Oligometastatic Breast Cancer Patients Research Articles

Adding Metastasis-Directed Therapy to Standard-of-Care Systemic Therapy for Oligometastatic Breast Cancer (EXTEND): a Multicenter, Randomized Phase II Trial

PurposePrior evidence suggests a progression-free survival (PFS) benefit from adding metastasis-directed therapy (MDT) to standard-of-care (SOC) systemic therapy for patients with some oligometastatic solid tumors. Randomized trials testing this hypothesis in breast cancer have yet to be published. We sought to determine whether adding MDT to SOC systemic therapy improves PFS in oligometastatic breast cancer. MethodsEXTEND is a multicenter phase II randomized basket trial testing the addition of MDT to SOC systemic therapy in patients with ≤5 metastases (NCT03599765). Patients were randomized 1:1 to MDT (definitive local treatment to all sites of disease, plus SOC systemic therapy) or to SOC systemic therapy only. Primary endpoint was PFS, and secondary endpoints included overall survival (OS), time to subsequent line of systemic therapy, and time to the appearance of new metastases. Exploratory analyses included quality of life (QOL) and systemic immune response measures. ResultsFrom September 2018 through July 2022, 22 and 21 patients were randomized to the MDT and no-MDT arms, respectively. At a median follow-up of 24.8 months, PFS was not improved with the addition of MDT to SOC systemic therapy (median PFS 15.6 months MDT vs 24.9 months no-MDT [hazard ratio {HR} 0.91; 95% CI 0.34–2.48, p=0.86]). Similarly, MDT did not improve OS, time to subsequent line of systemic therapy, or time to the appearance of new metastases (all p>0.05). No significant differences were found in QOL measures, systemic T-cell activation, or T-cell stimulatory cytokine concentration. ConclusionAmong patients with oligometastatic breast cancer, the addition of MDT to SOC systemic therapy did not improve PFS. These findings suggest that MDT may have no systemic benefit in otherwise unselected oligometastatic breast cancer patients, although this trial was limited by a heterogenous and small sample size and overperformance of both treatment arms.

Patterns of progression in oligometastatic hormone receptor positive breast cancer after first-line systemic treatment at the metastatic stage.

e13054 Background: In recent years, thanks to large, consecutive and retrospective series, knowledge of oligometastatic breast cancer (OMBC) has improved. However, the underlying pathophysiological mechanisms and patterns of progression of OMBC remain largely unknown. The aim of this study is to determine whether the limited capacity of OMBC to metastasize persisted in patients receiving first-line systemic treatment at the OMBC stage. To obtain a biologically homogeneous cohort, the analysis focused on hormone receptor positive (HR+) OMBC. Methods: We retrospectively reviewed all patients consecutively diagnosed and treated from 2012 to 2020 at our institution for synchronous and metachronous HR+ OMBC. Included were HR+ MBC patients with up to five metastases at diagnosis with no other criteria. Clinical and biological characteristics at diagnosis of first metastases, types of treatment (local ablative treatment of all sites (LAT) vs palliative treatment), outcomes and patterns of progression after a first line systemic treatment at the oligometastatic stage were recorded. Progression-free survival (PFS) and overall survival (OS) rates with a 95% confidence interval were estimated using the Kaplan Meier method. Results: Out of 1,686 patients treated for MBC at our institution between 2012 and 2020, 11.0% (186/1,686) met inclusion criteria. Among these 186 HR+ OMBC patients, 62.2% had SBR grade I/II HR+, and 19.3% had HER2+ OMBC. 93.5% patients had only one organ invaded, and 88.2% patients had one to three metastases at diagnosis. 66.7% had bone metastases, 60.2% had bone-only metastases, 18.3% had visceral (lung or liver) metastases, 14.5% had lymph node metastases and 6.5% had brain metastases. 35.5% of patients were treated with a curative intent including systemic treatment plus LAT. After a median follow-up of 73.4 months (95%CI= [69.3-76.8]), median PFS and OS were respectively 31.6 months (95%CI= [23.7-37.4]) and 90.9 months (95%CI= [70.0-109.9]). Five years PFS and OS were respectively 32.6 % (95%CI= [25.5-39.9]) and 66.3% (95%CI= [58.4-73.1]). During this period, 64.0% (119/186) of HR+ OMBC patients presented disease progression. Among the latter, 74.1% showed spread with no more than five metastases (oligoprogression), and 82.6% in only one organ. 27.7% (33/119) of patients were able to benefit from LAT. Conclusions: HR+ OMBC incidence is 11%. Among patients with progressive HR+ OMBC following first-line systemic treatment at the oligometastatic stage, a large majority presented oligoprogression and a substantial proportion were able to be treated by local ablative therapy with a curative intent at the time of this progression. The limited capacity of HR+ OMBC to metastasize thus persisted after a first-line systemic treatment. This could be an argument in favor of physiopathological mechanisms specific to oligometastatic disease.

Abstract PO3-06-04: Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience

Abstract Background The current definition, prognosis, and optimal treatment (tx) for oligometastatic breast cancer (OMBC) are not fully known. With advances in multimodality breast cancer (BC) tx and overall improvement in patient (pt) outcomes, it is important to identify baseline pt factors that confer better prognosis in OMBC and assess the impact of local/regional tx and metastasis (mets)-directed tx on survival outcomes. Methods We reviewed 105 Mayo Clinic pts with OMBC (up to 5 mets) from 2003 to 2021. Pts were excluded from analysis if they were misidentified as having OMBC (n=6), did not have a primary breast mass (n=1), developed de novo BC during tx (n=1), or were lost to follow up (n=2). Categorical variables were summarized as counts. Continuous variables were reported as medians. Kaplan-Meier method was used to estimate survival and the time from diagnosis to next tx at 1, 3, and 5 years. Log-rank test was used to compare survival rates between baseline factors. Univariate Cox proportional hazards models were performed on both baseline and time-dependent factors. All tests were two-sided with p-value < 0.05 considered statistically significant. Results Total pts included were 95. Median age was 49 (range, 26-86), most (93.6%) pts were White, and 46.8% were postmenopausal. Invasive ductal carcinoma (89.5%) was the most common BC type. Median survival was 10.8 years; 1-, 3-, and 5-year survival rates were 98.9%, 87.7%, and 81%, respectively. 58 pts (61.1%) required a change in tx due to disease progression. No significant survival difference was observed in pre- vs. postmenopausal pts (p=0.71) or in groups based on hormone receptor and/or human epidermal growth factor receptor 2 status. 47 pts (49.5%) received local/regional tx; no significant difference in survival (HR 0.57, 95% CI 0.23-1.40; p=0.217) or time to next tx (HR 0.67, 95% CI 0.39-1.15; p=0.144) was seen in this subgroup. Of these pts, 36 (76.6%) received neoadjuvant chemotherapy and/or immunotherapy, 5 of whom (10.6%) also started endocrine tx preoperatively. Overall, 11/47 pts (23.4%) received neoadjuvant endocrine tx. 20 pts received systemic tx without eventual surgery, and 5 pts got palliative radiation (RT). Biopsy-confirmed mets were noted in 76 pts (80%), with bone-only mets in 50%, 30 pts (31.6%) with viscera-only mets and 7 pts (7.4%) with both bone and visceral mets. 18 pts had suspected mets on imaging but did not undergo biopsy. The hazard of death was 6.34 times higher in pts with both bone and visceral mets than those with bone-only mets (p=0.008). Pts with viscera-only mets had higher survival at 2 and 3 years than pts with bone-only or both bone and visceral mets (p=0.093). Pts with 3 mets (7/76, 7.4%) had decreased survival at 1, 2, and 3 years compared to pts with 1-2 (65/76, 85.5%) mets (p=0.6). 67 pts (70.5%) received mets-directed tx; RT alone was the most common modality (52/67, 77.6%), followed by surgery (6/67, 9%), RT plus surgery (5/67, 7.5%), and ablation alone (3/67, 4.5%). There was no significant difference in survival (HR 1.27, 95% CI (0.53, 3.07), p=0.589) or time to next tx (HR 0.95, 95% CI (0.56, 1.63), p=0.856) in pts who received mets-directed tx. Multivariate analysis was not performed because most findings were not statistically significant in univariate analysis. Conclusions We did not find any significant differences in survival based on characteristics like menopausal status or site or number of mets in pts with OMBC. There was a trend toward improved survival in pts with viscera-only mets, but this finding requires validation. Local/regional and mets-directed tx did not improve survival; however, survival at 1, 3, and 5 years was excellent in this OMBC pt population. Our study was limited by low pt numbers and heterogeneity in the pt population. Findings need validation in larger studies. Citation Format: Tanmayi Pai, Raza Zarrar, Zhongwei Peng, Zhuo Li, Lauren Cornell, Kostandinos Sideras, Rohit Rao, Alvaro Moreno-Aspitia, Saranya Chumsri, Sarah McLaughlin, James Jakub, Emmanuel gabriel, Sanjay Bagaria, Laura Vallow, Santo Maimone, Pooja Advani. Clinical Features and Survival Outcomes of Oligometastatic Breast Cancer Patients: The Mayo Clinic Experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-06-04.

Survival outcomes for women with a solitary extracranial metastasis from breast cancer

BackgroundAggressive metastasis directed treatment of extracranial oligometastatic breast cancer with the aim of increasing disease-free survival has emerged as a new potential treatment paradigm, however there is currently a lack of data to assist in identifying the subset of patients who will potentially benefit most. This single-institute retrospective cohort study aimed to evaluate survival outcomes for patients with a solitary extracranial metastasis from breast cancer and to assess for significant prognostic factors. Methods and materialsMedical records of 70 female breast cancer patients with a solitary extracranial metastasis actively managed at the Peter MacCallum Cancer Centre (PMCC) Melbourne Campus between 2000 and 2019 were reviewed. Kaplan-Meier curves were used to estimate overall survival (OS), local progression free survival (LPFS) and distant progression free survival (DPFS). ResultsMedian follow-up period was 9.4 years. The study included 40 hormone receptor positive/HER2 negative (HR+HER2-), 14 hormone receptor positive/HER2 positive (HR+HER2+), 3 hormone receptor negative/HER2 positive (HR-HER2+), 9 triple negative (TNBC) and 4 unclassified breast cancer patients. 5-year OS rate for all patients was 46%, LPFS rate was 56% and DPFS was 20%. Tumour receptor group had a statistically significant association with OS and DPFS rates. TNBC patients had significantly poorer OS and DPFS rates in comparison to HR+HER2-patients. ConclusionAmong patients with a solitary extracranial metastasis from breast cancer, TNBC was associated with the poorest OS and DPFS rates. Identification of other significant prognostic factors for oligometastatic breast cancer patients may inform guidelines for metastasis directed treatments.

Definitive results of a prospective non-randomized phase 2 study on stereotactic body radiation therapy (sbrt) for medically inoperable lung and liver oligometastases from breast cancer

Background and purposeTo report mature results for local control and survival in oligometastatic (OM) breast cancer patients treated with stereotactic body radiotherapy (SBRT) on lung and/or liver lesions in a phase II trial. MethodsThis is a prospective non-randomized phase II trial (NCT02581670) which enrolled patients from 2015 to 2021. Eligibility criteria included: age > 18 years, ECOG 0–2, diagnosis of breast cancer, maximum of 4 lung/liver lesions (with a maximum diameter < 5 cm), metastatic disease confined to the lungs and liver or extrapulmonary or extrahepatic disease stable or responding to systemic therapy. The primary end-points were local control (LC) and treatment-related toxicities. The secondary end-points included overall survival (OS), distant metastasis-free survival (DMFS), time to next systemic therapy (TTNS), poly-progression free survival (PPFS). ResultsThe study included 64 patients with a total of 90 lesions treated with SBRT. LC at 1 and 2 years was 94.9 %, 91 % at 3 years. Median local control was not reached.Median OS was 16.5 months, OS at 1, 2 and 3 years was 87.5 %, 60.9 % and 51.9 %, respectively. Median DMFS was 8.3 months, DMFS at 1, 2 and 3 years was 38.1 %, 20.6 % and 16 % respectively. At univariate analysis, local response to SBRT was found to be statistically linked with better OS, DMFS and STFS. ConclusionSBRT is a safe and valid option in oligometastatic breast cancer patients, with very high rates of local control. An optimal selection of patients is likely needed to improve survival outcomes and reduce the rate of distant progression.

Phase II Trial of Definitive Therapy for Osseous Oligometastases in Breast Cancer

Phase II data for consolidative local therapy for oligometastatic disease demonstrated improved outcomes for various malignancies. However, a randomized phase II study of oligometastatic breast cancer patients testing predominantly ablative dose radiotherapy (RT) did not demonstrate progression-free survival (PFS) benefit. We conducted a single-arm phase II trial evaluating local therapy as part of the multidisciplinary management of breast cancer patients with limited bone metastases. Patients with synchronous (n = 15) and metachronous (n = 15) oligometastatic breast cancer involving ≤3 osseous sites were enrolled from July 2009 to April 2016 and treated to a total of 44 bone metastases. The trial closed early due to slow accrual. Following ≤9 months of systemic therapy, local therapy entailed surgery (n = 3) or RT delivered via conventional fractionation (≥60 Gy, n = 36) or stereotactic technique (27 Gy/3 fractions for spine mets, n = 6). When indicated, RT to the primary was delivered concurrently (n = 15). The primary endpoint was to determine PFS. Secondary endpoints were overall survival (OS), local control (LC) and toxicity. Outcomes were evaluated with Kaplan-Meier and univariate Cox proportional hazards analyses. Of the 30 patients included in the trial, 23 (77%) had ER+ or PR+/HER2- disease, 4 (13%) had Her2+ disease, and 3 (10%) were triple negative. Median age was 53, and 20 patients (67%) presented with 1 distant metastasis. A total of 21 patients (70%) experienced disease progression at a median 20.5 months (IQR: 8.2-41.2), including 5 local failures among 44 treated bone metastases (11%). At a median follow-up of 76.7 mon (IQR: 45.4-108.8), the median PFS was 37.8 mon, with 2- and 5-year rates (95% CI) of 60% (45-80%) and 32% (19-55%), respectively. The 2- and 5-year OS rates were 93% (85-100%) and 64% (48-85%), respectively, and the 2- and 5-year LC rates were 91% (80-100%) and 71% (51-98%). For patients who achieved LC, median PFS was 47.7 months (IQR 12.2-73.0). Twenty-one patients (70%) received cytotoxic chemotherapy with or without endocrine therapy for newly diagnosed oligometastatic disease. Nine patients (30%) were still alive with no evidence of disease (NED) at a median 96.9 mon (range: 47.7-158.6). PFS was worse among triple negative patients (p = 0.03), with no difference based on synchronous vs non-synchronous presentation (p = 0.10), receipt of cytotoxic chemotherapy prior to definitive therapy (p = 0.08) or Her2+ status (p = 0.21). There were no Grade ≥3 adverse events. Definitive, predominantly conventionally fractionated local therapy was associated with long-term NED status for 30% of patients with oligometastatic breast cancer involving osseous sites, with minimal treatment-associated toxicity. Developing randomized trials for breast cancer subsets may warrant consideration of standard fractionation regimen data and the need for strategies to identify patients who may benefit from definitive local therapy.

Ten-Year Outcomes of Stereotactic Body Radiotherapy for Oligometastatic Breast Cancer: Does Synchronous Oligometastatic Breast Cancer Benefit?

AimsThe benefit of stereotactic body radiotherapy (SBRT) in metachronous oligometastatic breast cancer (OMBC) has previously been described and its use in current clinical practice is established. The role of SBRT in the management of synchronous OMBC remains uncertain. The aim of this study was to compare outcomes of SBRT-treated synchronous OMBC with those of SBRT-treated metachronous OMBC. Materials and methodsThis was a retrospective analysis of consecutive extracranial OMBC patients treated with SBRT at a single institution between 2011 and 2022. Kaplan–Meier methods were used to calculate progression-free survival (PFS), overall survival, local control and distant control. Log-rank tests were used to test any differences. Cox regression was used for univariate and multivariate analyses to identify predictive factors. Toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5. ResultsIn total, 74 OMBC patients with 113 lesions were analysed. The median follow-up was 20 months (range 0–98). Seventy per cent of patients presented metachronously and 30% synchronously. 30 Gy in three fractions was most commonly prescribed, resulting in a median biologically effective dose (BED at α/β = 10) of 60 Gy (range 35.7–112.5 Gy). Forty-nine per cent of patients switched systemic therapy post-SBRT (median time to switch: 14 months, range 0–79). Two patients (2%) experienced grade 3 acute toxicities with no grade ≥4 toxicities. At 2 years overall survival was 92.4% and PFS 39.0%, local control 85.9% and distant control 37.0%. For metachronous and synchronous disease, respectively, 2-year local control rates were 86.5% and 85.8% and PFS rates were 35.3% and 48.3%. The median PFS of metachronous and synchronous disease were 18 months and 17 months, respectively (P = 0.86). Predictive factors on multivariate analysis were treated site for overall survival, change in systemic therapy post-SBRT for PFS and BED for local control. ConclusionOur data confirm SBRT as a well-tolerated treatment for OMBC with excellent local control rates regardless of metachronous or synchronous presentation. There is no suggestion that survival outcomes are inferior for synchronous disease. Further prospective studies are required to validate this finding.

Oligometastatic breast cancer and metastasis-directed treatment: an aggressive multimodal approach to reach the cure.

Metastatic breast cancer (BC) is considered an incurable disease and is usually treated with palliative intent. However, about 50% of metastatic BCs present with only a few metastatic lesions and are characterized by longer overall survival. These patients, defined as oligometastatic, could benefit from a multimodal approach, which combines systemic therapy with metastasis-directed treatment (stereotactic ablative therapy or surgery). The current definition of oligometastatic seems incomplete since it is based only on imaging findings and does not include biological features, and the majority of relevant data supporting this strategy comes from retrospective or non-randomized studies. However, the chance of reaching long-term complete remission or even a cure has led to the development of randomized trials investigating the impact of combined treatment in oligometastatic BC (OMBC). The SABR-COMET trial, the first randomized study to include BC patients, showed promising results from a combination of stereotactic ablative radiotherapy and systemic therapy. Considering the randomized trial's results, multidisciplinary teams should be set up to select OMBC patients who could achieve long-term survival with aggressive multimodal treatment.

Oligometastatic Breast Cancer Patients Treated with High-Dose Chemotherapy and Targeted Radiation: Long-Term Follow-Up of a Phase II Trial.

Simple SummaryBased on recent clinical trials, radiation is a standard treatment option for limited metastatic sites in metastatic breast cancer, with the potential to improve survival. This is typically given in the form of high-dose radiation called stereotactic body radiotherapy (SBRT). However, SBRT is a newer technology that is not on option for all patients and does not have long-term follow-up. Prior to the widespread implementation of SBRT, we performed a clinical trial utilizing high-dose chemotherapy and standard radiation for metastases in patients with limited metastatic breast cancer. In this research, we analyzed the long-term outcomes of these patients. We found that, despite not using SBRT, radiation provided promising long-term disease control and survival. Therefore, conventional radiation might still be considered if SBRT in not an option for a patient, and our results also help suggest what long-term outcomes of SBRT treatment might look like.Background: Patients with oligometastatic breast cancer (oMBC) may benefit from aggressive local therapy. We sought to assess the effects of consolidative radiation therapy (RT) on outcomes in oMBC patients treated on a prospective phase II trial of high-dose chemotherapy (HDCT). Methods: Between 2005 and 2009, 12 patients with oMBC (≤3 metastatic sites) cancer were treated on protocol. Patients were to receive tandem HDCT supported by hematopoietic cell rescue (HCR). All radiographically identifiable oligometastatic sites received targeted radiation. Results: HDCT was initiated at a median of 6.7 (3.5–12.7) months after diagnosis of oMBC. Hormone receptors (HR) were positive in 91.6% of patients, and HER2 was overexpressed in 25% of patients. Median radiation dose (EQD2) was 41.2 (37.9–48.7) Gy. Median follow-up was 13.1 (6.8–15.1) years for living patients. Ten-year PFS and OS were 33% (95%CI, 10–59%) and 55% (95%CI, 22–79%), respectively. Durable local control of treated lesions was 87.5%. At the last follow up, two patients remained progression free and two more were without evidence of disease following additional salvage treatment. Conclusions: Although modern systemic therapies have obviated the use of HDC, aggressive local therapy warrants further evaluation and fractionated radiotherapy is a viable alternative if SBRT is not available.

Survival and prognostic factors in oligometastatic breast cancer.

1089 Background: Clinical guidelines for the treatment of oligometastatic breast cancer (OMBC) propagate multimodality treatment including polychemotherapy and ablative local therapy for all detected disease. The aim of this aggressive approach is prolonged disease remission, or even cure, but randomized data to support this strategy lack and long-term outcomes are not well known. We report prognostic factors, and event-free survival (EFS) and overall survival (OS) in a real world, single center cohort of patients with OMBC with long-term follow-up. Methods: Patients with breast cancer and 1-3 distant metastatic lesions who underwent treatment in the Netherlands Cancer Institute were identified via text mining of medical files. We collected patient, tumor and treatment characteristics as well as recurrence and survival data from the medical records. The Kaplan-Meier method was used to calculate EFS and OS estimates, and Cox regression analyses to assess potential prognostic factors. Results: The cohort included 239 patients (of whom two males), diagnosed between 1997 and 2020. Median follow-up was 75.0 months. Fifty-one percent had hormone receptor (HR)-positive/ human epidermal growth factor receptor 2 (HER2)-negative disease, 20.1% had HER2-positive disease, and 19.2% had triple negative (TN) disease. Median age at OMBC diagnosis was 49.0 years and 47.3% of patients had synchronous disease (metastases ≤6 months of primary diagnosis). Most patients (81.2%) received chemotherapy and local therapy (surgery, radiotherapy and/or radiofrequency ablation) of all metastatic lesions (83.7%). Of 239 patients, 134 experienced disease recurrence with a median EFS of 40.0 months (95% confidence interval (CI): 28.6-51.4); 97/239 died and median OS was 93.0 months (95% CI 74.5-111.5). The table shows factors associated with favorable OS in multivariable analysis. Cox regression analysis for EFS showed similar results. Conclusions: In this large real world cohort of OMBC patients, EFS and OS compare favorably to survival in the general MBC population. HR-positive and/or HER2-positive subtypes, synchronous disease or long DFI, favorable response to first-line systemic therapy and local therapy of all distant lesions are independently associated with better survival. Future studies should be directed at optimizing patient selection and therapy choices in this population with the potential for cure. [Table: see text]

PD-0750 Outcome after stereotactic body radiotherapy (SBRT) for oligometastatic breast cancer patients

PD-0750 Outcome after stereotactic body radiotherapy (SBRT) for oligometastatic breast cancer patients

Distribution Characteristics and Prognostic Value of Immune Infiltration in Oligometastatic Breast Cancer.

BackgroundTo assess the distribution characteristics and the prognostic value of immune infiltration in female oligometastatic breast cancer patients.MethodsWe retrospectively analyzed the clinicopathological data of oligometastatic breast cancer (OMBC) patients diagnosed between June 2000 and January 2020. Immune markers were quantified by immunohistochemistry on FFPE tissues in paired normal breast tissues, primary breast cancers and oligometastatic lesions. Survival analyses were performed using the Kaplan-Meier curves and Cox-proportional hazards model.ResultsA total of 95 female OMBC patients visited Sun Yat-sen University Cancer Center between June 2000 and January 2020, and 33 of them had matched normal breast tissues, primary cancers and oligometastatic lesions and were reviewed in immune infiltration analysis. CD8 of primary tumors had a higher expression than that in matched normal tissues. The expressions of CD8 and FOXP3 were higher in the primary sites than that in the oligometastatic lesions. CD3, CD4 and CD8 were significantly lower in the intratumoral regions than that in the peritumoral regions both in primary and oligometastatic lesions. Notably, the high percentage of CD3 in the intratumoral oligometastatic lesions predicted the longer PFS and OS, and higher CD4 in the same lesions also predicted a better OS. There was obviously positive correlation between CD4/CD3 and Ki-67 in primary cancers and negative correlation between CD4/CD3 and ER in oligometastatic sites.ConclusionWe explored immune distribution and evolution in time and space in OMBC to provide new understandings for biological behaviors of this disease and further divided patients in different prognosis.

Stereotactic Body Radiation Therapy for Oligometastatic Breast Cancer: A Retrospective Multicenter Study.

IntroductionStereotactic radiotherapy may improve the prognosis of oligometastatic patients. In the literature, there is very little data available that is specific to breast cancer.Materials and MethodsWe conducted a multicenter retrospective study. The primary objective was to estimate progression-free survival after stereotactic body radiotherapy (SBRT) using Cyberknife of breast cancer oligometastases. The secondary objectives were to estimate overall survival, local control, and toxicity. The inclusion criteria were oligometastatic breast cancer with a maximum of five lesions distributed in one to three different organs, diagnosed on PET/CT and/or MRI, excluding brain metastases and oligoprogressions. This was combined with systemic medical treatment.FindingsForty-four patients were enrolled from 2007 to 2017, at three high-volume cancer centers. The patients mostly had one to two lesion(s) whose most widely represented site was bone (24 lesions or 44.4%), particularly in the spine, followed by liver (22 lesions or 40.7%), then pulmonary lesions (six lesions or 11.1%). The primary tumor expressed estrogen receptors in 33 patients (84.6%); the status was HER2+++ in 7 patients (17.9%). The median dose was 40 Gy (min-max: 15-54) prescribed at 80% isodose, the median number of sessions was three (min-max: 3-10). The median D50% was 42 Gy (min max 17-59). After a median follow-up of 3.4 years, progression-free survival (PFS) at one year, two years, and three years was 81% (95% CI: 66-90%), 58% (95% CI: 41-72%), and 45% (95% CI: 28-60%), respectively. The median PFS was 2.6 years (95% CI: 1.3 – 4.9). Overall survival at three years was 81% (95% CI: 63-90%). The local control rate at two and three years was 100%. Three patients (7.3%) experienced G2 acute toxicity, no grade ≥3 toxicity was reported.ConclusionThe PFS of oligometastatic breast cancer patients treated with SBRT appears long, with low toxicity. Local control is high. SBRT for oligometastases is rarely applied in breast cancer in light of the population in our study. Phase III studies are ongoing.

Stereotactic body radiotherapy to treat breast cancer oligometastases: A systematic review with meta-analysis

ObjectivesStereotactic ablative radiotherapy (SABR) has been reported to be an effective treatment for oligometastatic disease from different primary cancer sites. Here we assess the effectiveness and safety of SABR for oligometastatic breast cancer patients by performing a meta-analysis. MethodsFollowing PRISMA and MOOSE guidelines, a systematic review and meta-analysis was performed. Eligible studies were identified on Medline, Embase, Cochrane Library, and annual meetings proceedings from 1990 to June 2021. A meta-regression analysis was performed to assess if there was a correlation between moderator variables and outcomes, and a p-value <0.05 was considered significant. ResultsTen studies met criteria for inclusion, comprising 467 patients and 653 treated metastases. The 1- and 2-year local control rates were 97% (95% CI 95–99%), and 90% (95% CI 84–94%), respectively. Overall survival (OS) was 93% (95% CI 89–96%) at 1 year, 81% (95% CI 72–88%) at 2 years. The rate of any grade 2 or 3 toxicity was 4.1 % (95% CI 0.1–5%), and 0.7% (0–1%), respectively. In the meta-regression analysis, only prospective design (p = 0.001) and bone-only metastases (p = 0.01) were significantly associated with better OS. In the subgroup analysis, the OS at 2y were significantly different comparing HER2+, HR+/HER2(-) and triple negative breast cancer 100%, 86% and 32%, p = 0.001. For local control outcomes, hormone receptor status (p = 0.01) was significantly associated on meta-regression analysis. ConclusionSABR for oligometastatic breast cancer is safe and associated with high rates of local control. Longer follow-up of existing data and ongoing prospective trials will help further define the role of this management strategy.

Long-term outcomes of oligometastatic breast cancer patients treated with curative intent: an updated report.

Oligometastatic breast cancer (OMBC) is characterized by limited metastatic tumor numbers and sites. We have reported a 20-year overall survival (OS) rate and relapse-free rate (RFR) of 34.1% and 27.4%, respectively, in a retrospective analysis of OMBC patients treated with curative intent including a multidisciplinary approach. Metastatic breast cancer (MBC) is generally incurable; however, OMBC might be a potentially curable subset. The previous analysis included isolated locoregional recurrence (ILRR) cases, which differs from distant metastasis in treatment strategies. Therefore, in this study, we excluded ILRR cases and provided an update on clinical outcomes. We also performed a detailed subgroup analysis of OMBC patients by introducing new prognostic variables. Data of 73 OMBC patients, including 10 ILRR cases, treated in our institution between 1980 and 2010 were retrospectively analyzed. OMBC was defined as the presence of metastatic lesions in 1-2 organs, < 5 lesions per metastasized organ, and lesion diameter < 5cm. The median follow-up duration was 151 (range 12-350) months. Twenty-eight (44%) patients received local therapy. Excluding ILRR cases, the OS rates were 28.3% and 18.9% and RFRs were 26.7% at 20 and 25years, respectively. In multivariate analysis, single-organ involvement and three or fewer metastatic lesions per organ were associated with a longer progression-free and relapse-free interval (RFI). Relapse-free interval reached a plateau after 20years at approximately 25% probability. Patients with long-term survival without disease relapse are considered cured. Curative-intent therapy should be considered for OMBC patients, especially those with low tumor volume.

Abstract PS1-58: The role of resection of the primary tumour in patients with de novo oligometastatic breast cancer (OMBC)

Abstract Purpose: The role of resection of the primary tumour in management of patients with OMBC is controversial. Loco-regional treatment (LRT) with curative intent could be discussed considered for OMBC patients, who experience good response to systemic therapy. We retrospectively studied the impact of resection of the primary tumour on overall survival (OS) for de novo OMBC treated at Oscar Lambret Center in Lille.Patients and methods: Between 2005 and 2017, all consecutive patients were selected. De novo OMBC was defined by 1 to 5 metastases in 1 or 2 organs, diagnosed within three months after primary tumor. Clinical data, tumor characteristics, metastatic sites, locoregional treatment, systemic first line treatment were recorded retrospectively. We set up 2 groups according to therapeutic strategy. Group 1 patients were managed with a prior planned curative intent surgery and systemic treatments and group 2 included patients with systemic therapy alone, without plan of surgery.Results: 116 patients were included in our analysis; 78 patients in group 1 and 38 patients in group 2. Median age was 54,9 years (25,2-86,2) with no difference between both groups (p=0,08). TNM stage, cancer histologies were comparable in both groups, excluding that there were more HER2+ tumour in Group 2 (p=0.003). 81 patients underwent LRT, 69 patients in group 1 and 12 patients in group 2. 59% of them had radical mastectomy and 89% had axillary surgery. For 29% of them, surgery was performed before knowledge of metastatic disease. The other main indications of breast surgery included stable disease (50%), local progression (9%), palliation (5%), single metastasis (5%) and complete metastatic response after chemotherapy (2%). 59 of 81 patients had adjuvant radiotherapy. Regarding systemic first line treatment, patients in group 1 received more chemotherapy (63% vs 86%, p=0.01), anti-HER2 treatment was appropriate except for 6 patients because of heart disease and 69% of patients had hormone therapy with no difference in both groups. Regarding metastases at diagnosis, the mean number of metastases was 2,1 (SD=1,2), 103 patients (89%) had one metastatic site, and 13 patients (11%) had two metastatic sites, with no difference between both groups. Secondary bone involvement was most prevalent site (69%). There was no difference between both groups in metastasis distribution. Median OS was 70,2 months in our cohort. LRT did not improve OS (HR 1,23; 95% CI [0,75-2,00] p=0,41), even after adjustment on age and HER2 status. Median progression free survival (PFS) was 30,2 months in our cohort. LRT did not improve PFS in comparison with systemic treatment alone (HR 1,38; 95% CI [0,91- 2,11] p=0,13).Conclusion: We found that LRT did not improve outcome (PFS or OS) in OMBC patients. This is in line with recently issued large randomized phase III trial. LRT is not a standard of care in OMBC, nevertheless, further clinical studies are needed to better identify the subgroup of OMBC patients that could benefit from LRT, at least in term of quality of life. Citation Format: Charlotte Debuquoy, Claudia Regis, Jennifer Wallet, David Pasquier, Nicolas Penel, Marie-Cecile Le Deley, Marie-Pierre Chauvet, Emilie Kaczmarek. The role of resection of the primary tumour in patients with de novo oligometastatic breast cancer (OMBC) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-58.

Radical Conformal Radiotherapy versus Two-Dimensional Radiotherapy in Oligometastatic Breast Cancer Patients: Response, Toxicity, and Survival

AbstractBackground: oligometastatic breast cancer patients achieved better progression-free survival without significant toxicity, so this urge patients subgroups identification who might gain more benefit from aggressive local therapy. In comparison to antro posterior, post anterior, and direct post anterior techniques, 3-dimensional conformal irradiation delivered for treatment of lumbar vertebrae metastasis was much better in the decrease of bowel and spinal cord exposure. Aim of the work: to evaluate clinical outcome gains achieved by 3D radiotherapy versus 2D radiotherapy in certain breast cancer patients with bony oligo metastasis with expected favorable survival.Methods: In a retrospective cohort, 60 patients were enrolled in 2D versus 3D arm. Treatment and survival outcomes were observed. Results: 3D radiotherapy offer a significantly better pain response, local control, and lower toxicity than patients were received treatment delivery by 2D radiotherapy with p-value = 0.004,0.002 and 0.004 respectively, patients were delivered 2D radiotherapy had shown a progressive disease than those treated by 3D radiotherapy of statistical significance p-value = 0.01. The 3D arm was better than the 2D arm in the term of better significant PFS and nonsignificant OS, p-value = 0.04, 0.14 respectively. Conclusion:3D conformal radiotherapy is of great value in the improvement of local control, pain response, progression-free survival, and overall survival with a tolerable toxicity profile in breast cancer patients diagnosed with bony oligo metastasis.Keywords; Conformal radiotherapy, 2-dimensional radiotherapy, oligometastatic, breast cancer

165P Immune characterization of the de novo oligometastatic breast cancer

De novo oligometastatic breast cancer (OMBC) is a rare presentation of advanced stage breast cancer (BC) with ≤ 5 metastatic lesions at diagnosis. Its clinical management is not well defined because of varying definitions, lack of specific biomarkers and lack of dedicated prospective clinical studies. Here, we investigated tumor immune microenvironment, classical clinic-pathological parameters including treatment and correlated them with survival in a cohort of de novo OMBC patients to better characterize this disease entity.

Local Treatment in Addition to Endocrine Therapy in Hormone Receptor-Positive and HER2-Negative Oligometastatic Breast Cancer Patients: A Retrospective Multicenter Analysis

Background: Recent trials have provided robust evidence demonstrating that endocrine therapy with/without targeted therapy, such as cyclin-dependent kinase 4/6 inhibitors or mTOR (mammalian target of rapamycin) inhibitors, effectively halts disease progression in hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. We investigated the survival impact of local treatment of metastases as a first-line treatment after metastasis in HR-positive and HER2-negative breast cancer patients with a very low metastatic volume. Materials and Methods: From a retrospectively constructed database for three institutes, we identified HR-positive and HER2-negative breast cancer patients with recurrent distant oligometastatic disease after initially curative treatment. De novo stage 4 patients were excluded, and only those with recurrent metastatic disease were included. Oligometastatic disease was defined as follows: (1) ≤2 metastatic lesions in a single organ, (2) a maximal diameter ≤3 cm, and (3) organ involvement, including the lung, liver, adrenal gland, bone, or distant lymph nodes. Local treatment comprised surgery or radiotherapy. Progression-free survival (PFS) and overall survival (OS) were investigated. Results: Forty-nine patients were included; 33 underwent local treatment. Of these 33 patients, 5 underwent surgical resection and 27 received radiotherapy. One patient underwent both surgical resection and radiotherapy. Median PFS was significantly longer among the patients with local treatment than among the patients without local treatment (30.0 vs. 18.0 months, p = 0.049). In multivariate analysis, local treatment was shown to prolong PFS. However, median OS after metastasis did not differ with regard to local treatment (72.3 vs. 91.0 months, p = 0.272). Conclusion: We showed that local treatment could positively affect disease progression in HR-positive and HER2-negative oligometastatic breast cancer.

Oligometastatic breast cancer.

Metastatic breast cancer (MBC) is considered as incurable. The group of patients with oligometastatic disease (a few metastatic lesions and organs involved) apparently have better prognosis. It is claimed that, these patients could be treated with curative intent, and multidisciplinary aggressive approach should be considered. Despite the lack of strong data it is increasingly accepted in clinical practice. Currently, the appropriate candidate would be young woman with good performance status, low tumour burden with long disease-free interval. Because for them with already favorable nature of their disease, aggressive treatment has greater chances to improve survivals. Local ablative treatment (radiotherapy/surgery) has a crucial role in this setting. Available mainly from retrospective in nature long-term results are encouraging but need confirmation in prospective randomized studies. In this review, I discuss the definition of oligometastatic disease, its nature, currently available data and ongoing prospective randomized trials dedicated to oligometastatic breast cancer patients.