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1.
Ann Surg Oncol ; 28(4): 2138-2145, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32920723

ABSTRACT

BACKGROUND: Diagnosis of atypical breast lesions (ABLs) leads to unnecessary surgery in 75-90% of women. We have previously developed a model including age, complete radiological target excision after biopsy, and focus size that predicts the probability of cancer at surgery. The present study aimed to validate this model in a prospective multicenter setting. - METHODS: Women with a recently diagnosed ABL on image-guided biopsy were recruited in 18 centers, before wire-guided localized excisional lumpectomy. Primary outcome was the negative predictive value (NPV) of the model. RESULTS: The NOMAT model could be used in 287 of the 300 patients included (195 with ADH). At surgery, 12 invasive (all grade 1), and 43 in situ carcinomas were identified (all ABL: 55/287, 19%; ADH only: 49/195, 25%). The area under the receiving operating characteristics curve of the model was 0.64 (95% CI 0.58-0.69) for all ABL, and 0.63 for ADH only (95% CI 0.56-0.70). For the pre-specified threshold of 20% predicted probability of cancer, NPV was 82% (77-87%) for all ABL, and 77% (95% CI 71-83%) for patients with ADH. At a 10% threshold, NPV was 89% (84-94%) for all ABL, and 85% (95% CI 78--92%) for the ADH. At this threshold, 58% of the whole ABL population (and 54% of ADH patients) could have avoided surgery with only 2 missed invasive cancers. CONCLUSION: The NOMAT model could be useful to avoid unnecessary surgery among women with ABL, including for patients with ADH. CLINICAL TRIAL REGISTRATION: NCT02523612.


Subject(s)
Breast Neoplasms , Carcinoma in Situ , Carcinoma, Ductal, Breast , Carcinoma, Intraductal, Noninfiltrating , Biopsy , Breast/pathology , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma in Situ/pathology , Carcinoma, Ductal, Breast/diagnostic imaging , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/surgery , Female , Humans , Hyperplasia/pathology , Prospective Studies , Unnecessary Procedures
2.
Br J Cancer ; 122(6): 759-765, 2020 03.
Article in English | MEDLINE | ID: mdl-32001832

ABSTRACT

BACKGROUND: Few data are available on survival and predictive factors in early breast cancer (BC) patients treated with neoadjuvant endocrine therapy (NET). METHODS: This is a pooled analysis of two multicentre, randomised non-comparative phase 2 clinical trials evaluating neoadjuvant anastrozole and fulvestrant efficacy for postmenopausal HR+/HER2- breast cancer patients: HORGEN (NCT00871858) and CARMINA02 (NCT00629616) studies. RESULTS: In total, 236 patients were included in CARMINA02 and HORGEN trials. Modified intention-to-treat analysis was available for 217 patients. Median follow-up was 65.2 months. Relapse-free survival (RFS) and overall survival (OS) at 5 years were 83.7% (95% CI: 77.9-88) and 92.7% (95% CI: 88.2-95.6), respectively, with no difference between treatment arms. On univariate analysis, tumour staging (T2 vs T3-4; p = 0.0001), Ki-67 at surgery (≤10% vs >10%; p = 0.0093), pathological tumour size (pT1-2 vs pT3-4; p = 0.0012) and node status (pN negative vs positive; p = 0.007), adjuvant chemotherapy (p = 0.0167) and PEPI score (PEPI group I + II vs III; p = 0.0004) were associated with RFS. No events were observed in patients with pathological response according to the Sataloff classification. Multivariate analysis showed that preoperative endocrine prognostic index (PEPI) group III was associated with significantly worse RFS (p = 0.0069, hazard ratio = 3.33 (95% CI: 1.39-7.98)). CONCLUSIONS: Postmenopausal HR+/HER2- breast cancer patients receiving NET generally have a favourable outcome. The PEPI score identifies a subset of patients of poorer prognosis who are candidates for further additional treatment.


Subject(s)
Breast Neoplasms/drug therapy , Neoadjuvant Therapy/methods , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Female , Humans , Prognosis , Survival Analysis , Time Factors
3.
Clin Breast Cancer ; 20(2): e164-e172, 2020 04.
Article in English | MEDLINE | ID: mdl-31780381

ABSTRACT

BACKGROUND: Ductal carcinoma in situ (DCIS) represents 15% of all breast cancers in France. The first national survey was conducted in 2003. The present multi-center real-life practice survey aimed at assessing possible changes in demographic, clinical, pathologic, and treatment features. MATERIAL AND METHODS: From March 2014 to September 2015, patients diagnosed with DCIS from 71 centers with complete information about age, diagnostic features, and treatment modalities were prospectively included. RESULTS: A total of 2125 patients with a median age of 58.6 years from 71 centers were studied. DCIS was diagnosed by mammography in 87.5% of cases. Preoperative biopsy was performed in 96% of cases. The median tumor size was 15 mm. Nuclear grade was low, intermediate, and high in 12%, 36%, and 47% of cases, respectively. Margins were considered to be negative in 83% of cases. Overall mastectomy and lumpectomy rates were 25% and 75%, respectively. The immediate breast reconstruction rate was 50%. Sentinel node biopsy and axillary dissection rates were 41% and 2.6%, respectively. After lumpectomy, 97% of patients underwent radiotherapy, and 32% received a boost dose. Only 1% of patients received endocrine therapy. Compared with our previous survey, the median tumor size remained the same, and the proportion of high-grade lesions increased by 9%. The mastectomy rate decreased by 4%. CONCLUSIONS: The clinical practice identified in this survey complies with French DCIS guidelines. About 10% of patients with low-grade DCIS may be eligible to participate in treatment de-escalation trials.


Subject(s)
Breast Neoplasms/therapy , Carcinoma, Intraductal, Noninfiltrating/therapy , Guideline Adherence/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/standards , Antineoplastic Agents, Hormonal/therapeutic use , Biopsy/standards , Biopsy/statistics & numerical data , Breast/diagnostic imaging , Breast/pathology , Breast/surgery , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Carcinoma, Intraductal, Noninfiltrating/epidemiology , Carcinoma, Intraductal, Noninfiltrating/pathology , Chemotherapy, Adjuvant/methods , Chemotherapy, Adjuvant/standards , Chemotherapy, Adjuvant/statistics & numerical data , Female , France/epidemiology , Humans , Mammaplasty/standards , Mammaplasty/statistics & numerical data , Mammography/standards , Mammography/statistics & numerical data , Mastectomy/methods , Mastectomy/standards , Mastectomy/statistics & numerical data , Medical Oncology/standards , Middle Aged , Practice Patterns, Physicians'/standards , Prospective Studies , Radiotherapy, Adjuvant/methods , Radiotherapy, Adjuvant/standards , Radiotherapy, Adjuvant/statistics & numerical data , Surveys and Questionnaires , Treatment Outcome
4.
Breast Cancer Res Treat ; 175(2): 379-387, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30759288

ABSTRACT

BACKGROUND: Invasive lobular carcinomas (ILCs) represent approximately 10% of all breast cancers. Despite this high frequency, benefit of adjuvant chemotherapy (CT) is still unclear. METHODS: Our objective was to investigate the impact of CT on survival in ILC. Patients were retrospectively identified from a cohort of 23,319 patients who underwent primary surgery in 15 French centers between 1990 and 2014. Only ILC, hormone-positive, human epidermal growth factor 2 (HER2)-negative patients who received adjuvant endocrine therapy (ET) were included. End-points were disease-free survival (DFS) and overall survival (OS). A propensity score for receiving CT, aiming to compensate for baseline characteristics, was used. RESULTS: Of a total of 2318 patients with ILC, 1485 patients (64%) received ET alone and 823 (36%) received ET + CT. We observed a beneficial effect of addition of CT to ET on DFS and OS in multivariate Cox model (HR = 0.61, 95% confidence interval, CI [0.41-0.90]; p = 0.01 and 0.52, 95% CI [0.31-0.87]; p = 0.01, respectively). This effect was even more pronounced when propensity score matching was used. Regarding subgroup analysis, low-risk patients without CT did not have significant differences in DFS or OS compared to low-risk patients with CT. CONCLUSION: ILC patients could derive significant DFS and OS benefits from CT, especially for high-risk patients.


Subject(s)
Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Lobular/drug therapy , Chemotherapy, Adjuvant , Adult , Aged , Breast/drug effects , Breast/pathology , Carcinoma, Ductal, Breast/epidemiology , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/pathology , Carcinoma, Lobular/epidemiology , Carcinoma, Lobular/genetics , Carcinoma, Lobular/pathology , Disease-Free Survival , Female , Humans , Lymphatic Metastasis , Middle Aged , Receptors, Estrogen/genetics , Risk Factors , Treatment Outcome
5.
Breast Cancer Res Treat ; 173(1): 111-122, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30238274

ABSTRACT

BACKGROUND: Tumour features associated with isolated invasive breast cancer (BC) ipsilateral local recurrence (ILR) after breast conservative treatment (BCT) and consequences on overall survival (OS) are still debated. Our objective was to investigate these points. METHODS: Patients were retrospectively identified from a cohort of patients who underwent BCT for invasive BC in 16 cancer centres. End-points were ILR rate and OS. The impact of ILR on OS was assessed by multivariate analysis (MVA) for all patients and according to endocrine receptors (ERs) and grade or tumour subtypes. RESULTS: Of 15,570 patients, ILR rate was 3.1%. Cumulative ILR rates differed according to ERs/grade (ERs+/Grade2: HR 1.42, p = 0.010; ERs+/Grade3: HR 1.41, p = 0.067; ERs-: HR 2.14, p < 0.0001), endocrine therapy (HR 2.05, p < 0.0001) and age < 40-years old (HR 2.28, p = 0.005) in MVA. When MVA was adjusted on tumour subtype, the latter was the only independent factor. OS-after-ILR was significantly different according to ILR-free intervals (HR 4.96 for ILR-free interval between 2 and 5-years and HR 9.00 when < 2-years, in comparison with ≥ 5-years). CONCLUSION: ERs/Grade status, lack of endocrine therapy and tumour subtypes predict isolated ILR risk in patients treated with BCT. Short ILR-free-intervals represent a strong pejorative factor for OS. These results may help selecting initial treatment as well as tailoring ILR systemic chemotherapy.


Subject(s)
Breast Neoplasms/pathology , Breast Neoplasms/therapy , Mastectomy, Segmental/methods , Adult , Aged , Breast Neoplasms/mortality , Chemoradiotherapy , Cohort Studies , Disease-Free Survival , Female , Humans , Middle Aged , Multivariate Analysis , Neoplasm Recurrence, Local , Prognosis , Receptors, Estrogen/metabolism , Retrospective Studies , Risk Factors
6.
BMC Cancer ; 18(1): 1153, 2018 Nov 21.
Article in English | MEDLINE | ID: mdl-30463611

ABSTRACT

BACKGROUND: Three randomized trials have concluded at non inferiority of omission of complementary axillary lymph node dissection (cALND) for patients with involved sentinel node (SN). However, we can outline strong limitations of these trials to validate this attitude with a high scientific level. We designed the SERC randomized trial ( ClinicalTrials.gov , number NCT01717131) to compare outcomes in patients with SN involvement treated with ALND or no further axillary treatment. The aim of this study was to analyze results of the first 1000 patients included. METHODS: SERC trial is a multicenter non-inferiority phase 3 trial. Multivariate logistic regression analysis was used to identify independent factors associated with adjuvant chemotherapy administration and non-sentinel node (NSN) involvement. RESULTS: Of the 963 patients included in the analysis set, 478 were randomized to receive cALND and 485 SLNB alone. All patient demographics and tumor characteristics were balanced between the two arms. SN ITC was present in 6.3% patients (57/903), micro metastases in 33.0% (298), macro metastases in 60.7% (548) and 289 (34.2%) were non eligible to Z0011 trial criteria. Whole breast or chest wall irradiation was delivered in 95.9% (896/934) of patients, adjuvant chemotherapy in 69.5% (644/926), endocrine therapy in 89.6% (673/751) and the proportions were similar in the two arms. The overall rate of positive NSN was 19% (84/442) for patients with cALND. Crude rates of positive NSN according to SN status were 4.5% for ITC (1/22), 9.5% for micro metastases (13/137), 23.9% for macro metastases (61/255) and were respectively 29.36% (64/218), 9.33% (7/75) and 7.94% (10/126) when chemotherapy was administered after cALND, before cALND and for patients without chemotherapy. CONCLUSION: The main objective of SERC trial is to demonstrate non inferiority of cALND omission. A strong interaction between timing of cALND and chemotherapy with positive NSN rate was observed. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov , number NCT01717131 October 19, 2012.


Subject(s)
Breast Neoplasms/therapy , Lymph Node Excision/methods , Outcome Assessment, Health Care/methods , Sentinel Lymph Node/pathology , Adult , Aged , Aged, 80 and over , Axilla , Breast Neoplasms/pathology , Chemotherapy, Adjuvant/methods , Female , Humans , Logistic Models , Middle Aged , Multivariate Analysis , Neoplasm Micrometastasis , Outcome Assessment, Health Care/statistics & numerical data , Sentinel Lymph Node Biopsy
7.
BMC Surg ; 16(1): 74, 2016 Nov 15.
Article in English | MEDLINE | ID: mdl-27846840

ABSTRACT

BACKGROUND: To estimate the proportion of elderly patients (>70 years) with breast cancer eligible for an Exclusive IntraOperative RadioTherapy (E-IORT) and to evaluate their local recurrence-free survival rate. METHODS: This retrospective study examining two cohorts focuses on patients over 70 years old: a multi-centric cohort of 1411 elderly patients and a mono-centric cohort of 592 elderly patients. All patients underwent conservative surgery followed by external radiotherapy for T0-T3 N0-N1 invasive breast cancer, between 1980 and 2008. RESULTS: Within each cohort two groups were identified according to the inclusion criteria of the RIOP trial (R group) and TARGIT E study (T group). Each group was divided into two sub-groups, patients eligible (E) or non-eligible (nE) for IORT. The population of patients that were eligible in the TARGIT E study but not in the RIOP trial were also studied in both cohorts. The proportion of patients eligible for IORT was calculated, according to the eligibility criteria of each study. A comparison of the 5-year local or locoregional recurrence-free survival rate between eligible vs non-eligible patients was made. In both cohorts, the proportion of patients eligible according to the RIOP trial's eligibility criteria was 35.4 and 19.3%, and according to the TARGIT E study criteria was 60.9 and 45.3%. The 5-year locoregional recurrence-free survival rate was not significantly different between RE and RnE groups, TE and TnE groups. In both cohorts RE and (TE-RE) groups were not significantly different. CONCLUSIONS: Our results encourage further necessary studies to define and to extend the eligibility criteria for per operative exclusive radiotherapy.


Subject(s)
Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/radiotherapy , Carcinoma, Ductal, Breast/surgery , Mastectomy , Radiotherapy, Adjuvant , Adult , Age Factors , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/mortality , Disease-Free Survival , Female , Humans , Intraoperative Care , Middle Aged , Patient Selection , Retrospective Studies , Treatment Outcome , Young Adult
8.
Cardiovasc Intervent Radiol ; 38(5): 1237-43, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26183466

ABSTRACT

AIM: To present our single-centre prospective experience on the use of cryoablation (CA) applied to treat primary breast cancer (BC) in a cohort of patients unsuitable for surgical treatment. MATERIALS AND METHODS: Twenty-three consecutive post-menopausal female patients (median age 85 years; range 56-96) underwent percutaneous CA of unifocal, biopsy-proven BC, under ultrasound/computed tomography (US/CT) guidance. Clinical and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) follow-ups were systematically scheduled at 3, 12, 18 and 24 months. Local tumour control was assessed by comparing baseline and follow-up DCE-MRI. RESULTS: Twenty-three BC (median size 14 mm) were treated under local anaesthesia (78.3 %) or local anaesthesia and conscious sedation (21.7 %). Median number of cryo-probes applied per session was 2.0. A "dual-freezing" protocol was applied for the first ten patients and a more aggressive "triple-freezing" protocol for the remaining 13. Median follow-up was 14.6 months. Five patients recurred during follow-up and two were successfully re-treated with CA. Five patients presented immediate CA-related complications: four hematomas evolved uneventfully at 3-month follow-up and one skin burn resulted in skin inflammation and skin retraction at 3 and 12 months, respectively. CONCLUSIONS: Percutaneous CA is safe and well tolerated for non-resected elderly BC patients. Procedures can be proposed under local anaesthesia only. Given the insulation properties of the breast gland, aggressive CA protocols are required. Prospective studies are needed to better understand the potential role of CA in the local treatment of early BC.


Subject(s)
Breast Neoplasms/surgery , Cryosurgery , Magnetic Resonance Imaging , Postoperative Complications/diagnosis , Aged , Aged, 80 and over , Breast/pathology , Breast/surgery , Contrast Media , Female , Follow-Up Studies , Humans , Image Enhancement , Middle Aged , Prospective Studies , Radiography, Interventional , Tomography, X-Ray Computed , Treatment Outcome , Ultrasonography, Interventional
9.
Br J Cancer ; 113(4): 585-94, 2015 Aug 11.
Article in English | MEDLINE | ID: mdl-26171933

ABSTRACT

BACKGROUND: The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment. METHODS: One hundred and twenty post-menopausal patients were randomised to receive 1 mg anastrozole (61 patients) or 500 mg fulvestrant (59 patients) for 6 months. Genomic DNA copy number profiles were generated for a subgroup of 20 patients before and after treatment. RESULTS: A total of 108 patients were evaluable for efficacy and 118 for toxicity. The objective response rate determined by clinical palpation was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 53.8% (95% CI=39.5-67.8) in the fulvestrant arm. The breast-conserving surgery rate was 58.9% (95% CI=45.0-71.9) in the anastrozole arm and 50.0% (95% CI=35.8-64.2) in the fulvestrant arm. Pathological responses >50% occurred in 24 patients (42.9%) in the anastrozole arm and 13 (25.0%) in the fulvestrant arm. The Ki-67 score fell after treatment but there was no significant difference between the reduction in the two arms (anastrozole 16.7% (95% CI=13.3-21.0) before, 3.2% (95% CI=1.9-5.5) after, n=43; fulvestrant 17.1% (95%CI=13.1-22.5) before, 3.2% (95% CI=1.8-5.7) after, n=38) or between the reduction in Ki-67 in clinical responders and non-responders. Genomic analysis appeared to show a reduction of clonal diversity following treatment with selection of some clones with simpler copy number profiles. CONCLUSIONS: Both anastrozole and fulvestrant were effective and well-tolerated, enabling breast-conserving surgery in over 50% of patients. Clonal changes consistent with clonal selection by the treatment were seen in a subgroup of patients.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Estradiol/analogs & derivatives , Nitriles/therapeutic use , Postmenopause/drug effects , Triazoles/therapeutic use , Aged , Aged, 80 and over , Anastrozole , Estradiol/therapeutic use , Female , Fulvestrant , Humans , Middle Aged
10.
Am J Surg ; 208(5): 756-763, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24814311

ABSTRACT

BACKGROUND: To examine outcomes of neoadjuvant endocrine therapy in daily practice to inform decision making. METHODS: We retrospectively selected 204 patients who received neoadjuvant endocrine therapy with T2 (≥30 mm) or T3 tumors, examining subsequent breast-sparing surgery and long-term outcomes. RESULTS: Neoadjuvant endocrine therapy was administered for 7.3 months (median) and breast-sparing surgery was achievable in 53% of patients. Smaller initial tumor size and modified version of the Scarff-Bloom and Richardson grades 1 to 2 were associated with breast-sparing surgery. Disease progression during treatment was 6.9%; actuarial risk of local relapse was 3% at 5 years and 15% at 10 years. Five- and 10-year metastasis relapse-free survival was 78% and 63%, respectively. Grade 3, negative progesterone receptors, and absence or slow response to neoadjuvant therapy were associated prognostic factors. CONCLUSION: These daily practice data provide important information about feasibility, efficacy, and long-term results of neoadjuvant endocrine therapy and can be used to inform patients for decision making between mastectomy and endocrine induction therapy.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents, Hormonal/therapeutic use , Aromatase Inhibitors/therapeutic use , Breast Neoplasms/drug therapy , Mastectomy, Segmental , Neoadjuvant Therapy , Tamoxifen/therapeutic use , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Decision Making , Female , Humans , Mastectomy, Segmental/statistics & numerical data , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplasm Staging , Patient Participation , Retrospective Studies , Survival Analysis , Treatment Outcome
11.
J Clin Oncol ; 31(32): 4054-9, 2013 Nov 10.
Article in English | MEDLINE | ID: mdl-24043739

ABSTRACT

PURPOSE: Adjuvant radiotherapy (RT) after a local excision (LE) for ductal carcinoma in situ (DCIS) aims at reduction of the incidence of a local recurrence (LR). We analyzed the long-term risk on developing LR and its impact on survival after local treatment for DCIS. PATIENTS AND METHODS: Between 1986 and 1996, 1,010 women with complete LE of DCIS less than 5 cm were randomly assigned to no further treatment (LE group, n = 503) or RT (LE+RT group, n = 507). The median follow-up time was 15.8 years. RESULTS: Radiotherapy reduced the risk of any LR by 48% (hazard ratio [HR], 0.52; 95% CI, 0.40 to 0.68; P < .001). The 15-year LR-free rate was 69% in the LE group, which was increased to 82% in the LE+RT group. The 15-year invasive LR-free rate was 84% in the LE group and 90% in the LE+RT group (HR, 0.61; 95% CI, 0.42 to 0.87). The differences in LR in both arms did not lead to differences in breast cancer-specific survival (BCSS; HR, 1.07; 95% CI, 0.60 to 1.91) or overall survival (OS; HR, 1.02; 95% CI, 0.71 to 1.44). Patients with invasive LR had a significantly worse BCSS (HR, 17.66; 95% CI, 8.86 to 35.18) and OS (HR, 5.17; 95% CI, 3.09 to 8.66) compared with those who did not experience recurrence. A lower overall salvage mastectomy rate after LR was observed in the LE+RT group than in the LE group (13% v 19%, respectively). CONCLUSION: At 15 years, almost one in three nonirradiated women developed an LR after LE for DCIS. RT reduced this risk by a factor of 2. Although women who developed an invasive recurrence had worse survival, the long-term prognosis was good and independent of the given treatment.


Subject(s)
Breast Neoplasms/radiotherapy , Carcinoma in Situ/radiotherapy , Carcinoma, Ductal, Breast/radiotherapy , Adult , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Carcinoma in Situ/mortality , Carcinoma in Situ/surgery , Carcinoma, Ductal, Breast/mortality , Carcinoma, Ductal, Breast/surgery , Combined Modality Therapy , Female , Humans , Kaplan-Meier Estimate , Mastectomy, Segmental , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/mortality , Proportional Hazards Models , Radiotherapy, Adjuvant , Treatment Outcome
12.
BMC Med Genomics ; 5: 54, 2012 Nov 27.
Article in English | MEDLINE | ID: mdl-23186559

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 = 6.7 x 10(-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.


Subject(s)
Breast Neoplasms/genetics , Comparative Genomic Hybridization , Genomic Instability , Adult , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Cluster Analysis , Female , Follow-Up Studies , Gene Expression Profiling , Genome, Human , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Middle Aged , Mutation , Prognosis , Recurrence , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
13.
Cancer ; 116(13): 3093-101, 2010 Jul 01.
Article in English | MEDLINE | ID: mdl-20564641

ABSTRACT

BACKGROUND: 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. METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.


Subject(s)
Breast Neoplasms/pathology , Endothelium, Vascular/pathology , Adult , Breast Neoplasms/blood supply , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Female , Humans , Lymphatic Metastasis/pathology , Neoplasm Metastasis , Prognosis
14.
BMC Med Res Methodol ; 10: 20, 2010 Mar 16.
Article in English | MEDLINE | ID: mdl-20233435

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.


Subject(s)
Breast Neoplasms/pathology , Neoplasm Metastasis , Proportional Hazards Models , Statistics as Topic , Survival Analysis , Female , Humans , Kaplan-Meier Estimate , Prognosis , Receptors, Estrogen , Receptors, Progesterone
16.
Hist Sci Med ; 42(2): 175-6, 2008.
Article in French | MEDLINE | ID: mdl-19230319

ABSTRACT

Bergonié, a famous doctor in Bordeaux, visited Madrid and was visited by Spanish colleagues when he was at the head of the military hospital of Grand-Lebrun. He was a friend of king Alfonso.


Subject(s)
Hospitals, Military/history , Famous Persons , France , History, 19th Century , History, 20th Century , Spain
17.
Radiother Oncol ; 85(3): 355-61, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18023492

ABSTRACT

BACKGROUND AND PURPOSE: Breast sarcoma (BS) is a rare tumour. While surgical resection is the primary treatment, the role of radiation therapy (RT) and chemotherapy remains unclear. This study aimed at defining prognostic factors and treatment strategies. MATERIALS AND METHODS: Data from 103 patients treated between 1976 and 2002 were collected. The median age was 55 years (range: 13-86); the median histological tumour size was 4.45 cm (range: 0.8-22). There were 42 angiosarcomas. Surgery consisted of wide excision in 34 cases, and total mastectomy in 69 cases. A total dose of 50 Gy in 25 fractions was delivered in 50 patients. At the completion of treatment, 89 patients had no residual tumour. RESULTS: After a median follow-up of 64 months, 56 patients developed recurrent disease: 38 presented a local relapse and 37 developed distant metastases. The 5-year disease-free survival (DFS) and overall survival (OS) were 44% (95% confidence interval [CI], 39-49%) and 55% (95% CI, 50-60%), respectively. In multivariate analysis, favourable prognostic factors for better local control were: no residual tumour after treatment, no cellular pleomorphism, and histology other than angiosarcoma. For DFS, the five favourable prognostic factors were non-menopausal status, no residual tumour after treatment, non-angiosarcoma histology, absence of tumour necrosis, and grade 1-2 histology. CONCLUSION: While angiosarcoma has the worst prognosis, the outcome of the other types of sarcomas may be worsened by residual tumour after loco-regional treatment and high grade histology, a classical prognostic factor of the other soft tissue sarcomas. During surgical procedure axillary dissection is not mandatory.


Subject(s)
Breast Neoplasms/therapy , Hemangiosarcoma/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Breast Neoplasms/mortality , Disease-Free Survival , Female , Hemangiosarcoma/mortality , Humans , Middle Aged , Prognosis , Retrospective Studies , Treatment Outcome
18.
J Clin Oncol ; 25(24): 3664-9, 2007 Aug 20.
Article in English | MEDLINE | ID: mdl-17485709

ABSTRACT

PURPOSE: To determine the optimal injection path for blue dye and radiocolloid for sentinel lymph node (SLN) biopsy in early breast cancer. PATIENTS AND METHODS: A prospective randomized multicentric study was initiated to compare the peritumoral (PT) injection site to the periareolar (PA) site in 449 patients. RESULTS: The detection rate of axillary SLN by lymphoscintigraphy was significantly higher (P = .03) in the PA group (85.2%) than in the PT group (73.2%). Intraoperative detection rate by blue dye and/or gamma probe was similar (99.11%) in both groups. The rate of SLN detection was somewhat higher in the PA group than in the PT group: 95.6% versus 93.8% with blue dye (P = .24) and 98.2% versus 96.0% by probe (P = .16), respectively. The number of SLNs detected by lymphoscintigraphy and by probe was significantly higher in the PA group than in the PT group, 1.5 versus 1.2 (P = .001) and 1.9 versus 1.7 (P = .02). The blue and hot concordance was 95.6% in the PA group and 91.5% in the PT group (P = .08). The mean ex vivo count of the SLN was significantly higher in the PA group than in the PT group (P < .0001). CONCLUSION: This study strongly validates the PA injection technique given the high detection rate (99.1%) of SLN and the high concordance (95.6%) between blue dye and the radiotracer, as well as higher significant ex and in vivo counts, improving SLN probe detection.


Subject(s)
Coloring Agents/administration & dosage , Mastectomy, Segmental , Radiopharmaceuticals/administration & dosage , Rosaniline Dyes/administration & dosage , Sentinel Lymph Node Biopsy/methods , Technetium Tc 99m Sulfur Colloid/administration & dosage , Adult , Aged , Aged, 80 and over , Axilla , Female , Humans , Injections , Intraoperative Period , Lymph Nodes/diagnostic imaging , Middle Aged , Radionuclide Imaging
20.
Eur J Radiol ; 54(1): 55-61, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15797293

ABSTRACT

We retrospectively analysed mammographies of 909 ductal carcinoma in situ (DCIS) (1980-1999) and compared our results to those of literature. Microcalcifications were present in 75% of the cases, and soft-tissue abnormalities in 27% cases with association with calcifications in 14% of cases. Palpable masses were found in 12% of the cases and nipple discharge was present in 12% of the cases. The radiographic-pathologic correlation allowed to suspect the DCIS "aggressiveness" on radiologic signs. Granular, linear, branching and/or galactophoric topography of the microcalcifications were correlated with necrosis, grade 3, comedocarcinoma type. A number of microcalcifications higher than 20 was correlated with necrosis and grade 3. Mammographic size was correlated to histologic size. Masses were correlated with grade 1. A diagnosis strategy can be proposed with a multidisciplinar approach.


Subject(s)
Breast Neoplasms/diagnostic imaging , Carcinoma in Situ/diagnostic imaging , Carcinoma, Ductal, Breast/diagnostic imaging , Mammography , Adult , Aged , Aged, 80 and over , Breast Neoplasms/pathology , Calcinosis/diagnostic imaging , Carcinoma in Situ/pathology , Carcinoma, Ductal, Breast/pathology , Chi-Square Distribution , Female , Humans , Middle Aged , Retrospective Studies
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