De Novo Metastatic Breast Cancer Research Articles

Abstract PS08-09: Impact of HER2 expression dynamics on the real-world activity of trastuzumab deruxtecan for metastatic breast cancer (RELIEVE)

Abstract Background: trastuzumab deruxtecan (T-DXd) is a standard treatment for patients (pts) with HER2-positive (HER2+) and HER2-low metastatic breast cancer (MBC). HER2-low expression has been shown to be a highly unstable biomarker, and no data exists on the activity of T-DXd among pts with changes in HER2 status over time. Furthermore, limited data exists on the performance of regimens administered after progression on T-DXd. Methods: We analyzed data for pts with MBC receiving T-DXd at Dana-Farber Cancer Institute between 7/2017 - 2/2023 and at Duke Cancer Center between 3/2020 - 4/2022. The disease was categorized HER2+ if IHC 3+ or ISH-amplified at any time point; HER2-negative cases were categorized as HER2-low (IHC 2+/ISH- or IHC 1+) or HER2-0 (IHC 0) based on the last biopsy before T-DXd; the HER2 status for the primary tumor and at first metastatic diagnosis were also collected. We determined time to next treatment (TTNT), overall survival (OS), toxicities with T-DXd, TTNT based on dynamic HER2 status and TTNT with post-T-DXd regimens. Genomic data was available for 58 pts using an in-house NGS assay on archival tumor samples. Results: A total of 191 pts were included in the analysis (126 HER2+, 44 HER2-low, 21 HER2-0). Median age at metastatic diagnosis was 50.9 (range 21 - 78), 26% had de-novo MBC and 38% had history of brain metastases before T-DXd. The proportion of hormone receptor (HR)-positive tumors based on the last biopsy prior to T-DXd was 53% in HER2+, 68% in HER2-low and 57% in HER2-0; pts within each cohort had received a median of 2 prior lines of chemotherapy before T-DXd (range 0 - 9). With a median follow-up of 10.4 months, median TTNT was 10.4 months for HER2+, 7.6 months for HER2-low and 3.7 months for HER2-0 MBC (p < 0.001). Switch in HER2 status between primary tumor and pre-T-DXd biopsy significantly impacted outcomes, with the shortest TTNT observed in pts switching from HER2-low to HER2-0 (TTNT 3.0 months) compared with 5.6 months if switching from HER2-0 to HER2-low, and 9.4 months if having stable HER2-low status (p=0.006). Conversely, HER2 status switch within the metastatic setting did not impact outcomes (Table 1). No difference in TTNT was seen regardless of HR status (negative vs positive, 7.4 vs 10.2 months, p=0.25) or number of prior chemotherapies (≤2 vs >2, 10.1 vs 8.8 months, p=0.50). Median OS is shown in Table 1. At last follow-up, 55 pts remain on T-DXd (28.8%), 108 progressed (56.5%), 28 stopped due to toxicity (14.7%). A total of 22 pts (11.5%) developed interstitial lung disease (ILD, 6.2% grade [G]1, 3.1% G2, 1.6% G3, 0.5% G4, no G5). ILD occurred after a median of 8 months from T-DXd initiation and resolved in 63.6% of the cases, with a median time to resolution of 4 months (2 months for grade 1 events). 5 pts (2.6%) developed cardiotoxicity. T-DXd was dose reduced in 61 pts (31.9%), most often for fatigue (14.7%), nausea/vomiting (9.9%) or hematological toxicity (6.3%). Among 105 pts receiving post-T-DXd treatments, TTNT was 4 months for HER2+, 3.1 months for HER2-low and 4.3 months for HER2-0 MBC (p=0.62). Pts with HER2-negative tumors and ERBB2 hemizygous deletions (6/58, 10.3 %) had a TTNT with T-DXd of 4.1 months, vs 7.6 months without ERBB2 deletions (p=0.41). Additional biomarker data will be presented at the meeting. Conclusions: T-DXd showed promising real-world activity in pretreated pts with MBC, with the longest TTNT observed among pts with HER2+ disease or with stable HER2-low disease over time. Real world TTNT is relatively short post-T-DXd and further studies evaluating resistance mechanisms and optimal treatments in this setting are needed. Table 1 – TTNT and OS among patients with metastatic breast cancer receiving T-DXd and post-T-DXd regimens according to HER2 status The activity of T-DXd significantly differed according to the HER2 status of the disease, with the longest TTNT observed among patients with HER2+ disease (at any timepoint in time) and among patients with stable HER2-low disease over time. Regimens administered immediately after T-DXd achieved a similar performance irrespective of the HER2 status of the disease, with a TTNT ranging between 3.1 and 4.3 months. Citation Format: Paolo Tarantino, Melissa Hughes, Ross Kusmick, Laura Alder, Alyssa Pereslete, Laura Noteware, Heather Moore, Amanda Van Swearingen, Tianyu Li, Hersh Gupta, Kalie Smith, Stefania Morganti, Janet Files, Kerry Sendrick, Simone Buck, Deborah Dillon, Rinath Jeselsohn, Yvonne Li, Andrew Cherniack, Aleix Prat, Nay Nwe Nyein Chan, David Rimm, Giuseppe Curigliano, Sarah Sammons, Carey Anders, Nancy Lin, Sara Tolaney. Impact of HER2 expression dynamics on the real-world activity of trastuzumab deruxtecan for metastatic breast cancer (RELIEVE) [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 PS08-09.

Abstract PO3-20-07: Five years and counting: A case of a 47-year-old female with De Novo Metastatic HER2 positive disease on multiple lines of treatment

Abstract HER2-positive breast cancer refers to a specific subtype of breast cancer characterized by the overexpression or amplification of the human epidermal growth factor receptor 2 (HER2) protein on the surface of cancer cells. The overexpression of HER2 leads to increased signaling pathways that promote cell growth and division, making HER2-positive breast cancer inherently more aggressive compared to other subtypes. The aggressive behaviour of HER2-positive disease may be attributed to its rapid cell growth, high metastatic potential, and increased risk of recurrence. Fortunately, there are targeted therapies that specifically inhibit the HER2 protein. These targeted treatments help to block HER2 signaling, slow down tumor growth, and reduce the risk of recurrence. We report a case 47 year old premenoapausal Filipino female diagnosed with de-novo metastatic HER2-positive breast cancer with liver and lung metastasis in 2018. Advised Pertuzumab Trastuzumab and Taxane therapy but due to financial constraints was amenable only to Trastuzumab and Paclitaxel. During treatment noted symptomatic cardiac decline, hence shifted to Lapatinib & Capecitabine, tolerated well with stable disease for 1 year. Disease then progressed to the contralateral breast, given 6 cycles of Ado Trastuzumab Emtansine with partial response followed by modified radical mastectomy of the right and toilet total mastectomy of the left breast. She was lost to follow up. Her cancer recurred 1 year later as skin lesions on chest wall. She was given 6 cycles of Ado Trastuzumab Emtansine, however still with progression as skin lesions on the chest. Patient was then given 5 cycles of Trastuzumab with Eribulin. Despite treatment, there was progression with symptomatic brain metastasis and further increase in size and number of skin metastasis of the chest wall. Lesions were noted to be ulcerating and bleeding. Hence patient underwent 5 of 5 sessions of Fractionated stereotactic radiation therapy and 10 of 10 sessions of palliative radiotherapy to the chest wall. Patient was then given Pertuzumab & Trastuzumab with note of improvement of chest wall lesions. However, after 7 cycles of treatment, noted progression again as skin metastasis on the chest wall. Hence patient was shifted to Trastuzumab Deruxtecan. At the time of writing, the patient has had a good response with Fam-Trastuzumab Deruxtecan-nxki with partial resolution of her skin metastases on the chest with stable disease of lung and brain target lesions. No bleeding or ulcerations of the lesions and no recurrence of dizziness or imbalance reported. The patient will continue to receive Fam-Trastuzumab Deruxtecan-nxki until disease progression and/or unacceptable toxicity. Here we have a case of patient with extended survival after being fortunate to have received multiple lines of treatment for the disease. In this case we were able to apply the advances of research in HER2-positive breast cancer and see it in the clinical setting. Thus, ultimately translating to extended overall survival for the patient. We see the importance of continuous research on HER2-positive breast cancer disease and how these studies have helped us in overcoming treatment resistance, understanding disease progression, tailoring of therapies to individual patients, optimizing treatment outcomes, developing new therapies, and enhancing the quality of life for patient. Ongoing research continues to explore new therapeutic approaches and strategies to further improve outcomes for individuals with metastatic HER2-positive breast cancer. This is truly an exciting time for cancer research because what used to be a very deadly disease is now becoming something that we are able manage. Citation Format: Sofia Dominique Unson, Rubi Li. Five years and counting: A case of a 47-year-old female with De Novo Metastatic HER2 positive disease on multiple lines of treatment [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 PO3-20-07.

Twenty-five Years Overall Survival Prognostic Value of the Lymph Node Ratio in De Novo Metastatic Breast Cancer.

The lymph node ratio (LNR) indicates the number of involved lymph nodes divided by the number of lymph nodes found during axillary exploration. This study investigated the prognostic value of the LNR in de novo metastatic breast cancer (dnMBC). We hypothesized that LNR might predict long-term survival even in cases where the disease has already disseminated beyond the regional stage. Patients with dnMBC were selected from the Surveillance, Epidemiology, and End Results (SEER) 9-registries database 1988-2012. Positive lymph nodes (npos) were categorized as pN0 (npos=0), pN1 (npos=1 to 3), pN2 (npos=4 to 9), and pN3 (npos≥10). The LNR was categorized as Lnr0 (LNR=0), Lnr1 (LNR=0.01 to 0.20), Lnr2 (LNR=0.21 to 0.65), and Lnr3 (LNR≥0.65). The prognostic values were compared using Gini's mean difference Δ of the restricted mean overall survival time (RMST) according to npos versus LNR groups. A total of 12,085 patients with dnMBC had LNR data. At 25 years follow-up, the npos RMSTs were 10.4, 5.1, 5.8, and 5.0 years, for pN0 to pN3, respectively. The npos Gini's Δ was 2.8 years (standard error ±0.2). The LNR RMSTs were 10.4, 9.9, 7.6, and 4.0 years for Lnr0 to Lnr3, respectively. Δ for LNR was 3.6 (±0.2) years. Among node positive cases, the LNR low-risk group had an RMST of 9.9 years, approaching node-negative cases, while the high-risk group had an RMST of 4.0 years. LNR identified different prognostic groups, suggesting a possible role of lymph node involvement as a marker of lymphangiogenesis or lymphatic changes in the immune microenvironment, which warrants further investigation in dnMBC.

Development and Methodological Validation of a Modified Staging System for de Novo Metastatic Breast Cancer

Validation of a new method for prognostication of de novo metastatic breast cancer (dnMBC) to better reflect the heterogenecity of the disease. To perform external methodological validation of the Plichta staging system, a novel prognostic system for de novo metastatic breast cancer (dnMBC). This retrospective cohort study used a multicenter, nationwide, population-based Danish Breast Cancer Group database to validate the new method. Participants were patients with dnMBC diagnosed between 2010 and 2019. Data were analyzed from April to June 2023. A recursive partitioning analysis (RPA) was performed, as demonstrated by Plichta and colleagues, to group patients with similar overall survival (OS) based on clinical factors. The main outcome was to group patients into 4 prognostic groups based on 3-year OS as stage IVa, greater than 70%; stage IVb, 50% to 70%; stage IVc, 25% to less than 50%; or stage IVd, less than 25%. Bootstrapping was applied for 1000 iterations, with final stage assignments based on the most commonly occurring assignment. A total of 1859 women were included with a median (IQR) age of 69 (57-77) years. With a median potential follow-up of 89.9 (95% CI, 86.4-95.1) months and a median OS of 31.7 (95% CI, 29.5-34.1) months, the RPA stratified patients into 10 groups, with organ sites, estrogen receptor status, and human epidermal growth factor receptor 2 status as the key clinical factors. Three-year survival rates ranged from 62% (95% CI, 56%-69%) to 8% (95% CI, 3%-21%), which were further combined into 3 stage groups: IVb, 59.4% (95% CI, 56.2%-62.8%); IVc, 39.4% (95% CI, 36.2%-43.0%); and IVd, 15.4% (95% CI, 11.2%-21.3%) (P < .001). Following bootstrapping, an IVa group emerged, resulting in 4 stage groups with separate 3-year OS rates identified as IVa, 75.8% (95% CI, 67.8%-84.7%); IVb, 58.8% (95% CI, 55.5%-62.3%); IVc, 39.2% (95% CI, 35.8%-43.0%); and IVd, 14.4% (95% CI, 10.8%-19.4%) (P < .001). These findings provide external and independent validation of the methods applied in the novel Plichta staging system for dnMBC. This could guide future revisions of the current American Joint Committee on Cancer staging guidelines and may be incorporated as a stratification factor in clinical trials.

Impact of Primary Breast Surgery on Overall Survival of Patients With De Novo Metastatic Breast Cancer: A Systematic Review and Meta-Analysis.

Breast surgery in cases of de novo metastatic breast cancer (MBC) is associated with improved outcomes in retrospective studies, although the results of randomized controlled trials (RCTs) are conflicting. We aimed to investigate whether surgery in this context prolongs patient survival. We performed a systematic review of the literature to identify RCTs comparing surgery of primary breast cancer to no surgery in patients with de novo MBC. Cochrane Library, Embase, Medline (OVID), and Web of Science were searched with latest update in July 2023, while conference proceedings were manually searched. Data concerning patient and tumor characteristics, as well as outcomes, were extracted. A meta-analysis with random effects models was performed considering heterogeneity between trials. Overall, 3255 entries were identified and 5 RCTs fulfilled all inclusion criteria, which had enrolled 1381 patients. The overall estimation in the intention-to-treat population showed no benefit for patients who had surgical excision of the primary breast tumor (HR = 0.93; 95% CI, 0.76-1.14). No subgroups in terms of receptor status or patterns of metastasis seemed to benefit from surgery, except for younger/premenopausal patients (HR = 0.74, 95% CI, 0.58-0.94). Breast surgery was associated with improved local progression-free survival (HR = 0.37, 95% CI, 0.19-0.74). Surgery of the primary tumor in patients with de novo MBC does not prolong survival, except possibly in younger/premenopausal patients. Breast surgery should be offered within the context of well-designed clinical trials examining the issue.

¿Está indicada la irradiación del tumor primario en el estadio IV?

De-novo metastatic breast cancer is a rare entity, occurring in 3–10% of cases. The most common treatment for these patients is systemic therapy (chemotherapy, hormonal therapy, targeted therapies, and combinations of these). The subgroup of patients with oligometastatic disease and low systemic disease burden may benefit more from adding a locoregional treatment. This literature review aims to analyze the benefits and disadvantages of locoregional treatment in patients with de-novo oligometastatic breast cancer. Retrospective series report that this subgroup of patients may benefit from locoregional treatment, despite presenting with metastatic disease, by improving overall survival and local control. Additionally, several retrospective series have shown that locoregional treatment with surgery, surgery and adjuvant radiotherapy, or exclusive radiotherapy present similar results in local control. Therefore, exclusive radiotherapy may be a viable alternative in these patients. In recent years, attempts have been made to demonstrate the trend of retrospective series in prospective trials. These studies have shown great heterogeneity. Some with positive results in improving overall survival and others with negative results, but not statistically significant. The main limitation of retrospective series is the selection bias, which could explain the differences in the results obtained. For this reason, locoregional treatment in these patients should be approached by multidisciplinary teams on an individualized basis, with greater consideration for oligometastatic patients.

Should Locoregional Treatment be Performed in de novo Metastatic Breast Cancer? A Retrospective Single-centre Experience

Purpose: De novo metastatic breast cancer (DMBC) represents approximately 6% of patients with breast cancer [1]. The role of locoregional treatment (LRT) remains controversial, with conflicting trial evidence [2–4]. Palliative systemic therapy remains the mainstay of treatment. We report the impact of different LRTs on breast cancer survival in this heterogeneous disease.

Novel Prognostic Staging System for Patients With De Novo Metastatic Breast Cancer.

Given the heterogeneity and improvement in outcomes for metastatic breast cancer (MBC), we developed a staging system that refines prognostic estimates for patients with metastatic cancer at the time of initial diagnosis, de novo MBC (dnMBC), on the basis of survival outcomes and disease-related variables. Patients with dnMBC (2010-2016) were selected from the National Cancer Database (NCDB). Recursive partitioning analysis (RPA) was used to group patients with similar overall survival (OS) on the basis of clinical T category, grade, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2, histology, organ system site of metastases (bone-only, brain-only, visceral), and number of organ systems involved. Three-year OS rates were used to assign a final stage: IVA: >70%, IVB: 50%-70%, IVC: 25 to <50%, and IVD: <25%. Bootstrapping was applied with 1,000 iterations, and final stage assignments were made based on the most commonly occurring assignment. Unadjusted OS was estimated. Validation analyses were conducted using SEER and NCDB. At a median follow-up of 52.9 months, the median OS of the original cohort (N = 42,467) was 35.4 months (95% CI, 34.8 to 35.9). RPA stratified patients into 53 groups with 3-year OS rates ranging from 73.5% to 5.7%; these groups were amalgamated into four stage groups: 3-year OS, A = 73.2%, B = 61.9%, C = 40.1%, and D = 17% (log-rank P < .001). After bootstrapping, the survival outcomes for the four stages remained significantly different (log-rank P < .001). This staging system was then validated using SEER data (N = 20,469) and a separate cohort from the NCDB (N = 7,645) (both log-rank P < .001). Our findings regarding the heterogeneity in outcomes for patients with dnMBC could guide future revisions of the current American Joint Committee on Cancer staging guidelines for patients with newly diagnosed stage IV disease. Our findings should be independently confirmed.

Loco-Regional Treatment of the Primary Tumor in De Novo Metastatic Breast Cancer Patients Undergoing Front-Line Chemotherapy.

Loco-regional therapy (LRT) in de novo metastatic breast cancer (MBC) has been investigated in several clinical trials, with heterogeneous and conflicting results. We conducted a retrospective study of de novo MBC patients treated with front-line chemotherapy (FLC) followed by LRT of the primary tumor. Our aims were to evaluate the characteristics, treatment, and oncological outcomes in terms of progression-free survival (PFS), distant progression-free survival (DPFS), and overall survival (OS) of de novo MBC. We also investigated possible subgroups of patients with better outcomes according to menopausal status, biological sub-type, location, number of metastases, and radiologic complete response after FLC. We included 61 patients in the study. After a median follow-up of 55 months, disease progression occurred in 60.7% of patients and 49.2% died. There were no significant differences in PFS, DPFS, and OS between different subgroups of de novo MBC patients. A trend toward better PFS and DPFS was observed in triple-positive tumors, without a statistically significant difference in OS. No specific subgroup of de novo MBC patients showed a statistically significant survival advantage after FLC followed by LRT of the primary tumor.

MSR128 Swedish Nationwide Register Data as a Low-Cost Resource to Detect Drug-Repurposing Signals: A Study on De Novo Metastatic Breast Cancer Patients

Electronic health records have recently been highlighted as a low-cost resource to accelerate cancer therapeutics by drug repurposing discovery (Wu et al., JCO Clinical Cancer Informatics 2019:3, 1-9). The aim of this study was to test this approach on Swedish nationwide register data focusing on breast cancer cases with distant metastasis at initial diagnosis (de novo mBC). To demonstrate the feasibility of this methodology we i) evaluated the nine drug candidates identified by Wu et al. on our dataset, ii) generated drug repurposing hypotheses based on prescription drugs given to patients during metastatic breast cancer diagnosis/treatment.

Clinical Characteristics and Survival Outcomes of Patients with De Novo Metastatic Breast Cancer.

Though less than 5% of patients with breast cancer present with De Novo Metastasis (dnMBC) in Western societies, this percentage may reach 30% in developing countries. In this study, we present survival outcomes of patients diagnosed with dnMBC treated at a tertiary center in a developing country. Using hospital-based database, consecutive patients with dnMBC diagnosed between 2013 and 2017 were identified. Demographic data, tumor characteristics, types of treatment, and survival data were retrospectively collected. A total of 435 patients were included; median age (range) at time of diagnosis was 51 (24-85) years. Most of the tumors expressed hormone receptors (81% Estrogen Receptor positive, 77% Progesterone Receptor positive). Human epidermal growth factor receptor-2 (HER2) overexpression was reported in 134 (30.9%) patients, while only 24 (5.5%) had Triple Negative (TN) disease. Bone, lung and liver were the most common sites of metastasis involved in 70.6%, 36.1%, and 32.0%, respectively. The median Overall Survival (OS) for all patients was 38 months, and 5-year OS was 32.6%. On univariate analysis, high tumor grade, advanced T-stage, TN-disease and metastasis to multiple sites, but not HER2 status, were associated with poor OS. On multivariate analysis, high tumor grade (Hazard Ratio =1.6, p=0.002), advanced T-stage (Hazard Ratio=1.6, p=0.003), and triple negative status (Hazard Ratio= 2.1, p=0.008) predicted poor OS. The overall survival of patients with dnMBC remains poor. Better understanding of the disease behavior and factors affecting survival is required for optimal utilization of available regimens and new drugs to hopefully improve patients' outcomes.

Exploring the Value of Additional Primary Tumour Excision Combined with Systemic Therapy Administered in Different Sequences for Patients with de Novo Metastatic Breast Cancer

Introduction Uncertainty still remains regarding the survival improvement derived from immediate surgery or subsequent surgery in addition to systemic therapy for patients with de novo metastatic breast cancer. The current study aimed to examine the effect of combined treatment administered in different sequences on the survival of these patients. Materials and Methods We conducted a retrospective cohort study of patients with de novo stage IV breast cancer in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2019. Patients were categorized into 3 groups: (1) systemic therapy without primary surgery, (2) systemic therapy after primary surgery, and (3) systemic therapy before primary surgery. Cumulative incidence curves with Gray's test were used to compare breast cancer-specific death (BCSD) between groups. Kaplan–Meier curves with the log-rank test were applied to compare overall survival (OS) between groups. A competing risk model and a proportional hazards model were generated to adjust for important prognostic factors. Propensity score matching (PSM) was performed in the primary survival analysis. Stratified analysis was also performed. Results Patients who underwent systemic therapy after primary surgery and who underwent systemic therapy before primary surgery both showed a significantly reduced risk of BCSD compared to patients who received systemic therapy without primary surgery [subdistribution hazard ratio (SHR): 0.74; 95% confidence interval (CI): 0.69–0.79; and P < 0.001, and SHR: 0.62; 95% CI: 0.56–0.67; and P < 0.001, respectively]. A statistically significant disparity was also noted in OS. In the setting of single-organ metastasis, including the bone, lung, and liver, patients receiving the combination therapy showed an improved prognosis compared with patients receiving systemic therapy without primary surgery. Conclusions Additional primary tumour excision, whether before or after systemic therapy, may provide survival benefits for patients presenting with de novo metastatic breast cancer, especially for patients with single-organ disease involving the bone, lung, and liver but not the brain. Further investigations mainly focused on these carefully selected candidates are required to improve personalized treatment for metastatic breast cancer.

64Cu-SAR-Bombesin PET-CT Imaging in the Staging of Estrogen/Progesterone Receptor Positive, HER2 Negative Metastatic Breast Cancer Patients: Safety, Dosimetry and Feasibility in a Phase I Trial.

Breast cancers are most frequently oestrogen receptor (ER) and progesterone receptor (PR) positive and [18F]Fluorodeoxyglucose PET-CT (FDG) has lower sensitivity for these subtypes. The gastrin-releasing peptide receptor (GRPR) is overexpressed in ER+/PR+ breast cancers. This study assessed the safety and potential of [64Cu]Cu-Sarcophagine (SAR)-Bombesin PET/CT (BBN) in re-staging metastatic ER+/PR+/human epidermal growth-factor-2-negative (HER2-) breast cancer. Seven patients with metastatic ER+/PR+/HER2- breast cancer undergoing staging underwent [64Cu]Cu-SAR-BBN PET-CT. Bloods, vital signs and electrocardiogram, blood tracer-clearance and dosimetry were undertaken. GRPR status was assessed in available metastatic biopsy samples. Staging with conventional imaging ([18F]FDG, bone scan and diagnostic CT) was within 3 weeks of [64Cu]Cu-SAR-BBN PET/CT. PET scans were assessed visually and quantitatively. Seven patients underwent imaging. One of the seven had de-novo metastatic breast cancer and six of the seven recurrent metastatic disease. Two of the seven had lobular subtype. No adverse events were reported. All seven patients were positive on conventional imaging (six of seven on FDG). [64Cu]Cu-SAR-BBN imaging was positive in five of the seven. Both [64Cu]Cu-SAR-BBN-negative patients had disease identified on [18F]FDG. One patient was [64Cu]Cu-SAR-BBN positive/[18F]FDG negative. Four of seven patients were [64Cu]Cu-SAR-BBN positive/[18F]FDG positive. In these four, mean SUVmax was higher for [64Cu]Cu-SAR-BBN than [18F]FDG (SUVmax 15 vs. 12). In the classical lobular subtype (two of seven), [64Cu]Cu-SAR-BBN was more avid compared to [18F]FDG (SUVmax 20 vs. 11, and 20 vs. <3). Dosimetry calculations estimated whole-body effective dose for 200 MBq of [64Cu]Cu-SAR-BBN to be 1.9 mSv. [64Cu]Cu-SAR-BBN PET/CT appears safe and may have diagnostic value in metastatic ER+/PR+/HER2- breast cancer, particularly the lobular subtype. Further evaluation is warranted.

Impact of Surgery in De Novo Metastatic Breast Cancer after Systemic Disease Control

Background: Systemic chemotherapy is the standard of care for patients with metastatic breast cancer, with an undecided role in surgery. Limited data is available for the role of surgery on the overall survival of stage 4 breast cancer in regards to luminal subtypes of patients. This is a retrospective data analysis comparing overall survival benefit and disease-free survival in stage IV breast cancer after systemic treatment and systemic disease control concerning luminal classification in the last five years. Method: Patients who had surgery and no surgery after systemic treatment and disease control were compared for 5 years overall survival as the primary endpoint and disease-free survival as the secondary endpoint. The survival benefit was also compared in regards to tumor biology (ER/PR, HER2 status) Results: Data included 430 patients, 244 in surgery and 186 in no surgery group. At one year survival for surgery performed and not performed was not significant. Five-year overall survival for surgery performed and not performed was 84.4% and 74.6%. A statistically highly significant difference in survival rates was observed (p&lt;0.0001). The mortality rate was 15.6% in surgery performed and 25.4% in the no-surgery group which showed a significant difference among the two study groups (p=0.011). We found statistically significant differences in luminal B (p=0.01) and triple-negative breast cancer patients (p=0.001) for survival rates in surgery performed and not performed groups. Conclusion: Surgery has a positive impact on overall survival in Stage 4 patients with systemic disease control even in high-risk luminal B, Her 2 Positive, and triple-negative breast cancer patients. There was no significant difference observed in disease-free survival who were operated on or not. However, there was no local recurrence in the operated group. Keywords: Metastatic breast cancer: Neoadjuvant chemotherapy, local breast surgery, Luminal sub-types

Primary-Site Local Therapy for Patients with De Novo Metastatic Breast Cancer: An Educational Review.

Until 2001, the paradigm guiding the management of women with de novo metastatic breast cancer (dnMBC) stipulated that primary-site locoregional therapy (PSLT) did not alter the course of metastatic disease and was necessary only for palliation of symptoms. Since 2002, retrospective data have begun questioning this paradigm. However, selection biases driving an observed survival advantage associated with PSLT in dnMBC were quickly recognized and led to several randomized clinical trials (RCTs) addressing this question. Four published RCTs have since tested the value of PSLT added to systemic therapy (ST) or not, with overall survival (OS) as the primary end point. The results of three published trials show no OS benefit for the addition of PSLT: Indian Tata Memorial, U.S./Canada E2108, and Austrian POSYTIVE (although POSYTIVE did not reach full accrual). The fourth RCT (Turkey, MF07-01) shows an OS benefit for PSLT at 5 years (42 % vs 24 % in the ST arm; hazard ratio [HR], 0.66; 95 % confidence interval [CI], 0.49-0.88). However, the 5-year survival in the PSLT arm of MF07-01 is similar to that in both arms of E2108, suggesting that the worse survival in the ST arm of MF07-01 is a result of biologically worse disease (from imbalanced randomization). Locoregional control was improved by PSLT in all trials, but without improvement in quality of life. The current evidence fails to refute the 20th century paradigm guiding management of de novo metastatic breast cancer. Discussion continues regarding the survival value of PSLT for patients with bone-only disease or oligometastases, but unbiased evidence is lacking.

172P Long-term follow-up of randomized controlled trial (RCT) of locoregional treatment versus not of the primary tumour in de-novo metastatic breast cancer

We had earlier reported no difference in overall survival (OS) at a median follow up of 26 months of the first RCT comparing loco-regional treatment (LRT) vs not (no LRT) for the primary tumour in women with de novo metastatic breast cancer. We also noted then, a significant improvement in loco-regional progression free survival (PFS) and a significant detriment in distant PFS in LRT arm which reproduced findings of earlier animal experiments.

Factors Associated with Time to Progression and Overall Survival in Patients with De Novo Metastatic Breast Cancer: A Colombian Cohort.

PurposeAbout 10% of breast cancer (BC) is diagnosed in stage IV. This study sought to identify factors associated with time to progression (TTP) and overall survival (OS) in a cohort of patients diagnosed with de novo metastatic breast cancer (MBC), from a single cancer center in Colombia, given that information on this aspect is limited.MethodologyAn observational, analytical, and retrospective cohort study was carried out. Time to progression and OS rates were estimated using the Kaplan–Meier survival functions. Cox models were developed to assess association between time to progression and time to death, using a group of fixed variables.ResultsOverall, 175 patients were included in the study; 33.7% of patients had luminal B HER2-negative tumors, 49.7% had bone involvement, and 83.4% had multiple metastatic sites. Tumor biology and primary tumor surgery were the variables associated with TTP and OS. Patients with luminal A tumors had the lowest progression and mortality rates (10 per 100 patients/year (95% CI: 5.0-20.0) and 12.6 per 100 patients/year (95% CI: 6.9-22.7), respectively), and patients with triple-negative tumors had the highest progression and mortality rates (40 per 100 patients/year (95% CI: 23.2-68.8) and 44.1 per 100 patients/year (95% CI: 28.1-69.1), respectively). Across the cohort, the median TTP was 2.1 years (95% CI: 1.6; the upper limit cannot be reached) and the median OS was 2.4 years (95% CI: 2-4.3).ConclusionsIn this cohort, patients with luminal A tumors and those who underwent tumor surgery given that they presented clinical benefit (CB) after initial systemic treatment, had the lowest progression and mortality rates. Overall, OS was inferior to other series due to high tumor burden and difficulties in accessing and continuing oncological treatments.

Survival in Women with De Novo Metastatic Breast Cancer: A Comparison of Real-World Evidence from a Publicly-Funded Canadian Province and the United States by Insurance Status.

Metastatic breast cancer (MBC) patient outcomes may vary according to distinct health care payers and different countries. We compared 291 Alberta (AB), Canada and 9429 US patients < 65 with de novo MBC diagnosed from 2010 through 2014. Data were extracted from the provincial Breast Data Mart and from the National Cancer Institute’s SEER program. US patients were divided by insurance status (US privately insured, US Medicaid or US uninsured). Kaplan-Meier and log-rank analyses were used to assess differences in OS and hazard ratios (HR) were estimated using Cox models. Multivariate models were adjusted for age, surgical status, and biomarker profile. No difference in OS was noted between AB and US patients (HR = 0.92 (0.77–1.10), p = 0.365). Median OS was not reached for the US privately insured and AB groups, and was 11 months and 8 months for the US Medicaid and US uninsured groups, respectively. The 3-year OS rates were comparable between US privately insured and AB groups (53.28% (51.95–54.59) and 55.54% (49.49–61.16), respectively). Both groups had improved survival (p < 0.001) relative to the US Medicaid and US uninsured groups [39.32% (37.25–41.37) and 40.53% (36.20–44.81)]. Our study suggests that a universal health care system is not inferior to a private insurance-based model for de novo MBC.

Genomic Characterization of De Novo Metastatic Breast Cancer

De novo metastatic breast cancer (dnMBC) represents a minority of MBC cases, and as such, its genomics are poorly understood. Characterizing the genomics of dnMBC represents an opportunity to delineate metastatic drivers in the absence of treatment selection. In this review, we first summarize the literature of the genomics of MBC which showed that MBCs have greater mutational burden than early stage, treatment naïve breast cancers. We then turn to recent studies that have sought to focus on dnMBC. We propose that understanding genomic differences between dnMBC and relapsed MBC can inform treatment choices. Finally, we discuss translational strategies to better dissect the genomics of dnMBC.

Prognostic Score for De Novo Metastatic Breast Cancer With Liver Metastasis and Its Predictive Value of Locoregional Treatment Benefit.

BackgroundThere is a significant survival difference and lack of effective treatment among breast cancer patients with liver metastasis. This present study aimed to construct a novel prognostic score for predicting the prognosis and locoregional treatment benefit of de novo metastatic breast cancer with liver metastasis (BCLM).MethodsIn total, 2,398 eligible patients between 2010 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. They were assigned to the training set including 1,662 patients (2010–2014) and validation set comprising 736 patients (2015–2016) depending on the time of diagnosis. The prognostic score was based on regression coefficients in the multivariate Cox regression analysis. And then, patients were stratified into low-, intermediate-, and high-risk groups by the prognostic score. The discrimination and calibration of prognostic score were evaluated using time-dependent receiver operating characteristic (ROC) curves analysis and calibration curves, respectively. Subgroup analysis was performed to evaluate locoregional surgery and chemotherapy benefit in different risk groups.ResultsAge, race, insurance and marital status, T stage, pathological grade, molecular subtypes, and extrahepatic metastasis were identified as independent prognostic variables in the prognostic score. The prognostic score showed high discrimination power with an area under the curve (AUC) of 0.77 and 0.72 and excellent agreement suggested by calibration plots in the training and validation sets, respectively. Intermediate-risk [hazard ratio (HR) 2.39, 95% confidence interval (CI) 2.09–2.73, P<0.001] and high-risk groups (HR 4.88; 95% CI 4.13–5.76; P<0.001) had significantly worse prognosis in comparison with the low-risk group. The median overall survival (OS) in three prognostic groups were 44, 18, and 7 months, with a 3-year survival rate of 56, 23, and 7%, respectively. Apart from the high-risk group (HR 0.79; 95% CI 0.56–1.10; P=0.157), the low-risk (HR 0.64; 95% CI 0.49–0.84; P=0.001) and intermediate-risk groups (HR 0.68; 95% CI 0.55–0.85; P=0.001) could benefit from the surgery of primary site, while chemotherapy improved prognosis in all risk groups.ConclusionsA prognostic score was developed to accurately predict the prognosis of de novo BCLM patients. Moreover, it may be useful for further subdividing them into different risk groups and helping guide clinicians in treatment decisions.