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Purpose: The French National Cancer Institute has developed, in partnership with the French National Authority for Health, breast cancer-specific Care Quality, and Safety Indicators (BC QIs). With regard to the most common form of cancer, our aim is to support local and national quality initiatives, to improve BC pathways and outcomes, reduce heterogeneity of practice and regional inequities. In this study, we measure the BC QIs available in the French National medico-administrative cancer database, the French Cancer Cohort, for 2018., Materials and Methods: BC QIs are developed according to the RAND method. QIs are based on good clinical practice and care pathway recommendations. QI computation should be automatable without any additional workload for data collection. They will be published annually for all stakeholders, and especially hospitals., Results: Finally, ten feasible and pertinent QIs were selected. In France, BC care was found to be close to compliance with most QIs: proportion of patients undergoing biopsy prior to first treatment (94.5%), proportion of patients undergoing adjuvant radiotherapy after breast-conserving surgery for BC (94.5%), proportion of women undergoing radiotherapy within 12 weeks after surgery and without chemotherapy (86.2%), proportion of DCIS patients undergoing immediate breast reconstruction (54.3%) and proportion of women with NMIBC undergoing breast reintervention (14.4%). However, some are still far from their recommended rate. In particular, some QIs vary considerably from one region, or one patient, to another., Conclusion: Each result needs to be analyzed locally to find care quality leverage. This will strengthen transparency actions aimed at the public., Competing Interests: Disclosure The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Adjuvant radiotherapy is an essential component of the treatment of breast cancer. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. A boost dose over the tumour bed is required if the patient is younger than 50 years-old. Partial breast irradiation could be routinely proposed as an alternative to whole breast irradiation, but only in selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neoadjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra- and infraclavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Hypofractionation regimens (42.5Gy in 16 fractions, or 41,6Gy en 13 or 40Gy en 15) are equivalent to conventional irradiation and must prescribe after tumorectomy in selected patients. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with or after radiotherapy., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

During the last two decades the number of breast implants used in aesthetic, oncologic and risk reducing surgery has increased substantially mainly due to the improvement and confirmed safety of these devices. Since identification of the first case of anaplastic large cell lymphoma associated with a breast implant (BIA-ALCL) 20 years ago, there has been an increase in the number of reports of this very rare disease, demonstrating a clear association with breast implants. Whilst the majority of cases are localised and cured by implant removal and full capsulectomy, a small percentage require chemotherapy and the mortality rate is very low. The evidence linking BIA-ALCL to implant surface texturing, as the majority of cases were diagnosed in patients with textured implants, has raised concerns about the long term safety of these devices resulting in patient and regulatory authority concerns globally. We hereby present the current published knowledge about the link between BIA-ALCL and implant surface texture and a review of current regulatory and professional body advice across Europe, which may enable a better understanding of this rare disease, how to manage and ultimately prevent it. We conclude by giving EUSOMA recommendation, towards the unnecessary change in attitudes towards implant based surgery, according to the most recent available published evidence as long as patients are properly informed about the risk of BIA-ALCL., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Breast irradiation after breast-conserving surgery is essential for maximizing local control and overall survival. The increase of breast cancer (BC) incidence, constraints of classical five weeks (w) radiation regimens and scarcity of radiotherapy units have led to test short hypofractionated WBRT schemes. One pilot study and three prospective randomized trials have tested various hypofractionated regimens of WBRT. About 7000 patients were included and follow-up ranged from 5 to 12 years. The conclusion of these trials is similar, showing local control and toxicity equivalent to these of the standard regimens. Three schemes are now clearly validated: 42.5Gy/16fr/3w, 40Gy/15fr/3w, or 42Gy/13fr/5w. However, the majority of included patients had favorable prognostic factors, were treated to the breast only and the boost dose, when indicated, was delivered with a standard fractionation. Therefore, we recommend the regimens preferentially in patients treated to the breast only, and without nodal involvement. These studies did not evaluate the addition of a boost dose with a hypofractionated scheme. If a boost is to be given, a standard fractionation should be used. Particular care should be taken to avoid heterogeneities leading to high fraction doses to organs at risk (lung and heart)., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

In breast cancer, radiotherapy is an essential component of the treatment. After conservative surgery for an infiltrating carcinoma, radiotherapy must be systematically performed, regardless of the characteristics of the disease, because it decreases the rate of local recurrence and by this way, specific mortality. Partial breast irradiation could not be proposed routinely but only in very selected and informed patients. For ductal carcinoma in situ, adjuvant radiotherapy must be also systematically performed after lumpectomy. After mastectomy, chest wall irradiation is required for pT3-T4 tumours and if there is an axillary nodal involvement, whatever the number of involved lymph nodes. After neo-adjuvant chemotherapy and mastectomy, in case of pN0 disease, chest wall irradiation is recommended if there is a clinically or radiologically T3-T4 or node positive disease before chemotherapy. Axillary irradiation is recommended only if there is no axillary surgical dissection and a positive sentinel lymph node. Supra and infra-clavicular irradiation is advised in case of positive axillary nodes. Internal mammary irradiation must be discussed case by case, according to the benefit/risk ratio (cardiac toxicity). Dose to the chest wall or the breast must be between 45-50Gy with a conventional fractionation. A boost dose over the tumour bed is required if the patient is younger than 60 years old. Hypofractionation (42.5 Gy in 16 fractions, or 41.6 Gy en 13 or 40 Gy en 15) is possible after tumorectomy and if a nodal irradiation is not mandatory. Delineation of the breast, the chest wall and the nodal areas are based on clinical and radiological evaluations. 3D-conformal irradiation is the recommended technique, intensity-modulated radiotherapy must be proposed only in case of specific clinical situations. Respiratory gating could be useful to decrease the cardiac dose. Concomitant administration of chemotherapy in unadvised, but hormonal treatment could be start with radiotherapy., (Copyright © 2016. Published by Elsevier SAS.)

Purpose: Ductal carcinoma in situ represents 15 to 20% of all breast cancers. Breast-conserving surgery and whole breast irradiation was performed in about 60% of the cases. This study reports local recurrence rates in patients with ductal carcinoma in situ treated by breast-conserving surgery and whole breast irradiation with or without boost and/or tamoxifen and compares different therapeutic options in two European countries., Patients and Methods: From 1998 to 2007, 819 patients with pure ductal carcinoma in situ were collected, both in France (266) and Italy (553). Median age was 56. All underwent breast-conserving surgery and whole breast irradiation; 391 (48%) received a boost (55% in France and 45% in Italy, P=0.017) and 173 (22.5%) tamoxifen (4.5% in France and 32% in Italy, P<0.0001)., Results: With a 90-month median follow-up, there were 51 local recurrences (6.2%), including 27 invasive (53%). The 5- and 10-year local recurrence rates were 4% and 8.6%. Two patients developed axillary recurrence and 12 (1.5%) metastases (seven after invasive local recurrence); 41 (5%) patients had contralateral breast cancer. In the multivariate analysis, high nuclear grade and lack of tamoxifen are the most powerful predictors of local recurrence, with 2.6 (95% confidence interval [95% CI]: 1.74-3.89, P=0.0012) and 2.85 (95% CI: 1.42-5.72, P=0.04) odds ratio (OR) estimates, respectively. Age, margin status and boost did not influence local recurrence rates., Conclusions: This study confirms the ductal carcinoma in situ treatment heterogeneity among countries and the unfavourable prognostic role of nuclear grade. Tamoxifen reduces local recurrence rates and might be considered for some subgroups of patients, but further confirmation is required. The boost usefulness still remains unclear., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

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., (© 2016 Société Française du Cancer. Publié par Elsevier Masson SAS.)

Purpose: Several studies showed a breast cancer downstaging due to screening. A first national survey was conducted in France in 2001-2002 to evaluate in the current clinical practice the clinicopathological features and treatments of 1049 firstly operated breast cancers. In order to assess the impact of the national screening program implemented in all regions in France in 2004, a new survey was performed in 2007-2008., Material: The new survey included 1433 firstly operated breast cancers prospectively collected. These new data were compared to the results of the first national survey., Results: According to TN classification, we found in the second survey T0: 27.6%, T1: 48.6%, T2: 21.3%, T3T4: 3.8% and Tx: 0.7%. Infiltrating ductal and lobular carcinomas represented 80% and 13% of tumours. Hormone receptors were positive in 85.3% and Her-2 overexpressed in 12.4% of tumours (83.9% and 20.6% in the first survey); 68.2% and 32% were pN0 and pN1-3. Lumpectomy and mastectomy were performed in 77% and 23% of the cases. Axillary dissection, sentinel node biopsy or both were performed in 42.6%, 41% and 16.4% of the cases, respectively. Radiotherapy, chemotherapy, hormonotherapy and trastuzumab were given to 93%, 51%, 83% and 9.3% of the patients. Compared with the results from the first survey, we found an increase of infraclinical lesions (T0 from 8.4 to 27.6%) and a wide decrease of pN+ rate (from 44% to 32%). The mastectomy rate was constant (23%), as well as radiotherapy use, whereas chemotherapy use decreased from 62.8 to 55.6%., Conclusion: A complete national screening coverage clearly provides a favourable modification of breast cancer clinicopathological features. Both locoregional and adjuvant treatments were greatly downscaled., (Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Objectives: The optimal treatment for male breast cancer is not known because male breast cancer is a rare disease. It represents as little as 0.6% of all breast cancers and less than 1% of human cancers. The aim was to analyze the clinical, histological and therapeutic characteristics of 95 men cared for breast cancer between 2000 and 2010 in four hospitals, and determine predictors of poor prognosis to improve care of male breast cancer., Methods: This study is a multi-institutional survey, retrospective, involving four French institutions: Cancer Institute of the West (ICO), Reunion Island South hospital group, the hospital group of Dax, and the Bergonié Institute. All carcinomas in situ or invasive breast occurred in male patients were included. An analysis of clinical, histological and therapeutic features was performed. Statistical analysis of our study focused on the overall survival of patients and specific method of Kaplan-Meier, enabling search for predictors of poor prognosis., Results: The mean age was 65 years. Thirty-seven percent of patients were overweight or obese. It was in 88% of cases of palpable tumor whose average size was 26.29mm. Ninety patients, none had a lesion palpable T0, 44% T1 tumors, 38% T2 tumors, 3% had a T3 tumors, and finally 10% T4 tumors. The histological type was the most common invasive ductal carcinoma (87%). He found a similar proportion of patients with or without lymph node involvement. N+ patients, capsular rupture was observed in 29% of cases. Receptor positivity was found, estrogen in 95% of cases and progesterone in 83% of cases. Additional irradiation was performed in 75% of patients and chemotherapy in 37% of patients. Overall survival was 79.2% at five years and 70.8% at ten years. Age, tumor size and histological capsular rupture are factors that significantly influence the overall survival and specific., Conclusion: Male breast cancer is a different pathology of breast cancer in women. The majority of recommendations suggest treating men who are diagnosed with breast cancer, using the guidelines applied to postmenopausal women treatments. There is no study based on male population that has evaluated these treatment modalities in terms of impact on survival. The diagnosis is usually made at later stages, and tumor size is often greater. Histological characteristics also differ. However, the treatment is almost identical., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Purpose: Ductal carcinoma in situ overall prognosis is excellent, but after breast conserving surgery, with or without radiotherapy, local recurrences can lead to locoregional or distant evolution and death. However, there are few data on optimal local recurrences treatment and long-term impact on survival., Patients and Methods: This study included 195 women treated from 1985 to 1996 by conservative surgery (CS) or conservative surgery followed by radiotherapy (CS+RT), presenting local recurrences, with a 156-month median follow-up., Results: Eighty-two out of 195 (42%) local recurrences were non-invasive (in situ) and 113 (58%) invasive. In situ local recurrence was discovered by mammography in 80.5% of the cases versus 47.5% for invasive local recurrence (P=0.0001). Salvage mastectomy was used in 53% of the cases after conservative surgery and 75% after conservative surgery followed by radiotherapy. The axillary nodal involvement rates were 11.8% and 25.8% among 17 and 62 patients with in situ and invasive local recurrences. Among 113 patients with invasive local recurrences and 82 with in situ local recurrences, 19 (16.8%) and three (3.6%) developed metastases, respectively. Among invasive local recurrences, comedocarcinoma subtype was highly predictive of subsequent metastases (32% versus 4.4%, P<0.0007)., Conclusion: Invasive local recurrence after ductal carcinoma in situ treatment could be a dramatic event, fully changing long-term prognosis. Early mammographic local recurrence diagnosis (if possible still at non-invasive stage) seems essential to avoid or minimize metastatic risk. Mastectomy remains the safest option but, in some cases, a new conservative approach could be discussed., (Copyright © 2013. Published by Elsevier SAS.)

Postoperative radiotherapy remains essential in breast cancer in 2012. After conserving surgery, it reduces local recurrence risks from 50 to 70%, both for ductal carcinoma in situ and invasive cancers. This was confirmed in several randomized trials and three meta-analyses. The boost increases local control in invasive cancers, but its role should be better defined in ductal carcinoma in situ. Among the latter, there is no clearly identified subgroup for which radiotherapy could be avoided. Local recurrence risk factors are now well-identified both for ductal carcinoma in situ and invasive cancers, with an inclusion, for the latter, of new molecular subgroups. After mastectomy, radiotherapy reduces local recurrence rates from 60 to 70%, especially among patients with axillary nodal involvement, with, in parallel, a 7 to 9% increased survival rate. In order to reduce the waiting list and to avoid under treatment, especially in the elderly, several hypofractionated radiotherapy schemes have been developed for several years. Three randomized trials confirmed similar results to classical radiotherapy. For ten years, several techniques of partial breast irradiation have been developed, with various doses and treated volumes. The optimal indications should be defined according to the new international guidelines., (Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

The French National Cancer Institute (INCa) and Société française de sénologie et pathologie mammaire (SFSPM), in collaboration with a multidisciplinary experts group, have published the French national clinical practice guidelines on a selection of 11 currently debated questions regarding the management of invasive breast cancer. Those guidelines are based on a comprehensive analysis of the current published evidence dealing with those issues, secondly reviewed by 100 reviewers. Radiotherapy was concerned by five of the 11 questions: indications for the boost after whole gland irradiation; hypofractionated radiotherapy; partial breast irradiation; indications for mammary internal nodes irradiation, and indications of radiotherapy after neo-adjuvant chemotherapy., (Copyright © 2012. Published by Elsevier SAS.)

The continuous increase of breast cancer (BC) incidence, the logistic constraints of the protracted standard 5-week radiations regimen have led to test short hypofractionated whole breast radiation therapy schemes. Three prospective randomized trials and a pilot trial have been published. Large numbers of patients were included, with follow-up duration ranging from 5 to 12 years. The conclusions of these trials were similar, showing local control and toxicity equivalent to those of the standard regimen, and supporting the use of three schemes: 42.5 Gy/16 fractions/3 weeks, 40 Gy/15 fractions/3 weeks or 41.6 Gy/13 fractions/5 weeks. However, the patients in these trials had favourable prognostic factors, were treated to the breast only and the boost dose, when indicated, was delivered with a standard fractionation. Hypofractionated treatment can only be recommended in patients treated to the breast only, without nodal involvement, with grade<3 tumours and who are not candidate to chemotherapy. If a boost is to be given, a standard fractionation should be used. Particular care should be taken to avoid heterogeneities leading to high fractional doses to organs at risk (lung and heart)., (Copyright © 2011. Published by Elsevier SAS.)

Background: After breast conservative treatment (BCT), young age is a predictive factor for recurrence in patients with Ductal Carcinoma In Situ (DCIS) of the breast. The purpose of this study was to evaluate predictive factors for recurrence and outcomes in these younger women (under 40 years) treated for pure DCIS., Methods: From 1974 to 2003, 207 cases were collected in 12 French Cancer Centers. Median age was 36.3 years and median follow-up 160 months. Seventy four (35.8%) underwent mastectomy, 67 (32.4%) lumpectomy alone and 66 (31.9%) lumpectomy plus radiotherapy., Results: 37 recurrences occurred (17.8%): 14 (38%) were in situ and 23 (62%) invasive. After BCT, the overall rate of recurrence was 27% (33% in the lumpectomy plus radiotherapy group vs. 21% in the lumpectomy alone group). Comedocarcinoma subtype (p = 0.004), histological size more than 10 mm (p = 0.011), necrosis (p = 0.022) and positive margin status (p = 0.019) were statistically significant predictive factors for recurrence. The actuarial 15-year rates of local recurrence were 29%, 42% and 37% in the lumpectomy alone, lumpectomy and whole breast radiotherapy and lumpectomy + whole breast radiotherapy with additional boost groups respectively. After recurrence, the 10-year overall survival rate was 67.2%., Conclusion: High recurrence rates (mainly invasive) after BCT in young women with DCIS are confirmed. BCT in this subgroup of patients is possible if clear and large margins are obtained, tumor size is under 11 mm and necrosis- and/or comedocarcinoma-free., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

From March 2003 to April 2004, were prospectively collected in France 1,289 ductal carcinoma in situ (DCIS) with data on diagnosis, patient and tumour characteristics, and treatments. Median age was 56 years (range, 30-84). DCIS was diagnosed by mammography in 87.6% of patients. Mastectomy (M), conservative surgery alone (CS) and conservative surgery with radiotherapy (CS + RT) were performed in 30.5, 7.8 and 61.7% of patients, respectively. Sentinel node biopsy (SNB) and axillary dissection (AD) were performed in 21.3 and 10.4% of patients, respectively. Hormone therapy was administered to 13.4% of the patients. Nuclear grade was low in 21% of patients, intermediate in 38.5% and high in 40.5%. Excision was considered complete in 92% (CS) and 88.3% (CS + RT) of patients. Treatment modalities varied widely according to region: mastectomy rate, 20-37%; adjuvant RT, 84-96%; hormone treatment, 6-34%. Our survey on current DCIS management in France has highlighted correlations between pathological features (tumour size, margin, grade) and treatment options, with several similar variations to those observed in recent UK and US studies.

In Western countries, about 25% of breast cancers (BC) occur in women older than 70 years old. Local control is a crucial step to cure disease, because locoregional relapse (LRR) is a major risk factor of subsequent metastases. After mastectomy, radiotherapy (RT) confirmed a very high value (regardless of age) in several trials and meta-analyses, especially in case of high LRR risk factors (i.e. axillary nodal involvement). Globally, RT reduces LRR rates by 60-70% and also increases long-term survival rates by 8-9%. After breast conserving surgery, several trials and meta-analyses confirmed that RT decreases 10-year local recurrence rates from 20-25 to 5-8%. RT replacement by hormonal treatment leads to a significantly higher LRR rate. Hypofractionated RT schemes could usefully apply to elderly people, but partial breast irradiation techniques are still under investigation. Finally, all elderly fitted women should receive adjuvant RT according to general guidelines with optimal technique in order to avoid cardiotoxicity. Indeed, under-treatment has an unfavourable effect on long-term survival.

Breast cancer (BC) is the first female cancer in France, accounting for 49,240 new cases in 2004. Approximately 80% of those tumors have positive hormone receptors (HR). Tamoxifen was used in four chemoprevention randomized trials, as well as another SERM (Selective Estrogen Receptor Modulation), raloxifen. This review analyses the updated results of these trials. All trials have shown that the risk of developing HR positive BC was reduced by tamoxifen or raloxifen, but without impact on HR negative BC and overall survival. Moreover, several unfavorable side effects (thrombo-embolic accidents and uterine cancers) have been observed. A new assessment of BC risk factors seems necessary, including not only family history and some histopathological abnormalities (e.g. atypical hyperplasia), but also new elements such as high bone and breast density and thoracic irradiation at young age (Hodgkin's disease). Indeed, tamoxifen efficacy seems optimal in very "high-risk" women. Therefore, the creation of a new and most comprehensive "risk model" is necessary as well as a tailored SERM use (maybe with other compounds), in order to optimize results and reduce potential side effects.

Male breast cancer (MBC) is considered as a rare disease comprising about 1% of all breast cancers. As compared to women breast cancer, MBC has some similarities and also some particularities related to age, comorbidities, breast volume, diagnostic delay, prognosis and survival. Modified radical mastectomy (MRM) with axillary dissection is the gold standard. Sentinel lymph node dissection is a promising option for early stages. Adjuvant radiation is proposed because of the high frequency of node involvement and central tumor location. In hormone receptor positive tumors tamoxifen remains the gold standard endocrine therapy because of the lack of data on aromatase inhibitors. Adjuvant chemotherapy can be proposed to high-risk patients while trastuzumab should be an option in breast cancer that overexpresses HER2. In the setting of considerable evolution in the management of women breast cancer, this review aimed to point out on the similarities and particularities of MBC and the future challenges to improve MBC outcome.

Background: Trastuzumab (T) combined with chemotherapy has been recently shown to improve outcome in HER2-positive breast cancer (BC). The aim of this study was to evaluate the toxic effects of concurrent radiation therapy (RT) and T administration in the adjuvant setting., Patients and Methods: Data of 146 patients with stages II-III HER2-positive BC were recorded. Median age was 46 years. In all, 32 (23%) and 114 (77%) patients received a weekly and a 3-week T schedule, respectively. A median dose of 50 Gy was delivered after surgery. Internal mammary chain (IMC) was irradiated in 103 (71%) patients., Results: Grade >2 dermatitis and esophagitis were noted in 51% and 12%, respectively. According to the Common Toxicity Criteria v3.0 scale and HERA (HERceptin Adjuvant) trial criteria, respectively, 10% and 6% of the patients had a grade >/=2 of left ventricular ejection fraction (LVEF) decrease after RT. Multivariate analyses revealed two independent prognostic factors: weekly T administration (for LVEF decrease) and menopausal status (for dermatitis). Higher level of T cumulative dose (>1600 mg) was only borderline of statistical significance for acute esophagitis toxicity., Conclusion: We showed that weekly concurrent T and RT are feasible in daily clinical practice with, however, a decrease of LVEF. Cardiac volume sparing and patient selections for IMC irradiation are highly recommended. Longer follow-up is warranted to evaluate late toxic effects.

After a dominant role for more than 30 years, tamoxifen has been progressively replaced by aromatase inhibitors as adjuvant treatment for breast cancer in the menopaused woman. We present here a recall of the mechanisms of action involved together with a review of clinical trials leading to the current situation. Giving trial results in detail, we discuss the current evidence as well as open questions. The populations concerned and trial methodologies are analyzed. Comparative tolerance is detailed. Several questions remain open, either due to the lack of evidence to be obtained from ongoing trials or sufficient follow-up. The evidence presented is commented in light of the American (ASCO) and European (Saint-Gallen) or French (Saint-Paul) guidelines.

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.

The increasing incidence of DCIS during the past 20 years needs a continuous evaluation of the treatment strategies and a multidisciplinary decision process. The management of the DCIS remains a challenging issue in 2003. Mastectomy should still be considered as the reference treatment which is able to guarantee cure in almost all cases, whereas breast conserving surgery followed by radiation therapy is associated with 7-10% of local recurrence. However, the increasing knowledge of the predictive factors of the local recurrence allows to propose a conservative treatment strategy to a large amount of patients, without negative impact on their prognosis. This review presents the arguments that permit to justify the reasoned choice of the different therapeutic options according to the clinico-pathological situations.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of french cancer centers (FNCLCC), the 20 french cancer centers, 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 develop clinical practice guidelines for non metastatic breast cancer patients according to the definitions of the Standards, Options and Recommendations project., Methods: Data were identified by searching Medline, web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 148 independent reviewers., Results: This article presents the chapter radiotherapy resulting from the 2001 update of the version first published in 1996. The modified 2001 version of the standards, options and recommendations takes into account new information published. The main recommendations are: (1) Breast irradiation after conservative surgery significantly decrease the risk of local recurrence (level of evidence A) and the decrease in the risk of local recidive after chest wall irradiation is greater as the number of risk factors for local recurrence increases (level of evidence A). (2) After conservative surgery, a whole breast irradiation should be performed at a minimum dose of 50 Gy in 25 fractions (standard, level of evidence A). (3) A boost in the tumour bed should be performed in women under 50 years, even if the surgical margins are free (standard, level of evidence B). (4) Internal mammary chain irradiation is indicated for internal or central tumours in the absence of axillary lymph node involvement (expert agreement) and in the presence of lymph node involvement (standard, level of evidence B1). (5) Sub- and supra-claviculr lymph node irradiation is indicated in patients with axillary node involvement (standard, level of evidence B1).

Axillary nodal involvement (ANI) remains an essential prognostic factor for breast cancer patients, as it implies the necessity of systemic adjuvant treatment and locoregional irradiation. Axillary dissection (AD) contributes to improved local disease control and may increase survival. However, AD results in a 10%-25% incidence of long-term side effects, particularly lymphedema. Moreover, many small primary lesions with low risk of ANI are now discovered by screening, and it is not clear whether AD should be used routinely in all such patients. Sentinel lymph node biopsy (SLNB) is a selective procedure that allows selective staging of the axilla with few side effects. However, indications for SLNB are not precisely defined yet, so some patients may be understaged and the axillary relapse rate may increase. This study was conducted to help clinicians assess the risk of ANI and analyzed six clinical and histological parameters to optimally recognize patients who might benefit from SLNB, with a minimal risk of false-negative rate. We retrospectively analyzed the ANI risk among 893 women treated by conservative surgery and radiation for T0, T1, or T2 invasive tumours < 3 cm in size. All patients underwent AD with sampling of a minimum of seven lymph nodes. In each case, we assessed the clinical and pathological tumor size, histological subtype (including grading), tumor location, age at diagnosis, and breast size. The global ANI rate in the entire cohort was 25.3%. In multivariate analysis, three variables were significantly predictive of the ANI risk: tumor size (P < 0.0001), histological subtype (P = 0.0005), and breast size (P = 0.004). By combining these parameters, we were able to define three categories of women with low (< 20%), intermediate (21%-25%), and high (> 25%) ANI risk. We suggest that women with nonpalpable (T0), T1 grade 1/2, and T2 < 3 cm tumors of medullary, mucinous, tubular, or papillary histological subtype are the best candidates for SLNB. For other patients with a higher ANI risk tumor, AD may still remain the best procedure to obtain accurate staging and definitive local control.

The locoregional control is a crucial step in the achievement of a cancer cure. After mastectomy, the locoregional irradiation clearly reduces the chest wall and nodal relapses, especially with initial lesions more than 5 cm or with nodal involvement and/or large lymphatic or vascular emboli. Two recent randomized trials confirmed the benefit of well-adapted locoregional irradiation. In the Danish trial, including premenopausal "high-risk" women treated by mastectomy and chemotherapy (CMF protocol), the radiotherapy reduced the locoregional relapses from 32 to 9% (P < 0.001) and increased the 10-year survival rates from 45 to 54% (P < 0.001). These results are now also confirmed in a postmenopausal group, with an increased 10-year survival rate of 36 to 45% (P < 0.001). In the Canadian trial, locoregional relapse rate decreased from 25 to 13% and 10-year survival rate increased from 56 to 65%. The meta-analysis published in 1995 by the Early Breast Cancer Trialist Collaborative Group (EBCTCG) showed only a modest benefit due to locoregional irradiation in breast cancer. However, when small trials and older trials started before 1970 are excluded due to imperfect methodologies and for inadequate irradiation techniques, the benefit of the "modern" radiotherapy appears significant in the 7,840 patients selected in this way. Thus, since the locoregional irradiation can avoid some metastatic evolutions developed only after "local" or "nodal" relapse, it must be integrated in a multidisciplinary strategy. Nevertheless, this treatment must be safe and this is possible by the use of new techniques, including the definition of anatomical volumes and previsional dosimetry. The most important point concerns the treatment of the internal mammary nodes, especially when previous chemotherapy including anthracyclines was performed. The use of a direct field, with at least 40% of the dose delivered by electrons in an alternating scheme, is recommended to ensure very good protection of the heart and lungs.

Thirty-seven breast/ovarian or breast-only cancer families selected on a regional basis have been analyzed for mutations at BRCA1. By combining direct sequence analysis and protein truncation test, mutations were detected in 14 families (38%). We found seven different mutations, two of which have not been described before. Mutations at BRCA1 were present in 60% of breast/ovarian and 32% of breast-only cancer families. Mutations were frequent in families with at least one breast cancer case before age 40 (44%) and/or one bilateral breast cancer case (54%). Two mutations, namely 3600del11 and G1710X, are frequent in the population native from northeastern France. Oriented BRCA1 analysis should facilitate carrier detection in breast and/or ovarian cancer families stemming from this French area.

Context: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the 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 outcome for cancer patients. The methodology is based on literature systematic review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery., Objectives: To develop clinical practice guidelines according to the definitions of Standards, Options and Recommendations for endocrine therapy in patients with non metastatic breast cancer., Methods: Data have been identified by literature search using Medline, Embase, Cancerlit and Cochrane databases - until july 1999 - and the personal reference lists of the expert group. Once the guidelines were defined, the document was submitted for review to 125 independent reviewers., Results: The main recommendations for the endocrine therapy of patients with non metastatic breast cancer are: 1) Endocrine therapy modalities depend on menopausal status or age of women: ovarian suppression for premenopausal women, antiestrogen drug therapy for postmenopausal women (standard). 2) Tamoxifen (20 mg/d - 5 years) is beneficial to women with positive estrogen receptor tumor (standard, level of evidence A). There is no indication of tamoxifen treatment for women with negative estrogen receptor tumor (standard, level of evidence A). 3) For postmenopausal women with positive estrogen receptor tumor, tamoxifen is the standard adjuvant treatment (level of evidence A). For postmenopausal women with negative estrogen receptor, adjuvant chemotherapy has to be considered (option, level of evidence A). No adjuvant treatment has to be considered for women with poor health condition (option). 4) For premenopausal women with estrogen receptor tumor, results of clinical trials of chemotherapy versus endocrine therapy, suggest a benefit for endocrine therapy. However, there is no sufficient evidence to consider endocrine therapy alone as a standard adjuvant treatment. 5) For premenopausal women, chemotherapy + ovarian suppression or chemotherapy + tamoxifen are not better than chemotherapy alone (level of evidence A). 6) For postmenopausal women, administration of chemotherapy plus adjuvant tamoxifen versus the same tamoxifen alone, is of additional benefit in reducing recurrences but not in prolonging overall survival (standard, level of evidence A). 7) Balance of known benefits (delay to recurrence and death) and risks (side-effects of therapy) for adjuvant chemoendocrine therapy has to be taken into consideration before decision making. Chemoendocrine therapy can be indicated for women at high risk of developing metastatic disease (recommendation, experts agreement).

Locoregional control is a crucial step in the achievement of breast cancer cure. In ductal carcinoma in situ, breast irradiation significantly reduces the rates of local recurrence whatever the histological subtypes, as demonstrated by the NSABP-B17 trial (25.8% of local recurrences without radiotherapy vs. 11.4% with radiotherapy). In infiltrating breast carcinomas, complementary breast irradiation has been shown to significantly improve the local control and slightly the overall survival in five randomized trials. Following mastectomy, locoregional irradiation clearly reduces the chest wall and nodal relapse rates, especially in case of lesions more than 5 cm or with nodal involvement and/or large lymphatic or vascular emboli. Two recent randomized trials confirmed the benefit of well-adapted locoregional irradiation in all subgroups, especially in patients with one to three axillary involved nodes. In the Danish trial (including premenopausal high-risk women), radiotherapy reduced locoregional relapses from 32 to 9% (p < 0.001) and increased the 10-year survival rate from 45 to 54% (p < 0.001). In the Canadian trial, locoregional relapse rate decreased from 25 to 13% and the 10-year survival rate increased from 56 to 65%. The meta-analysis published in 1995 by the EBCTCG showed only a modest benefit due to locoregional irradiation in breast cancer. However, when small or old trials were excluded due to imperfect methodology or inadequate irradiation techniques, the benefit of modern radiotherapy became much more evident in a population of 7,840 patients. Locoregional irradiation appears to be able to reduce the risk of metastatic evolution occurring after local or nodal relapse and must be integrated in a multidisciplinary strategy. Treatment toxicity (especially toxicity due to irradiation of internal mammary nodes) is of special concern, as anthracycline-based chemotherapy is prescribed more often. The use of a direct field, with at least 60% of the dose delivered by electrons alternating with photons is recommended to protect the heart and lungs.

Purpose: In a retrospective analysis, our aim was to evaluate the immediate tolerance and the early and late complications of abdomino-pelvic radiotherapy in the Centre Alexis-Vautrin (France)., Patients and Methods: From 1st January 1983 to 31st December 1993, 117 patients were treated at Centre Alexis Vautrin in Nancy for epithelial ovarian cancer by abdominal and/or pelvic irradiation after surgery. They were aged from 24 to 85 with a median of 56 years. There were ten patients with stage I (9%), 28 patients with stage II (24%), 60 patients with stage III (61%) and 19 patients with stage IV (16%) disease. Results of surgery were determined as follows: satisfactory with absence of tumoral residuum in 26% cases (30 patients) and with residuum inferior to 20 mm in 46% cases (52 patients; incomplete in 26% cases (31 patients) either because of residuum superior in 20 mm and/or incomplete surgery; and not evaluable in 3% cases (four patients). Seventy-seven patients were sent to the Centre for postoperative treatment (66% patients of the series), 48 of them (62.4%) after non-satisfactory surgery, 29 after satisfactory surgery (37.6%). Chemotherapy was administered to only 104 patients (89% cases), and contained platinum salts and cyclophosphamid for 87% of these patients. Fourteen patients (12%) received a single irradiation dose after surgery: three in stage I, three with poor evaluation of the disease in the initial stage, three with medical contraindications to chemotherapy treatment, six with contraindications due to advanced age (?? Makes 15 ). Histologically, 46% of patients had a serous adenocarcinoma, 9% a mucinous adenocarcinoma, 11% an endometrioid adenocarcinoma, 2% a clear cell adenocarcinoma, 1% an undifferentiated adenocarcinoma, and 31% an epithelial carcinoma without any other indication. The histological grade which was recently introduced was rarely indicated. Complementary radiotherapeutic treatment consisted of pelvic irradiation for 14 patients (12%), abdomino-pelvic irradiation for 63 patients (54%), and total abdominal irradiation with a pelvic boost for 40 patients (34%)., Results: The immediate tolerance to irradiation can be considered as globally satisfactory since 9% of the patients (ten cases) had no problems and 64% of the patients developed a minor intolerance easily controlled by symptomatic treatments. There were also digestive complications: nausea, vomiting and diarrhea for 66% of the patients (50 cases); to a lesser extent, 20% of the cases experienced associated digestive and hematological complications (15 patients); 9% isolated hematological troubles such as anemia (seven patients); 4% digestive complications (three patients) and 1% hematological and urinary digestive troubles (one patients). Late irradiation sequelae were evaluated for 89 patients with a follow-up lasting from 4 months to 11 years. Sixty-six patients had no sequelae, eleven patients had minor tolerability problems--mainly digestive for more than half of them. Five patients presented severe complications, including hematological problems such as chronic thrombopenia in two cases, urinary-problems in two other cases, and one patient presented with a case of histologically proven malabsorption. Two patients presented major problems; one case of radic cystitis and one of radic bowel. Two patients died of iatrogenic causes: one of induced leukemia, the other of treatment-induced digestive and renal complications. The overall survival rate was 30% at 5 years and 22% at 10 years. It was 90% at 5 and 10 years for stage I patients, 60% at 5 years and 30% at 10 years for stage II patients, 22% at 5 years and 8% at 10 years for stage III patients, and finally 10% at 5 years for stage IV patients., Conclusion: In this retrospective analysis of 117 epithelial ovarian cancers, treated over 10 years and which all received pelvic and/or abdominal irradiation, we can conclude that this treatment is globally well tolerated and that it yields a

Purpose: Though Hodgkin's disease (HD) is one of the malignancies in which considerable progress has been made, long-term side effects have been observed, second primary cancer being the most significant. Several recent reports have indicated an increased risk of breast cancer (BC) in girls and young women among HD patients., Materials and Methods: In a retrospective multicenter analysis, 63 women treated for HD subsequently developed BC. Results that were obtained in 13 women (21%) who developed either synchronous (five cases) or metachronous (eight cases) BC were analyzed. The median age at diagnosis of HD was 19 years. Seven patients underwent exclusive radiotherapy (RT) (including "mantle" supradiaphragmatic irradiation) and six received concomittant radiation therapy and chemotherapy., Results: The first breast tumor occurred after a median delay of 16 years. According to the TNM classification, we showed nine stage T0 (non palpable lesions), four stage T1, five stage T2, one stage T3, two stage T4 and five stage Tx BC. Seventeen infiltrating carcinomas, two fibrosarcomas and seven ductal carcinomas in situ were observed. Among 15 axillary dissections performed for invasive carcinomas, histological involvement was found in 10 cases. Seventeen tumors were treated by mastectomy and nine patients underwent conservative surgical treatment. With a 70-month median follow-up (range: 15-125), three patients developed locoregional recurrence and four other metastases. At present, eight are alive with no evidence of disease and one died of intercurrent disease., Conclusion: According to previous works, BC represents 6.3 to 9% of all second cancers occurring after HD treatment. The risk is higher in young women treated before 20 years of age, especially before 15 years of age. Factors that favour the development of secondary BC are: supradiaphragmatic irradiation, very young age at treatment, chemotherapy with alkylating agents, and probably genetic factors. We conclude that young women and girls treated for HD should be carefully monitored at least 10 years after the end of the treatment for HD, using clinical examination, mammography and ultrasonography. The optimal rythm of this follow-up is not yet clearly defined. Moreover, after multidisciplinary concertation, we suggest that secondary BC be sometimes treated by conservative radiosurgical approach.

Tamoxifen is the anti-estrogen the most widely used in breast cancer. The duration of its prescription, as adjuvant treatment, tends to increase (5 years, and even more) and now it is used in chemoprevention. A slight increase of thromboembolic complications was noted in some studies. This article evaluates the frequency of thromboembolic accidents (TEA) in 441 postmenopausal patients treated by an association of conservative radiosurgery, tamoxifen +/- chemotherapy, for a breast carcinoma T0, T1T2 < 4 cm. Nineteen patients (4.3%), all in remission, presented a TEA, between 1 and 44 months after the beginning of the tamoxifen treatment. We observed seven pulmonary embolisms (PE), 11 deep venous thromboses (DVT) and an acute arterial ischemia. Two patients aged 74 and 80 years died, the others had a favourable evolution under anticoagulant treatment. Among these 19 patients, six presented known risks factors (phlebitis, cardiovascular disorders) and ten had a "favouring circumstance" aggravating the risk of TEA (surgical operation, severe infection, fracture). Their median age was 65 years (61 for all the 441 patients). We noted eight cases of breast lobular cancer (42%) among these 19 patients (11% for all the patients). Among postmenopausal patients, the indication of tamoxifen must be evaluated according to the benefits expected in those with high risk factors of TEA (history of heart failure, obesity, spread varix, age > 65 years). In case of DVT and/or PE, this treatment seems contra-indicated. In case of "favouring circumstances", a hypocoagulant or systematic anticoagulant treatment must be proposed. In case of combined chemotherapy, it is better to start tamoxifen at the end of the treatment. These simple prophylactic measures should allow to reduce significantly the risk of TEA in postmenopausal patients with adjuvant anti-estrogenotherapy.