Selected reaction monitoring mass spectrometry (SRM-MS) evaluation of HER2 equivocal breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12510-e12510
Author(s):  
William Jeffery Edenfield ◽  
Krupa Merchant ◽  
Julie C. Martin ◽  
Leylah Drusbosky ◽  
Mary Helen Elliott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Dynamic Range ◽  
Ductal Carcinoma ◽  
Selected Reaction Monitoring ◽  
Her2 Status ◽  
Reaction Monitoring ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive

e12510 Background: Human epidermal growth factor receptor type 2 (HER2) is a significant driver of breast oncogenesis and has been found to be amplified in one-fifth of all breast cancers. Identification of cell surface over-expression of HER2 can be completed using immunohistochemistry (IHC), while amplification of the gene can be detected using fluorescence in situ hybridization (FISH) or differential polymerase chain reaction (PCR). Definitive diagnostic standards for each detection method are established, however approximately 5-10% of breast cancer patients have a HER2 status of “double equivocal,” offering little guidance to directing therapy. Previously, selected reaction monitoring mass spectrometry (SRM-MS) illustrated the dynamic range of HER2 positive protein expression by IHC or amplified FISH to have a threshold determination of 740amol.We hypothesized that this method could delineate which ‘double equivocal’ patients may indeed express enough HER2 to be candidates for targeted therapy. Methods: Overall, 76 invasive breast cancer samples identified as equivocal by IHC and FISH between 1/1/2010 and 12/31/2017 were evaluated. Typical demographic and clinicopathologic data were collected to include age, race, histology, size, hormone receptor status, treatments and outcomes. HER2 levels in each equivocal sample were quantitated using SRM-MS. Data were analyzed using Fisher’s t-tests, chi-square and ANOVA (p < 0.05). Results: Using the 740 amol/ng as the SRM-MS cut-off for HER2 positivity, the group was divided into two cohorts. No significant differences were found for demographic or pathologic variables. While identified HER2 levels were between 209.1-1286.6amol, 18 patients had SRM-MS results above the threshold but outcomes were not correlated with treatment received. Conclusions: We report the largest series of doubly equivocal HER2 patients evaluated with SRM-MS. For patients with invasive ductal carcinoma, SRM-MS was not able to identify patients for whom HER2 directed therapy would be a benefit. Future plans include an assessment of this cohort with an RNA seq algorithm given the high degree of accuracy we have shown with known HER2 positives and negatives.

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.

scholarly journals Rate of reclassification of HER2-equivocal breast cancer cases to HER2-negative per the 2018 ASCO/CAP guidelines and response of HER2-equivocal cases to anti-HER2 therapy

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241775
Author(s):  
James Crespo ◽  
Hongxia Sun ◽  
Jimin Wu ◽  
Qing-Qing Ding ◽  
Guilin Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Disease ◽  
Cancer Center ◽  
Her2 Status ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Testing ◽  
Primary Disease ◽  
The Impact

Purpose The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guideline on HER2 testing in breast cancer permits reclassification of cases with HER2-equivocal results by FISH. The impact of such reclassification is unclear. We sought to determine the proportion of HER2-equivocal cases that are reclassified as HER2-negative and the impact of anti-HER2 therapy on survival in HER2-equivocal cases. Methods We reviewed medical records of breast cancer patients who had HER2 testing by fluorescence in stitu hybridization (FISH) and immunohistochemistry (IHC) performed or verified at The University of Texas MD Anderson Cancer Center during April 2014 through March 2018 and had equivocal results according to the 2013 ASCO/CAP guideline. The population was divided into 2 cohorts according to whether the biopsy specimen analyzed came from primary or from recurrent or metastatic disease. HER2 status was reclassified according to the 2018 ASCO/CAP guideline. Overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier method, and the relationship between anti-HER2 therapy and clinical outcomes was assessed. Results We identified 139 cases with HER2-equivocal results according to the 2013 ASCO/CAP guideline: 90 cases of primary disease and 49 cases of recurrent/metastatic disease. Per the 2018 ASCO/CAP guideline, these cases were classified as follows: overall, HER2-negative 112 cases (80%), HER2-positive 1 (1%), and unknown 26 (19%); primary cohort, HER2-negative 85 (94%), HER2-positive 1 (1%), unknown 4 (4%); and recurrent/metastatic, HER2-negative 27 (55%) and unknown 22 (45%). Five patients in the primary-disease cohort and 1 patient in the recurrent/metastatic-disease cohort received anti-HER2 therapy. There was no significant association between anti-HER2 therapy and OS or EFS in either cohort (primary disease: OS, p = 0.67; EFS, p = 0.49; recurrent/metastatic-disease, OS, p = 0.61; EFS, p = 0.78. Conclusions The majority of HER2-equivocal breast cancer cases were reclassified as HER2-negative per the 2018 ASCO/CAP guideline. No association between anti-HER2 therapy and OS or EFS was observed. HER2-equivocal cases seem to have clinical behavior similar to that of HER2-negative breast cancers.

Expression of hormone receptors ERα, ERβ and PgR in HER2-positive breast cancers

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10525-10525
Author(s):  
M. Litwiniuk ◽  
V. Filas ◽  
J. Moczko ◽  
R. Kaleta ◽  
J. Breborowicz
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Detection System ◽  
Statistical Significance ◽  
Her2 Status ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

10525 Background: HER-2/neu gene is amplified and overexpressed in 15–20% of invasive breast cancers. HER2-positive breast cancers have a worse prognosis than HER2-negative tumors and distinctive clinical features. They express hormone receptors for estrogen (ERα) and for progesterone (PgR) less frequently than HER2-negative tumors. The identification of the other human estrogen receptor, receptor beta (ERβ), raises a question of ERβ occurrence in HER2-positive breast cancer. Patients and methods: Formalin-fixed, paraffin embedded tissues from 90 patients with invasive HER2-positive breast cancer and from 99 patients with HER2-negative breast cancer were used in this study. The HER2 status was analyzed using HercepTest TM (IHC), and IHC 2+ results were confirmed with FISH test. Immunostaining for ERα, ERβ and PgR was performed using monoclonal antibodies against ERα, PgR (DakoCytomation) and against ERβ (CHEMICON). The EnVision detection system was applied. The data were analyzed using nonparametric Fisher-Freeman-Halton test; the statistical significance was considered when p < 0.5. Results: Only 33% of the HER2-positive breast cancers were ERα-positive compared with 63% in the HER2-negative group (p < 0.001). The expression of ERβ protein was observed in almost equal frequency in both groups (57% of HER2-positive breast cancers and 57.7% of HER2-negative tumors, p = 0.889). The expression of PgR was observed in 30% of HER2-positive breast cancers and in 68.7% of HER2-negative tumors (p < 0.001). Conclusion: The expression of ERβ (unlike that of ERα and PgR) was similar in HER2-positive and in HER2-negative breast cancers. Thus, ERβ may be a potential target in future endocrine therapy for women with HER2-positive breast cancers. No significant financial relationships to disclose.

scholarly journals Microvessel Density and Mammaglobin A Expression as Prognostic Markers in Molecular Types of Breast Cancer

2019 ◽  
Vol 70 (7) ◽  
pp. 2671-2676
Author(s):  
Adriana Andreea Jitariu ◽  
Amalia Raluca Ceausu ◽  
Adriana Meche ◽  
Cristian Nica ◽  
Amelia Burlea ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Microvessel Density ◽  
Ductal Carcinoma ◽  
Hot Spot ◽  
Histopathological Diagnosis ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Mean Values

Increased microvessel density (MVD) values in breast cancer correlate with tumor growth and progression while mammaglobin (MGB) expression in tumor cells is associated with a favorable prognosis. We aim to evaluate and correlate MVD values with MGB expression in molecular types of breast cancer specimens and to determine their utility as prognostic biological markers. A number of 52 breast cancer specimens were included in the study. Specimens were processed for routine histopathological diagnosis followed by the molecular classification by means of estrogen (ER), progesterone (PR) and HER2 immunohistochemical reactions. After performing immunohistochemistry for CD34 and MGB, MVD evaluation was made using the �hot spot� method for each case and MGB was scored between 0 (negative) and +3 (strong positive) depending on the intensity and distribution of the staining. MGB expression in tumor cells and MVD mean values were extremely variable. The greatest MVD mean values were obtained in luminal B followed by HER2, luminal A and triple negative breast cancer (TNBC) (95.33, 69, 62, and 40, respectively). MGB expression in the tumor cells generally ranged from mild to weak and was strong only in a few invasive ductal carcinoma cases. In cases with TNBCs the expression of MGB in tumor cells was weak and focal or negative. This variability was noticed between the molecular types of breast cancers and even within the same molecular type. In a restricted number of cases, MGB positive tumors were associated with low MVD values while the negative cases were characterized by increased MVD mean values. The variable results we obtained regarding the correlation between MVD and MGB in breast cancer specimens may indicate a rather restricted use of MVD/MGB in estimating breast cancer patients� prognosis.

Profiling receptor tyrosine kinase fusions in Chinese breast cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15092-e15092
Author(s):  
Zhonghua Tao ◽  
Xichun Hu ◽  
Wen-Ming Cao ◽  
Jianxia Liu ◽  
Ting Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinase ◽  
Cancer Patients ◽  
Tyrosine Kinases ◽  
Breast Cancer Subtype ◽  
Stage Iv ◽  
Tyrosine Kinase Domain ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive

e15092 Background: Receptor tyrosine kinases (RTKs) are a class of tyrosine kinases that regulate cell-to-cell communication and control a variety of complex biological functions. Dysregulation of RTK signaling partly due to chromosomal rearrangements leads to novel tyrosine kinase fusion oncoproteins which are possibly driver alterations to cancers. Targeting some RTK fusions with specific tyrosine kinases inhibitors (TKIs) is an effective therapeutic strategy across a spectrum of RTK fusion-related cancers. However, there is still a paucity of extensive RTK fusion investigations in breast cancer. We aimed to characterize RTK fusions in Chinese breast cancer patients. Methods: An in-house sequencing database of 1440 Chinese breast cancer patients using a 520-gene NGS sequencing panel was thoroughly reviewed. RTK fusion was defined as an in-frame fusion with the tyrosine kinase domain of the RTK completely retained with the only exception of ERBB2 fusion which was not counted due to its unclear significance. Concomitant mutations and TMB were also analyzed and calculated. Patients’ clinical characteristics were retrieved from case records. Results: 27 RTK fusion-positive breast cancers (12 tissues + 15 plasmas) were identified, patients had a median age of 52 years. Triple-negative breast cancer subtype comprised 37% with luminal and HER2 positive subtypes being 40.8% and 22.2%, respectively. 77.8% of patients were at stage IV and 22.2% at stage I-III. Ten were treatment naïve. RTK fusions occurred in 2% of breast cancers in our database, compared with the prevalence of 0.6% and 1.3% in MSKCC and TCGA, respectively. In the subset of stage IV patients, our database showed a significantly higher RTK fusion frequency than that in MSKCC (3.2% vs. 0.6%, p = 0.013). FGFR2 fusions were seen most commonly (n = 7), followed by RET (n = 4), ROS1 (n = 3), NTRK3 (n = 3), BRAF (n = 2), and NTRK1 (n = 2). Other RTK fusions including ALK, EGFR, FGFR1, FGFR3, MET, and NTRK2 were identified in one patient each. Of note, the normalized abundance of RTK fusion (fusion AF/max AF) correlated negatively with TMB (r = -0.48, p = 0.017). Patients with TMB < 4 (Muts/Mb) displayed a higher fusion abundance than those with TMB ≥ 4 (Muts/Mb) (p = 0.018), suggesting a higher likelihood of subclonal nature for RTK fusions in TMB-high patients. Moreover, CREBBP mutation only co-occurred with FGFR2 fusion (p = 0.012), while NTRK3 fusion and TP53 mutation were mutually exclusive (p = 0.019). Conclusions: This is the first study comprehensively delineating the prevalence and spectrum of RTK fusions in Chinese breast cancers. Further study is ongoing to identify the enriched subpopulation which may benefit from RTK fusion inhibitors.

Comparison of HER2 Status by Fluorescence in Situ Hybridization and Immunohistochemistry to Predict Benefit From Dose Escalation of Adjuvant Doxorubicin-Based Therapy in Node-Positive Breast Cancer Patients

2005 ◽  
Vol 23 (19) ◽  
pp. 4287-4297 ◽  
Author(s):  
Lynn G. Dressler ◽  
Donald A. Berry ◽  
Gloria Broadwater ◽  
David Cowan ◽  
Kelly Cox ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Cancer Patients ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Node Positive ◽  
Positive Breast Cancer

Purpose HER2 is a clinically important tumor marker in breast cancer; however, there is controversy regarding which method reliably measures HER2 status. We compared three HER2 laboratory methods: immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR), to predict disease-free survival (DFS) and overall survival (OS) after adjuvant doxorubicin-based therapy in node-positive breast cancer patients. Methods This is a Cancer and Leukemia Group B (CALGB) study, using 524 tumor blocks collected from breast cancer patients registered to clinical trial CALGB 8541. IHC employed CB11 and AO-11-854 monoclonal antibodies; FISH used PathVysion HER2 DNA Probe kit; PCR utilized differential PCR (D-PCR) methodology. Results Cases HER2 positive by IHC, FISH and D-PCR were 24%, 17%, and 18%, respectively. FISH and IHC were clearly related (κ = 64.8%). All three methods demonstrated a similar relationship for DFS and OS. By any method, for patients with HER2-negative tumors, there was little or no effect of dose of adjuvant doxorubicin-based therapy. For patients with HER2-positive tumors, all three methods predicted a benefit from dose-intense (high-dose) compared with low- or moderate-dose adjuvant doxorubicin-based therapy. Conclusion FISH is a reliable method to predict clinical outcome following adjuvant doxorubicin-based therapy for stage II breast cancer patients. There is a moderate level of concordance among the three methods (IHC, FISH, PCR). None of the methods is clearly superior. Although IHC-positive/FISH-positive tumors yielded the greatest interaction with dose of therapy in predicting outcome, no combination of assays tested was statistically superior.

Early-stage male breast cancer: A 10-year experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11630-e11630
Author(s):  
N. Gercovich ◽  
E. Gil Deza ◽  
M. Russo ◽  
C. Garcia Gerardi ◽  
C. Diaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Male Breast Cancer ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Male Breast ◽  
Stage I ◽  
Stage Ii ◽  
Breast Cancers ◽  
Breast Cancer Patients

e11630 Introduction: Male breast cancer is very rare, representing only between 0.7% and 1% of all breast cancers, and only half of them are early stage cases. Objective: The present study has been designed with the aim of studying retrospectively the clinical onset and evolution of male invasive breast cancer patients (stages I and II) treated at IOHM between 1997 and 2008. Methods: The records of 3,000 breast cancer cases followed between 1997 and 2008 were searched, looking for male stage I and II breast cancer patients. A database was designed following the recommendations of the Directors of Surgical Pathology of the USA. The information registered encompassed: adjuvant treatments, recurrence date and date of final consultation or death. Results: Twelve pts were identified. Mean age (range)= 66 yo (50–89 yo). Tumoral type= Invasive Ductal Carcinoma 12 pt. Tumoral subtype= NOS 9 pt (75%) Apocrine 2 pt (17%) Micropapillar 1 pt (8%). Nottingham´s grade= Grade 2: 8 pt, Grade 3: 3 pt, N/A=1 pt. Stage= I= 6 pt, II=6 pt. ER (Positve= 9 pt, Negative=1 pt, N/A= 2 pt). PR (Positve= 8 pt, Negative= 2 pt, N/A=2 pt). Her2neu (0+= 3 pt, 1+= 3 pt, 2+= 2 pt, N/A= 4 pt). Surgery= Mastectomy= 11 pt, Lumpectomy 1= pt. Radiotherapy=5 pt. Adjuvance= No=2 pt, Hormonotherapy (HT)= 3 pt, Chemotherapy (CHT) = 3 pt, CHT+HT= 4 pt. Recurrence= Yes= 2 pt, No= 10 pt. Survival: Dead= 1 pt, Alive =11 pt. Mean Time To Progression= Stage I =66 months, Stage II =42 months. Global survival: Stage I =66 months, Stage II =52 months. Conclusions: 1. Twelve stage I and II male breast cancer patients were identified out of 3000 (0.4%) breast cancer cases diagnosed and followed in the past 10 years at the IOHM. 2. Mastectomy was the surgical procedure in 11 of the 12 cases 3. Ten pt underwent adjuvant treatment. 4. With a mean follow up time of 60 months, all stage I patients are alive and there were no recurrences. Two of the 6 stage II pts progressed and one died. No significant financial relationships to disclose.

Utilization of anti-HER2 regimens among HER2-positive metastatic breast cancer patients.

2020 ◽  
Vol 38 (29_suppl) ◽  
pp. 282-282
Author(s):  
Sandhya Mehta ◽  
Jinlin Song ◽  
Melissa Pavilack ◽  
Jipan Xie ◽  
Xiaoyu Nie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Targeted Therapies ◽  
Metastatic Breast ◽  
Cancer Registries ◽  
Additional Treatment ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Her2 Positive

282 Background: HER2-positive (+) metastatic breast cancer (mBC) has a poor prognosis and many patients require multiple lines of HER2 targeted regimens. This study aims to examine the treatment sequencing of anti-HER2 regimens for HER2+ mBC among Medicare beneficiaries. Methods: A retrospective study was conducted using linked 1999-2016 Surveillance, Epidemiology, and End Results (SEER) cancer registries and Medicare claims. Adults patients who had mBC diagnosis, HER2+ status documented in SEER or claims of ≥1 anti-HER2 drug, continuous enrollment in Medicare from the date of mBC diagnosis until end of study period/death, and 2 anti-HER2 regimens with or without chemotherapy (Ch) or hormonal therapy (HT) were included. Discontinuation of anti-HER2 regimen was defined as the absence of claims for all anti-HER2 drugs for >60 days, or initiation of a different anti-HER2 drug. Re-initiation of the same regimen after >60 days was considered as a new regimen. The first two anti-HER2 regimens and subsequent therapies were summarized. Results: 804 patients with 2 anti-HER2 regimens were included. Trastuzumab (T) based regimen (defined as: T±Ch/HT; without other anti-HER2 drugs) was the most common 1st regimen (82%), followed by T+ pertuzumab (P) (14%) and lapatinib (L) (3%). For the 2nd regimen, T (52%) was most common, followed by T+P (18%), L (11%), trastuzumab emtansine (T-DM1) (11%) and T+L (7%). After a 2nd regimen, 578 (72%) initiated a subsequent therapy, with over half switching to non-targeted therapies [52%; HT alone (35%), Ch±HT (17%)] followed by T (17%), T-DM1 (12%) and T+P (7%). Among those with subsequent therapy, 2 T-based regimens followed by HT alone (21%) was the most common sequence. After the 1st regimen, 52% patients reused the same anti-HER2 drugs in the 2nd regimen, 21% added another anti-HER2 drug and 27% switched to a different anti-HER2 regimen. After the 2nd regimen, 14% reused anti-HER2 drugs and 6% added another anti-HER2 drug, 25% switched to a different anti-HER2 regimen; 15% reused anti-HER2 drugs from the 1st regimen. Conclusions: Trastuzumab based regimen was the mainstay of anti-HER2 drug regimens during the study timeframe. Despite availability of multiple anti-HER2 drugs, reuse of prior anti-HER2 drugs and switching to non-targeted therapies alone were common after using 2 anti-HER2 regimens. These findings underscore the unmet needs in later lines of therapy. Recently approved anti-HER2 agents may provide additional treatment options for pre-treated HER2+ metastatic breast cancer patients.

scholarly journals Combining CD47 blockade with trastuzumab eliminates HER2-positive breast cancer cells and overcomes trastuzumab tolerance

2021 ◽  
Vol 118 (29) ◽  
pp. e2026849118
Author(s):  
Rosalynd Upton ◽  
Allison Banuelos ◽  
Dongdong Feng ◽  
Tanuka Biswas ◽  
Kevin Kao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibody ◽  
Cancer Patients ◽  
Early Stage ◽  
Regulatory Protein ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Gene ◽  
Her2 Positive

Trastuzumab, a targeted anti-human epidermal-growth-factor receptor-2 (HER2) monoclonal antibody, represents a mainstay in the treatment of HER2-positive (HER2+) breast cancer. Although trastuzumab treatment is highly efficacious for early-stage HER2+ breast cancer, the majority of advanced-stage HER2+ breast cancer patients who initially respond to trastuzumab acquire resistance to treatment and relapse, despite persistence of HER2 gene amplification/overexpression. Here, we sought to leverage HER2 overexpression to engage antibody-dependent cellular phagocytosis (ADCP) through a combination of trastuzumab and anti-CD47 macrophage checkpoint immunotherapy. We have previously shown that blockade of CD47, a surface protein expressed by many malignancies (including HER2+ breast cancer), is an effective anticancer therapy. CD47 functions as a “don’t eat me” signal through its interaction with signal regulatory protein-α (SIRPα) on macrophages to inhibit phagocytosis. Hu5F9-G4 (magrolimab), a humanized monoclonal antibody against CD47, blocks CD47’s “don’t eat me” signal, thereby facilitating macrophage-mediated phagocytosis. Preclinical studies have shown that combining Hu5F9-G4 with tumor-targeting antibodies, such as rituximab, further enhances Hu5F9-G4’s anticancer effects via ADCP. Clinical trials have additionally demonstrated that Hu5F9-G4, in combination with rituximab, produced objective responses in patients whose diffuse large B cell lymphomas had developed resistance to rituximab and chemotherapy. These studies led us to hypothesize that combining Hu5F9-G4 with trastuzumab would produce an anticancer effect in antibody-dependent cellular cytotoxicity (ADCC)-tolerant HER2+ breast cancer. This combination significantly suppressed the growth of ADCC-tolerant HER2+ breast cancers via Fc-dependent ADCP. Our study demonstrates that combining trastuzumab and Hu5F9-G4 represents a potential new treatment option for HER2+ breast cancer patients, even for patients whose tumors have progressed after trastuzumab.

Long-term follow-up and factors of survival of HER-2 positive breast cancer patients treated either by neoadjuvant trastuzumab docetaxel (TAXHER-S01 study) or by neoadjuvant trastuzumab docetaxel carboplatin (GETN[A]1 study)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11507-e11507
Author(s):  
L. Favier ◽  
M. Liegard ◽  
S. Guiu ◽  
I. van Praagh ◽  
R. Largillier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Rank Test ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Weekly Docetaxel ◽  
Metastatic Relapse ◽  
Positive Breast Cancer

e11507 Background: Almost 20% of breast cancers over express Her2, which is associated with a more aggressive phenotype and with a decreased survival. Nevertheless, trastuzumab (T) has been a revolutionary step in the adjuvant and in the metastatic treatments of Her2 positive breast cancers. Here, we focus on neoadjuvant T and try to determine the factors correlating with disease free survival and with overall survival in Her2 positive breast cancer treated with T based neoadjuvant chemotherapy. Methods: Data from two published T based neoadjuvant phases II were used: the TAX-HER trial which studied the use of 6 courses of 3 weekly docetaxel with weekly neoadjuvant T (scheme TH) (Coudert et. al. Annals of Oncology 2006) and the GET(N)A-1 trial which studied the use of 6 courses of 3 weekly docetaxel and carboplatin along with weekly neoadjuvant T (scheme TCH) followed by 3 weekly adjuvant T (Coudert et. al. JCO 2007). Moreover, additional patients from our institution and treated by neoadjuvant TH and adjuvant T were included. Survival curves were estimated using Kaplan-Meier methods and compared by log-rank test. Results: Data was available for 128 patients. 62 patients (48.4%) received neoadjuvant TH from whom 39 did not receive adjuvant T. 66 (51.6%) received neoadjuvant TCH and adjuvant T. Tumors characteristics were as followed: 65 (50.7%) SBR 1–2, 54 (42.19%) SBR 3, 49 (38.28%) hormonal receptors (RH) negative and 72 (56.25%) RH positive. The rate of pathological complete response (pCR) (Chevalier 1/2) was 39.6%. Overall survival (OS) for the entire cohort was 74,8 months. Relapse was defined as local, regional, metastatic relapse or death. Survival without relapse (SR) was 74.8 months. No difference was noted in OS and in SR according to the type of chemotherapy, TH or TCH. pCR did significantly influence SR (p = 0. 03) and survival without local recurrence (SLR) (p = 0.04) but neither OS nor survival without metastatic relapse (SMR). Multivariate analysis demonstrated that OS was correlated with node response (as defined by sataloff grade NA or NB) (p=0.0275) and the use of hormonal therapy in RH positive tumors (p=0.0724). [Table: see text]

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