Surgery For Early Breast Cancer Research Articles

Abstract PO5-22-05: ULTRA-HYPOFRACTIONATED ADJUVANT RADIATION THERAPY FOR BREAST CANCER (UK FAST FORWARD TRIAL): A REAL LIFE SCENARIO ANALYSIS IN A DEVELOPING COUNTRY

Abstract Introduction: Selected patients showed non-inferior outcomes after conservative surgery for early breast cancer in the FAST-Forward UK (26Gy in 5 fractions) when compared to standard to date treatment. This study triggered an important change in radiation therapy routines across the world. We aimed to establish a pattern of treatment related events at a third-world country cancer center. Methods: We retrospectively analyzed all patients treated with 26Gy in 5 fractions (1 week) from January 2020 to June 2023. All data was exported and analyzed for demographics. A clinical profile was traced, dosimetric parameters and side effects assessed based on individual inquiries to each patient, per and post treatment. A strict medical record was kept in order to understand patterns of side effects and results. Results: 101 individuals were identified. Mean age was 64 years, 48 (47%) patients experienced radiation dermatitis of any grade, 33 (32%) grade 1, 9 (8%) grade 2, 6 grade 3 or 4 (5%). Patients older than 60 years showed to be a significant factor for dermatitis development (34 over a total of 48 - 70%) and 8 (53%) over 15 had grade 2 or higher dermatitis. 27 (26%) developed radiation dermatitis during sessions. 21 (20%) took 7 or less days to heal; 27 (26%) had a recovery longer than one week at an average age of 65 years - being the majority of dermatitis grade 1. Reported toxicities were sharp pain 31 (30%), burning pain 24 (23%), edema 17 (16%) and pruritus 5 (4%). At the time of this study was completed, 3 reported deaths (2%) were reported - with a 97% rate of survival. Conclusions: The fast forward trial regimen has 3 years since its publication. Our study shows that in a selected group of breast cancer patients, this novel model has shown to be a safe alternative for adjuvant radiation therapy following breast conservative surgery, results corroborating with published data. To the best of our knowledge, this is the largest single center group analyzed and published. Citation Format: Renne Bart, Daniel Przybysz, Ramon Ferrari, Leonardo Franco, Carlos Almeida, Paulo Canary. ULTRA-HYPOFRACTIONATED ADJUVANT RADIATION THERAPY FOR BREAST CANCER (UK FAST FORWARD TRIAL): A REAL LIFE SCENARIO ANALYSIS IN A DEVELOPING COUNTRY [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 PO5-22-05.

Assessment of inferior pedicle therapeutic mammoplasty as apart of volume displacement techniques of oncoplastic breast surgery for early breast cancer

Assessment of inferior pedicle therapeutic mammoplasty as apart of volume displacement techniques of oncoplastic breast surgery for early breast cancer

Acute adverse events of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for early breast cancer in Japan: an interim analysis of the multi-institutional phase II UPBEAT study.

The applicability of ultra-hypofractionated (ultra-HF) whole-breast irradiation (WBI) remains unknown in Japanese women. This study aimed to evaluate the safety and efficacy of this approach among Japanese women and report the results of an interim analysis performed to assess acute adverse events (AEs) and determine whether it was safe to continue this study. We enrolled Japanese women with invasive breast cancer or ductal carcinoma in situ who had undergone breast-conserving surgery, were aged ≥ 40years, had pathological stages of Tis-T3 N0-N1, and had negative surgical margins. Ultra-HF-WBI was delivered at 26Gy in five fractions over one week. When the number of enrolled patients reached 28, patient registration was paused for three months. The endpoint of the interim analysis was the proportion of acute AEs of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) within three months. Of the 28 patients enrolled from seven institutes, 26 received ultra-HF-WBI, and 2 were excluded due to postoperative infections. No AEs of grade ≥ 3 occurred. One patient (4%) experienced grade 2 radiation dermatitis, and 18 (69%) had grade 1 radiation dermatitis. The other acute grade 1 AEs experienced were skin hyperpigmentation (n = 10, 38%); breast pain (n = 4, 15%); superficial soft tissue fibrosis (n = 3, 12%); and fatigue (n = 1, 4%). No other acute AEs of grade ≥ 2 were detected. Acute AEs following ultra-HF-WBI were within acceptable limits among Japanese women, indicating that the continuation of the study was appropriate.

The Accessible Clinical Application Progress of Supine Fixation Technique in Radiotherapy After Breast Conserving Surgery for Early Breast Cancer in China

Radiation therapy (radiotherapy) is one of the important methods for comprehensive treatment of breast cancer. Radiotherapy after breast conserving surgery for early breast cancer can not only achieve local control rate and long-term survival rate similar to total mastectomy, but also meet patients' pursuit of higher quality of life. With the development of intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), helical tomotherapy (HT), and other advanced radiotherapy technique, the consistency of patient position fixation during radiotherapy is the key to ensure the implementation of accurate radiotherapy. Due to the special and high activity of breast organs, there is no unified fixation method for breast conserving postoperative radiotherapy. This article reviews the clinical application and research progress of various accessible supine fixation techniques in early breast cancer postoperative radiotherapy in recent years. This paper analyzes the clinical application method and clinical application effect of various techniques, compares the advantages and disadvantages of each technology. It is found that breast bracket is the most widely used for classical breast cancer radiotherapy. In any fixation technique, it is still a practical problem for the clinic to solve the problem of the normal location of the breast activity and the consistency of the radiation. It is recommended that the position of the supposition fixation technique should be selected according to the patient's BMI, breast size and target area.

Whole breast ultrafractionation radiotherapy after breast‐conserving surgery in early breast cancer: A single‐center, prospective, observational study from China

AbstractObjectiveThis single‐center, prospective, observational study was designed to investigate the toxicities, patient‐reported outcome (PRO), and dosimetric analysis of whole breast ultrafractionation radiotherapy (RT) after breast‐conserving surgery (BCS) in early breast cancer (BC).Patients and methodsPatients diagnosed with BC stage I, II and treated with BCS were enrolled. A dose of 26 Gray (Gy) in five fractions was prescribed to the whole breast and tumor bed. Clinical endpoints included toxicities, PRO, and dosimetric analysis. PRO was measured by the European Organization for Research and Treatment of Cancer general quality of life questionnaire (EORTC QLQ‐C30) and the BC‐specific questionnaire (EORTC QLQ‐BR23) questionnaires.ResultsBetween January 2022 and June 2023, 62 female patients were enrolled. The median age was 45 years. Most patients (83.9%) were diagnosed with pathological stage I disease. The median planning target volume (PTV) was 456.4 mL. The minimum, maximum, and mean doses, and D95 (dose of PTV irradiated volume more than 95%) to PTV were 20.2, 28.8, 27.2, and 26.3 Gy, respectively. The median mean lung dose and percentage lung volume receiving 8 Gy (V8) were 3.6 Gy and 13.4%, respectively. The median mean heart dose, V1.5 (percentage of organ volume irradiated with 1.5 Gy or higher), and V7 (percentage of organ volume irradiated with 7 Gy or higher) were 0.6 Gy, 6.8%, and 0.4%, respectively. Cosmetic effects before RT showed no obvious differences compared to that post RT. No toxicities of grade 3 or higher occurred. Five patients had asymptomatic radiation pneumonia (grade 1), and 12 patients had radiation dermatitis (grade 1). No factor was significantly related to radiation dermatitis or radiation pneumonia. For the EORTC QLQ‐C30 and QLQ‐BR23 questionnaires, all function and symptom scores before RT had no significant differences compared with that after RT, 1−2 months after RT, and 3−4 months after RT. Ultrafractionation RT did not worsen PRO. The 1‐year crude local control was 100%.ConclusionWhole breast ultrafractionation RT after BCS in early BC has no severe toxicities and does not affect PRO. These results need to be further validated with a longer follow‐up and a larger sample size.

Accelerated partial breast irradiation: Current evidence and future developments

AbstractWhole breast irradiation after breast‐conserving surgery for early breast cancer has become one of the standard treatment modes for breast cancer and yields the same effect as radical surgery. Accelerated partial breast irradiation (APBI) as a substitute for whole breast irradiation for patients with early breast cancer is a hot spot in clinical research. APBI is characterised by simple high‐dose local irradiation of the tumour bed in a short time, thus improving convenience for patients and saving costs. The implementation methods of APBI mainly include brachytherapy, external beam radiation therapy, and intraoperative radiotherapy. This review provides an overview of the clinical effects and adverse reactions of the main technologies of APBI and discusses the prospects for the future development of APBI.

A Clinical Analysis of Prognosis and Patient-Reported Outcomes of Oncoplastic Breast-Conserving Surgery for Early Breast Cancer: A Retrospective Cohort Study.

Approximately 25-30% of patients suffer from breast deformity and/or asymmetry after conventional breast-conserving surgery (CBCS). Generally, it is thought that oncoplastic breast-conserving surgery (OBCS) results in an improved cosmetic result; however, studies comparing the prognosis and aesthetic outcomes of CBCS and OBCS in early breast cancer (EBC) are inadequate. A total of 143 patients were included in this retrospective cohort study; 53 underwent OBCS and 90 underwent CBCS. The resected weight, complications, esthetic results, patient satisfaction, and recurrence rate were compared between the groups. Patient-reported outcomes (PRO) were assessed by the BREAST-Q questionnaire. The mean age of the patients in OBCS group was 43.8 years. This was younger than that in CBCS group (49.1 years, p < 0.001). Postoperative complications (11.3% vs. 8.9%, p = 0.64) and re-excision (5.7% vs. 6.7%, p > 0.99) rates were similar. The OBCS group had higher breast satisfaction and psychosocial well-being than the CBCS group (75 vs. 63, p < 0.001 and 84 vs. 77, p = 0.05); however, sexual well-being (56 vs. 66, p = 0.05) and physical well-being (65 vs. 76, p < 0.001) were worse in OBCS. After 42.3 (range: 12.6-69.2)-month median follow-up, no difference in event-free survival (EFS) was demonstrated between the groups (p = 0.13). Although OBCS has the better aesthetic outcomes and identical oncological safety in comparison with CBCS, the sexual and physical well-being in OBCS are not improved for Asian patients. Hence, choosing an appropriate procedure may be more important for the typically small to moderate-sized breasts characteristic of Asian females unlike Westerners. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Adjuvant therapeutic strategy decision support for an elderly population with localized breast cancer: A monocentric cohort retrospective study.

Guidelines for the management of elderly patients with early breast cancer are scarce. Additional adjuvant systemic treatment to surgery for early breast cancer in elderly populations is challenged by increasing comorbidities with age. In non-metastatic settings, treatment decisions are often made under considerable uncertainty; this commonly leads to undertreatment and, consequently, poorer outcomes. This study aimed to develop a decision support tool that can help to identify candidate adjuvant post-surgery treatment schemes for elderly breast cancer patients based on tumor and patient characteristics. Our approach was to generate predictions of patient outcomes for different courses of action; these predictions can, in turn, be used to inform clinical decisions for new patients. We used a cohort of elderly patients (≥ 70 years) who underwent surgery with curative intent for early breast cancer to train the models. We tested seven classification algorithms using 5-fold cross-validation, with 80% of the data being randomly selected for training and the remaining 20% for testing. We assessed model performance using accuracy, precision, recall, F1-score, and AUC score. We used an autoencoder to perform dimensionality reduction prior to classification. We observed consistently better performance using logistic regression and linear discriminant analysis models when compared to the other models we tested. Classification performance generally improved when an autoencoder was used, except for when we predicted the need for adjuvant treatment. We obtained overall best results using a logistic regression model without autoencoding to predict the need for adjuvant treatment (F1-score = 0.869).

Utility of radiotherapy for the management of local tumor progression in patients with early breast cancer

The generally accepted standard in early breast cancer surgery today is breast-conserving surgery with external beam radiation therapy, which is comparable in results to previously widely performed radical mastectomy and even has an advantage in terms of overall survival and control. Until now, there are areas of discussion and a number of questions remain related to the methodology of irradiation of patients with breast cancer, namely: is it advisable to irradiate the axillary zone after radical resection for early breast cancer? Does irradiation of axillary lymph nodes provide regional control comparable to lymphadenectomy, and whether it can be an alternative to lymph node dissection? Whether provides an irradiation of axillary lymph nodes comparable with regional lymph node dissection the control over patients with a positive sentry lymph node? A lot of studies have been published so far, answers to questions derived from what we present in this work.

Microwave ablation without subsequent lumpectomy versus breast-conserving surgery for early breast cancer: a propensity score matching study

Purpose To compare the efficacy of ultrasound-guided percutaneous microwave ablation (MWA) without subsequent lumpectomy and breast-conserving surgery (BCS) in patients with early breast cancer (BC). Materials and methods This retrospective cohort study enrolled 106 patients with early BC (T0/1/2 N0/1 M0) treated by MWA (n = 21) or BCS (n = 85) from October 2014 to December 2020. Propensity score matching (PSM) was performed to balance the baseline characteristics between MWA and BCS groups. The tumor progression, overall survival (OS), disease-specific survival (DSS), complications, and cosmetic results were compared. Results After PSM, there were 21 patients with balanced baseline characteristics in each group. After a median follow-up of 43 months (range, 15–89 months), there was no significant difference in tumor progression (10% vs 2%, p = 0.18), OS (96% vs 99%, p = 0.36), DSS (100% vs 99%, p > 0.99), and complications (0% vs 19%, p = 0.58). The operation time of MWA was shorter (60 min vs 101 min, p < 0.001) than that of BCS. For the management of metastatic lymph nodes, five (5/21, 24%) patients with six metastatic nodes underwent ablation in the MWA group and three patients (3/21, 14%) with six metastatic nodes underwent axillary lymph node dissection in the BCS group. All the patients in the MWA group reported excellent cosmetic results, but 29% of BCS patients expressed dissatisfaction with breast asymmetry (10%) and scar formation (19%) (p < 0.001). Conclusion This pilot study indicated that in selected early BC patients, microwave ablation without subsequent lumpectomy had comparable tumor control effect with breast-conserving surgery and better cosmetic results at an intermediate follow-up. Highlights MWA without subsequent lumpectomy has a comparable interim survival effect and better cosmetic results as BCS in the treatment of selected early breast cancer. MWA has the potential to be a viable and promising therapeutic option for breast cancer patients reluctant or intolerant to surgery with the advantage of minimal invasion.

Peritumoral infiltration of local anesthetic before surgery in early breast cancer: a comment

This is a comment on a study recently published about peritumoral infiltration of local anesthetic before surgery in early breast cancer. Previously, animal models and a randomized study for stage IV breast cancer patients inferred that the removal of the primary tumor resulted in increased growth factors and worse distant disease control. Therefore, breast cancer surgery might not be a strictly local intervention. In this new randomized study, the intervention was a peritumoral infiltration of local anesthetic — lidocaine 0.5% in the six tumor margins, as an attempt to limit the systemic repercussions of surgery. Although the adjuvant treatment available for the study seems outdated, leading us to question the external validation, limited resources may have increased the power of surgery. Unknown mechanisms during surgery can change the patient’s journey, and it is our duty to look at surgical studies with due seriousness.

High wavenumber Raman spectroscopy for intraoperative assessment of breast tumour margins.

Optimal oncological results and patient outcomes are achieved in surgery for early breast cancer with breast conserving surgery (BCS) where this is appropriate. A limitation of BCS occurs when cancer is present at, or close, to the resection margin - termed a 'positive' margin - and re-excision is recommended to reduce recurrence rate. This is occurs in 17% of BCS in the UK and there is therefore a critical need for a way to assess margin status intraoperatively to ensure complete excision with adequate margins at the first operation. This study presents the potential of high wavenumber (HWN) Raman spectroscopy to address this. Freshly excised specimens from thirty patients undergoing surgery for breast cancer were measured using a surface Raman probe, and a multivariate classification model to predict normal versus tumour was developed from the data. This model achieved 77.1% sensitivity and 90.8% specificity following leave one patient out cross validation, with the defining features being differences in water content and lipid versus protein content. This demonstrates the feasibility of HWN Raman spectroscopy to facilitate future intraoperative margin assessment at specific locations. Clinical utility of the approach will require further research.

Optimal radiotherapy after breast-conserving surgery for early breast cancer: A network meta-analysis of 23,418 patients

PurposeIn order to explore whether partial breast irradiation can replace hypofractionated whole breast irradiation and whether the former two are superior to conventional fractionated whole breast irradiation, we conducted a network meta-analysis based on the data from the latest randomized controlled trials to evaluate the efficacy of these radiotherapy modalities. Material and methodsData from eligible studies were analyzed to determine the published events for ipsilateral breast tumor recurrence, distant metastasis, total deaths, and non-breast cancer-related deaths. In the case of low or high heterogeneity, the fixed-effect or random-effect model was used for statistical analysis respectively. NMA was performed by using the node-splitting model for two-category data among three radiotherapies based on a Bayesian method. ResultsA total of 23,418 patients were included in 16 studies. For ipsilateral breast tumor recurrence, both pairwise (OR=1.9; CI95%: 1.2 -2.8; p<0.05) and indirect (OR=1.7; CI95%: 1.2 -2.4; p<0.05) comparison of three radiotherapies by network meta-analysis showed that conventional fractionated whole breast irradiation was significantly better than partial breast irradiation. Indirect comparison of three radiotherapies by network meta-analysis showed that hypofractionated whole breast irradiation was significantly better than partial breast irradiation (OR=1.6; CI95%: 1.0 -2.5; p<0.05). Network and paired meta-analyses found no significant differences in other endpoints among the three radiotherapies. ConclusionOverall, this network meta-analysis showed that partial breast irradiation was related to the increase of ipsilateral breast tumor recurrence compared with hypofractionated or conventional fractionated whole breast irradiation in patients with early-stage breast cancer.

Lack of Prognostic Value of Pretreatment Neutrophil-to-Lymphocyte Ratio in Early Breast Cancer

Background: Breast cancer is a highly heterogeneous disease with large differences in the risk of recurrence. An elevated neutrophil-to-lymphocyte ratio (NLR) is correlated with a poor prognosis in a variety of tumors, and although it is still controversial in breast cancer, there are multiple studies, including meta-analysis, suggesting this. The purpose of this study was to analyze the prognostic value of preoperative NLR in an Argentine population of patients with nonmetastatic breast cancer, not exposed to neoadjuvant treatment. Methods: Retrospective multicenter cohort study that includes patients over 18 years of age from three centers in the city and province of Buenos Aires who have had surgery for early breast cancer between January 1, 1999, and December 31, 2014. Based on the previous literature, a cutoff value of 2.0 was defined. Results: A total of 791 patients were eligible for the analysis. Median age was 55 years (IQR 45–65). Median NLR was 1.92 (IQR 1.50–2.56). The distribution of groups according to the 8th edition of the AJCC was 54.1% for stage I, 35.6% stage II, and 10.4% stage III. Among the different tumor phenotypes, 79.0% were HR+/HER2−, 11.4% were HR+ or−/HER2+, and 9.2% were HR−/HER2−. With a median follow-up of 5.3 years, 112 patients (14.2%) had disease recurrence. Stage III patients had a higher NLR than stage I and stage II patients (p = 0.002). The rest of the clinical and pathological characteristics did not show differences in the groups according to NLR. There were no differences in relapse-free survival according to the NLR (p = 0.37), and itdid not change after adjusting for other prognostic variables. Conclusion: We consider it is important to determine the efficacy of prognostic markers that are easily accessible and of simple, systematic application. However, NLR does not appear to be an independent prognostic factor for recurrence in our population. In this sense, we consider it is important to publish negative results in order to avoid publication bias.

The impact of neoadjuvant treatment (NAT) on surgery in early breast cancer (EBC): A real-world data study.

e12609 Background: NAT is being used with increasing frequency in the multimodal treatment of EBC. Oncologically, NAT provides an opportunity to assess response to early systemic therapy and tailor adjuvant treatment. The surgical objective of NAT is down staging the tumor, which may lead to improved chances of breast conservation surgery; potentially decreasing surgical morbidity. Down staging of axillary disease may also lead to minimizing the need for complete axillary lymph node dissection (ALND) and its associated surgical morbidity. We aimed to describe the potential impact of NAT on surgical de-escalation in the primary breast tumor and axilla in patients (pts) with HER2-positive, node-positive EBC treated in the community setting. Methods: We conducted a retrospective cohort study using a nationwide US electronic health record-derived de-identified database (Flatiron Health). Pts were diagnosed from Jan 1, 2011 to Sep 30, 2021, had reported clinical staging cN≥1, underwent primary breast surgery (index date), and had records indicating initiation of systemic treatment before surgery. Early clinical benefit includes, post-NAT: a) nodal pathologic complete response (pCR; pN=0); b) pCR (absence of residual invasive disease in the breast and axillary lymph nodes at NAT completion, subsequently confirmed at primary surgery); c) down staging (lowered T or N stage). Surgical operations recorded at index date were ALND and sentinel node excision (SNE), mastectomy (MT), and lumpectomy (LT). Results: 174 pts were included. At diagnosis, median age was 55 years, 162 pts (93%) presented with invasive ductal carcinoma, and &lt;5 had bilateral BC. 124 pts (71%) were treated with dual HER2 blockade. As for early clinical benefit, nodal pCR was achieved in 106 pts (61%), pCR in 90 (52%), and down staging in 137 (79%). Types of surgical procedure for the axilla were SNE only for 62 pts (36%), ALND only for 84 (48%), and SNE and ALND for 26 (15%). Surgical procedures for the breast were MT for 118 pts (68%), of which 59 were bilateral, and LT for 55 (32%). Compared with not achieving nodal pCR, achieving nodal pCR was associated with increased odds of SNE only (odds ratio [OR] 2.59 [95% confidence interval (CI) 1.28, 5.53]), decreased odds of ALND (OR 0.47 [95% CI 0.23, 0.93]), increased odds of LT (OR 2.05 [95% CI 1.00, 4.39]), and decreased odds of MT (OR 0.47 [95% CI 0.22, 0.96]). Conclusions: In a real-world population of pts with HER2-positive EBC, NAT use was associated with early clinical benefit, potentially leading to less invasive primary surgery of the breast and axilla. The high use of MT and bilateral MT despite a high pCR rate demonstrates the multiple factors at play behind surgical and pt decision making. These data illustrate how NAT use can benefit pts by de-escalating surgical treatment options. Limitations include the modest sample size and lack of association between early and long-term clinical benefit.

Primary results of ANZ 1002: Post-operative radiotherapy omission in selected patients with early breast cancer trial (PROSPECT) following pre-operative breast MRI.

572 Background: Selective use of radiotherapy (RT) after surgery for early breast cancer (EBC) has been an elusive goal. The role of breast MRI in localised EBC is controversial. We aimed to determine if preoperative MRI could identify patients with EBC in whom the ipsilateral invasive recurrence (IIR) rate was sufficiently low without RT, such that RT might be safely omitted. Here we report primary and secondary outcomes, and imaging/biopsy findings for occult lesions. Methods: PROSPECT is a prospective single-arm study. Criteria for omission of RT included age at least 50, nil/minimal or mild Background Parenchymal Enhancement (BPE) on MRI, unifocal pT1N0 cancer, not Triple Negative (TNBC), no LVI. All patients who underwent PROSPECT MRI were included in the analysis. Imaging findings on MMG, US and MRI were documented and all biopsies were recorded. Pathology of lesions identified by MRI was described. The primary outcome was the IIR at 5 years of those treated without RT. An IIR rate of 5% or less was considered acceptable. The protocol specified primary analysis occurred after the 100th patient reached 5 years follow up in May 2021. Results: Between 9/2011 and 5/2019, 443 patients had MRI after diagnosis. BPE was nil/minimal or mild in 344 patients. MRI detected 194 occult lesions in 144 (33%) patients; 139 (72%) were ipsilateral. 61 MMG/US occult malignant lesions - 36 invasive and 25 DCIS - were identified in 48 patients (11% of total cohort). Of 38 ipsilateral lesions in 32 patients (7% of total cohort), 23 were DCIS, 4 were T1a, 7 T1b and 4 T1c. 201 patients were treated on trial without RT. The median age was 63 years (range: 50 to 84), median tumour size 11 mm (range: 2 to 20), grade 1 (104), grade 2 (86) or grade 3 (11). The rate of IIR at 5 years was 1% (1/101). There were 2 IIRs at 4.6 and 7.7 years follow up, 1 regional recurrence, and 1 patient with both a regional and distant recurrence with 1 breast cancer death. There was 1 contralateral (CL) breast cancer, 1 CL DCIS, 2 other cancer diagnoses and 1 death from other causes. Of 242 patients undergoing MRI but not in the main study, median age was 63 range: 50-80, median tumour size, 13mm (range: 4-145). 9 underwent mastectomy (2% of total cohort). Followup is complete for 235. There was 3 IIR, 3 CL primary and no distant metastases or breast cancer deaths. Conclusions: Breast MRI in selected, low risk patients identified occult malignancy in 11% of patients. At a median of 5 years follow up the IIR and other breast cancer events was very low. This suggests that local recurrences may be due to occult breast cancers, and MRI may allow the identification of truly localised cancers for which radiation may be safely omitted. The event rate for the entire cohort was very low, suggesting that identification of occult malignancy in apparently unifocal EBC is beneficial. Confirmatory trials are needed. Clinical trial information: 12610000810011.

Impact of preoperative staging with contrast-enhanced mammography for localized breast cancer management.

A precise evaluation of the disease extent is mandatory before surgery for early breast cancer (EBC). Contrast-enhanced mammography (CEDM) is a recent technique that may help define adequate surgery. This retrospective study included consecutive patients referred to a cancer center between November 2016 and July 2017 for biopsy-confirmed invasive EBC management. The primary objective was to evaluate the rate of surgical changes after incorporating the results of the preoperative staging examination, including CEDM. A total of 231 patients were screened for inclusion, and 132 patients were included, corresponding to 134 lesions. The first surgical plan was modified for 33 patients (25%), which represented 34 lesions. For 8 patients (6%), the surgery was cancelled in preference for neoadjuvant chemotherapy; for 16 patients (12.1%), the primary tumor procedure was enlarged; and for 23 patients (17.4%) the lymph node management was modified. Surgery was changed only due to the CEDM results for 24 patients (18.5%) and consisted of a more invasive procedure due to a more extended, multifocal or multicentric lesion than seen on the standard imaging. Anatomopathological surgery piece findings were well correlated with contrast-enhanced mammography results. Overall, there was no increase in the delay between the planned date of surgery and the effective surgical procedure (median 0 days). CEDM added to preoperative staging helped define better surgical management without increasing delay in the surgical procedure. CEDM is a reliable technique that should be considered as part of preoperative staging for EBC.

Abstract P3-19-16: Impact of targeted intraoperative (TARGIT-IORT) tumor bed boost during breast conserving surgery for early breast cancer on breast cancer associated and non-breast cancer associated mortality and morbidity

Abstract Introduction: Targeted intraoperative radiotherapy (TARGIT - IORT) as a tumor bed boost during breast conserving surgery is an established option for women with early breast cancer. In a previous study our group could demonstrate a beneficial effect of TARGIT-IORT on overall survival after neoadjuvant chemotherapy driven by non-breast cancer mortality, especially from cardiac or pulmonary diseases. This was in line with results of TARGIT-A trial that demonstrated an improved overall survival after TARGIT-IORT that was driven by other causes of death than breast cancer but in our analysis we could not exclude a selection bias because we had no data regarding pulmonary and cardiac co-morbidities. In this study we present an analysis of breast cancer associated and non-breast cancer associated mortality and morbidity in a lower risk population treated with TARGIT-IORT boost or external boost (EBRT) and with a complete dataset of pulmonary and cardiac co-morbidities at baseline. Material/Methods: In this non-randomized cohort study involving 125 patients with early breast cancer we compared outcomes of 59 patients who received a tumor bed boost with IORT (TARGIT-IORT) during lumpectomy versus 66 patients with external (EBRT) boost. All patients received whole breast radiotherapy. Local recurrence rates, distant recurrence rates, mortality, causes of death and incidence of new pulmonary and cardiac morbidity were compared. The small event rate did not allow a formal comparison, so the results are reported descriptively. Results: There were no statistically significant differences between the two groups regarding age, menopausal status, nodal status, ER status, PR status, HER2 status, tumor size, grading, cardiac or pulmonary diseases and hypertension. Median follow up was 60 months. Local recurrence occurred in 3 cases in the EBRT group (4.5%) and 4 cases in the TARGIT-IORT group (6.8%). Distant recurrences were observed in 5 cases in the EBR group (7.6%) and 3 cases in the TARGIT-IORT group (5.1%). 9 patients in the EBRT group (13.6%) died in the follow-up of 60 months and 6 patients (10.2%) in the TARGIT-IORT group. No death from a pulmonary disease occurred and the incidence of new pulmonary and new cardiac diseases showed no difference between both groups with 3 cases in the EBRT group (4.5%) and 2 cases in the TARGIT-IORT group (3.4%). Death from cardiac disease occurred with an incidence of 7 cases in the EBRT group (10.6%) and only 2 cases in the TARGIT-IORT group (3.4%). 2 patients in the EBRT group died of breast cancer (3.0%) whereas this did not happen at all in the TARGIT-IORT group. Conclusion: This analysis of an average risk group of breast cancer patients well balanced for pulmonary and cardiac co-morbidities demonstrates that TARGIT-IORT as an anticipated boost is not inferior to external beam radiotherapy boost. Trends for an improved overall survival after TARGIT-IORT have been reported before. The trend for a lower incidence of death from cardiac disease is in line with earlier considerations that TARGIT-IORT may induce miR-223 in the peritumoral breast tissue resulting in a downregulation of the local expression of epidermal growth factor (EGF) and a decreased activation of epidermal growth factor receptor (EGFR). This mechanism could explain an effect of TARGIT-IORT on the vascular system. In the currently recruiting TARGIT-B study this aspect will be prospectively investigated. Citation Format: Hans-Christin Kolberg, Stephanie Gutberlet, Jayant S Vaidya, Maja Krajewska, György Lövey, Oliver Hoffmann, Miltiades Stephanou, Cornelia Kolberg-Liedtke. Impact of targeted intraoperative (TARGIT-IORT) tumor bed boost during breast conserving surgery for early breast cancer on breast cancer associated and non-breast cancer associated mortality and morbidity [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 P3-19-16.

Abstract OT1-04-03: Sentinel lymph node biopsy versus no axillary surgery in early breast cancer clinically and ultrasonographically node negative: A multicentre prospective randomized controlled trial (VENUS trial)

Abstract Background: In early breast cancer, sentinel lymph node biopsy (SLNB) has become the gold standard of axillary evaluation. Although it has less morbidity than axillary lymph node dissection, it may still cause sequelae. Currently, patients selection for SNB has been through physical examination, but presents low sensitivity and high false negative rate. Thus, ultrasonography with biopsy of suspected lymph nodes increases the accuracy. In an attempt to further reduce the morbidity of axillary surgery, it was hypothesized that it would be possible to avoid SLNB in women with early breast cancer. The aim of this study is to compare the SLNB with no axillary surgery as an approach to the axilla in early breast cancer and negative axilla clinical and ultrasonographical. Our trial includes some subsets excluded in others similar ongoing trials: patients that will undergo mastectomy and will receive primary systemic therapy. Trial design: A multicenter, phase III, prospective, open-label, non-inferiority randomized clinical trial, including 10 study sites in Brazil that will randomize 800 early breast cancer patients.Eligibility criteria: Inclusion: woman, age ≥ 18 years, histologic diagnostic of breast carcinoma, tumor ≤ 5 cm (T1 and T2) in all exams, clinically node-negative, ultrasound node-negative or negative core biopsy/fine needle aspiration if suspect lymph node (in this situation is mandatory lymph node tissue in pathologic exam). Exclusion: metastatic disease in biopsy or image before treatment, pregnancy, breastfeed, previous diagnostic of invasive neoplasia (excluding skin cancer no melanoma). It will be allowed mastectomy and neoadjuvant treatment if patient has negative axilla and T1-2 pre-systemic therapy.Intervention and stratification: Participants in experimental group will not be undergo axillary surgery and in control group will be submitted at SLNB. The randomization will be 1:1 ratio and stratified by: tumor size (T1 and T2) and age (≥50 and &amp;lt; 50 years)Specific aims: the primary objective is to access whether omission of axillar surgery is not inferior than SLNB in term of disease-free survival (DFS) at 5 years (primary endpoint). Secondary endpoints are overall survival, locoregional free survival, axillary recurrence rate, to describe surgical early and later complications and to evaluate costs of procedure SLNB or no. Statistical methods: with type I error 5%, power 80% and risk ratio 0.8, considering DFS at 5 years 90% in control group non-inferior DFS at 5 years 85% in experimental group, it was calculated sample size of 400 patients randomized and with follow up in each group (lost estimated 10%). Chi-squares and Fisher's tests will be used for the univariate analyzes, and logistic regression models for adjusted analyzes. Disease-free survival analysis, disease-free survival at a distance, and overall survival will be performed, which will be compared between groups using Kaplan-Meyer curves, log-rank tests and Cox Proportional Hazards-adjusted analyzes. The analyzes will be made intention-to-treat and per protocol.Present and target accrual: the trial was activated at November 2019 and 92 patients were accrued on July 7th 2021. The estimative of finish recruitment is in 2025 and the first data analyses will be made in 2029. The trial is registered in ReBEC (Brazilian register): RBR-8g6jbf. Contact information: Prof. Dr. Giuliano Duarte, - Univertidade Estadual de Campinas - CAISM - UNICAMP, giulianomduarte@gmail.com Citation Format: Giuliano Mendes Duarte, Danielle Cristina Myiamoto Araújo, Rodrigo Menezes Jales, Júlia Yoriko Shinzato, Cassio Cardoso Filho, Renato Zocchio Torresan, Fabrício Palermo Brenelli, Maria Beatriz de PaulaLeite Kraft, Sergio Carlos Barros Esteves, Luis Otávio Zanatta Sarian, Rosemar MecedoSousa Rahal, Ruffo de Freitas, Jr, Eduardo Carvalho Pessoa, Clecio Ênio Murta Lucena, Andrea PiresSouto Damin, Jorge Villanova Biazus, Vinicius Milani Budel, Idan de Oliveira, Jr, Rene Aloisio da Costa Vieira, Júlio César Narciso Gomes. Sentinel lymph node biopsy versus no axillary surgery in early breast cancer clinically and ultrasonographically node negative: A multicentre prospective randomized controlled trial (VENUS trial) [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 OT1-04-03.

Abstract P3-20-01: Increased distant recurrence following margin involvement in early invasive breast cancer in two large UK cohorts

Abstract Involved margins after surgery for early breast cancer increase the risk of local recurrence (LR), but international guidelines suggest that’ no tumour’ on ink is sufficient margin clearance after breast conserving surgery (BCS). Data on the effect of margin clearance on distant recurrence (DR) are lacking. Our aim was to determine the association between margin involvement, recurrence (DR) and breast cancer deaths. Methods Data from breast cancer units in Greater Manchester (GM) and the UK National Cancer Registry (NCRAS) were analysed. Margin status was prospectively recorded after surgery according to National Health Service Breast Screening Pathology (NHSBSP) minimum pathology data standards All patients underwent curative surgery and received adjuvant therapy according to local guidelines. Patients not undergoing curative surgery(T4, inflammatory or metastatic cancer) were excluded .Cox-proportional hazards models investigated factors associated with LR, DR and risk of breast cancer death.NCRAS records breast cancer deaths . Results GM analysis included 3270 patients from 2010 to 2014, 2295 (70.2%) had margins (&amp;gt;2mm) ,302 (9.2%) close (1-2mm) margin clearance and 673 (20.6%) involved (&amp;lt;1mm) margins. Median age was 61 years (range 24-100 years) and median follow up was 64.4 months (range 0.0-126.6 months). Breast Conserving Surgery (n=2030) and Mastectomy (n=1240) surgery was used as appropriate and most patients underwent adjuvant radiotherapy (71%) and/or hormone therapy (84%).160 patients (4.9%) developed LR and 231 patients (7.06%) DR. Time-to-DR (p=0.035) and time-to-LR (p=0.012) differed by margin status. At 5-years, the probability of LR was 3.1%, 3.5% and 5.8% and for DR was 4.9%, 5.9% and 7.1% for clear, close and involved margins, respectively. After multivariable adjustment, involved margins&amp;lt;1mm were associated with increased hazard of DR (HR 1.459, 95% CI: 1.050, 2.027, p=0.025) and LR (HR 1.79, 95% CI: 1.21, 2.63, p=0.004) compared to a clear margin&amp;gt;2mm. For Breast Conservation margins&amp;lt;1mm increased DR (HR 2.09,1.22-3.58:p&amp;lt;0.009 ) compared to clear margins. Similar findings were found in several subgroup analyses including screening, symptomatic and by cancer treatments. NCRAS data from 2010-2013 included 40,849 patients with invasive cancer of whom 27,589 margins &amp;gt;1mm (67.5%) and 3,935 (9.6%) were classed as “clear margins” and 9,325 (22.8%) cancer patients had involved margins &amp;lt;1mm, There were 3,160 deaths from breast cancer with a median follow-up of 80.2 months. Multivariate analysis in NCRAS indicated excess cancer mortality (HR 1.18 (95% CI 1.08-1.28) in the 9325 (22.8%) patients with margins &amp;lt;1mm (p&amp;lt;0.001), tumour stage (stage 3 HR 7.01 (6.28-7.82), p&amp;lt;0.001), age (HR 1.02 (1.02-1.03, p&amp;lt;0.001), symptomatic detection (HR 2.21 (1.98-2.46), p&amp;lt;0.001) and lower socio-economic status HR 1.31 (1.16-1.47, p&amp;lt;0.001). Conclusions Margins&amp;gt;1mm were associated with reduced DR and should be essential surgical management. Current guidelines about surgical margins need to be re-evaluated to achieve reduced DR and cancer deaths. Citation Format: Nigel James Bundred, Sarah Michael, John Broggio, Anne Armstrong, Glen Martin, Mohamed Absar, Jane Ooi. Increased distant recurrence following margin involvement in early invasive breast cancer in two large UK cohorts [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 P3-20-01.