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Locoregional tumor burden and risk of mortality in metastatic breast cancer.

ABSTRACT: The role of lymph node involvement and tumor size in metastatic disease including breast cancer is unclear. Here, nodal metastasis and T stage on the risk of mortality were investigated in de novo metastatic breast cancer population (35812 patients) in the Surveillance, Epidemiology, and End Results (SEER) Program database in the United States. We found an association between all-cause mortality and regional node involvement (adjusted hazard ratio [HR] = 1.45, 95% confidence interval [CI] 1.36-1.55, p < 0.0001) or T stage (HR = 1.20, 95% CI 1.14-1.25, p < 0.0001), independent of known clinicopathologic measurements. Number of positive nodes, and size and chest wall involvement of the breast tumors exhibited similar significance for breast cancer-specific mortality in the population (p < 0.0001 each), and all-cause mortality in hormone receptor (HR)-positive/HER2-negative (HR⁺/HER2^-), HR⁺/HER2⁺, HR^-/HER2⁺ and triple-negative metastatic breast cancer subtypes. Thus, nodal involvement and T stage are independent risk factors for mortality in the population of de novo metastatic breast cancer.

SUBMITTER: Yang SX

PROVIDER: S-EPMC8983737 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Locoregional tumor burden and risk of mortality in metastatic breast cancer.

Yang Sherry X SX Hewitt Stephen M SM Yu John J

NPJ precision oncology 20220405 1

The role of lymph node involvement and tumor size in metastatic disease including breast cancer is unclear. Here, nodal metastasis and T stage on the risk of mortality were investigated in de novo metastatic breast cancer population (35812 patients) in the Surveillance, Epidemiology, and End Results (SEER) Program database in the United States. We found an association between all-cause mortality and regional node involvement (adjusted hazard ratio [HR] = 1.45, 95% confidence interval [CI] 1.36-1 ...[more]

PMID: 35383277

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Project description:Metastatic breast cancers have historically been presumed to have the same predictive biomarkers as the initial primary tumor. We compared the expression of these biomarkers in a large paired tissue microarray (TMA) series of primary and subsequent relapsed tumors.Using the British Columbia Cancer Agency Breast Cancer Outcomes Unit database, patients with biopsy-proven relapses were identified and linked to a large TMA series of primary breast cancers from 1986-1992. Charts were reviewed, and tissue blocks of the metastatic cancer were collected to create a separate TMA. Immunohistochemical assessment with the same antibodies and conditions was performed for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER)-2 on both the primary and relapsed tumors.One hundred sixty cases were received that had tumor adequate for analyses. Of these, 71.9% had no changes in either the ER or PR status or HER-2 status. Of the 45 (28.1%; 95% confidence interval [CI], 21.2%-35.1%) tumors that did have changes in receptor status, 7.5% were in-breast recurrences or new breast primaries, 4.4% had changes in PR status only and were therefore deemed clinically irrelevant, and 19.4% (95% CI, 13.3%-25.5%) had changes in either the ER or HER-2 status from regional or distant relapses. Five percent of tumors had a receptor status change going from ER(+) or PR(+) to ER(-) or PR(-); 9.4% went from ER(-) or PR(-) to ER(+) or PR(+). With regard to HER-2 status, 3.8% of tumors went from positive to negative and 1.3% went from negative to positive. For all discordant cases, biopsies of the relapsed lesion were obtained prior to initiation of first-line treatment for metastatic disease. In the primary tumors that were ER(+), time to relapse was significantly shorter in the discordant relapsed cases than in the concordant ones (p = .0002). Changes in loss or gain of either biomarker were seen across the discordant cases.A significant proportion of relapsed tumors had changes in either ER or HER-2 status, which would dramatically alter treatment recommendations and clinical behavior. This study suggests that biopsies of relapsed and metastatic breast cancers should be performed routinely in clinical practice.

Project description:Objective: Recently, performing locoregional surgical treatment still remains debatable in patients with metastatic breast cancer (MBC). Current study aimed to develop prognostic nomograms for predicting the long-term survival in MBC patients with or without surgical intervention, thereby assisting clinicians in making individualized choice. Methods: The training set included 5173 patients who were diagnosed with MBC in 2010-2013 from the Surveillance, Epidemiology, and End Results Program, while the validation set comprised 2924 patients diagnosed in 2014-2015. Multivariant Cox hazard model was applied to determine the independent risk factors for overall survival (OS) and breast cancer specific survival (BCSS). Then, individualized pre- and postoperative nomograms for predicting 1- or 3-year survival probabilities were constructed accordingly. Internal and external validations were conducted to determine the accuracy of these nomograms by calculating concordance index (C-index) and plotting calibration curves. Results: The survival analysis indicated that surgical management conferred improved OS and BCSS in patients with metastatic breast cancer. Age, T stage, grade, distant metastatic site, ER, PR and HER2 status, radiation, and chemotherapy were independent risk factors for OS and BCSS both in surgery and non-surgery group. All these factors were subsequently incorporated into the nomogram which showed acceptable predictive capabilities with C-index range of 0.65-0.80 both in training set and external validation set. In addition, a preoperative nomogram incorporating variables capable of being determined before surgery was also built with C-index above 0.70 both in training and validation set. Conclusion: Surgical management in patients with metastatic breast cancer suggests a potential survival advantage. In addition, these well-validated pre- and postoperative nomograms may provide a useful tool to assist clinicians in treatment decision-making and in evaluating patients' long term prognosis.

Project description:BackgroundThere are scarce data of the costs of non-small cell lung cancer (NSCLC) recurrence in Spain. The objective of this study is to assess the economic burden of disease recurrence, for both locoregional and/or metastatic relapses, after appropriate early-stage NSCLC treatment in Spain.Materials and methodsA two-round consensus panel of Spanish oncologists and hospital pharmacists was conducted to collect information on patient's flow, treatments, use of healthcare resources and sick leaves in patients with relapsed NSCLC. A decision-tree model was developed to calculate the economic burden of disease recurrence after appropriate early-stage NSCLC. Both direct and indirect costs were considered. Direct costs included drug acquisition and healthcare resources costs. Indirect costs were estimated using the human-capital approach. Unit costs were obtained from national databases (euros of 2022). A multi-way sensitivity analysis was performed to provide a range to the mean values.ResultsAmong a cohort of 100 patients with relapsed NSCLC, 45 patients would have locoregional relapse (36.3 would eventually progress to metastasis and 8.7 would be considered in remission) and 55 patients would have metastatic relapse. Over time, 91.3 patients would experience a metastatic relapse (55 as first relapse and 36.6 after previous locoregional relapse). The overall cost incurred by the 100-patients cohort is €10,095,846 (€9,336,782 direct costs, €795,064 indirect costs). The average cost of a locoregional relapse is €25,194 (€19,658 direct costs, €5536 indirect costs), while the average cost a patient with metastasis who receives up to 4 lines of treatment is €127,167 (€117,328 direct, €9839 indirect).ConclusionsTo our knowledge, this is the first study that specifically quantifies the cost of relapse in NSCLC in Spain. Our findings shown that the overall cost of a relapse after appropriate treatment of early-stage NSCLC patients is substantial, and it increases considerably in the metastatic relapse setting, mainly due to the high cost and long duration of first-line treatments.

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Locoregional tumor burden and risk of mortality in metastatic breast cancer.

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Locoregional tumor burden and risk of mortality in metastatic breast cancer.

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