Surgery of the primary tumour in patients presenting with de novo metastatic breast cancer: to do or not to do?
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ABSTRACT:
SUBMITTER: Poggio F
PROVIDER: S-EPMC5786910 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
Publications
Surgery of the primary tumour in patients presenting with de novo metastatic breast cancer: to do or not to do?
Poggio Francesca F Lambertini Matteo M de Azambuja Evandro E
ESMO open 20180127 1
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Project description:BackgroundBreast 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.MethodsWe 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.ResultsOverall, 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).ConclusionSurgery 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.
| S-EPMC10769792 | biostudies-literature
Project description:IntroductionUncertainty 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 methodsWe 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.ResultsPatients 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.ConclusionsAdditional 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.
| S-EPMC9436631 | 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:PurposeThe efficacy of primary site surgery in patients with de novo stage IV breast cancer remains controversial. However, few real-world studies have evaluated the benefits of local surgery on the primary site of stage IV breast cancer in China. The purpose of this study was to investigate the role of local surgery in the de novo stage IV breast cancer.Materials and methodsWomen with metastatic breast cancer at diagnosis were identified from Guangxi medical university cancer hospital (China) database from 2009 to 2017. The clinical and tumor features, surgical treatment, and survival rates were compared between surgical and non-surgical patients.ResultsTwo hundred forty-three patients were included, of whom 125 underwent primary site surgery. Patients who underwent surgery were more often had small primary tumors, fewer lymph node metastases, and had less visceral involvement. Patients in the surgery group had dramatically longer OS (median 35 vs 22 months, log-rank P=0.006). Stratified survival analysis showed that patients with bone metastasis alone or ≤3 metastasis benefit from surgery, while patients with visceral metastasis did not benefit from surgery. In multivariate analysis, surgical treatment, estrogen receptor status, progesterone receptor status and visceral metastases remained independent factors for survival.ConclusionSurgical resection of the primary site can improve survival in selected de novo stage IV breast cancer patients.
| S-EPMC7811446 | biostudies-literature
Project description:The debate about surgical resection of primary tumor (PT) in de novo metastatic breast cancer (MBC) patients persists. We explored this approach's outcomes in patients included in a retrospective registry, named El Álamo, of breast cancer patients diagnosed in Spain (1990-2001). In this analysis we only included de novo MBC patients, 1415 of whom met the study's criteria. Descriptive, Kaplan-Meier and Cox regression analyses were carried out. Median age was 63.1 years, 49.2% of patients had single-organ metastasis (skin/soft tissue [16.3%], bone [33.8%], or viscera [48.3%]). PT surgery (S) was performed in 44.5% of the cases. S-group patients were younger, had smaller tumors, higher prevalence of bone and oligometastatic disease, and lower prevalence of visceral involvement. With a median follow-up of 23.3 months, overall survival (OS) was 39.6 versus 22.4 months (HR = 0.59, p < 0.0001) in the S- and non-S groups, respectively. The S-group OS benefit remained statistically and clinically significant regardless of metastatic location, histological type, histological grade, hormone receptor status and tumor size. PT surgery (versus no surgery) was associated with an OS benefit suggesting that loco-regional PT control may be considered in selected MBC patients. Data from randomized controlled trials are of utmost importance to confirm these results.
| S-EPMC6934456 | biostudies-literature
Project description:ImportanceRegional nodal irradiation (RNI) for node-positive breast cancer reduces distant metastases and improves survival, albeit with limited reduction in regional nodal recurrences. The mechanism by which RNI robustly reduces distant metastases while modestly influencing nodal recurrences (ie, the presumed target of RNI) remains unclear.ObjectiveTo determine whether some distant metastases putatively arise from occult regional nodal disease and whether regional recurrences otherwise remain largely undetected until an advanced cancer presentation.Design, setting, and participantsThis cohort study examined patients presenting with de novo stage IV breast cancer to the Memorial Sloan Kettering Cancer Center in New York, New York, from 2006 to 2018. Medical records were reviewed to ascertain clinicopathological parameters, including estrogen receptor status and survival. Pretreatment positron emission tomography-computed tomography (PET-CT) imaging was reviewed to ascertain the extent of regional nodal involvement at metastatic diagnosis using standard nodal assessment criteria. A subset underwent regional lymph node biopsy for diagnostic confirmation and served to validate the radiographic nodal assessment. Data analysis was performed from October 2019 to February 2020.ExposuresUntreated metastatic breast cancer.Main outcome and measuresThe primary outcome was the likelihood of regional nodal involvement at the time of metastatic breast cancer presentation and was determined by reviewing pretreatment PET-CT imaging and lymph node biopsy findings.ResultsAmong 597 women (median [interquartile range] age, 53 [44-65] years) with untreated metastatic breast cancer, 512 (85.8%) exhibited regional lymph node involvement by PET-CT or nodal biopsy, 509 (85%) had involvement of axillary level I, 328 (55%) had involvement in axillary level II, 136 (23%) had involvement in axillary level III, 101 (17%) had involvement in the supraclavicular fossa, and 96 (16%) had involvement in the internal mammary chain. Lymph node involvement was more prevalent among estrogen receptor-negative tumors (92.4%) than estrogen receptor-positive tumors (83.6%). Nodal involvement at the time of metastatic diagnosis was not associated with overall survival.Conclusions and relevanceThese findings suggest that a majority of patients with de novo metastatic breast cancer harbor regional lymph node disease at presentation, consistent with the hypothesis that regional involvement may precede metastatic dissemination. This is in alignment with the findings of landmark trials suggesting that RNI reduces distant recurrences. It is possible that this distant effect of RNI may act via eradication of occult regional disease prior to systemic seeding. The challenges inherent in detecting isolated nodal disease (which is typically asymptomatic) may account for the more modest observed benefit of RNI on regional recurrences. Alternative explanations of nodal involvement that arises concurrently or after metastatic dissemination remain possible, but do not otherwise explain the association of RNI with distant recurrence.
| S-EPMC7547365 | 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: Not available
| S-EPMC8798394 | 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:The purpose of this study was to determine the change in overall survival (OS) for patients with de novo metastatic breast cancer (dnMBC) over time. We conducted a retrospective cohort study with 1981 patients with dnMBC diagnosed between January 1995 and December 2017 at The University of Texas MD Anderson Cancer Center. OS was measured from the date of diagnosis of dnMBC. OS was compared between patients diagnosed during different time periods: 5-year periods and periods defined according to when key agents were approved for clinical use. The median OS was 3.4 years. The 5- and 10-year OS rates improved over time across both types of time periods. A subgroup analysis showed that OS improved significantly over time for the estrogen-receptor-positive/HER2-positive (ER+/HER2+) subtype and exhibited a tendency toward improvement over time for the ER-negative (ER-)/HER2+ subtype. In addition, median OS was significantly longer in patients with non-inflammatory breast cancer (p = 0.02) and patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all p < 0.0001). These findings showed that OS at 5 and 10 years after diagnosis in patients with dnMBC improved over time. The significant improvements in OS over time for the ER+/HER2+ subtype and the tendency toward improvement for the ER-/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.
| S-EPMC8198851 | biostudies-literature