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Radiation therapy is a corner stone of breast cancer treatment as it has been shown postoperatively that it improves local control and overall survival. In recent years, multidisciplinary therapeutic strategies have evolved considerably for early-stage breast cancer, both surgically and in terms of systemic treatments or radiation therapy. Each of these developments affects other treatment components and open up new questions allowing even more personalized treatments. Essentially normofractionated a few years ago, breast radiation therapy is today very largely moderately or even ultra hypofractionated. De-escalation of the surgery of the axilla has changed the indications for lymph node radiation therapy keeping similar efficacy with reduced toxicity. Indications for radiation therapy after neoadjuvant chemotherapy remain based on pre-chemotherapy staging pending the results of ongoing randomized studies. The addition of a boost to the tumor bed significantly reduces the risk of local recurrence, but the magnitude of this benefit decreases with increasing age. The main risk factors for local recurrence are young age, the associated extended ductal in situ component, hormone receptor negative and high-grade status. The results of the simultaneous integrated boost (SIB) seem similar with normo- or moderately hypofractionated radiation therapy regimen., (Copyright © 2023 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: The study aims to assess the feasibility, safety, and tolerability of CareMin650, a new photobiomodulation device, in patients treated by radiotherapy (RT) and to collect preliminary data on efficacy for prevention and treatment of oral mucositis (OM) and radiation dermatitis (RD)., Methods: Safe PBM is a French, multicentric, prospective, non-comparative study which include patients with head and neck cancer (H&NC, cohort A) or breast cancer (BC, cohort B) treated in prophylactic (cohorts A1 and B1) or curative setting (cohort A2 and B2). Prophylactic treatment was administered from D1 to end of RT, at a dose of 3 J/cm 2 . Curative treatment started when a grade 1 to grade 3 lesion had occurred and was pursued until end of RT. Primary endpoint was incidence of device-related adverse events (AEs). OM and RD lesions were graded according to CTCAE V3., Results: Overall, 72 patients were included (22, 9, 23, and 18 in cohorts A1, A2, B1, and B2, respectively). No device-related AE was reported after 1312 CareMin650 sessions. In cohorts A1 and B1, median time to first OM or RD lesion was 20 days. One BC patient developed G3 RD after completion of RT and discontinuation of CareMin650. Four H&NC patients developed G3 OM. In cohorts A2 and B2, lesions improved or stabilized in 71% of patients. Rates of satisfaction were high among patients and users., Conclusion: CareMin650 is feasible, safe, and well tolerated for preventive or curative treatment of OM and RD in cancer patients treated with RT. Preliminary efficacy results are promising., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neoadjuvant fluoropyrimidine (5FU or capecitabine)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is still unclear., Methods: To identify clinical trials combining oxaliplatin in preoperative CRT or perioperative chemotherapy for LARC published until March 2021, we searched PubMed and the Cochrane Library. We also searched for relevant ASCO conference abstracts. The primary endpoint was disease-free survival (DFS). Data were extracted from every study to perform a meta-analysis using Review Manager (version 5.3)., Results: A total of seven randomized clinical trials (ACCORD-12, CARO-AIO-04, FOWARC, JIAO, NSABP, PETACC-6, and STAR-01) with 5782 stage II or III rectal cancer patients were analyzed, including 2727 patients with OXP + 5FU regimen and 3055 patients with 5FU alone. Compared with the 5FU alone group, the OXP + 5FU regimen improved DFS (HR = 0.90, 95% CI: 0.81-0.99, p = 0.03) and pathologic complete response (pCR) (OR = 1.21, 95% CI: 1.07-1.37, p = 0.002). Patients treated with the OXP + 5FU regimen had significantly less metastatic progression (OR = 0.79; 95% CI, 0.67 to 0.94; p = 0.007). Considering adverse events (AEs), there was more grade 3-4 diarrhea with OXP + 5FU (OR = 2.41, 95% CI: 1.74-3.32, p < 0.00001). However, there were no significant differences grade 3-4 hematologic AEs (OR = 1.16, 95% CI: 0.87-1.57, p = 0.31)., Conclusions: Our meta-analysis with long-term results from the randomized studies showed a benefit of the addition of OXP + 5FU regiment in terms of DFS, metastatic progression, and pCR rate that did not translate to improved OS.

Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer., Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival., Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSI and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008)., Conclusions: The combined molecular subtype-RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and molecular subtype could be useful in guiding radiation therapy-based decisions in breast cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To identify predictors for infiltrating carcinoma and lymph node involvement, before immediate breast reconstructive surgery, in patients with an initial diagnosis of extensive pure ductal carcinoma in situ of the breast (DCIS)., Patients and Methods: Between January 2000 and December 2009, 241 patients with pure extensive DCIS in preoperative biopsy had underwent mastectomy. Axillary staging (sentinel node and/or axillary dissection) was performed in 92% (n = 221) of patients. Patients with micro-invasive lesions at initial diagnosis, recurrence or contralateral breast cancer were excluded., Results: Respectively 14% and 21% of patients had a final diagnosis of micro-invasive carcinoma (MIC) and invasive ductal carcinoma (IDC). Univariate analysis showed that the following variables at diagnosis were significantly correlated with the presence of either MIC or IDC in the mastectomy specimen: palpable tumor (p = 0.002), high grade DCIS (p = 0.002) and detection of an opacity by mammography (p = 0.019). Axillary lymph node (ALN) involvement was reported in 9% of patients. Univariate analysis suggested that a body mass index higher than 25 (p = 0.007), a palpable tumor (p = 0.012) and the detection of an opacity by mammography (p = 0.044) were associated with an increased rate of ALN involvement., Conclusion: Skin-sparing mastectomy and immediate breast reconstruction (IBRS) has become increasingly popular, especially for patients with extended DCIS of the breast. This study confirmed that extended DCIS is associated with a substantial risk of finding MIC or IDC on the surgical specimen but also ALN involvement. Adjuvant systemic treatment and/or radiotherapy could be indicated for some of these patients after the surgery. Patients should be informed of the rate of 1) complications associated to IBRS that will potentially delay the introduction of systemic or local therapy 2) complications associated to radiotherapy after IBRS., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The lack of pathologic breast cancer response to neoadjuvant chemotherapy (NCT), a negative prognostic factor, has prompted the addition of chemotherapy to adjuvant radiotherapy. This study aims to investigate prospectively the toxicities of adjuvant concurrent chemoradiotherapy versus radiotherapy alone., Patients and Methods: Two groups of patients treated for breast cancer between 1997 and 2002 by NCT, surgery, and radiotherapy with or without concurrent chemotherapy, were matched on age, body mass index (BMI), treatment period, treated side, and surgery type. Late toxicity was prospectively evaluated according to the CTCAE v3.0. Acute toxicity was derived from the medical charts., Results: A total of 52 patients were matched. Median follow-up was 10 years. Acute toxicity was higher in the chemoradiotherapy group compared with the radiotherapy alone group: 37% patients versus 10% experienced a grade 2/3 epithelitis (P=0.002); 48% versus 8% experienced a grade ≥1 mucositis (P=0.00001). Late toxicity was not significantly different in both univariate (51% vs. 49%; P=0.79) and multivariate analyses adjusted on the BMI (P=0.08). In univariate analysis, only the BMI tended to be predictive of toxicity (P=0.07)., Conclusions: Concurrent chemoradiotherapy after NCT and surgery was associated with increased acute toxicity but not long-term toxicity. The efficacy of this therapeutic strategy should be evaluated to better define its indications.

Purpose: Prospective monocentric study of the toxicities related to concurrent administration of trastuzumab to breast radiotherapy., Patients and Methods: One hundred and seventy-three patients were treated between June 2003 and March 2009 by concurrent trastuzumab with normofractionated radiotherapy. Trastuzumab was delivered every 3 weeks (8mg/kg in the first infusion then 6mg/kg) during a median time of 12 months (2-62). Left ventricular ejection fraction was assessed by echocardiography or cardiac scintigraphy at baseline, before and after radiotherapy, every 3 months for 1 year and annually. A left ventricular ejection fraction strictly lower than 55% was considered as altered. All toxicities were evaluated using Common Terminology Criteria for Adverse Effects version 3.0., Results: Median follow-up was 52 months (17-88). Median age was 52 years (25-83). One hundred and thirty-four patients (77.5%) received radiotherapy to the internal mammary chain. Acute grade 1, 2 and 3 epithelitis was described in 132 (76.3%), 32 (18.5%) and six patients (3.4%), respectively. At 23 months, grade 1 and 2 fibrosis was observed in 31 and eight patients, respectively (18.8 and 4.6%). Left ventricular ejection fraction remained normal for 159 patients (91.9%) before radiotherapy. Among them, 18 (11.3%) experienced a left ventricular ejection fraction alteration, eight (5.0%) at the completion of radiotherapy. Congestive heart failure occurred in one patient (0.6%)., Conclusions: Toxicities related to the association of trastuzumab to breast radiotherapy were mild. Further follow-up is warranted., (Copyright © 2013 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To actualize and to detail guidelines used in technical radiotherapy and indications for innovative radiation technologies in early axillary node negative breast cancer (BC)., Methods: Dosimetric and treatment planning studies, phase II and III trials, systematic reviews and retrospective studies were all searched (Medline(®) database). Their quality and clinical relevance were also checked against validated checklists. A level of evidence was associated for each result., Results: A total of 75 references were included. Adjuvant BC radiotherapy (50Gy/25 fractions/5 weeks followed by a tumor boost of 16Gy/8 fractions) is still the standard of care. Overall treatment time could be shortened for patients who present with low local relapse risk BC by using either hypofractionated whole breast irradiation; or accelerated partial breast irradiation. BC IMRT is not used in current practice., Conclusion: Our group aimed to provide guidelines for technical and clinical applications of innovative BC radiation technologies., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Molecular signatures may become of use in clinical practice to assess the prognosis of breast cancers. However, although international consensus conferences sustain the use of these new markers in the near future, concerns remain about their degree of discordance and cost-effectiveness in different international settings. The present study aims to validate Ki67 as prognostic factor in a large cohort of early-stage (pT1-pT2, pN0) breast cancer patients., Methods: 456 patients treated in 1995-1996 were identified in the Institut Curie database. Ki67 (MIB1) was retrospectively assessed by immunohistochemistry for all cases. The prognostic value of this index was compared to that of histological grade (HG), Estrogen receptor (ER) and HER2 status. Distant disease free interval, loco-regional recurrence, time-lapse from first metastatic diagnosis to death were analyzed., Results: All 456 patients were treated by lumpectomy plus axillary dissection and radiotherapy. 27 patients (5.9%) received systemic treatment. Tumors were classified as HG1 in 35%, HG2 in 42% and HG3 in 23% of cases. ER was expressed in 86% of the tumors, HER2 in 5% and 14% were triple negative. The median follow-up was 151 [5-191] months. Distant and loco-regional disease recurrences were observed in 16% and 18%, respectively. High (>20%) Ki67 rate [HR = 3 (1.8-4.8), p<10e-06] and HG3 [HR = 4.4 (2.2-8.6), p = 0.00002] were associated with an increased rate of distant relapse. In multivariate analysis, the Ki67 remained the only significant prognostic factor in the subgroups of ER positive HER2 negative [HR = 2.6 (1.5-4.6), p = 0.0006] and ER positive HER2 negative HG2 tumors [HR = 2.2 (1.01-4.8), p = 0.04]., Conclusions: We validate the prognosis value of the Ki67 rate in small size node negative breast cancer. We conclude that Ki67 is a potential cost-effective decision marker for adjuvant therapy in early-stage HG2, pT1-pT2, pN0, breast cancers.

The majority of patients who develop liver metastases in metastatic colorectal cancer (mCRC) has often unresectable disease. Several new methods of nonsurgical ablation have been tested with variable success. Helical tomotherapy (HT), such as intensity-modulated radiation therapy (IMRT) or stereotactic body radiotherapy therapy, is a recent radiation therapy technique which can provide simultaneous and precise targeting of multiple lesions, while sparing normal tissues. We retrospectively assess the feasibility and the tolerance of IMRT with capecitabine followed by hepatic surgery in mCRC patients. This original observation suggests that HT could be safely integrated in the multidisciplinary management of patients with metastatic colorectal cancer as an alternative to surgery or other local ablation therapies.

In early-stage breast cancer, radiotherapy delivered after conservative surgery leads to a reduction in the risk of local recurrences by approximately two thirds. However, some local recurrences can occur in a previously irradiated region and be relevant for a second radiotherapy, exposing to an increased risk of adverse effects. We describe here the observation of a 66-year-old woman treated for a triple negative ductal infiltrative carcinoma of the left breast, who presented an early locoregional recurrence, notably as skin nodules, developed within the irradiated volume and progressing on chemotherapy. The patient was treated by re-irradiation performed concomitantly to oral chemotherapy by capecitabine., (Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Aim: To retrospectively assess the acute and long-term toxicity using aromatase inhibitors (AI) therapy concurrently with hypofractionated radiotherapy (HFRT) in breast cancer patients., Methods: From November 1999 to October 2007, 66 patients were treated with breast HFRT and concurrent AI. In 63 patients (95.5%), HFRT delivered a total dose of 32.5 Gy to the whole breast within 5 wk (five fractions, one fraction per week). Other fractionations were chosen in three patients for the patients' personal convenience. A subsequent boost to the tumor bed was delivered in 35 patients (53.0%). Acute toxicities were scored according to the Common Toxicity Criteria for Adverse Events v3. Late toxicity was defined as any toxicity occurring more than 6 mo after completion of HFRT and was scored according to the Late Effects Normal Tissue Task Force-Subjective, Objective, Management and Analytic scale., Results: At the end of the HFRT course, 19 patients (28.8%) had no irradiation-related toxicity. Acute grade 1-2 epithelitis was observed in 46 patients (69.7%). One grade 3 toxicity (1.5%) was observed. With a median follow-up of 34 mo (range: 12-94 mo), 31 patients (47%) had no toxicity, and 35 patients (53%) presented with grade 1-2 fibrosis. No grade 3 or greater delayed toxicity was observed., Conclusion: We found that AI was well tolerated when given concurrently with HFRT. All toxicities were mild to moderate, and no treatment disruption was necessary. Further prospective assessment is warranted.

Purpose: To report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery., Patients and Methods: Medical records of 72 women who developed either ductal carcinoma in situ or stage I-III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed., Results: Median age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40 Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%)., Conclusions: Breast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position., (Copyright © 2012 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expression profile of a larger data set., Experimental Design: Gene expression tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the gene expression profile of the 343 breast cancers and to identify subgroups that differ for their risk of local recurrence., Results: The previous local recurrence signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene sets. Hierarchical clustering of all 343 breast cancers did not show any grouping reflecting local recurrence status. Genes related to proliferation were found differentially expressed between patients with or without local recurrence only in triple-negative tumors. Supervised classification revealed no significant gene set predictive for local recurrence or able to outperform classification based on clinical variables., Conclusions: Although the previously identified local recurrence signature was robust on another platform, we were neither able to validate it on an independent data set, nor able to define a strong gene expression classifier for local recurrence using a larger data set. We conclude that there are no significant differences in gene expression pattern in tumors from patients with and without local recurrence after breast-conserving treatment.

Purpose: To report clinical and pathologic characteristics and outcome of breast cancer (BC) after irradiation for Hodgkin's lymphoma (HL) in women treated at the Institut Curie, with a special focus on the breast-conserving option., Methods and Materials: Medical records of 72 women who developed either ductal carcinoma in situ or Stage I-III invasive carcinoma of the breast after HL between 1978 and 2009 were retrospectively reviewed., Results: Median age at HL diagnosis was 23 years (range, 14-53 years). Median total dose received by the mediastinum was 40 Gy, mostly by a mantle-field technique. Breast cancers occurred after a median interval of 21 years (range, 5-40 years). Ductal invasive carcinoma and ductal carcinoma in situ represented, respectively, 51 cases (71%) and 14 cases (19%). Invasive BCs consisted of 47 cT0-2 tumors (82%), 5 cN1-3 tumors (9%), and 20 Grade 3 tumors (35%). Locoregional treatment for BCs consisted of mastectomy with (3) or without (36) radiotherapy in 39 patients and lumpectomy with (30) or without (2) adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast-conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were, respectively, 74.5% (95% confidence interval [CI], 64-88%) and 82% (95% CI, 72-93%) for invasive carcinoma and 100% (95% CI, 100 -100%) and 92% (95% CI, 79-100%) for in situ carcinoma. In patients with invasive tumors, the 5-year distant disease-free survival rate was 79% (95% CI, 69-91%), and 13 patients died of progressive BC. Contralateral BC was diagnosed in 10 patients (14%)., Conclusions: Breast-conserving treatment can be an option for BCs that occur after HL, despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position, to protect the underlying heart and lung., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the effect of postmastectomy radiotherapy (PMRT) in Stage II-III breast cancer patients with negative lymph nodes (pN0) after neoadjuvant chemotherapy (NAC)., Patients and Materials: Of 1,054 breast cancer patients treated with NAC at our institution between 1990 and 2004, 134 had pN0 status after NAC and mastectomy. The demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The effect of PMRT on locoregional recurrence-free survival and overall survival (OS) was evaluated by multivariate analysis, including known prognostic factors., Results: Of the 134 eligible patients, 78 (58.2%) received PMRT and 56 (41.8%) did not. At a median follow-up time of 91.4 months, the 5-year locoregional recurrence-free survival and OS rate was 96.2% and 88.3% with PMRT and 92.5% and 94.3% without PMRT, respectively (p = NS). The corresponding values at 10 years were 96.2% and 77.2% with PMRT and 86.8% and 87.7% without PMRT (p = NS). On multivariate analysis, PMRT had no effect on either locoregional recurrence-free survival (hazard ratio, 0.37; 95% confidence interval, 0.09-1.61; p = .18) or OS (hazard ratio, 2.06; 95% confidence interval, 0.71-6; p = .18). This remained true in the subgroups of patients with clinical Stage II or Stage III disease at diagnosis. A trend was seen toward poorer OS among patients who had not had a pathologic complete in-breast tumor response after NAC (hazard ratio, 6.65; 95% confidence interval, 0.82-54.12; p = .076)., Conclusions: The results from the present retrospective study showed no increase in the risk of distant metastasis, locoregional recurrence, or death when PMRT was omitted in breast cancer patients with pN0 status after NAC and mastectomy. Whether the omission of PMRT is acceptable for these patients should be addressed prospectively., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: This phase II trial aimed to investigate the efficacy of concurrent radio- (RT) and chemotherapy (CT) in the preoperative setting for operable, non-metastatic breast cancer (BC) not amenable to initial breast-conserving surgery (BCS)., Patients and Methods: From 2001 to 2003, 59 women were included. CT consisted of four cycles of 5-FU, 500 mg/m(2)/d, continuous infusion (d1-d5) and vinorelbine, 25 mg/m(2) (d1 and d6). Starting concurrently with the second cycle, RT delivered 50 Gy to the breast and 46 Gy to the internal mammary and supra/infra-clavicular areas. Breast surgery and lymph node dissection were then performed. Adjuvant treatment consisted of a 16 Gy boost to the tumor bed after BCS, FEC (four cycles of fluorouracil 500 mg/m(2), cyclophosphamide 500 mg/m(2), and epirubicin 100 mg/m(2), d1; d21) for pN1-3 and hormone-therapy for positive hormone receptors BC., Results: The in-breast pathological complete response rate was 27%. BCS was performed in 41 (69%) pts. Overall and distant-disease free survivals at 5 years were respectively 88% [95% CI 80-98] and 83% [95% CI 74-93] whereas locoregional and local controls were 90% [95% CI 82-97] and 97% [95% CI 92-100]. Late toxicity (CTCAE-V3) was assessed in 51 pts (86%) with a median follow-up of 7 years [5-8]. Four (8%) experienced at least one grade III toxicities (one telangectasia and three fibroses). Cosmetic results, assessed in 35 of the 41 pts (85%) who retained their breasts, were poor in four pts (11%)., Conclusion: Preoperative concurrent administration of RT and CT is an effective regimen. Long-term toxicity is moderate. This association deserves further evaluations in prospective trials., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Genomic grade (GG) is a 97-gene signature which improves the accuracy and prognostic value of histological grade (HG) in invasive breast carcinoma. Since most of the genes included in the GG are involved in cell proliferation, we performed a retrospective study to compare the prognostic value of GG, Mitotic Index and Ki67 score., Methods: A series of 163 consecutive breast cancers was retained (pT1-2, pN0, pM0, 10-yr follow-up). GG was computed using MapQuant Dx(R)., Results: GG was low (GG-1) in 48%, high (GG-3) in 31% and equivocal in 21% of cases. For HG-2 tumors, 50% were classified as GG-1, 18% as GG-3 whereas 31% remained equivocal. In a subgroup of 132 ER+/HER2- tumors GG was the most significant prognostic factor in multivariate Cox regression analysis adjusted for age and tumor size (HR = 5.23, p = 0.02)., Conclusions: In a reference comprehensive cancer center setting, compared to histological grade, GG added significant information on cell proliferation in breast cancers. In patients with HG-2 carcinoma, applying the GG to guide the treatment scheme could lead to a reduction in adjuvant therapy prescription. However, based on the results observed and considering (i) the relatively close prognostic values of GG and Ki67, (ii) the reclassification of about 30% of HG-2 tumors as Equivocal GG and (iii) the economical and technical requirements of the MapQuant micro-array GG test, the availability in the near future of a PCR-based Genomic Grade test with improved performances may lead to an introduction in clinical routine of this test for histological grade 2, ER positive, HER2 negative breast carcinoma.

Purpose: Neoadjuvant chemotherapy generally induces significant changes in the pathological extent of disease and challenges the standard indications of adjuvant postmastectomy radiation therapy. We retrospectively evaluated the impact of postmastectomy radiation therapy in breast cancer patients with negative lymph nodes (pN0) after neoadjuvant chemotherapy., Patients and Materials: Among 1054 breast cancer patients treated with neoadjuvant chemotherapy in our institution between 1990 and 2004, 134 patients had pN0 status after neoadjuvant chemotherapy and mastectomy. Demographic data, tumor characteristics, metastatic sites, and treatments were prospectively recorded. The impact of postmastectomy radiation therapy on locoregional recurrence-free survival and overall survival was evaluated by multivariate analysis including known prognostic factors., Results: Among 134 eligible patients, 78 patients (58.2%) received postmastectomy radiation therapy, and 56 patients (41.8%) did not. With a median follow-up time of 91.4 months, the 10-year locoregional recurrence-free survival and overall survival rates were 96.2% and 77.2% with postmastectomy radiation therapy and 86.8% and 87.7% without radiation therapy, respectively (no significant difference). In multivariate analysis, there was a trend towards poorer overall survival among patients who did not have a pathologically complete primary tumour response after neoadjuvant chemotherapy (hazard ratio [HR], 6.65; 95% CI, 0.82-54.12; P=0.076). Postmastectomy radiation therapy had no effect on either locoregional recurrence-free survival (HR, 0.37; 95% CI, 0.09-1.61; P=0.18) or overall survival (HR, 2.06; 95% CI, 0.71-6; P=0.18). There was a trend towards poorer overall survival among patients who did not have pathologically complete in-breast tumour response after neoadjuvant chemotherapy (HR, 6.65; 95% CI, 0.82-54.12; P=0.076)., Conclusions: This retrospective study showed no increase in the risk of distant metastasis, locoregional recurrence or death when postmastectomy radiation therapy was omitted in breast cancer patients with pN0 status after neoadjuvant chemotherapy and mastectomy. Whether the omission of postmastectomy radiation therapy is acceptable for these patients should be addressed prospectively., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To assess the benefit of breast surgery for inflammatory breast cancer., Patients and Methods: This retrospective series was based on 232 patients treated for inflammatory breast cancer. All patients received primary chemotherapy followed by either exclusive radiotherapy (118 patients, 51%) or surgery with or without radiotherapy (114 patients, 49%). The median follow-up was 11 years., Results: The two groups were comparable apart from fewer tumors smaller than 70 mm (43% vs 33%, P=0.003), a higher rate of clinical stage N2 (15% vs 5%, P=0.04) and fewer histopathological grade 3 tumors (46% vs 61%, P<0.05) in the no-surgery group. The addition of surgery was associated with a significant improvement in locoregional disease control (P=0.04) but with no significant difference in overall survival rates or disease-free intervals. Late toxicities were not significantly different between the two treatment groups except for a higher rate of fibrosis in the no-surgery group (P<0.0001), and more lymphedema in the surgery group (P=0.002)., Conclusion: Our data suggest an improvement in locoregional control in patients treated by surgery, in conjunction with chemotherapy and radiotherapy, for inflammatory breast cancer., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To assess the use of trastuzumab concurrently with whole brain radiotherapy (WBRT) for patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer., Methods and Materials: Between April 2001 and April 2007, 31 patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer were referred for WBRT with concurrent trastuzumab. At brain progression, the median age was 55 years (range, 38-73), and all patients had a performance status of 0-2. The patients received trastuzumab 2 mg/kg weekly (n = 17) or 6 mg/kg repeated every 21 days (n = 14). In 26 patients, concurrent WBRT delivered 30 Gy in 10 daily fractions. In 6 patients, other fractionations were chosen because of either poor performance status or patient convenience., Results: After WBRT, radiologic responses were observed in 23 patients (74.2%), including 6 (19.4%) with a complete radiologic response and 17 (54.8%) with a partial radiologic response. Clinical responses were observed in 27 patients (87.1%). The median survival time from the start of WBRT was 18 months (range, 2-65). The median interval to brain progression was 10.5 months (range, 2-27). No Grade 2 or greater acute toxicity was observed., Conclusion: The low toxicity of trastuzumab concurrently with WBRT should probably not justify delays. Although promising, these preliminary data warrant additional validation of trastuzumab as a potential radiosensitizer for WBRT in brain metastases from breast cancer in the setting of a clinical trial., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We report our experience of bevacizumab-based chemotherapy (BBCT) followed by whole-brain radiation therapy (WBRT) for breast cancer (BC) patients (pts) with inoperable brain metastases (BM) or who refused surgery. This is a retrospective study of seven metastatic BC pts treated at the Institut Curie with at least one course of BBCT before WBRT, with a delay of ≤ 12 months between the two treatments. Toxicity was scored according to the common terminology criteria for adverse events (v4. 2010). Median age was 56 years (41-65). Median follow-up was 5.9 months (0.4-24.6). The median dose of bevacizumab was 10 mg/kg. Median number of cycles BBCT was six (5-17). Different chemotherapy regimens were used, the most common combination was paclitaxel-bevacizumab. WBRT was delivered in ten fractions, five fractions/week, for two weeks, to a total of 30 Gy. One pt underwent stereotactic radio surgery (SRS) after WBRT. No pt received BBCT during RT. Most common reported side-effects were nausea (n = 4), headache (n = 3), vomiting (n = 1), and vertigo (n = 3). All pts had mild or moderate grade ≤ 2 neurologic toxicity. There were no radiological signs of necrosis or cerebral ischemia. BBCT before WBRT was not associated with severe brain toxicity. Because of the limited number of pts, the different BBCT regimens, and important delays between treatments, these results must be confirmed prospectively.

Purpose: Radio-induced early skin reactions still remain a clinical challenge. Preliminary results with Hyaluronic acid, one of the most recent topical products used in this indication are proving interesting. To evaluate the efficacy of Hyaluronic acid compared to placebo., Material and Methods: Breast cancer patients with grade 1-2 radio-induced dermatitis during postoperative radiotherapy were eligible. They were randomised to receive either hyaluronic acid (A) or a simple emollient (B). The primary endpoint was the clinical evaluation of the erythema (success versus failure). Secondary endpoints were the evaluation of skin colorimetry, pain, and quality of life., Results: Two-hundred patients were enrolled (A=99, B=101). Ninety-five patients per treatment arm could be evaluated. Failures occurred in 23 patients (24%) in the hyaluronic acid arm, and 32 (34%) in the emollient arm (p=0.15). Seventy-three patients (36.5%) prematurely stopped the treatment without any ensuing difference between the two arms. Body mass index and the size of the epithelitis were both independently associated with the failure of the local treatment. The relative reduction of colorimetric levels was 20% in the hyaluronic acid group, and 13% in the emollient group (p=0.46). Concerning the quality of life assessment, there was a trend towards a lower level of pain in patients receiving hyaluronic acid (p=0.053)., Conclusions: The present study showed no significant difference between hyaluronic acid and simple emollient in the treatment of acute radio-induced dermatitis. There was however a trend towards an improvement in both pain level and skin colorimetry., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

When focusing on heart disease, most available studies split the two different parts of the adjuvant treatment, i.e., systemic therapies and radiation therapy, making it difficult to implement efficient strategies for preventing treatment-induced cardiac toxicity. This paper reviews the current understanding of treatments-induced cardiac toxicity in a global approach. Many factors should be considered when assessing the cardiac hazard. Treatment-related risk factors include heart dose exposure, chemotherapy, targeted agents such as HER2 inhibitors, but also endocrine agents, or anesthetic procedure. Patients' characteristics should also be taken into account. Age, menopausal status, stress, previous history of cardiac disease, genetic profile, and body mass index could all impact on cardiac function after adjuvant therapies. Cardiac toxicity should not be analyzed as the consequence of a specific therapy, but should be considered as the result of additive or supra-additive toxicities. By this way, it will be possible to implement new strategies for preventing treatment-induced cardiac toxicity., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Purpose: Patients with permanent cardiac pacemakers occasionally require radiotherapy. Therapeutic irradiation may cause pacemakers to malfunction due to the effects of ionizing radiation or electromagnetic interference. We studied the breast cancer patients who needed breast and/or chest wall and lymph node irradiation to assess the feasibility and tolerance in this population of patients., Patients and Methods: From November 2008 to December 2009, more than 900 patients received radiotherapy for their breast cancer in our department using megavoltage linear accelerator (X 4-6 MV and electrons). Among them, seven patients were with permanent pacemaker. All patients have been treated to the breast and chest wall and/or lymph nodes. Total dose to breast and/or chest wall was 50 Gy/25 fractions and 46 Gy/23 fractions to lymph nodes. Patients who underwent conserving surgery followed by breast irradiation were boosted when indicated to tumour bed with 16 Gy/8 fractions. All patients were monitored everyday in presence of radiation oncologist to follow the function of their pacemaker. All pacemakers were controlled before and after radiotherapy by the patients' cardiologist., Results: Seven patients were referred in our department for postoperative breast cancer radiotherapy. Among them, only one patient was declined for radiotherapy and underwent mastectomy without radiotherapy. In four cases the pacemaker was repositioned before the beginning of radiotherapy. Six patients, aged between 48 and 84 years underwent irradiation for their breast cancer. Four patients were treated with conserving surgery followed by breast radiotherapy and two with mastectomy followed by chest wall and internal mammary chain, supra- and infra-clavicular lymph node irradiation. The dose to the pacemaker generator was kept below 2 Gy. There was no pacemaker dysfunction observed during the radiotherapy., Conclusion: The multidisciplinary work with position change of the pacemaker before radiotherapy and everyday monitoring permitted the safe treatment of our patients. Updated guidelines are definitely needed with more details about acceptable doses at the different parts of the pacemaker., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To determine whether exclusive radiotherapy could be a therapeutic option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancers (EBC)., Patients and Methods: Between 1985 and 1999, 1477 patients received néoadjuvante chemotherapy for early breast cancer considered to be too large for primary conservative surgery. Of 165 patients with complete clinical response, 65 were treated by breast surgery (with radiotherapy) and 100 by exclusive radiotherapy., Results: The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the exclusive radiotherapy group. There were no significant differences in overall, disease-free and metastasis-free survivals. Five-year and 10-year overall survivals were 91 and 77% in the no surgery group and 82 and 79% in the surgery group, respectively (P = 0.9). However, a non-significant trend towards higher locoregional recurrence rates (LRR) was observed in the no surgery group (31 vs. 17% at 10 years; P = 0.06). In patients with complete responses on mammography and/or ultrasound, LRR were not significantly different (P=0.45, 10-year LRR: 21 in surgery vs. 26% in exclusive radiotherapy). No significant differences were observed in terms of the rate of cutaneous, cardiac or pulmonary toxicities., Conclusion: Surgery is a key component of locoregional treatment for breast cancers that achieved complete clinical response to neoadjuvant chemotherapy., (Copyright © 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: We retrospectively assessed the use of trastuzumab concurrently with whole-brain radiotherapy (WBRT) for brain metastases., Patients and Methods: From April 2001 to April 2007, 31 patients with brain metastases from HER2-positive breast cancer were referred for WBRT with concurrent trastuzumab. In most cases, concurrent WBRT delivered 30 Gy in 10 daily fractions. In six patients, other fractionations were chosen because of either poor performance status or patients’ convenience., Results: At time of brain progression, median age was 55 years (range: 38 to 73 years) and all patients had a performance status of 0 to 2. Median time to brain progression was 10.5 months. Following WBRT, radiological responses were observed in 23 patients (74.2%), including six patients (19.4%) with complete radiological responses and 17 patients (54.8%) with partial radiological response. Clinical responses were observed in 27 patients (87.1%). Median survival from the start of WBRT was 18 months (range: two to 65 months). No grade 2 or more acute toxicity was observed., Conclusion: Our results suggest that trastuzumab concurrently with WBRT may have a potential clinical impact with low toxicity. Although promising, these preliminary data warrant further validation of trastuzumab as radio sensitizer for WBRT in brain metastases from breast cancer in the setting of a clinical trial. Larger prospective studies are needed to confirm these results.

Purpose: To determine whether the exclusive use of radiotherapy (ERT) could be a treatment option after complete clinical response (cCR) to neoadjuvant chemotherapy (NCT) for early breast cancer (EBC)., Methods and Materials: Between 1985 and 1999, 1,477 patients received NCT for EBC considered too large for primary conservative surgery. Of 165 patients with cCR, 65 patients were treated with breast surgery (with radiotherapy) and 100 patients were treated with ERT., Results: The two groups were comparable in terms of baseline characteristics, except for larger initial tumor sizes in the ERT group. There were no significant differences in overall, disease-free and metastasis-free survival rates. Five-year and 10-year overall survival rates were 91% and 77% in the no-surgery group and 82% and 79% in the surgery group, respectively (p = 0.9). However, a nonsignificant trend toward higher locoregional recurrence rates (LRR) was observed in the no-surgery group (31% vs. 17% at 10 years; p = 0.06). In patients with complete responses on mammography and/or ultrasound, LRR were not significantly different (p = 0.45, 10-year LRR: 21% in surgery vs. 26% in ERT). No significant differences were observed in terms of the rate of cutaneous, cardiac, or pulmonary toxicities., Conclusions: Surgery is a key component of locoregional treatment for breast cancers that achieved cCR to NCT., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To assess the benefit of breast surgery for inflammatory breast cancer (IBC)., Methods and Materials: This retrospective series was based on 232 patients treated for IBC. All patients received primary chemotherapy followed by either exclusive radiotherapy (118 patients; 51%) or surgery with or without radiotherapy (114 patients; 49%). The median follow-up was 11 years., Results: The two groups were comparable apart from fewer tumors <70 mm (43% vs. 33%, p = 0.003), a higher rate of clinical stage N2 (15% vs. 5%, p = 0.04), and fewer histopathologic Grade 3 tumors (46% vs. 61%, p <0.05) in the no-surgery group. The addition of surgery was associated with a significant improvement in locoregional disease control (p = 0.04) at 10 years locoregional free interval 78% vs. 59% but with no significant difference in overall survival rates or disease-free intervals. Late toxicities were not significantly different between the two treatment groups except for a higher rate of fibrosis in the no-surgery group (p <0.0001) and more lymphedema in the surgery group (p = 0.002)., Conclusion: Our data suggest an improvement in locoregional control in patients treated by surgery, in conjunction with chemotherapy and radiotherapy, for IBC. Efforts must be made to improve overall survival., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Several authors have underscored a strong relation between the molecular subtypes and the axillary status of breast cancer patients. The aim of our work was to decipher the interaction between this classification and the probability of a positive sentinel node biopsy., Materials and Methods: Our dataset consisted of a total number of 2654 early-stage breast cancer patients. Patients treated at first by conservative breast surgery plus sentinel node biopsies were selected. A multivariate logistic regression model was trained and validated. Interaction covariate between ER and HER2 markers was a forced input of this model. The performance of the multivariate model in the training and the two validation sets was analyzed in terms of discrimination and calibration. Probability of axillary metastasis was detailed for each molecular subtype., Results: The interaction covariate between ER and HER2 status was a stronger predictor (p = 0.0031) of positive sentinel node biopsy than the ER status by itself (p = 0.016). A multivariate model to determine the probability of sentinel node positivity was defined with the following variables; tumour size, lympho-vascular invasion, molecular subtypes and age at diagnosis. This model showed similar results in terms of discrimination (AUC = 0.72/0.73/0.72) and calibration (HL p = 0.28/0.05/0.11) in the training and validation sets. The interaction between molecular subtypes, tumour size and sentinel nodes status was approximated., Discussion: We showed that biologically-driven analyses are able to build new models with higher performance in terms of breast cancer axillary status prediction. The molecular subtype classification strongly interacts with the axillary and distant metastasis process.

Background: To evaluate the skin and heart toxicity of a concurrent adjuvant trastuzumab-radiotherapy for breast cancer (BC), especially in the case of internal mammary chain (IMC) irradiation., Material and Methods: Prospective study of 106 patients treated between 06/2003 and 03/2007 by concurrent trastuzumab-radiotherapy for non-metastatic BC. Left ventricular ejection fractions (LVEF) was assessed at baseline, before and after radiotherapy and then every 4-6 months. All toxicities were evaluated using CTCAEV3., Results: Median age was 52 years (25-76). Chemotherapy with anthracycline was administered in 92% of patients. All patients received trastuzumab every three weeks (8 mg/kg followed by 6 mg/kg) for a median duration of 12 months (3-40). The IMC was irradiated in 83% of patients. There were: 87 grade 1, 14 grade 2 and 2 grade 3 skin reactions. There were 13 oesophagitis: 9 grade 1; 3 grade 2, and 1 grade 3. Out of 101 patients with assessments after 6 months, late telangiectasia grade 1 occurred in 5 patients, local pain grade 1 in 19 patients and grade 2 in 3 patients, fibrosis grade 1 in 16 patients. A reversible grade ≥2 left ventricular systolic dysfunction occurred in 6 patients., Conclusion: In this prospective study of breast cancer patients treated with trastuzumab-radiotherapy with, in most cases, anthracycline-based chemotherapy and IMC irradiation, both the rate of abnormal LVEF after concurrent trastuzumab-radiotherapy and the skin toxicity were deemed acceptable. Further follow-up is needed., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the accuracy of a boost technique., Methods and Materials: Twenty-two patients underwent tumorectomy with placement of two or more clips in the surgical cavity before breast remodeling. Preoperative and postoperative computed tomography scans, with match-point registration, were performed on all patients. The relationship between the location of the gross tumor volume (GTV), defined on the preoperative scan, and clip clinical target volume (CTV) (clips with a 5-mm margin on the postoperative scan) was then studied, by use of commercial volume analysis software., Results: Of the patients, 4 had two clips, 2 had three clips, 8 had four clips, and 8 had five clips. The median GTV was 1.06 mL (range, 0.2-5.3 mL); clip CTV ranged from 2.4 to 21.5 mL. Volumetric analysis showed that in 7 cases (32%), there was no intersection between the GTV and the clip CTV, with the following distribution: 4 patients with two clips, 1 patient with three clips, 1 patient with four clips, and 1 patient with five clips. The common contoured volume was defined as the percent ratio between the intersection of the GTV and clip CTV and the GTV. It was found to be significantly increased if three or more clips were used vs. only two clips (common contoured volume, 35.45% vs. 0.73%; p = 0.028). Finally, the GTV and clip CTV volume relationship can be presented as follows: 12.5% to 33% overlap in 8 patients (36.4%), 50% to 75% in 5 patients (22.7%), and greater than 90% in 2 patients (9%)., Conclusions: The use of three or more clips during tumorectomy increases the accuracy of tumor bed delineation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD(+). The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD(+) at the enzyme's activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated.

Purpose: To assess the efficacy of exclusive hypo-fractionated radiotherapy (HFRT) without previous breast-conserving surgery (BCS) in elderly women., Materials and Methods: From 1995 to 1999, we have treated with breast-conserving treatment 396 patients older than 70 years with early-stage breast cancer (T1,T2 tumours) at the Institut Curie, Paris, France. Seventy-nine consecutive elderly non-metastatic patients treated for early breast cancer have been treated with HFRT. Of them, 50 underwent BCS followed by HFRT of 32.5 Gy/5 fractions/5 weeks, and 29 patients (presented with different co-morbidities, inoperable or patients' refusal, and/or transportation problems) received the same HFRT schedule followed by a 13 Gy boost (two fractions of 6.5 Gy) as exclusive radiotherapy treatment. This population of 29 patients has been studied. In case of hormonal positive status, hormonal therapy was also proposed to the patients., Results: There was a median follow-up of 93 months (9-140 months). At 7-year follow-up, the cause-specific survival was 96.4% (confidence interval (CI) 95: 89.8.6-100%), the metastasis-free survival rate was 92.4% (CI 95: 82.8-100%) and the loco-regional control rate was 95.8% (CI 95: 88.2-100%)., Conclusions: This long-term follow-up retrospective study demonstrated acceptable local control and good outcome in elderly patients treated by exclusive HFRT for early breast cancer. However, large-scale prospective randomised trials are needed to confirm these results., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Breast cancer is a rare disease in young women. Its incidence has remained remarkably constant over the last decades, contrary to what has happened in older patients. Age is a major prognostic factor for local control after breast-conserving treatments, which does not seem to be entirely explained by the poor prognostic features that are more commonly associated with breast cancers in young women. A better knowledge of the prognostic factors for local control, and, whenever possible, those pertaining specifically to the young age group, is key, not only to better select the patients who would benefit the most from a breast-conserving approach but also to enhance the local control when this option has been elected. These prognostic factors can be related to the patient, the tumor and the treatment they receive. Finally, we will present a perspective of what the future could hold, both in terms of the selection of the patients and of a more customized therapeutic approach.

The aim of this study was to present the simplified rules of delineation of lymph node (LN) volumes in breast irradiation. Practical rules of delineation of LN areas were developed in the Department of Radiation Oncology of the Institut Curie. These practical guidelines of delineation were based on different specific publications in the field of breast and LN anatomy. The principal characteristic of these rules is their clearly established relationship with anatomical structure, which is easy to find on CT slices. The simplified rules of delineation have been published in pocket format as the illustrated atlas "Help of delineation for breast cancer treatment". In this small pocket guide, delineation using the practical rules is illustrated, with examples from anatomical CT slices. It is shown that there is an improvement in delineation after the use of these simplified rules and the guide. In conclusion, this small guide is useful for improving everyday practice and decreasing the differences in target delineation for breast irradiation between institutions and observers.

Background and Purpose: To evaluate the dosimetry of helical tomotherapy (HT) and three-dimensional conformal radiotherapy (3D-CRT) in breast cancer patients undergoing whole breast radiation with simultaneous integrated boost (SIB) of the tumor bed., Material and Methods: Thirteen patients with breast cancer treated by lumpectomy and requiring whole breast radiotherapy with tumor bed boost were planned using both HT and 3D-CRT using the field-in-field technique. The whole breast and tumor bed were prescribed 50.68 Gy and 64.4 Gy, respectively, in 28 fractions. Dosimetries for both techniques were compared., Results: Coverage of the whole breast was adequate with both techniques (V(95%)=96.22% vs. 96.25%, with HT and 3D-CRT, respectively; p=0.64). Adequate tumor bed coverage was also achieved, although it was significantly lower with HT (V(95%)=97.18% vs. 99.72%; p<0.001). Overdose of the breast volume outside the tumor bed was significantly lower with HT (V(54.23 Gy)=12.47% vs. 30.83%; p<0.001). Ipsilateral lung V(20 Gy) (6.34% vs. 10.17%; p<0.001), V(5 Gy) (16.54% vs. 18.53%; p<0.05) and mean dose (4.05 Gy vs. 6.36 Gy; p<0.001) were significantly lower with HT. In patients with left-sided tumors, heart V(30 Gy) (0.03% vs. 1.14%; p<0.05) and mean dose (1.35 Gy vs. 2.22 Gy; p<0.01) were significantly lower with HT, but not V(5 Gy). Contralateral breast V(5 Gy) (0.27% vs. 0.00%; p<0.01) and maximum dose were significantly increased with HT., Conclusions: In breast cancer treated with SIB, both HT and 3D-CRT provided adequate target volume coverage and low heart doses. Tumor bed coverage was slightly lower with HT, but HT avoided unnecessary breast overdosage while improving ipsilateral lung dosimetry., ((c) 2010 Elsevier Ireland Ltd. All rights reserved.)

We present a computational method, TuMult, for reconstructing the sequence of copy number changes driving carcinogenesis, based on the analysis of several tumor samples from the same patient. We demonstrate the reliability of the method with simulated data, and describe applications to three different cancers, showing that TuMult is a valuable tool for the establishment of clonal relationships between tumor samples and the identification of chromosome aberrations occurring at crucial steps in cancer progression.

Purpose: Following breast-conserving surgery for DCIS, reexcision before radiotherapy is recommended when margins are close or involved. We investigated whether an additional radiation dose could replace reexcision., Methods: We selected 208 women with DCIS of the breast treated with breast-conserving surgery between 1992 and 2002 who had either close margins (< 2 mm) (89 pts) or focally (< 1 mm) or minimally (1-15 mm) involved margins (119 pts). Sixty-one patients (29%) underwent reexcision before irradiation and 147 patients (71%) received breast irradiation with boost, without reexcision., Results: Median follow-up was 89 months. Median age was 53 years with 7 patients less than 41. Involved margins were less frequent in the non reexcision group than in the reexcised group (50% vs. 74%, p = 0.0019). All other clinical and histological features were comparable. Median whole-breast radiation dose was 50 Gy. Median total doses to the tumour bed were 67 Gy (range, 45-77) and 60 Gy (range, 46-74), respectively (p < 0.0001). Of the 61 reexcised patients, 56% had residual DCIS and 6% had invasive cancer. Six underwent a mastectomy for persistent margin involvement. Seven-year locoregional failure rates were 9.3% without, and 9.6% with reexcision (ns). No differences were observed when adjusting for margin status., Conclusion: In carefully selected patients with close (< 2 mm) or focally/minimally involved margins, reexcision may be avoided and satisfactory local control achieved by increasing the radiation dose to the tumour bed to at least 66 Gy. These results only apply to patients older than 40 and would need confirmation in independent series.

Purpose: To evaluate the long-term cause-specific survival (CSS), locoregional recurrence-free survival (LRFS), and metastases-free survival (MFS) in elderly breast cancer patients receiving adjuvant normofractionated (NF) or hypofractionated (HF) radiotherapy (RT)., Methods and Materials: Between 1995 and 1999, 367 women aged >or=70 years with nonmetastatic Stage T1 or T2 tumors were treated by breast-conserving surgery and adjuvant RT at the Institut Curie. They underwent wide tumor excision with or without lymph node dissection followed by RT. They received either a NF-RT schedule, which delivered a total dose of 50 Gy (25 fractions, 5 fractions weekly) to the whole breast, followed by a boost to the tumor bed when indicated, or a HF-RT schedule, which delivered a total dose of 32.5 Gy (five fractions of 6.5 Gy, once weekly) with no subsequent boost. The HF-RT schedule was indicated for the more elderly patients., Results: A total of 317 patients were in the NF-RT group, with 50 in the HF-RT group. The median follow-up was 93 months (range, 9-140). The 5- and 7-year CSS, LRFS, and MFS rates were similar in both groups. The 5-year NF-RT and HF-RT rate was 96% and 95% for CSS, 95% and 94% for LRFS, and 94% and 95% for MFS, respectively. The 7-year NF-RT and HF-RT rate was 93% and 87% for CSS, 93% and 91% for LRFS, and 92% and 93% for MFS, respectively., Conclusion: According to the findings from this retrospective study, the HF-RT schedule is an acceptable alternative to NF-RT for elderly patients. However, large-scale prospective randomized trials are needed to confirm these results.

Purpose: Given the scarcity of malignant phyllode tumours of the breast and the absence of consensus regarding their management justify the need for institutional retrospective evaluations of clinical practices., Patients and Methods: Retrospective study with central pathology review of the 25 consecutive patients treated at the Institut Curie (Paris, France) between 1969 and 2006 for non metastatic malignant phyllodes tumors of the breast. The median follow-up was 65 months (7-257 months)., Results: Median age at diagnosis was 52 years (20-64 years). Breast surgery was conservative in five patients (20%). Surgical margins were wide (> 10mm), narrow, involved or unknown in respectively 17 (68%), three (12%), three (12%) and two (8%) patients. Median tumour size was 65 mm (12-250 mm). Adjuvant radiotherapy was delivered in seven (28%) patients (two patients, post-tumorectomy; five patients, post-mastectomy) and 13 patients (52%) received anthracycline-based adjuvant chemotherapy. Five-year overall survival rate was 91% (95% CI, 80-100%). Five patients (20%) developed distant metastases (one after chemotherapy) and three (12%) locoregional relapse (one after tumorectomy and unknown margin without radiotherapy, two after mastectomy and involved margins with radiotherapy)., Conclusion: Wide breast surgery (that can be conservative in selected patients) is the mainstay of the treatment of non metastatic malignant phyllodes tumors of the breast. To better determine the respective roles of adjuvant systemic treatment and radiotherapy, further clinical studies and the search for new prognostic and predictive factors remain necessary.

The purpose of the study was to evaluate the individual variability of anatomical and radiological delineation for breast cancer radiotherapy (RT) in preparation for new techniques and to propose practical solutions to improve delineation in everyday practice. In the first phase, a patient with stage T3N3M0 breast cancer and complete response after neoadjuvant chemotherapy was assessed by CT scan in the treatment position before RT. 11 radiation oncologists (5 breast cancer specialists and 6 residents) independently delineated the breast and lymph node (LN) regions before definition of target volumes. Organs at risk (heart, lung, thyroid and brachial plexus) were also delineated. All regions (breast, axilla, supraclavicular LN, infraclavicular LN and internal mammary chain) were delineated and compared in terms of volume. Comparative analysis was performed with Aquilab software. Differences in the clinical and radiological assessment were observed between the various radiation oncologists. Simplified rules of delineation were developed in the department. Using these rules, the second patient's CT was delineated by the same physicians and better results were observed. Simplified rules of delineation were developed. In conclusion, major differences in anatomical and radiological delineation for breast cancer RT were observed among the physicians. This study led to the development of written delineation protocols. The study is ongoing with evaluation of the dosimetric impact and definition of different target volumes.

Purpose: Prospective monocentric study of the skin and heart tolerance of a concurrent administration of trastuzumab (T) and radiotherapy (RT) for breast cancer (BC)., Patients and Methods: From February 2004 to January 2007, 57 patients (pts), were treated by a concomitant administration of T and normo-fractionated RT of either whole breast (+/-boost) or chest. The perfusion of T started either with or after chemotherapy (CT). Left ventricular ejection fractions (LEVF), assessed at baseline, before start of RT, after completion of RT and then every four to six months with either echocardiography or multiple gated acquisition scanning, were considered normal if greater or equal to 50% or stated so by the cardiologist. Inclusion criteria included a normal LVEF at baseline. Skin toxicity was evaluated using CTCAEV3. Median age was 49 years (25-80). CT with anthracycline was administered in 84% (total dose 300 mg/m(2)). All but one patient (treated weekly) received T every three weeks (8 mg/kg followed by 6 mg/kg) for a median duration of 12 months (6-33). The internal mammary chain was irradiated in 88% of cases. Median follow-up for LVEF assessment was 13 months (2-33)., Results: LVEF at pre-RT were normal in 54 pts (100%, three Missing Data [MD]), at post-RT in 56 pts (98%, no MD) and at last follow-up in 53 pts (95%, one MD). There were two grade 0, 44 grade I and 11 grade II skin reactions. For the 27 patients with a skin toxicity assessment after six months, late skin toxicity was grade 0 in 22 pts, grade 1 in four, grade 2 in one., Conclusion: Provided that the technique is adapted, the acute skin and heart toxicities of the concomitant administration of T-RT appeared satisfactory. More patients and longer follow-up are still mandatory.

Purpose: To assist in the determination of breast and nodal volumes in the setting of radiotherapy for breast cancer and establish segmentation guidelines. Materials and methods. Contrast metarial enhanced CT examinations were obtained in the treatment position in 25 patients to clearly define the target volumes. The clinical target volume (CTV) including the breast, internal mammary nodes, supraclavicular and subclavicular regions and axxilary region were segmented along with the brachial plexus and interpectoral nodes. The following critical organs were also segmented: heart, lungs, contralateral breast, thyroid, esophagus and humeral head., Results: A correlation between clinical and imaging findings and meeting between radiation oncologists and breast specialists resulted in a better definition of irradiation volumes for breast and nodes with establishement of segmentation guidelines and creation of an anatomical atlas., Conclusion: A practical approach, based on anatomical criteria, is proposed to assist in the segmentation of breast and node volumes in the setting of breast cancer treatment along with a definition of irradiation volumes.