Indications For Postmastectomy Radiotherapy Research Articles

Intraoperative frozen section of subareolar tissue in nipple-sparing mastectomy: Towards a less is more approach

BackgroundNipple preservation contributes to aesthetic outcome and quality of life in women undergoing Skin-Sparing Mastectomy (SSM) with immediate breast reconstruction for the treatment of breast cancer. Intraoperative Frozen Section (IFS) has been advocated to facilitate conversion from Nipple-Sparing Mastectomy (NSM) to SSM in cases with positive subareolar margins. This study investigated the application of IFS at our comprehensive cancer centre. MethodsIn this single-centre retrospective study, for all patients who underwent therapeutic NSM with IFS from 2000 to 2021 pathological reports, patient- and tumour characteristics were retrieved. ResultsIn total 640 women were included in whom 662 intended NSMs with IFS had been performed. Sensitivity and specificity of frozen section compared with definitive histopathology were 75.2% and 98.5% respectively. In six women with a false positive result, the nipple had been removed. In 16 out of 32 women with a false negative result, the nipple was excised in a second procedure. In total 115 nipples were resected. In 40% of these nipples, no residual disease was detected. DiscussionIFS is a moderately sensitive and highly specific diagnostic tool to detect positive subareolar margins. An alternative approach is to omit frozen section but take intraoperative biopsies of the sub areolar margin, which are postoperatively analysed with definitive formalin-fixed paraffin-embedded histopathology. This allows for shared decision making regarding nipple excision in cases where minimal disease is found in subareolar tissue or cases with an indication for post-mastectomy radiotherapy.

Abstract GS4-05: Phase II randomized trial of conventional versus hypofractionated post-mastectomy proton radiotherapy

Abstract Purpose/Objectives: Proton therapy is under investigation in breast cancer as a strategy to reduce heart and lung exposure, which is associated with late cardiopulmonary adverse events and secondary malignancy. To date, studies investigating postmastectomy radiotherapy (PMRT) with protons have used conventional fractionation. We hypothesized that condensing treatment to 15 fractions would be safe based on evidence that breast cancer is more sensitive to higher dose fractions than surrounding normal tissues. Materials/Methods: We conducted a randomized non-inferiority phase II trial comparing conventional and hypofractionated proton PMRT with primary endpoint of 24-month complication rate (defined as grade 3 or higher late adverse events using CTCAE, v 4.0 and/or unplanned surgical intervention in patients undergoing mastectomy with reconstruction). With a 10% non-inferiority margin the study ensured 80% power and had a one sided-type I error rate of 0.05. Cardiotoxicity was assessed with serial transthoracic conventional and 2-dimensional speckle tracking echocardiography (2D-STE). Eligibility included age ≥ 18 years with non-inflammatory breast cancer resected by mastectomy with indications for PMRT. Assignment of treatments was balanced with respect to immediate breast reconstruction (IBR). Conventional fractionation group received 50 Gy in 25 fractions of 2 Gy, and hypofractionation group received 40.05 Gy in 15 fractions of 2.67 Gy (RBE 1.1). Target volume included the chest wall and axillary, supraclavicular, and internal mammary lymph nodes. All patients were treated with multi-field optimized pencil beam scanning (intensity modulated proton therapy). Results: Between 2016 and 2018, 82 patients were enrolled and randomized (41 conventional, 41 hypofractionation). Median patient age was 52 years. 32.9% were staged T3-T4 and 79.3% node positive at diagnosis. 57 of 82 patients (69.5%) elected IBR. The median mean heart dose was 0.49 Gy and the median ipsilateral lung volume receiving 40% of prescription or greater (V40%) was 13.6%. No significant changes on conventional or 2D-STE at end-of-treatment or 3-month follow-up compared to baseline were observed. The rate of ≥ grade 2 acute dermatitis was lower with hypofractionation (44% vs 15%, p = 0.006). Other ≥ grade 2 acute adverse events including esophagitis (0 vs 5%), infection (5% vs 2.4%) and skin hyperpigmentation (7.3% vs 4.8%) were not significantly different between the two arms. With a median follow-up of 38.3 months, the 24-month complication rate was conventional 14.6% vs hypofractionation 17.1% (absolute difference 2.4%, p=0.17, 95% CI [-, 15.7%]). In patients with IBR, 6 of 28 (21.4%) conventional and 7 of 29 (24.1%) hypofractionated patients developed complications (p =0.80). There was no significant difference in 3-year disease-free survival between the conventional (89.4%; 95% CI 80.0 – 99.8%) and hypofractionated (92.4%, 95% CI 84.5 – 100.0%) arms (p = 0.91). One local recurrence occurred in the hypofractionated arm simultaneous with regional and distant relapse. The remaining 6 recurrences were isolated distant events. Conclusions: Proton PMRT provided excellent locoregional control and normal tissue sparing. There were no subclinical echocardiographic changes indicative of radiation-induced cardiac dysfunction. Hypofractionation resulted in comparable disease control, tolerability and reconstruction outcomes as conventional fractionation. Although non-inferiority of hypofractionation could not be established based on the upper bound of the 95% confidence interval for complication rate being greater than 10%, both conventional and hypofractionation may be considered appropriate regimens for ongoing phase 3 randomized trials comparing photon and proton radiotherapy. Citation Format: Robert Mutter, Sharmila Giri, Briant Fruth, Nicholas Remmes, Aman Anand, Kathryn Ruddy, Hector Villarraga, Sebastian Santos Patarroyo, Elizabeth Yan, Kenneth Merrell, Lisa McGee, Tamara Vern-Gross, Bradley Stish, Robert Gao, Judy C. Boughey, Sean Park, Kimberly Corbin, Carlos Vargas. Phase II randomized trial of conventional versus hypofractionated post-mastectomy proton radiotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-05.

Abstract ED6-3: How to reconcile novel reconstructive techniques with the need to radiate

Abstract The indication for postmastectomy radiotherapy (PMRT) is mainly based on tumor stage and the extent of lymph node involvement. The results of EBCTCG meta-analysis (EBCTCG Lancet, 2014) support the need of radiation therapy (RT) for patients with one to three axillary metastatic lymph nodes (LN), as well as for patients with > 3 affected LN. In nearly 40% of patients with mastectomy (ME) RT is required. According to the plastic surgery statistics report 2020 approximately 80% of patients seeking breast reconstruction in the USA receive an implant-based breast reconstruction (IBBR), while 18% undergo autologous reconstruction (ASoPS 2020). PMRT, regardless of reconstructive method, has been found to have a detrimental effect on outcomes with increased postoperative complications and decreased patient satisfaction. Nevertheless, even in this cohort the number of breast reconstruction (BR) is increasing over time. Surgical techniques for ME and BR are advancing constantly. With the increasing use of skin-sparing ME (SPM) techniques, particularly nipple-sparing ME (NSM), one stage IBBR (single-stage direct-to-implant, DTI) become more popular. With the availability of supportive materials such as synthetic/biological mesh or acellular dermal matrix (ADM) there has been a significant improvement in pre-pectoral implant reconstruction. The impact of PMRT on the outcomes of pre-pectoral IBRR has been recently summarized in a systemic review and meta-analysis by Awadeen (Aesth Plast Surg, 2022). Wound infection, capsular contraction and implant loss were significantly more frequent in the irradiated than in the non-irradiated breasts. Several studies describe the delayed/2-stage IBBR in the setting of PMRT as more promising and discuss different timings of exchange from expanders to implant. In one systematic review, PMRT to permanent implants reduced the rate of reconstructive failure compared to TE (J Surg Oncol,2015). After prosthetic-based BR and RT, conversion to autologous reconstruction can always be considered. Recommendations for immediate autologous reconstruction vary when PMRT is required. PMRT can result in wound complications, fat necrosis and volume loss, but overall cosmetic results are better than with IBBR and PMRT. When undergoing delayed reconstruction after PMRT, the optimal time from PMRT to reconstruction is unknown. In patients with a history of RT, NCCN-guidelines (V.4.2022) recommend autologous reconstruction as the preferred reconstruction option. Fat grafting, which can optimize tissue perfusion and wound healing, is playing an emerging role in breast surgery. Lipofilling can be used to improve the thickness of the mastectomy flap and to recontour breast defects after PMRT. There is an increasing awareness for better understanding of the different reconstruction types to define target volumes depending on the varying risk for residual tissue and potential recurrences. The ESTRO-ACROP guidelines discuss adapted dose distribution in accordance with the different locations of the implant (pre-or sub-pectoral) (Radiotherapy and Oncology, 2019). The risks and benefits of immediate versus delayed as well as implant-based versus autologous reconstruction must be considered for each individual patient and should be planned in a multidisciplinary setting, especially when PMRT is required. Citation Format: Christine Solbach. How to reconcile novel reconstructive techniques with the need to radiate [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED6-3.

Protocol for the postoperative radiotherapy in N1 breast cancer patients (PORT-N1) trial, a prospective multicenter, randomized, controlled, non-inferiority trial of patients receiving breast-conserving surgery or mastectomy

BackgroundPostoperative radiotherapy (PORT) could be useful for pN1 breast cancer patients who have undergone breast-conserving surgery (BCS) or mastectomy. However, the value of regional nodal irradiation (RNI) for BCS patients, and the indications for post-mastectomy radiotherapy (PMRT) for pN1 breast cancer mastectomy patients, have recently been challenged due to the absence of relevant trials in the era of modern systemic therapy. “PORT de-escalation” should be assessed in patients with pN1 breast cancer.MethodsThe PORT-N1 trial is a multicenter, randomized, phase 3 clinical trial for patients with pN1 breast cancer that compares the outcomes of control [whole-breast irradiation (WBI) and RNI/PMRT] and experimental (WBI alone/no PMRT) groups. PORT-N1 aims to demonstrate non-inferiority of the experimental group by comparing 7-year disease-free survival rates with the control group. Female breast cancer patients with pT1-3 N1 status after BCS or mastectomy are eligible. Participants will be randomly assigned to the two groups in a 1:1 ratio. Randomization will be stratified by surgery type (BCS vs. mastectomy) and histologic subtype (triple-negative vs. non-triple-negative). In patients who receive mastectomy, dissection of ≥5 nodes is required when there is one positive node, and axillary lymph node dissection when there are two or three positive nodes. Patients receiving neoadjuvant chemotherapy are not eligible. RNI includes a “high-tangent” or wider irradiation field. This study will aim to recruit 1106 patients.DiscussionThe PORT-N1 trial aims to verify that PORT de-escalation after BCS or mastectomy is safe for pN1 breast cancer patients in terms of oncologic outcomes and capable of reducing toxicity rates. This trial will provide information crucial for designing PORT de-escalation strategies for patients with pN1 breast cancer.Trial registrationThis trial was registered at ClinicalTrials.gov (NCT05440149) on June 30, 2022.

Postmastectomy radiotherapy: a review.

We review the role of postmastectomy radiotherapy (PMRT) in the management of patients with early breast cancer. PMRT in patients with 4 or more involved axillary lymph nodes is the current standard of care but the indications for PMRT in patients with 1-3 involved nodes remain controversial. The Early Breast Cancer Trialists' Collaborative Group meta-analysis of randomised trials of PMRT provides the most comprehensive level 1 evidence base. However, its applicability in contemporary practice in the context of recent multidisciplinary advances in surgery, radiation therapy and systemic therapy remains challenging. The lack of consensus on the indications for PMRT in patients with 1-3 positive nodes underpins the variations in the national and international guidelines on PMRT. We emphasise the need for contemporary randomised trial data, and the potential to refine patient selection for PMRT using novel biomarkers of recurrence and radiosensitivity.

Breast reconstruction and radiotherapy: a literature review

Breast cancer is the most common malignancy in women worldwide. After mastectomy, many women wish to reconstruct the affected breast and immediate breast reconstruction has been proven oncologically safe compared to mastectomy only. In addition, indications for post-mastectomy radiotherapy (PMRT) sessions are becoming more frequent, due to their relationship with reduced mortality and locoregional recurrence. For this reason, many women who opted for immediate reconstruction underwent radiotherapy with implants or expanders. The objective of this study was to compare the outcome of patients with breast cancer undergoing adjuvant radiotherapy after breast reconstruction with an implant or expander with that of patients who did not need irradiation. A literature review was carried out on the CAPES Journal Portal. The studies are unanimous when it comes to the increased risk of complications between control groups and patients who have undergone PMRT. Reconstruction failure rates were lower and the esthetic results were better in surgeries with implants compared with tissue expanders. Autologous surgeries are apparently safe and should be considered in the context of PMRT. This review did not find sufficient scientific evidence to determine the best technique and the best period for radiotherapy in PMRT indications. The choice of the surgical technique and the time of radiotherapy must be at the discretion of the surgeon and multidisciplinary team of each service, always in a shared decision with the patient.

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.

Adjuvant radiation therapy after immediate implant-based breast reconstruction

The role of radiotherapy in the postmastectomy setting with substantial lymph node burden or locally advanced disease has been well described. In the last decade, the indications for postmastectomy radiotherapy (PMRT) have expanded in light of a measurable disease-free survival benefit, even in T1–2N1-patient subgroup. Concurrently, immediate breast reconstruction (IBR) rates after mastectomy are rapidly increasing. Optimal integration of IBR and PMRT is challenging, as PMRT has a known deleterious effect on reconstruction outcomes and IBR has been reported to pose challenges to PMRT delivery. Implant-based reconstruction is the most common type of IBR performed nowadays. This article reviews the current problems regarding integration of the implant-based IBR with optimum radiation delivery and discusses the advantages and disadvantages of each reconstruction method with PMRT.

Abstract OT3-06-01: Prevention and management of residual breast tissue following radical mastectomy and skin-sparing and nipple-sparing mastectomy in oncologic and high-risk breast cancer patients - A multicentre questionnaire study

Abstract 1. Background As the presumed oncological risk of skin-sparing (SSM) and nipple-sparing mastectomy (NSM) putatively relies on remaining fibroglandular tissue within the nipple-areolar-complex and the skin flap complete resection of breast parenchyma is of uttermost importance. Contrary, residual fibroglandular tissue has been detected in up to 50% of breast specimens following NSM and 13% after SSM. Studies focusing on the prevention and management of residual breast tissue (RBT) are scarce. 2. Trial design and eligibility criteria A prospective multicenter questionnaire study addressing the subjects preventive measures, targeted flap thickness and detection and management of RBT will be performed. Certified breast care centres in Austria, Germany, Switzerland, England and the United States of America will be contacted via E-mail and asked to participate in the study. The following questions will be asked via a web-based questionnaire: I. General data including institution, profession, number of operations the institution/ the participating surgeon performs in 1 year II. Preventive Measures i. In case of NSM/SSM do you determine the thickness of the subcutaneous tissue preoperatively? ii. In case of NSM or SSM do you mark sites where fibroglandular breast tissue approximates closely to the skin preoperatively? iii. Do you perform a frozen subareolar biopsy in the course of NSM? iv. What do you use for breast tissue preparation to separate breast tissue from the pectoralis major muscle/from the skin? III.Flap thickness i. What is your target flap thickness when you perform NSM/SSM in patients with breast cancer/in high-risk patients? ii. Are there factors that influence your target flap thickness? IV. Detection of residual breast tissue i. Do you screen for residual breast tissue following radical ME/NSM/SSM? ii. What imaging modality do you use for aftercare? iii. Is the imaging modality you use for aftercare patient-dependent or standardized? iv. When do you perform the first breast imaging in the course of aftercare after the completion of reconstruction in patients with breast cancer/in high-risk patients? V. Management of residual breast tissue i. Is residual breast tissue an indication for reoperation in a patient with breast cancer and negative resection margins/in a high-risk patient? ii. Is residual breast tissue an indication for post-mastectomy radiotherapy in a patient with breast cancer and negative resection margins? iii. In case of residual breast tissue do you intensify your follow-up care? 3. Aims The primary objective of the study is to assess the applied preventive and treatment measures of RBT following mastectomy in oncologic and high-risk breast cancer patients in certified breast care centres in Austria, Germany, Switzerland, England and the USA. Based on these expert opinions guidelines for the course of action regarding RBT will be developed. 4. Statistical methods Descriptive statistics will be performed. Citation Format: Christine Deutschmann, Georg Pfeiler. Prevention and management of residual breast tissue following radical mastectomy and skin-sparing and nipple-sparing mastectomy in oncologic and high-risk breast cancer patients - A multicentre questionnaire study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-06-01.

Metastatic Lobular Carcinoma of the Breast Presenting with Small Bowel Metastases: Case Report and Literature Review

Introduction: Invasive lobular carcinoma (ILC) is the second most common histologic type of breast cancer, representing 5% to 15% of invasive tumors. ILC tends to spread to bones, lungs, central nervous system, reproductive organs, and the gastrointestinal tract (GI tract). The most commonly affected organs in the GI tract are the stomach, small intestine, followed by colon and rectum. Case presentation: A 78-year-old woman who was referred to our institution after having a bowel obstruction that required a diagnostic laparoscopy where they identified an obstructing ulcerative lesion in the distal ileum that was managed with a segmental bowel resection. Pathology report showed an invasive lobular breast carcinoma that occluded 90% of the bowel lumen. A PET/CT scan revealed a left breast tumor with increased metabolism. The patient was staged as a clinical cT4b, cN0, cM1 left breast invasive lobular carcinoma (ER/PgR positive, HER-2 negative). She was managed with endocrine therapy with Letrozole (an eight-week course). A follow-up PET/CT showed a peritoneal hypermetabolic nodule adjacent to the previous ileal anastomosis. The lesion decreased in size and metabolic activity. In a multidisciplinary fashion, the endocrine therapy was extended for another three months. Another follow-up PET/CT scan was performed three months after the identification of the peritoneal implant that showed that the nodule increased in size and in metabolism. The lesion continued to decrease significantly in size and became metabolically inactivity. Due to the good breast response and the possibility that the ileal nodule could be a granuloma, she underwent an exploratory laparoscopy with excision of the peritoneal nodule, and a modified left radical mastectomy with immediate breast reconstruction (complex wound closure). The final pathology report of the nodule was negative for malignancy. She continued on endocrine therapy and underwent whole breast irradiation four weeks after the operation. Currently, she is free of disease with no evidence of local, regional, or distant recurrence, and she is still on endocrine therapy. Discussion: The time interval between primary breast cancer and gastrointestinal involvement may range from synchronous presentation to as long as 30 years. The clinical manifestations in GI lobular breast cancer metastasis may range from non-specific complaints to acute GI symptoms, such as a bowel obstruction. There are multiple controversies in the management of ILC. Systemic treatment should be initiated as soon as possible. Indications for postmastectomy radiotherapy are also controversial, given the propensity for multifocal/multicentric tumors and late recurrences, sometimes in atypical locations. Five years of postoperative adjuvant hormonal therapy is an option for women with poor prognosis. Remissions are observed in 32% to 53% of patients. Conclusion: Metastatic lobular carcinoma of the breast has a wide range of clinical presentations. Patients with a history of breast cancer who present with new GI tumors should have these lesions evaluated for evidence of metastasis through histopathologic and immunohistochemical analysis, this will allow for appropriate management. Currently, breast cancer management involves a multidisciplinary approach including surgery, radiotherapy, and systemic medical therapy, and the treatment must be tailored to the patient’s needs.

Preoperative Radiotherapy Trials to Facilitate Immediate Breast Reconstruction after Mastectomy

Postmastectomy radiotherapy (PMRT) is often a component of treatment algorithms for locally advanced or node-positive breast cancer. Breast reconstruction may be delayed or not performed due to negative effects of PMRT on the reconstruction. Administering radiotherapy in the preoperative setting allows for immediate breast reconstruction (IBR) to be performed in patients who have indications for PMRT and desire IBR. This review summarizes the current literature on this new concept. Most prospective treatment protocols included neoadjuvant systemic therapy followed by radiotherapy (RT) dose of 50–50.4 Gy conventionally fractionated and mastectomy with immediate autologous reconstruction after 6–8 weeks. There were no cases of IBR being aborted due to technical complications and overall postoperative complications ranged from 3 to 36%. These were typically non-operatively managed, and cosmetic results when evaluated were favorable. Initial oncologic outcomes indicate low locoregional recurrence rates (≤ 10%) and high 5-year overall survival rates of 87–98%. Although published studies are heterogeneous in nature, they suggest that preoperative RT followed by mastectomy with IBR is technically feasible and safe. Larger prospective studies with longer follow-up times may establish this as a new standard in the multidisciplinary treatment of high-risk breast cancer.

04. Post-mastectomy radiotherapy in patients with immediate breast reconstruction – Results from the iBRA-2 (Immediate Breast Reconstruction and Adjuvant therapy) prospective cohort study

Introduction: Long-term data now indicates that post-mastectomy radiotherapy (PMRT) may positively impact on overall survival. As a result, the indications for PMRT are widening. Rates of immediate breast reconstruction (IBR) are increasing, but IBR remains controversial in the context of planned PMRT. The aim of this study was to examine current practice of PMRT in patients undergoing mastectomy with and without IBR in the iBRA-2 prospective cohort study.

Prognostic factors for breast cancer patients with T1-2 tumor and 1-3 positive axillary nodes treated using total mastectomy without radiotherapy.

Prospective randomized trials have demonstrated that postmastectomy radiotherapy (PMRT) improves not only locoregional recurrence-free survival, but also overall survival for node-positive breast cancer patients. Subset analyses in previous trials have shown that improvement of overall survival with PMRT is not always demonstrated for patients with 1-3 positive nodes. Indications for PMRT are still marginal for patients with pathological invasion 5cm in diameter and 1-3 positive nodes. The aim of this study was to clarify poor prognostic factors for breast cancer patients with pathological invasion size 5cm and 1-3 positive nodes. Participants comprised 428 breast cancer patients with T1-2 tumor and 1-3 positive axillary nodes (pT1-2N1) treated using total mastectomy without radiotherapy. Correlations between clinicopathological characteristics and 10-year Kaplan-Meier estimates of locoregional recurrence-free survival, disease-free survival, and overall survival were retrospectively analyzed. Median follow-up was 98months. Locoregional recurrence was observed in 20 patients (4.7%), and distant recurrence was observed in 70 patients (16.4%). Disease-free survival rate was 80.8%, and overall survival rate within the study period was 90%. Multivariate analysis demonstrated that favorable prognostic factors for locoregional recurrence-free survival were the presence of chemotherapy and positive hormone receptor status, and for disease-free survival were presence of chemotherapy, pT1 tumor, and single positive node. Physicians may consider these favorable prognostic factors in decision to eliminate PMRT from patients with the borderline indications.

2062. Patterns of Post-Mastectomy Radiotherapy In Patients With Immediate Breast Reconstruction – Results From The Ibra-2 (Immediate Breast Reconstruction And Adjuvant Therapy) Prospective Cohort Study

Background: Long-term data now indicates that post-mastectomy radiotherapy (PMRT) may positively impact on overall survival. As a result, the indications for PMRT in women with breast cancer are widening. Rates of immediate breast reconstruction (IBR) are increasing, but IBR remains controversial in the context of planned PMRT. The current practice of PMRT is unknown. The aim was this study was to determine patterns of PMRT in patients undergoing mastectomy with and without IBR in the iBRA-2 prospective cohort study.

Radiotherapy and breast reconstruction.

Indications for post mastectomy radiotherapy are widening to a larger group of mastectomy patients and breast reconstruction rates following mastectomy are rising all over the world, this leading breast surgeons to face breast reconstruction in a growing number of patients who will undergo radiotherapy. Increased morbidity is associated with all forms of breast reconstruction in the setting of postmastectomy radiotherapy and in patients who previously underwent chest wall radiotherapy. Different attitudes towards breast reconstruction in the radiotherapy setting are presented in literature. The level of evidence and quality of studies investigating breast reconstruction in the setting of PMRT and in patients who previously underwent chest wall radiotherapy are low. The reconstructive option in the radiotherapy setting must be tailored on the single patient according with patients' characteristics and wishes, always considering that the best reconstructive timing must be driven by the best oncological timing.

A prognostic score model to determine which breast cancer patients with 1-3 positive lymph nodes after modified radical mastectomy should receive radiotherapy.

There is no consensus on the indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes. To identify patients for whom PMRT may be indicated, we used a prognostic score model with the SEER database to retrospectively analyze 8049 patients with one to three positive lymph nodes who underwent mastectomy with or without PMRT between 2010 and 2013. Kaplan-Meier analysis showed that PMRT patients had better overall survival (OS) than no-PMRT patients (P < 0.001); however, there was no difference in cancer-specific survival (CSS) (P = 0.530). Multivariate analysis with Cox regression showed that grade (P < 0.001), tumor size (P < 0.001), and progesterone receptor status (P < 0.001) were independent prognostic factors for OS. To diminish bias, we used 1:1 propensity score matching analysis and prognosis score model, which revealed that PMRT patients had better OS and CSS than no-PMRT patients (P < 0.001). In a concrete subgroup analysis of PMRT patients, significant improvements in OS were observed in patients scoring 0, 1, or 2. PMRT patients scoring 2 also had improved CSS. The magnitude of the OS and CSS difference with PMRT correlated with the prognostic score (P < 0.001). These results suggest PMRT in breast cancer patients with one to three positive lymph nodes should be based on patient factors, tumor biology, and prognostic score.

Erratum to: Axillary Micrometastases and Isolated Tumor Cells Are Not an Indication for Post-mastectomy Radiotherapy in Stage 1 and 2 Breast Cancer.

Randomized trials demonstrate equivalent locoregional control with sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) for T1–2 micrometastatic breast cancer, but include few mastectomy patients. Consensus is lacking on indications for post-mastectomy radiotherapy (PMRT) in this population. Herein, we evaluate locoregional recurrence (LRR) in an unselected, modern cohort of T1–2 breast cancer patients with micrometastases or isolated tumor cells (ITCs; N0i+/N1mi) having a mastectomy. We identified patients with T1–2N0i+/N1mi breast cancer treated with mastectomy from January 2006 to December 2011. Recurrent, bilateral, and neoadjuvant cases were excluded. The primary outcome of interest was LRR. Overall, 352 patients [211 (60%) with ITCs and 141 (40%) with micrometastases] were identified. 162 (46%) patients had SLNB alone and one node was positive in 295 (84%) cases; 31 (9%) patients had PMRT and 95% had systemic therapy. At a median 6 years of follow-up, the overall crude LRR rate was 2.8% (n = 9), with no axillary recurrences, and the crude LRR rate was 3.9% among those who had SNB alone. Those with LRR had a median age of 55 years, median tumor size of 1.7 cm, and ductal histology; the majority were high-grade (89%) and estrogen receptor positive (78%), with one positive node (89%). There was no association between LRR and receipt of PMRT (p = 0.4), SLNB versus ALND (p = 0.2), or number of positive nodes (p = 0.7) using the log-rank test. LRR was infrequent among T1–2N0i+/N1mi patients treated with mastectomy without PMRT, with no axillary failures, suggesting that PMRT or nodal radiotherapy are not routinely indicated in this population.

Axillary Micrometastases and Isolated Tumor Cells Are Not an Indication for Post-mastectomy Radiotherapy in Stage 1 and 2 Breast Cancer.

Randomized trials demonstrate equivalent locoregional control with sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) for T1-2 micrometastatic breast cancer, but include few mastectomy patients. Consensus is lacking on indications for post-mastectomy radiotherapy (PMRT) in this population. Herein, we evaluate locoregional recurrence (LRR) in an unselected, modern cohort of T1-2 breast cancer patients with micrometastases or isolated tumor cells (ITCs; N0i+/N1mi) having a mastectomy. We identified patients with T1-2N0i+/N1mi breast cancer treated with mastectomy from January 2006 to December 2011. Recurrent, bilateral, and neoadjuvant cases were excluded. The primary outcome of interest was LRR. Overall, 352 patients [211 (60%) with ITCs and 141 (40%) with micrometastases] were identified. 162 (46%) patients had SLNB alone and one node was positive in 295 (84%) cases; 31 (9%) patients had PMRT and 95% had systemic therapy. At a median 6years of follow-up, the overall crude LRR rate was 2.8% (n=9), with no axillary recurrences, and the crude LRR rate was 3.9% among those who had SNB alone. Those with LRR had a median age of 55years, median tumor size of 1.7cm, and ductal histology; the majority were high-grade (89%) and estrogen receptor positive (78%), with one positive node (89%). There was no association between LRR and receipt of PMRT (p=0.4), SLNB versus ALND (p=0.2), or number of positive nodes (p=0.7) using the log-rank test. LRR was infrequent among T1-2N0i+/N1mi patients treated with mastectomy without PMRT, with no axillary failures, suggesting that PMRT or nodal radiotherapy are not routinely indicated in this population.

Are there patients with T1 to T2, lymph node-negative breast cancer who are "high-risk" for locoregional disease recurrence?

Indications for postmastectomy radiotherapy (PMRT) in patients with T1 to T2, lymph node-negative (N0) breast cancer with "high-risk" features are controversial. The European Organization for Research and Treatment of Cancer (EORTC) 22922 and National Cancer Institute of Canada Clinical Trials Group MA20 trials reporting improved 10-year disease-free survival with lymph node irradiation included patients with high-risk N0 disease, but, to the authors' knowledge, benefits in patients receiving modern systemic therapy are uncertain. The authors retrospectively identified patients with T1 to T2N0 disease who were treated with mastectomy from January 2006 through December 2011. High-risk features included age <40 years, multifocality/multicentricity, lymphovascular invasion, medial/central tumor location, and high nuclear grade. Among 672 eligible patients, only 15 received PMRT and were excluded. Of the remaining 657 patients, 187 (28%) had 1 high-risk feature and 449 patients (68%) had ≥ 2 high-risk features. A total of 36 patients with unknown tumor grade were excluded from risk analysis. Approximately 98% of patients underwent sentinel lymph node biopsy alone and 86% received adjuvant systemic therapy. At a median of 5.6 years of follow-up, the locoregional disease recurrence (LRR) rate was 4.7% (31 patients). Increasing tumor size was found to be associated with LRR (hazard ratio, 1.70; P = .006), whereas other high-risk features were not (all P > .05). Receipt of systemic therapy decreased the LRR rate (hazard ratio, 0.40; P = .03). Although crude LRR rates increased from 3.8% to 9.4% with 1 versus ≥ 4 high-risk features, the number of risk factors was not found to be significantly associated with LRR (P = .54). In the current study, a low crude LRR rate (4.7%) was observed in a large unselected cohort of patients with T1 to T2N0 breast cancer with high-risk features who were treated with mastectomy and systemic therapy without PMRT. Although increasing tumor size and the omission of systemic therapy were found to be predictive, other features did not confer a higher LRR risk either independently or together, and do not by themselves mandate the use of PMRT in this patient population. Cancer 2017;123:2626-33. © 2017 American Cancer Society.

Abstract P3-13-07: Are there patients with T1-T2, node-negative breast cancer who are high-risk for locoregional recurrence?

Abstract Background: Indications for post-mastectomy radiotherapy (PMRT) in T1-T2, node negative (N0) breast cancer patients with “high-risk” features are controversial based on lack of consensus as to what constitutes “high-risk”, and variable results of small retrospective studies. The EORTC 22922 and MA20 trials reporting improved 10-year disease-free survival with nodal irradiation included high-risk N0 patients but these patients were not analyzed separately and did not receive modern systemic therapy. We sought to evaluate long-term locoregional control in T1-T2N0 patients with high-risk features undergoing mastectomy in the contemporary era. Methods: We retrospectively identified patients with T1-T2N0 breast cancer with ≥1 high-risk feature treated with mastectomy from 1/2006-12/2011. High-risk features were defined as age &amp;lt;40 years, multifocal/multicentric disease, lymphovascular invasion (LVI), medial or central tumor location, and high nuclear grade. The primary outcome of interest was rate of LRR. Results: Among 672 patients meeting inclusion criteria, 187 (28%) had 1 risk factor: 21 (3%) were age &amp;lt;40 years, 132 (20%) were multifocal/multicentric, and 34 (5%) had LVI; 449 (67%) patients had ≥2 high-risk features, and 36 patients with unknown grade were excluded from risk analysis. PMRT was received by only 15 (2%) patients. Clinicopathologic characteristics of the 657 patients treated without PMRT are shown in Table 1. Table 1: Clinicopathologic characteristics, n = 657 Median (Range)Age, years49 (24-89)Tumor size, cm1.4 (&amp;lt;0.1-5.0) n (%)Ductal histology566 (86%)High nuclear grade*266 (40%)LVI232 (35%)Multifocal/multicentric447 (68%)Medial/central tumor226 (34%)Receptor status** ER+/HER2-438 (67%)HER2+123 (19%)ER-/HER2-70 (11%) n (%)Rate of LRR# of risk factors* 1183 (28%)3.8%2265 (40%)5.3%3143 (22%)4.9%4 or 532 (5%)9.4%*Unknown grade in 34 cases, excluded from risk analysis **Unknown receptor status in 26 cases Sentinel node biopsy alone was performed in 98% of these patients. A median of 4 lymph nodes were retrieved (range 1-15). Adjuvant systemic therapy was received by 86% of patients. At median 5.6 years of follow-up, overall LRR rate was 4.7% (n = 31), with the majority (55%) of events involving the chest wall. Increasing tumor size was associated with LRR (HR 1.70, 95% CI 1.26–2.29, p = 0.006), while age, histology, grade, subtype, LVI, multifocality/multicentricity, and tumor location were not (all p &amp;gt; 0.05). Although rate of LRR increased from 3.8% to 9.4% with 1 vs. ≥4 high-risk features, a comparison of 1 vs. 2 vs. 3 vs. ≥4 risk factors was not significant by Kaplan-Meier estimation (p = 0.54). Conclusions: A low LRR rate of 4.7% was seen in this large unselected cohort of T1-T2N0 cancers with "high-risk" features treated by mastectomy and systemic therapy without PMRT. While increasing tumor size was predictive, other features did not confer a higher risk of LRR either independently or together, and do not by themselves mandate the use of PMRT in this population. Citation Format: Mamtani A, Patil S, Stempel M, Morrow M. Are there patients with T1-T2, node-negative breast cancer who are high-risk for locoregional recurrence? [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 P3-13-07.