Bone-only Metastatic Breast Cancer Research Articles

Abstract PO4-05-05: Immune Activation Signatures for predicting CDKi primary response in advanced breast cancer patients

Abstract Background Cyclin Dependent Kinase inhibitors (CDKi’s) in combination with Endocrine Therapy (ET) have changed the first line management of patients with the most common subtype (HR+, HER2-) of metastatic breast cancer (MBC), improving progression-free survival (PFS) and overall survival. However, in approved indications for advanced breast cancer, approximately 20% of patients have been observed to have no response to CDKi’s and ET, and to progress after starting these therapies. Unlike other targeted therapeutics, there is no companion diagnostic or other clinically reliable biomarker for clinical decision support to indicate which patients will and will not benefit from CDKi therapy. Methods We have developed a novel platform that measures the Immune Activation Signature of patient plasma samples. Via simple measurements of the total concentration of protein-incorporated amino acid residues within patient plasma samples, the platform is designed to reveal changes in the proportion of immunoglobulins and albumin, and class-switching among immunoglobulins. For that purpose, we use Bioorthogonal chemical labelling reactions to label the protein-incorporated amino acids residues within the plasma. We measured the plasma samples of N=30 HR+, HER2- MBC patients, median age 54 years old, who were baseline naïve for CDKi’s treatment (16 on palbociclib, 11 on ribociclib, and 3 on abemaciclib) and ET. Eighteen patients had metastatic visceral disease and 12 patients had bone-only MBC. All patients were prospectively followed, and response assessed according to RECIST criteria on a CT scan every 3-months. Results Non-responding patients developed objective progressive disease during the first 6 months after starting CDKis and ET. In this cohort, 4 patients (13%) were classified as non-responders. The median PFS in non-responding patients was 4.5 months (4.03-5.02) and the median PFS in the cohort of responding patients was 16.6 months (6.8 – 40.9). The Immune Activation Signatures of the Responding and Non-Responding patients are shown in table 1. We analyzed the results with classical statistics and machine learning. A multivariate analysis of variance (MANOVA) test of the null hypothesis that the Immune Activation Signatures of Non-Responders and Responders are the same gave p = 0.00388. We analyzed the measured Immune Activation Signatures using a supervised machine learning classifier and observed in a held-back validation set correct prediction of 100% of non-responding patients and 95% accurate predictions overall. Conclusions According to these results, this platform may provide a clinically helpful biomarker for clinical decision support in the advanced or aggressive breast cancer context (patients with visceral metastasis bordering on visceral crisis), or for patient stratification in new indications. Table. Immune Activation Signature measurements (mean values in Clinical Outcome) Citation Format: Luis Costa, Cong Tang, Emma Yates, Qi Shi, Wesley Sukdao, Patricia Corredeira, Gonçalo Costa, Helena Pais, Catarina Abreu, Leonor Ribeiro, Rita Teixeira de Sousa, Sofia Torres, André Mansinho, Sandra Casimiro, Ana Cavaco, Patricia Alves, Angela Rodrigues, Lisiana Szeneszi, Gonçalo Bernardes. Immune Activation Signatures for predicting CDKi primary response in advanced 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 PO4-05-05.

Abstract PO5-05-12: Loco-regional Treatment in De Novo Bone Only Metastatic Breast Cancer; Prospective, Multi-Institutional Real-World Data, BOMETIN, Protocol MF14-1a

Abstract Introduction: The impact of loco-regional treatment (LRT) on survival in de novo bone-only metastatic breast cancer (BC) is controversial. The aim of this study is to assess the effect of LRT on survival utilizing international, prospectively acquired data in this cohort of patients. Materials and Methods: Patients with de novo metastatic BC with bone-only metastases were divided into two groups: those receiving systemic therapy only (ST) and those undergoing LRT. Patients who received LRT were divided into two groups: those who received ST after LRT (LRT+ST arm) and those who received ST prior to LRT (ST+LRT arm). Solitary or multiple bone metastases were classified, and factors associated with disease progression were analyzed. Results: There were a total of 744 patients with de novo bone-only metastatic BC treated at each of the participating institutions between 2014 and 2022, with 372 (50%) participants in each arm. Median follow-up was 48 months (32-66, 25-75%). Patients in the LRT group were significantly younger than the ST group [50 (42, 60) vs 55 (44, 66), p=0.0001]. There were no significant differences in grade, Her2 neu and triple negative status, receipt of hormonal therapy and intervention to metastatic sites. During follow-up, 58% (n=217) of patients in ST arm and 32% (n=120) of patients in LRT arm died (p< 0.001). Local progression was observed in 20% of the patients in the ST arm whereas it was 9% in the LRT arm (p=0.0001). Systemic progression occurred more in ST arm; 66% (n=244) compared to 41% (n=152) of patients in LRT group (p< 0.001). The Hazard of death was 64% lower in LRT group than in ST group (HR: 0.36, 95% CI: 0.29-0.45), p<0.0001). The burden of metastatic disease was significantly different between groups with the solitary bone metastasis rate higher in LRT group than the ST only group (50% vs 24%, p< 0.001). However, the LRT group had better overall survival for both solitary (HR: 0.38, 95% Cl: 0.26-0.55) and multiple (HR: 0.38, 95% Cl: 0.29-0.51) bone metastases patients. Within the LRT group, survival rates were similar whether the breast surgery was performed before or after ST.Multivariate Cox analysis showed that LRT and ER/PR positivity significantly decrease the hazard of death (p< 0.05). Conclusion: Analysis of this large multi-institutional patient cohort provides further evidence that LRT improves overall survival and lowers loco-regional recurrence in patients with de novo bone-only metastatic BC. In breast cancer patients with bone-only metastases at presentation, the decision for LRT should be made through a multidisciplinary approach with consideration of surgical therapy at the primary tumor. Citation Format: Atilla Soran, Serdar Ozbas, Lutfi Dogan, Didem Can Trabulus, Jamila El-Azrhi, Kazim Senol, Berk Goktepe, Shruti Zaveri, Salyna Meas, Umut Demirci, Hasan Karanlik, Aykut Soyder, Ahmet Dağ, Ahmet Bilici, Mutlu Dogan, Mehmet Ali Nahit Sendur, Hande Koksal, Mehmet Ali Gulcelik, Neslihan Cabıoğlu, Levent Yeniay, N. Zafer Utkan, Nuri Karadurmus, Gul Daglar, Turgay Simsek, Birol Yildiz, Cihan Uras, Mustafa Tukenmez, Cihangir Ozaslan, Niyazi Karaman, Arda Isik, Berkay Demirors, Efe Sezgin, Vahit Ozmen, Anthony Lucci. Loco-regional Treatment in De Novo Bone Only Metastatic Breast Cancer; Prospective, Multi-Institutional Real-World Data, BOMETIN, Protocol MF14-1a [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-12.

Clinical Value of Surgery and Establishment a Predictive Model for Breast Cancer Patients with Bone-Only Metastasis.

Whether to perform surgery on breast cancer with initial bone metastasis is heatedly debated. The aim of this study was to assess the efficacy of surgery to prolong survival time towards breast cancer patients with bone-only metastasis, and create a prognostic nomogram to predict long-term survival. Patients diagnosed with bone-only metastatic breast cancer from 2010 to 2015 were included in this study. National Cancer Database (NCDB) was used to obtain patients' data. A total of 7751 patients were included for final analysis, among which 3114 (40.2%) patients had received specialized breast surgery and 4637 (59.8%) had not. Patients who had undergone surgery showed a superior overall survival (OS) compared to patients without surgery (multivariate: HR (hazard ratios) = 0.58; 95% CI (confidence interval) [0.54-0.62]; p < 0.001). Moreover, survival benefit from surgery was also true in almost all subgroups. Prognostic nomogram to individually predict patients' long-term survival rate exhibited an acceptable predictive capability, with a C-index around 0.7 both in training and validation cohorts. Clinicopathological factors included in the nomogram could discriminate patients into subgroup with different prognoses. Our data suggests that surgery may enhance OS in patients with initial bone-only metastatic breast cancer. Additionally, the created nomogram showed an acceptable could predict patients' long term survival.

Unveiling bone metastasis: Exploring histological subtypes of breast cancer in Indonesia's tertiary referral hospital

IntroductionThe histological grade of a tumor is an important prognostic indicator in both primary breast cancer and metastatic. We aimed to show the distribution of bone metastasis locations across different histological subtypes of breast cancer and how they relate to each. MethodsThe cohort retrospective study comprised 65 patients diagnosed with bone-only metastatic breast cancer, all female. The secondary statistics for 2014 to 2022 were derived from breast cancer registration data collected to determine the relationships between patterns of bone metastases sites and histopathological grading in various histological categories. ResultsThe average age was 44.28±9.80 years (25–62 years), with 38 patients (58.5%) diagnosed with Invasive Ductal Carcinoma (IDC) and 27 patients (41.5%) with Invasive Lobular Carcinoma (ILC). Grade III were found in 34 patients (50.8%), Grade II in 31 patients (47.7%) and Grade I in one patient (1.5%). The most common sites of bone metastases are costae, followed by femur, vertebrae and pelvic. Vertebrae and costae metastasis are significantly correlated with histological grading and breast cancer pathology (p: 0.027 and 0.033, respectively). ConclusionThere is a considerable difference between vertebrae and costae metastasis in terms of histological grading and breast cancer pathology which indicates the higher grade contains a greater variety of bone metastases sites.

Clinical Characteristics, Prognostic Factors and Treatment Outcomes of Patients with Bone-Only Metastatic Breast Cancer.

IntroductionBone is the most frequent site of breast cancer metastasis. Differences between those who present with de novo bone-only metastasis (BOM) and those who progress to bone-only disease following a diagnosis of early-stage breast cancer are not clear. Such differences in clinical course might have an impact on the aggressiveness of treatment. This study presents the clinical and pathological features, along with treatment outcomes, of breast cancer patients with BOM in relation to the timing and type of bone metastasis.Patients and MethodsPatients with breast cancer and BOM were retrospectively reviewed. De novo BOM was defined as bone metastasis diagnosed at presentation or within the first 4 months of follow-up. Treatment outcomes of patients with de novo, compared to those with subsequent BOM, are presented.Results242 patients, median age (range) at diagnosis was 52 (27–80) years were enrolled. The majority of the patients (77.3%) had de novo BOM with multiple sites of bone involvement (82.6%). At a median follow-up of 37.7 months, the median overall survival (OS) for patients with de novo BOM disease was significantly shorter than those who developed so subsequently; 40.8 months (95% CI, 51.1–184.1) compared to 80.9 months (95% CI, 36.4–47.9), p < 0.001. Tumor grade, hormone receptor status and type of bone lesions (lytic versus sclerotic) had a significant impact on survival outcomes.ConclusionBreast cancer with de novo BOM is a distinct clinical entity with unfavorable prognosis and is associated with shorter survival. Several risk factors for poor outcomes were identified and might inform treatment plans.

Abstract PS14-22: Clinical characteristics, prognostic factors and treatment comes of patients with bone-only metastatic breast cancer

Abstract Introduction: Despite efforts in advancing early detection programs, 5-20% of breast cancer patients present with distant metastases at diagnosis. Bone is the most frequent site of breast cancer metastasis, noted in 60-80% of metastatic breast cancer (MBC) patients, and is the first site of metastatic disease in 25-40% of patients. The outcome of patients with bone-only MBC (BOM) is usually better than those with visceral metastasis. However, differences between those who present with De-novo BOM and those who progress to bone-only disease following a diagnosis of early stage breast cancer is not clear. Such differences in clinical course might have an implication on aggressiveness of treatment.The aim of the study is to present the clinical and pathological features along with treatment outcomes of breast cancer patients with BOM in relation to timing and type of bone metastasis. Known prognostics factors that affects treatment outcome will be presented.Patients and Methods: Patients with De-novo and those who progressed after an initial diagnosis of early-stage breast cancer with bone-only metastasis diagnosed, treated and followed up at our institution between 2006 and 2018 were included. Data related to characteristic such as, grade, hormonal status, HER-2 status were collected from our electrical medical records, pathology and radiology reports. De-novo BOM was defined as bone metastasis diagnosed at presentation or within the first 4 months of follow up. Results: A total of 242 patients fulfilled our inclusion criteria and were included in the analysis. The median age (range) at diagnosis was 52 (27-80) years. Majority of the patients (77.3%) had De-novo BOM and multiple sites of bone involvement was identified in 82.6%. High- grade (G-III), HER2-positive and hormone receptor (HR)-negative disease were identified in 27.2%, 18.2% and 8.7%, respectively. Majority of the patients were treated with endocrine therapy while 31(12.9%) patients received chemotherapy at presentation.With a median follow up of 37.7 months, 185 (76.4%) of patients progressed, the median time to progression was 17.1 months (range 3-280m). The median overall survival (OS) for patients with de novo BOM disease was significantly shorter than those who developed subsequent bone metastasis; 40.8 months (95% CI, 51.1-184.1) compared to 80.9 months (95% CI, 36.4-47.9), p &amp;lt; 0.001. Tumor grade, HR status and type of bone lesions (lytic or sclerotic) have significant impact on 5-year OS as detailed in Table-1 Conclusions: Bone-only metastasis breast cancer is distinct clinical entity with a favorable prognosis and a prolonged overall survival. Several risk features for poor OS were identified and might be useful tool to design future clinical trials to trigger upscaling endocrine therapy to include newly introduced resistance modulating agents. Characteristics5-year Progression-Free Survival5-year Overall SurvivalPercentageP-valuePercentageP-valueAge (year)&amp;lt;5022.70.5544.90.21≥5022.739.2Tumor gradeI27.30.00564.90.01II23.343.6III9.626.6HER2Negative23.10.0343.60.79Positive15.632.9Estrogen receptors (ER)Negative16.30.1513.70.005Positive23.144.5Progesterone receptors (PR)Negative17.70.0920.60.004Positive23.345.5Number of bone lesionsMultiple20.60.0839.10.08Single34.554.8Type of bone metastasisLytic28.20.9346.00.01Sclerotic21.554.9Mixed14.643.0Time of bone metastasisDe novo13.4&amp;lt;0.00135.5&amp;lt;0.001Late49.060.5 Citation Format: Lina Marei, Dina Braik, Ayat Taqash, Hikamt Abdel-Razeq. Clinical characteristics, prognostic factors and treatment comes of patients with bone-only metastatic breast cancer [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 PS14-22.

Similar Prognosis of Patients with Bone-only Metastatic Breast Cancer and Visceral Metastasis

Background: Bone-only metastatic breast cancer is believed to be non-life-threatening, and mild therapy is frequently selected to avoid adverse events of drug therapy. However, the prognoses of such patients are not well studied. Methods: Patients who received drug therapies for metastatic breast cancer between 2004 and 2016 at our institution were divided into the “Bone-only metastasis”, “non-visceral”, and “visceral” groups based on the mode of the first metastasis, and the efficacy of the first-line therapy and survival of these patients were compared. Results: There were 131 eligible patients, and the bone-only metastasis, non-visceral, and visceral groups included 26, 25, and 80 patients, respectively. The median survival time (MST) of the overall survival (OS) in each group was 35.1, 34.9, and 37.4 months, respectively (p=0.71). The clinical benefit rates of first-line therapy in the bone-only metastasis, non-visceral, and visceral groups were 66.7%, 45%, and 69.3%, respectively, and the MST of the time to treatment failure (TTF) in each group was 6.3, 5.5, and 5.8 months, respectively, showing that the efficacy of first-line therapy did not significantly differ among the groups. In the bone-only metastasis group, patients with &lt;5 metastases tended to have a good prognosis, and those with a low nuclear grade and long first-line therapy duration had a significantly better prognosis than others. Conclusion: The patients with bone-only metastasis had a similar prognosis and treatment response to those with other modes of metastasis, and the patients with a good response to the first-line therapy had a good prognosis.

Real-life prognosis of 5041 bone-only metastatic breast cancer patients in the multicenter national observational ESME program.

Background:Bone-only (BO) metastatic breast cancer (MBC) is considered a more favorable entity than other MBC presentations. However, only few retrospective series and data from selected randomized controlled trials have been reported so far.Methods:Using the French national multicenter ESME (Epidemiological Strategy and Medico Economics) Data Platform, the primary objective of our study was to compare the overall survival (OS) of patients with BO versus non-BO MBC at diagnosis, with adjustment on main prognostic factors using a propensity score. Secondary objectives were to compare first-line progression-free survival (PFS1), describe treatment patterns, and estimate factors associated with OS.Results:Out of 20,095 eligible women, 5041 (22.4%) patients had BO disease [hormone-receptor positive (HR+)/human epidermal growth-factor-receptor-2 negative (HER2−), n = 4 102/13,229 (31%); HER2+, n = 644/3909 (16.5%); HR−/HER2−, n = 295/2 957 (10%)]. BO MBC patients had a better adjusted OS compared with non-BO MBC [52.1 months (95% confidence interval (CI) 50.3–54.1) versus 34.7 months (95% CI 34.0–35.6) respectively]. The 5-year OS rate of BO MBC patients was 43.4% (95% CI 41.7–45.2). They also had a better PFS1 [13.1 months (95% CI 12.6–13.8) versus 8.5 months (95% CI 8.3–8.7), respectively]. This observation could be repeated in all subtypes. BO disease was an independent prognostic factor of OS [hazard ratio 0.68 (95% CI 0.65–0.72), p < 0.0001]. Results were concordant in all analyses.Conclusion:BO MBC patients have better outcomes compared with non-BO MBC, consistently, through all MBC subtypes.

Comparison of Whole-Body MRI, CT, and Bone Scintigraphy for Response Evaluation of Cancer Therapeutics in Metastatic Breast Cancer to Bone

Background CT and bone scintigraphy have limitations in evaluating systemic anticancer therapy (SACT) response in bone metastases from metastatic breast cancer (MBC). Purpose To evaluate whether whole-body MRI enables identification of progressive disease (PD) earlier than CT and bone scintigraphy in bone-only MBC. Materials and Methods This prospective study evaluated participants with bone-only MBC between May 2016 and January 2019 (ClinicalTrials.gov identifier: NCT03266744). Participants were enrolled at initiation of first or subsequent SACT based on standard CT and bone scintigraphy imaging. Baseline whole-body MRI was performed within 2 weeks of entry; those with extraosseous disease were excluded. CT and whole-body MRI were performed every 12 weeks until definitive PD was evident with one or both modalities. In case of PD, bone scintigraphy was used to assess for bone disease progression. Radiologists independently interpreted images from CT, whole-body MRI, or bone scintigraphy and were blinded to results with the other modalities. Systematic differences in performance between modalities were analyzed by using the McNemar test. Results Forty-five participants (mean age, 60 years ± 13 [standard deviation]; all women) were evaluated. Median time on study was 36 weeks (range, 1-120 weeks). Two participants were excluded because of unequivocal evidence of liver metastases at baseline whole-body MRI, two participants were excluded because they had clinical progression before imaging showed PD, and one participant was lost to follow-up. Of the 33 participants with PD at imaging, 67% (22 participants) had PD evident at whole-body MRI only and 33% (11 participants) had PD at CT and whole-body MRI concurrently; none had PD at CT only (P < .001, McNemar test). There was only slight agreement between whole-body MRI and CT (Cohen κ, 0.15). PD at bone scintigraphy was reported in 50% of participants (13 of 26) with bone progression at CT and/or whole-body MRI (P < .001, McNemar test). Conclusion Whole-body MRI enabled identification of progressive disease before CT in most participants with bone-only metastatic breast cancer. Progressive disease at bone scintigraphy was evident in only half of participants with bone progression at whole-body MRI. © RSNA, 2020 Online supplemental material is available for this article.

Abstract P2-19-01: Impact of bone-only metastatic breast cancer on outcome in a real-life setting: A comprehensive analysis of 5,041 women from the ESME database

Abstract Background: Bone-only (BO) metastatic breast cancer (MBC), defined as bone as unique site of metastasis at MBC diagnosis, is thought to carry a better prognosis among MBC. However, only small retrospective series and data from selected randomized controlled trials have been reported so far. Based on a national database, we aimed at providing a large comprehensive analysis of BO MBC, and at evaluating its impact on clinical outcome. Methods: The ESME MBC platform (NCT03275311) is a French multicenter retrospective real-life database using a clinical trial-like methodology to collect data from 18 French Comprehensive Cancer Centers. It includes data from each newly diagnosed MBC patient having initiated at least one treatment between 2008 and 2016. BO cases occurring in women were retrieved and compared to the overall non-BO population, regarding treatment effects and survival. Results: Of the 22,463 women selected in the database, 5,041 (22.4%) patients with BO disease were identified. Most (N=4,102, 81.4%) had HR+/HER2- disease while 644 (12.8%) and 295 (5.9%) patients had HER2+ or HR-/HER2- disease, respectively. Compared to non-BO MBC, BO MBC patients were older in the global cohort and in HR-/HER2- patients (mean age 61.0y versus 59.5y, and 59.3y vs 56.4y, all p&amp;lt;0.0001, respectively), and tumor histology was more frequently a lobular carcinoma in the global cohort, in HR+/HER2- and in HR-/HER2- patients (18.6% vs 10.8%, 20.6% vs 15.2%, 13.8% vs 3.2%, all p&amp;lt;0.0001, respectively). In addition, metastatic disease occurred de novo more frequently in BO MBC patients (37.9% versus 29.2%) (p&amp;lt;0.0001), and a statistically significant difference was also observed within each tumor subtype group. The management of bone disease included bisphosphonates or denosumab, radiotherapy, and invasive bone metastasis procedures in 3,913 (77.6%), 2,929 (58.1%), and 1,154 (22.9%) patients, respectively. Median follow up was 52.4 months (95% CI [50.8-54.2]) in BO population and 50.9 months (95% CI [49.7-51.8]) in non-BO population. BO MBC patients had improved median progression-free survival (PFS) 1, regarding first-line treatment, and overall survival (OS) compared to non-BO MBC, globally and within each tumor subtype group (Table). Indeed, 5-year OS rates reached up to 43%, 54% and 16% in HR+/HER2-, HER2+ and HR-/HER2- BO MBC groups, respectively. This suggests that a substantial number of these patients could be considered as long survivors. In the BO MBC cohort, de novo BO MBC patients had a higher 5-year OS rate than relapsed BO MBC patients. BO disease was an independent prognostic factor of OS (hazard ratio 0.68 (95% CI [0.65-0.72]), p&amp;lt;0.0001) together with age, tumor subtype, grade, adjuvant treatment and metastatic-free interval. Conclusion: This large comprehensive study is the largest cohort of BO MBC to date. BO MBC has a distinct presentation from non-BO MBC and carry a better prognosis compared to non-BO MBC. A significant proportion of BO MBC patients have a very long survival and may benefit from aggressive local therapy, as stereotactic radiotherapy. Dedicated studies are warranted to tailor the management of these patients. Funding: This work was supported by UNICANCER. The ESME MBC database is supported by an industrial consortium (Roche, Pfizer, AstraZeneca, MSD, Eisai and Daiichi Sankyo). Data collection, analyses and publications are totally managed by R&amp;D UNICANCER independently of the industrial consortium. TableBOBOBOBOnon-BOnon-BOnon-BOnon-BON (%)median OS monthsmedian PFS1 months5-year OS rate %N (%)median OS monthsmedian PFS1 months5-year OS rate %(95% CI)(95% CI)(95% CI)(95% CI)(95% CI)(95% CI)Overall population5,041 (100%)52.1 (50.3-54.1) 13.1 (12.6-13.8) 43.41 (41.66-45.15)15,054 (100%)34.7 (34.0-35.6) 8.5 (8.3-8.7) 30.55 (29.62-31.48)HR+/HER-4,102 (81.4%)52.6 (50.5-54.8)13.6 (13.0-14.3)43.52 (41.56-45.46)9,127 (60.6%) 39.0 (37.8-40.1)9.6 (9.3-9.9)32.69 (31.47-33.93)HER2+644 (12.8%)66.4 (59.8-71.9) 14.9 (12.9-17.3) 54.49 (49.54-59.16)3,265 (21.7%) 46.5 (44.2-48.9)10.6 (10.1-11.3)39.88 (37.77-41.98)HR-/HER2-295 (5.9%)20.8 (18.3-27.4) 5.6 (4.9-7.5)16.21 (11.21-22.02)2,662 (17.7%) 14.3 (13.6-15.1)4.8 (4.6-5.0)10.89 (9.4-12.5)De novo MBC patients1,909 (37.9%)58.6 (55.4-62.1)17.9 (17.0-18.9)48.24 (45.28-51.14)4,399 (29.2%) ---Relapsed MBC patients3,132 (62.1%)48.3 (46.5-50.5)10.7 (10.2-11.2)40.51 (38.34-42.67)10,655 (70.8%)--- Citation Format: Marion Bertho, Julien Fraisse, Anne Patsouris, Paul Cottu, Suzette Delaloge, David Pérol, Anne Jaffré, Anthony Goncalves, Marie-Paule Lebitasy, Véronique D'Hondt, Florence Dalenc, Jean-Marc Ferrero, Christelle Levy, Patrick Arveux, Roman Rouzier, Frédérique Penault-Llorca, Lionel Uwer, Jean-Christophe Eymard, Mathias Breton, Michaël Chevrot, Marianne Leheurteur, Michel Velten, Gaëtane Simon, Jean-Sébastien Frenel. Impact of bone-only metastatic breast cancer on outcome in a real-life setting: A comprehensive analysis of 5,041 women from the ESME database [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-19-01.

Abstract P2-13-13: For women with bone-only metastatic breast cancer, is there a benefit to primary prevention?

Abstract Background: The prognosis of patients with estrogen receptor positive (ER+) bone-only metastatic breast cancer (B-MBC) is good, with the average life expectancy extending years with contemporary management. In the general population, studies investigating the impact of screening programs designed to detect disease as early as possible in otherwise asymptomatic patients have consistently shown reduction in morbidity and mortality but outcomes among patients living with B-MBC has not been adequately addressed. This study aimed to investigate the rate at which patients with ER+ breast cancer metastatic only to bone underwent cholesterol, breast cancer, colon cancer, and lung cancer screening and to determine if this screening had any impact on overall survival and cause of death. Methods: We conducted a retrospective chart review of patients treated for ER+ B-MBC at the Lifespan Cancer Institute in Providence, RI between 1/1/15 and 5/31/18. Each patient’s medical records and tumor registry information were reviewed. Data on these patients’ disease history were collected along with data on cholesterol, breast cancer, colon cancer, and lung cancer screening. Descriptive statistics were calculated using STATA statistical software. Results: A total of 48 patients with ER+ B-MBC were identified. Median overall survival from initial diagnosis of breast cancer was 148 months; measured from the diagnosis of bone metastasis, it was 52.4 months. Twenty-nine out of the 48 patients received cholesterol screening (60%), 14/48 had mammograms (29%), and only 8/48 had colonoscopy (17%). No patients underwent screening lung CT (Table 1). Compared to those who did not undergo screening, patients who were screened for cholesterol had significantly longer median overall survival (175.4 vs 106 months, respectively, p=.02) and those undergoing mammogram had a trend towards longer survival (187 vs 131 months, p=.08). Screening was not associated with a difference in rates of death attributed to breast cancer. No deaths due to other malignancies were identified. Of those undergoing mammography, only one abnormal report was identified, and biopsy of the lesion was benign. Table 1: Rate of abnormal screening results, median overall survival from index diagnosis, and death from index breast cancer.Abnormal screening resultMedian OS (months)95% CIp valueDeath from IBCp valueCholesterolscreened18/25175.4135 - 2160.02**1/20.30not screened10668 - 1445/6Mammogramscreened1/14187116 - 2590.08*3/40.60not screened131101 - 1626/10OS=overall survival. CI=confidence interval. IBC=index breast cancer. ** = p &amp;lt; 0.05. *= p &amp;lt; 0.1 Conclusions: A large proportion of patients with B-MBC undergo primary preventative screening measures, and of these, cholesterol screening is the most common. Screening was associated with longer overall survival, but did not change the rates of death due to breast cancer. These results suggest that clinicians are offering screening to a subgroup of women who are healthy despite B-MBC. However, our data suggest there is little benefit to screening, and this should be addressed in a larger dataset. Citation Format: Kristina A Fanucci, Mary Anne Fenton, Christine Duffy, Camille Higel-McGovern, Don Dizon. For women with bone-only metastatic breast cancer, is there a benefit to primary prevention? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-13-13.

Radiation therapy for bone-only metastases in breast cancer patients: A GOCO survey of current clinical practice.

The role of radiation therapy (RT) for patients with bone-only metastatic (BOM) breast cancer has not been investigated sufficiently. The aim of this survey was to evaluate current clinical practice in treating breast cancer patients with BOM in Radiation Therapy Departments in Catalonia and Occitania within the scope of the GOCO group. An electronic questionnaire was completed by experienced radiation oncologists from fourteen RT centers. The items surveyed the professional experience, therapeutic approach, technique, dose stereotactic body RT (SBRT) availability. All Radiation Oncology Departments (ROD) in Catalonia (12) and Occitania (2) responded to the survey. Eleven (78.5%) of the RODs advise RT for BOM as initial treatment in the oligometastatic setting. RT to asymptomatic bone oligometastases is more often restricted for "risky lesions". The most inconsistent approaches were the treatment for asymptomatic lesions, when to treat bone metastases with respect to systemic treatment (ST) and the indication for RT after a complete response to ST. While BOM breast cancer patients have a relatively good prognosis, there is a lack of consistency in their approach with RT. This can be explained by the absence of evidence-based guidelines and an incomplete availability of SBRT.

Abstract P1-18-04: CTCs and SUV to predict the efficacy of the bone-specific radiopharmaceutical agent radium-223 dichloride combined with hormonal therapy for hormone receptor-positive bone-dominant breast cancer metastasis

Abstract Background: Radium-223 dichloride (Ra-223) is a targeted alpha particle-based radiotherapeutic that has a localized cytotoxic effect on bone metastases. We sought to determine whether the circulating tumor cell (CTC) count and the presence of CTCs in epithelial-mesenchymal transition (EMT-CTCs) along with the standardized uptake value (SUV) on positron emission tomography-computed tomography (PET/CT) scans predict the efficacy of combined Ra-223 and hormonal therapy in patients with hormone receptor (HR)-positive bone-dominant metastatic breast cancer. Patients and Methods: In this single-center phase 2 study (NCT02366130), 36 patients received Ra-223 (55 kBq/kg intravenously) on day 1 and then every 4 weeks for six cycles. Patients also received a standard care endocrine monotherapy. One non-bone metastatic site was allowed. The number of prior endocrine therapies was not limited and one prior chemotherapy was allowed for metastasis. Response was evaluated using the PET Response Criteria in Solid Tumors (PERCIST) with PET/CT at baseline, 6 and 9 months (mo) later. The CTC count (CellSearch) and the presence of EMT-CTCs (AdnaTest) was determined at baseline, 6 and 9 mo later. Progression-free survival (PFS) time was calculated to evaluate efficacy. Results: Seven patients (20%) had a non-bone metastatic site. The median number of prior therapies for metastasis was 1 (range, 0-4). Six patients (17%) received chemotherapy. The median CTC count at baseline was 4 (range, 0-306). Only four patients (11%) were positive for EMT-CTCs at baseline. The median follow-up time was 14.7 mo (95% confidence interval [CI], 13.2 mo-not reached [NR]). The disease control rate at 9 mo was 46% in 33 patients who reached 9 mo or progressed up to 9 mo. The tumor response rate at 6 mo was 52% (complete/partialresponse rate; 22/30 %) in 27 patients whose disease was evaluable using PERCIST. The SUV on PET/CT decreased significantly at 6 and 9 mo after baseline (average decreases of 1.5 (p=0.0004) and 2.5 (p=0.0054), respectively). The median PFS duration was 7.4 mo (95% CI, 4.8 mo-NR). The median bone PFS was 16 mo (95% CI, 7.3 mo-NR). Patients with bone-only metastasis (N=28, 80%) had a significantly longer median PFS duration than did patients with non-bone metastases at baseline (N=7, 20%) (13.8 mo versus 4.5 mo; p=0.017). Patients without prior treatment (N=12, 34%) tended to have longer median PFS durations than did those who underwent prior treatment (N=23, 66%) (16.8 mo versus 4.8 mo; p=0.1865). Also, patients with &amp;lt;5 CTCs at baseline (N=19, 54%) tended to have longer median PFS durations than did those with ≥5 CTCs (N=16, 46%) (13.8 mo versus 4.8 mo; p=0.1277). EMT-CTCs status did not predict efficacy. Conclusions: Bone-only metastatic breast cancer and SUV suppression by Ra-223 are predictive of efficacy. Patients with baseline &amp;lt;5 CTC count tended to have better outcomes than did those with ≥5 CTCs. Combined treatment with Ra-223 and a hormonal agent is especially effective at controlling bone metastasis in patients with HR-positive breast cancer. Bone-only metastatic disease and CTC count should be factored in future clinical trial designs. Citation Format: Ueno NT, Tahara RK, Reuben JM, Gao H, Saigal B, Fujii T, Lucci A, Ibrahim NK, Damodaran S, Shen Y, Liu DD, Hortobagyi GN, Tripathy D, Lim B, Chasen BA. CTCs and SUV to predict the efficacy of the bone-specific radiopharmaceutical agent radium-223 dichloride combined with hormonal therapy for hormone receptor-positive bone-dominant breast cancer metastasis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-18-04.

Abstract P1-18-06: First-line treatment for endocrine sensitive bone-only metastatic breast cancer: Is more always better?

Abstract The standard first-line for endocrine sensitive metastatic breast cancer (BC) is represented by endocrine therapy. Several phase III clinical trials searched for more effective endocrine strategies. Nevertheless, the use of combinations for the first-line treatment of bone-only disease (BoD) is widely discussed, due to its indolent course. Our meta-analysis aims to explore the role of new endocrine strategies in BoD. A systematic review of electronic databases was conducted to identify the phase III clinical trials comparing the standard AI to novel experimental strategies. The hazard ratios (HR) for PFS were pooled in a meta-analysis. The heterogeneity of the data was evaluated by Chi-square Q test and I2 statistic. 8 studies were included in the analyses. 4 trials explored the role of CDK4/6 inhibitors (Monaleesa2 and 7, Monarch3 and Paloma2), 2 trials analyzed Fulvestrant + AI (SWOG and FACT), one trial studied Fulvestrant monotherapy (FALCON), while one trial evaluated the association between Bevacizumab and Letrozole (ALLIANCE). 6 trials reported data regarding the BoD, while 2 trials included the BoD in the non-visceral disease. Overall, the meta-analyses showed a PFS advantage for the experimental arms [HR 0.70 p 0.012], with a significant moderate/high heterogeneity [I2 66.48% p 0.004]. Only the FALCON and Paloma2 showed a significant improvement in PFS, respectively for Fulvestrant and Palbociclib + Letrozole. Considering only trials reporting data for BoD, the experimental arms significantly improved the PFS [HR 0.66 p 0.005], with a low/moderate non-significant heterogeneity [I2 44.95% p 0.106]. The novel strategies showed to be able to improve the PFS of BoD. Nonetheless, only Palbociclib + Letrozole provided statistically significant data of advantage in this setting. In clinical trials, BoD is often included in the non-visceral disease subgroup. Future clinical trials should take into account the differences in natural history and better prognosis of BoD, in order to define the best approach to these patients. Citation Format: Toss A, Venturelli M, Sperduti I, Isca C, Molinaro E, Barbieri E, Piacentini F, Omarini C, Cortesi L, Cascinu S, Moscetti L. First-line treatment for endocrine sensitive bone-only metastatic breast cancer: Is more always better? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-18-06.

337P - First-line treatment for endocrine sensitive bone-only metastatic breast cancer: Is more always better?

337P - First-line treatment for endocrine sensitive bone-only metastatic breast cancer: Is more always better?

US Food and Drug Administration Pooled Analysis to Assess the Impact of Bone-Only Metastatic Breast Cancer on Clinical Trial Outcomes and Radiographic Assessments.

Purpose The outcome and proportion of patients with bone-only (BO) metastatic breast cancer (MBC) has not been well described. We sought to describe the differential outcomes of patients with BO MBC in clinical trials and explore whether there was a discrepancy in radiographic reads between investigator and blinded independent central review. Methods We pooled and analyzed data on 10,521 patients from 13 prospective trials submitted for MBC treatment in initial or supplemental New Drug or Biologics License Applications from 2005. Three subsets were evaluated: BO, bone with other metastases (BWO), and no bone metastases (NBM). Early discordance rate and late discordance rate were calculated from 3,733 and 2,813 patients subject to a blinded independent central review, respectively. Results Bone metastases were identified in 49% (range: 42% to 73%) of patients across trials. BO disease was present in 12.5% (range: 4% to 26%), dependent on subtype. Investigator-assessed progression-free survival (PFS) and overall survival (OS) for the pooled trials demonstrated improved outcomes for the BO subgroup compared with other subgroups (BO v BWO PFS hazard ratio [HR], 0.64; 95% CI, 0.591 to 0.696; BO v NBM PFS HR, 0.70; 95% CI, 0.65 to 0.76; BO v BWO OS HR, 0.56; 95% CI, 0.50 to 0.61; BO v NBM OS HR, 0.68; 95% CI, 0.61 to 0.76). The BO subgroup has a higher early discordance rate and lower late discordance rate than the BWO and NBM subgroups. Conclusion To our knowledge, this review is the largest analysis to date of the BO subgroup of MBC and suggests this subgroup may have a distinct natural history. There also seems to be a difference in how the local investigators assessed progression events in the BO subgroup when compared with the other two groups.

Increased risk of SSEs in bone-only metastatic breast cancer patients treated with zoledronic acid

BackgroundBone represents one of the most common sites to which breast cancer cells metastasize. Patients experience skeletal related adverse events (pathological fractures, spinal cord compressions, and irradiation for deteriorated pain on bone) even during treatment with zoledronic acid (ZA). Therefore, we conducted a retrospective cohort study to investigate the predictive factors for symptomatic skeletal events (SSEs) in bone-metastasized breast cancer (b-MBC) patients. MethodsWe retrospectively collected data on b-MBC patients treated with ZA. Patient characteristics, including age, subtype, the presence of non-bone lesions, the presence of multiple bone metastases at the commencement of ZA therapy, duration of ZA therapy, the time interval between breast cancer diagnosis and the initiation of ZA therapy, and type of systemic therapy, presence of previous SSE were analyzed using multivariable logistic regression analysis. ResultsThe medical records of 183 patients were reviewed and 176 eligible patients were analyzed. The median age was 59 (range, 30–87) years. Eighty-seven patients were aged ≥60 years and 89 patients were aged < 60 years. The proportions of patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-positive disease were 81.8%, 63.1%, and 17.6%, respectively. Fifty-three patients had bone-only MBC at the commencement of ZA therapy. SSEs were observed in 42 patients. In the multivariable logistic regression analysis, bone-only MBC but not a breast cancer subtype was an independent risk factor for an SSE during ZA therapy (odds ratio: 3.878, 95% confidence interval: 1.647–9.481; p = 0.002). ConclusionsBone-only MBC patients are more likely to experience an SSE even after treatment with ZA.

Long term survival of bone-only metastatic breast cancer benefit from bone-window CT: a case report

Long term survival of bone-only metastatic breast cancer benefit from bone-window CT: a case report

Abstract P6-01-02: Flourine-18-fluorodeoxyglucose positron emission tomography for the evaluation of response to therapy in bone-dominant metastatic breast cancer: Examination in patients enrolled on UPCC 17113

Abstract Background: Response of bone-only (BO) and bone-dominant (BD) metastatic breast cancer (mBC) to therapy is difficult to assess by conventional imaging. UPCC 17113 is a single institution prospective cohort study evaluating FDG PET at early and conventional follow up intervals, 4 and 12 weeks respectively, in patients with hormone receptor (HR) positive mBC receiving endocrine therapy. The objective of this study is to assess the relationship between changes relative to baseline in standard uptake values (SUV) of specific bone lesions and progression free survival (PFS). We will also explore change in SUV as it relates to overall survival (OS) and skeletal related events (SRE). We present interim results. Methods: Enrolled patients were ≥18 years with biopsy proven or documented clinically obvious HR-positive BD/BO mBC due to start new endocrine therapy. Any line endocrine therapy was allowed. FDG PET was performed at baseline, 4 and 12 weeks after initiation of new therapy. SUVmax for the 5 most metabolically active osseous lesions, excluding sites previously treated by radiation or surgery, were recorded at baseline, 4- and 12- week time-points. Average index lesion SUVmax (sum SUVmax/#lesions) and % change from baseline were calculated. Decline of ≥30% from baseline was defined as significant. Results: As of 6/1/2015, 11 patients were enrolled. All patients have completed the 4-week scan and 8 have completed the 12-week scan. Five and 6 out of the 11 patients had BO and BD HR-positive mBC respectively. Detectable changes in SUV from baseline were noted in all patients at both 4 and 12 weeks, with a 37% overall decline in average index lesion SUVmax at 4 weeks. 8 of 11 patients had a ≥30% decline, in SUV at 4 weeks averaging 46%. Five of the 6 patients in this group who completed the 12-week scan had a sustained decline averaging 50% from the baseline. Of note, the average decline between 4 and 12 weeks in this group was only 8%. Despite having an overall decline from baseline of 44%, the sixth patient in this group had an increase between 4 and 12 weeks of 22%. Three of the 11 patients had a &amp;lt;30% decline at 4 weeks with an average decline of 12%. Of the two patients in this group with 12 week scans, both had average increase of 25% from 4 weeks to 12 weeks, and an average overall increase from baseline of 12%. Conclusions: There are detectable changes in FDG SUV of osseous lesions at 4 and 12 weeks following initiation of endocrine therapy in patients with BO or BD HR positive mBC. Our interim results demonstrate the emergence of 3 groups of patients: (1) those who have a &amp;lt;30% decline at 4 weeks and increase of SUV at 12 weeks, (2) those who have a ≥30% decline in SUV at 4 weeks with sustained decline at 12 weeks, and (3) those who have a ≥30% reduction in SUV at 4 weeks but who do not have a sustained decline at 12 weeks. These interim results suggest that early FDG PET/CT may provide information on mBC response to endocrine therapy and insight into timing of response and progression. As more patients are enrolled and complete the studies, clearer patterns will emerge which will be correlated with PFS, OS and SRE. Citation Format: Lynch MC, Mankoff D, Bradbury AR, Domchek S, Glick JH, Matro J, DeMichele A, Clark AS. Flourine-18-fluorodeoxyglucose positron emission tomography for the evaluation of response to therapy in bone-dominant metastatic breast cancer: Examination in patients enrolled on UPCC 17113. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-01-02.

Tumour response interpretation with new tumour response criteria vs the World Health Organisation criteria in patients with bone-only metastatic breast cancer

Background:We compared the utility of a new response classification (MDA; based on computed tomography (CT), magnetic resonance imaging (MRI), plain radiography (XR), and skeletal scintigraphy (SS)) and the World Health Organisation response classification (WHO; based on XR and SS) in stratifying breast cancer patients with bone-only metastases with respect to progression-free survival (PFS), overall survival (OS), and clinical response.Methods:We retrospectively reviewed 41 patients with bone-only metastatic breast cancer and assigned responses according to the MDA and WHO criteria. We analysed whether the MDA or WHO response classifications correlated with PFS and OS.Results:With the MDA criteria, there were significant differences in PFS between patients classified as responders and those classified as nonresponders (P=0.025), but with the WHO criteria, there were not. Neither criteria distinguished responders from nonresponders in terms of OS. MDA response criteria correlated better than WHO response criteria with clinical response assessment.Conclusions:The MDA classification is superior to the WHO classification in differentiating between responders and nonresponders among breast cancer patients with bone-only metastases. Application of the MDA classification may allow bone lesions to be considered measurable disease. Prospective study is needed to test the MDA classification among patients with bone metastasis.