Oligometastatic Breast Cancer Research Articles

3216: Can we predict response after stereotactic body radiotherapy in oligometastatic breast cancer?

3216: Can we predict response after stereotactic body radiotherapy in oligometastatic breast cancer?

Outcomes of De Novo Oligometastatic Breast Cancer Treated With Surgery of Primary and Metastasis Directed Radiotherapy.

With sensitive imaging for breast cancer, the question arises whether present-day oncologists treat dOMBC with palliative systemic therapy (ST), which, a few years earlier, would have been treated with curative intent. We retrospectively analyzed outcomes of dOMBC treated with curative intent using a combination of surgery, metastasis-directed radiotherapy (RT), and adjuvant/neoadjuvant ST and have also explored the possible role of total lesional glycolysis of metastases and p53 immunohistochemistry in predicting outcomes. Data were collected from a prospectively maintained database using electronic medical records and Radiation Oncology Information System. In the study, dOMBC was defined as up to 3 metastatic sites, all amenable to treatment with ablative RT and primary and axillary disease amenable to curative surgery. Patients were treated with surgery, ST, and RT. Patients underwent either breast conservation surgery or modified radical mastectomy. Patients were treated with 6 to 8 cycles of chemotherapy in the neoadjuvant and/or adjuvant setting. Hormone receptor-positive patients received either tamoxifen or aromatase inhibitors. Trastuzumab was offered to Her-2-neu receptor-positive patients. RT included locoregional RT and metastases-directed ablative body RT. The median progression-free survival was 39 months (95% CI: -28.7 to 50.1mo). Two and 3 year estimated disease-free survival (DFS) was 79% and 60.5%, respectively. The median overall survival was not reached. The estimated 3-year overall survival was 87.3%. Total lesional glycolysis of metastases score and p53 status did not affect DFS. Combination treatment of surgery, metastases-directed ablative RT, and ST may provide prolonged DFS in dOMBC.

Oligometastatic breast cancer. When is the time for local treatments?

Oligometastatic breast cancer. When is the time for local treatments?

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.

Neoadjuvant pertuzumab, docetaxel, carboplatin, and trastuzumab (PTCH) regimen in patients with HER2 positive early, locally advanced, and oligometastatic breast cancer: Real-world Indian experience.

e12556 Background: Pertuzumab/docetaxel/carboplatin/trastuzumab (PTCH) regimen constitutes one of the standard neoadjuvant treatments in human epidermal growth factor receptor-2 (HER2) positive breast cancer. The real-world outcomes of its use from the Indian sub-continent are lacking. Methods: We retrospectively reviewed the medical records of 114 HER2-positive BC patients presenting with nonmetastatic or oligometastatic disease and treated with a uniform PTCH regimen in a neoadjuvant setting at the All India Institute of Medical Sciences, New Delhi, India, between Jan 2015 to May 2023. Total six cycles of PTCH [pertuzumab (840 mg loading followed by 420 mg), docetaxel (75 mg/m2), carboplatin (AUC 6), trastuzumab (8 mg/kg loading followed by 6 mg/kg) q21 days] were administered with primary GCSF prophylaxis. The primary outcome was invasive disease-free survival (iDFS). The secondary outcomes included pathological complete response (pCR) rates, overall survival (OS), and toxicity. Adjuvant trastuzumab is used for patients achieving pCR, while for patients not achieving pCR option of adjuvant trastuzumab emtansine (T-DM1) or trastuzumab was decided based on patient affordability. Results: One hundred and fourteen (114) patients were included with a median age of 47 years (range, 23-70). Overall, 52 (45.6%) patients had hormone-positive disease and 73 (64.01%) were premenopausal. Forty patients (35.08%) had stage II, 62 (54.38%) had stage III, and 12(10.5%) had oligometastatic disease. Sixty-one (53.5%) patients underwent breast conservation surgery and pCR was observed in 62 (54.38%) cases. With a median follow-up of 31 months, the 3-year iDFS was 81.5% and overall OS was not reached. Median iDFS was 33 months in patients with node-positive disease and was not reached in patients with node-negative disease. Three-year iDFS was 68.1% in patients who achieved pCR and 49.8% in those who did not achieve pCR (p=0.001). Grade 3/4 toxicity was seen in 26.7% of patients which caused dose modification and interruption in 13.9% of patients. The most common grade 3/4 toxicity was diarrhea in16 (14.03%) cases and thrombocytopenia in 11 (9.6)% cases . Febrile neutropenia was seen in 4 (3.5%) patients. Four patients (3.5%) had a reversible decrease in cardiac left ventricular ejection fraction. Conclusions: In a real-world context, PTCH is an effective and safe anthracycline-free regimen for use in curative (adjuvant and neoadjuvant) setting for HER2 positive breast cancer in Indian women Using neoadjuvant PTCH may improve pCR and obviate the need for adjuvant T-DM1 after surgery making it a cost-effective strategy in limited recourse setting. The survival outcomes were significantly better among those with node-negative disease and among those who achieved a pCR.

Current management practices of de novo oligometastatic breast cancer: Real-world data from a physician survey.

1104 Background: De novo oligometastatic breast cancer (oligo-mBC) is generally defined as < 5 lesions at the time of diagnosis and represent a steadily increasing subset of metastatic cancers. Several retrospective studies demonstrated prolonged overall survival (OS) for select patients with oligo-mBC when treated with multimodality therapy (chemotherapy, surgery, and radiation). However, randomized trials that tested surgical resection of the primary tumor, or radiation of oligometastases (including recurrent and de novo disease) showed no OS benefit. No randomized trials to date have tested all 3 treatment modalities combined (as used with curative intent in early-stage disease). Current NCCN guidelines do not include specific recommendations for de novo oligo-mBC, the St Gallen International guidelines allow multimodality therapy for carefully selected patients. We surveyed practicing medical oncologists through the ASCO survey pool regarding their use of multimodality therapy in de novo oligo-mBC. Methods: An online survey was sent to the ASCO Research survey pool (N=999) between 11/14/23 – 12/29/23, 193 ASCO members completed the survey. Data was confidential and anonymous. Results: The majority (76-79%) of respondents recommend starting with palliative systemic chemotherapy. If patients have a response to initial chemotherapy, 42-54% recommend ablative radiation to all residual lesions, and 38-52% recommended surgical resection of the primary tumor. Overall, multimodality therapy is recommended sometimes by 29-36%, often by 19-29%, almost never by 32-41%, and never by 2-7% of respondents. Recommendations varied by disease subtype (Table). Conclusions: These survey data indicate varied practices in the treatment of de novo oligo-mBC. This highlights the need for future randomized clinical trials to investigate whether there may be survival benefit by receptor subtype in de novo oligo-mBC treated with curative intent multimodality therapy as used in locally advanced cancers. [Table: see text]

Advancements in oligometastatic breast cancer: a comprehensive review of current strategies and the role of artificial intelligence.

In the dynamic landscape of Breast Cancer (BC), Oligo- Metastatic Breast Cancer (OMBC) presents unique challenges and opportunities. This comprehensive review delves into current strategies for addressing OMBC, covering locoregional and site-specific metastasis management, and addressing both surgical and minimally invasive therapies as essential components. Moreover, the transformative role of Artificial Intelligence (AI) is spotlighted. However, while the future looks promising, several limitations need addressing, including the need for further research, especially in diverse patient populations and resource-challenged settings. AI implementation may require overcoming the lack of Electronic Health Records acceptance in resource-challenged countries, which contributes to a scarcity of large datasets for AI training. As AI continues to evolve, validation and regulatory aspects must be continually addressed for seamless integration into clinical practice. In summary, this review outlines the evolving landscape of OMBC management, emphasizing the need for comprehensive research, global collaboration, and innovative AI solutions to enhance patient care and outcomes.

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.

Abstract PO4-22-06: Outcomes following Stereotactic Radiotherapy in Oligometastatic Breast Cancer: a single centre retrospective review

Abstract Introduction: Stereotactic radiotherapy (SABR) is an increasingly used treatment for oligometastatic disease with evidence of survival benefit shown in the SABR-COMET trial. However, the benefit in oligometastatic breast cancer has been brought into question following initial results from the NRG-BR002 trial. Methods: A retrospective review of all patients with primary breast cancer treated with stereotactic radiotherapy for oligometastases at our institution was carried out. A total of 31 patients received treatment to 36 lesions between August 2015 and December 2022. Results: Neither median overall survival nor progression free survival were reached after median follow up time of 21.5 months. Hormone receptor status as follows: ER+, HER2- (n=25), ER+, HER2+ (n=4,), TNBC (n=2). The majority of lesions treated were bony metastases (92%, of which 17 vertebral and 11 pelvic lesions). The majority had oligometastatic disease at time of SABR (67%), with 33% treated for oligoprogression. Most patients were on systemic anti-cancer therapy (SACT) at the time of SABR, or had a planned start of SACT shortly following treatment. Breakdown of systemic therapy as follows: Endocrine therapy (ET) alone 9 patients (29%), CDK4/6 inhibitor plus ET 13 patients (42%), chemotherapy 3 patients (10%), antibody drug conjugate 2 (6%), anti-HER2 therapy + ET 2 patients (6%), none 2 patients (6%). All patients also received bone-targeted agents (zoledronic acid or denosumab). Local control was achieved in 33 lesions (92%), all of which were bony lesions. Local control was maintained in both patients who were not on SACT: one patient with ER+ HER2- disease developed distant progression after 27 months, the other with TNBC remains disease free after 13 months. Loss of local control was observed in all non-bony sites (lung, IMC node, peri-ureteric soft tissue mass) at a median interval of 10 months (range 7-43 months). 14 patients subsequently developed distant disease progression at median interval of 15 months (range 0-43 months). 12 month progression free survival was 77%. 13 patients received further SACT at median interval of 16 months. Conclusions: SABR for bony metastases from breast cancer has excellent local control rates in combination with systemic treatment but may also give patients significant time off treatment. Questions remain regarding the ideal sequencing and combination of SABR and SACT, particularly in hormone receptor positive patients where there are a number of lines of effective SACT. Citation Format: Sophie Lynch, Sugeeta Sukumar, Elinor Sawyer, Daniel Smith, Christy Goldsmith. Outcomes following Stereotactic Radiotherapy in Oligometastatic Breast Cancer: a single centre retrospective review [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 PO4-22-06.

Abstract PO2-05-11: Patient Perspectives on the Value of Stereotactic Body Radiotherapy (SBRT) in the Management of Breast Cancer: The PERSPECTIVE Study

Abstract Background: Oligometastatic disease describes limited metastases amenable to local therapy such as stereotactic body radiotherapy (SBRT). Within the UK National Health Service (NHS), SBRT is a standard of care for up to 3 metachronous sites of oligometastatic breast cancer (OMBC), offering high local control rates with low toxicity. The SABR-COMET study demonstrated improved progression-free survival (PFS) and overall survival (OS) with SBRT compared to standard of care in a number of oligometastatic cancers, including breast cancer [1]. Conversely, the NRG-002 trial results suggest no PFS or OS improvement with the addition of SBRT to standard systemic therapy in OMBC [2]. The OS data for this study are yet to mature and in the meantime the results of other prospective studies are awaited. As patients’ attitudes and perspectives govern their preferences around treatment decisions, it is vital to understand whether PFS and OS are the most important considerations for patients. This study aims to explore patients’ perspective on the role of SBRT in breast cancer management. Their views will help inform future trial endpoints and support clinicians to support patients with their decision making and expectations. Methods: We conducted an exploratory qualitative study with focus groups and individual interviews, to understand participants knowledge, views and opinions on SBRT in treating breast cancer. All patients were asked to watch an educational video about SBRT in advance of participating in the interviews. An interview guide with open-ended questions was developed. Breast cancer patients were recruited using a purposive sampling matrix based on the patients age, presence of metastatic disease and previous experience with radiotherapy. Each focus group had at least two moderators and all interviews were digitally recorded and then transcribed. The data were managed and coded using NVivo version 12 and analysed using a thematic analysis approach. Results: A total of 18 breast cancer patients participated in this study, with 7 (39%) having primary disease and 11 (61%) with metastatic disease. The study included two focus groups (group one = 5 patients; group two = 9 patients) and four individual interviews conducted between May and June 2023. The participants had a median age of 54 years (range 38-74). The majority of participants (83%) had previous experience with radiotherapy, with 4 (27%) having received SBRT previously for their OMBC. Only 2 (2%) patients who had not previously received SBRT were aware of it before participating in this study. Most of the patients (78%) were Caucasian and 72% had attained at least an undergraduate degree level of education. Throughout the study, three main themes emerged: theme 1 - participants experience with radiotherapy; theme 2 - interests and considerations regarding SBRT (including desired treatment outcomes) and theme 3 - willingness to consider SBRT in absence of a survival benefit. Extending their life was unanimously described as the most important desired outcome of SBRT, followed by quality of life. Other desired treatment outcomes expressed included reduction of tumour size, minimal collateral damage/side effects, relief of symptoms, avoidance of recurrence and increase in time to change of systemic therapy. Conclusion: In our study, while extension of life was a desired treatment outcome of SBRT for OMBC, all participants expressed willingness to consider SBRT for its potential benefits in local control and durable pain control, even in absence of a survival benefit.

Abstract PO1-12-02: Impact of Discontinuation of Denosumab on Bone Health in Breast Cancer Patients

Abstract Denosumab (Dmab), an inhibitor of osteoclast activity and proliferation is approved for treatment of women on aromatase inhibitor (AI) therapy for early breast cancer (60 mg Q 6-months) and metastatic disease (120 mg Q 4-weeks) to protect against bone loss and prevention of skeletal-related events (SREs). 60 mg given twice a year has shown fracture reduction, especially in women on aromatase inhibitor therapy, and recent data supports benefits in disease free survival, bone-metastasis free-survival and overall survival with Dmab in early breast cancer. It appears superior in reduction of SREs versus zoledronic acid (ZA) in established skeletal metastatic disease; thus, a preferred choice in the oncology setting. In the osteoporosis setting, withdrawal of Dmab therapy leads to a “rebound” increase of bone resorption, rapid bone loss and potential vertebral fractures. Increased risk of spontaneous and multiple vertebral fractures has been seen in this patient population. To prevent this, after discontinuation of Dmab, the addition of another anti-resorptive such as ZA is initiated. Dmab withdrawal events are uncommonly reported in patients with metastatic skeletal disease due to generally poor prognosis. Dmab given as 120 mg/month in this setting may need to be curtailed for a variety of indications including hypocalcemia, major dental procedures, osteonecrosis of the jaw or atypical femoral fracture. In the oncologic setting, it is unclear if discontinuation of Dmab will lead to rebound bone resorption or increased incidence of fractures. We describe the case is of a 32-year-old woman with a history of T2N3M1, oligometastatic breast cancer (solitary bone metastases at L1, biopsy-proven) that was ER/PR/HER2 positive. She was treated with neoadjuvant trastuzumab, pertuzumab, taxotere and carboplatin followed by bilateral mastectomy, and radiation to chest wall and L1. She received total estrogen blockade initially with GnRH-agonist and exemestane and ultimately bilateral salpingo-oophorectomy plus exemestane. She continues pertuzumab and trastuzumab (80 treatments to date) for the past 5 years and denosumab 120 mg/month for 14 treatments and then every 3 months, 20 total treatments. Development of hip pain (regular runner) and concern for atypical fracture vs metastatic disease led to bone scan and PET/CT. Metastatic disease was ruled out and stress reaction was diagnosed. Dmab therapy was discontinued with monitoring of her metabolic bone turnover. 1 year after her last Dmab injection, bone turnover markers began to increase and ultimately demonstrated a very significant “rebound phenomenon.” Subsequently, a single dose of 120 mg denosumab decreased bone markers to previously low levels which remain low on routine monitoring, table below. In future, ZA will be initiated and continued on a yearly basis. Dmab has replaced ZA in managing bone health in breast cancer patients. Many oncologists use this without the assistance of bone health endocrinologists, who are an integral part of our cancer center. Bone modifying agents are often discontinued without consideration of the negative impact this may have. As this is a major survivorship issue, we document this case with literature review, to raise awareness for oncologists prescribing these medications. Citation Format: Susan Tannenbaum, Alvaro Alvarez Soto, Pamela Taxel. Impact of Discontinuation of Denosumab on Bone Health in Breast Cancer Patients [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 PO1-12-02.

Abstract PO2-06-02: Characteristics and Treatment Patterns of de novo Oligometastatic Stage IV Breast Cancer: A Single-Center Retrospective Cohort Study

Abstract Background: Retrospective studies suggest that patients with oligometastatic breast cancer (≤ 5 metastatic lesions) have improved prognosis and may benefit from multimodality treatment. Randomized clinical trials, however, with mostly recurrent oligometastatic breast cancer have not shown improved prognosis with this approach. Real-world data on de novo oligometastatic stage IV (oligo-stage IV) disease are limited. We therefore investigated differences in 5-year mortality in patients with de novo oligo-stage IV vs de novo extensive-stage IV breast cancer who received curative vs palliative chemotherapy at our institution. Methods: In a retrospective cohort design, using the Yale tumor registry, we identified de novo stage IV breast cancer (metastatic to distant sites at diagnosis), diagnosed 2012-2016. Clinical characteristics and treatment patterns were compared between oligo-stage IV vs extensive-stage IV. Curative regimens were defined as TCHP or AC-THP for HER2+, ddAC- >T or TC for ER+, and ddAC- >T for TNBC. Palliative regimens were defined as THP for HER2+ or single agent chemotherapy. 5-year mortality rates were calculated from date of diagnosis to date of death, with living patients censored at date of last contact. Kaplan-Meier curves were estimated and compared using log-rank tests. Multivariable Cox proportional hazards models assessed the association between oligo-stage IV vs extensive-stage IV breast cancer, curative vs palliative regimen, and 5-year mortality. Models were adjusted for receptor status, age at diagnosis, receipt of surgery, and radiation. Models were then stratified by receptor status. Results: Of the 202 de novo stage IV cases, 140 (69.3%) were extensive-stage IV and 62 (30.4%) were oligo-stage IV. A larger proportion of oligo-stage IV vs extensive-stage IV was TNBC (19.4% vs 8.8%, p=0.03), lower proportion was ER+ (65.6% vs 81.5%, p=0.01), and no difference in HER2 (30.5% vs 29.0%, p=0.83). Higher proportion of oligo-stage IV vs extensive-stage IV received curative chemotherapy (24.2% vs 7.9%, p < 0.001) and breast surgery (25.0% vs 13.6%, p < 0.001). There was no difference in receipt of radiation to distant sites (25.0% vs 27.5%, p=0.70). Patients who received curative vs palliative chemotherapy were younger (55.3 vs 62.1yo, p=0.02). Oligo-stage IV had lower 5-year mortality (64.7%) vs extensive-stage IV (70.6%; HR=0.58, 95% CI 0.39-0.89), with no significant difference in 5-year mortality between curative vs palliative chemotherapy. When stratifying by receptor status, ER+ had the strongest association between oligo-stage IV and decreased 5-year mortality (HR=0.56, 95% CI 0.34 – 0.92). There was no significant association between surgery or radiation and 5-year mortality (HR = 0.62, 95% CI 0.38-0.99; HR= 1.33, 95% CI 0.91-1.95, respectively). Only a small number of patients received all 3 components; curative chemotherapy, surgery, and radiation (N=5; 18.5%). The dose of radiation (palliative vs ablative) is unknown. Conclusions: Patients with oligo-stage IV breast cancer had lower 5-year mortality vs extensive-stage IV breast cancer. Neither curative intent chemotherapy, breast surgery nor radiation were associated with lower 5-year mortality. However, very few patients received all 3 modalities with curative intent. These results are consistent with prior randomized clinical trials that showed no survival benefit to escalating therapy, but leave the question unanswered if combining all 3 modalities may improve overall survival in de novo oligometastatic stage IV breast cancer. Multivariable-Adjusted Association Between Disease Status and 5-Year Mortality Among Patients with De Novo Stage IV Breast Cancer, Stratified by Receptor Status. *Further adjusted for age at diagnosis; HR – hazard ratio, CI – confidence interval Citation Format: Deanna Blansky, Maryam Lustberg, Lajos Pusztai, Mariya Rozenblit. Characteristics and Treatment Patterns of de novo Oligometastatic Stage IV Breast Cancer: A Single-Center Retrospective Cohort Study [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 PO2-06-02.

Detecting Metastatic Patterns of Oligometastatic Breast Cancer: A Comparative Analysis of 18F-FDG PET/CT and Conventional CT Imaging.

Metastasis-directed therapy has the potential to improve progression-free and overall survival in oligometastatic disease (OMD). For breast cancer, however, randomized trials have failed so far to confirm this finding. Because the concept of metastasis-directed therapy in OMD is highly dependent on the accuracy of the imaging modality, we aimed to assess the impact of 18F-FDG PET/CT on the definition of OMD in breast cancer patients. Methods: Eighty patients with a total of 150 18F-FDG PET/CT images (between October 2006 and January 2022) were enrolled in this retrospective study at the Technical University of Munich. The inclusion criteria were OMD, defined as 1-5 distant metastases, at the time of 18F-FDG PET/CT. For the current study, we systemically compared the metastatic pattern on 18F-FDG PET/CT with conventional CT. Results: At the time of 18F-FDG PET/CT, 21.3% of patients (n = 32) had a first-time diagnosis of metastatic disease, 40.7% (n = 61) had a previous history of OMD, and 38% (n = 57) had a previous history of polymetastatic disease. In 45.3% of cases, the imaging modality (18F-FDG PET/CT vs. conventional CT) had an impact on the assessment of whether OMD was present. An identical metastatic pattern was observed in only 32% of cases.18F-FDG PET/CT detected additional metastases in 33.3% of cases, mostly in the nonregional lymph node system. Conclusion: The use of 18F-FDG PET/CT had a substantial impact on the definition of OMD and detection of metastatic pattern in breast cancer. Our results emphasize the importance of establishing a standardized definition for imaging modalities in future trials and clinical practices related to metastasis-directed therapy in breast cancer patients.

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.

Role of Interventional Radiology in Managing Primary and Metastatic Breast Cancer.

Percutaneous image-guided locoregional therapies are emerging in the treatment of primary and metastatic breast cancer. Cryoablation has emerged as the dominant ablative approach as an alternative to surgery for primary breast cancer in patients who do not wish to have surgery or are poor surgical candidates. Cryoablation is well tolerated and provides excellent local control and cosmesis. Thermal ablation may also be used in the treatment of oligometastatic breast cancer, allowing patients to achieve long disease-free intervals. Transarterial therapies have been studied in the treatment of oligoprogressive hepatic metastasis, though further supportive data would be helpful to demonstrate its efficacy.

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.

Locoregional Therapies for Primary and Metastatic Breast Cancer: AJR Expert Panel Narrative Review.

Minimally invasive locoregional therapies have a growing role in the multidisciplinary treatment of primary and metastatic breast cancer. Factors contributing to the expanding role of ablation for primary breast cancer include earlier diagnosis, when tumors are small, and increased longevity of patients whose condition precludes surgery. Cryoablation has emerged as the leading ablative modality for primary breast cancer owing to its wide availability, the lack of need for sedation, and the ability to monitor the ablation zone. Emerging evidence suggests that in patients with oligometastatic breast cancer, use of locoregional therapies to eradicate all disease sites may confer a survival advantage. Evidence also suggests that transarterial therapies-including chemoembolization, chemoperfusion, and radioembolization-may be helpful to some patients with advanced liver metastases from breast cancer, such as those with hepatic oligoprogression or those who cannot tolerate systemic therapy. However, the optimal modalities for treatment of oligometastatic and advanced metastatic disease remain unknown. Finally, locoregional therapies may produce tumor antigens that in combination with immunotherapy drive anti-tumor immunity. Although key trials are ongoing, additional prospective studies are needed to establish the inclusion of interventional oncology in societal breast cancer guidelines to support further clinical adoption and improved patient outcomes.

De Novo Oligometastatic Breast Cancer.

De novo oligometastatic breast cancer, a unique disease needing new treatment paradigms.

18F]NaF PET/CT imaging of response to single fraction SABR to bone metastases from breast cancer

Breast cancer commonly metastasises to the skeleton, and stereotactic ablative body radiation therapy (SABR) is an emerging treatment for oligometastatic disease. Accurately imaging bone metastases and their response to treatment is challenging. [18F]NaF-PET has a higher sensitivity and specificity than conventional bone scans for detecting breast cancer bone metastases. In this pre-defined secondary analysis of a prospective trial, we evaluated the change in [18F]NaF uptake after SABR. Patients with oligometastatic breast cancer received a single fraction of 20 Gy to up to three bone metastases. [18F]NaF-PET was acquired before and 12 months after SABR. Pre- and post-treatment [18F]NaF-PET images were registered to the treatment planning CT. The relative change in tumour SUVmax and SUVmean was quantified. The intersection of each of the radiation therapy isodose contours with a non-tumour bone was created. The change in SUVmean in sub-volumes of non-tumour bone receiving doses of 0–20 Gy was quantified. In total, 14 patients, with 17 bone metastases, were available for analysis. A total of 15 metastases exhibited a reduction in SUVmax; the median reduction was 42% and the maximum reduction 82%. An increased absolute reduction in SUVmax was observed with higher pre-treatment SUVmax. One patient exhibited increased SUVmax after treatment, which was attributed to normal peri-tumoural bone regeneration in the context of a bone metastasis. There was a median reduction of 15%–34% for non-tumour bone in each dose level.

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

Prior retrospective and prospective evidence have suggested a potential survival benefit of adding metastasis-directed therapy (MDT) to standard of care systemic therapy for oligometastatic breast cancer. This has led to the increased utilization of MDT in this setting despite the lack of randomized evidence to support this approach. Furthermore, the recent presentation of NRG-BR002 has questioned the value of MDT. Thus, we evaluated whether the addition of MDT to systemic therapy improves PFS in oligometastatic breast cancer. EXTEND (NCT03599765) is a phase II randomized basket trial for multiple solid tumors testing whether the addition of MDT improves PFS. The primary endpoint was pre-specified to be independently assessed and reported for the breast basket when a minimum of 6 months of follow-up had been reached. Patients with ≤5 metastases were randomized to standard of care systemic therapy with or without MDT. The choice of systemic therapy was at the discretion of the treating medical oncologist. Number of metastatic lesions and prior lines of systemic therapy for metastatic disease were used as stratification variables pre-randomization. The primary endpoint was progression-free survival (PFS) defined as time to randomization to date of clinical or radiographic progression or death. The study was designed to have 80% power to detect an improvement in median PFS from 18 to 36 months, with a type I error of 0.1. Between September 2018 to July 2022, 43 patients were randomized. 22 patients were assigned to the MDT arm, and 21 patients to the no MDT arm. Three patients were not evaluable. The MDT arm patients were older vs the no-MDT arm patients (median 61.5 years vs 48 years, p = 0.01). Otherwise, the arms were well-balanced. Overall, 8 patients had triple negative disease (18.6%), and 12 patients (30%) had de novo metastatic disease. Of those patients with de novo presentation randomized to MDT, all except one had the primary tumor treated with surgery and radiation. At a median follow-up of 19.4 months, 20 events were observed. Among the 40 evaluable patients, there were 5 deaths (3 in the MDT arm and 2 in the no MDT arm). There was no difference in PFS between the MDT and no MDT arms (median 15.6 v 24.9 months, p = 0.66). Similarly, there was no difference in the secondary endpoint of time to new metastatic lesion appearance between the MDT and no MDT arms (median 15.6 months vs not reached, p = 0.09). Two grade 3 toxicities were observed in the MDT arm, and 1 in the no MDT arm. Further analysis of correlative translational biomarkers, including immune markers and ctDNA, are ongoing. The addition of MDT to standard of care systemic therapy did not improve PFS or time to new metastatic lesion in patients with oligometastatic breast cancer. This data coupled with the recently presented NRG-BR002 results, suggests there is no benefit to MDT in an otherwise unselected oligometastatic breast cancer population.