Locoregional therapy in de novo metastatic breast cancer. The unanswered question.
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ABSTRACT:
SUBMITTER: Cardoso MJ
PROVIDER: S-EPMC8481928 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLocoregional therapy (LRT) in de novo metastatic disease is controversial with inconsistent results from randomized control trials (RCTs).MethodsRCTs comparing LRT and systemic therapy to standard therapy alone in de novo metastatic breast cancer were identified. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed and pooled in a meta-analysis using generic inverse variance. Overall survival (OS) and time to locoregional progression data were extracted for the intention to treat (ITT) population. Data on OS for pre-specified subgroups defined by tumor subtype and by site of metastases were also extracted.ResultsAnalyses included 4 trials comprising 970 patients. LRT included standard surgery to the primary breast tumor in all studies, and adjuvant radiation per standard of care was required in 3 studies. Compared to standard treatment, LRT was not associated with improved OS in the ITT population (HR 0.97, 95% CI 0.72-1.29, p = 0.81). However, LRT was associated with improved time to locoregional progression (HR 0.36, 95% CI 0.14-0.95, p = 0.04). LRT was not associated with improved OS in any tumor subtypes, including hormone receptor positive (HR 0.96, 95% CI 0.65-1.43), triple negative (HR 1.4, 95% CI 0.50-3.91) and human epidermal growth factor receptor 2 positive disease (HR 0.93, 95% CI 0.68-1.28). Additionally, LRT did not improve OS in bone only disease (HR 0.97, 95% CI 0.58-1.62) and in visceral disease (HR = 1.02, 95% CI 0.77-1.35). Our critical appraisal has identified some methodological problems in the design and conduct of the studies included that could affect the meta-analysis result.ConclusionsLRT in de novo metastatic breast cancer is not associated with improved OS. Results are consistent among different breast cancer subgroups. However, this conclusion should be interpreted with caution in view of the limitations identified in meta-analysis.
| S-EPMC8481908 | biostudies-literature
Project description: Not available
| S-EPMC6136929 | biostudies-literature
Project description:It is estimated that approximately 154000 women in the United States have stage IV breast cancer (BC). A subset of this group has metastatic disease at presentation, known as de novo stage IV disease. De novo stage IV BC accounts for approximately 6% of all BC diagnoses in the United States. Traditionally, stage IV BC patients are treated with primary systemic therapy with a palliative intent reserving possible locoregional treatment (LRT) as last resort. There has been a lot of interest in the role of LRT in de novo stage IV BC for the past decade with mixed conclusions. Although this review is not intended to be a comprehensive overview of all literature regarding this topic to date, we will review the recent findings in literature focusing on the studies with larger sample sizes to investigate the role of LRT in de novo stage IV BC.
| S-EPMC7502854 | biostudies-literature
Project description:The impact of treatment for the primary tumor on distant metastases and survival in primary metastatic breast cancer patients is controversial. Previous retrospective studies and meta-analyses suggested a survival benefit for the removal of the primary tumor. Early follow-up data from 2 prospectively randomized trials presented at San Antonio Breast Cancer Symposium 2013 could not confirm this. Only a very small subgroup of patients with solitary bone metastases seemed to profit from surgery, while patients with multiple visceral metastases showed a worse prognosis with initial surgery. There are no studies available with the primary aim to investigate the impact of axillary lymph node surgery or locoregional radiotherapy on the survival of stage IV breast cancer patients. Based on current data, locoregional treatment in primary metastatic breast cancer should not be recommended in patients with asymptomatic primary tumor as a matter of routine. More solid conclusion of the impact of primary tumor treatment in stage IV breast cancer patients on their prognosis will be reached with the completion of the ongoing prospectively randomized trials. Until these studies are completed, locoregional therapy, which can provoke additional morbidity in a metastatic setting with limited live expectancy, is exclusively indicated for palliative reasons.
| S-EPMC3995367 | biostudies-literature
Project description: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.
| S-EPMC8432710 | biostudies-literature
Project description:Systemic therapy has been viewed as the mainstay for de novo metastatic breast cancer (dnMBC). However, as dnMBC is highly heterogeneous both biologically and clinically, and with ever-improving systemic strategies, it has been implied that the local therapy of the primary tumor (PT) may be beneficial for certain patients with dnMBC. However, the results from retrospective studies have been questioned due to their selection bias and retrospective nature. To the best of our knowledge, there are two published randomized clinical trials addressing this issue with conflicting conclusions: i) TATA study from India indicated no overall survival (OS) superiority with early local radiotherapy (LRT); and ii) MF07-01 indicated a 5-year OS rate improvement of 17% with upfront LRT. The updated results of a randomized phase III ECOG-ACRIN E2108 trial released in the 2020 American Society of Clinical Oncology (ASCO) meeting reported a negative survival effect of early LRT treatment in patients with dnMBC responding to initial systemic treatment, despite LRT significantly reducing the locoregional failure. Thus, a number of issues, such as the exact value of LRT, the optimal means of LRT (surgery and/or RT to the PT), the ideal timing of LRT and the population most likely to benefit from LRT, warrant further investigation. Herein, the related studies focusing on these aspects were comprehensively reviewed and a decision algorithm was proposed to select suitable patients with dnMBC for reasonable LRT. Generally, upfront systemic therapy is recommended. For good respondents and a subgroup of favorable profiles (young age, good general condition, low tumor burden, hormone receptor-positive and so on), radical LRT including PT surgery followed by RT and the resection of distant metastases is recommended. LRT should also be administered if the PT is still symptomatic. LRT may benefit patients with dnMBC due to the following reasons: Control of the PT decreases tumor burden, eliminates the source of dissemination, enhances the sensitivity to therapy and exerts positive immunomodulation. Therefore, the treatment paradigm for dnMBC may change from 'palliative LRT' into 'curative LRT' in a highly selected entity with careful evaluation.
| S-EPMC10394734 | biostudies-literature
Project description:Patients presenting with de novo stage IV metastatic breast cancer have a complex disease which is normally treated with palliative intent and systemic therapy. However, there is mounting evidence that resection of the primary tumour and/or localised radiotherapy (locoregional therapy; LRT) could be associated with overall survival improvements. We aimed to conduct a meta-analysis to inform decision making. Using the PubMed, Cochrane and Ovid SP databases, a literature review and meta-analysis were conducted to assess the effect of LRT on overall survival. Studies were analysed for the impact of LRT on survival. All forms of LRT resulted in a significant 31.8% reduction in mortality (N?=?42; HR?=?0.6823 (95% CI 0.6365; 0.7314)). Surgical resection resulted in a significant 36.2% reduction in mortality (N?=?37; HR?=?0.6379 (95% CI 0.5974; 0.6811)). The prospective trials reported a 19.23% reduction in mortality which was not statistically significant (N?=?3, HR?=?0.8077 (95% CI 0.5704; 1.1438). 216 066 patients were included. This is the largest meta-analysis regarding this question to date. Our meta-analysis shows that LRT of the primary tumour seems to improve overall survival in de novo stage IV disease. Therefore, this therapeutic option should be considered in selected patients after a careful multidisciplinary discussion.
| S-EPMC7031518 | biostudies-literature
Project description:PurposeIn contrast to recurrence after initial diagnosis of stage I-III breast cancer [recurrent metastatic breast cancer (rMBC)], de novo metastatic breast cancer (dnMBC) represents a unique setting to elucidate metastatic drivers in the absence of treatment selection. We present the genomic landscape of dnMBC and association with overall survival (OS).Experimental designTargeted DNA sequencing (OncoPanel) was prospectively performed on either primary or metastatic tumors from 926 patients (212 dnMBC and 714 rMBC). Single-nucleotide variants, copy-number variations, and tumor mutational burden (TMB) in treatment-naïve dnMBC primary tumors were compared with primary tumors in patients who ultimately developed rMBC, and correlated with OS across all dnMBC.ResultsWhen comparing primary tumors by subtype, MYB amplification was enriched in triple-negative dnMBC versus rMBC (21.1% vs. 0%, P = 0.0005, q = 0.111). Mutations in KMTD2, SETD2, and PIK3CA were more prevalent, and TP53 and BRCA1 less prevalent, in primary HR+/HER2- tumors of dnMBC versus rMBC, though not significant after multiple comparison adjustment. Alterations associated with shorter OS in dnMBC included TP53 (wild-type: 79.7 months; altered: 44.2 months; P = 0.008, q = 0.107), MYC (79.7 vs. 23.3 months; P = 0.0003, q = 0.011), and cell-cycle (122.7 vs. 54.9 months; P = 0.034, q = 0.245) pathway genes. High TMB correlated with better OS in triple-negative dnMBC (P = 0.041).ConclusionsGenomic differences between treatment-naïve dnMBC and primary tumors of patients who developed rMBC may provide insight into mechanisms underlying metastatic potential and differential therapeutic sensitivity in dnMBC. Alterations associated with poor OS in dnMBC highlight the need for novel approaches to overcome potential intrinsic resistance to current treatments.
| S-EPMC7887078 | biostudies-literature
Project description:We aimed to determine the prognostic impact of time between primary breast cancer and diagnosis of distant metastasis (metastatic-free interval, MFI) on the survival of metastatic breast cancer patients.Consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight hospitals in the Southeast of the Netherlands were included and categorised based on MFI. Survival curves were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic impact of de novo metastatic breast cancer vs recurrent metastatic breast cancer (MFI ⩽24 months and >24 months), adjusted for age, hormone receptor and HER2 status, initial site of metastasis and use of prior (neo)adjuvant systemic therapy.Eight hundred and fifteen patients were included and divided in three subgroups based on MFI; 154 patients with de novo metastatic breast cancer, 176 patients with MFI <24 months and 485 patients with MFI >24 months. Patients with de novo metastatic breast cancer had a prolonged survival compared with patients with recurrent metastatic breast cancer with MFI <24 months (median 29.4 vs 9.1 months, P<0.0001), but no difference in survival compared with patients with recurrent metastatic breast cancer with MFI >24 months (median, 29.4 vs 27.9 months, P=0.73). Adjusting for other prognostic factors, patients with MFI <24 months had increased mortality risk (hazard ratio 1.97, 95% CI 1.49-2.60, P<0.0001) compared with patients with de novo metastatic breast cancer. When comparing recurrent metastatic breast cancer with MFI >24 months with de novo metastatic breast cancer no significant difference in mortality risk was found. The association between MFI and survival was seen irrespective of use of (neo)adjuvant systemic therapy.Patients with de novo metastatic breast cancer had a significantly better outcome when compared with patients with MFI <24 months, irrespective of the use of prior adjuvant systemic therapy in the latter group. However, compared with patients with MFI >24 months, patients with de novo metastatic breast cancer had similar outcome.
| S-EPMC4453676 | biostudies-other
Project description:Black women living in southern states have the highest breast cancer mortality rate in the United States. The prognosis of de novo metastatic breast cancer is poor. Given these mortality rates, we are the first to link nationally representative data on breast cancer mortality hot spots (counties with high breast cancer mortality rates) with cancer mortality data in the United States and investigate the association of geographic breast cancer mortality hot spots with de novo metastatic breast cancer mortality among Black women. We identified 7292 Black women diagnosed with de novo metastatic breast cancer in Surveillance, Epidemiology, and End Results (SEER). The county-level characteristics were obtained from 2014 County Health Rankings and linked to SEER. We used Cox proportional hazards models to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for mortality between hot spot and non-hot spot counties. Among 7292 patients, 393 (5.4%) resided in breast cancer mortality hot spots. Women residing in hot spots had similar risks of breast cancer-specific mortality (aHR = 0.99, 95% CI = 0.85 to 1.15) and all-cause mortality (aHR = 0.97, 95% CI = 0.84 to 1.11) as women in non-hot spots after adjusting for individual and tumor-level factors and treatments. Additional adjustment for county-level characteristics did not impact mortality. Living in a breast cancer mortality hot spot was not associated with de novo metastatic breast cancer mortality among Black women. Future research should begin to examine variation in both individual and population-level determinants, as well as in molecular and genetic determinants that underlie the aggressive nature of de novo metastatic breast cancer.
| S-EPMC7791608 | biostudies-literature