Resection of liver metastases from breast cancer: Effect of timing of surgery and estrogen receptor status on outcome.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 288-288
Author(s):  
D. E. Abbott ◽  
A. Brouquet ◽  
F. Meric-Bernstam ◽  
V. Valero ◽  
M. C. Green ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Liver Metastases ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Timing Of Surgery ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Best Response ◽  
Response To Chemotherapy

288 Background: The oncologic benefit of resecting liver metastases (LM) in breast cancer patients is unclear. Identifying predictors of improved outcome would be useful in selecting appropriate candidates for surgery. Methods: From 1997 to 2010, 86 breast cancer patients underwent LM resection. RECIST criteria were used to define the best response to chemotherapy as the optimal response at any time during the course of metastatic disease and the preoperative response to chemotherapy as the response immediately before LM resection. Univariate and multivariate analyses were used to identify predictors of survival. Results: Sixty-four patients (74%) had primary tumors that were either estrogen receptor (ER) or progesterone receptor (PR) positive. Fifty-three patients (62%) had solitary LM, and 73 patients (85%) had LM smaller than 5 cm. Sixty-five patients (76%) received preoperative chemotherapy, and 10 patients (12%) received 2 or more chemotherapy regimens before LM resection. Only 2 patients (3%) had progressive disease (PD) as a best response to chemotherapy, whereas 19 patients (29%) had PD as preoperative response to chemotherapy (p < 0.001). No perioperative mortality was observed. At a median follow-up of 62 months, the median durations of overall and disease-free survival were 57 and 14 months. Univariate analysis revealed that ER and PR primary tumor status, best response to chemotherapy, and preoperative response to chemotherapy were associated with overall survival after LM resection. On multivariate analysis, an ER-negative primary tumor (p=.009, hazard ratio [HR] = 3.3, 95% confidence interval [CI] =1.4-8.2) and preoperative disease progression (p=.003, HR = 3.8, 95% CI = 1.6-9.2) were independently associated with worse survival after LM resection. Conclusions: Resection of liver metastases in breast cancer patients with ER positive disease that is responsive to chemotherapy is associated with prolonged survival. Timing of surgery is critical and resection before progression is associated with better outcome. No significant financial relationships to disclose.

Estrogen receptor (ER) status of disseminated tumor cells in the bone marrow of breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21013-21013
Author(s):  
F. N. Tanja ◽  
N. Krawczyk ◽  
D. Wallwiener ◽  
S. Becker ◽  
E. Solomayer
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Primary Tumor ◽  
Hormone Receptor ◽  
Primary Breast Cancer ◽  
Disseminated Tumor Cells ◽  
Breast Cancer Patients ◽  
Primary Tumors

21013 Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer patients is associated with poor prognosis. These patients may benefit from adjuvant endocrine therapy since cytotoxic agents are not able to completely eliminate DTCs as previously shown. Only patients with hormone receptor positive breast cancer are eligible for hormonal treatment. The ERa status is routinely defined in primary tumor tissue. However, the ERa status of DTC may differ compared to the primary tumor. Therefore, the aims of this study were (1) to determine the ERa status of DTC in BM of breast cancer patients, (2) and to compare the ERa status of DTC and corresponding primary tumors. Methods: BM aspirates from 251 primary breast cancer patients were included into the study. A double immunofluorescence staining procedure was established for the identification of cytokeratin-positive (CK)/ERa positive cells. ERa status of the primary tumor was immunohistochemically assessed using the same antibody against ERa. Results: In 105 of 251 (42%) breast cancer patients CK-positive cells could be detected in BM. The number of detected cells ranged between 1 and 13 / cells per 2*106 mononuclear cells. Disseminated tumor cells demonstrated ERa positivity in 13 (12%) of these 105 patients. The ERa expression on DTC was heterogeneous in 10 of 13 (79%) patients. Concordance rate of ERa status between primary tumor and DTC was 27%. Only 11 of 83 patients with ER a positive tumors had also ERa positives DTC. Conclusions: (1)The hormone receptor status between primary tumor and corresponding DTC is disconcordant. (2)This discrepancy may explain the rate of non-responders to adjuvant endocrine therapy despite ER-positive primary tumors. (3)These patients may benefit from adjuvant therapy regimens based on antibody strategies or bisphosphonates. No significant financial relationships to disclose.

Effects of melatonin and doxorubicin on primary tumor and metastasis in breast cancer model

2021 ◽  
Vol 21 ◽  
Author(s):  
Gamze Tanriover ◽  
Sayra Dilmac ◽  
Gunes Aytac ◽  
Ammad Ahmad Farooqi ◽  
Muzaffer Sindel
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Metastatic Breast ◽  
Suppressor Cells ◽  
Metastatic Tumor ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Ample Evidence

Background: Melatonin exerts oncostatic effects on breast cancer via immunomodulation and anti-oxidation. Doxorubicin is an effective chemotherapeutic agent, but parallel studies also provide ample evidence of an off-target effect of Doxorubicin in breast cancer patients. Objective: Combinatorial use of doxorubicin and melatonin has not been comprehensively analyzed in breast cancer models. We hypothesized that the anti-oxidative, anti-proliferative and anti-inflammatory effects of melatonin could ameliorate the off-target effects of doxorubicin in breast cancer patients and enhance the anti-tumoral effects of doxorubicin. The goal of the study is to test this hypothesis in cancer cell lines and xenografted mice. Methods: The effects of Melatonin and doxorubicin on the cell viability were evaluated in 4T1-Brain Metastatic Tumor (4TBM). Furthermore, the effects of melatonin and doxorubicin on the primary tumors and systemic metastasis were evaluated in the xenografted mice. Lung and liver tissues were removed and metastasis analyses were performed. The levels of p65, phospho-STAT3, CD11b+, GR1+, Ki67, and cleaved caspase-3 proteins were determined with immunohistochemistry and western blot analysis. We examined the effects of melatonin and Melatonin+Doxorubicin combination therapy on 4TBM cells. Results: Our results showed that doxorubicin inhibited the proliferation of metastatic breast cancer cells while melatonin did not affect cells. Tumor growth and metastasis were markedly suppressed in melatonin alone and combination with doxorubicin. The expression of CD11b+ and GR1+ proteins which are indicators of myeloid-derived suppressor cells (MDSCs) were noted to be reduced in both primary tumor and metastatic tissues in melatonin and doxorubicin groups. Conclusion: The combination of melatonin with doxorubicin reduced primary tumor growth and distant metastasis. Based on these results, melatonin is a promising candidate for combinatory use with conventional chemotherapeutics for breast cancer treatment.

Can [F-18]FDG PET imaging predict early response to chemotherapy in breast cancer patients?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14577-e14577
Author(s):  
C. S. John ◽  
R. Madabushi ◽  
C. Farah ◽  
C. Lubas ◽  
G. Williams
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Pet Imaging ◽  
Meta Analysis ◽  
Statistical Significance ◽  
Early Response ◽  
Drug Uptake ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Response To Chemotherapy

e14577 Background: The purpose of this study was to perform a meta-analysis of literature data and see if [F-18]FDG and PET imaging can be used to predict the early response to chemotherapy based upon the measure of standard uptake value (SUV) or drug uptake ratio (DUR; a measure of glycolytic index) in breast cancer patients. This intervention may identify the responders for continued therapy or identify the non- responders for change of therapy. Methods: A literature search determined the number of studies that used PET-FDG imaging to monitor the response of various chemotherapies in breast cancer patients. A total of nine studies have been reviewed that used SUV/DUR as a measure of glycolytic activity of the primary tumors. The percent decrease of SUV over baseline was determined for chemotherapy cycle 1 and for subsequent cycles. A paired t-test was performed to see the statistical significance of the SUV decrease. Results: Five (n=158) studies presented the data in % mean reduction in SUV and four (n=59) studies presented SUV values for the individual patient. The average decrease in SUV in responders were 29% and 51% after first and second cycle, respectively. The non responders did not show significant change in SUV as compared to responders. Conclusion: The preliminary data mining and analysis strongly implies that PET imaging using [F-18]FDG may be used to monitor the progress of chemotherapy in breast cancer patients. This study was supported by a grant from OWH, FDA. The results do not represent official FDA position. No significant financial relationships to disclose.

scholarly journals Detection of Genomically Aberrant Cells within Circulating Tumor Microemboli (CTMs) Isolated from Early-Stage Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1409
Author(s):  
Marco Silvestri ◽  
Carolina Reduzzi ◽  
Giancarlo Feliciello ◽  
Marta Vismara ◽  
Thomas Schamberger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Early Stage ◽  
Early Stage Breast Cancer ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Associated Functions ◽  
Circulating Tumor Microemboli

Circulating tumor microemboli (CTMs) are clusters of cancer cells detached from solid tumors, whose study can reveal mechanisms underlying metastatization. As they frequently comprise unknown fractions of leukocytes, the analysis of copy number alterations (CNAs) is challenging. To address this, we titrated known numbers of leukocytes into cancer cells (MDA-MB-453 and MDA-MB-36, displaying high and low DNA content, respectively) generating tumor fractions from 0–100%. After low-pass sequencing, ichorCNA was identified as the best algorithm to build a linear mixed regression model for tumor fraction (TF) prediction. We then isolated 53 CTMs from blood samples of six early-stage breast cancer patients and predicted the TF of all clusters. We found that all clusters harbor cancer cells between 8 and 48%. Furthermore, by comparing the identified CNAs of CTMs with their matched primary tumors, we noted that only 31–71% of aberrations were shared. Surprisingly, CTM-private alterations were abundant (30–63%), whereas primary tumor-private alterations were rare (4–12%). This either indicates that CTMs are disseminated from further progressed regions of the primary tumor or stem from cancer cells already colonizing distant sites. In both cases, CTM-private mutations may inform us about specific metastasis-associated functions of involved genes that should be explored in follow-up and mechanistic studies.

Variations at HER2 and hormone receptor status in primary and metastatic sites of breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11023-e11023
Author(s):  
Nurcan Alhan ◽  
Samed Rahatli ◽  
Nadire Kucukoztas ◽  
Selim Yalcin ◽  
Mahmut Can Yagmurdur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Primary Tumor ◽  
Hormone Receptor Status ◽  
Her2 Expression ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Metastatic Lesions ◽  
Metastatic Sites ◽  
Primary Tissue

e11023 Background: Evaluation of hormone receptors (ER/PR) and Her2-Neu is important for hormonal and anti-Her2 treatments. The parameters are generally estimated in primary tumors and it is unclear whether re-evaluation of metastatic lesions will be effective during follow-up. Methods: The primary aim of this study was the compare Her2 and HR (ER/PR) status in primary and metastatic tissues of breast cancer patients. HR and Her2 expression in biopsy specimens obtained from primary tumor and their metastatic lesions of 44 breast cancer patients, followed-up during 1995-2010 at Baskent University Hospital were analyzed. Results: Of 44 patients 29.5% were found Her2 (+), 54,5 % ER (+) and 45.4% PR (+) in primary site. Metastatic regions excised or biopsied as following: Bone 31.8% (14/44), liver 27.3% (12/44), skin 25% (11/44), lung 9.1% (4/44), brain 4.5% (2%44), bone marrow 4.5 (2/44), ovaries 4.5% (2/44), stomach, abdominal LAP and pelvic mass 2.3% (3/44). Positification rate of ER status in metastatic sites was detected as 4.5% (2/44), when positive in primary tumors, negatification rate was detected as 20.5%. The positification rate of PR status in metastatic sites, while being negative in primary tissue was 13.6% (6/44); and negativication rate in metastatic lesions, being positive in primary tumor was 27.3% (12/44). The positivication rate of Her2 expression in metastatic lesions while being negative in primary tissue was 4.5% (2/44); and negativication rate while being positive in primary tumor was detected as 13.6% (6/44). When the hormone receptor status and Her2 expression of the patients followed-up are evaluated, receptor variation was detected in 23 of 44 patients. Conclusions: Our study confirms that biological properties of breast cancer may vary among primary tumors and asynchronised metastatic lesions. Further prospective studies are needed to better define the discordance of Her2 or HR status at primary tissue and metastatic sites.

scholarly journals MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sanne Løkkegaard ◽  
Daniel Elias ◽  
Carla L. Alves ◽  
Martin V. Bennetzen ◽  
Anne-Vibeke Lænkholm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cancer Patients ◽  
Endocrine Therapy ◽  
Endocrine Resistance ◽  
Predictive Marker ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Minichromosome Maintenance ◽  
Primary Tumors

AbstractResistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser315,33), CHK1(Ser317), and cdc25b(Ser323), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.

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