Background and purpose: To investigate intraoperative electron radiation therapy (IOERT) as a tumor bed boost during breast conserving surgery (BCS) followed by hypofractionated whole breast ...irradiation (HWBI) on age-correlated in-breast recurrence (IBR) rates in patients with low- to high-risk invasive breast cancer. Material and methods: BCS and IOERT (11.1 Gy) preceded a HWBI (40.5 Gy) in 15 fractions. Five-year IBR-rates were compared by a sequential ratio test (SQRT) with best evidences in three age groups (35−40 y and 41−50 y: 3.6%, >50 y: 2%) in a prospective single arm design. Null hypothesis (H0) was defined to undershoot these benchmarks for proof of superiority. Results: Of 1445 enrolled patients, 326 met exclusion criteria, leaving 1119 as eligible for analysis. After a median follow-up of 50 months (range 0.7−104), we detected two local recurrences, both in the age group >50 y. With no observed IBR, superiority was demonstrated for the patient groups 41−50 and >50 y, respectively. For the youngest group (35−40 y), no appropriate statistical evaluation was yet possible due to insufficient recruitment. Conclusions: In terms of five-year IBR-rates, Boost-IOERT followed by HWBI has been demonstrated to be superior in patients older than 50 and in the age group 41−50 when compared to best published evidence until 2010.
A long-term analysis by the Early Breast Cancer Trialist Group (EBCTG) revealed a strong correlation between local control and cancer-specific mortality. MicroRNAs (miRs), short (20-25 nucleotides) ...non-coding RNAs, have been described as prognosticators and predictors for breast cancer in recent years. The aim of the current study was to identify miRs that can predict local control after breast conserving therapy (BCT) in early stage breast cancer.
Clinical data of 46 early stage breast cancer patients with local relapse after BCT were selected from the institutional database. These patients were matched to 101 control patients showing identical clinical features but without local relapse. The study was conducted in two steps. (1) In the pilot study, 32 patients (16 relapses versus 16 controls) were screened for the most de-regulated microRNAs (= candidate microRNAs) in a panel of 1250 miRs by microarray technology. Eight miRs were found to be significantly de-regulated. (2) In the validation study, the candidate microRNAs were analyzed in an independent cohort of 115 patients (30 relapses versus 85 controls) with reverse transcription quantitative polymerase chain reaction (RT-qPCR). From these eight candidates, hsa-miR-375 could be validated. Its median fold change was 2.28 (Mann-Whitney U test, corrected p value = 0.008). In the log-rank analysis, high expression levels of hsa-miR-375 correlated with a significantly higher risk of local relapse (p = 0.003). In a multivariate analysis (forward stepwise regression) including established predictors and prognosticators, hsa-miR-375 was the only variable that was able to distinguish the statistical significance between relapse and control groups (raw p value = 0.000195 HR = 0.76, 95 % CI 0.66-0.88; corrected p value = 0.005).
Hsa-miR-375 predicts local control in patient with early stage breast cancer, especially in estrogen receptor α (ER-α)-positive patients. It can therefore serve as an additional molecular marker for treatment choice independently from known predictors and prognosticators. Validation in larger prospective studies is warranted.
In order to characterize the various subtypes of breast cancer more precisely and improve patients selection for breast conserving therapy (BCT), molecular profiling has gained importance over the ...past two decades. MicroRNAs, which are small non-coding RNAs, can potentially regulate numerous downstream target molecules and thereby interfere in carcinogenesis and treatment response via multiple pathways. The aim of the current two-phase study was to investigate whether hsa-miR-375-signaling through RASD1 could predict local control (LC) in early breast cancer.
The patient and treatment characteristics of 81 individuals were similarly distributed between relapse (
= 27) and control groups (
= 54). In the pilot phase, the primary tumors of 28 patients were analyzed with microarray technology. Of the more than 70,000 genes on the chip, 104 potential hsa-miR-375 target molecules were found to have a lower expression level in relapse patients compared to controls (
-value < 0.2). For RASD1, a hsa-miR-375 binding site was predicted by an in silico search in five mRNA-miRNA databases and mechanistically proven in previous pre-clinical studies. Its expression levels were markedly lower in relapse patients than in controls (
-value of 0.058). In a second phase, this finding could be validated in an independent set of 53 patients using ddPCR. Patients with enhanced levels of hsa-miR-375 compared to RASD1 had a higher probability of local relapse than those with the inverse expression pattern of the two markers (log-rank test,
-value = 0.069).
This two-phase study demonstrates that hsa-miR-375/RASD1 signaling is able to predict local control in early breast cancer patients, which-to our knowledge-is the first clinical report on a miR combined with one of its downstream target proteins predicting LC in breast cancer.
Multicentric breast cancer has been considered to be a contraindication for sentinel node (SN) biopsy (SNB). In this prospective multi-institutional trial, SNB-feasibility and accuracy was evaluated ...in 142 patients with multicentric cancer from the Austrian Sentinel Node Study Group (ASNSG) and compared with data from 3,216 patients with unicentric cancer.
Between 1996 and 2004, 3,730 patients underwent SNB at 15 ASNSG-affiliated hospitals. Patient data were entered in a multicenter database. One hundred forty-two patients presented with multicentric invasive breast cancer and underwent SNB.
Intraoperatively, a mean number of 1.67 SNs were excised (identification-rate, 91.5%). The incidence of SN metastases was 60.8% (79 of 130). This was confirmed by axillary lymph node dissection (ALND) in 125 patients. Of patients with positive SNs, 60.8% (48 of 79) showed involvement of nonsentinel nodes (NSNs), as did three patients with negative SNs (false-negative rate, 4.0). Sensitivity, negative predictive value, and overall accuracy were 96.0%, 93.3%, and 97.3%, respectively. Ninety-one percent of the patients underwent mastectomy, and 9% were treated with breast conserving surgery. None of the patients have shown axillary recurrence so far (mean follow-up, 28.8 months). Compared with 3,216 patients with unicentric cancer, there was a significantly higher rate of SN metastases as well as in NSNs, whereas there was no difference in detection and false-negative rates.
Multicentric breast cancer is a new indication for SNB without routine ALND in controlled trials. Given adequate quality control and an interdisciplinary teamwork of surgical, nuclear medicine, and pathology units, SNB is both feasible and accurate in this disease entity.
Boost IORT in Breast Cancer: Body of Evidence Sedlmayer, Felix; Reitsamer, Roland; Fussl, Christoph ...
International Journal of Breast Cancer,
01/2014, Letnik:
2014, Številka:
2014
Journal Article
Recenzirano
Odprti dostop
The term IORT (intraoperative radiotherapy) is currently used for various techniques that show decisive differences in dose delivery. The largest evidence for boost IORT preceding whole breast ...irradiation (WBI) originates from intraoperative electron treatments with single doses around 10 Gy, providing outstandingly low local recurrence rates in any risk constellation also at long term analyses. Compared to other boost methods, an intraoperative treatment has evident advantages as follows. Precision. Direct visualisation of the tumour bed during surgery guarantees an accurate dose delivery. This fact has additionally gained importance in times of primary reconstruction techniques after lumpectomy to optimise cosmetic outcome. IORT is performed before breast tissue is mobilised for plastic purposes. Cosmesis. As a consequence of direct tissue exposure without distension by hematoma/seroma, IORT allows for small treatment volumes and complete skin sparing, both having a positive effect on late tissue tolerance and, hence, cosmetic appearance. Patient Comfort. Boost IORT marginally prolongs the surgical procedure, while significantly shortening postoperative radiotherapy. Its combination with a 3-week hypofractionated external beam radiotherapy to the whole breast (WBI) is presently tested in the HIOB trial (hypofractionated WBI preceded by IORT electron boost), a prospective multicenter trial of the International Society of Intraoperative Radiotherapy (ISIORT).
Prepectoral implant placement is an innovative option for breast reconstruction, due to multiple advantages over subpectoral implant placement. The adoption of various ADMs and meshes supports the ...utilization of the prepectoral technique.
200 breasts were reconstructed with prepectoral implant placement after nipple-sparing mastectomy in a one-stage direct-to-implant procedure. The implants were completely covered and fixed with porcine ADMs (Strattice™ or Artia™), or with synthetic meshes (TIGR®). The pectoralis major muscle was not detached at all and kept intact entirely.
Minor complications included minimal nipple necrosis without further intervention and complete healing in 14 breasts (7.0%). Major complications comprised implant loss due to skin necrosis and wound infection in 7 breasts (3.5%), and hematoma with revision surgery in 8 breasts (4.0%). At a mean follow-up of 36 months cosmetic results were excellent and good in 180 breasts (90.0%), sufficient in 13 breasts (6.5%) and insufficient in 7 breasts (3.5%). Breast animation deformity and implant displacement could not be observed, while implant rotation was documented in 5 breasts (2.5%). Capsular contractures grade III or IV could not be observed neither in patients with previous radiotherapy nor in patients with radiotherapy to the reconstructed breast.
The single-stage direct-to-implant prepectoral implant placement after NSM with complete coverage of the implant with ADM or synthetic mesh represents a novel and feasible technique for breast reconstruction. This technique provides an alternative to the subpectoral implant placement with excellent cosmetic results avoiding the disadvantages of the subpectoral implant placement.
Abstract
Objective:
To evaluate the feasibility and complication rates of nipple-sparing mastectomy (NSM) and direct-to-implant breast reconstruction using a porcine acellular dermal matrix (ADM) for ...implant coverage.
Methods:
NSM and direct-to-implant breast reconstruction using a porcine ADM for implant coverage was performed in a series of 91 breasts in 63 patients. Technical results, complications, and cosmetic results were collected from patient records.
Results:
Short-term complications within one month comprised minor complications as minimal nipple necrosis in 13.2%, and infection in 1.1%. Major complications, as hemorrhage with surgical evacuation in 4.4%, and implant loss due to skin breakdown in 4.4%, totaled in 8.8%. Within three months after primary surgery 3 further severe complications with reoperation ocurred. In 87.9% no second surgical intervention was necessary and cosmetic results were good or excellent. After a mean follow-up of 12 months (range 5 - 35 months) no further complications could be observed. Patient satisfaction was high for 92.3% of the patients and subjective cosmetic result was excellent in 90.1% and satisfactory in 2.2%.
Conclusion:
Direct-to-implant breast reconstruction using a porcine ADM for implant coverage after NSM is an innovative approach resulting in a high patient satisfaction. The technique is challenging but feasible and complication rates are acceptably low.
Citation Format: Roland Reitsamer, Florentia Peintinger. Technical results and complication rates after nipple-sparing mastectomy and direct-to-implant breast reconstruction using porcine acellular dermal matrix for implant coverage abstract. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-14-10.
The standard treatment for early breast cancer comprises wide local excision, sentinel lymph node biopsy or axillary lymph node dissection, adjuvant medical treatment and radiotherapy to the whole ...breast. Many studies suggest that local control plays a crucial role in overall survival. The local recurrence rate is estimated to be 1% per year and varies between 4 and 7% after 5 years and up to 10 to 20% in the long-term follow up. On the basis of low local recurrence rates the concept of whole breast irradiation comes up for discussion, and partial breast irradiation (PBI) is increasingly under consideration. Intraoperative radiotherapy (IORT) is referred to as the delivery of a single high dose of irradiation directly to the tumor bed (confined target) during surgery. PBI (limited field radiation therapy, accelerated partial breast irradiation APBI) is the irradiation exclusively confined to a breast volume, the tumor surrounding tissue (tumor bed) either during surgery or after surgery without whole breast irradiation. Various methods and techniques for IORT or PBI are under investigation. The advantage of a very short radiation time or the integration of the complete radiation treatment into the surgical procedure convinces at a first glance. The promising short-term results of those studies must not fail to mention that local recurrence rates could probably increase and furthermore give rise to distant metastases and a reduction in overall survival. The combination of IORT in boost modality and whole breast irradiation has the ability to reduce local recurrence rates. The EBCTCG overview approves that differences in local treatment that substantially affect local recurrence rates would avoid about one breast cancer death over the next 15 years for every four local recurrences avoided, and should reduce 15-year overall mortality.
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