Radiation-induced Sarcoma Research Articles

Radiation-Induced Undifferentiated Pleomorphic Sarcoma in Thyroid: A Rare Occurrence

Radiation-Induced Undifferentiated Pleomorphic Sarcoma in Thyroid: A Rare Occurrence

Chronic Invasive Fungal Sinusitis Mimicking Malignancy Post-Radiotherapy: A Case Report.

Invasive fungal sinusitis is a life-threatening form of fungal rhinosinusitis. Due to the aggressive clinical presentation and radiological appearance, there is diagnostic difficulty in differentiating invasive fungal sinusitis from a malignant process. This is even more challenging in oncological patients who have undergone previous head and neck radiotherapy, due to possibility of a recurrence of primary malignancy and radiation-induced neoplasms. We report a rare case of invasive fungal sinusitis mimicking a malignancy in a post-radiotherapy patient.Our patient was a 68-year-old male, 25-years post-radiotherapy for nasopharyngeal carcinoma. He presented with a 3-month history of purulent sputum and right facial paraesthesia. Magnetic resonance imaging showed an irregular destructive enhancing mass of the greater wing of right sphenoid and pterygoid bone with extensive extension into nearby structures. In view of extensive local and bony invasion, and a history of radiotherapy, initial suspicions were that of primary malignancy, specifically radiation-induced sarcoma, and recurrence of nasopharyngeal carcinoma. He underwent transpterygoid biopsy of the lesion, and histopathology demonstrated Aspergillus species, with no malignancy identified.Our report highlights the diagnostic difficulties in the post-radiotherapy cancer patient presenting with symptoms suggestive of aggressive sino-nasal disease. Invasive fungal sinusitis closely mimics the clinical and radiological findings of several neoplastic processes. We discuss the clinical and radiological characteristics of pathologies that may mimic invasive fungal sinusitis. Histological examination remains the gold standard for diagnosis, and early fungal staining is crucial. Furthermore, one should not presume the initial histopathological diagnosis to be confirmatory of isolated fungal disease. Repeat radiological investigations for disease resolution and histopathologic re-evaluation if required should be performed, keeping in mind possibility of coexisting malignancy.

Clinicopathological and genetic characterization of radiotherapy-induced undifferentiated pleomorphic sarcoma following breast cancer: a case series of three tumors and comprehensive literature review

AimsCompared to primary breast sarcoma (BSs), radiotherapy-induced sarcoma (RIS) is a less frequent type of secondary breast sarcoma. Undifferentiated pleomorphic sarcoma (UPS) is an even rarer occurrence within the RIS category. This study aimed to present the clinicopathologic and molecular features of breast radiotherapy-induced UPS.MethodsA retrospective study was conducted at the Third Affiliated Hospital of Soochow University to analyze three patients with radiation-induced undifferentiated pleomorphic sarcoma (UPS) following breast cancer, spanning from 2006 to 2023. The clinical and pathological variables were extracted from the medical records, while immunohistochemistry was employed to analyze the immunophenotypes of these tumors. Genomic characteristics were assessed through DNA and RNA sequencing techniques. Another 15 cases from the literature were also reviewed to better characterize the tumor.ResultsThe affected areas encompass the chest wall and breasts, with an incubation period ranging from 6 to 17 years. The tumor cells exhibit pleomorphism and demonstrate a high degree of pathological mitosis. Notably, two cases displayed an accelerated disease progression, characterized by recurrent tumors and metastases occurring within short intervals of 48 and 7 months respectively subsequent to the initial diagnosis. The two prevailing identified genes were TP53 (2/3, 66.7%) and RB1 (1/3, 33.3%). Through analysis of somatic copy number variation (CNV), it was discovered that two oncogenes, MCL1 (1/3, 33.3%) and MYC (1/3, 33.3%), had experienced gains in CNV. The Tumor Mutational Burden (TMB) values for case 1, case 2, and case 3 were 5.9 mut/Mb, 1.0 mut/Mb, and 3.0 mut/Mb, respectively. Moreover, the analysis of RNA-NGS (next-generation sequencing) revealed the presence of a novel gene fusion, named COL3A1-GULP1, in case 2.ConclusionsBased on our thorough analysis of research findings and previous reports, it is evident that radiotherapy-induced UPS exhibits a highly diverse and frequently severe clinical and biological behavior. Identifying tumor formation using genome sequencing can help understand its biological behavior and determine personalized treatments.

Bone Radiation-Induced Sarcomas: Outcomes Based on Histology and Surgical Treatment: A Systematic Review of the Literature.

Bone radiation-induced sarcomas (B-RIS) are secondary neoplasms with reportedly worse overall survival than de novo bone sarcoma. Treatment strategy for these neoplasms remains uncertain. Our systematic review sought to assess overall survival based on histology and surgical intervention. A systemic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered in PROSPERO (438415). Studies describing oncologic outcomes of patients with B-RIS in the appendicular and axial skeleton were included. The Strengthening the Reporting of Observational Studies in Epidemiology checklist was used for quality assessment. Survival analysis by histologic subtype and surgery type was performed in a subset of 234 patients from 11 articles with individualized data. A total of 20 articles with a total of 566 patients were included. The most frequent location was the pelvis (27.7%), and the main histological types were osteosarcoma (69.4%), undifferentiated pleomorphic sarcoma (14.1%), and fibrosarcoma (9.2%). Limb-salvage and amputation were performed in 68.5% and 31.5% of cases, respectively. Local recurrence was 13%, without difference between limb-salvage surgery and amputation (p = 0.51). The metastasis rate was 42.3%. Five-year OS was 43.7% (95% confidence interval [CI], 33.3%-53.5%) for osteosarcoma, 31.5% (95% CI, 11.3%-54.2%) for UPS, and 28.1% (95% CI, 10.6%-48.8%) for fibrosarcoma. Five-year OS was 49.2% (95% CI, 35.3%-61.6%) for limb-salvage and 46.9% (95% CI, 29.1%-62.9%) for amputation. There was no difference in 5-year OS between histologic subtypes (p = 0.18) or treatment type (p = 0.86). B-RIS demonstrated poor OS at 5 years after initial management regardless of histology. Limb-salvage surgery was not associated with lower 5-year OS compared with amputation. Future studies should compare both groups while controlling for confounders. Level III. See Instructions for Authors for a complete description of levels of evidence.

Radiation-induced sarcoma in patients with nasopharyngeal carcinoma: a single-institution retrospective study

Objective:To analyze the clinical features, treatment methods and prognosis of radiation-induced sarcoma（RIS） of the head and neck after radiotherapy for nasopharyngeal carcinoma（NPC）, and explore its treatment strategies. Methods:A retrospective analysis was conducted on RIS patients after radiotherapy for NPC in the People's Hospital of Guangxi Zhuang Autonomous Region from January 2013 to October 2022. The time of onset, lesion location, pathological subtypes, imaging features and treatment outcomes were described, and the median survival time was statistically analyzed through follow-up. Results:This study included 10 patients with an interval of 2-27 years between NPC and RIS. The nasopharynx was the more common site of RIS, and osteosarcoma was the main pathological type. The median overall survival was 18 months. The median survival was 40 months in the surgery combined with the chemotherapy group, and 12 months in the surgery alone group. The 1-and 2-year cumulative survival rates were 48% and 36%, respectively. Prognostic analysis showed that gender, age of onset, time of sarcoma onset after radiotherapy and treatment methods might not be influencing factors for prognosis, and osteosarcomas presented a poorer prognosis than other pathological types. Conclusion:RIS is one of the most severe long-term adverse effects in patients with NPC. The prognosis of RIS is poor, and complete surgical resection of the tumor can improve patient survival rates. In cases where complete surgical resection is challenging, radiotherapy or chemotherapy may offer some improvement in tumor control.

Secondary radiation-induced sarcoma occurring as a rare complication of radiotherapy for a gonadotroph tumour

Secondary radiation-induced sarcoma occurring as a rare complication of radiotherapy for a gonadotroph tumour

TP53-associated early breast cancer: new observations from a large cohort.

A recent large, well-annotated international cohort of patients with Li-Fraumeni syndrome and early-stage breast cancer was examined for shared features. This multicenter cohort study included women with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic breast cancer diagnosed between 2002 and 2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were used to summarize proportions, and differences were assessed using χ2 or Wilcoxon rank sum tests. Metachronous contralateral breast cancer risk, radiation-induced sarcoma risk, and recurrence-free survival were analyzed using the Kaplan-Meier methodology. Among 227 women who met study criteria, the median age of first breast cancer diagnosis was 37 years (range = 21-71), 11.9% presented with bilateral synchronous breast cancer, and 18.1% had ductal carcinoma in situ only. In total, 166 (73.1%) patients underwent mastectomies, including 67 bilateral mastectomies as first breast cancer surgery. Among those patients with retained breast tissue, the contralateral breast cancer rate was 25.3% at 5 years. Among 186 invasive tumors, 72.1% were stages I to II, 48.9% were node negative, and the most common subtypes were hormone receptor-positive/HER2-negative (40.9%) and hormone receptor positive/HER2 positive (34.4%). At a median follow-up of 69.9 months (interquartile range = 32.6-125.9), invasive hormone receptor-positive/HER2-negative disease had the highest recurrence risk among the subtypes (5-year recurrence-free survival = 61.1%, P = .001). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%. We observed high rates of ductal carcinoma in situ, hormone receptor-positive, and HER2-positive breast cancers, with a worse outcome in the hormone receptor-positive/HER2-negative luminal tumors, despite appropriate treatment. Confirmation of these findings in further studies could have implications for breast cancer care in those with Li-Fraumeni syndrome.

Pelvic radiation-induced sarcoma following treatment of cervical cancer

Post-radiation sarcomas account for 0.5-5.5% of all sarcomas, and include extra skeletal osteosarcoma, fifibrosarcoma leiomyosarcoma, and malignant fifibrous histiocytoma. This article presents a case of a 53-year-old female who developed a mixed-type postradiation sarcoma three years after radiotherapy for cervical cancer. Unfortunately, the patient succumbed to the condition six months after undergoing pelvic clearance surgery. No prior relevant case reports have been identified in the literature. Consequently, we have systematically reviewed and summarized this case, conducting a comprehensive literature review to contribute valuable insights into the understanding of post-radiation sarcomas. Our objective is to underscore the importance of vigilance regarding these conditions and to provide clinicians with pertinent clinical data for informed decision-making in the realm of tumor radiotherapy.

Unusual Soft Tissue Uptake of Tc-99m MDP in Radiation-induced Sarcoma: Diagnostic Conundrum

Unusual Soft Tissue Uptake of Tc-99m MDP in Radiation-induced Sarcoma: Diagnostic Conundrum

Radiation-Induced Uterine Stromal Sarcoma: A Case Report and Review of the Literature

The radio-induced stromal sarcoma (RISS) is a rare clinical entity, being the second most common type of uterine mesenchymal neoplasm after leiomyosarcoma. Its incidence increases as survival after radiotherapy improves, and it often poses a therapeutic challenge. We report the case of a 58-year-old patient, followed since 2014 for initially classified stage IIb squamous cell carcinoma of the uterine cervix, treated with external pelvic radiotherapy and brachytherapy. After 6 years of surveillance, the patient presented with persistent pelvic pain. Clinical examination and pelvic MRI revealed the presence of a tumoral process in the uterine cervix with suspicious thickening of the endometrium. Morphological and immunohistochemical pathological study of the lesion confirmed its tumoral nature, indicative of a high-grade stromal sarcoma. Radiotherapy can induce malignant tumors after a latent period of several years. Radio-induced gynecological sarcomas are most often associated with a poor prognosis, emphasizing the need for careful and close monitoring after pelvic irradiation.

Treatment and Outcomes of Radiation-Induced Soft Tissue Sarcomas of the Extremities and Trunk—A Systematic Review of the Literature

Introduction: Radiation-induced soft tissue sarcomas (RISs) are rare secondary malignancies with a dire prognosis. The literature on the management of these tumors remains scarce due to their low incidence. Our systematic review sought to assess the treatment alternatives and outcomes of patients with RIS. Methods: A systematic review was conducted following the PRISMA guidelines. Our study was registered in PROSPERO (ID: CRD42023438415). Quality assessment was performed using the STROBE checklist. Weighted means for both continuous and categorical values were calculated. Results: Twenty-one studies comprising 1371 patients with RIS were included. The mean latency period from radiation to RIS diagnosis was 14 years, and the mean radiation dose delivered to the primary malignancy was 29.2 Gy. The most common histological type was undifferentiated pleomorphic sarcoma (42.2%), and 64% of all tumors were high-grade. The trunk was the most common location (59%), followed by extremities (21%) and pelvis (11%). Surgery was performed in 68% of patients and, among those with an appendicular tumor, the majority (74%) underwent limb-salvage surgery. Negative margins were attained in 58% of patients. Chemotherapy and radiotherapy were administered in 29% and 15% of patients, respectively. The mean 5-year overall survival was 45%, and the local recurrence and metastasis rates were 39% and 27%, respectively. Conclusions: In our study, the most common treatment was surgical resection, with RT and chemotherapy being administered in less than one third of patients. Patients with RIS exhibited poor oncologic outcomes. Future studies should compare RIS with de novo STS while controlling for confounders.

Radiation-associated sarcomas of bone and soft tissue: a clinicopathological analysis of 46 cases

Objective: To investigate the clinical, imaging, histological, and molecular features and the differential diagnosis of radiation-associated sarcomas of bone and soft tissue. Methods: Forty-six cases of radiation-associated sarcomas of the bone and soft tissue in Beijing Jishuitan Hospital from January 2010 to January 2022 were retrospectively analyzed; and the imaging, histological features and immunophenotype were examined. Results: There were 33 females and 13 males, aged from 18 to 74 years, with a mean of 52 years. The most common site of radiation-associated sarcomas were the limbs and spine (15 cases), followed by the chest (9 cases). The primary diseases included epithelial tumors (15 breast cancer, 6 cervical cancer, and 5 bowel cancer), hematolymphoid tumors, bone and soft tissue tumors and infectious lesions. The latent period of radiation-associated sarcomas ranged from 2-22 years, with an average of 11.6 years. Histopathologically, the morphology was divergent from the primary tumor. The most common malignant tumor type was undifferentiated sarcoma (22 cases), followed by osteosarcoma (16 cases). The immunophenotype of radiation-related sarcoma was almost the same as the corresponding soft tissue sarcoma. Conclusions: Radiation-induced sarcoma has a wide range of primary tumor types and its imaging, morphology and immunohistochemical features are similar to those of the primary sarcoma of bone and soft tissue. Clinical correlation is often recommended for the differential diagnosis.

Personalized 3D printed implants in the treatment of extensive chest wall tumors: clinical cases

3D printing has opened new opportunities for the development of personalized systems for prosthetics of extensive chest wall defects after radical surgical interventions for malignant tumors. However, risk factors for an adverse outcome of such operations have not yet been identified.Clinical cases. A 65-year-old man with primary chondrosarcoma of the V rib, underwent surgical resection of three ribs, plasty with local tissues, and an individual 3D printed titanium implant was installed on the sternum and IV-VI ribs. Follow up for 26 months showed no complaints or signs of recurrence. A 52-year-old woman with radiation-induced soft tissue sarcoma of the chest wall, that developed 9 years after radiation for breast cancer, underwent resection of four ribs and pectoral muscles and a 3D printed titanium implant was installed on the sternum and II-V ribs. The operation was complicated by the marginal necrosis of the soft tissue flap and infection of the endoprosthesis, which required removal of the metal structure and reconstruction using TRAM flap. After 9 months, a local recurrence of the tumor was diagnosed. Discussion. As a factor of a positive outcome in a man should be noted a thick layer of subcutaneous fat with muscle tissue, due to which plastic surgery was performed, covering the defect without tension. An extensive resection of the pectoral muscles in a woman created a tissue deficit. Another factor of an unfavorable outcome can be considered the radio-induced nature of the sarcoma. Further research is needed to improve the strategy for selecting patients with malignant tumors of the chest wall for prosthetics.

Characteristics and therapeutic strategies of brain and cranial radiation-induced sarcoma: analysis of 165 cases from our case experience and comprehensive review.

Radiation-induced sarcoma (RIS) is among the neoplasms potentially caused by radiation therapy (RT) for brain tumors. However, the clinical characteristics of and ideal treatment for RIS are unclear. We analysed our case experience and conducted a comprehensive literature review to reveal the characteristics of brain and cranial RIS. We analysed 165 cases of RIS from the literature together with the RIS case treated at our institution. In each case, the latency period from irradiation to the development of each RIS and the median overall survival (OS) of the patients was analysed by Kaplan-Meier analysis. Spearman's correlation test was used to determine the relationship between the latency period and radiation dose or age at irradiation. The mean age at the development of RIS was 39.63±17.84years. The mean latency period was 11.79±8.09years. No factors associated with early development of RIS were detected. The median OS was 11months, with fibrosarcoma showing significantly shorter OS compared with osteosarcoma and other sarcomas (p=0.0021), and intracranial RIS showing a worse prognosis than extracranial RIS (p<0.0001). Patients treated with surgery (p<0.0001) and postoperative chemotherapy (p=0.0157) for RIS presented significantly longer OS, whereas RT for RIS was not associated with a survival benefit. Although prognosis for RIS is universally poor, pathological characteristics and locations are associated with worse prognosis. Surgery and chemotherapy may be the ideal treatment strategies for RIS.

Radiation-Induced Right Pectoralis Muscle Sarcoma after Breast Cancer: Case Report and Review of the Literature

Radiation-induced sarcoma of the breast is a rare but serious complication of radiation therapy for breast cancer. Although the risk of this complication is low, patients who have undergone radiation therapy for breast cancer should have regular follow-up to detect any signs of new tumor or recurrence. Imaging tests such as CT or MRI can be used to screen for radiation-induced sarcoma. If radiation-induced sarcoma is detected, the recommended treatment includes complete surgical removal followed by postoperative radiation therapy.

Genomic profiling of radiation-induced sarcomas reveals the immunological characteristics and its response to immune checkpoint blockade.

Radiation-induced sarcomas (RISs) have poor prognosis and lack effective treatments. Its genome and tumor microenvironment are not well characterized and need further exploration. Here, we perform whole exome (WES) and mRNA sequencing (mRNA-seq) on patient with RISs and primary sarcomas (WES samples 46 vs 48, mRNA-seq samples 16 vs 8, mainly in head and neck), investigate the anti-tumor effect of PD-1 blockade in RIS-PDX models, and analyze clinical data of RIS patients treated with chemotherapy alone or combined with an anti-PD-1 antibody. Compared to primary sarcomas, RISs manifested different pattern of copy number variations, significantly higher number of predicted strong MHC-binding neoantigens, and significantly increased immune cell infiltration. Clinical data showed that the combinatorial use of chemotherapy and PD-1 blockade achieved a higher overall response rate (ORR) (36.67% vs 8.00%, p = 0.003), longer overall survival (31.9 months vs 14.8 months, p = 0.014) and longer progression free survival (4.7 months vs 9.5 months, p = 0.032) in RIS patients compared to single chemotherapy. Elevated genomic instability and higher immune cell infiltrations was found in RISs than primary sarcomas. Moreover, higher efficacy of chemotherapy plus PD-1 blockade was observed in animal experiment and clinical practice. These evidence indicated the promising application of immune checkpoint inhibitors in the treatment of RISs.

Radiation-induced sarcomas following childhood cancer - A Canadian Sarcoma Research and Clinical Collaboration Study (CanSaRCC).

Radiation-induced sarcoma (RIS) is a late toxicity of radiation therapy (RT) usually associated with poor prognosis. Due to ongoing improvements in childhood cancer treatment and patient outcomes, RIS may become more prevalent notwithstanding evolving indications for RT. Due to limited reported studies, we sought to review our experience with RIS in survivors of pediatric cancer. Data were collected on RIS patients following treatment for childhood cancer (initial diagnosis <18 years) identified in the CanSaRCC database. Additionally, details on the protocol guidance at time of treatment were compared with current guidelines for the same disease. Among 12 RIS identified, median age at initial diagnosis was 3.5 years (range 0.16-14) and the latency from RT to RIS diagnosis was 24.5 (range 5.4-46.2) years. Initial diagnoses included neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, Wilms tumor, retinoblastoma and Hodgkin's Lymphoma. RIS histologies included osteosarcoma and soft tissue sarcomas. In comparison to protocols followed at time of diagnosis to current ones (2022), 7/12 (58%) patients would have required RT. RIS treatment included chemotherapy, radiation and surgery in 3/11 (27%), 10/11 (90%), and 7/11 (63%) patients, respectively. With a median follow-up time of 4.7 years from diagnosis of RIS, 8 (66%) patients were alive and 4 (33%) had died of progressive RIS. RIS is a serious late effect of radiotherapy in childhood cancer; however, radiation remains an integral component of primary tumor management and requires participation from a specialized multi-disciplinary team, aiming to mitigate RIS and other potential late effects.

Radiation-Induced Sarcomas of the Breast: A Review of a 20-Year Single-Center Experience.

Background Radiation-induced sarcomas (RISs) are histologically proven sarcomas within or around a previously irradiated site, per Cahan's criteria. RIS incidence is higher in breast cancer compared to other solid cancers and the prognosis remains poor given limited treatment options. This study aimed to review 20-year experience with RISs at a large tertiary care center. Methodology Using our institutional cancer registry database, we included patients meeting Cahan's criteria diagnosed between 2000 and 2020. Patient demographics, oncologic treatment, and oncologic outcomes data were collected. Descriptive statistics were used to describe demographic data. Oncologic outcomes were assessed using the Kaplan-Meier method. Results A total of 19 patients were identified. The median age at RIS diagnosis was 72 years (range = 39-82 months), and the median latency period for the development of RIS was 112 months (range = 53-300 months). All patients underwent surgery, three patients received systemic therapy, and six patients received re-irradiation as salvage treatment. The median follow-up time was 31 months (range = 6-172 months) from the diagnosis of RIS. Overall, five patients had local recurrence, and one patient developed distant metastases. The median time to progression was seven months (range = 4-14 months). The progression-free survival (95% confidence interval (CI)) at two years was 56.1% (37.4-84.4%). At follow-up two years after the diagnosis of sarcoma, the overall survival (95% CI) was 88.9% (75.5-100%). Conclusions While breast RIS remains rare, when managed in a large tertiary care center, overall survival outcomes appear favorable. A significant proportion of patients recur locally after maximal treatment and require salvage therapy to improve outcomes. These patients should be managed in high-volume centers where multidisciplinary expertise is available.

Radiation-Induced Undifferentiated Pleomorphic Sarcoma after Breast Conserving Therapy: Case Report

Introduction: Breast sarcoma is a rare form of malignancy that arises from connective tissue, comprising less than 5% of all sarcomas. Undifferentiated pleomorphic sarcoma (UPS) of the breast is a rare and aggressive subtype of radiation-induced sarcoma that can occur in treated breast cancer patients. The diagnosis is challenging and often missed due to the low incidence, long latency period, unspecific imaging finding, and difficulties in clinical and histological detection. Case report: A 56-year-old woman was diagnosed with early-stage triple-negative breast cancer in 2013 and underwent breast-conserving therapy (BCT). After five years follow-up, she developed mastalgia and breast induration, and after mammography and ultrasound without suspicious lesions, a magnetic resonance imaging (MRI) was performed and showed a highly suggestive malignancy mass measuring 8.0 cm and invading the chest wall. The core biopsy revealed a spindle cells malignant tumor, negative for pan cytokeratin and most of immuno-histochemical markers, suggesting sarcoma, but requiring investigation of surgical specimen to exclude metaplastic carcinoma. She underwent Halsted radical mastectomy, full-thickness left anterior chest wall resection contemplating segments of the 4th and 5th ribs and reconstruction with synthetic mesh. The surgical specimen evidenced a UPS with clear margins. The patient had good postoperative recovery and remains in follow-up with the mastology team. Conclusion: This report shows that radiation-induced sarcomas of the breast can be difficult to diagnose, and how later treatment can demand a major surgery with higher morbidity. Prognosis may improve if detected early.

Abstract PD14-09: PD14-09 The effect of timing of TP53 genetic testing on treatment and outcomes among women with Li-Fraumeni syndrome and breast cancer

Abstract Background: Li-Fraumeni syndrome (LFS) is a pan-cancer predisposition syndrome caused by pathogenic germline TP53 variants. Breast cancer (BC) is the most prevalent tumor in women with LFS. The risk of secondary malignancies, including multiple primary BCs, other LFS-related cancers, radiation-induced sarcomas, and local recurrences are important clinical concerns in the LFS setting. The diagnosis of LFS may influence treatment decisions and outcomes. Methods: In this international multicenter study, we analyzed women with pathogenic or likely pathogenic germline TP53 variants and BC (DCIS or invasive breast carcinoma) diagnosed 2002-2022 from three retrospective LFS cohorts (Dana Farber Cancer Institute, USA; Institut Gustave Roussy, France; Hospital Sírio-Libanês, Brazil). We excluded carriers of TP53 unconfirmed possibly mosaic variants, carriers of a 2nd pathogenic variant in another BC susceptibility gene, and those with missing data related to timing of genetic testing (TGT) or date of 1st BC diagnosis (dx). The overall cohort was divided in two groups: genetic testing before or at 1st BC dx (group A) and those with testing ≥1 year after 1st BC dx (group B). In cases with synchronous bilateral BC, we included the tumor of higher risk of recurrence (invasive, higher stage, more aggressive tumor biology) and excluded the other. The chi-square test was used to measure the association between TGT and other categorical variables. Results: 209 patients (pts) met criteria for this analysis. The median age of 1st BC dx was 35 years (IQR, 31-42). BC was the 1st cancer dx in 87.5% of the pts. Among 1st breast tumors, 38 were DCIS, 147 were early-stage BC (61 I, 49 II, 37 III) and 7 stage IV (17 missing). There were no differences between groups A and B regarding staging at dx. Missense TP53 variants were the most common type of germline mutation (n=154, 73.6%), with 60.4% (n=93) in the DNA-binding domain and 38.9% (n=60) in the tetramerization domain. Median follow-up from 1st BC dx was 6 years (IQR, 3-10). 53.1% of pts (n=111) underwent TP53 germline testing only after 1st BC dx. Family history of BC &amp;lt; 50 and non-BC malignancy prior to or synchronous with 1st BC dx were not associated with TGT (p=0.3 and p=0.2, respectively). 35.4% of pts developed a second primary BC (25 ipsilateral; 49 contralateral). Among pts without synchronous bilateral BC or metastatic BC at dx, 97 pts underwent contralateral risk reducing mastectomy (CRRM), 56.7% (55/97) as part of treatment surgery for the 1st BC. CRRM uptake was associated with TGT (A 70.3% vs B 41.6%, p=0.001). Of 194 pts with detailed data on surgical treatment (1st BC), 146 underwent mastectomies and 48 breast conserving surgery (BCS). Group A had more mastectomies (79.5% vs 61.2%, p=0.001) and less radiation therapy (10.2% vs 45.9%, p&amp;lt; 0.001). Among the irradiated pts, 9.8% (n=5) developed sarcomas in the irradiated field. Thirty-eight pts had BC recurrence: 21 loco-regional (A 6 vs B 15, p&amp;lt; 0.05), mostly in-breast, and 17 distant relapses. There was a significant statistical association between TGT and type of BC surgery (p=0.001), radiation-therapy (p&amp;lt; 0.001), CRRM uptake (p=0.001) and local relapses (p&amp;lt; 0.05). Conclusion: This analysis of BC in our sizable cohort of LFS patients with treatment data confirms that, timing of genetic testing affects some treatment options and outcomes, including surgical procedures and use or avoidance of radiation. These decisions appear to influence the risk of local recurrence or additional primary BC and radiation-induced sarcoma. Recognition of germline TP53 variants in breast cancer patients as part of genetic testing at diagnosis appears to have implications for treatment options and outcomes. Citation Format: Renata Sandoval, Michele Bottosso, Natalia Polidorio, Brittany Bychkovsky, Benjamin Verret, Alessandra Gennari, Sophie Hyman, Maria Isabel Achatz, Olivier Caron, Fabrice Andre, Judy Garber. PD14-09 The effect of timing of TP53 genetic testing on treatment and outcomes among women with Li-Fraumeni syndrome and breast cancer [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 PD14-09.