scholarly journals Comprehensive characterization of distinct genetic alterations in metastatic breast cancer across various metastatic sites

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Soojin Cha ◽  
Esak Lee ◽  
Hong-Hee Won
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Large Scale ◽  
Metastatic Breast ◽  
Genetic Alterations ◽  
Driver Mutations ◽  
Site Specific ◽  
Metastatic Site ◽  
Treatment Naïve ◽  
Metastatic Sites

AbstractMetastasis is the major cause of death in breast cancer patients. Although previous large-scale analyses have identified frequently altered genes specific to metastatic breast cancer (MBC) compared with those in primary breast cancer (PBC), metastatic site-specific altered genes in MBC remain largely uncharacterized. Moreover, large-scale analyses are required owing to the low expected frequency of such alterations, likely caused by tumor heterogeneity and late dissemination of breast cancer. To clarify MBC-specific genetic alterations, we integrated publicly available clinical and mutation data of 261 genes, including MBC drivers, from 4268 MBC and 5217 PBC patients from eight different cohorts. We performed meta-analyses and logistic regression analyses to identify MBC-enriched genetic alterations relative to those in PBC across 15 different metastatic site sets. We identified 11 genes that were more frequently altered in MBC samples from pan-metastatic sites, including four genes (SMARCA4, TSC2, ATRX, and AURKA) which were not identified previously. ARID2 mutations were enriched in treatment-naïve de novo and post-treatment MBC samples, compared with that in treatment-naïve PBC samples. In metastatic site-specific analyses, associations of ESR1 with liver metastasis and RICTOR with bone metastasis were significant, regardless of intrinsic subtypes. Among the 15 metastatic site sets, ESR1 mutations were enriched in the liver and depleted in the lymph nodes, whereas TP53 mutations showed an opposite trend. Seven potential MBC driver mutations showed similar preferential enrichment in specific metastatic sites. This large-scale study identified new MBC genetic alterations according to various metastatic sites and highlights their potential role in breast cancer organotropism.

scholarly journals Phenotypic discordance between primary and metastatic breast cancer in the large-scale real-life multicenter French ESME cohort

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Thomas Grinda ◽  
Natacha Joyon ◽  
Amélie Lusque ◽  
Sarah Lefèvre ◽  
Laurent Arnould ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Large Scale ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Multivariable Analysis ◽  
Real Life ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Risk Of Death

AbstractExpression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.

Eribulin efficacy based on type of metastatic site: a real-life study in heavily pretreated metastatic breast cancer

2017 ◽  
Vol 13 (11s) ◽  
pp. 5-10 ◽  
Author(s):  
Angela Prestifilippo ◽  
Daniele Grippaldi ◽  
Giusi Blanco ◽  
Lorenzo Memeo ◽  
Ivana Puliafito ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Real Life ◽  
Metastatic Breast ◽  
Metastatic Site ◽  
Life Study ◽  
Heavily Pretreated ◽  
Real Life Study

High efficacy and low toxicity of the combination of vinorelbine and capecitabine as second line treatment in metastatic breast cancer previously treated with taxanes and/or anthracyclines

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10719-10719 ◽  
Author(s):  
G. Orphanos ◽  
A. Alexopoulos ◽  
G. Ioannidis ◽  
C. Kandylis ◽  
A. Ardavanis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
Line Treatment ◽  
Second Line ◽  
Previously Treated ◽  
Statistical Planning ◽  
Metastatic Sites ◽  
Ecog Ps

10719 Background: Capecitabine and Vinorelbine have shown considerable activity given as single agent or in combination with other drugs. The aim of this single institution ph.II study is to evaluate the response to the combination of Capecitabine and Vinorelbine given as second line treatment in patients with metastatic breast cancer previously treated with taxanes and/or anthracyclines. Methods: The regimen consists of Capecitabine 2000 mg/m2 D1-D14 and Vinorelbine 20 mg/m2 D1,D8 q 3 weeks for six cycles. Evaluation of response was accomplished with CT scan after the third and sixth cycle. Patients with disease progression after cycle 3 are taken off protocol. Patients with gr 2/3 granulocytopenia are given G-CSF for all subsequent cycles and there is a 20% dose reduction in both drugs for patients with gr 4 granulocytopenia. Results: 30 pts have been enrolled so far; according to statistical planning the total number of accrued pts should reach 63. Median age 55 yrs (30–76), median ECOG PS 1 (0–2), pre/postmenopausal 6/24. Number of metastatic sites: 1 in 6 pts, 2 in 15 pts, 3 in 6 pts and 4 in 3 pts. A total of 146 cycles was administered. Overall response rate 50% with CR in 2 (6.7%) pts, PR in 13 (43.3%) pts. Stable disease was observed in 4 (13.3%) pts, 8 (26.6%) pts had progressive disease and 3 (10%) were non evaluable. Toxicity: anemia gr 2 in 2 (6.7%) pts and gr 3 in 1 (3.3%) ptn, thrombocytopenia gr2 in 2 (6.7%) pts, granulocytopenia gr 2/3 in 17 (56.7%) pts and gr4 in 1 (3.3%) ptn. Gr 1/2 nausea or vomiting was observed in 5 (16.6%) pts and gr 3/4 in 2 (6.7%) pts. Vinorelbine induced phlebitis in 3 (10%) pts, gr1/2 diarrhea in 3 (10%) and fungal infection of the nail beds in 2 (6.7%) pts. Conclusions: Preleminary results suggest that the Capecitabine and Vinorelbine combination is an active and safe regimen for second line metastatic breast cancer treatment. The study remains open to achieve the planned patient accrual. No significant financial relationships to disclose.

Trastuzumab-resistant HER2-positive metastatic breast cancer: Comparing results of lapatinib and capecitabine in brain and other metastatic sites.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e11505-e11505
Author(s):  
E. J. Cortes ◽  
M. Bomfim ◽  
B. V. Freitas ◽  
F. Muller ◽  
E. R. Silva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Metastatic Sites

Tesetaxel: Activity of an oral taxane as first-line treatment in metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1016-1016 ◽  
Author(s):  
Andrew David Seidman ◽  
Lee Steven Schwartzberg ◽  
Joyce O'Shaughnessy ◽  
Gabriella D'Andrea ◽  
Peter Rubin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Estrogen Therapy ◽  
Metastatic Breast ◽  
Hypersensitivity Reactions ◽  
Highly Active ◽  
Line Therapy ◽  
Grade 3 ◽  
Metastatic Sites

1016 Background: Tesetaxel, unlike standard taxanes (docetaxel, paclitaxel), is not a substrate for Pgp, a major cause of taxane resistance in tumor models. In a DU4475 breast cancer xenograft that overexpresses Pgp, tesetaxel induced a 94% reduction in tumor size, markedly exceeding the activity of docetaxel (46%) and paclitaxel (26%). Tesetaxel is associated with substantially less neuropathy preclinically than equi-myelotoxic doses of docetaxel. In clinical studies to date, tesetaxel is not associated with hypersensitivity reactions (0% incidence in > 450 patients [pts]), thus eliminating the need for premedication and extended observation. In a prior study, tesetaxel (27-35 mg/m2 Q3 wks) achieved a 38% partial response (PR) rate as 2nd-line therapy in pts with metastatic breast cancer (MBC) who had progressed after multidrug anthracycline-containing regimens. To extend these data, we initiated a phase 2 study of tesetaxel as 1st-line therapy in women with MBC. Methods: Eligibility included MBC; HER2-; ECOG PS 0-1; and adequate organ function. Adjuvant chemotherapy (including taxanes) was allowed. Tesetaxel was administered orally without anti-allergic premedication at a starting dose of 27 mg/m2 once every 3 wks. Overall response rate (ORR; RECIST) was the primary endpoint. Results: All 45 pts have been accrued. Median age is 58 y (range 36-80); median time from diagnosis, 4.0 y (range 0-21); triple negative status, 8 pts at diagnosis, 14 at time of metastasis. Metastatic sites are lung (22 pts), lymph nodes (22), liver (24), and bone (21). Prior treatment includes anti-estrogen therapy (32 pts), adjuvant chemotherapy (31), prior taxane (25), and radiotherapy (28). ORR in 24 pts evaluable for response is 50% (1 CR [4%], 11 PR [46%]); 5 responding pts had prior taxane therapy. Neutropenia is the most common ≥ Grade 3 adverse event with 50% of cases observed after dose escalation to 35 mg/m2; febrile neutropenia and Grade 3 peripheral neuropathy occurred in 2 pts each. There were no hypersensitivity reactions. Conclusions: Tesetaxel is highly active in 1st-line MBC and overcomes multiple limitations of standard taxanes. Updated ORR and PFS for all pts will be presented. Weekly dosing will be evaluated in a new cohort of pts.

Lapatinib efficacy according to metastatic sites in trastuzumab pretreated patients with HER2-positive metastatic breast cancer: An analysis form IntERB registry in the Czech Republic.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11072-e11072 ◽  
Author(s):  
Peter Grell ◽  
Vit Kandrnal ◽  
Bortlicek Zbynek ◽  
Rostislav Vyzula
Keyword(s):  
Breast Cancer ◽  
Czech Republic ◽  
Metastatic Breast Cancer ◽  
Kinase Inhibitor ◽  
Metastatic Breast ◽  
Skin Toxicity ◽  
Skeletal Metastasis ◽  
Complete Response ◽  
Her2 Positive ◽  
Metastatic Sites

e11072 Background: Lapatinib is an oral dual tyrosin kinase inhibitor of EGFR and HER2 and compared to trastuzumab penetrates to CNS. We evaluated efficacy and safety of lapatinib treatment according to different metastatic sites involvement using data from IntERB registry that has been initiated and run by Czech Society for Oncology and Institute of Biostatistics and Analyses at Masaryk University, Brno, Czech Republic. Methods: An analysis included 213 patients with HER2 positive metastatic breast cancer treated from January 2007 to September 2011. Lapatinib was mostly administered orally 1250mg/day with capecitabine (2000mg/m2 D1-14), 16 patients received lapatinib in monotherapy. All patients had experienced progression during prior trastuzumab based therapy. Results: Median age was 56 years (range 23 – 78). Median duration of lapatinib therapy was 20.6 weeks (range 1–146). Complete response was achieved in 13 patients (6.1%), partial response in 31 (14.6%), stable disease in 118 (55.4%). In 26 disease have progressed (12.2%); response could not be assessed in 25 patients (11.7%). PFS for whole group was 7.1 months (95% CI 5.9-8.5). Overall survival was 17.2m (95% CI 15.8-18.6), probability of 6m OS was 80.3% and 1-year OS was 64%. Metastatic sites specific survival was evaluated in 103 patients. CNS dissemination was initially diagnosed in 31 patients (30.1%), PFS in this group was 6.2m (95% CI 3.3-9.1), OS was not reached, 6-m OS was 67.3%. In non-CNS group (skeletal metastasis in 49.5%, lung 38.8%, hepatic 36.9%, lymphatic 17.5%, other 15.5%) was PFS 6.3m (95% CI 1.6-11.1), OS 22.0m (95% CI 15.3-28.8) and 6-m OS was 88.2%. Most common toxicities were diarrhea in 11.7% patients, rash/skin toxicity in 10.8%, nausea/vomitus in 5.2% and hepatotoxicity in 2.3%. No cardiac toxicity was reported. Therapy was discontinued due toxicity in 9.0%. Conclusions: Lapatinib in combination with capecitabine proved its efficacy in trastuzumab pretreated HER2 positive metastatic breast cancer. Even in patients with CNS involvement was achieved a notable PFS and OS, comparable to non-CNS group of patients. Therapy was well tolerated.

HER2/neu status in primary breast cancer and in metastatic site as detected using FNA.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11502-e11502
Author(s):  
Francesco Giotta ◽  
Maria Consilia Asselti ◽  
Stella Petroni ◽  
Onsina Popescu ◽  
Vincenza Rubini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Proliferative Activity ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Significant Loss ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Metastatic Site ◽  
Her 2 ◽  
Metastatic Sites

e11502 Background: As for hormonal receptor (ER, PgR), also human epidermal growth factor receptor-2 (HER-2) expression in breast cancer primitive tumor (PT) could be different from that of metastatic site (MS). These differences arise some questions about clinically useful information given and accuracy of methods to detect biological features. Fine Needle Aspiration (FNA) of metastatic sites could be an available tool to characterize biologic pattern of lesions, using immunocytochemical and/or molecular assay. The aim of the study is to compare prognostic and predictive factors obtained from PT and corresponding MS. Methods: Thirty-eight consecutive metastatic breast cancer patients underwent FNA on metastatic sites in order to re-evaluate receptor status, proliferative activity and HER-2/Neu amplification. In MS the material was achieved using FNA with a 21-23 G needle and obtaining monolayer and the corresponding cito-inclusion. MS were localized in liver (21), lung (8) and distant lymph-nodes (9). ERs, PgRs and Ki-67 were detected in both PT and MS, in 38 cases by immunochemistry, whereas HER-2/Neu amplification was detected on citoinclusion in 35 evaluable cases by FISH. Results: ERs, PgRs and Ki-67 were detected in both PT and in MS, in 36, 34, 25 out of 38 cases respectively, showing a significant loss of hormonal receptors and a decreased proliferative activity in MS versus PT (t-test p: 0.0195, <0.0001 and 0.0120 respectively). Regarding to HER-2/Neu amplification, 28 out of 35 evaluable cases were not amplified while 6 were amplified both in PT and in MS (Pearson Test: r=0.9 p: <0.0001). Another case, HER/Neu amplified in TP, after therapy with trastuzumab resulted not amplified in MS. Conclusions: According to other authors, our data demonstrated that the lost of HER/Neu amplification in MS is a possible event and that FNA samples of MS are available for HER/Neu detection.

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