Postmastectomy Radiotherapy Group Research Articles

The impact of adjuvant radiotherapy for cosmetic results after immediate breast reconstruction based on the tissue expander and permanent implant

Background. One of the causes of complications in breast cancer patients after immediate breast reconstruction (IBR) is postmastectomy radiation therapy (PMRT).Aim. Retrospective analysis of the results of IBR, and evaluating the effect of PMRT on the frequency and type of complications.Materials and methods. Between 2015 and 2021, 798 patients underwent IBR with tissue expander or implant in N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia. PMRT was performed in 375 patients (group 1). The remaining 423 patients did not receive PMRT (group 2). Complications, including reconstructive failure (RF), Baker grade III/IV capsular contracture (CC), were recorded and analyzed.Results. Finally, cosmetic result analyzed in 521 patients. In 281 patients of PMRT group (group 1) IBR with expander or implant were performed in 144 and 137 cases, respectively. In the 240 patients without PMRT (group 2), IBR with expander was performed in 81 patients, with implant – in 159 cases. Pooled analysis revealed that overall rate of complications in the PMRT group was 33.8 % (in 95 of 281 patients), in non-irradiation patients – 22.9 % (in 55 of 240 patients), p <0.01. In group 1, RF were recorded in 67 (23.8 %) patients, in group 2 – in 44 (18.3 %) patients, p >0.05. CC in group 1 were detected in 28 (10 %) patients, in group 2 in 11 (4.6 %) patients, p <0.05. In patients with permanent implants RF were detected in 21 (14.6 %) of irradiation patients and in 22 (13.8 %) non-irradiation patients (p >0.2). On the contrary, CC were mentioned in 22 (16.1 %) of irradiated patient and in 8 (5 %) patients that didn’t receive PMRT, p <0.005. After reconstruction with expander RF were diagnosed in 46 (31.9 %) patients after PMRT and in 22 (27.2 %) non-irradiation patients, p >0.2. CC were observed in 6 (4.2 %) patients from PMRT group and in 3 (3.7 %) patients treated without PMRT, p >0.2.Conclusion. PMRT in patients after IBR with simultaneous installation of a permanent implant is characterized by a decrease in the incidence of RF, but an increase in the incidence of CC.

Ipsilateral recurrence and breast cancer outcomes in carriers of BRCA1/2 pathogenic variants according to locoregional treatments.

e12584 Background: Our previous study of 255 breast cancer (BC) patients, carriers of BRCA1/2 pathogenic variants (PV), showed that patients who underwent mastectomy without post-mastectomy radiotherapy (PMRT) had higher rates of local recurrence (LR) than those who underwent PMRT or breast-conserving therapy (BCT). Our aim was to verify our previous findings in a larger cohort. Methods: Clinical data was extracted from the medical records of BRCA1/2 mutation carriers with BC, treated at a single institution between 1/2006-12/2022. Data extracted included demographics, tumor characteristics, disease stage, surgical and oncological treatment, use of RT and disease outcomes. Results: Overall, 481 BC patients with BRCA1/2 germline mutations were identified, 20 of them presented with synchronous bilateral disease. Median follow-up time was 75.3 months (range 12.5-211). After excluding 16 patients with metastatic de novo disease and 1 patient not operated for medical reasons, 464 patients with 484 primary tumors were analyzed. Of these, 234 (48.3%) mastectomies (84% were skin- or nipple-sparing, SSM/NSM, 16% total mastectomy) and 250 (51.7%) BCT were performed. In the non-PMRT group (n=153) there was earlier disease stage at diagnosis (77.6% of tumors were Tis and T1N0) compared to the PMRT group (n=81) and BCT group (4.9% and 45%, respectively, p<0.001). All had free surgical margins. LR rate in the study cohorts was 20/153 breasts (13.1%) in the non-PMRT group compared with 1/81 breasts (1.2%) in the PMRT group (p=0.003), and 16/250 (6.4%) in the BCS group (p=0.024). All but one recurrence were invasive. Cumulative incidence of LR at 5 and 10 years was 14.1% and 15.9% in the non-PMRT, compared to 4.4% and 9.4% in BCT group, respectively (p=0.034). No significant difference in overall survival was observed (p=0.39). Conclusions: BRCA1/2 PV carriers treated with mastectomy without PMRT had higher rates of LR than those who underwent mastectomy and PMRT or BCT, despite earlier stage disease. Further studies are needed to compare these outcomes to non- BRCA1/2 carriers and find means to improve local control in these patients.

Abstract PO3-22-04: PMRT Decision with low prediction of genomic test score in pT3N0M0 luminal breast cancer: Protocol MF22-02: International multicenter real-world data

Abstract Background: In current guidelines, there is no definite recommendation regarding postmastectomy radiation therapy (PMRT) in patients with luminal pT3N0M0 breast cancer (BC). The goal of this study is to determine whether PMRT could be safely omitted for a specific subgroup of those patients. Methods and Materials: There were 202 women from 16 centers with pT3N0M0 hormone receptor (HR) positive, Her2 neu (-) BC who underwent mastectomy, were analyzed retrospectively. None of the patients received neoadjuvant chemotherapy. Three patients were excluded because of positive surgical margins. The patients were divided into two groups, PMRT (+) (n=130) and PMRT (-) (n=69). Groups were compared in terms of overall survival, loco-regional recurrence rate, and distant metastases regarding Magee score (MS) (< 18 are considered low risk) (https://path.upmc.edu/onlineTools/mageeequations.html), menopausal status, axillary surgery, pathology, lymphovascular invasion (LVI), adjuvant chemotherapy, and adjuvant endocrine therapy. Results: The majority of the patients had invasive ductal carcinoma (49%, n=98). There was no significant difference regarding tumor size, axillary surgery, and adjuvant endocrine therapy between the two groups (p=0.82, p=0.28, p=0.12, respectively). LVI was 49% (n=98) and it was greater in PMRT (+) group (25% vs. 10%; p=0.01). PMRT (+) patients received more chemotherap(66% vs. 30%; p< 0.001), had more grade 3 tumors (28% vs. 9%, p=0.005), and more premenopausal (49% vs. 22%; p=0.0001). At a median follow-up of 51.3 months for the PMRT (-) group and 65.9 months for the PMRT (+) group (p=0.041), 9% (n=6) of patients from the PMRT (-) group and 2% (n=3) from the PMRT (+) group developed locoregional recurrence (LRR) (p=0.047). There was no difference in local recurrence (1% in PMRT (-) group vs. 2% in PMRT (+); p=0.7) and distant recurrence (7% in PMRT (-) group vs. 3% in PMRT (+); p=0.16) between patients who received PMRT and not had PMRT. Further comparison of the LRR in the PMRT (-) and PMRT (+) groups in patients with an MS < 18 did not show a significant difference (3% vs. 4%; p=0.64). However, among patients with a Magee score ≥18, the PMRT (-) group had a higher LRR rate compared to the PMRT (+) group (11% vs. 2%; p=0.01). In patients with an MS≥18, the administration of PMRT correlates with statistically significantly better LRR-free survival (HR 0.19; 95%CI 0.05 – 0.79; p=0.02). Conclusions: Our findings imply that when considering PMRT for BC with pT3N0M0, HR (+), and Her2 neu (-), clinicians can benefit from a combination of pathological risk factors and recurrence prediction models. Patients with MS< 18 receiving PMRT or not appear to experience a comparable rate of recurrence. Citation Format: Atilla Soran, Caleb King, Parul N. Barry, Rohit Bhargava, Hasan Karanlik, Melis Gultekin, Ferah Yiıdız, Aykut Soyder, Berk Goktepe, Kazim Senol, Caglar Guzel, Ebru Sen Oran, Levent Yeniay, Ahmet Dağ, Selman Emiroglu, Didem Can Trabulus, Alper Coskun, Neslihan Cabioglu, Hagigat Veliyeva, N. Zafer Utkan, Berkay Demirors, Efe Sezgin, John A. Vargo. PMRT Decision with low prediction of genomic test score in pT3N0M0 luminal breast cancer: Protocol MF22-02: International multicenter real-world data [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-22-04.

Outcomes with and without postmastectomy radiotherapy for pT3N0-1M0 breast cancer: An institutional experience.

The objective of this study is to comprehensively evaluate the therapeutic efficacy of postmastectomy radiotherapy (PMRT) in treating patients with pT3N0-1M0 breast cancer within the context of modern therapeutic strategies. Clinical data from patients with pT3N0-1M0 breast cancer who underwent mastectomy from January 2005 to December 2018 at our institution were retrospectively analyzed. The study involved a total of 222 participants, with 112 individuals undergoing PMRT and 110 individuals not receiving it. The median follow-up duration was 77 months (range: 6-171 months). The entire cohort demonstrated 5-year disease-free survival (DFS) and overall survival (OS) rates of 85.1% and 91.0%, respectively, along with a locoregional recurrence (LRR) rate as low as 7.2%. The PMRT group showed significantly better 5-year DFS (90.2% vs. 80.0%, p = 0.02) and OS (95.5% vs. 86.4%, p = 0.012) rates, as well as a lower LRR rate (4.5% vs. 10.0%, p = 0.122), compared to the group without PMRT. Cox regression analysis confirmed the independent prognostic significance of PMRT for both DFS (p = 0.040) and OS (p = 0.047). Following propensity score matching (PSM), the analysis included 100 matched patients, revealing an improved prognosis for those who received PMRT (DFS: p = 0.067; OS: p = 0.043). Our study reveals favorable prognoses for pT3N0-1M0 breast cancer patients treated within contemporary therapeutic approaches. The pivotal role of PMRT in this context is evident. However, due to the retrospective design of our study and the relatively limited sample size, further investigation is imperative to validate and enhance these initial findings.

Surgical and patient-reported outcomes in an Asian female population with or without adjuvant radiotherapy after immediate free perforator flap breast reconstruction: A retrospective review

BackgroundThe majority of English literature has reported on the somewhat conflicted outcomes of the effect of radiotherapy on immediate breast reconstruction. However, data specifically related to patients of Asian descent has been scarce. This retrospective study aims to shed light on this topic to aid in the management of this group of patients. MethodsAll patients who received immediate free perforator flap-based breast reconstruction under a single surgeon over a 10-year period were included in the study. Patient characteristics, oncological and surgical data were collected. Patients were divided into post-mastectomy radiotherapy (PMRT) and non-PMRT groups. The final aesthetic outcome was assessed by a surgeon-reported outcome questionnaire. Patient satisfaction and psychological outcomes were assessed using validated patient-reported outcome (PRO) questionnaire (BREAST-Q), breast reconstruction, and postoperative module. ResultsA total of 101 women, with an average age of 44.7 ± 8.4 underwent perforator flap-based reconstruction. Fifteen patients received PMRT, with remaining 86 patients in the non-PMRT group. The mean duration of follow-up was over 5 years (p = 0.514). The recurrence rate was acceptable in the PMRT group (3/15, p = 0.129). There were no significant differences in complication rates between the two groups (p = 1.000). The aesthetic outcomes were comparable (p = 0.342). PRO appears to be lower in the PMRT group. ConclusionsImmediate breast reconstruction with PMRT in the local patient cohort is oncologically safe, acceptable complication profile, revision rate, and aesthetic outcome. PRO showed lower scores in several categories, which differ from normative data generated in the Western population. Further studies will need to examine the confounding effects of radiation in this specific population.

Long-term Surgical and Patient-Reported Outcomes Comparing Skin-Preserving, Staged Versus Delayed Microvascular Breast Reconstruction.

Skin-preserving, staged, microvascular, breast reconstruction often is preferred in patients requiring postmastectomy radiotherapy (PMRT) but may lead to complications. We compared the long-term surgical and patient-reported outcomes between skin-preserving and delayed microvascular breast reconstruction with and without PMRT. We conducted a retrospective, cohort study of consecutive patients who underwent mastectomy and microvascular breast reconstruction between January 2016 and April 2022. The primary outcome was any flap-related complication. The secondary outcomes were patient-reported outcomes and tissue-expander complications. We identified 1002 reconstructions (672 delayed; 330 skin-preserving) in 812 patients. Mean follow-up was 24.2 ± 19.3months. PMRT was required in 564 reconstructions (56.3%). In the non-PMRT group, skin-preserving reconstruction was independently associated with shorter hospital stay (β - 0.32, p = 0.045) and lower odds of 30-days readmission (odds ratio [OR] 0.44, p=0.042), seroma (OR 0.42, p=0.036), and hematoma (OR 0.24, p=0.011) compared with delayed reconstruction. In the PMRT group, skin-preserving reconstruction was independently associated with shorter hospital stay (β - 1.15, p<0.001) and operative time (β - 97.0, p<0.001) and lower odds of 30-days readmission (OR 0.29, p=0.005) and infection (OR 0.33, p=0.023) compared with delayed reconstruction. Skin-preserving reconstruction had a 10.6% tissue expander loss rate and did not differ from delayed reconstruction in terms of patient-reported satisfaction with breast, psychosocial well-being, or sexual well-being. Skin-preserving, staged, microvascular, breast reconstruction is safe regardless of the need for PMRT, with an acceptable tissue expander loss rate, and is associated with improvedflap outcomes and similar patient-reported quality of life to that of delayed reconstruction.

Post-mastectomy radiation therapy in HER-2 positive breast cancer after primary systemic therapy: Pooled analysis of TRYPHAENA and NeoSphere trials

PurposeThe role of post-mastectomy radiation therapy (PMRT) following primary systemic therapy (PST) in HER-2 positive breast cancer (Her2 + BC) remains poorly understood. The current study evaluates PMRT based on the pathological response to PST in Her2 + BC. Methods and materialsTRYPHAENA and NeoSphere are randomized phase II trials that investigated PST for Her2 + BC. Our study is a pooled analysis of both trials, including 312 node-positive patients treated with HER-2 targeted PST followed by mastectomy with or without PMRT. The primary endpoint is loco-regional recurrence-free survival (LRRFS). ResultsOur analysis included 172 (55%) patients who achieved complete nodal pathological response (ypN0) and 140 (45%) patients who did not. Patients with ypN0 had a 5-year LRRFS of 97% in both, the PMRT and no PMRT, groups (p = 0.94). Patients with ypN + had 5-year LRRFS of 89% in the PMRT group and 82% in the no PMRT group (p = 0.17). Patients with ypN1 (n = 62) disease who received PMRT (n = 40) had a 5-year LRRFS of 85% as compared to 89% in those who did not (n = 22); (p = 0.60). A significant LRRFS difference was noted in patients with ypN2-3 (n = 78) disease who received PMRT (n = 53) compared to those who did not (n = 25) (5-year LRRFS 92% vs. 75%; p = 0.019). On multivariate analysis, clinical nodal disease at diagnosis and ypN0 were significantly associated with loco-regional recurrence (LRR). ConclusionsHer2 + BC patients who achieve ypN0 after PST have excellent locoregional-control which supports de-escalation of PMRT. In contrast, patients with ypN2-3 disease derive significant benefit from PMRT. Clinical nodal stage at presentation and ypN0 status are significantly associated with LRR risk in Her2 + BC.

The prognostic differences and the effect of postmastectomy radiotherapy between post-chemotherapy ypT1-2ypN1 and de novo pT1-2N1 breast cancer.

The prognosis and the value of postmastectomy radiotherapy (PMRT) between post-chemotherapy ypT1-2ypN1 and de novo pT1-2N1 breast cancer (BC) remain controversial. We aimed to evaluate the prognostic differences and the effect of PMRT between the two patient subsets. Patients diagnosed with pT1-2N1M0 BC were identified between 2010 and 2018. The study endpoints were overall survival (OS), breast cancer-specific survival (BCSS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS). The chi-square test, Kaplan-Meier method and Cox regression analysis were used for data analysis. Total number of 2103 pT1-2N1M0 BC patients were included in the study, including 270 post-chemotherapy (97 without PMRT, 173 with PMRT) and 1833 de novo cases (993 without PMRT, 840 with PMRT). No significant differences were found between post-chemotherapy ypT1-2ypN1 and de novo pT1-2N1 BC patients in 5-year OS (p=0.068), BCSS (p=0.054), LRFS (p=0.241), DMFS (p=0.104) or DFS (p=0.08). PMRT did not improve any survival outcome in patients receiving neoadjuvant chemotherapy; however, the PMRT group had a better 5-year BCSS (97.0% vs. 95.8%, p= 0.033) in de novo pT1-2N1 BC. Cox multivariate analysis demonstrated that PMRT was a significant independent predictor of BCSS (HR 0.628; 95% CI, 0.403-0.978; p= 0.04) in de novo pT1-2N1 patients. There seemed no survival difference in post-chemotherapy ypT1-2ypN1 and de novo pT1-2N1 BC patients with contemporary systemic therapy. In addition, PMRT might be exempted in patients with post-chemotherapy ypT1-2ypN1 BC, while not in patients with de novo pT1-2N1 BC.

Reconstructive complications and early toxicity in breast cancer patients treated with proton-based postmastectomy radiation therapy.

Postmastectomy radiation therapy (PMRT) decreases the risk of locoregional recurrence and increases overall survival rates in patients with high-risk node positive breast cancer. While the number of breast cancer patients treated with proton-based PMRT has increased in recent years, there is limited data on the use of proton therapy in the postmastectomy with reconstruction setting. In this study, we compared acute toxicities and reconstructive complications in patients treated with proton-based and photon-based PMRT. A retrospective review of our institutional database was performed to identify breast cancer patients treated with mastectomy with implant or autologous reconstruction followed by PMRT from 2015 to 2020. Baseline clinical, disease, and treatment related factors were compared between the photon-based and proton-based PMRT groups. Early toxicity outcomes and reconstructive complications following PMRT were graded by the treating physician. A total of 11 patients treated with proton-based PMRT and 26 patients treated with photon-based PMRT were included with a median follow-up of 7.4 months (range, 0.7-33 months). Six patients (55%) in the proton group had a history of breast cancer (3 ipsilateral and 3 contralateral) and received previous RT 38 months ago (median, range 7-85). There was no significant difference in mean PMRT (p = 0.064) and boost dose (p = 0.608) between the two groups. Grade 2 skin toxicity was the most common acute toxicity in both groups (55% and 73% in the proton and photon group, respectively) (p = 0.077). Three patients (27%) in the proton group developed grade 3 skin toxicity. No Grade 4 acute toxicity was reported in either group. Reconstructive complications occurred in 4 patients (36%) in the proton group and 8 patients (31%) in photon group (p = 0.946). Acute skin toxicity remains the most frequent adverse event in both proton- and photon-based PMRT. In our study, reconstructive complications were not significantly higher in patients treated with proton- versus photon-based PMRT. Longer follow-up is warranted to assess late toxicities.

Comparing Radiotherapy (RT) Late Toxicities to the Reconstructed DIEP Flap in Breast Cancer Patients Treated with Neoadjuvant RT (NART) vs. Post-Mastectomy RT (PMRT)

<h3>Purpose/Objective(s)</h3> The use of PMRT in patients undergoing immediate Deep Inferior Epigastric Perforator (DIEP) flap reconstructions is well known to cause significant long-term toxicity such as flap contracture, fat necrosis and cosmetic detriment. This can lead to significant long-term pain and impact on quality of life (QOL) (Yun et al, 2018). On the other hand, NART prior to the DIEP reconstruction performed in our institution has been shown to have no detriment in safety and local control but the long-term impact on the DIEP reconstruction remains unclear (Chidley et al, 2021). The aim of this retrospective study is to compare the long-term consequences of NART followed by DIEP versus immediate DIEP with PMRT on the reconstruction. <h3>Materials/Methods</h3> Retrospective comparison of long-term toxicities was done on the patient cohort who underwent NART followed by DIEP reconstruction (from 03/2013 to 09/2019) and patients who had immediate DIEP reconstruction followed by RT (from 01/2013 to 05/2021). Clinical examination was performed to assess the presence of fat necrosis (graded using the Wagner classification et al. 2013) and flap contracture. Breast cosmesis was graded using the Kroll classification (Kroll et al, 1994). Statistical analysis was performed to identify the rate of cosmesis problem, fat necrosis and flap contracture between these two patient's cohorts. <h3>Results</h3> Total of 155 patients who underwent NART and 31 patients who went through PMRT were analyzed. The median age of each cohort is 48 and 49 respectively for NART vs PMRT (p=0.26). Majority of patients in the NART and PMRT cohort received 50.4Gy/28# (78.6% [121] vs 74.2% [23]). Median follow up for NART and PMRT group was 32.5 months and 28.8 months respectively. No difference in local control was reported (98.1% NART vs 100% PMRT). Patients who had NART reported a higher satisfaction rating with their cosmesis. This was reported as ‘excellent to good' in 96.1% for NART compared to 80.1% for PMRT p<0.001. In addition, the risk of developing a flap contracture was significantly increased in patients who had PMRT (1.9% NART vs 41.9% PMRT; p<0.001). This was described as minimal in 29% and moderate in 12.9%. The risk of developing fat necrosis rate was also significantly increased in patients who had PMRT (12.9% NART vs 19.4% PMRT; p<0.001). While all fat necrosis in the NART cohort was grade 2, 50% of patients in the PMRT cohort had pain as well (grade 4). <h3>Conclusion</h3> Our retrospective analysis suggests that PMRT following immediate DIEP has significantly higher risk of late toxicities compared to NART followed by DIEP reconstruction. Whether this translates to a meaningful impact on QOL can only be determined by a randomized study.

The Role of Post-Mastectomy Radiation Therapy in Patients with pT3N0 Breast Cancer and Low Genomic Recurrence Score

<h3>Purpose/Objective(s)</h3> The role of post-mastectomy radiotherapy (PMRT) in patients with pT3 pN0 breast cancer remains controversial. We previously showed a correlation between PMRT and improved overall survival (OS) in pT3N0 patients who do not receive chemotherapy. However, it is unknown whether this correlation extends to patients with low genomic recurrence score (RS). In this analysis, we used the National Cancer Database (NCDB) to investigate the benefit of PMRT in pT3N0 patients with low RS. <h3>Materials/Methods</h3> We performed an analysis of NCDB patients with pT3N0 breast cancer who had low Oncotype DX RS (ORS) (< 25) and did not receive systemic chemotherapy. Patients were matched for baseline patient, tumor, and treatment characteristics using inverse probability of treatment weighting to minimize the impact of potential confounding variables. We stratified patients based on receipt of PMRT and compared OS using Kaplan-Meier estimates. Univariate and doubly-robust multivariable analyses were used to correlate PMRT and various baseline characteristics with OS. <h3>Results</h3> We identified 444 patients with pT3N0 breast cancer who had undergone mastectomy and had low-risk genomic assay scores who did not receive systemic chemotherapy. After IPTW matching, there were no significant differences in baseline patient characteristics. In the PMRT group, 44% received treatment to the chest-wall only, and 66% patients received chest wall and regional nodal irradiation. PMRT was associated with improved overall survival on both the univariate (HR=0.201; 95% CI=0.05-0.78; p=0.021) and doubly-robust multivariable analyses (HR=0.128; 95% CI=0.02-0.66; p=0.014). Receipt of endocrine therapy was also found to significantly improve overall survival (p=0.02). We attempted to repeat the analysis in patients with RS >25 who received chemotherapy, but we only identified a total of 78 such patients and could not perform a robust analysis. <h3>Conclusion</h3> This cohort analysis shows a strong correlation between PMRT and improved OS in pT3N0 patients with low ORS who do not receive chemotherapy. It is possible that with the de-escalation of chemotherapy and axillary surgery in this patient population in the modern era, the benefit of locoregional treatment with radiotherapy is magnified. Our analysis suggests that prospective data are needed before de-escalation of radiotherapy for these patients based on ORS.

Effect of postmastectomy radiotherapy on pT1-2N1 breast cancer patients with different molecular subtypes: A real-world study based on the inverse probability of treatment weighting method.

To investigate the significance of postmastectomy radiotherapy (PMRT) for different molecular subtypes of female breast cancer T1-2N1M0 based on inverse probability of treatment weighting (IPTW). The data of breast cancer patients diagnosed between 2010 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) database were extracted. According to the status of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2), the patients were classified into luminal-A (HR+/HER2-), luminal-B (HR+/HER2+), HER2-enriched (HR-/HER2+), and TNBC (HR-/HER2-) subtypes. The association between radiation therapy and breast cancer-specific survival (BCSS) and Overall survival (OS) was retrospectively analyzed. Inverse probability of treatment weighting (IPTW) was applied to balance measurable confounders. Among the 16 894 patients, 6 055 (35.8%) were in the PMRT group and 10 839 (64.2%) were in the nonPMRT group, with a median follow-up of 48 months. There were 1003 deaths from breast cancer and 754 deaths from other causes. After IPTW, the covariates between groups reached complete equilibrium, the multifactorial Cox regression analysis showed that PMRT significantly prolonged OS and BCSS in Luminal-A and TNBC subtype breast cancer patients, yet it brought little significant survival advantage in Luminal-B and HER2-enriched subtype patients. Our study demonstrates a beneficial impact for PMRT on OS and BCSS among Luminal-A and TNBC subtype breast cancer patients with T1-2N1 disease.

Optimal Timing of Delayed Microvascular Breast Reconstruction after Radiation Therapy.

The purpose of this study was to determine the optimal timing of delayed microvascular breast reconstruction after completion of postmastectomy radiation therapy (PMRT). The authors evaluated whether the timing of reconstruction after PMRT completion affects the development of major postoperative complications. We hypothesize that delayed microvascular breast reconstruction can be safely performed within 12 months of PMRT completion. A retrospective chart review of microvascular, autologous breast reconstructions at Brigham and Women's Hospital from 2007 to 2019 was performed. Logistic regression analysis and marginal estimation methods were used to estimate the probability of any major complication (flap compromise requiring operative intervention, hematoma formation requiring evacuation, infection requiring readmission, and flap necrosis requiring operative debridement) occurring in 2-month intervals after PMRT. Patients were classified as having undergone reconstruction 0 to 12 months after PMRT (group 1), 12 to 18 months after PMRT (group 2), or 18 to 50 months after PMRT (group 3). A total of 303 patients were identified. All patients received postmastectomy radiation (n = 143 group 1, n = 57 group 2, n = 103 group 3). Mean follow-up time was 71.4 ± 38 months. Patients in group 1 were significantly younger and more likely to have undergone neoadjuvant chemotherapy (p < 0.05). Major complications occurred in 10% of patients. There was no significant difference in the development of major complications between the three groups (p = 0.57). Although not statistically significant, the probability of any major complication peaked 2 to 6 months after PMRT completion. There was no significant difference in major complications among patients who underwent delayed, microvascular breast reconstruction within versus beyond 1 year of PMRT completion. These findings suggest that delayed microvascular breast reconstruction can be safely performed beginning 6 months after PMRT completion.

Abstract P3-19-27: Prognostic impact of postmastectomy radiation therapy in breast cancer patients with T1, 2 and 1-3 lymph nodes from Japan Breast Cancer Registry

Abstract Background: The effectiveness of postmastectomy radiation therapy (PMRT) in patients with pT1-2 and 1-3 lymph node metastases remains controversial in the current clinical practice. Patients and Methods: Using data from the Japanese National Clinical Database (NCD) between 2004 and 2012, we evaluated the association of PMRT with recurrence and breast cancer mortality. Patients who underwent mastectomy and axillary node dissection and were diagnosed as pT1-2 with 1-3 node metastases were enrolled. Patients who received presurgical treatment were excluded. We compared clinicopathological factors and prognosis between patients with PMRT (PMRT group) and without PMRT (No-PMRT group). The primary endpoint was the locoregional recurrence (LRR) rate. We also assessed the impact of PNRT according to the number of node metastasis. We considered death as a competing event.Results: Among 8,914 enrolled patients, PMRT group included 492 patients (5.5%), and No-PMRT group did 8,422 patients (94.5%). Patients of PMRT group were younger, had a larger tumor and more node metastases than patients of No-PMRT group. There is no difference in breast cancer subtype between two groups. A median observation time was 6.3 years (arnge 5.0- 9.7 years). There was no significant difference between PMRT group and No-PMRT group in LRR rate (4.0% v.s. 5.0%, P=0.61), any recurrence rate (13.8% v.s. 11.8%, P=0.23), and breast cancer mortality rate (6.0% v.s. 4.3%, P=0.08) at 5 years. Multivariate analysis revealed no significant association between PMRT and LRR while LRR is significantly associated with tumor size larger than 2cm (hazard ratio [HR] 1.48, 95%confidence interval [CI] 1.21-1.82 in 2.1-3.5cm, HR 1.97, 95%CI 1.53-2.53 in 3.6-5.0cm) 2 (HR1.25 95%CI 1.02-1.52) or 3 node metastases (HR 1.40. 95%CI 1.10-1.79), triple-negative subtype (HR 1.64, 95%CI 1.21-2.23). According to the number of node metastasis, LRR in PMRT group was significantly lower than that of No-PMRT group among patients with 3 node metastases (2.6% v.s. 7.0%, P=0.03) while there was no significant difference between two groups among patients with 1 or 2 node metastases. In multivariate analysis, HR was relatively lower in patients with 3 node metastases (HR 0.37, 95%CI 0.11 -1.19) comparing to the patients with 1 (HR 0.97, 95%CI 0.53- 1.77) or 2 node metastases (HR 1.06, 95%CI 0.53-2.09). Tumor size was significantly associated with LRR in patients with 1 (HR 1.51, 95%CI 1.13- 2.02) or 2 node metastases (HR 1.45, 95%CI 1.02-2.07). Chemotherapy was significantly associated with LRR among the patients with 2 (HR 0.57, 95%CI 0.40-0.82) or 3 node metastases (HR 0.4, 95%CI 0.25-0.65).Conclusions: Among the patients with T1-2 and 1-3 node metastases, PMRT was not associated with a reduced risk of LRR in the latest Japanese cohort. Advances in systemic therapy might the main reason to reduce the LRR rate rather than PMRT in this population. The administration of PMRT should be tailored considering the individual risks of LRR, such as 3 node metastases. Citation Format: Akimitsu Yamada, Naoki Hayashi, Hiraku Kumamaru, Masayuki Nagahashi, Shiori Usune, Hiroaki Miyata, Takashi Ishikawa, Kazutaka Narui, Itaru Endo, Shigeru Imoto, Shinji Ohno, Hiromitsu Jinno. Prognostic impact of postmastectomy radiation therapy in breast cancer patients with T1, 2 and 1-3 lymph nodes from Japan Breast Cancer Registry [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-27.

Abstract P3-21-03: Timing of post-mastectomy radiation therapy and autologous reconstruction outcomes: A retrospective review

Abstract Introduction: Post-mastectomy radiation therapy (PMRT) is an important adjuvant treatment in patients with locally advanced breast cancer, shown to decrease the rate of locoregional recurrence and improve overall survival. Autologous breast reconstruction is the standard-of-care in patients who require PMRT. However, there is no clear superior approach regarding the optimal timing of reconstruction in these patients. Our goal was to compare outcomes between patients who underwent autologous reconstruction either before or after undergoing PMRT. Methods: We performed a retrospective chart review of patients who underwent all stages of mastectomy, autologous reconstruction, and PMRT at UCSF between 2015 and 2021. Clinical and surgical characteristics and complications were collected and assessed. We then matched these patients by age, BMI and autologous reconstruction type to a cohort of patients who underwent both mastectomy and autologous reconstruction at UCSF who did not require PMRT. Groups were compared by both timing of and receipt of radiation. Results: Nineteen patients underwent mastectomy, autologous reconstruction, and PMRT at UCSF between 2015 and 2021. Thirteen of these patients underwent reconstruction after receiving PMRT, while six of these patients underwent reconstruction followed by PMRT. These nineteen patients were matched by age, BMI and flap type to a cohort of 19 patients who underwent mastectomy and autologous reconstruction at UCSF. The cumulative early complication rate was 16% in the radiated group and 21% in the non-radiated group. This included infection requiring IV antibiotics, hematoma, wound breakdown, mastectomy flap necrosis, and arterial or venous thrombosis [see Table 1 for breakdown by group]. No flap loss occurred in any group. Fat necrosis was observed in 16% of radiated patients and 11% of non-radiated patients. Revision rates were equal between the radiated and non-radiated groups at 58% (including currently planned revisions). There was no strong correlation between complication rate and either total radiation dose or time between radiation and reconstruction (r=-0.5 and r=-0.1). Discussion: Complication rates between all groups were similar. Notably, the only observed infections, both requiring admission and IV antibiotics, occurred in the pre-reconstruction PMRT group. Given the potential for tissue expander infection and increased number of outpatient visits, further investigation is warranted in immediate autologous reconstruction in those patients who require PMRT, not only to decrease the hospital and patient burden, but to improve patient satisfaction. Larger cohort studies are required to draw further conclusions on the effect of PMRT and timing of autologous reconstruction, and to investigate patient-reported outcomes. Table 1.Complication rate by groupComplicationRadiated. Pre-recon PMRT. Post-recon PMRTNon-radiatedCumulative early complications16%. 15%. 17%21%Infection11%. 16%. 0%0%Hematoma0%. 0%. 0%5%Wound breakdown11%. 8%. 17%5%Mastectomy flap necrosis5%. 0%. 17%11%Arterial or venous thrombosis0%. 0%. 0%5%Fat necrosis16%. 15%. 17%11%Revision58%. 62%. 50%58% Citation Format: Laura Barnes, Deborah Martins, Merisa Piper. Timing of post-mastectomy radiation therapy and autologous reconstruction outcomes: A retrospective review [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-21-03.

Patterns of postmastectomy radiation therapy in clinically node-positive breast cancerpatients with pathologically negative lymph nodes after neoadjuvant chemotherapy.

To analyze postmastectomy radiation therapy (PMRT) utilization and its association with overall survival (OS) in patients presenting with node-positive breast cancer who are pathologically node-negative (ypN0) after neoadjuvant chemotherapy (NAC). Using the National Cancer Data Base (NCDB), we identified patients diagnosed between 2004 and 2013 with clinical T1-4 node-positive nonmetastatic breast cancer who received NAC and underwent mastectomy with pathologically negative lymph node sampling. Multivariable regression models identified factors associated with PMRT use. The Cox proportional hazards model was used to evaluate predictors of mortality. The study included 8766 clinically node-positive patients who met the study criteria. PMRT was delivered to 61.5% of patients. Overall PMRT utilization rate increased over the study period from 54.4% in 2004 to 65.2% in 2011. Predictors of PMRT use included larger tumor size, increasing clinical N stage, higher grade disease, receipt of hormone therapy, and a greater number of lymph nodes examined. The unadjusted 5-year OS was 84.1% in the PMRT group and 83.8% in the non-PMRT group (p = NS). PMRT was not significantly associated with survival on multivariable analysis (hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.73-1.03). The delivery of PMRT has increased over time in women presenting with clinically node-positive breast cancer who convert to ypN0 after NAC. While we identified multiple independent socioeconomic and clinical predictors of both PMRT utilization and survival, PMRT itself was not significantly associated with survival.

Post-mastectomy Radiation Therapy in Triple-Negative Breast Cancer Patients: Analysis of the BEATRICE Trial.

Post-mastectomy radiation therapy (PMRT) improves locoregional control and overall survival in patients with breast cancer. With the evolution of systemic therapy, the benefit of PMRT in patients with triple-negative disease requires further evaluation. BEATRICE is a phase III randomized clinical trial that examined the efficacy of bevacizumab in patients with triple-negative breast cancer (TNBC). The current study is a retrospective analysis of data on patients enrolled and treated with mastectomy and systemic therapy. The primary endpoint was determining the effect of PMRT on locoregional recurrence rates (LRR). Hazard ratios were estimated using Cox regression, and LRR curves were generated by the Kaplan-Meier method. In total, 940 patients were included in our analysis, of whom 359 (38.2%) received PMRT while 581 (61.8%) did not. At median follow-up of 5 years, no significant difference in LRR was noted between the PMRT and no PMRT groups in node-negative patients (HR = 1.09). Patients with N1 disease had 5-year LRR-free survival of 96% for PMRT versus 91% for no PMRT (HR = 0.46). Most N2 patients received PMRT and had 5-year LRR-free survival of 76%. PMRT benefit in TNBC patients treated with modern systemic therapy is lower than historical reports. Delivery of PMRT in patients with N1 disease enrolled in the BEATRICE trial was not shown to improve local control. As this might be due to patient selection for PMRT, future randomized controlled trials are required to assess the role of PMRT in this patient population.

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.

76P The clinical survival benefit of postmastectomy radiotherapy patients screened form T1-2N1M0 breast cancer according to tumour size and the number of lymph nodes

The prognostic value of postmastectomy radiotherapy (PMRT) in T1-2N1 breast cancer patients remains controversial. The aim of this study was to evaluate the benefit of PMRT in overall survival (OS) of T1-2N1 breast cancer patients based on the combination of lymph node numbers and tumor size. We used data extracted from the Surveillance, Epidemiology, and End Results program. Women diagnosed as T1-2N1M0 breast cancet betweent 2004 and 2015 was abstracted. The primary outcome was overall survival. Multivariate Cox proportional hazard models were used to estimate the independent prognostic factors and to assess hazard ratios (HR) and their 95% confidence intervals (CI) with OS. Subgroup analysis of patients with different node positive number and tumor size were enrolled in our study. A total of 29366 patients included the final analysis, 20167 (68.7%) patients in no-PMRT group and 9199 (31.3%) patients in PMRT group. Multivariable Cox model analysis showed that radiotherapy could improve the overall survival (Hazard ratio [HR]0.89;95%CI 0.83-0.96, P=0.001) for T1-2N1 breast cancer patients. Subgroup analysis based on different tumor burden types showed that there was not all survival benefit to every subgroup. Analysis shows the benefits of PMRT are associated with exaltation in breast cancer overall survive rate among the patients with tumor size 4-5 cm and two or three positive lymph nodes respectively (HR 0.69; 95%CI 0.51-0.94; P=0.017or HR0.65; 95%CI 0.44-0.95; P= 0.027,separately). PMRT also has a beneficial effect for the patients with tumor size 2-3 cm and three positive lymph nodes (HR 0.61; 95%CI 0.48-0.78; P<0.001), but not in the others. The integration of tumor size and the number of positive lymph nodes status seems to be a reliable predictor of overall survival from radiotherapy, which may enable physician to make clinical decision more precisely and effectually about PMRT, especially in the low -risk breast cancer subgroup.

Utility of post mastectomy radiotherapy among patients with T1/ T2 N1 disease: A retrospective cohort study

BackgroundPakistan has the highest incidence of breast cancer among Asian Countries but there is insufficient representation of local data addressing breast cancer treatment and outcome. We sought to determine the role of post-mastectomy radiotherapy (PMRT) in T1- T2 breast cancer with 1–3 positive axillary lymph nodes. MethodsData was reviewed retrospectively of total 755 patients out of which 291 received PMRT and 464 did not from two large breast cancer centres. ResultsWith a median follow up of 78 months, 4 (4.5%) patients developed loco regional recurrence (LRR) in the PMRT group while a substantial number 74 (24.4%) recurred in the non PMRT group (p = 0.000). Loco regional free survival rate (LRFS) and overall survival rate (OS) was significantly better for PMRT patients than non-PMRT patients (P = <0.000). Multivariate analysis identified young age, lymphovascular invasion, extra capsular extension, triple negative and ER/PR negative were independent prognostic factors affecting loco regional free survival (LRFS). ConclusionDisease recurrence is a substantial issue in 1–3 node group despite early stage, PMRT has an instrumental effect in improving LRFS and OS.