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Purpose: This study evaluates the benefit of a virtual bolus method for volumetric modulated arc therapy (VMAT) plan optimization to compensate breast modifications that may occur during breast treatment., Methods: Ten files were replanned with VMAT giving 50 Gy to the breast and 47 Gy to the nodes within 25 fractions. The planning process used a virtual bolus for the first optimization, then the monitors units were reoptimized without bolus, after fixing the segments shapes. Structures and treatment planning were exported on a second scanner (CT) performed during treatment as a consequence to modifications in patient's anatomy. The comparative end-point was clinical target volume's coverage. The first analysis compared the VMAT plans made using the virtual bolus method (VB-VMAT) to the plans without using it (NoVB-VMAT) on the first simulation CT. Then, the same analysis was performed on the second CT. Finally, the level of degradation of target volume coverage between the two CT using VB-VMAT was compared to results using a standard technique of forward-planned multisegment technique (Tan-IMRT)., Results: Using a virtual bolus for VMAT does not degrade dosimetric results on the first CT. No significant result in favor of the NoVB-VMAT plans was noted. The VB-VMAT method led to significant better dose distribution on a second CT with modified anatomies compared to NoVB-VMAT. The clinical target volume's coverage by 95% (V95%) of the prescribed dose was 98.9% [96.1-99.6] on the second CT for VB-VMAT compared to 92.6% [85.2-97.7] for NoVB-VMAT (P = 0.0002). The degradation of the target volume coverage for VB-VMAT is not worse than for Tan-IMRT: the median differential of V95% between the two CT was 0.9% for VMAT and 0.7% for Tan-IMRT (P = 1)., Conclusion: This study confirms the safety and benefit of using a virtual bolus during the VMAT planning process to compensate potential breast shape modifications., (© 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Objectives: To describe the French routine use of G-CSF in patients treated for breast cancer as per the EORTC recommendations., Patients and Methods: A prospective multicenter observational study conducted between February 2008 and September 2009 in 869 breast cancer patients treated by chemotherapy (CT) and for whom G-CSF treatment will be delivered in primary (PP) or secondary prophylaxis., Results: The mean age was 55 years. A total of 80.3% of CT was in neoadjuvant/adjuvant setting (NAS). PP was delivered in 78.9% of the NAS patients and 67.5% in metastatic situation. Of the 702 evaluable patients, incidences of severe (SN) and febrile neutropenias (FN) in patients who received PP were 9.3% and 4.2%, respectively. In patients who did not received G-CSF at first cycle, SN and FN were 12.4% and 7.3%, respectively. The use of PP was mainly driven by the type of CT for patients treated in the NAS and by patient or disease related risk factors in the locally advanced/metastatic setting., Conclusion: This study has shown that the use of G-CSF was in accordance with the 2010 updates of the EORTC recommendations. However, G-CSF appears more widely used in the routine practice., (Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

We compared two intensity-modulated radiotherapy techniques for left-sided breast treatment, involving lymph node irradiation including the internal mammary chain. Inverse planned arc-therapy (VMAT) was compared with a forward-planned multi-segment technique with a mono-isocenter (MONOISO). Ten files were planned per technique, delivering a 50-Gy dose to the breast and 46.95 Gy to nodes, within 25 fractions. Comparative endpoints were planning target volume (PTV) coverage, dose to surrounding structures, and treatment delivery time. PTV coverage, homogeneity and conformality were better for two arc VMAT plans; V95%(PTV-T) was 96% for VMAT vs 89.2% for MONOISO. Homogeneity index (HI)(PTV-T) was 0.1 and HI(PTV-N) was 0.1 for VMAT vs 0.6 and 0.5 for MONOISO. Treatment delivery time was reduced by a factor of two using VMAT relative to MONOISO (84 s vs 180 s). High doses to organs at risk were reduced (V30(left lung) = 14% using VMAT vs 24.4% with MONOISO; dose to 2% of the volume (D2%)(heart) = 26.1 Gy vs 32 Gy), especially to the left coronary artery (LCA) (D2%(LCA) = 34.4 Gy vs 40.3 Gy). However, VMAT delivered low doses to a larger volume, including contralateral organs (mean dose [Dmean](right lung) = 4 Gy and Dmean(right breast) = 3.2 Gy). These were better protected using MONOISO plans (Dmean(right lung) = 0.8 Gy and Dmean(right breast) = 0.4 Gy). VMAT improved PTV coverage and dose homogeneity, but clinical benefits remain unclear. Decreased dose exposure to the LCA may be clinically relevant. VMAT could be used for complex treatments that are difficult with conventional techniques. Patient age should be considered because of uncertainties concerning secondary malignancies., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Study of the prognostic impact of multidrug resistance gene expression in the management of breast cancer in the context of adjuvant therapy. This study involved 171 patients treated by surgery, adjuvant chemotherapy+/-radiotherapy+/-hormonal therapy (mean follow-up: 55 months). We studied the expression of multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein (MRP1), and glutathione-S-transferase P1 (GSTP1) using a standardised, semiquantitative rt-PCR method performed on frozen samples of breast cancer tissue. Patients were classified as presenting low or high levels of expression of these three genes. rt-PCR values were correlated with T stage, N stage, Scarff-Bloom-Richardson (SBR) grade, age and hormonal status. The impact of gene expression levels on 5-year disease-free survival (DFS) and overall survival (OS) was studied by univariate and multivariate Cox analysis. No statistically significant correlation was demonstrated between MDR1, MRP1 and GSTP1 expressions. On univariate analysis, DFS was significantly decreased in a context of low GSTP1 expression (P = 0.0005) and high SBR grade (P = 0.003), size > or = 5 cm (P = 0.038), high T stage (P = 0.013), presence of intravascular embolus (P = 0.034), and >3 N+ (P = 0.05). On multivariate analysis, GSTP1 expression and the presence of ER remained independent prognostic factors for DFS. GSTP1 expression did not affect OS. The levels of MDR1 and MRP1 expression had no significant influence on DFS or OS. GSTP1 expression can be considered to be an independent prognostic factor for DFS in patients receiving adjuvant chemotherapy for breast cancer.

Purpose: To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer., Patients and Methods: A series of 271 patients, treated by surgery, radiotherapy+/-systemic therapy was analysed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, N=37), DIP and medium or high SPF (DMH, N=76), ANEUP and low SPF (AL, N=24), ANEUP and medium or high SPF (AMH, N=68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model)., Results: On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N- patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N- stage I and II breast cancer.

Purpose: To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer., Patients and Methods: A series of 271 patients, treated by surgery, radiotherapy +/- systemic therapy was analyzed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, n=37), DIP and medium or high SPF (DMH, n=76), ANEUP and low SPF (AL, n=24), ANEUP and medium or high SPF (AMH, n=68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model)., Results: On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N- patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N- stage I and II breast cancer.

Purpose: To evaluate our updated data concerning survival and locoregional control in a prospective study of locally advanced noninflammatory breast cancer (LABC) after primary chemotherapy (CT) followed by external preoperative irradiation (RT)., Methods and Materials: Between 1982 and 1998, 120 patients (75 Stage IIIA, 41 Stage IIIB, and 4 Stage IIIC according to AJCC staging system 2002) were treated by four courses of induction CT with anthracycline-containing combinations followed by preoperative RT (45 Gy to the breast and nodal areas) and a fifth course of CT. Three different locoregional approaches were proposed depending on tumor characteristics and tumor response. After completion of local therapy, all patients received a sixth course of CT and a maintenance adjuvant CT regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months., Results: Mastectomy and axillary dissection were performed in 49 patients (with residual tumor larger than 3 cm in diameter or located behind the nipple or with bifocal tumor), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumor bed; 32 had residual mass < or =3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site). Ten-year actuarial local failure rate was 13% after RT alone, 23% after wide excision and RT, and 4% after mastectomy (p = 0.1). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumor size (<6 cm vs. > or =6 cm in diameter, p = 0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (Stage IIIA-B vs. IIIC, p = 0.0003), N-stage (N0 vs. N1-2a, and 3c, p = 0.017), initial tumor size (<6 cm vs. > or =6 cm in diameter, p = 0.008), and tumor response after induction CT and preoperative RT (clinically complete response + partial response vs. nonresponder, p = 0.0015). In the nonconservative breast treatment group, of the 32 patients with no change in clinical tumor size after induction CT, the 10-year metastatic disease-free survival rate was 59% with only one local relapse. Arm lymphedema was noted in 17% (14 of 81) after axillary dissection and in 2.5% (1 of 39) without axillary dissection. Cosmetic results were satisfactory in 70% of patients treated by RT alone and in 51.5% of patients after wide excision and RT., Conclusion: Despite the poor prognosis of patients with LABC resistant to primary anthracycline-based regimen, aggressive locoregional management using preoperative RT and mastectomy with axillary dissection offers a possibility of long-term survival with low local failure rate for patients without extensive nodal disease. On the other hand, the rate of local failure seems to be high in patients with clinical partial tumor response after induction CT and breast-conserving treatment combining preoperative RT and large wide excision.

Purpose: To evaluate our updated data concerning survival and locoregional control in a study of locally advanced non inflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation., Patients and Methods: Between 1982 and 1998, 120 patients (75 stage IIIA, 41 stage IIIB, and 4 stage IIIC according to AJCC staging system 2002) were consecutively treated by four courses of induction chemotherapy with anthracycline-containing combinations followed by preoperative irradiation (45 Gy to the breast and nodal areas) and a fifth course of chemotherapy. Three different locoregional approaches were proposed, depending on tumour characteristics and tumour response. After completion of local therapy, all patients received a sixth course of chemotherapy and a maintenance adjuvant chemotherapy regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months., Results: Mastectomy and axillary dissection were performed in 49 patients (with residual tumour larger than 3 cm in diameter or located behind the nipple or with bifocal tumour), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumour bed; 32 had residual mass or=6 cm in diameter, p =0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (stage IIIA-B vs. IIIC, p =0.0003), N-stage (N0 vs. N1-2a, and 3c, p =0.017), initial tumour size (<6 vs. >or=6 cm in diameter, p =0.008), and tumour response after induction chemotherapy and preoperative irradiation (clinically complete response + partial response vs. non-response, p =0.0015). In the non conservative breast treatment group, of the 32 patients with no change in clinical tumour size after induction chemotherapy, the 10-year metastatic disease-free survival rate was 59% with only one local relapse. Arm lymphedema was noted in 17% (14 of 81) following axillary dissection and in 2.5% (1 of 39) without axillary dissection. Cosmetic results were satisfactory in 70% of patients treated by irradiation alone and in 51.5% of patients after wide excision and irradiation., Conclusion: Despite the poor prognosis of patients with locally advanced non inflammatory breast cancer resistant to primary anthracycline-based regimen, aggressive locoregional management using preoperative irradiation and mastectomy with axillary dissection offers a possibility of long term survival with low local failure rate for patients without extensive nodal disease. On the other hand, the rate of local failure seems to be high in patients with clinical partial tumour response following induction chemotherapy and breast-conserving treatment combining preoperative irradiation and large wide excision.

Purpose: - To identify predicting factors of local control and survival after isolate local failure by statistical analysis of the data after breast-conserving treatment for early breast cancer., Methods and Patients: - In time of local failure, mean age was 54.7 years old, mean tumor size was 19.3 mm and recurrence was more often infiltrating ductal carcinoma (88%). Local recurrence was unifocal in 44 cases and localised outside of the site of the primary tumorectomy in 35 cases. Local failure treatment was a radical mastectomy or parietectomy (53 patients). Hormonotherapy was delivered in 36 patients and chemotherapy was delivered in 26 patients. Mean follow-up was 62 months., Results: - Fifteen patients developed second local recurrence in a mean time of 36 months. Five years local control rate was 68% after the first local failure. Surgery treatment (non-conservative surgery vs. conservative surgery) was the only factor which influenced local control. Six patients developed homolateral axillary and/or supraclavicular node recurrence. Twelve patients underwent metastasis in a mean time of 36 months after the first local recurrence. Five years metastasis free survival rate was 80%. Peritumoral vascular invasion in time of the first local failure increased metastasis risk and node recurrence. Second local failure did not alter metastasis free survival., Conclusion: - Peritumoral vascular invasion in time of the first local failure decreased node and metastasis free survival. Surgery should be radical, but the place of chemotherapy and hormonotherapy was not definite.