Metastasectomy versus radiation of secondary sites in stage IV breast cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 1094-1094
Author(s):  
Nadeem Bilani ◽  
Leah Elson ◽  
Elizabeth Blessing Elimimian ◽  
Hong Liang ◽  
Diana Saravia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Surgical Resection ◽  
Metastatic Breast ◽  
Secondary Site ◽  
Receptor Subtype ◽  
Stage Iv Breast Cancer ◽  
Prospective Trials ◽  
The Impact ◽  
The Brain

1094 Background: Prospective trials have yielded mixed results on the utility of surgery in metastatic breast cancer (mBC). Thus far, however, studies have focused primarily on the impact of lumpectomy or mastectomy. We previously showed that a combined approach involving resection of primary and secondary sites (i.e. ‘metastasectomy’) in patients with limited mBC was associated with improved overall survival (OS). We sought to evaluate the effect on OS of two approaches to loco-regional therapy (LRT) at secondary sites: metastasectomy versus radiation therapy. Methods: This is a retrospective analysis of patients diagnosed with mBC from 2010-2017 using the National Cancer Database. We identified 5 cohorts of patients by site of metastasis: mBC involving only 1) bone, 2) brain, 3) liver, or 4) lung; and 5) patients with metastasis involving >1 site. For each cohort, we used Kaplan-Meier (KM) models with log-rank testing to evaluate differences in OS, by the LRT approach at secondary sites (radiation versus metastasectomy). Prior to KM modeling, chi-squared statistics were used in each cohort to assess whether age, race, Charlson/Deyo score (CDS) for comorbidity, and receptor subtype were potential confounders of survival. The KM models were adjusted accordingly, as per the table below. Results: 53.4%) were between 50-70 years old, White (n=53,409, 78.9%), and had hormone receptor (HR)-positive/HER2 receptor-negative breast cancer. N=12,362 patients received radiation therapy at either the bone, brain, liver, or lung; while n=2674 underwent surgical resection of a metastatic site. Of patients with metastasis to 1 site (n=44,451), n=30,341(68.3%) involved the bone, n=1,119 (2.5%) involved the brain, n=5,227 (11.8%) involved the liver, and n=7,764 (17.5%) involved the lung. N=24,017 patients had metastatic disease involving > 1 site. KM modeling revealed superior OS of patients undergoing metastasectomy versus radiation of secondary sites in all 5 cohorts (p<0.05). The difference in median OS (ΔmOS) by LRT approach was more pronounced when metastasis involved only the liver (41.6 months) or lung (48.6 months), versus only the brain (9.7 months) or bone (8.7 months). Conclusions: Metastasectomy appears to confer a superior benefit for OS compared to radiation of secondary sites, particularly in patients with secondary site involvement limited to the liver or lung. More research is needed from prospective trials investigating surgical resection of metastatic sites.[Table: see text]

The impact of HER2 phenotype of circulating tumor cells in metastatic breast cancer: a study in 107 patients

2014 ◽  
Vol 74 (S 01) ◽  
Author(s):  
M Wallwiener ◽  
AD Hartkopf ◽  
S Riethdorf ◽  
J Nees ◽  
FA Taran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Metastatic Breast ◽  
The Impact

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Interacting Protein ◽  
Primary Tumors ◽  
Free Survival ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

scholarly journals Impact of Pharmaceutical Prophylaxis on Radiation-Induced Liver Disease Following Radioembolization

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1992
Author(s):  
Max Seidensticker ◽  
Matthias Philipp Fabritius ◽  
Jannik Beller ◽  
Ricarda Seidensticker ◽  
Andrei Todica ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liver Disease ◽  
Positive Impact ◽  
Metastatic Breast ◽  
Normal Liver ◽  
Liver Parenchyma ◽  
Breast Cancer Patients ◽  
Radiation Induced ◽  
The Impact

Background: Radioembolization (RE) with yttrium-90 (90Y) resin microspheres yields heterogeneous response rates in with primary or secondary liver cancer. Radiation-induced liver disease (RILD) is a potentially life-threatening complication with higher prevalence in cirrhotics or patients exposed to previous chemotherapies. Advances in RILD prevention may help increasing tolerable radiation doses to improve patient outcomes. This study aimed to evaluate the impact of post-therapeutic RILD-prophylaxis in a cohort of intensely pretreated liver metastatic breast cancer patients; Methods: Ninety-three patients with liver metastases of breast cancer received RE between 2007 and 2016. All Patients received RILD prophylaxis for 8 weeks post-RE. From January 2014, RILD prophylaxis was changed from ursodeoxycholic acid (UDCA) and prednisolone (standard prophylaxis [SP]; n = 59) to pentoxifylline (PTX), UDCA and low-dose low molecular weight heparin (LMWH) (modified prophylaxis (MP); n = 34). The primary endpoint was toxicity including symptoms of RILD; Results: Dose exposure of normal liver parenchyma was higher in the modified vs. standard prophylaxis group (47.2 Gy (17.8–86.8) vs. 40.2 Gy (12.5–83.5), p = 0.017). All grade RILD events (mild: bilirubin ≥ 21 µmol/L (but <30 μmol/L); severe: (bilirubin ≥ 30 µmol/L and ascites)) were observed more frequently in the SP group than in the MP group, albeit without significance (7/59 vs. 1/34; p = 0.140). Severe RILD occurred in the SP group only (n = 2; p > 0.1). ALBI grade increased in 16.7% patients in the MP and in 27.1% patients in the SP group, respectively (group difference not significant); Conclusions: At established dose levels, mild or severe RILD events proved rare in our cohort. RILD prophylaxis with PTX, UDCA and LMWH appears to have an independent positive impact on OS in patients with metastatic breast cancer and may reduce the frequency and severity of RILD. Results of this study as well as pathophysiological considerations warrant further investigations of RILD prophylaxis presumably targeting combinations of anticoagulation (MP) and antiinflammation (SP) to increase dose prescriptions in radioembolization.

scholarly journals The impact of sociodemographic factors on the utilization of radiation therapy in breast cancer patients in Estonia: a register-based study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Fereshteh Shahrabi Farahani ◽  
Keiu Paapsi ◽  
Kaire Innos
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Cancer Registry ◽  
Psychosocial Support ◽  
Sociodemographic Factors ◽  
Stage I ◽  
Equal Access ◽  
Administrative Databases ◽  
The Impact ◽  
Over Time

Abstract Background Radiation therapy is an important part of multimodal breast cancer treatment. The aim was to examine the impact of sociodemographic factors on radiation therapy use in breast cancer (BC) patients in Estonia, linking cancer registry data to administrative databases. Methods Estonian Cancer Registry provided data on women diagnosed with BC in Estonia in 2007–2018, including TNM stage at diagnosis. Use of radiation therapy within 12 months of diagnosis was determined from Estonian Health Insurance Funds claims, and sociodemographic characteristics from population registry. Receipt of radiation therapy was evaluated over time and by clinical and sociodemographic factors. Poisson regression with robust variance was used to calculate univariate and multivariate prevalence rate ratios (PRR) with 95 % confidence intervals (CI) for receipt of radiation therapy among stage I–III BC patients age < 70 years who underwent primary surgery. Results Overall, of 8637 women included in the study, 4310 (50 %) received radiation therapy within 12 months of diagnosis. This proportion increased from 39 to 58 % from 2007 to 2009 to 2016–2018 (p < 0.001). Multivariate regression analysis showed that compared to women with stage I BC, those with more advanced stage were less likely to receive radiation therapy. Receipt of radiation therapy increased significantly over time and was nearly 40 % higher in 2016–2018 than in 2007–2009. Use of radiation therapy was significantly lower for women with the lowest level of education compared to those with a university degree (PRR 0.88, 95 % CI 0.80–0.97), and for divorced/widowed women (PRR 0.95, 95 % CI 0.91–0.99) and single women (PRR 0.92, 95 % CI 0.86–0.99), compared to married women. Age at diagnosis, nationality and place of residence were not associated with receipt of radiation therapy. Conclusions The study showed considerable increase in the use of radiation therapy in Estonia over the study period, which is in line with increases in available equipment. The lack of geographic variations suggests equal access to therapy for patients living in remote regions. However, educational level and marital status were significantly associated with receipt of radiation therapy, highlighting the importance of psychosocial support in ensuring equal access to care.

Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer

2016 ◽  
Vol 34 (25) ◽  
pp. 2961-2968 ◽  
Author(s):  
Charlotte Fribbens ◽  
Ben O’Leary ◽  
Lucy Kilburn ◽  
Sarah Hrebien ◽  
Isaac Garcia-Murillas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Advanced Breast Cancer ◽  
Metastatic Breast ◽  
Advanced Breast ◽  
Phase Iii ◽  
Wild Type ◽  
Estrogen Receptor Positive ◽  
Esr1 Mutations ◽  
The Impact

Purpose ESR1 mutations are selected by prior aromatase inhibitor (AI) therapy in advanced breast cancer. We assessed the impact of ESR1 mutations on sensitivity to standard therapies in two phase III randomized trials that represent the development of the current standard therapy for estrogen receptor–positive advanced breast cancer. Materials and Methods In a prospective-retrospective analysis, we assessed ESR1 mutations in available archived baseline plasma from the SoFEA (Study of Faslodex Versus Exemestane With or Without Arimidex) trial, which compared exemestane with fulvestrant-containing regimens in patients with prior sensitivity to nonsteroidal AI and in baseline plasma from the PALOMA3 (Palbociclib Combined With Fulvestrant in Hormone Receptor–Positive HER2-Negative Metastatic Breast Cancer After Endocrine Failure) trial, which compared fulvestrant plus placebo with fulvestrant plus palbociclib in patients with progression after receiving prior endocrine therapy. ESR1 mutations were analyzed by multiplex digital polymerase chain reaction. Results In SoFEA, ESR1 mutations were found in 39.1% of patients (63 of 161), of whom 49.1% (27 of 55) were polyclonal, with rates of mutation detection unaffected by delays in processing of archival plasma. Patients with ESR1 mutations had improved progression-free survival (PFS) after taking fulvestrant (n = 45) compared with exemestane (n = 18; hazard ratio [HR], 0.52; 95% CI, 0.30 to 0.92; P = .02), whereas patients with wild-type ESR1 had similar PFS after receiving either treatment (HR, 1.07; 95% CI, 0.68 to 1.67; P = .77). In PALOMA3, ESR1 mutations were found in the plasma of 25.3% of patients (91 of 360), of whom 28.6% (26 of 91) were polyclonal, with mutations associated with acquired resistance to prior AI. Fulvestrant plus palbociclib improved PFS compared with fulvestrant plus placebo in both ESR1 mutant (HR, 0.43; 95% CI, 0.25 to 0.74; P = .002) and ESR1 wild-type patients (HR, 0.49; 95% CI, 0.35 to 0.70; P < .001). Conclusion ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.

scholarly journals Prospective Study Evaluating the Impact of Tissue Confirmation of Metastatic Disease in Patients With Breast Cancer

2012 ◽  
Vol 30 (6) ◽  
pp. 587-592 ◽  
Author(s):  
Eitan Amir ◽  
Naomi Miller ◽  
William Geddie ◽  
Orit Freedman ◽  
Farrah Kassam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prospective Study ◽  
Treatment Plan ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Primary Tumors ◽  
Receptor Status ◽  
Metastatic Recurrence ◽  
The Impact

Purpose Decisions about treatment for women with metastatic breast cancer are usually based on the estrogen (ER), progesterone (PgR), and human epidermal growth factor receptor 2 (HER2) status of the primary tumor. Retrospective data suggest that discordance between primary and metastatic lesions leads to detrimental outcome. This prospective study investigated receptor status of primary tumors and metastases in the same patient and assessed the impact of discordance on patient management and survival. Patients and Methods Biopsies of suspected metastases were analyzed for ER, PgR, and HER2. Primary tumors and metastases were analyzed using similar methodology. The treating oncologist indicated a treatment plan before and after biopsy to determine whether the result influenced management. Patients were followed up for progression or death. Results Of 121 women undergoing biopsy, 80% could be analyzed for receptor status. Discordance in ER, PgR, and HER2 between the primary and the metastasis was 16%, 40%, and 10%, respectively. Biopsy led to a reported change of management in 14% of women (95% CI, 8.4% to 21.5%). Fine-needle aspiration and biopsy of bone led to reduced ability to analyze receptors. After a median follow-up of 12 months, there were no trends for an association between receptor discordance and either time to treatment failure or overall survival. Conclusion Biopsy of metastases is technically feasible. Clinicians alter immediate management in one of seven patients on the basis of results of the biopsy, and discordance is not then associated with detrimental effects on outcome. Tissue confirmation should be considered in women with breast cancer and suspected metastatic recurrence.

scholarly journals Explainable machine learning can outperform Cox regression predictions and provide insights in breast cancer survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Arturo Moncada-Torres ◽  
Marissa C. van Maaren ◽  
Mathijs P. Hendriks ◽  
Sabine Siesling ◽  
Gijs Geleijnse
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Explicit Knowledge ◽  
Cox Regression ◽  
Metastatic Breast ◽  
Gradient Boosting ◽  
Support Vector ◽  
Netherlands Cancer Registry ◽  
Extreme Gradient Boosting ◽  
The Impact

AbstractCox Proportional Hazards (CPH) analysis is the standard for survival analysis in oncology. Recently, several machine learning (ML) techniques have been adapted for this task. Although they have shown to yield results at least as good as classical methods, they are often disregarded because of their lack of transparency and little to no explainability, which are key for their adoption in clinical settings. In this paper, we used data from the Netherlands Cancer Registry of 36,658 non-metastatic breast cancer patients to compare the performance of CPH with ML techniques (Random Survival Forests, Survival Support Vector Machines, and Extreme Gradient Boosting [XGB]) in predicting survival using the $$c$$ c -index. We demonstrated that in our dataset, ML-based models can perform at least as good as the classical CPH regression ($$c$$ c -index $$\sim \,0.63$$ ∼ 0.63 ), and in the case of XGB even better ($$c$$ c -index $$\sim 0.73$$ ∼ 0.73 ). Furthermore, we used Shapley Additive Explanation (SHAP) values to explain the models’ predictions. We concluded that the difference in performance can be attributed to XGB’s ability to model nonlinearities and complex interactions. We also investigated the impact of specific features on the models’ predictions as well as their corresponding insights. Lastly, we showed that explainable ML can generate explicit knowledge of how models make their predictions, which is crucial in increasing the trust and adoption of innovative ML techniques in oncology and healthcare overall.

Impact of Medicaid expansion on two-year mortality among stage IV breast cancer (BC) patients according to race.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6525-6525
Author(s):  
Catalina Malinowski ◽  
Xiudong Lei ◽  
Hui Zhao ◽  
Sharon H. Giordano ◽  
Mariana Chavez Mac Gregor
Keyword(s):  
Breast Cancer ◽  
Low Income ◽  
Stage Iv ◽  
Medicaid Expansion ◽  
Risk Of Death ◽  
Stage Iv Breast Cancer ◽  
Increased Risk ◽  
The Impact ◽  
Expansion Period ◽  
White Patients

6525 Background: Inadequate access to healthcare services is associated with worse outcomes. Disparities in access to cancer care are more frequently seen among racial/ethnic minorities, uninsured patients, and those with low socioeconomic status. A provision in the Affordable Care Act called for expansion of Medicaid eligibility in order to cover more low-income Americans. In this study, we evaluate the impact of Medicaid expansion in 2-year mortality among metastatic BC patients according to race. Methods: Women (aged 40-64) diagnosed with metastatic BC (stage IV de novo) between 01/01/2010 and 12/31/2015 and residing in states that underwent Medicaid expansion in 01/2014 were identified in the National Cancer Database. For comparison purposes, 2010-2013 was considered the pre-expansion period and 2014-2015 the post-expansion period. We calculated 2-year mortality difference-in-difference (DID) estimates between White and non-White patients using multivariable linear regression models. Results are presented as adjusted differences (in % points) between groups in the pre- and post-expansion periods and as adjusted DID with 95%CI. Covariates included age, comorbidity, BC subtype, insurance type, transfer of care, distance to hospital, region, residence area, education, income quartile, facility type and facility volume. In addition, overall survival (OS) was evaluated in pre- and post-expansion periods via Kaplan-Meier method and Cox proportional hazards models; results are presented as 2-year OS estimates, hazard ratios (HRs), and 95% CIs. Results: Among 7,675 patients included, 4,942 were diagnosed in the pre- and 2,733 in the post-expansion period. We observed a reduction in 2-year mortality rates in both groups according to Medicaid expansion. Among Whites 2-year mortality decreased from 42.5% to 38.7% and among non-Whites from 45.4% to 36.4%, resulting in an adjusted DID of -5.2% (95%CI -9.8 to -0.6, p = 0.027). A greater reduction in 2-year mortality was observed among non-Whites in a sub-analysis of patients who resided in the poorest quartile (n = 1372), with an adjusted DID of -14.6% (95%CI -24.8 to -4.4, p = 0.005). In the multivariable Cox model, during the pre-expansion period there was an increased risk of death for non-Whites compared to Whites (HR 1.14, 95% CI 1.03 to 1.26, P = 0.04), however no differences were seen in the post-expansion period between the two groups (HR 0.93, 95% CI 0.80 to 1.07, P = 0.31). Conclusions: Medicaid expansion reduced racial disparities by decreasing the 2-year mortality of non-White patients with metastatic breast cancer and reducing the gap when compared to Whites. These results highlight the positive impact of policies aimed at improving equity and increasing access to health care.

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