scholarly journals Extracellular Matrix Features Discriminate Aggressive HER2-Positive Breast Cancer Patients Who Benefit from Trastuzumab Treatment

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 434
Author(s):  
Ilona Rybinska ◽  
Marco Sandri ◽  
Francesca Bianchi ◽  
Rosaria Orlandi ◽  
Loris De Cecco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Gene Expression Pattern ◽  
Response To Therapy ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Trastuzumab Treatment ◽  
Worse Prognosis

We previously identified an extracellular matrix (ECM) gene expression pattern in breast cancer (BC), called ECM3, characterized by a high expression of genes encoding structural ECM proteins. Since ECM is reportedly implicated in response to therapy of BCs, the aim of this work is to investigate the prognostic and predictive value of ECM3 molecular classification in HER2-positive BCs. ECM3 resulted in a robust cluster that identified a subset of 25–37% of HER2-positive tumors with molecular aggressive features. ECM3 was significantly associated with worse prognosis in two datasets of HER2-positive BCs untreated with adjuvant therapy. Analyses carried out on two of our cohorts of patients treated or not with adjuvant trastuzumab showed association of ECM3 with worse prognosis only in patients not treated with trastuzumab. Moreover, investigating a dataset that includes gene profile data of tumors treated with neoadjuvant trastuzumab plus chemotherapy or chemotherapy alone, ECM3 was associated with increased pathological complete response if treated with trastuzumab. In the in vivo experiments, increased diffusion and trastuzumab activity were found in tumors derived from injection of HER2-positive cells with Matrigel that creates an ECM-rich tumor environment. Taken together, these results indicate that HER2-positive BCs classified as ECM3 have an aggressive phenotype but they are sensitive to trastuzumab treatment.

Observational study on adjuvant trastuzumab in HER2-positive early breast cancer patients

2015 ◽  
Vol 11 (10) ◽  
pp. 1493-1500 ◽  
Author(s):  
G Mustacchi ◽  
F Puglisi ◽  
AM Molino ◽  
D Crivellari ◽  
C Ghiotto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Observational Study ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab

Paclitaxel, carboplatin and trastuzumab (TCH) achieves high pathological complete remission rate after in vivo response directed 2–4 cycles of doxorubicin and cyclophosphamide (AC) in breast cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10583-10583
Author(s):  
R. S. Mehta ◽  
T. Schubbert ◽  
K. Kong
Keyword(s):  
Breast Cancer ◽  
Complete Remission ◽  
Remission Rate ◽  
Maximal Response ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Topoisomerase Ii Alpha ◽  
Gm Csf ◽  
Pathological Complete Remission

10583 Background: A pathological complete remission (pCR) predicts improved survival in breast cancer (BC). Treatment with AC followed by concurrent TCH improved pCR rates to 87.5% in Her2 positive 8-patient pilot study (SABCS 2004, abs #1110), confirmed by a subsequent phase II study. We hypothesized that response adjusted AC (2–4 cycles), TCH (3–4 cycles) sequence targets topoisomerase II alpha amplified and deleted clone, respectively (SABCS 2005, abs # 5056). We report here the combined analysis of the Her2 positive (fluorescence in situ hybridization + or immunohistochemistry 3+) subset of these studies. Material and Methods: Thirty-one patients with stage IIB-IV BC were accrued. Twenty-eight of 31 patients received AC in a dose dense manner with GM-CSF support. Patients received carboplatin calculated at AUC of 2 and paclitaxel at 80 mg/m2 for 3 weeks followed by 1 week of rest (1 cycle) for a maximum of 4 cycles. Concurrent trastuzumab 4 mg/kg loading dose, then 2 mg/kg/wk was administered for 12–16 weeks. Results: Twenty-nine of 31(94%, CI, 0.79–1) patients showed a clinical complete or partial response (cCR, or cPR). Nineteen of 27 patients (70%, CI, 0.50–0.86) achieved a pCR at surgery; two additional patients had ≤3 mm residual invasive cancer; and lymph node negativity rate was 73%. Of the 3 additional patients with cCR, 1died (underlying cirrhosis), 1 refused surgery, and 1 awaits surgery. A fourth patient with cPR awaits surgery. Ninety percent of the patients (28/31, CI, 0.74–0.98) are alive, and 77% (24/31, CI, 0.59–0. 90) are progression free at median follow up of 19 months (range 6–35 months). Median ejection fraction by echocardiogram was 60% (range 50–74); no patient had clinical cardiac dysfunction. One patient each on GM-CSF and peg-GCSF developed neutropenic fever. Conclusion: Short course of TCH following response adjusted 2–4 cycles of AC will have an improved therapeutic ratio with minimum cardiac toxicity and maximal response. [Table: see text] [Table: see text]

Myocardial HER2 expression with 111In-DTPA-trastuzmab scan in patients shortly after anthracycline treatment

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3057-3057
Author(s):  
P. J. Perik ◽  
M. N. Lub-De Hooge ◽  
P. L. Jager ◽  
M. A. De Korte ◽  
J. A. Gietema ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Xenograft Model ◽  
Metastatic Breast ◽  
Optimal Timing ◽  
Her2 Overexpression ◽  
Compensatory Mechanism ◽  
Her2 Expression ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab

3057 Background: The monoclonal antibody trastuzumab, apart from antitumor effect, can induce cardiotoxicity, particularly when combined with anthracyclines. Myocardial HER2 upregulation may serve, transiently, as a compensatory mechanism induced by cardiac stress. Previously we showed in a xenograft model that 111In-DTPA-trastuzumab scintigraphy can detect HER2 positive lesions (Br J Pharmacol 2004;143:99–106) but that myocardial 111In-DTPA-trastuzumab uptake was found in only 1 of 17 anthracycline-pretreated HER2-positive metastatic breast cancer patients (ESMO 2004#50). This low number may be related to the long interval between anthracycline administration (median 11 months) and performed scan in these patients. To evaluate whether myocardial HER2 expression is induced by anthracyclines, we performed 111In-DTPA-trastuzumab scans in patients shortly after anthracycline treatment. Methods: Patients who completed 4–6 cycles of anthracycline-based chemotherapy (< 3 weeks after last dose) underwent gammacamera imaging 48 and 96 h after iv administration of 150 MBq 111In-DTPA-trastuzumab (5mg). Results: 10 anthracycline-treated patients, 8 as adjuvant breast cancer treatment and 2 for metastatic sarcoma have been enrolled. Myocardial 111In-DTPA-trastuzumab uptake was observed in 5/10 anthracycline-treated patients who all were without symptomatic cardiac dysfunction. Conclusions: Shortly after completion of anthracycline treatment myocardial HER2 overexpression was detectable in 50% of the patients. This may be a transient phenomenon. 111In-DTPA-trastuzumab scan after anthracycline treatment prior to adjuvant trastuzumab may identify patients more susceptible for trastuzumab-induced cardiotoxicity. This important observation may add to optimal timing of trastuzumab therapy i.e. when HER2/neu expression in the heart is negative (again). [Table: see text]

The potential benefit of trastuzumab-based therapy upon lapatinib progression in heavily preatreated patients with advanced HER2 positive breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11576-e11576
Author(s):  
Anastasios L. Boutis ◽  
Sofia Chatzileontiadou ◽  
Nikolaos Diamantopoulos ◽  
Athanasios Pouptsis ◽  
Chariklia Fotiou
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Ductal Carcinoma ◽  
Advanced Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Metastatic Setting ◽  
Increased Risk

e11576 Background: Overexpression of human epidermal growth factor receptor 2 (HER2) occurring in about 20% of breast cancers is associated with increased risk of disease recurrence and worse prognosis. Despite the advent of therapies that target HER2, particularly, trastuzumab and lapatinib, that have altered the natural course of HER2-positive advanced breast cancer, tumor progression remains inevitable. New agents are in clinical development, but up to date there are limited data to direct the treatment of patients after lapatinib progression. Methods: We retrospectively searched for HER2-positive advanced breast cancer patients treated at our clinic, who received both trastuzumab-based therapy and lapatinib upon trastuzumab-progression in the metastatic setting. Thirty patients, all female, suffering from HER2-positive advanced breast cancer were identified. HER-2 positivity was assessed by immunohistochemistry (IHC 3+) or chromogenic in situ hybridization (CISH+). Results: Of the 30 patients, 83.3% had invasive ductal carcinoma; 60% had positive hormone receptor status, and 80% grade 3 tumours. Half of the patients received adjuvant trastuzumab. Median age was 57 years, range 37-79 years. 36.6% were switched to lapatinib after a median of three (range 2-6 lines) trastuzumab-based treatment lines. In 8 pts (37.5%) trastuzumab was re-started after lapatinib progression. In 7 of these patients, trastuzumab was combined with chemotherapy. Median progression free survival and overall survival in these patients was 4.75 and 8.87 months respectively. 3 patients received bevacizumab-based therapy upon lapatinib failure. Conclusions: Trastuzumab rechallenge after lapatinib progression may be active in a subgroup of heavily pre-treated patients. Clinical benefit of this strategy has to be balanced especially in limited resource settings with unavailability of novel agents or early phase clinical trials. As of now, there is no uniform accepted standard to define the optimal treatment approach of patients upon lapatinib progression showing the real need for new therapies in this population.

De-escalating adjuvant trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer: A systemic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 524-524
Author(s):  
Hadar Goldvaser ◽  
Korzets Ceder Yasmin ◽  
Daniel Shepshelovich ◽  
Rinat Yerushalmi ◽  
Michal Sarfaty ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cardiac Dysfunction ◽  
Early Stage ◽  
Nodal Involvement ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Trastuzumab Treatment ◽  
Her2 Positive Breast Cancer ◽  
One Year ◽  
Positive Breast Cancer

524 Background: One year of adjuvant trastuzumab in combination with chemotherapy is the standard of care in early-stage HER2 positive breast cancer. Existing data on shortening trastuzumab treatment show conflicting results. Methods: A search of PubMed and conferences identified randomized trials that compared abbreviated trastuzumab therapy to one year of treatment in early-stage HER2 positive breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for disease free survival (DFS) and overall survival (OS). Data on the number of DFS and distant relapse events were also collected as were the number of patients at risk in each group. Subgroup analyses evaluated the effect of nodal involvement, estrogen receptor (ER) expression and the duration of abbreviated trastuzumab (9-12 weeks versus 6 months). Odds ratios (ORs) and 95% CI were computed for pre-specified cardiotoxicity events including cardiac dysfunction and congestive heart failure (CHF). Results: Analysis included 6 trials comprising 11603 patients. In most studies adjuvant chemotherapy included anthracyclines and taxanes. Shorter trastuzumab treatment was associated with worse DFS (HR = 1.14, 95% CI 1.05-1.25, p = 0.002) and OS (HR = 1.15, 95% CI 1.02-1.29. p = 0.02). The effect on DFS was not influenced by ER status (p for the subgroup difference = 0.23), nodal involvement (p = 0.44) or the different duration of trastuzumab in the experimental arm (p = 0.08). In absolute terms, after an estimated median follow-up of 71 months, shorter treatment with trastuzumab was associated with an absolute increase in DFS events of 2.3%. Shorter trastuzumab treatment was associated with lower odds of cardiac dysfunction (OR = 0.67, 95% CI 0.55-0.81, p < 0.001) and CHF (OR = 0.66, 95% CI 0.50-0.86, p = 0.003). Conclusions: Compared to one year, shorter duration of adjuvant trastuzumab is associated with significantly worse DFS and OS, despite favorable cardiotoxicity profile. One year of trastuzumab should remain the standard adjuvant treatment in early-stage HER2 positive breast cancer with appropriate cardiac monitoring.

scholarly journals Elevated microRNA-125b levels predict a worse prognosis in HER2-positive breast cancer patients

2016 ◽  
Vol 13 (2) ◽  
pp. 867-874 ◽  
Author(s):  
Yanwei Luo ◽  
Xinye Wang ◽  
Weihong Niu ◽  
Heran Wang ◽  
Qiuyuan Wen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Worse Prognosis ◽  
Positive Breast Cancer
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