Low Overall Survival in Women With De Novo Metastatic Breast Cancer: Does This Reflect Tumor Biology or a Lack of Access to Health Care?

PURPOSE As a result of its epidemiologic and therapeutic aspects, metastatic breast cancer (MBC) is a highly relevant clinical condition. This study aimed to estimate overall survival (OS) in women with de novo MBC in a Brazilian population. PATIENTS AND METHODS Patients were identified in the Goiânia population-based cancer registry between 1995 and 2011. All women with metastatic disease at diagnosis were included in the study. OS was analyzed at 5 and 10 years of follow-up. We used the Kaplan-Meier estimator and Cox regression for statistical analysis. RESULTS Over the 16-year period covered by the study, 5,289 women were diagnosed with breast cancer in Goiânia. Of these, 277 women (5.2%) had MBC. OS rates at 5 and 10 years were 19.9% and 7.3%, respectively. The mean OS time of women treated in the public health system was 7.5 months shorter than in women who had private health care (19.7 v 27.2 months, respectively). In the univariable analysis, the following factors were statistically significant for OS: T3/4 staging, histologic grade 3, progesterone receptor status, tumor phenotype, breast surgery, CNS metastasis at initial presentation, and surgery for resection of metastasis. In multivariable analysis, initial CNS metastasis (hazard ratio, 3.09; 95% CI, 1.16 to 8.19) and breast surgery (hazard ratio, 0.45; 95% CI, 0.25 to 0.78) remained independent prognostic factors. CONCLUSION OS was lower than rates found in specialist centers in Brazil and in developed countries. Several intrinsic and extrinsic factors were significant in predicting OS. Despite the difference in the 5-year survival rate, the type of access to health care was not significant in the multivariable analysis of the entire period.

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Changes in Overall Survival Over Time for Patients With de Novo Metastatic Breast Cancer

10.20944/preprints202105.0093.v1 ◽

2021 ◽

Author(s):

Toshiaki Iwase ◽

Tushaar Vishal Shrimanker ◽

Ruben Rodriguez-Bautista ◽

Onur Sahin ◽

Anjali James ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

De Novo ◽

Metastatic Breast ◽

Locoregional Therapy ◽

Cancer Center ◽

Her2 Positive ◽

Time Periods ◽

Over Time

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. Median OS was significantly longer in patients with non-inflammatory breast cancer (P = .02) and in patients with ER+ disease, progesterone-receptor-positive disease, HER2+ disease, lower nuclear grade, locoregional therapy, and metastasis to a single organ (all P &lt;.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 ER-/HER2+ subtype suggest the contribution of HER2-targeted therapy to survival.

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Early Locoregional Breast Surgery and Survival in de novo Metastatic Breast Cancer in the Multicenter National ESME Cohort

Annals of Surgery ◽

10.1097/sla.0000000000004767 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Judicaël Hotton ◽

Amélie Lusque ◽

Léa Leufflen ◽

Mario Campone ◽

Christelle Levy ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

De Novo ◽

Breast Surgery ◽

Metastatic Breast

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The contribution of clinical subtype to survival differences among patients with de novo and recurrent metastatic breast cancer (dMBC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1030 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1030-1030

Author(s):

Danielle Marie File ◽

Tomas Pascual ◽

Allison Mary Deal ◽

Amy Wheless ◽

Elizabeth Claire Dees ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Triple Negative ◽

De Novo ◽

Multivariable Analysis ◽

Metastatic Breast ◽

Clinical Staging ◽

Lower Grade ◽

Significant Difference ◽

Metastatic Sites

1030 Background: Patients with de novo metastatic breast cancer (dMBC) have superior median overall survival (mOS) compared to recurrent metastatic breast cancer (rMBC). Whether patient characteristics, prior treatment, tumor stage and innate biological differences contribute to this observation is unknown. Methods: Clinical and pathological data from patients diagnosed with MBC from 2011 to 2017 at the University of North Carolina (UNC) was obtained from the prospective UNC Metastatic Breast Cancer Clinical Database (223 dMBC, 607 rMBC). Only patients with known survival status were included. Subtype was determined by hormone receptor (HR) and HER2 staining of the primary tumor. Pathologic staging results were used when available, otherwise clinical staging was used. Patient and tumor characteristics were compared using chi-square testing, and survival outcomes by Cox proportional hazards modeling. Results: 26.9% of patients with MBC presented with dMBC, with significant variation in the ratio of dMBC to rMBC across subtypes. In particular, there were more cases of HER2+ dMBC than rMBC (26.9% vs 14.0%) and fewer cases of triple negative dMBC (20.6% vs 35.3%)(p-value < 0.001). Nearly half of all cases of HR-/HER2+ MBC were de novo (48.2%). dMBC was significantly associated with older age (p = 0.002), lower grade (p = 0.027), higher T and N stage (p < 0.001) and African American race (30% vs 22%, p = 0.022). There was no significant difference in proportion of patients with visceral metastatic disease or in number of metastatic sites at diagnosis. Median follow up was 39 months in both cohorts. mOS was 12 months greater in dMBC than rMBC (34m vs 22m, p < 0.001). These differences were significant across all subtypes except HR+/HER2+. The difference in mOS between dMBC and rMBC was greatest in the HR-/HER2+ subgroup (45m vs 15m, p = 0.006). In multivariable analysis, dMBC remained associated with improved survival (adjusted hazard ratio 0.59, p < 0.001) independent of variables including age, race, subtype, grade and number of metastatic sites at diagnosis. Conclusions: Patients with dMBC have significantly better prognosis than those with rMBC. This improved outcome is in part due to subtype variation, with more triple negative and fewer HER2+ tumors in rMBC, however these differences largely remained when stratified by subtype. In multivariable analysis, de novo presentation of MBC remained an independently significant contributor to longer survival. Further investigation should focus on biologic differences between dMBC and rMBC.

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Breast surgery in de novo metastatic breast cancer

European Journal of Cancer ◽

10.1016/s0959-8049(18)30465-9 ◽

2018 ◽

Vol 92 ◽

pp. S79

Author(s):

P. Chan ◽

S. Kuah ◽

S. Lu ◽

M.H. Goh ◽

J. Chen ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

De Novo ◽

Breast Surgery ◽

Metastatic Breast

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Radiation therapy to the primary tumor for de novo metastatic breast cancer and overall survival in a retrospective multicenter cohort analysis

Radiotherapy and Oncology ◽

10.1016/j.radonc.2019.12.019 ◽

2020 ◽

Vol 145 ◽

pp. 109-116 ◽

Cited By ~ 2

Author(s):

Elvire Pons-Tostivint ◽

Youlia Kirova ◽

Amélie Lusque ◽

Mario Campone ◽

Julien Geffrelot ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Radiation Therapy ◽

Metastatic Breast Cancer ◽

Primary Tumor ◽

De Novo ◽

Cohort Analysis ◽

Metastatic Breast ◽

Multicenter Cohort

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Changes in Overall Survival over Time for Patients with de novo Metastatic Breast Cancer

Cancers ◽

10.3390/cancers13112650 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2650

Author(s):

Toshiaki Iwase ◽

Tushaar Vishal Shrimanker ◽

Ruben Rodriguez-Bautista ◽

Onur Sahin ◽

Anjali James ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

De Novo ◽

Metastatic Breast ◽

Locoregional Therapy ◽

Cancer Center ◽

Her2 Positive ◽

Time Periods ◽

Over Time

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.

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Survival in Women with De Novo Metastatic Breast Cancer: A Comparison of Real-World Evidence from a Publicly-Funded Canadian Province and the United States by Insurance Status

Current Oncology ◽

10.3390/curroncol29010034 ◽

2022 ◽

Vol 29 (1) ◽

pp. 383-391

Author(s):

Marie-France Savard ◽

Elizabeth N. Kornaga ◽

Adriana Matutino Kahn ◽

Sasha Lupichuk

Keyword(s):

Breast Cancer ◽

Health Care ◽

Metastatic Breast Cancer ◽

De Novo ◽

Private Insurance ◽

Metastatic Breast ◽

The United States ◽

Insurance Status ◽

The Us ◽

Privately Insured

Metastatic breast cancer (MBC) patient outcomes may vary according to distinct health care payers and different countries. We compared 291 Alberta (AB), Canada and 9429 US patients < 65 with de novo MBC diagnosed from 2010 through 2014. Data were extracted from the provincial Breast Data Mart and from the National Cancer Institute’s SEER program. US patients were divided by insurance status (US privately insured, US Medicaid or US uninsured). Kaplan-Meier and log-rank analyses were used to assess differences in OS and hazard ratios (HR) were estimated using Cox models. Multivariate models were adjusted for age, surgical status, and biomarker profile. No difference in OS was noted between AB and US patients (HR = 0.92 (0.77–1.10), p = 0.365). Median OS was not reached for the US privately insured and AB groups, and was 11 months and 8 months for the US Medicaid and US uninsured groups, respectively. The 3-year OS rates were comparable between US privately insured and AB groups (53.28% (51.95–54.59) and 55.54% (49.49–61.16), respectively). Both groups had improved survival (p < 0.001) relative to the US Medicaid and US uninsured groups [39.32% (37.25–41.37) and 40.53% (36.20–44.81)]. Our study suggests that a universal health care system is not inferior to a private insurance-based model for de novo MBC.

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Bevacizumab in combination with a taxane for the first-line treatment of HER2-negative metastatic breast cancer

Health Technology Assessment ◽

10.3310/hta15suppl1-01 ◽

2011 ◽

Vol 15 (Suppl 1) ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

M Rodgers ◽

M Soares ◽

D Epstein ◽

H Yang ◽

D Fox ◽

...

Keyword(s):

Breast Cancer ◽

Quality Of Life ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

De Novo ◽

Controlled Trial ◽

Indirect Comparison ◽

Metastatic Breast ◽

Open Label

This paper presents a summary of the evidence review group (ERG) report into the use of bevacizumab (Avastin®, Roche) in combination with a taxane for the treatment of untreated metastatic breast cancer (mBC). The main clinical effectiveness data were derived from a single, open-label randomised controlled trial (RCT) (E2100) that evaluated the addition of bevacizumab to weekly (q.w.) paclitaxel in patients with human epidermal growth factor receptor 2-negative mBC who had not previously received chemotherapy for advanced disease. This trial reported statistically significant increases in median progression-free survival (PFS) for the addition of bevacizumab (5.8–11.3 months). Median overall survival was not significantly different between the two groups; whether this is a true null finding or due to crossover between treatment arms cannot be established, as relevant data were not collected. The manufacturer reported that the addition of bevacizumab to paclitaxel q.w. therapy was associated with a significant improvement in quality of life, as measured by FACT-B (functional assessment of cancer therapy for breast cancer) scores. However, the ERG noted that these results were based on extreme imputed values, the removal of which led to non-significant differences in quality of life. The manufacturer conducted an indirect comparison. However, owing to methodological limitations and concerns about the validity and exchangeability of the included trials, the ERG did not consider the findings to be reliable. One additional relevant RCT [AVADO (Avastin and Docetaxel); BO17708] evaluating the addition of bevacizumab to docetaxel was excluded from the manufacturer’s submission. This was summarised by the ERG. In terms of response rate and PFS, AVADO reported a markedly smaller benefit of adding bevacizumab to docetaxel than that reported for adding bevacizumab to q.w. paclitaxel in E2100. AVADO also reported no statistically significant effect of combination therapy versus docetaxel in terms of overall survival. The manufacturer developed a de novo economic model that considered patients with the same baseline characteristics as women in the E2100 trial. The model assessed BEV + PAC – bevacizumab 10 mg/kg every 2 weeks in combination with paclitaxel 90 mg/m2 weekly for 3 weeks followed by 1 week of rest; PAC q.w. – paclitaxel (monotherapy) 90 mg/m2 weekly for 3 weeks followed by 1 week of rest; DOC – docetaxel (monotherapy) 75 mg/m2 on day 1 every 21 days (considered current UK NHS clinical practice in the submission); and GEM + PAC – gemcitabine 1250 mg/m2 on days 1 and 8 plus paclitaxel 175 mg/m2 on day 1 every 21 days. Pairwise comparisons were made between BEV + PAC and PAC (using the E2100 trial), BEV + PAC and DOC, and BEV + PAC and GEM + PAC. Based on NHS list prices, the manufacturer’s model estimated incremental cost-effectiveness ratios (ICERs) for BEV + PAC of £117,803, £115,059 and £105,777 per QALY gained, relative to PAC, DOC and GEM + PAC regimens, respectively. If the NHS Purchasing and Supply Agency prices for PAC with a 10-g cap on the cost per patient of BEV were used instead, the ICERs for BEV + PAC were estimated at £77,314, £57,753 and £60,101 per QALY, respectively. The submission suggested that the regimen of BEV + DOC is not cost-effective because it is considered less effective and more costly than BEV + PAC. Analysis by the ERG suggested that alternative assumptions can increase the ICERs further and, based on current prices, no plausible changes to the model assumptions will bring the ICERs for BEV + PAC lower.

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Objective Response to First-Line Treatment as a Predictor of Overall Survival in Metastatic Breast Cancer: A Retrospective Analysis from Two Centers over a 25-Year Period

Breast Care ◽

10.1159/000519729 ◽

2021 ◽

pp. 1-8

Author(s):

Alexios Matikas ◽

Athanasios Kotsakis ◽

Maria Perraki ◽

Dora Hatzidaki ◽

Konstantinos Kalbakis ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Objective Response ◽

Multivariable Analysis ◽

Metastatic Breast ◽

Progression Free Survival ◽

Subsequent Treatment ◽

First Line ◽

Term Survival

Introduction: The purpose of this study was to study the efficacy of subsequent treatment lines for metastatic breast cancer (MBC), as well as the association between radiologic objective response rate (ORR) and overall survival (OS). Methods: In this retrospective study, consecutive patients treated for MBC in two centers in Greece from January 1, 1992, to December 31, 2016, were identified and clinicopathologic data regarding tumor characteristics and administered treatments were collected. The efficacy per treatment line in terms of ORR, progression-free survival (PFS) and OS, as well as the prognostic value of ORR at first line were investigated. Results: A total of 977 patients with MBC were identified; 950 received any treatment. At first line, ORR was 43.5%, PFS 11.4 months (95% CI 10.4–12.4), and median OS 52.4 months (95% CI 47.7–57.1). Lower ORR and shorter PFS were observed with each subsequent line. Median OS was significantly longer for patients that had an objective response at first line, 61.9 months (95% CI 51.1–69.7) for responders versus 41.3 months (95% CI 44.1–63.3) for nonresponders (p < 0.001). In multivariable analysis, failure to achieve an objective response was an independent predictor of poor survival (hazard ratio 1.70, 95% CI 1.34–2.15, p < 0.001). Conclusion: Late treatment lines for MBC seem to have limited efficacy, while response to first-line therapy is associated with long-term survival. The latter should be considered in the treatment strategy of patients with MBC.

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