Publications by authors named "Bruno Cutuli"

34 Publications

The 2018 assisi think tank meeting on breast cancer: International expert panel white paper.

Crit Rev Oncol Hematol 2020 Jul 22;151:102967. Epub 2020 Apr 22.

Radiation Oncology, University of Perugia and Perugia General Hospital, Perugia, Italy. Electronic address:

We report on the second Assisi Think Tank Meeting (ATTM) on breast cancer which was held under the auspices of the European Society for RadioTherapy & Oncology (ESTRO). In discussing in-depth current evidence and practice it was designed to identify grey areas in diverse forms of the disease. It aimed at addressing uncertainties and proposing future trials to improve patient care. Before the meeting, three key topics were selected: 1) primary systemic therapy, mastectomy, breast reconstruction and post-mastectomy radiation therapy, 2) therapeutic options in ductal carcinoma in situ, and 3) therapy de-escalation in early stage breast cancer. Clinical practice in these areas was investigated by means of an online questionnaire. The time lapse period between the survey and the meeting was used to review the literature and on-going clinical trials. At the ATTM both were discussed in depth and research protocols were proposed.
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http://dx.doi.org/10.1016/j.critrevonc.2020.102967DOI Listing
July 2020

Ductal Carcinoma in Situ: A French National Survey. Analysis of 2125 Patients.

Clin Breast Cancer 2020 04 22;20(2):e164-e172. Epub 2019 Aug 22.

Department of Radiation Oncology, Institut Curie, Paris, France.

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.
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http://dx.doi.org/10.1016/j.clbc.2019.08.002DOI Listing
April 2020

[Ductal carcinoma in situ in 2019: Diagnosis, treatment, prognosis].

Authors:
Bruno Cutuli

Presse Med 2019 Oct 22;48(10):1112-1122. Epub 2019 Oct 22.

Institut du cancer Courlancy Reims, 38, rue du Courlancy, 51100 Reims, France. Electronic address:

Ductal carcinoma in situ (DCIS) currently represents up to 15% of the newly diagnosed breast cancers, and are almost always detected by microcalcifications. Global prognosis is good (3% of 15-year specific mortality) but invasive local recurrences (LR) can lead to metastasis in 12-15% of the cases. Breast conserving surgery with whole breast irradiation is the main treatment (reducing LR by 50%), but mastectomy (with or without reconstruction) is performed in about 30% of the cases due to wide lesion size and/or multicentricity. The role of tamoxifen remains unclear. Axillary dissection is needless but sentinel node biopsy is proposed in case of micro-invasion suspicion (large lesions with high grade). The main factors of LR are young age (≤40 years) incomplete excision, and high nuclear grade with comedonecrosis. Several studies on "therapeutic descalation" are still ongoing in order to identify the "low risk" DCIS (about 10% of the cases) in which radiotherapy could be safely omitted.
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http://dx.doi.org/10.1016/j.lpm.2019.08.018DOI Listing
October 2019

Challenges in Radiotherapy.

Breast Care (Basel) 2019 Jun 4;14(3):152-158. Epub 2019 Jun 4.

Polyclinique Courlancy, Reims, France.

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http://dx.doi.org/10.1159/000500847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600036PMC
June 2019

Should Adjuvant Radiation Therapy Be Systematically Proposed for Male Breast Cancer? A Systematic Review.

Anticancer Res 2018 01;38(1):23-31

Department of Radiation Oncology, François Baclesse Anticancer Center, Caen, France

Background: Guidelines for radiotherapy in male breast cancer (MBC) are lacking. Some extrapolate the results from female breast cancer trials, while others advocate systematic adjuvant irradiation. We evaluated clinical practices and outcomes with respect to radiation therapy in MBC treated with locoregional irradiation in the adjuvant setting using a systematic literature review.

Material And Methods: We included studies with data about adjuvant radiotherapy published between 1984 and 2017 and including at least 40 patients.

Results: We found 29 retrospective series, 10,065 men were diagnosed with breast cancer; 3-100% (mean=54%) received adjuvant radiotherapy. Tumor size and nodal involvement were the strongest prognostic factors. Approximatively half of all cases had nodal metastases. Radiation therapy improved locoregional control in six series, overall survival in three and distant metastasis-free survival in one.

Conclusion: MBC is diagnosed at a highly advanced stage and may be linked with poorer outcomes. Adjuvant radiation therapy must, at least, be proposed to men with positive nodes. Despite the large number of cases gathered here, arguments for radiotherapy in other prognostic subgroups (especially in pN0) may exist but are not well supported.
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http://dx.doi.org/10.21873/anticanres.12187DOI Listing
January 2018

Quality indicators in breast cancer care: An update from the EUSOMA working group.

Eur J Cancer 2017 11 28;86:59-81. Epub 2017 Sep 28.

Radiology, Rome, Italy.

In 2010, EUSOMA published a position paper, describing a set of benchmark quality indicators (QIs) that could be adopted by breast centres to allow standardised auditing and quality assurance and to establish an agreed minimum standard of care. Towards the end of 2014, EUSOMA decided to update the paper on QIs to consider and incorporate new scientific knowledge in the field. Several new QIs have been included to address the need for improved follow-up care of patients following primary treatments. With regard to the management of elderly patients, considering the complexity, the expert group decided that, for some specific quality indicators, if centres fail to meet the minimum standard, older patients will be excluded from analysis, provided that reasons for non-adherence to the QI are specified in the clinical chart and are identified at the review of the clinical records. In this way, high standards are promoted, but centres are able to identify and account for the effect of non-standard treatment in the elderly. In the paper, there is no QI for outcome measurements, such as relapse rate or overall survival. However, it is hoped that this will be developed in time as the databases mature and user experience increases. All breast centres are required to record outcome data as accurately and comprehensively as possible to allow this to occur. In the paper, different initiatives undertaken at international and national level to audit quality of care through a set of QIs have been mentioned.
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http://dx.doi.org/10.1016/j.ejca.2017.08.017DOI Listing
November 2017

[Not Available].

Authors:
Bruno Cutuli

Bull Cancer 2016 Jun;103(6 Suppl 1):S105-9

Institut du Cancer Courlancy, 38, rue de Courlancy, 51100 Reims. Electronic address:

REFLEXIONS ABOUT NEW STRATEGIES OF RADIOTHERAPY FOR EARLY BREAST CANCER: Radiotherapy (RT) remains a major treatment element in early breast cancer, with a major impact on local control and survival. For ductal carcinoma in situ (DCIS), RT reduces local recurrence (LR) rates by 50 to 60 % after conservative surgery (both in situ and invasive). This was confirmed by four randomized trials and one meta-analysis. For infiltrating breast cancers (IBC), RT also reduces LR rates by 65 to 75 % after conservative surgery. Boost allows an additional reduction of LR. RT is efficient in all age categories, but hypofractionated schemes are particularly adapted to elderly women. Partial breast irrradiation techniques are very much heterogeneous and lack follow-up. They should be used in LR low-risk patients only and in the frame of controlled studies. Locoregional RT for high-risk patients (especially in pN+) remains essential to reduce the locoregional recurrence rate and to increase survival, as confirmed in several meta-analyses. Four studies showed a survival benefit (2-3 %), thanks to internal mammary chain irradiation in LR high-risk patients. Moreover, axillary RT seems to be a likely valuable alternative to axillary dissection in case of sentinel node invasion. Finally, with the modern techniques and dosimetric optimization, RT toxicity was reduced, or even cancelled, arousing hope for a better increased benefit for the patients in the future.
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http://dx.doi.org/10.1016/S0007-4551(16)30154-0DOI Listing
June 2016

[Ductal carcinoma in situ diagnosis: 3 French national guidelines].

Ann Pathol 2016 Jun 25;36(3):166-73. Epub 2016 May 25.

Département « Recommandations et bon usage du médicament », direction des recommandations, du médicament et de la qualité de l'expertise, Institut national du cancer, 52, avenue André-Morizet, 92513 Boulogne Billancourt cedex, France.

Objective: Since the last guidelines published by the French National Cancer Institute (INCa) and the learning society "Société française de sénologie et de pathologie mammaire (SFSPM)" in 2009 about diagnosis and management of ductal carcinoma in situ, new data raised issues about overdiagnosis and its consequences, overtreatment. Therefore, an update was necessary, to provide healthcare professionals up-to-date guidelines and study therapeutic desescalation in particular.

Methods: The clinical practice guidelines development process is based on systematic literature review and critical appraisal by a multidisciplinary experts workgroup. The recommendations are thus based on the best available evidence and experts agreement. Prior to publication, the guidelines are also reviewed by more than 100 independent practitioners in cancer care delivery.

Results: This article presents French guidelines about MRI and vacuum assisted breast biopsy indications for DCIS diagnosis and the management of low-grade DCIS.
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http://dx.doi.org/10.1016/j.annpat.2016.03.012DOI Listing
June 2016

Hypofractionated irradiation in elderly patients with breast cancer after breast conserving surgery and mastectomy : Analysis of 205 cases.

Radiat Oncol 2015 Aug 4;10:161. Epub 2015 Aug 4.

Radiation Oncology Department, Institut de Cancérologie de l'Ouest, Nantes, France.

Background: Several randomized trials and meta-analyses confirmed a wide benefit of radiotherapy (RT), both after breast conserving surgery (BCS) and mastectomy. However, many elderly women don't receive RT. Hypofractionated (HF) RT allows « simplified » and more accessible treatments with equivalent results to classic RT in three large randomized trials. However, there are few available data on HF-RT for nodal irradiation, as well as for the boost.

Methods: We evaluated patients treated for IBC by HF-RT between 2004 and 2012 in two regional cancer centres. We used an original scheme delivering 45 Gy in 15 fractions three times a week, both after BCS or mastectomy, with or without nodal irradiation. After BCS, a 9 Gy boost in 3 fractions was delivered. Local, regional and distant recurrences were assessed, as well as acute and late cutaneous, cardiac or pulmonary toxicities.

Results: 205 patients were analysed, 116 after BCS (57 %) and 89 after mastectomy (43 %). Median age was 81 years (range: 52-91); 44 % had axillary nodal involvement (pN+). The Nottingham Prognostic Index (NPI) scored 0, 1, 2 and 3 in 10 %, 27 %, 44 % and 19 % of the cases. A nodal HF-RT was delivered in 65 patients (32 %) and boost in 98 patients (84 % of BCS) by 9 Gy/3 fr scheme. Fifty (24 %) patients underwent chemotherapy and 156 (75 %) hormonal treatment. With a 49-month median follow-up, 3/116 (2.6 %) patients and 4/89 (4.5 %) had local recurrence (LR) after BCS and mastectomy, respectively. The overall 5-year LR rate was 4.4 %. In univariate and multivariate analysis, LR risk factors were: high NPI (HR 5.46; p = 0.028), and triple negative tumour (HR 9.78; p = 0.006). Only 8 (4.5 %) patients had grade III skin toxicity; 29 (14 %) late fibrosis and 16 (8 %) telangiectasia. No pulmonary or cardiac toxicity was observed.

Conclusion: Our HF-RT scheme (with or without nodal irradiation) confirms in elderly patients the data from randomized trials, both after BCS or mastectomy. Toxicity seems very acceptable but requires a longer follow-up. A larger evaluation is still ongoing in several other centres in France.
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http://dx.doi.org/10.1186/s13014-015-0448-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4554320PMC
August 2015

Lobular carcinoma in situ (LCIS) of the breast: is long-term outcome similar to ductal carcinoma in situ (DCIS)? Analysis of 200 cases.

Radiat Oncol 2015 May 6;10:110. Epub 2015 May 6.

Sylia-Stat, Bourg-la-Reine, France.

Background: Lobular carcinomas in situ (LCIS) represent 1-2% of all breast cancers. Both significance and treatment remain widely debated, as well as the possible similarities with DCIS.

Materials And Methods: Two hundred patients with pure LCIS were retrospectively analyzed in seven centres from 1990 to 2008. Median age was 52 years; 176 patients underwent breast-conserving surgery (BCS) and 24 mastectomy. Seventeen patients received whole breast irradiation (WBRT) after BCS and 20 hormonal treatment (15 by tamoxifen).

Results: With a 144-month median follow-up (FU), there were no local recurrences (LR) among 24 patients treated by mastectomy. With the same FU, 3 late LR out of 17 (17%) occurred in patients treated by BCS and WBRT (with no LR at 10 years). Among 159 patients treated by BCS alone, 20 developed LR (13%), but with only a 72-month FU (17.5% at 10 years). No specific LR risk factors were identified. Three patients developed metastases, two after invasive LR; 22 patients (11%) developed contralateral BC (59% invasive) and another five had second cancer.

Conclusions: LCIS is not always an indolent disease. The long-term outcome is quite similar to most ductal carcinomas in situ (DCIS). The main problems are the accuracy of pathological definition and a clear identification of more aggressive subtypes, in order to avoid further invasive LR. BCS + WBRT should be discussed in some selected cases, and the long-term results seem comparable to DCIS.
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http://dx.doi.org/10.1186/s13014-015-0379-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428244PMC
May 2015

Radiotherapy in DCIS, an underestimated benefit?

Radiother Oncol 2014 Jul 5;112(1):1-8. Epub 2014 Jul 5.

Dr. Bernard Verbeeten Institute, Tilburg, The Netherlands.

Often considered an "indolent" disease for which a treatment de-escalation is advocated, ductal carcinoma in situ (DCIS) of the breast has been recently shown to be associated with a significant increase in long-term mortality in case of invasive local recurrence (LR). The publication of data from four randomised trials did not prevent the continuation of the debates about the pros and cons of postoperative radiation therapy (PORT) for optimal DCIS management. Actually only partial answers regarding the impact of PORT on local control had been brought by these randomised trials among others due to differences in pathological assessment among these controlled studies. A biologically heterogeneous disease, DCIS is characterised by a large variation in clinical behaviour, which hampers the identification of those patients for whom PORT might be considered as an overtreatment. At the light of the most recent biological and clinical studies, this review tries to identify accurately the LR risks associated with both tumour- and patient-related factors and to analyse the treatment-related parameters impacting significantly on the patient outcome.
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http://dx.doi.org/10.1016/j.radonc.2014.06.011DOI Listing
July 2014

Breast ductal carcinoma in situ.

Int J Surg Oncol 2012 6;2012:753267. Epub 2012 Nov 6.

Breast Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 300 East 66th Street New York, NY 10065, USA.

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http://dx.doi.org/10.1155/2012/753267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3503298PMC
December 2012

Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG) and European Society of Breast Cancer Specialists (EUSOMA).

Lancet Oncol 2012 Apr 30;13(4):e148-60. Epub 2012 Mar 30.

Sandro Pitigliani Medical Oncology Unit, Istituto Toscano Tumori, Hospital of Prato, Prato, Italy.

As the mean age of the global population increases, breast cancer in older individuals will be increasingly encountered in clinical practice. Management decisions should not be based on age alone. Establishing recommendations for management of older individuals with breast cancer is challenging because of very limited level 1 evidence in this heterogeneous population. In 2007, the International Society of Geriatric Oncology (SIOG) created a task force to provide evidence-based recommendations for the management of breast cancer in elderly individuals. In 2010, a multidisciplinary SIOG and European Society of Breast Cancer Specialists (EUSOMA) task force gathered to expand and update the 2007 recommendations. The recommendations were expanded to include geriatric assessment, competing causes of mortality, ductal carcinoma in situ, drug safety and compliance, patient preferences, barriers to treatment, and male breast cancer. Recommendations were updated for screening, primary endocrine therapy, surgery, radiotherapy, neoadjuvant and adjuvant systemic therapy, and metastatic breast cancer.
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http://dx.doi.org/10.1016/S1470-2045(11)70383-7DOI Listing
April 2012

Breast cancer occurred after Hodgkin's disease: clinico-pathological features, treatments and outcome: analysis of 214 cases.

Crit Rev Oncol Hematol 2012 Jan 17;81(1):29-37. Epub 2011 Feb 17.

Radiation Oncology Department, Polyclinique de Courlancy, 38 rue de Courlancy, 51100 Reims, France.

Background: Secondary tumours (ST) represent a major concern in survivors of Hodgkin's disease (HD). Breast cancer (BC) is the most frequent ST among young treated women.

Material And Methods: One hundred and eighty-nine women treated for HD by radiotherapy (RT) and/or chemotherapy (CT) subsequently developed 214 BCs.

Results: Median age at HD diagnosis was 25 years (34% were less than 20). Median interval between HD and BC was 18.6 years, with a 42-year median age at first BC. According to the TNM classification, there were 30 (14%) T0 (non palbable lesions), 86 (40%) T1, 56 (26%) T2, 13 (6%) T3T4 and 29 (14%) Tx. There were 25 (13.2%) contralateral BC. 160 (75%) and 15 (7%) tumours were infiltrating ductal and lobular carcinomas, 7 (3.3%) were other subtypes and 27 (22%) DCIS. The rate of axillary nodal involvement was 32%. Among 203 operated tumours, 79 (39%) were treated by breast conserving surgery (BCS), with RT in 56 (71%) cases. CT and hormonal treatment were delivered in 51% and 45% of the patients. With a 50-month median follow-up, local recurrence occurred in 12% of the tumours (9% after mastectomy, 21% after lumpectomy alone and 13.7% after lumpectomy with RT). Metastasis occurred in 47 (26%) patients. The risk factors were pN+, pT, high SBR grade and young age (< 50 years). The ten-year overall and specific survival rates were 53% and 63.5%, respectively. The ten-year specific survival rates were 79% for pT0T1T2, 48% for pT3T4 (p = 0.0002) and 79% for pN0 versus 38.5% for pN+ (p = 0.00026). Among 67 deaths, 43 (73%) were due to BC.

Conclusion: Patients and physicians should be aware that BC is the most frequent secondary tumour in young women treated for HD. The new RT modalities (lower doses and involved fields) may decrease the risk in the future. However, these women require a careful monitoring as from 8 to 10 years after HD treatment, combining mammography, ultrasound and MRI according to several ongoing studies. BC with whole breast irradiation is feasible in some selected cases.
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http://dx.doi.org/10.1016/j.critrevonc.2011.01.005DOI Listing
January 2012

Multidisciplinary meeting on male breast cancer: summary and research recommendations.

J Clin Oncol 2010 Apr 22;28(12):2114-22. Epub 2010 Mar 22.

Division of Medical Oncology, University of Washington, 825 Eastlake Ave, E. MS G3-630, Seattle, WA 98109, USA.

Male breast cancer is a rare disease, accounting for less than 1% of all breast cancer diagnoses worldwide. Most data on male breast cancer comes from small single-institution studies, and because of the paucity of data, the optimal treatment for male breast cancer is not known. This article summarizes a multidisciplinary international meeting on male breast cancer, sponsored by the National Institutes of Health Office of Rare Diseases and the National Cancer Institute Divisions of Cancer Epidemiology and Genetics and Cancer Treatment and Diagnosis. The meeting included representatives from the fields of epidemiology, genetics, pathology and molecular biology, health services research, and clinical oncology and the advocacy community, with a comprehensive review of the data. Presentations focused on highlighting differences and similarities between breast cancer in males and females. To enhance our understanding of male breast cancer, international consortia are necessary. Therefore, the Breast International Group and North American Breast Cancer Group have joined efforts to develop an International Male Breast Cancer Program and to pool epidemiologic data, clinical information, and tumor specimens. This international collaboration will also facilitate the future planning of clinical trials that can address essential questions in the treatment of male breast cancer.
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http://dx.doi.org/10.1200/JCO.2009.25.5729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860409PMC
April 2010

The effect of adjuvant radiotherapy on mortality differs according to primary tumor location in women with node-positive breast cancer.

Strahlenther Onkol 2009 Mar 28;185(3):161-8; discussion 169. Epub 2009 Mar 28.

Oncology Center, UZ Brussel, Jette, Belgium.

Purpose: To evaluate the prognostic significance of primary tumor location and to examine whether the effect of adjuvant radiotherapy on survival varies according to tumor location in women with axillary node-positive (ALN+) breast cancer (BC).

Patients And Methods: Data were abstracted from the SEER database for 24,410 women aged 25-95 years, diagnosed between 1988-1997 with nonmetastatic T1-T2, ALN+ BC. Subgroup analyses were performed using interactions within proportional hazards models. Event was defined as death from any cause. Prognostic variables were selected using Akaike Information Criteria. Joint significances of subgroups were evaluated with Wald test.

Results: Median follow-up was 10 years. In joint models, statistically significant interactions were found between tumor location, nodal involvement, type of surgery, and radiotherapy. Factorial presentation of interactions showed consistent 13% proportional reduction of mortality in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with mastectomy. In this subgroup, use of radiotherapy was associated with a 16% proportional increase in mortality.

Conclusion: Medial tumor location is a significant adverse prognostic factor that should be considered in treatment decision- making for women with ALN+ BC. Improved survival was observed with radiotherapy use in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with postmastectomy radiotherapy. These findings raise concern that the favorable effect of radiotherapy may be offset by excess toxicities in the latter subgroup.
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http://dx.doi.org/10.1007/s00066-009-1921-zDOI Listing
March 2009

Breast conserving treatment (BCT) for stage I-II breast cancer in elderly women: analysis of 927 cases.

Crit Rev Oncol Hematol 2009 Jul 8;71(1):79-88. Epub 2008 Nov 8.

Department of Radiation Oncology, Polyclinique de Courlancy, 38 rue de Courlancy, 51100 Reims, France.

Introduction: Few breast conserving treatment (BCT) data include women older than 70.

Material: 910 women older than 70 were treated by BCT for stage I-II BC, with 670 pT(1) (72.3%), 245 pT(2) (26.4%) and 12 pT(x) (1.3%). Axillary nodal involvement occurred in 30.7% of cases. ER and PgR were positive in 85% and 71% of cases. Radiotherapy (RT) was delivered in all patients, tamoxifen in 55.8% and chemotherapy in 4.8%.

Results: With a 65-month median follow-up, 28 (3%) local recurrences (LR) and 83 (9.1%) metastases occurred. Second cancer occurred in 51 (5.6%) patients. The 8-year overall survival (OS) and disease-specific survival (DSS) rates were 74% and 90%. The 8-year OS and DSS rates were 77% and 92% versus 65% and 84% in pT(1) versus pT(2) patients (p=0.01). 676 patients were in complete remission (74.3%); 22 were evolutive (2.4%). 206 patients died (22.6%).

Conclusion: Our study confirms the excellent local control in elderly patients treated by BCT with RT and identifies subgroups at high risk of distant relapse that should be treated more aggressively.
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http://dx.doi.org/10.1016/j.critrevonc.2008.09.011DOI Listing
July 2009

Current management of DCIS: a review.

Breast Cancer Res Treat 2008 Sep 28;111(1):1-10. Epub 2007 Sep 28.

The London Breast Institute, The Princess Grace Hospital, 45 Nottingham Place, London, W1U 5NY, UK.

Ductal carcinoma in-situ (DCIS) is a heterogeneous disease, in terms of its radiological characteristics, histological morphology and molecular attributes. This diversity is reflected in its natural history and influences optimal treatment strategy. A significant proportion of DCIS lesions behave in a clinically benign fashion and do not progress to invasive disease. Reliable identification of these patients could allow treatment to be less radical or safely omitted. Management should be tailored to the individual within the context of a multidisciplinary team. Approaches such as biological profiling and molecular analysis represent an opportunity to improve our understanding of the tumour biology of this condition and rationalise its treatment. This article reviews the management strategies for DCIS in the context of recent randomized trials, including the role of sentinel lymph node biopsy, adjuvant radiotherapy and tamoxifen.
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http://dx.doi.org/10.1007/s10549-007-9760-zDOI Listing
September 2008

Strategies in treating male breast cancer.

Authors:
Bruno Cutuli

Expert Opin Pharmacother 2007 Feb;8(2):193-202

Radiation Oncology Department, Polyclinique de Courlancy, 38 rue de Courlancy, 51100 Reims, France.

Male breast cancer is rare. Median age at diagnosis is approximately 65 years, and > 35% of male breast cancers occur in elderly men. Retroareolar lump is the most frequent symptom, and 25-30% of tumours are T(4) lesions. Infiltrating ductal carcinoma represents almost 90% of the cases, and 10% are ductal carcinoma in situ. Axillary nodal involvement is present in 50-60% of the cases. Estrogen and progesterone receptors are positive in 75-92% and 54-77% of the cases. Mastectomy with axillary dissection remains the standard treatment. Sentinel lymph node biopsy could be proposed in small tumours (< or = 2 cm). Locoregional radiotherapy is very often indicated. Tamoxifen is the standard adjuvant treatment, but chemotherapy is proposed in young men with axillary nodal involvement and/or negative hormone receptors. Tumour size and, more particularly, histopathological axillary involvement are the strongest predictive factors for both locoregional recurrence and metastasis. Globally, the prognosis is similar to that in women (at identical stage), but the intercurrent death rate is higher due to the important impact of comorbidities and second neoplasm.
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http://dx.doi.org/10.1517/14656566.8.2.193DOI Listing
February 2007

Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer.

J Clin Oncol 2007 Jan 11;25(3):292-300. Epub 2006 Dec 11.

Biostatistics and Epidemiology Unit, Department of Medicine, , Institut Gustave-Roussy, Villejuif, France.

Purpose: To determine the risk factors for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after breast cancer.

Patients And Methods: We conducted a case-control study among women treated for breast cancer between 1985 and 2001 in French general hospitals, cancer centers, or clinics. We included 182 AML and MDS patients and 534 matched controls. Breast cancer characteristics, type of treatment, and family history of cancer were compared in both groups.

Results: The risk of AML/MDS was increased after topoisomerase-II inhibitor-based chemotherapy (P < 10-16) and was higher for mitoxantrone-based chemotherapy than for anthracycline-based chemotherapy (relative risk [RR] = 15.6; 95% CI, 7.1 to 34.2; and RR = 2.7; 95% CI, 1.7 to 4.5, respectively). After adjustment for other treatment components, the risk of AML/MDS in patients who received radiotherapy was multiplied by 3.9 (95% CI, 1.4 to 10.8) but was not increased by alkylating agents. Patients receiving granulocyte colony-stimulating factor (G-CSF) support had an increased risk of AML/MDS (RR = 6.3; 95% CI, 1.9 to 21), even when controlling for chemotherapy doses. Similar results were obtained when AML and MDS were considered separately.

Conclusion: This large case-control study demonstrates that the risk of AML/MDS is much higher with mitoxantrone-based chemotherapy than with anthracyclines-based chemotherapy in a population of women recently treated for breast cancer. The risk of AML/MDS associated with mitoxantrone must be kept in mind when using this drug to treat diseases other than breast cancer (eg, prostate cancer or multiple sclerosis). In addition, our study suggests the need to monitor the long-term effects of G-CSF therapy.
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http://dx.doi.org/10.1200/JCO.2006.05.9048DOI Listing
January 2007

Heterogeneity of ductal carcinoma in situ and its effects on management.

Lancet Oncol 2006 Sep;7(9):756-65

St George's Medical School, London, UK.

Data derived from histopathological analysis, natural history, radiological characteristics, molecular markers, and clinical outcome indicate that ductal carcinoma in situ (DCIS) is a heterogeneous disease, meaning that no one treatment strategy is best, but rather that treatment should be personalised and entail a systematic and rigorous multidisciplinary approach. Many women with DCIS will develop actual invasive carcinoma over time, whereas others-especially those with low-grade cancers-will not. At the moment, identification of patients at low risk of recurrence risk is very difficult (that is, such people for whom further treatment beyond lumpectomy is not needed). In this context, molecular profiling analysis is a promising method to guide management decisions. In this Review, various treatment strategies for DCIS will be reviewed, highlighting the limitations of randomised trials. Furthermore, discussions about the role of sentinel-node biopsy and tamoxifen in disease management; locoregional recurrence; and special clinical scenarios such as recurrent disease, DCIS after thoracic radiotherapy, ductal carcinoma with concurrent lobular carcinoma in situ, and DCIS in elderly people and in men will be presented.
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http://dx.doi.org/10.1016/S1470-2045(06)70861-0DOI Listing
September 2006

The management of lobular carcinoma in situ (LCIS). Is LCIS the same as ductal carcinoma in situ (DCIS)?

Eur J Cancer 2006 Sep 28;42(14):2205-11. Epub 2006 Jul 28.

Molecular and Cellular Pathology, School of Medicine, The University of Queensland, Mayne Medical School, Brisbane, QLD 4006, Australia.

Lobular carcinoma in situ was first described over 60 years ago. Despite the long history, it continues to pose significant difficulties in screening, diagnosis, management and treatment. This is partly due its multi-focal and bilateral presentation, an incomplete understanding of its biology and natural history and perpetuation of misconceptions gathered over the last decades. In this review, the working group on behalf of EUSOMA has attempted to summarise the current thinking and management of this interesting lesion.
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http://dx.doi.org/10.1016/j.ejca.2006.03.019DOI Listing
September 2006

A French national survey on infiltrating breast cancer: analysis of clinico-pathological features and treatment modalities in 1159 patients.

Breast Cancer Res Treat 2006 Jan 27;95(1):55-64. Epub 2005 Oct 27.

Department of Oncology and Radiotherapy, Polyclinique de Courlancy, Reims, France.

Background: Despite the approximate 42,000 yearly new cases of breast cancer in France, there have been very few exhaustive studies on the clinicopathological features and treatment options of this disease.

Methods: Thus, a prospective, non-selective, nationwide survey on infiltrating breast cancer (IBC) was conducted in France from September 2001 to April 2002, in order to assess the epidemiological features of newly diagnosed disease, the prognostic and predictive variables with a special emphasis on hormone receptors, and the current approaches to therapy in everyday clinical practice.

Results: In total, 1159 patients were evaluable (median age 57 years); two-thirds of women were postmenopausal and 38% had undergone hormonal replacement therapy (HRT). Ductal and lobular infiltrating cancers represented 82.3% and 11.6% of cases, respectively. Most tumours expressed oestrogen (79.7%) and progesterone (69.7%) receptors. Overexpression of the human epidermal growth factor receptor-2 oncogene was found in 20.6% of the assessed cases. IBC diagnosed in women under HRT presented significantly better clinico-pathological features than in non-users. All patients underwent surgery as first treatment: 77.5% breast-conserving surgery (BCS) and 22.5% mastectomy; 1024 patients also underwent axillary surgery. The overall axillary lymph-node involvement rate was 44.4%. Radiotherapy was proposed in 98% and 83% of the women who had undergone BCS and mastectomy, respectively. Adjuvant chemotherapy was delivered in 58.7% of patients and hormonal treatment was provided in 76.5% of patients; tamoxifen was the most widely used hormonal treatment.

Conclusions: This study showed a trend for global downstaging of IBC (with favourable clinico-pathological features), leading to a high rate of BCS. Postoperative treatments were widely used, in accordance with national and international guidelines. Use of aromatase inhibitors and taxanes was limited, but is likely to rise in the future.
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http://dx.doi.org/10.1007/s10549-005-9034-6DOI Listing
January 2006

[Standards, Options and Recommendations for the management of ductal carcinoma in situ of the breast (DCIS): update 2004].

Bull Cancer 2005 Feb;92(2):155-68

Oncologue radiothérapeute, Polyclinique de Courlancy, Reims

The " Standards, Options and Recommendations " (SOR) project, started in 1993, is a collaboration between the Federation of French Cancer Centres (FNCLCC), the 20 French cancer centres, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. Objectives : To update the Standards, Options and Recommendations clinical practice guidelines for the management of ductal carcinoma in situ of the breast (DCIS). Methods : The working group identified the questions requiring up-dating from the previous guideline. Medline(r) and Embase(r) were searched using specific search strategies from year 1996 to year 2003. In addition several Internet sites were searched in October 2002. Results : Clinical guidelines have been defined for the management of diagnosis, treatment, follow-up, and treatment of recurrence of DCIS. The issue of hormone replacement therapy has also been addressed in the context of DCIS.
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February 2005

Breast-conserving surgery and radiotherapy: a possible treatment for lobular carcinoma in situ?

Eur J Cancer 2005 Feb;41(3):380-5

Department of Radiation Oncology, Polyclinique de Courlancy, 38 rue de Courlancy, 51100 Reims, France.

Lobular carcinoma in situ (LCIS) is generally treated by conservative surgery alone and less often by mastectomy. We report our experience using conservative surgery and whole breast irradiation (WBI) for the treatment of patients with LCIS. From 1980 to 1992, 25 women with a median age of 54 years underwent lumpectomy (20) or quadrantectomy (5) and WBI (median dose: 52 Gy) for treatment of their LCIS. Five cases had palpable lesions, 19 were found by mammography alone and one case was found due to nipple discharge. Twelve women received tamoxifen at 20 mg/day for 2 years. With a median follow-up of 153 months (range 58-240), only one local recurrence was observed. The global rate of bilateral carcinoma was 17.6% (two synchronous and one metachronous). Until now, no case of LCIS treated by lumpectomy and radiation therapy has been reported in detail in the literature. After biopsy alone for LCIS, a subsequent infiltrating carcinoma occurs in approximately 15% of cases. Thus, classical radiosurgical therapy should represent an interesting alternative both for limited surgery alone and mastectomy, both of which have been proposed as sole treatments for LCIS.
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http://dx.doi.org/10.1016/j.ejca.2004.09.017DOI Listing
February 2005

Is radiotherapy needed after adequate local excision of localized DCIS?

Authors:
Bruno Cutuli

Int J Fertil Womens Med 2004 Sep-Oct;49(5):231-6

Department of Radiation Oncology, Polyclinique de Courlancy, Reims, France.

Despite the fact that mastectomy remains the safest treatment for ductal carcinoma in situ, breast conserving surgery is still a frequent option. Three randomized trials (NSABP B17- EORTC 10853- UK DCIS) have confirmed a statistically significant reduction of LR rate by the addition of a whole breast irradiation at 50 Gy (RT). The rate of LR, both in situ and invasive, has been reduced by 45-55% with RT, e.g. in the NSABP B-17 trial, with a 129-month follow-up, the overall LR rate decreased from 31.7% to 15.7% (p = 0.001). The RT benefit was confirmed in all subgroups of patients, even with a lack of advantage on survival. Two large retrospective studies (in France and California) also confirmed the benefit of RT after lumpectomy, but with small differences in the subgroup with large excision (and margin width > or = 10 mm). On the other hand, invasive LR can give a 15-20% subsequent metastasis rate. Today, the current whole breast RT using megavoltage photons and provisional CT-scan-based dose distribution is resulting in less than 1% of complications. Until now, no studies have clearly identified patients with a sufficiently low LR risk to justify the lack of RT after lumpectomy. Finally, DCIS treatment requires a close multidisciplinary collaboration; moreover surgery and radiotherapy should be used jointly to obtain optimal long-term local control, such as for so many tumors.
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March 2005

Breast-conserving therapy for stage I-II breast cancer in elderly women.

Int J Radiat Oncol Biol Phys 2004 Sep;60(1):71-6

Department of Radiation Oncology, Polyclinique de Courlancy, 38 rue de Courlancy, Reims 51100, France.

Purpose: To assess breast-conserving therapy results in elderly patients with early-stage breast cancer (clinical Stage I-II).

Methods And Materials: Between 1979 and 1998, 196 women (200 treated breasts) aged > or =70 years (median age, 72.5 years) were treated with breast-conserving therapy (lumpectomy or quadrantectomy with axillary lymph node dissection and radiotherapy). Pathologic axillary node involvement was found in 51 patients (28%). Two-thirds of patients received tamoxifen, and 16% received chemotherapy.

Results: At a median follow-up of 59 months, 3 patients (1.5%) had developed local recurrence and 20 (10.2%) distant metastases. The overall survival rate was 81% and 62% at 5 and 10 years, respectively. The corresponding disease-specific survival rates were 92% and 88%. Axillary nodal involvement was the only statistically significant risk factor for the development of metastases (p = 0.0035). Arm mobility impairment and arm lymphedema each occurred in 5 patients. In another 5 patients, a thromboembolic event occurred during tamoxifen treatment.

Conclusion: Elderly women tolerate breast-conserving therapy, including radiotherapy, well and have excellent rates of locoregional control and disease-specific survival.
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http://dx.doi.org/10.1016/j.ijrobp.2004.02.029DOI Listing
September 2004