Adjuvant Postmastectomy Radiotherapy Research Articles

Autologous Breast Reconstruction and Radiotherapy: Consensus Report of the German-Speaking Society for Reconstructive Microsurgery (GSRM)

Autologous postmastectomy breast reconstruction is associated with favourable long-term clinical outcomes and superior patient-reported outcomes (PROMs) compared with implant-based reconstruction. However, adjuvant radiotherapy has traditionally been considered a relative contraindication to immediate flap-based reconstruction due to its unpredictable effects on the reconstructive outcome. While modern adjuvant postmastectomy radiotherapy (PMRT) has been able to significantly reduce acute and chronic radiation-induced complications, plastic surgeons still hesitate to offer immediate autologous reconstruction to patients expected to undergo adjuvant radiotherapy. More recently, evidence has emerged suggesting a paradigm shift in favour of immediate autologous reconstruction despite subsequent radiotherapy. At the 44th Annual Meeting of the German-speaking Society for Reconstructive Microsurgery (GSRM) in Bern, Switzerland, a workshop discussed the literature on PMRT and autologous breast reconstruction, aiming to establish consensus among the participants. Several areas of agreement were identified, including the goals of postmastectomy reconstruction, specifically the creation of a soft and sensitive breast symmetrical in shape and size to the unaffected breast via the safest procedure possible. The importance of preserving the maximum amount of native breast skin envelope through skin- and nipple-sparing approaches was emphasised. Finally, a consensus was reached that PMRT should no longer be considered a contraindication to immediate autologous breast reconstruction.

A Comparative Study of Cardiac Toxicity Analysis in Hypo-Fractionated Vs Conventionalfractionated Adjuvant Radiotherapy in Post-Mastectomy Leftbreast Carcinoma

Background: Post-mastectomy adjuvant radiotherapy improves long-term survival by reducing the risk of loco-regional recurrence in breast cancer patients with high-risk features. Considering radiation therapy to the left sided chest wall heart is an important organ at risk. Hypo-fractionated radiotherapy is increasingly being used due to involvement of fewer treatment sessions and is almost radio-biologically equivalent to conventionally fractionated radiotherapy. Objective: This study was conducted to evaluate cardiac toxicities between hypo and conventionally fractionated radiotherapy. Methods: This quasi-experimental study was done at the National Institute of Cancer Research and Hospital, Mohakhali, Dhaka from January 2019 to December 2019, 60 patients were purposively assigned into two groups and each group included 30 patients. Arm A: received Conventional fractionated radiotherapy (50Gy/25 fractions over 5 weeks, at 2Gy/fraction). Arm B: received Hypo- fractionated radiotherapy (40.05 Gy in 15 fractions over 3 weeks at 2.67 Gy/fraction). Echocardiography (ECHO), Electrocardiography (ECG) was performed to find the cardiac toxicities. Results: The mean age of the patients in arm A was 50.03 ± 6.82 years and that of arm B was 48.08 ± 5.08 years. No significant statistical difference was found between the two groups regarding socio-demographic variables and clinical presentations. Most of the patients in both arms showed grade 0 cardiac toxicity (arm A: 70% and arm B: 80%) & few showed grade 1 cardiac toxicity (arm A: 20% and arm B: 13.3%) and three patients (10.0%) in arm A and two patients (6.66%) in arm B had shown grade 2 cardiac toxicities six months after treatment. However, this difference was statistically not significant (p >0.05). Before treatment, the ejection fraction (EF) of arm A and arm B were 63.3 ± 5.621 and 64.7± 4.991. Six months after treatment the EF of both arms decreased (arm A 60.2 ± 4.051 & arm B 60.9 ± 5.121) but the difference was statistically not significant (p >0.05). Conclusion: Hypo-fractionated radiotherapy in the adjuvant setting for the treatment of left breast cancer has no additional cardiac toxicity in comparison to conventionally fractionated radiotherapy while maintaining same efficacy. J Bangladesh Coll Phys Surg 2024; 42: 169-175

Target volume coverage in clinically designed radiotherapy plan of post-mastectomy adjuvant radiotherapy of breast cancer patients in comparison with radiation therapy oncology group-based contoured plan: A dosimetric study.

Conventional field radiotherapy based on anatomical landmarks has been the traditional treatment for breast cancer. Having proven efficacy, it is still the current standard of treatment. The Radiation Therapy Oncology Group (RTOG) has published guidelines for contouring target volumes in postmastectomy patients. The impact of this guideline in the current clinical practice is less known; hence, we have analyzed dose-volume histograms (DVHs) for these plans and compared them with the proposed treatment plans to treat RTOG-defined targets. RTOG consensus definitions were used to contour the target volumes in 20 previously treated postmastectomy patients. The prescription was 42.4 Gy in 16 fractions. DVHs were generated from clinically designed plans that had actually been delivered to each patient. For comparing dose to target volumes, new plans were generated with the goal of covering 95% of volume to 90% of prescribed dose. In RTOG contoured Group, coverage improved for the supraclavicular (V90 = 83 vs. 94.9%, P < 0.05) and chest wall (V90 = 89.8 vs. 95.2%, P < 0.05). Axillary nodal coverage improved for Level-1(V90 = 80.35 vs. 96.40%, P < 0.05), Level-II (V90 = 85.93 vs. 97.09%, P < 0.05) and Level III (V90 = 86.67 vs. 98.6%, P < 0.05). The dose to the ipsilateral lung is increased (V20 = 23.87 vs. 28.73%, P < 0.05). Low dose to heart is increased in left-sided cases (V5 = 14.52 vs. 16.72%, P < 0.05) while same in right-sided cases. The study shows that radiotherapy using the RTOG consensus guidelines improves coverage to target volumes with a nonsignificant increase in normal organ dose compared to that based on anatomical landmarks.

Post-mastectomy adjuvant radiotherapy for direct-to-implant and two-stage implant-based breast reconstruction: A meta-analysis

In recent years, immediate replacement with a prosthesis (direct-to-implant, DTI) is gaining more popularity than two-staged methods (tissue expander followed by an implant, TEI). The safety of immediate implant-based breast reconstruction (IBR) is debatable when postmastectomy radiotherapy (PMRT) is indicated. This meta-analysis aims to evaluate the outcomes of DTI and TEI procedures followed by PMRT. Studies searched in the PubMed/Embase/The Cochrane Library databases (1995-2021) were filtered by exclusion criteria. Cases were divided into PMRT and non-irradiated groups, PMRT with a permanent implant or tissue expander. The outcomes were capsular contracture and other complications. A total of 22 studies with 6964 patients were included. PMRT increased the risk of capsular contracture in DTI patients and caused other complications in TEI patients. In PMRT and non-irradiated groups, the mean rates of capsular contracture were 17.01% versus 3.30% (p<0.01) in IBR and 15.49% versus 5.70% (p<0.01) in DTI. The mean rates of other complications were 22.59% versus 11.29% (p<0.01) in IBR, 31.88% versus 27.87% (p=0.35) in DTI, and 22.11% versus 9.90% (p<0.01) in TEI. Implants and tissue expanders caused a similar rate of capsular contracture and other complications. PMRT is related to a higher risk of complication and capsular contracture in IBR, including DTI procedure. This negative effect may not be related to the type of breast contents during radiotherapy.

Safety and efficacy of immediate autologous breast reconstruction after mastectomy in patients undergoing neoadjuvant chemoradiotherapy for locally advanced breast cancer.

Immediate autologous breast reconstruction (IABR) offers fewer surgeries with better psychosocial, quality of life and aesthetic outcomes. In high-risk patients or those with locally advanced breast cancer (LABC), adjuvant postmastectomy radiotherapy decreases local recurrence and improves survival. However, it has negative effects on the reconstructed flap. Reversing the treatment protocol using neoadjuvant radiotherapy may minimise the negative effects on the reconstructed breast in women requesting IABR. We assessed the safety and efficacy of women who underwent mastectomy and IABR post-neoadjuvant chemoradiotherapy (NACRT) for LABC. A cohort study using a retrospective and prospective analysis was performed on women with LABC who underwent mastectomy and IABR post-NACRT between 1998 and 2018. All reconstructions were performed by oncoplastic breast surgeons from a single unit. Outcome measures analysed included surgical complications, flap failure, loco-regional recurrence, overall and disease-free survival. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This study was approved by the institutional review board. A total of 28 women with a median age of 50 (33-64) were included. 25% underwent TRAM flap and 75% underwent LD flap reconstruction. The median period of follow-up was 61 months. Post-NACRT, 35.7% achieved complete pathological response (PCR). 3/28 (10.7%) had early complications (2 implant and 1 donor site infection). 7% underwent revision surgery. There was no flap loss. 1/28 (3.5%) had loco-regional recurrence, 3.2% had distant metastasis, and 2.5% had breast cancer related mortality. In women with LABC, NACRT followed by mastectomy and IABR is safe and may not compromise oncological and cosmetic outcomes. If offers the benefits of immediate breast reconstruction and avoids delaying adjuvant therapy.

Practical Model to Optimize the Strategy of Adjuvant Postmastectomy Radiotherapy in T1-2N1 Breast Cancer With Modern Systemic Therapy.

PurposeThe effect of adjuvant irradiation after mastectomy in early-stage breast cancer patients remains controversial. The present study aims to explore the clinical benefit obtained from adjuvant radiotherapy among post-mastectomy pT1-2N1 breast cancer patients who received adjuvant modern systemic therapy.MethodsMedical records of consecutive patients with pT1-2N1 breast cancer who received mastectomy in our institution between January 2009 and December 2016 were retrospectively reviewed. High-risk features consist of patient age, number of positive lymph nodes, T stage, and Ki67 index, which were developed previously at our institution using early-stage breast cancer patients after mastectomy without adjuvant radiotherapy. Differences of survival and local recurrence were compared between no-postmastectomy radiotherapy (PMRT) and PMRT group according to number of risk factors. The time-to-event curves were calculated by the Kaplan–Meier methods and compared by the log-rank test. Propensity score matching (PSM) was performed to reduce the imbalances in patient characteristics.ResultsA total of 548 patients were enrolled (no-PMRT: 259 and PMRT: 289). After a median follow-up of 69 months, the 5-year rate of DFS, BCSS, and LRR in the overall cohort was 90.2%, 97.4%, and 3.6%, respectively. PMRT did not significantly improve DFS, BCSS, and LRRFS in the whole cohort. Patients were divided into low-risk (with no or one risk factor) and high-risk (with two or more risk factors) groups. According to the univariable and multivariable analysis, high-risk group (HR = 1.81, 95% CI 1.11–2.98, p = 0.02) was demonstrated as an independent risk factor for DFS. For the high-risk group, PMRT significantly improved DFS from 81.4% to 91.9% and BCSS from 95.5% to 98.6% and decreased the 5-year rate of LRR from 5.6% to 1.4%, respectively (p < 0.01, p = 0.05, and p = 0.06). However, no survival benefit from PMRT was observed in the low-risk group in terms of DFS, BCSS, and LRR (p = 0.45, p = 0.51, and p = 0.99, respectively). In multivariate analysis, PMRT remained an independent prognostic factor for DFS (HR = 0.50, 95% CI 0.24–1.00, p = 0.05) in the high-risk group. After PSM analysis, the survival benefit of PMRT was sustained in high-risk patients.ConclusionPMRT significantly improved DFS in high-risk pT1-2N1 breast cancer patients, but not in low-risk patients. Independent validation of our scoring system is recommended.

Adjuvant postmastectomy radiotherapy might be associated with better survival in women with heart failure receiving total mastectomy

BackgroundTo date, no data on the effect of adjuvant postmastectomy radiotherapy (PMRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF).Patients and methodsWe enrolled 646 women with left-breast IDC at clinical stages I–IIIC and HFrEF receiving radical total mastectomy (TM) followed by adjuvant PMRT or non-adjuvant PMRT. We categorized them into two groups based on their adjuvant PMRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score–weighted population to obtain hazard ratios (HRs).ResultsIn the IPTW-adjusted model, adjuvant PMRT (adjusted HR [aHR]: 0.52; 95% confidence interval [CI]: 0.37–0.74) was a significant independent prognostic factor for all-cause death (P = 0.0003), and the aHR (95% CI) of LRR and DM for adjuvant PMRT was 0.90 (0.79–0.96; P = 0.0356) and 0.89 (0.54–1.50; P = 0.6854), respectively, compared with the nonadjuvant PMRT group.ConclusionAdjuvant PMRT was associated with a decrease in all-cause death, and LRR in women with left IDC and HFrEF compared with nonadjuvant PMRT.

Outcomes of Adjuvant Hypofractionated Radiotherapy in the Treatment of Post-Mastectomy Breast Cancer Patients

<h3>Purpose/Objective(s)</h3> This is a retrospective study to assess loco-regional control, disease free survival (DFS) and overall survival (OS) of adjuvant hypofractionated radiotherapy (HF RT) compared to conventionally fractionated radiotherapy (CF RT) in post-mastectomy breast cancer patients. <h3>Materials/Methods</h3> From Jan 2007 to Dec 2016, 1077 women were diagnosed with breast cancer and received adjuvant post-mastectomy radiotherapy (PMRT) in the clinical oncology department of one institution. <h3>Results</h3> We had 477 patients treated with CF RT regimen and 600 patients treated with HF RT regimen following mastectomy. The median age at diagnosis was 49 years, 48 years in (CF RT) and 50 years in (HF RT); <i>P</i> = 0.011. Fifty percent of all study patients had stage III disease. Of all study patients, 93.4% received chemotherapy and 82.8% received hormonal treatment. In the HF RT group, 68 % started RT after more than 6 months from surgery date, while 53.4 % in the CF RT group started RT after more than 6 months following surgery; <i>P</i> < 0.001. The highest proportion (83.5 %) of patients received regional nodal irradiation (RNI) in the HF RT group versus 75.2 % in the CF RT group; <i>P</i> = 0.003. HF RT dose was mostly 40 Gy/15 Fx (57.8%), and 42 Gy/ 16 Fx (36.5%). Radiotherapy was delivered by 3-D Conformal radiotherapy. The majority of patients had no delay or delay 5 days or less due to treatment interruption during course; 74.2% in CFRT and 78.1% in HFRT group; <i>P</i> < 0.001. The HF RT group showed lower incidence of overall relapse; 20% vs 30.6% in CF RT group (OR 0.56, 95% CI 0.43 - 0.75) <i>P</i> < 0.001, loco-regional failure 5.8% vs 10.5% in CF RT group (OR 0.53, 95% CI 0.34 - 0.83) <i>P</i> = 0.005, and distant metastasis 16.7% vs 25.8% in CF RT group (OR 0.58, 95% CI 0.43 - 0.77) <i>P</i> < 0.001. The 5-year DFS in the CF RT group was 71.7%, while in the HF RT regimen group was 75.4% (<i>P</i> = 0.049). The 5-year OS in the CF RT group was 86.6%, while in the HF RT regimen group was 88% (<i>P</i> = 0.027). Reported late side effects included cardiac events (5 patients in CFRT and 1 patient in HF RT group), lung fibrosis (11 patients in CFRT and 9 patients in HF RT group) and rib fracture in 1 patient in CF RT group <h3>Conclusion</h3> Our data suggest that adjuvant HF RT may offer slightly better DFS and OS in post-mastectomy patients without increasing late toxicity.

Postmastectomy radiation therapy following pathologic complete nodal response to neoadjuvant chemotherapy: A prelude to NSABP B-51?

PurposeThe utility of post-mastectomy radiotherapy (PMRT) in women with a nodal complete response (CRn) to neoadjuvant chemotherapy (NAC) is unknown. The NSABP B-51 trial is evaluating this question, but has not reported results thus far. Therefore, we sought to answer this question with the National Cancer Database. MethodsThe National Cancer Database was queried for women with cT1–4N1-3M0 breast cancer who had undergone NAC and were ypN0 upon mastectomy. Statistics included multivariable logistic regression, Kaplan-Meier overall survival (OS) analysis, Cox proportional hazards modeling, and construction of forest plots. ResultsOf 14,690 women, 10,092 (69%) underwent adjuvant PMRT and 4598 (31%) did not. The median follow-up was 55.6 months. In all patients, the 10-year OS was 76.3% for PMRT and 78.6% without (p = 0.412). There were no notable effects of PMRT on OS based on age or the axillary management (number of nodes removed). Specifically, in the NSABP B-51 population of cT1–3 cN1 patients, the 10-year OS was 82.6% for PMRT and 80.0% without (p = 0.250). PMRT benefitted women with increasing cT stage (i.e. cT3–4), increasing ypT stages (with the exception of ypT4 potentially owing to small sample sizes), and cN3 cases (p < 0.05 for all). ConclusionsIn the absence of published results from NSABP B-51, this assessment of over 14,000 women from a contemporary US database revealed that PMRT may be most useful for a “moderately-high” risk group – women with more advanced primary and/or nodal disease at diagnosis, yet with tumor biology favorable enough that the disease does not progress or remain stable after NAC. The OS findings notwithstanding, this study cannot exclude potential differences between groups in recurrence-free survival, which is the primary endpoint of NSABP B-51, While the results of the NSABP B-51 will confirm optimal management for patients with limited nodal disease having a CRn following NAC, the present results suggest PMRT should remain the standard of care for more advanced disease than NSABP B-51 eligibility criteria.

Outcomes in Patients with pT3N0M0 Breast Cancer with and without Postmastectomy Radiotherapy.

PurposeThe role of adjuvant postmastectomy radiotherapy (PMRT) remains controversial for patients with pT3N0M0 breast cancer, especially when patients are treated with the updated adjuvant chemotherapy. Our study aimed to compare locoregional recurrence-free survival (LRFS), disease-free survival (DFS), and breast cancer-specific survival (BCSS) in pT3N0M0 patients with and without postmastectomy radiotherapy.Patients and MethodsBetween October 2000 and 8 September 2016, the database of the Breast Cancer Center of Shanghai yielded 114 patients with node-negative non-metastatic breast cancer larger than 5 cm. Univariate and multivariate analyses were performed to assess the risk factors for survivals. Differences between the two groups were compared using the Log rank test.ResultsFifty-nine (51.8%) of the patients received adjuvant PMRT. The median follow-up was 62.3 months. Five-year LRFS was 100% in the PMRT group vs 98.1% in the non-PMRT group (P=0.17); 5-year DFS was 97.1% for the entire cohort, 98.0% for the PMRT group vs 96.2% for the non-PMRT group (P=0.18). Univariate analysis identified that family history of malignant tumors, lymphovascular invasion (LVI), or triple-negative breast cancer (TNBC) molecular subtype were associated with higher locoregional recurrence (LRR) (P<0.05). No PMRT was the only risk factor independently associated with poorer DFS (P=0.048) on multivariate analysis. No difference in BCSS was observed between the two groups.ConclusionThe present study demonstrated a low LRR rate and good survival for node-negative breast cancer >5 cm. Patients with family history of malignant tumors, TNBC subtype, LVI positivity, or grade 3 disease are at high risk for LRR and might benefit from PMRT.

Postmastectomy Radiotherapy Using 5040 cGy in 28 Fractions for Patients with Immediate Breast Reconstruction: Institutional Outcomes

For patients planned to undergo adjuvant postmastectomy radiotherapy (PMRT) for breast cancer, immediate breast reconstruction (IBR) has been considered a relative contraindication. Delayed wound healing, increased risk of capsular contracture, fat necrosis, poor cosmesis, and rates of reoperation are of concern. Patients who have undergone IBR at our institution with an indication for PMRT are prescribed extended fractionation as per institutional policy. The aim of this quality assurance project is to review rates of reoperation for patients who received PMRT after IBR with autologous tissue (AT), tissue expanders (TE), or permanent implants (PI). Using a patient information system, patients were identified who underwent adjuvant PMRT to the chest wall and regional nodes to a total dose of 5040 cGy in 28 fractions between January 1, 2013 and January 31, 2019. Radiotherapy plans were reviewed. Medical records were reviewed for patient and treatment characteristics, and unexpected reoperation rate. Seventy-three patients underwent IBR and PMRT. Eleven (15.1%) patients had AT, 24 (32.9%) had TE, and 38 (52.1%) had PI. Twenty-four patients (32.9%) had documented cosmetic complications (including capsular contracture and asymmetry) after PMRT requiring reoperation. Cosmetic complications (CC) leading to reoperation were documented in 45.5% of patients with AT, 37.5% of patients with TE, and 26.3% of patients with PI. The mean elapsed time from PMRT completion to reoperation for cosmetic complications was 12.3 months (range = 2.3-33.1 months). Most patients received either adjuvant or neoadjuvant chemotherapy (97.3%). Of the patients having CC leading to reoperation compared to those without complication, a higher proportion received neoadjuvant chemotherapy, but this difference was not statistically significant (39.1% vs 19.4%, p = 0.135). For patients with CC leading to reoperation, there was a significantly higher volume of chest wall receiving ≥5040 cGy (851cc vs 680 cc, p = 0.023). Bolus was slightly more common in patients with CC but this difference was not statistically significant (91.7% vs 81.5, p = 0.461). For our cohort of patients receiving PMRT after IBR, the rate of CC is comparable to those quoted elsewhere. Interestingly, for our cohort, patients having PI had the lowest rate of CC leading to reoperation compared those with AT and TE. Patients with CC had a higher volume of chest wall receiving ≥ 5040 cGy. Further dosimetric analysis is needed to determine if there is a correlation with capsule dose and cosmetic outcomes.

01. IS POST MASTECTOMY RADIOTHERAPY BENEFICIAL IN THE SETTING OF A COMPLETE PATHOLOGICAL RESPONSE AFTER NEO ADJUVANT CHEMOTHERAPY FOR BREAST CANCER? SYSTEMATIC REVIEW AND META-ANALYSIS OF THE LITERATURE

Data from the EBCTCG meta-analysis demonstrates that adjuvant post mastectomy radiotherapy (PMRT) improves loco-regional control (LRR) and overall survival (OS) in breast cancer patients with positive axillary lymph node disease. None of the trials included in the meta-analysis encompassed patients treated with neo-adjuvant chemotherapy (NAC). This study systematically reviewed the literature to identify LRR rates following PMRT for patients with a complete pathological response (pCR) after receiving NAC.

Can a subgroup at high risk for LRR be identified from T1-2 breast cancer with negative lymph nodes after mastectomy? A meta-analysis.

Purpose: To identify a subgroup at high risk for loco-regional recurrence (LRR) from T1-2 breast cancer with negative lymph nodes (N0) after mastectomy by using a meta-analysis.Methods and materials: Published studies on the relationship between clinical features and LRR of breast cancer were identified from public databases, including PubMed, EMBASE, and the Cochrane Library. High-risk features for LRR in this patient population were defined based on the pooled results of meta-analysis.Results: For the meta-analysis, a total of 11244 breast cancers with pT1-2N0 after mastectomy from 20 publications were included for analysis. The pooled results indicated that age (hazard ratio (HR) 1.77, P=0.001), lymphovascular invasion (LVI) (HR 2.23, P<0.001), histologic grade (HR 1.66, P<0.001), HER2 status (HR 1.65, P=0.027), menopausal status (HR 1.36, P=0.015), and surgical margins (HR 2.56, P=0.014) were associated with a significantly increased risk of developing LRR in this patient population group, but not for tumor size (HR 1.32, P=0.23), systematic therapy (HR 1.67, P=0.20), and hormonal receptor status (HR 1.04, P=0.73).Conclusion: In the current study, patients with young age, positive LVI, high histologic grade, HER-2 positive, premenopausal, and positive surgical margins have an increased risk of developing LRR. Further prospective trials are needed to clearly define the role of adjuvant postmastectomy radiotherapy in T1-2N0 breast cancer at high risk of developing LRR.

Locoregional recurrence-associated factors and risk-adapted postmastectomy radiotherapy for breast cancer staged in cT1-2N0-1 after neoadjuvant chemotherapy.

ObjectiveIn order to identify risk factors associated with locoregional recurrence (LRR) and assess the role of postmastectomy radiotherapy (PMRT) in early breast cancer (BC), managed with neoadjuvant chemotherapy (NAC) and mastectomy, a retrospective analysis of BC diagnosed with clinical stage T1-2N0-1 was conducted.Patients and methodsA total of 217 patients were included in this analysis. The median age was 50 years (24–72 years). The clinical stage distributions were cT1 in 15 cases, cT2 in 202, cN0 in 53, and cN1 in 161 cases. All patients were treated with NAC and mastectomy, and 128 patients received PMRT.ResultsWith a median follow-up time of 61 months, the 5-year cumulative LRR rate was 12%. Multivariate analysis demonstrated that pathological N stage, lymph-vascular invasion, and histological grade were independent prognostic factors associated with LRR. A nomogram model based on these factors was established, based on which the patients were deeply stratified into low- and high-risk group. In the low-risk group, radiotherapy did not decrease LRR (3.3% in PMRT group, 1.7% in no PMRT group, P=0.192). While in the high-risk group, PMRT significantly decreased LRR (21.8% in PMRT group, 42.2% in no PMRT group, P=0.031).ConclusionLymph-vascular invasion, histological grade, as well as pathological N stage were important prognostic factors associated with LRR in BC patients staged in cT1-2N0-1, who were managed with NAC and mastectomy. In our cohort, not only clinical and pathological stage information but also other risk factors were taken into consideration when adjuvant PMRT was recommended. In the high-risk subgroup, PMRT significantly improved the prognosis.

The Influence of Radiotherapy on the Mechanical Properties of Silicone Breast Implants.

Background:Silicone breast implants have been used for decades for cosmetic breast augmentation or reconstruction after mastectomy. In selected cases, postmastectomy adjuvant radiotherapy is given with the breast implants in situ. Previous clinical studies have shown that radiotherapy may lead to complications such as capsular contracture and infection and that removal of the implant may be required. Yet, the effect of radiotherapy on silicone breast implants themselves is unknown. The aim of this study was to investigate if irradiation of breast implants influences their mechanical properties.Methods:This was an ex vivo study on 32 ready-to-use silicone breast implants (Mentor and Silimed). Half of the implants of each brand were irradiated with 1 × 60 Gy, the other half were not irradiated. Tensile, mechanical hysteresis, and rheology tests were performed. Differences in mechanical properties between the irradiated and nonirradiated implants were determined.Results:No significant differences were found in tensile strength, mechanical hysteresis, and rheological properties between irradiated and nonirradiated implants.Conclusions:Breast implants’ mechanical properties for these 2 brands were not significantly affected after single-dose irradiation in an ex vivo setting.

Immediate Two-Stage Prosthetic Breast Reconstruction Failure: Radiation Is Not the Only Culprit.

Immediate prosthetic breast reconstruction produces a satisfactory aesthetic result with high levels of patient satisfaction. However, with the broader indication for postmastectomy adjuvant radiation therapy, many patients are advised against immediate breast reconstruction because of concerns of implant loss and infection, particularly as most patients also require chemotherapy. This retrospective cohort study examines outcomes for patients who underwent immediate two-stage prosthetic breast reconstruction after mastectomy with or without adjuvant chemotherapy or radiotherapy. Between 1998 and 2010, 452 patients undergoing immediate two-stage prosthetic breast reconstruction involving a total of 562 breasts were included in this study. Stage 1 was defined as insertion of the temporary expander, and stage 2 was defined as insertion of the final silicone implant. Postoperative adjuvant radiotherapy was recommended with a tissue expander in situ for 114 patients. Complications, including loss of prosthesis, seroma, and infection, were recorded and analyzed. Cosmetic result was assessed using a four-point scale. Postoperative prosthesis loss was 2.7 percent, 5.3 percent for patients undergoing adjuvant chemotherapy and increasing to 11.3 percent for patients receiving chemotherapy plus radiotherapy. Chemotherapy and radiotherapy independently were the main, statistically significant risk factors for expander or implant loss [incidence rate ratio, 13.85 (p = 0.012) and 2.23 (p = 0.027), respectively]. Prosthesis loss for patients undergoing combination chemotherapy plus radiotherapy was also significant [incidence rate ratio, 4.791 (p < 0.001)]. These findings serve to better inform patients on risk in weighing treatment options. Postmastectomy radiation therapy doubles the risk of prosthesis loss over and above adjuvant chemotherapy but is an acceptable option following immediate two-stage prosthetic breast reconstruction in a multidisciplinary setting. Therapeutic, III.

Intrinsic subtypes and benefit from postmastectomy radiotherapy in node-positive premenopausal breast cancer patients who received adjuvant chemotherapy – results from two independent randomized trials

Background: The study of the intrinsic molecular subtypes of breast cancer has revealed differences among them in terms of prognosis and response to chemotherapy and endocrine therapy. However, the ability of intrinsic subtypes to predict benefit from adjuvant radiotherapy has only been examined in few studies.Methods: Gene expression-based intrinsic subtyping was performed in 228 breast tumors collected from two independent post-mastectomy clinical trials (British Columbia and the Danish Breast Cancer Cooperative Group 82b trials), where pre-menopausal patients with node-positive disease were randomized to adjuvant radiotherapy or not. All patients received adjuvant chemotherapy and a subgroup of patients underwent ovarian ablation. Tumors were classified into intrinsic subtypes: Luminal A, Luminal B, HER2-enriched, Basal-like and Normal-like using the research-based PAM50 classifier.Results: In the British Columbia study, patients treated with radiation had an overall significant lower incidence of locoregional recurrence compared to the controls. For Luminal A tumors the risk of loco-regional recurrence was low and was further lowered by adjuvant radiation. These findings were validated in the DBCG 82b study. The individual data from the two cohorts were merged, the hazard ratio (HR) for loco-regional recurrence associated with giving radiation was 0.34 (0.19 to 0.61) overall and 0.12 (0.03 to 0.52) for Luminal A tumors.Conclusions: In both postmastectomy trials, patients with Luminal A tumors turned out to have a significant lower incidence of loco-regional recurrence when randomized to adjuvant radiotherapy, leaving no indication to omit postmastectomy adjuvant radiation in pre-menopausal high-risk patients with Luminal A tumors. It was not possible to evaluate the effect of radiotherapy among the other subtypes because of limited sample sizes.

Abstract: The Influence of Radiotherapy on Silicone Breast Implants

INTRODUCTION: Silicone breast implants have been used for decades for cosmetic breast augmentation or reconstruction after mastectomy1. In selected cases, postmastectomy adjuvant radiotherapy is given with the breast implants in situ. Previous clinical studies showed that adjuvant radiotherapy may lead to several complications such as capsular contracture, infection and removal of the implant.2,3 Yet, the effect of radiotherapy on silicone breast implants themselves is unknown. The aim of this study was to investigate if radiotherapy, as used in clinical postmastectomy radiotherapy, influences the mechanical properties of silicone breast implants. METHODS: This was an ex vivo study on 32 ready-to-use silicone breast implants (Mentor n= 16 & Silimed n= 16). Half of the implants (n= 8) of each brand were irradiated with 60 Gy, the other half (n= 8) was not irradiated. Mechanical tests performed included tensile tests, mechanical hysteresis and rheology. The difference in mechanical properties between the irradiated and non-irradiated implants of both brands was determined. RESULTS: No significant differences were found in tensile strength, mechanical hysteresis and rheology properties between irradiated and non-irradiated implants. CONCLUSIONS: Breast implants’ mechanical properties for two brands are not significantly affected by postmastectomy radiotherapy in an ex vivo setting. Reference Citations: 1. Regulatory History of Breast Implants in the U.S. Food and Drug Administration September 2013; Available from: http://www.fda.gov/medicaldevices/productsandmedicalprocedures/implantsandprosthetics/breastimplants/ucm064461.htm 2. Ascherman, J.A., Hanasono, M.M., Newman, M.I. et al. Implant reconstruction in breast cancer patients treated with radiation therapy Plast Reconstr. Surg 117: 359–365, 2006. 3. Cordeiro, P.G., Pusic, A.L., Disa, J.J. et al. Irradiation after immediate tissue expander/implant breast reconstruction: outcomes, complications, aesthetic results, and satisfaction among 156 patients Plast Reconstr. Surg 113: 877–881, 2004.

Delaying implant-based mammary reconstruction after radiotherapy does not decrease capsular contracture: An in vitro study

The most common complications of irradiated implant-based mammary reconstruction are fibrosis and capsular contracture. The indications for postmastectomy adjuvant radiotherapy have considerably broadened. Facing an increased number of patients who will require radiotherapy, most guidelines recommend delaying reconstruction after radiotherapy to prevent long-term fibrotic complications. Does radiotherapy permanently alter cellular properties which will adversely affect implant-based reconstruction? If so, is there a benefit in delaying reconstruction after radiotherapy? Our invitro model simulates two implant-based mammary reconstruction approaches: the irradiated implant and the delayed implant reconstructions by using an implant inset beneath healthy non-irradiated tissue post radiotherapy. We performed cell culture of fibroblasts and endothelial cells to simulate these two surgical conditions. Irradiated fibroblasts simulate the capsular tissue seen around the breast implant. The delayed reconstruction approach is simulated by non-irradiated fibroblasts conditioned with supernatant culture media obtained from irradiated endothelial cells. Irradiation induced fibrosis through fibroblast differentiation into myofibroblasts, as demonstrated by increased α-smooth-muscle actin levels in fibroblasts. This constitutes the basis for scar tissue contraction observed in irradiated implant-based breast reconstruction. Irradiation of endothelial cells induced irreversible cell cycle arrest known as senescence and secretion of the profibrotic connective tissue growth factor. Non-irradiated fibroblasts conditioned with culture media obtained from irradiated endothelial cells exhibited myofibroblast differentiation and the expression of fibrotic phenotype akin to capsular contracture. Our results demonstrate that radiotherapy causes irreversible cellular changes, which permanently alter the microenvironment in favor of fibrosis. Given that these changes are permanent, delaying reconstruction does not present an advantage in preventing capsular contracture.

Abstract P1-10-01: Utilization and outcomes of post-mastectomy radiotherapy in women with 1-3 positive axillary nodes following neoadjuvant chemotherapy: A multiply-imputed, propensity-adjusted National cancer database analysis

Abstract Background: Use of post-mastectomy radiotherapy (PMRT) following neoadjuvant chemotherapy (NAC) varies widely. The combined analysis of NSABP B1724 studies suggests a higher risk of locoregional recurrence for women with persistently positive lymph nodes following NAC. The impact of PMRT on survival in the subset of patients with 1 to 3 positive nodes after NAC is not clear and the goal of the current study is to evaluate practice patterns and the impact of PMRT on survival in this subset of patients. Methods: The National Cancer Database was queried for women who underwent NAC followed by mastectomy and had 1-3 persistent axillary lymph nodes with or without adjuvant PMRT. A propensity score was generated to account for indication bias under two circumstances: one with the original dataset and one following a multiple imputation to complete the dataset to allow for a more accurate propensity score generation. Factors impacting utilization of PMRT were calculated with backwards-selection binary regression. Kaplan-Meier with log-rank test and Cox-regression analyses were used for survival. Results: Within the queried cohort of 14,895 women from 2006-2012, 70% of women received PMRT following NAC with 1-3 positive axillary lymph nodes. One lymph node was positive in 56%, 2 in 25.9%, and 3 in 18.1%. PMRT was utilized in 67.3% of women with 1 node positive, 71.5% with 2 nodes positive, and 76.2% with 3 nodes positive. Factors associated with the usage of PMRT were: residence on the east coast in a highly populated region with proximity to the treatment center, later year of diagnosis (71% of women in 2012), younger age, non-African American race, non-Hispanic descent, private insurance, higher clinical stage, triple negative/high grade histology, pathologic T4, greater number of axillary node positive, positive margins or LVSI, greater number of nodes examined, and use of adjuvant hormonal therapy (all p&amp;lt;.05). Median follow up was 40.1 months (range: 2.6-106.9 months). Prior to multiple imputation, a propensity score was generated which accounted for 28.7% of cases. PMRT did not have an impact on survival within the limited analysis. In a pooled propensity-adjusted Cox analysis following multiple imputation to complete the dataset, PMRT was found to have an OS HR of 0.878 (95%CI 0.806-0.957, p=.003). Five year overall survival rates with and without PMRT were 77.6% and 75.4% (p&amp;lt;.001). For 1-3 positive nodes respectively, 5-year overall survival rates with and without PMRT were: 79.7% vs. 79.1% (p=.041), 77.3% vs. 70.8% (p&amp;lt;.001), and 71.8% vs. 68.0% (p=.004). Conclusions: In a population-based analysis of women who underwent neoadjuvant chemotherapy prior to mastectomy, post-mastectomy radiotherapy appears to confer a survival advantage in women with 1-3 residual axillary lymph nodes. There continues to be a wide variation in practice nation-wide with a significant number of women with persistently positive 1-3 axillary lymph nodes not receiving PMRT. Citation Format: Horne ZD, Gebhardt BJ, Balasubramani GK, Beriwal S. Utilization and outcomes of post-mastectomy radiotherapy in women with 1-3 positive axillary nodes following neoadjuvant chemotherapy: A multiply-imputed, propensity-adjusted National cancer database analysis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-10-01.