scholarly journals O76: SERUM JAM-A AS A PREDICTOR OF TREATMENT RESISTANCE IN BREAST CANCER PATIENTS

2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
EJ Rutherford ◽  
CE Richards ◽  
AO Leech ◽  
ADK Hill ◽  
AM Hopkins
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumour Progression ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Beaumont Hospital ◽  
Treatment Resistance ◽  
Therapeutic Resistance ◽  
Breast Cancer Patients ◽  
Her2 Positive

Abstract Introduction Junctional Adhesion Molecule-A (JAM-A) has important physiological functions in epithelial and endothelial barriers, but its overexpression has also been linked with tumour progression and poor prognosis in various malignancies. Since JAM-A can be enzymatically cleaved (cJAM-A) and has been detected in the bloodstream, we hypothesized that cJAM-A shed from tumours overexpressing JAM-A may represent a possible predictor of treatment resistance in breast cancer. Method An assay was optimised to detect cJAM-A in serum/plasma. Samples were obtained from HER2-positive breast cancer patients (n=20) in Beaumont Hospital. Independently, serial samples were obtained from a Canadian cohort of locally advanced breast cancer (LABC) patients (n=53). Result Serum cJAM-A levels in therapy-resistant patients was significantly higher than those in treatment-sensitive patients (p<0.05) in an Irish cohort of HER2 positive patients. In a diverse international cohort of LABC patients, the development of metastatic disease was associated with higher levels of cJAM-A (p<0.05) as well as shorter time to progression (p<0.05). Conclusion Our data suggest that cJAM-A merits further investigation as a novel biomarker enabling prospective identification of patients at greatest risk of developing therapeutic resistance. Take-home message Our data suggest that cJAM-A merits further investigation as a novel biomarker enabling prospective identification of patients at greatest risk of developing therapeutic resistance.

Efficacy and safety of neoadjuvant chemotherapy of sequential doublets and dose dense plus trastuzumab in HER2-positive locally advanced breast cancer patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11089-11089
Author(s):  
E. Grande ◽  
A. Sanchez-Muñoz ◽  
A. García-Tapiador ◽  
A. Ortega-Granados ◽  
A. Jaén-Morago ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cancer Patients ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Chemotherapeutic Agents ◽  
Advanced Breast ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Number Of Patients

11089 Background: Neoadjuvant therapy for breast cancer constitutes an excellent test to evaluate the sensitivity to chemotherapeutic agents and/or new biological agents against specific targets as trastuzumab and Her2. Furthermore, pathologic complete response (pCR) is a surrogate marker for disease-free and overall survival. Methods: The objective was to determine the efficacy in terms of pCR rates and the safety profile of the doublets plus trastuzumab schedule administered for the neoadjuvant setting of locally advanced breast cancer patients. A total of 20 patients with histologically confirmed locally invasive Her2-positive breast carcinoma were included. The median age was 43. Mean tumour size was 5.1 cm. Treatment consisted of a first sequence with epirubicin 90 mg/m2 and cyclophophamide 600 mg/m2 for 3 cycles, and a second sequence with paclitaxel 150 mg/m2 and gemcitabine 2500 mg/m2 for six cycles. All drugs were administered on day 1, every two weeks with prophylactic growth factor supports. Weekly trastuzumab was administered at a dose of 2mg/kg (4 mg/kg loading dose), concomitantly with paclitaxel and gemcitabine. Subsequently, patients underwent surgery and received radiotherapy and/or adjuvant hormonal therapy according to institutional practice Results: Objective clinical response was achieved in all patients. 10 (50%) pCR were obtained. With a median follow up of 18.2 months (3–38), 17 patients (85%) are alive without disease progression, and 3 (15%) showed recurrence and 1 of whom died. Treatment was well tolerated, 1 patient experienced 1 episode of grade 4 neutropenia and 2 patients had grade 3 neutropenia. 1 patient discontinued the treatment due to hypersensitivity reaction to paclitaxel. Asymptomatic decrease in cardiac ejection fraction with subsequent normalization was seen in 1 case. Conclusions: Despite of the small number of patients, results have shown a high pCR rate in this group of breast cancer patients with poor prognostic. The schedule seems to be feasible and tolerable and further studies with the doublet sequences plus trastuzumab are warranted on the neoadjuvant Her2 positive breast cancer patients No significant financial relationships to disclose.

scholarly journals Association between tumor molecular subtype, clinical stage and axillary pathological response in breast cancer patients undergoing complete pathological remission after neoadjuvant chemotherapy: potential implications for de-escalation of axillary surgery

2021 ◽  
Vol 13 ◽  
pp. 175883592199667
Author(s):  
Jin Hong ◽  
Yiwei Tong ◽  
Jianrong He ◽  
Xiaosong Chen ◽  
Kunwei Shen
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Molecular Subtype ◽  
Locally Advanced Breast Cancer ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Luminal B ◽  
Axillary Surgery

Background: Axillary node status is used in clinical practice to guide the selection of axillary surgery in breast cancer patients. However, to date, the optimal axillary management following neoadjuvant therapy (NAT) for breast cancer remains controversial. Our study aimed to investigate the association of molecular subtype, clinical stage, and ypN status after NAT in breast cancer patients, especially those achieving breast pathological complete remission (pCR). Patients and methods: Patients receiving ⩾4 cycles of NAT were retrospectively included between January 2009 and January 2020. ypN status was compared among patients with different breast pCR statuses, clinical stages, and molecular subtypes in univariate and multivariate analyses. Results: A total of 1999 patients were included: 457 (22.86%), 884 (44.22%), and 658 (32.92%) patients with cT1-2N0, cT1-2N1, and locally advanced breast cancer (LABC), respectively. Altogether, 435 (21.8%) patients achieved breast pCR: 331 with ypN– and 104 with ypN+ status. Patients achieving breast pCR had a significantly lower ypN+ rate than those without pCR [23.9% versus 62.5%, odds ratio (OR) = 0.14, 95% confidence interval (CI) = 0.09–0.21]. For patients with breast pCR, the ypN+ rate was 6.4%, 25.7%, and 33.9% in cT1-2N0, cT1-2N1, and LABC patients, respectively ( p < 0.001). Furthermore, the ypN+ rate was 30.8%, 16.8%, 17.5%, 29.6%, and 27.6% in breast pCR patients with the Luminal A, Luminal B (HER2+), HER2-amplified, Luminal B (HER2–), and triple-negative subtype, respectively. Luminal B (HER2+) (OR = 0.20, 95% CI = 0.05–0.82) and HER2-amplified (OR = 0.19, 95% CI = 0.05–0.83) tumors were associated with lower ypN+ rates. Moreover, 100% of breast pCR patients with cT1-2N0 and HER2-positive disease achieved pathological pN0. Conclusion: In breast pCR patients after NAT, clinical stage and molecular subtype were significantly associated with ypN status. Patients with cT1-2N0 and HER2-positive disease who achieved breast pCR had a very low ypN+ rate, possibly indicating the possibility for de-escalation of axillary surgery in this patient subgroup.

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