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Natalie Jones,
Françoise Bonnet,
Sana Sfar,
Marie Lafitte,
Delfine Lafon,
Ghislaine Sierankowski,
Véronique Brouste,
Guillaume Banneau,
Christine Tunon de Lara, Marc Debled,
Gaëtan Mac Grogan,
Michel Longy,
Nicolas Sevenet
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ABSTRACT: PTEN plays a well-established role in the negative regulation of the PI3K pathway which is frequently activated in several cancer types, including breast cancer. A nuclear function in the maintenance of chromosomal stability has been proposed for PTEN but is yet to be clearly defined. In order to improve understanding of the role of PTEN in mammary tumorigenesis in terms of a possible gene dosage effect, its PI3K pathway function and its association with p53, we undertook comprehensive analysis of PTEN status in 135 sporadic invasive ductal carcinomas. Four PTEN status groups were defined; complete loss (19/135, 14%), reduced copy number (19/135, 14%), normal (86/135, 64%) and complex (11/135, 8%). Whereas the PTEN complete loss status was significantly associated with estrogen receptor (ER) negativity (P=0.006) and in particular the basal-like phenotype (P<0.0001), a reduced PTEN copy number was not associated with hormone receptor status or a particular breast cancer subtype. Overall, PI3K pathway alteration was suggested to be involved in 59% (79/134) of tumours as assessed by HER2 overexpression, PIK3CA mutation or a complete loss of PTEN. A complex PTEN status was identified in a tumour subgroup which displayed a specific, complex DNA profile at the PTEN locus with a strikingly similar highly rearranged pan-genomic profile. All of these tumours had relapsed and were associated with a poorer prognosis in the context of node negative disease (P = 1.4x10(-13) ) thus may represent a tumour subgroup with a common molecular alteration which could be targeted to improve clinical outcome. © 2013 Wiley Periodicals, Inc.
International Journal of Cancer 01/2013; · 5.44 Impact Factor
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Françoise Bonnet,
Mickael Guedj,
Natalie Jones,
Sana Sfar,
Véronique Brouste,
Nabila Elarouci,
Guillaume Banneau,
Béatrice Orsetti,
Charlotte Primois,
Christine Tunon de Lara, Marc Debled,
Isabelle de Mascarel,
Charles Theillet,
Nicolas Sévenet,
Aurélien de Reynies,
Gaëtan Macgrogan,
Michel Longy
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ABSTRACT: BACKGROUND: Despite entering complete remission after primary treatment, a substantial proportion of patients with early stage breast cancer will develop metastases. Prediction of such an outcome remains challenging despite the clinical use of several prognostic parameters. Several reports indicate that genomic instability, as reflected in specific chromosomal aneuploidies and variations in DNA content, influences clinical outcome but no precise definition of this parameter has yet been clearly established. METHODS: To explore the prognostic value of genomic alterations present in primary tumors, we performed a comparative genomic hybridization study on BAC arrays with a panel of breast carcinomas from 45 patients with metastatic relapse and 95 others, matched for age and axillary node involvement, without any recurrence after at least 11 years of follow-up. Array-CGH data was used to establish a two-parameter index representative of the global level of aneusomy by chromosomal arm, and of the number of breakpoints throughout the genome. RESULTS: Application of appropriate thresholds allowed us to distinguish three classes of tumors highly associated with metastatic relapse. This index used with the same thresholds on a published set of tumors confirms its prognostic significance with a hazard ratio of 3.24 [95CI: 1.76-5.96] p = 6.7x10-5 for the bad prognostic group with respect to the intermediate group. The high prognostic value of this genomic index is related to its ability to individualize a specific group of breast cancers, mainly luminal type and axillary node negative, showing very high genetic instability and poor outcome. Indirect transcriptomic validation was obtained on independent data sets. CONCLUSION: Accurate evaluation of genetic instability in breast cancers by a genomic instability index (G2I) helps individualizing specific tumors with previously unexpected very poor prognosis.
BMC Medical Genomics 11/2012; 5(1):54. · 3.69 Impact Factor
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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
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ABSTRACT: Desmoid tumors are rare mesenchymal neoplasms without metastatic potential. Despite the benign nature of this condition, some patients develop disease progression despite all locoregional options for care. Aggressive forms of desmoid tumors may induce morbidity that can lead to physical impairment and mortality that is occasionally observed as a result of local infiltrative growth and tissue invasion, in particular with abdominal disease. Few therapeutic options are available for patients with recurrent/unresectable desmoid tumors. Several studies have suggested the potential benefit of antiestrogens such as tamoxifen in this setting. Here we report the first description of the efficacy of an aromatase inhibitor in a patient with a desmoid tumor.
Future Oncology 04/2012; 8(4):483-6. · 3.16 Impact Factor
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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
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ABSTRACT: While the over-representation of the elderly in the breast cancer population is projected to dramatically increase within the next two decades, data on chemotherapy for elderly patients with metastatic breast carcinoma (MBC) remain very limited. The aim of the present study is to investigate whether elderly patients included in clinical studies for MBC are representative of the population seen during usual clinical practice. Firstly, a review of the literature was performed identifying 39 publications about chemotherapy for MBC focusing on elderly patients and we examined patient characteristics in each of these publications. Comparison of the age distribution of patients included in these studies with that of a large cohort of consecutive MBC patients aged 65years who received chemotherapy in our institution over the last ten years (n=573) indicated that trials tend to include relatively younger patients. Furthermore, criteria to assess external validity of the results are seldom reported. Possible ways to improve the applicability of results such as increasing the minimum age for inclusion and the use of CGA are proposed.
Cancer treatment reviews 05/2011; 37(8):590-8. · 5.30 Impact Factor
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ABSTRACT: Randomized controlled trials (RCTs) represent the best evidence in oncology practice. The aim of this study was to assess the reporting quality of sarcoma RCTs and to identify significant predictors of quality.
Two investigators searched MEDLINE for pediatric and adult bone and soft tissue sarcoma RCTs published between January 1988 and December 2008. The quality of each report was assessed by using a 15-point overall reporting quality score based on 15 items from the revised Consolidated Standards of Reporting Trials (CONSORT) statement (overall quality score [OQS] range, 0 to 15 points). Concealment of allocation, appropriate blinding, and analysis according to intention-to-treat principle were assessed separately because of their crucial methodologic importance by using a 3-point key methodologic index score (MIS; range, 0 to 3).
We retrieved 72 relevant RCTs that included 16,029 patients. The median OQS was 9.5. Allocation concealment, blinding, and analysis by intent to treat were reported only in 21 (29%), nine (12.5%), and 23 (32%) of the 72 RCTs, respectively. The median MIS was 1 with a minimum of 0 and a maximum of 2. On multivariate analysis, publication after 1996 and high impact factor remained independent and significant predictors of improved OQS. The sole variable associated with improved MIS was the publication of chemotherapy-only trials.
Although the overall quality of sarcoma RCTs reporting has improved over time, reporting of key methodologic issues remains poor. This may lead to biased interpretation of sarcoma trial results.
Journal of Clinical Oncology 02/2011; 29(9):1204-9. · 18.37 Impact Factor
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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
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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
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Etienne G C Brain,
Cécile Mertens,
Véronique Girre,
Frédérique Rousseau,
Emmanuel Blot,
Sophie Abadie,
Lionel Uwer,
Emmanuelle Bourbouloux,
Isabelle Van Praagh-Doreau,
Loic Mourey,
Sylvie Kirscher,
Brigitte Laguerre,
Emmanuelle Fourme,
Sylvia Luneau,
Jean Genève, Marc Debled
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ABSTRACT: Breast cancer is a disease of ageing. Functional independence in elderly patients, measured with the Katz activities of daily living (ADL) scale, predicts overall survival and the need for welfare support. Few prospective studies have examined the feasibility of adjuvant chemotherapy and its impact on autonomy in women over 70 years of age with high-risk breast cancer. This multicentre phase II trial was designed to assess the impact of adjuvant anthracycline-based chemotherapy on these patients' autonomy.
In a two-stage Fleming design, women aged ≥70 years with histologically proven hormone-receptor-negative early breast cancer and a significant risk of recurrence (pN+ or "high risk" pN0) received 4 cycles of nonpegylated liposomal doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 3 weeks postoperatively, on an outpatient basis. The primary endpoint was the change in the ADL score during chemotherapy. Secondary endpoints include comprehensive geriatric, quality-of-life and acceptability assessments, tolerability, and long-term outcome. The results for the primary endpoint and other scales at completion of adjuvant chemotherapy are reported here, while long-term follow-up is not yet complete.
Forty patients (median age 75 [70-82]) were enrolled between February 2006 and November 2007. Chemotherapy had no deleterious impact on ADL, cognition, mental status, or the frequency of comorbidities. In contrast, the number of patients at risk of malnutrition, based on the Mini Nutritional Assessment, more than doubled between baseline and the end of chemotherapy, rising from 15% to 38%. Quality-of-life deteriorated in terms of social and role functioning, likely owing to fatigue, loss of appetite, nausea and vomiting. Treatment acceptability was good. The main adverse effect was neutropenia, 15% of the patients experiencing febrile neutropenia. No cardiac toxicity or toxic deaths occurred.
This study demonstrates the feasibility of an adjuvant chemotherapy regimen combining nonpegylated liposomal doxorubicin and cyclophosphamide in fit elderly women <85 years with breast cancer. Although chemotherapy had an impact on social and role functioning, autonomy was not impaired and toxicity was acceptable. Special attention should be paid to nutritional status before and after treatment.
Critical reviews in oncology/hematology 10/2010; 80(1):160-70. · 5.27 Impact Factor
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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
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ABSTRACT: The Cox model relies on the proportional hazards (PH) assumption, implying that the factors investigated have a constant impact on the hazard - or risk - over time. We emphasize the importance of this assumption and the misleading conclusions that can be inferred if it is violated; this is particularly essential in the presence of long follow-ups.
We illustrate our discussion by analyzing prognostic factors of metastases in 979 women treated for breast cancer with surgery. Age, tumour size and grade, lymph node involvement, peritumoral vascular invasion (PVI), status of hormone receptors (HRec), Her2, and Mib1 were considered.
Median follow-up was 14 years; 264 women developed metastases. The conventional Cox model suggested that all factors but HRec, Her2, and Mib1 status were strong prognostic factors of metastases. Additional tests indicated that the PH assumption was not satisfied for some variables of the model. Tumour grade had a significant time-varying effect, but although its effect diminished over time, it remained strong. Interestingly, while the conventional Cox model did not show any significant effect of the HRec status, tests provided strong evidence that this variable had a non-constant effect over time. Negative HRec status increased the risk of metastases early but became protective thereafter. This reversal of effect may explain non-significant hazard ratios provided by previous conventional Cox analyses in studies with long follow-ups.
Investigating time-varying effects should be an integral part of Cox survival analyses. Detecting and accounting for time-varying effects provide insights on some specific time patterns, and on valuable biological information that could be missed otherwise.
BMC Medical Research Methodology 03/2010; 10:20. · 2.67 Impact Factor
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CancerSpectrum Knowledge Environment 02/2010; 102(4):275-6; author reply 276-7. · 14.07 Impact Factor
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ABSTRACT: Abstract
Background
The Cox model relies on the proportional hazards (PH) assumption, implying that the factors investigated have a constant impact on the hazard - or risk - over time. We emphasize the importance of this assumption and the misleading conclusions that can be inferred if it is violated; this is particularly essential in the presence of long follow-ups.
Methods
We illustrate our discussion by analyzing prognostic factors of metastases in 979 women treated for breast cancer with surgery. Age, tumour size and grade, lymph node involvement, peritumoral vascular invasion (PVI), status of hormone receptors (HRec), Her2, and Mib1 were considered.
Results
Median follow-up was 14 years; 264 women developed metastases. The conventional Cox model suggested that all factors but HRec, Her2, and Mib1 status were strong prognostic factors of metastases. Additional tests indicated that the PH assumption was not satisfied for some variables of the model. Tumour grade had a significant time-varying effect, but although its effect diminished over time, it remained strong. Interestingly, while the conventional Cox model did not show any significant effect of the HRec status, tests provided strong evidence that this variable had a non-constant effect over time. Negative HRec status increased the risk of metastases early but became protective thereafter. This reversal of effect may explain non-significant hazard ratios provided by previous conventional Cox analyses in studies with long follow-ups.
Conclusions
Investigating time-varying effects should be an integral part of Cox survival analyses. Detecting and accounting for time-varying effects provide insights on some specific time patterns, and on valuable biological information that could be missed otherwise.
BMC Medical Research Methodology. 01/2010;
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ABSTRACT: In the setting of recurrent events, research studies commonly count only the first occurrence of an outcome in a subject. However this approach does not correctly reflect the natural history of the disease. The objective is to jointly identify prognostic factors associated with locoregional recurrences (LRR), contralateral breast cancer, distant metastases (DM), other primary cancer than breast and breast cancer death and to evaluate the correlation between these events.
Patients (n = 919) with a primary invasive breast cancer and treated in a cancer center in South-Western France with breast-conserving surgery from 1990 to 1994 and followed up to January 2006 were included. Several types of non-independent events could be observed for the same patient: a LRR, a contralateral breast cancer, DM, other primary cancer than breast and breast cancer death. Data were analyzed separately and together using a random-effects survival model.
LRR represent the most frequent type of first failure (14.6%). The risk of any event is higher for young women (less than 40 years old) and in the first 10 years of follow-up after the surgery. In the combined analysis histological tumor size, grade, number of positive nodes, progesterone receptor status and treatment combination are prognostic factors of any event. The results show a significant dependence between these events with a successively increasing risk of a new event after the first and second event. The risk of developing a new failure is greatly increased (RR = 4.25; 95%CI: 2.51-7.21) after developing a LRR, but also after developing DM (RR = 3.94; 95%CI: 2.23-6.96) as compared to patients who did not develop a first event.
We illustrated that the random effects survival model is a more satisfactory method to evaluate the natural history of a disease with multiple type of events.
BMC Cancer 01/2010; 10:697. · 3.01 Impact Factor
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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
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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
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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, amplification
Modern Pathology 12/2008; 22(3):403-409. · 4.79 Impact Factor
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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
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Journal of Clinical Oncology 10/2008; 26(27):4514-5; author reply 4515. · 18.37 Impact Factor
