9) in the FEC group (n=318; hazard ratio 0·84, 98% CI 0·63-1·14; p=0·17). In patients with TP53 wild-type tumours, 5-year PFS was 66·8% (95% CI 61·4-71·6) in the T-ET group (n=398) and 64·7% (59·6-69·4) in the FEC group (n=427; 0·89, 98% CI 0·68-1·18; p=0·35). For all patients, irrespective of TP53 status, 5-year PFS was 65·1% (95% CI 61·6-68·3) in the T-ET group and 60·8% (57·3-64·2) in the FEC group (0·85, 98% CI 0·71-1·02; p=0·035). At the sites using FEC100 versus T-ET, the most common grade 3 or 4 adverse events were febrile neutropenia (75 [9%] of 803 vs 173 [21%] of 809, respectively), and neutropenia (653 [81%] vs 730 [90%], respectively). At the sites using tailored FEC versus T-ET, the most common grade 3 or 4 adverse events were febrile neutropenia (ten [8%] of 118 vs 26 [22%] of 116, respectively), and neutropenia (100 [85%] vs 115 [99%], respectively). Two patients died of toxicity during or within 30 days of chemotherapy completion and without disease relapse (one in each group). Although TP53 status was prognostic for overall survival, it was not predictive of preferential sensitivity to taxanes. TP53 status tested by use of the yeast assay in this patient population cannot be used to select patients for an anthracycline-based chemotherapy versus a taxane-based chemotherapy. US National Cancer Institute, La Ligue Nationale Contre le Cancer, European Union, Pharmacia, and Sanofi-Aventis.The lancet oncology 06/2011; 12(6):527-39. · 14.47 Impact Factor -
Article: Analyses adjusting for selective crossover show improved overall survival with adjuvant letrozole compared with tamoxifen in the BIG 1-98 study.
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ABSTRACT: Among postmenopausal women with endocrine-responsive breast cancer, the aromatase inhibitor letrozole, when compared with tamoxifen, has been shown to significantly improve disease-free survival (DFS) and time to distant recurrence (TDR). We investigated whether letrozole monotherapy prolonged overall survival (OS) compared with tamoxifen monotherapy. Of 8,010 postmenopausal women with hormone receptor-positive, early breast cancer enrolled on the Breast International Group (BIG) 1-98 study, 4,922 were randomly assigned to 5 years of continuous adjuvant therapy with either letrozole or tamoxifen. Of 2,459 patients enrolled in the tamoxifen treatment arm, 619 (25.2%) selectively crossed over to either adjuvant or extended letrozole after initial trial results were presented in January 2005. To gain better estimates of relative treatment effects in the presence of selective crossover, we used inverse probability of censoring weighted (IPCW) modeling. Weighted Cox models, by using IPCW, estimated a statistically significant, 18% reduction in the hazard of an OS event with letrozole treatment (hazard ratio [HR], 0.82; 95% CI, 0.70 to 0.95). Estimates of 5-year OS on the basis of IPCW were 91.8% and 90.4% for letrozole and tamoxifen, respectively. The HRs of DFS and TDR events by using IPCW modeling were 0.83 (95% CI, 0.74 to 0.94) and 0.80 (95% CI, 0.67 to 0.94), respectively (P < .05 for DFS, OS, and TDR). Median follow-up was 74 months. Adjuvant treatment with letrozole, compared with tamoxifen, significantly reduces the risk of death, the risk of recurrent disease, and the risk of recurrence at distant sites in postmenopausal women with hormone receptor-positive breast cancer.Journal of Clinical Oncology 02/2011; 29(9):1117-24. · 18.37 Impact Factor -
Article: Retraction--Validation of gene signatures that predict the response of breast cancer to neoadjuvant chemotherapy: a substudy of the EORTC 10994/BIG 00-01 clinical trial.
The lancet oncology 02/2011; 12(2):116. · 14.47 Impact Factor -
Article: Ductal carcinoma in situ of the breast: influence of age on diagnostic, therapeutic, and prognostic features. Retrospective study of 812 patients.
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ABSTRACT: The objective of this retrospective study was to identify prognostic, diagnostic, and therapeutic disparities between younger (≤ 40 years) and older (> 40 years) women with ductal carcinoma in situ (DCIS) of the breast. From 1971 to 2001, all patients treated for DCIS at Institut Bergonié were included in our analyses. Follow-up data was collected over 10 years. We used univariate and multivariate analyses to investigate patient-, disease-, and treatment-related factors predictive of diagnostic, histological, therapeutic, and prognostic DCIS criteria. A total of 812 patients were eligible including 731 women aged >40 years and 81 women ≤40 years. Younger women with DCIS were more likely to receive a mastectomy and less likely to receive radiotherapy. Young age and initial surgical treatment (lumpectomy and especially nonfree margins) were revealed as predictive of recurrence in multivariate analyses. Young age represents a recurrence risk independent of histological and clinical characteristics of the tumor. Initial treatment, especially for nonfree margins, is also a predictive factor. Appropriate initial surgery with particularly wide margins appears essential for the treatment of young women with DCIS.Annals of Surgical Oncology 11/2010; 18(5):1372-9. · 4.17 Impact Factor -
Article: First-line chemotherapy for metastatic breast cancer in patients ≥75 years: a retrospective single-centre analysis.
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ABSTRACT: Data on chemotherapy for elderly patients with metastatic breast carcinoma (MBC) are limited. We performed a 7-year retrospective analysis of MBC patients at our institution receiving first-line chemotherapy aged ≥75 years. Of 117 patients, 103 received monotherapy (67 capecitabine, 29 vinorelbine, 5 docetaxel, 2 liposomal doxorubicin) and 14 received polychemotherapy (12 anthracycline-based, 2 vinorelbine-gemcitabine). Chemotherapy demonstrated acceptable tolerability. Median progression-free survival (PFS) and overall survival (OS) from initiation of chemotherapy were 6.2 months and 13.8 months, respectively. At 2 years, 25% of patients were alive; however, 25% died within 3 months of beginning chemotherapy. Independent prognostic factors for longer PFS were good performance status, absence of visceral disease and capecitabine treatment. Good performance status and lack of visceral disease were also significant for OS. These results suggest that palliative chemotherapy should not be systematically excluded in this setting, but should be carefully discussed as it appears to be feasible with apparent benefit in selected patients.Critical reviews in oncology/hematology 10/2010; 80(1):171-9. · 5.27 Impact Factor -
Article: Results of a phase II study comparing three dosing regimens of fulvestrant in postmenopausal women with advanced breast cancer (FINDER2).
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ABSTRACT: The Faslodex Investigation of Dose evaluation in Estrogen Receptor-positive advanced breast cancer (FINDER)2 study evaluated the efficacy, safety, and pharmacokinetics (PK) of three fulvestrant dosing regimens. FINDER2 enrolled Western postmenopausal women recurring or progressing after prior endocrine therapy. Primary endpoint: objective response rate (ORR); secondary endpoints: time to progression (TTP), clinical benefit rate (CBR), tolerability, and PK parameters. Patients were randomized to receive fulvestrant: 250 mg/month (approved dose [AD]); 250 mg plus loading dose (loading dose [LD]; 500 mg on day 0, 250 mg on days 14, 28, and monthly thereafter); or 500 mg (high dose [HD]; 500 mg/month plus 500 mg on day 14 of Month 1). Treatment continued until disease progression or discontinuation. 144 patients were randomized: fulvestrant AD (n = 47); LD (n = 51); HD (n = 46). ORRs were: 8.5% (95% confidence interval [CI]: 2.4, 20.4%), 5.9% (1.2, 16.2%), and 15.2% (6.3, 28.9%) in the AD, LD, and HD arms, respectively. CBRs were: 31.9% (95% CI: 19.1, 47.1%), 47.1% (32.9, 61.5%), and 47.8% (32.9, 63.1%) for the AD, LD, and HD arms, respectively. Median TTP (months) was numerically longer for HD (6.0) and LD (6.1) versus AD (3.1). Tolerability was similar across dosing regimens. Steady-state plasma fulvestrant concentrations were predictable and achieved earlier with LD and HD. While there appeared to be a trend toward improved efficacy with HD and LD versus AD, no significant differences could be shown. A parallel study (FINDER1) has reported similar findings in Japanese patients.Breast Cancer Research and Treatment 09/2010; 123(2):453-61. · 4.43 Impact Factor -
Article: Is it useful to detect lymphovascular invasion in lymph node-positive patients with primary operable breast cancer?
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ABSTRACT: Lymphovascular invasion (LVI) is a widely recognized prognostic factor in lymph node-negative breast cancers. However, there are only limited and controversial data about its prognostic significance in lymph node-positive patients. Among 931 patients operated on and monitored at the authors' institution for an invasive breast carcinoma between 1989 and 1992, all 374 lymph node-positive breast cancers entered the study (median follow-up, 126 months). LVI was present in 46% of tumors and was associated with age < or = 40 years (P = .02), high histological grade (P = .01), and negative estrogen receptor status (P = .032), but not with tumor size, number of involved lymph nodes, or HER-2/neu status. LVI was an independent prognostic factor for distant metastases (P = .002). Furthermore, in HER-2/neu-negative/hormone receptor-positive (n = 287) tumors, the number of independent prognostic factors (LVI, age, histological grade, number of involved lymph nodes, and tumor size) was associated with a 5-years metastasis-free survival ranging from 100% if no factors (n = 25) to 89% +/- 2% if 1 or 2 factors (n = 186) and 67% +/- 6 if 3, 4, or 5 factors (n = 76) were present (P < .001). LVI is an independent prognostic factor in lymph node-positive breast cancer and merits further prospective investigations as a decision tool in the adjuvant chemotherapy setting.Cancer 07/2010; 116(13):3093-101. · 4.77 Impact Factor -
Article: Re: Population-based study of peritumoral lymphovascular invasion and outcome among patients with operable breast cancer.
CancerSpectrum Knowledge Environment 02/2010; 102(4):275-6; author reply 276-7. · 14.07 Impact Factor -
Article: Efficacy of trastuzumab in routine clinical practice and after progression for metastatic breast cancer patients: the observational Hermine study.
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ABSTRACT: The Hermine study observed the use of trastuzumab for metastatic breast cancer (MBC) in routine practice, including patients who received trastuzumab treatment beyond progression (TBP). The study observed 623 patients for > or = 2 years. Treatment was given according to oncologists' normal clinical practices. Endpoints included duration of treatment, efficacy, and cardiac safety. The TBP subanalysis compared overall survival (OS) in 177 patients who received first-line trastuzumab and either continued trastuzumab for > or = 30 days following progression or stopped at or before progression. The median treatment duration was 13.3 months. In the first-, second-, and third-line or beyond treatment groups, the median time to progression (TTP) were 10.3 months, 9.0 months, and 6.3 months, and the median OS times were 30.3 months, 27.1 months, and 23.2 months, respectively. Heart failure was observed in 2.6% of patients, although no cardiac-associated deaths occurred. In the TBP subanalysis, the median OS duration from treatment initiation and time of disease progression were longer in patients who continued receiving trastuzumab TBP (>27.8 months and 21.3 months, respectively) than in those who stopped (16.8 months and 4.6 months, respectively). However, the groups were not completely comparable, because patients who continued trastuzumab TBP had better prognoses at treatment initiation. The median TTP was longer in patients who continued trastuzumab TBP (10.2 months) than in those who stopped (7.1 months). The Hermine findings confirm that the pivotal trials of first-line trastuzumab treatment in MBC patients are applicable in clinical practice. The subanalysis suggests that trastuzumab TBP offers a survival benefit to MBC patients treated with first-line trastuzumab.The Oncologist 01/2010; 15(8):799-809. · 3.91 Impact Factor -
Article: First-line capecitabine monotherapy for slowly progressing metastatic breast cancer: do we need aggressive treatment?
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ABSTRACT: Primary treatment goals in less aggressive metastatic breast cancer (MBC) are prolonged survival, good quality of life and control of the disease and its symptoms. High activity, oral administration and no alopecia make capecitabine monotherapy attractive in slowly evolving disease. We retrospectively analysed 226 patients who had received single-agent capecitabine as 1st-line chemotherapy at our institution. The median interval between breast cancer diagnosis and MBC was 52 months (range 0-479); 76% had received endocrine therapy for MBC, 58% had visceral involvement and 30% had 3 or more metastatic sites. The median starting dose was 1,000 mg/m(2) twice daily. Disease was improved in 56% of the patients (median duration: 13.2 months) and stabilised in 20%. Median time to treatment failure was 8.8 months (95% CI: 7.1-10.5); median overall survival from initiating capecitabine was 23.6 months (95% CI: 19.7-27.4). Prior adjuvant chemotherapy, endocrine therapy for MBC, visceral disease, hormone receptor status and initial capecitabine dose did not influence time to treatment failure. Among 161 patients <75 years, 90% received further chemotherapy. Based on these findings, 1st-line capecitabine should be considered in slowly progressing disease, offering an active, well-tolerated oral treatment with minimal toxicity and no alopecia. More toxic treatments may be reserved for more aggressive disease.Oncology 11/2009; 77(5):318-27. · 2.27 Impact Factor -
Article: Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer.
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ABSTRACT: The aromatase inhibitor letrozole, as compared with tamoxifen, improves disease-free survival among postmenopausal women with receptor-positive early breast cancer. It is unknown whether sequential treatment with tamoxifen and letrozole is superior to letrozole therapy alone. In this randomized, phase 3, double-blind trial of the treatment of hormone-receptor-positive breast cancer in postmenopausal women, we randomly assigned women to receive 5 years of tamoxifen monotherapy, 5 years of letrozole monotherapy, or 2 years of treatment with one agent followed by 3 years of treatment with the other. We compared the sequential treatments with letrozole monotherapy among 6182 women and also report a protocol-specified updated analysis of letrozole versus tamoxifen monotherapy in 4922 women. At a median follow-up of 71 months after randomization, disease-free survival was not significantly improved with either sequential treatment as compared with letrozole alone (hazard ratio for tamoxifen followed by letrozole, 1.05; 99% confidence interval [CI], 0.84 to 1.32; hazard ratio for letrozole followed by tamoxifen, 0.96; 99% CI, 0.76 to 1.21). There were more early relapses among women who were assigned to tamoxifen followed by letrozole than among those who were assigned to letrozole alone. The updated analysis of monotherapy showed that there was a nonsignificant difference in overall survival between women assigned to treatment with letrozole and those assigned to treatment with tamoxifen (hazard ratio for letrozole, 0.87; 95% CI, 0.75 to 1.02; P=0.08). The rate of adverse events was as expected on the basis of previous reports of letrozole and tamoxifen therapy. Among postmenopausal women with endocrine-responsive breast cancer, sequential treatment with letrozole and tamoxifen, as compared with letrozole monotherapy, did not improve disease-free survival. The difference in overall survival with letrozole monotherapy and tamoxifen monotherapy was not statistically significant. (ClinicalTrials.gov number, NCT00004205.)New England Journal of Medicine 09/2009; 361(8):766-76. · 53.30 Impact Factor -
Article: Prediction of HER2 gene status in Her2 2+ invasive breast cancer: a study of 108 cases comparing ASCO/CAP and FDA recommendations.
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ABSTRACT: Most Her2 testing guidelines recommend that all cases scoring Her2 2+ by immunohistochemistry should be analyzed by fluorescent in situ hybridization (FISH) to determine HER2 status to confirm eligibility for Trastuzumab therapy in breast cancer. The aim of our study was to determine HER2 gene and chromosome 17 (CEN17) status in a series of 108 Her2 2+ consecutive cases and study the correlation between pathological characteristics of the tumors and HER2 amplification. Invasive breast cancers were tested by FISH using the Dako HER2 FISH pharmDx kit. The Her2 immunohistochemistry protocol was performed using the polyclonal AO485 antibody (Dako) diluted to 1:1500. HER2 and CEN17 status were correlated to tumor SBR grade, mitotic count, estrogen receptor, progesterone receptor status and percentage of Her2 immunohistochemistry-positive cells. Following Food and Drug Administration guidelines, ie, HER2/CEN17 ratio >or=2 and an HER2 copy number >4, amplified cases were observed in 36 (33%) and 49 (45%) cases, respectively, and following American Society of Clinical Oncology/College of American Pathologists guidelines, ie, HER2/CEN17 ratio >2.2 and an HER2 copy number >6, amplified cases represented 30 and 24% of the study population, respectively. Chromosome 17 polysomy (CEN17 >2.25) was observed in 39 (36%) tumors. Significant positive correlations were found between FISH HER2 amplified cases and Her2 immunostaining >60% (P=1.1.10(-5)), SBR grade 3 (P=0.0001), nuclear atypia (P=0.03) and mitotic count (P=0.008). By multivariate analysis, Her2 immunostaining >60% (P<10(-3)) and SBR grade 3 (P<10(-3)) were independent factors predicting HER2 amplification status irrespective to cutoff guidelines. All SBR grade 3 cases with more than 60% Her2+ cells had an HER2/CEN17 ratio >or=2, only one had a ratio <or=2.2. In our series of consecutive Her2 2+ cases, one-third demonstrated HER2 amplification, and one-third had chromosome 17 polysomy. Pathological factors, in particular SBR grade 3 and more than 60% Her2+ cells, were significantly correlated with HER2 amplification.Modern Pathology 01/2009; 22(3):403-9. · 4.79 Impact Factor -
Article: Prediction of HER2 gene status in Her2 2+ invasive breast cancer: a study of 108 cases comparing ASCO/CAP and FDA recommendations
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ABSTRACT: Most Her2 testing guidelines recommend that all cases scoring Her2 2+ by immunohistochemistry should be analyzed by fluorescent in situ hybridization (FISH) to determine HER2 status to confirm eligibility for Trastuzumab therapy in breast cancer. The aim of our study was to determine HER2 gene and chromosome 17 (CEN17) status in a series of 108 Her2 2+ consecutive cases and study the correlation between pathological characteristics of the tumors and HER2 amplification. Invasive breast cancers were tested by FISH using the Dako HER2 FISH pharmDx® kit. The Her2 immunohistochemistry protocol was performed using the polyclonal AO485 antibody (Dako®) diluted to 1:1500. HER2 and CEN17 status were correlated to tumor SBR grade, mitotic count, estrogen receptor, progesterone receptor status and percentage of Her2 immunohistochemistry-positive cells. Following Food and Drug Administration guidelines, ie, HER2/CEN17 ratio ≥2 and an HER2 copy number >4, amplified cases were observed in 36 (33%) and 49 (45%) cases, respectively, and following American Society of Clinical Oncology/College of American Pathologists guidelines, ie, HER2/CEN17 ratio >2.2 and an HER2 copy number >6, amplified cases represented 30 and 24% of the study population, respectively. Chromosome 17 polysomy (CEN17 >2.25) was observed in 39 (36%) tumors. Significant positive correlations were found between FISH HER2 amplified cases and Her2 immunostaining >60% (P=1.1.10−5), SBR grade 3 (P=0.0001), nuclear atypia (P=0.03) and mitotic count (P=0.008). By multivariate analysis, Her2 immunostaining >60% (P<10−3) and SBR grade 3 (P<10−3) were independent factors predicting HER2 amplification status irrespective to cutoff guidelines. All SBR grade 3 cases with more than 60% Her2+ cells had an HER2/CEN17 ratio ≥2, only one had a ratio ≤2.2. In our series of consecutive Her2 2+ cases, one-third demonstrated HER2 amplification, and one-third had chromosome 17 polysomy. Pathological factors, in particular SBR grade 3 and more than 60% Her2+ cells, were significantly correlated with HER2 amplification.Keywords: HER2, FISH, immunohistochemistry, amplificationModern Pathology 12/2008; 22(3):403-409. · 4.79 Impact Factor -
Article: Activity of fulvestrant versus exemestane in advanced breast cancer patients with or without visceral metastases: data from the EFECT trial.
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ABSTRACT: Patients with visceral metastases (VM: lung and/or liver metastases) are generally regarded as being less responsive to hormonal therapy, and chemotherapy often becomes the default treatment. This paper reports a subgroup analysis from EFECT (The Evaluation of Faslodex versus Exemestane Clinical Trial) examining the efficacy of fulvestrant and exemestane in patients with or without VM. EFECT is a randomised, double-blind, multicentre, Phase III trial in postmenopausal women with advanced breast cancer progressing or recurring after prior non-steroidal aromatase inhibitor therapy. Overall, approximately 57% of patients in EFECT had visceral involvement. Fulvestrant and exemestane demonstrated clinical benefit in 29.1% and 27.2% of patients with VM, respectively. Median duration of response was 13.5 vs 10.8 months and median duration of clinical benefit was 9.9 vs 8.1 months, respectively. These results encourage the use of endocrine agents such as fulvestrant in treating patients with advanced breast cancer and VM.Breast Cancer Research and Treatment 12/2008; 117(1):69-75. · 4.43 Impact Factor -
Article: D2-40 in breast cancer: should we detect more vascular emboli?
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ABSTRACT: Peritumoral emboli assessed on hematoxylin-eosin-stained slides are taken into account for treatment of patients with operable breast cancer. We assessed whether immunostaining with D2-40 improves the prognostic significance of emboli in a group of tumors with a large immunohistochemical sampling and a long-term follow-up. Topography, number, and extension of hematoxylin-eosin and D2-40 emboli were compared in 94 node-negative breast cancers (median number of immunostained slides per tumor: 3). Metastasis-free survival of patients with or without hematoxylin-eosin and/or D2-40 emboli were evaluated (median follow-up of 178 months). Hematoxylin-eosin emboli were detected in 14 (15%) tumors and were located at distance from the tumor. D2-40 emboli were detected in 39 (41%) tumors and was often multiple (n=30), extensive (n=23), located within (n=13), close to (n=10) or at distance from the tumor (n=16). The 12 distant hematoxylin-eosin and D2-40 emboli were located in the same vessels (seven missed at the first hematoxylin-eosin examination and secondarily diagnosed by D2-40 staining). A difference in metastasis-free survival was found only between patients with no D2-40 emboli and those with distant D2-40 emboli (P=0.02). D2-40 emboli located within or close to the tumor had no prognostic value. Comparing the metastasis-free survival of patients with or without hematoxylin-eosin emboli, the prognostically unfavorable significance of hematoxylin-eosin emboli was improved when taking into account the seven patients with missed emboli at the first examination and secondarily diagnosed by D2-40 staining (P=0.006 vs 0.003). To conclude, D2-40 increases the diagnostic sensitivity of emboli in breast carcinoma and the high incidence of D2-40 emboli might be related to the number of immunostained slides per case. Nevertheless, only distant D2-40+ emboli had a prognostic impact. In practice, D2-40 might be useful to detect missed hematoxylin-eosin emboli especially in cases without any other prognostically unfavorable criterion.Modern Pathology 10/2008; 22(2):216-22. · 4.79 Impact Factor -
Article: Epithelial atypia: a marker risk of concomitant or subsequent breast carcinoma?
Journal of Clinical Oncology 10/2008; 26(27):4514-5; author reply 4515. · 18.37 Impact Factor -
Article: Distinction between isolated tumor cells and micrometastases in breast cancer: is it reliable and useful?
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ABSTRACT: In routine practice, the distinction between isolated tumor cells (ITC) and micrometastases (MIC) in patients with breast cancer is sometimes difficult to discern. The authors assessed differences in classifying patients according to the American Joint Commission on Cancer (AJCC) and the International Union Against Cancer (UICC) definitions and method of sizing. We assessed the characteristics of metastatic deposits in only 1 involved lymph node in 337 patients with operable breast cancer (median follow-up, 15.3 years). When sizing multiple clusters, either the diameter of the area with close clusters (Method 1) or the size of the largest cluster (Method 2) was taken into account. Patients were classified and their survival was assessed according to the 2 sizing methods and the criteria used for definitions (size in AJCC; size and topography in UICC). With the AJCC definitions, 32 patients would be differently classified according to the method of sizing. With the UICC definitions, some patients with parenchymal ITC would be classified as pN1mi, 38 by Method 1 and 53 by Method 2. Some pathologists would classify the 66 patients who had isolated capsular vascular invasion as pN0. Classification was uncertain in 136 (40%) to 151 (45 %) patients. Survival was not significantly different between pN0(i+) and pN1(mi) patients. The distinction between ITC and MIC was often difficult and without any prognostic significance. Precise guidelines are more useful for staging than for therapy. Thus, complete axillary dissection is usually performed in pN0(i+) and pN1(mi) patients, whereas chemotherapy is not indicated or debatable when MIC is the only 1 pejorative criterion.Cancer 05/2008; 112(8):1672-8. · 4.77 Impact Factor
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Institutions
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2011
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IEO - Istituto Europeo di Oncologia
Milano, Lombardy, Italy
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2002–2010
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Institut Bergonié
Bordeaux, Aquitaine, France
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2007
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International Breast Cancer Study Group
Bern, BE, Switzerland
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2006
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Schweizerischen Arbeitsgemeinschaft für Klinische Krebsforschung
Bern, BE, Switzerland
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2005
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Medical University of Vienna
- Institut für Sozialmedizin
Vienna, Vienna, Austria
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