Multidisciplinary treatments increase overall survival in patients with newly diagnosed stage IV breast cancer: An analysis of 2010–2014 SEER data

Purpose Overall, breast cancer mortality has been declining in the United States, but survival studies of patients with stage IV disease are limited. The aim of this study was to evaluate trends in and factors affecting survival in a large population-based cohort of patients with newly diagnosed stage IV breast cancer. Patients and Methods We searched the Surveillance, Epidemiology, and End Results registry to identify female patients with stage IV breast cancer diagnosed between 1988 and 2003. Patients were divided into three groups according to year of diagnosis (1988 to 1993, 1994 to 1998, and 1999 to 2003). Survival outcomes were estimated by the Kaplan-Meier method, and Cox models were fit to determine the characteristics independently associated with survival. Results We identified 15,438 patients. Median age was 62 years. Median follow-up was 16 months, 18 months, and 11 months in periods 1988 to 1993, 1994 to 1998, and 1999 to 2003, respectively. Median breast cancer–specific survival was 23 months. In the multivariate model, earlier year of diagnosis, grade 3 disease, increasing age, being unmarried, hormone receptor–negative disease, and no surgery were all independently associated with worse overall and breast cancer–specific survival. With each successive year of diagnosis, black patients had an increasingly greater risk of death compared with white patients (hazard ratio, 1.03; 95% CI, 1.00 to 1.06; P = .031). Conclusion The survival of patients with newly diagnosed stage IV breast cancer has modestly improved over time, but these data suggest that the disparity in survival between black and white patients has increased.

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Abstract P3-06-14: Increase in the proportion of stage IV breast cancer amongst young women with newly diagnosed breast cancer, report from the National cancer data base, 1998-2009

10.1158/0008-5472.sabcs13-p3-06-14 ◽

2013 ◽

Author(s):

K Yao ◽

C Tomasz ◽

C Pesce ◽

D Huo ◽

WJ David ◽

...

Keyword(s):

Breast Cancer ◽

Data Base ◽

Young Women ◽

Stage Iv ◽

National Cancer Data Base ◽

Newly Diagnosed ◽

Cancer Data ◽

Stage Iv Breast Cancer

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Patient and Tumor Characteristics Associated with Primary Tumor Resection in Women with Stage IV Breast Cancer: Analysis of 1988–2003 SEER Data

Breast Diseases A Year Book Quarterly ◽

10.1016/s1043-321x(09)79262-8 ◽

2009 ◽

Vol 20 (2) ◽

pp. 141-142

Author(s):

T.A. King ◽

M. Morrow

Keyword(s):

Breast Cancer ◽

Primary Tumor ◽

Tumor Resection ◽

Stage Iv ◽

Primary Tumor Resection ◽

Tumor Characteristics ◽

Stage Iv Breast Cancer ◽

Seer Data

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The impact of primary surgery on stage IV breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1113 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1113-1113

Author(s):

Ella Harris ◽

Malcolm R. Kell ◽

Reem Salman ◽

Maurice Stokes ◽

Tom Gorey

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Stage Iv ◽

Primary Carcinoma ◽

Primary Surgery ◽

Primary Disease ◽

Stage Iv Breast Cancer ◽

Stage Iv Disease ◽

The Impact

1113 Background: The role of primary surgery in metastatic breast cancer is unclear. Here in we have performed metaanalysis on available data to assess the role of surgery on oncological outcome in patients with stage IV breast cancer. Methods: A comprehensive search for published trials that examined outcome following removal of primary disease in stage IV breast cancer was performed using MEDLINE and cross referencing available data. Reviews of each study were conducted, and data were extracted. Primary outcome was overall survival related to surgical removal of primary disease. Results: We identified 15 relevant studies of which 10 were appropriate for analysis. Data was available on 28,693 patients with stage IV disease, of whom 52.8% underwent removal of the primary carcinoma. Patients undergoing primary surgery in this setting were more likely to be alive at 3 years 40% vs. 22% (OR 2.32 CI 2.08-2.6, p<0.01 (surgery vs. no surgery)). Analysis of subgroups for selection to surgery or not, favoured smaller tumours, fewer comorbidities, fewer metastases (p<0.01). There was no difference between the two groups in location of metastases, grade of tumour or receptor status. Conclusions: Patients undergoing removal of primary carcinoma in the setting of stage IV breast cancer appear to have an improved overall survival. However the available data suggest that these surgical patients probably have better prognosis stage IV disease than those patients not undergoing surgery.

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Impact on overall survival of primary tumor extirpation in breast cancer patients who present with stage IV disease

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.598 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 598-598

Author(s):

J. E. Lang ◽

R. Rao ◽

L. Feng ◽

F. Meric-Bernstam ◽

I. Bedrosian ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Cancer Patients ◽

Primary Tumor ◽

Survival Benefit ◽

Stage Iv ◽

Breast Cancer Patients ◽

Stage Iv Breast Cancer ◽

Stage Iv Disease

598 Background: Limited data exists regarding optimal local therapy for patients who present with stage IV breast cancer with an intact primary tumor. Two retrospective series, from the National Cancer Data Base and the Geneva Cancer Registry, showed that surgery may improve overall survival in these patients. Our institutional experience demonstrated improved metastatic progression-free survival after a median follow-up of 32.1 months but did not show a survival benefit at short term follow-up. We evaluated the impact of local control on overall (OS) and disease-specific survival (DSS) in this population after a longer follow-up interval to determine if a survival benefit could be demonstrated from local surgical treatment for selected patients with stage IV breast cancer. Methods: We reviewed the records of all patients at our institution who presented from 1997–2002 with stage IV disease with an intact primary tumor. OS and DSS were estimated by the Kaplan-Meier method. The log-rank test was used to compare the difference in survival between surgical and non-surgical patients. Multivariate statistical analysis was performed using the Cox proportional hazards model. Results: Of 220 patients identified with stage IV disease with an intact primary tumor, 80 (36%) underwent surgical resection of the primary tumor; 39 (49%) had segmental mastectomy and 41 (51%) had a total mastectomy. There were 140 (64%) patients who did not undergo surgery. The median follow-up duration from time of presentation to our institution was 58.6 months and the median OS time after presentation was 45.8 months. After adjustment for covariates, surgery was associated with improved OS (p=0.03) and DSS (p=0.04) compared to the non-surgical group. Conclusions: With a median follow-up time of 58.6 months, patients who presented with stage IV breast cancer with an intact primary tumor treated surgically had significantly improved OS and DSS compared to patients who did not undergo surgery. Our findings may be limited by a selection bias. Therefore, we feel that the issue of surgical intervention for the primary tumor in stage IV breast cancer patients deserves to be carefully studied in a well-designed, prospective, multi-center trial. No significant financial relationships to disclose.

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Outcomes for black versus white women with stage IV breast cancer enrolled on investigator-initiated clinical trials at Emory.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1086 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1086-1086

Author(s):

Princess Ekpo ◽

Mylin Ann Torres ◽

Manali Rupji ◽

Jeffrey M. Switchenko ◽

Preeti Subhedar ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Clinical Trials ◽

Black Women ◽

White Women ◽

Metastatic Breast ◽

Stage Iv ◽

Black And White ◽

Stage Iv Breast Cancer ◽

Significant Difference

1086 Background: Black women are 40% more likely to die from their breast cancer compared to White women. Inadequate representation of Blacks in clinical trials may contribute to health care inequity. Emory’s Winship Cancer Institute (WCI) in Atlanta serves a significant Black population and has a unique opportunity to engage these underrepresented patients in clinical trials. We aimed to assess clinical outcomes in Black versus White women with metastatic breast cancer (MBC) enrolled on investigator-initiated clinical trials (IITs) at Emory. Methods: Black and White women with MBC enrolled on IITs conducted at WCI between 1/2009 and 1/2019 were retrospectively evaluated. Descriptive statistics were generated for all patient characteristics. Univariate analyses and a multiple logistic regression model were used to assess the effect of age and race on clinical response, length of time on trial, number of therapy lines prior to trial enrollment, and toxicity on trial. Overall survival was assessed using Kaplan Meier analysis. Results: Sixty-two women with MBC were included [White, n = 41 (66%), and Black, n = 21 (34%), p = 0.55]. Over 90% of women were enrolled on phase II clinical trials and received targeted therapy. Mean age at clinical trial consent was 53.2 and 55.9 years in Black and White women, respectively (p = 0.36). While the majority of women had hormone-receptor positive disease, a higher percentage of Blacks had triple negative breast cancer (29% vs. 17% in Whites, p = 0.39). Black women had fewer lines of systemic therapy prior to trial enrollment (2.86 vs. 4.3, respectively, p = 0.017) and were enrolled on trial for less time than White women (5.67 mo vs. 7.83 mo, respectively, p = 0.22). There were no differences in toxicity rates among patients enrolled on IITs based on race. Black women were more likely to have progressive disease (PD) on trial (45% in Blacks vs. 20% in Whites, p = 0.05). While there was no significant difference in overall survival (p = 0.482), there was a trend towards shorter survival in Black women (51.3 mos vs. 64 mos, respectively). Conclusions: Black women with MBC who enrolled on IIT trials at Emory had worse treatment response and a trend towards poorer survival compared to White women. More research is needed to determine whether this is due to adverse biology. These results reinforce the need for exploration of biomarkers of response by race and ethnicity and improved representation of Blacks in clinical trials to inform real world efficacy.

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Surgical possibilities in the treatment of advanced and locally recurrent breast cancers

Orvosi Hetilap ◽

10.1556/oh.2014.29891 ◽

2014 ◽

Vol 155 (37) ◽

pp. 1461-1468 ◽

Cited By ~ 1

Author(s):

Zoltán Mátrai ◽

Ferenc Rényi Vámos

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Surgical Treatment ◽

Primary Tumour ◽

Large Body ◽

Stage Iv ◽

Surgical Reconstruction ◽

Surgical Removal ◽

Stage Iv Breast Cancer ◽

Locally Recurrent

Stage IV breast cancer is an incurable but treatable condition. Therapy of distant metastatic disease consists primarily of systemic and symptomatic treatments, while the role of surgery is subordinate. Conventional medical treatments result in 18–24 months average overall survival, and about 5–20% 5-year overall survival. However, it seems that in selected cases with solitary or oligometastases, mainly in those which respond well to drug therapy, the aggressive surgical removal of both the primary tumour and visceral metastases results in a survival advantage. After accurate evaluation of the patients, the indication for surgical treatment should be established through a biological and multidisciplinary approach. Other possible indications for surgical treatment are ulceration, bleeding, hygienic conditions undignified of human life, central nervous system metastases, acute neurological disorders, hydro- and pneumothorax greatly reducing respiratory surface and impending fractures. Surgical procedures include simple pleural drainage, minimal invasive techniques, large body cavity surgeries, extensive resection of soft tissue and chest wall due to the primary tumor, and plastic surgical reconstruction as well. Scientific assessment of the oncological value of surgical oncological interventions in stage IV. breast cancer require further multicentric prospective comparative studies. The present paper provides a broad review of the literature on surgical interventions and results in patients with breast cancer and remote metastases, and the surgical options of locally recurrent tumours. Orv. Hetil., 2014, 155(37), 1461–1468.

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Induction of Immune Responses and Improved Survival after Infusions of T Cells Armed with Anti-CD3 X Anti-Her2/Neu Bispecific Antibody in Stage IV Breast Cancer Patients (Phase I).

Blood ◽

10.1182/blood.v110.11.2747.2747 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2747-2747 ◽

Cited By ~ 1

Author(s):

Lawrence G. Lum ◽

Ritesh Rathore ◽

Don Dizon ◽

Ding Wang ◽

Zaid Al-Kadhimi ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

T Cells ◽

Immune Responses ◽

Phase I ◽

Median Survival ◽

Bispecific Antibody ◽

Stage Iv ◽

Entire Study ◽

Stage Iv Breast Cancer

Abstract Women with stage IV metastatic breast cancer (mBrCa) have limited treatment options since toxicities from chemotherapy and radiotherapy become limiting. Non-toxic immunotherapy approaches to improve targeting and cytotoxicity directed at breast cancer are needed. Our earlier study showed that anti-CD3 activated T cells (ATC) could be expanded in culture and then armed with anti-CD3 × anti-Her2/neu bispecific antibody (HER2Bi). The armed ATC mediate enhanced specific cytotoxicity, proliferate, and induce cytokine/chemokine secretion (J Hematotherapy & Stem Cell Res10:247, 2001). In a Phase I trial using ATC armed with Her2Bi, 18 Stage IV BrCa patients (pts) were treated with 8 infusions (twice/week) for 4 weeks totaling 40 (6 pts), 80 (2 pts), 160 (7 pts), and 320(1 pt) billion ATC armed with Her2Bi without dose-limiting toxicities. The most frequent side-effects were chills, fever, and hypotension that were easily controlled with medications. Two stage IV mBrCa patients had minor responses with decreases in CEA (35.2 to 4.1 ng/ml) or CA 27-29 (57.7 to 35.6 U/ml) and one pt had partial response with a decreased liver metastatic lesion. None of the pts developed human anti-mouse antibodies levels above10 ng/ml. Immunoaffinity-depletion of BiAb-armed ATC from PBMC of a high risk IV mBrCa pt at post-treatment time points showed an increase in anti-BrCa tumor cell activity exhibited by endogenous immune cells that persisted up to 4 months after treatment. Increasing proportions and absolute numbers of CD25+ cells in CD4+ and CD8+ subsets were observed as a function of treatment with nearly all CD4+ and CD8+ cells being CD25+ by 1 week post-final infusion. Significant treatment-associated elevations (several log increases over baseline) of circulating IFNγ, TNFα, IL-2, IL-5, IL-10, IL-12p70, and IL-13 were detected in serum of nearly all of the patients beginning 1–2 weeks after initiation of infusions. Particularly remarkable was the 3 log increase of mean (n=9) serum IL-12p70 from 0 to 1200 pg/ml. There was a Th1 shift that persisted during therapy. To date, results from the phase I clinical trial suggest that Her2Bi-armed ATC activate the endogeneous immune system to generate an adaptive immune responses despite the presence of high tumor burdens. The figure shows the overall survival for 18 women (All) treated on the phase I protocol with the median survival not yet defined for the HER2/neu 3+ group and the entire study group. The median survival for the 9 pts with Her2/neu negative disease was 21.5 months. Together these data are encouraging and strongly suggest infusions of armed targeted T cells may immunized the patient against their own tumor antigens leading to immunoreactivity manifested as the development of a persistent CTL response that may lead to improved overall survival. Figure Figure

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