scholarly journals Tumor-associated autoantibodies from mouse breast cancer models are found in serum of breast cancer patients

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sasha E. Stanton ◽  
Ekram Gad ◽  
Erik Ramos ◽  
Lauren Corulli ◽  
James Annis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transgenic Mouse ◽  
Mammary Tumor ◽  
Tumor Antigens ◽  
Ductal Carcinoma ◽  
Breast Tumors ◽  
Breast Cancer Patients ◽  
Tumor Models ◽  
Her2 Positive ◽  
Mouse Mammary Tumor

AbstractB cell responses to tumor antigens occur early in breast tumors and may identify immunogenic drivers of tumorigenesis. Sixty-two candidate antigens were identified prior to palpable tumor development in TgMMTV-neu and C3(1)Tag transgenic mouse mammary tumor models. Five antigens (VPS35, ARPC2, SERBP1, KRT8, and PDIA6) were selected because their decreased expression decreased survival in human HER2 positive and triple negative cell lines in a siRNA screen. Vaccination with antigen-specific epitopes, conserved between mouse and human, inhibited tumor growth in both transgenic mouse models. Increased IgG autoantibodies to the antigens were elevated in serum from women with ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC). The autoantibodies differentiated women with DCIS from control with AUC 0.93 (95% CI 0.88–0.98, p < 0.0001). The tumor antigens identified early in the development of breast cancer in mouse mammary tumor models were conserved in human disease, and potentially identify early diagnostic markers in human breast tumors.

Uncommon breast malignancies: Presentation pattern, treatment options and outcome in a single Institution experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22174-e22174
Author(s):  
C. Bareggi ◽  
D. Consonni ◽  
B. Galassi ◽  
D. Gambini ◽  
E. Locatelli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Treatment Options ◽  
Radical Mastectomy ◽  
Breast Tumors ◽  
Conservative Surgery ◽  
Stage I ◽  
Stage Ii ◽  
Breast Cancer Patients ◽  
Tubular Carcinoma

e22174 Background: Uncommon breast tumors are often neglected by large clinical trials, even if their incidence is not so low. Methods: We investigated stage, treatment and outcome of 112 patients affected by uncommon breast cancer, out of 2,185 breast cancer patients diagnosed and followed in our Institution from January 1985 to October 2008. Results: Rare subtypes were represented as follows: tubular 2.7% (58 pts), mucinous 1.1% (25 pts), medullary 1% (21 pts), papillary 0.4% (8 pts). Median age at diagnosis was 56.5 years among patients with tubular histotype, 68.9 years for mucinous, 55 and 61.7 years for medullary and papillary, respectively. Stage I tumors were 87.7% among patients with tubular differentiation, 60% for mucinous, 26.3% for medullary and 50% for papillary, (compared to 45.7% in invasive ductal carcinoma: 1,626 pts). Stage II represented 12.3% among patients with tubular carcinoma, 32% for mucinous, 57.9% for medullary and 37.5% for papillary. Surgical option for stage I and stage II was usually conservative surgery (quadrantectomy, lumpectomy) plus local radiotherapy, followed by estrogenic blockade. In stage III radical mastectomy was often performed, followed by hormonal suppression. Median DFS for patients with tubular cancer was 4.1 years, for mucinous 3.7 years, 10.5 and 5.1 years for medullary and papillary, respectively. Median OS for patients with tubular cancer was 4.3 years, whereas for mucinous 4.2 years, for medullary 11 years and 5.3 years for papillary. Conclusions: In our retrospective analysis, uncommon breast tumors are often diagnosed at limited stages, resulting in good prognosis, with standard treatment. Further studies are warranted for a better management of these diseases. No significant financial relationships to disclose.

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.

Combination trastuzumab and chemotherapy to induce immunity to multiple tumor antigens in patients with HER2-positive metastatic breast cancer: NCCTG (Alliance) studies N0337 and N98-32-52.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 521-521 ◽  
Author(s):  
Raphael Clynes ◽  
Keith L. Knutson ◽  
Karla V. Ballman ◽  
Courtney L. Erskine ◽  
Nadine Norton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Combination Therapy ◽  
Tumor Antigens ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Multiple Tumor ◽  
Her2 Breast Cancer

521 Background: The addition of trastuzumab to chemotherapy improves responses to therapy and extends survival among patients with metastatic HER2 breast cancer. Several mechanisms have been proposed for the activity of this combination therapy. Trastuzumab, specifically, is thought to activate NK cells and blunt HER2 signaling. Prior work from us has shown that combination trastuzumab and chemotherapy induces HER2-specific antibodies which correlate with response to therapy. Despite that, it remains unclear whether the immunity that was induced was due to complexing of non-tumor derived HER2 or antigen derived from the tumor site. In the present work, we addressed this question by assessing if combination therapy induced epitope spreading to tumor antigens other than HER2. Methods: Pre-and post-treatment sera were obtained from 56 women enrolled in 2 NCCTG clinical trials, N0337 and 98-32-52. IgG antibodies to HER2 intracellular domain (HER2), p53, IGFBP2, CEA and tetanus toxoid (TT) were examined using ELISAs. Sera from an age-matched group (N=56) of controls and 12 patients treated in the adjuvant setting were also examined. Results: Prior to therapy, metastatic patients had higher IgG levels (≥ 2-fold) to p53 and HER2 but not CEA, IGFBP2 and TT, relative to the controls. Similarly, adjuvant patients had elevated IgGs to multiple tumor antigens prior to therapy, relative to controls. Following therapy, levels of IgG to IGFBP2, HER2, and p53 increased in 81% of metastatic patients, with mean increases of 3.2 (±0.6 sem), 6.2 (±2.7) and 2.7 (±0.7) fold, respectively (p<0.05). Levels of antibodies to TT and CEA were not elevated by treatment. In contrast, IgGs were not increased in adjuvant patients; consistent with the idea that immunity depends on the presence of threshold levels of antigens. Conclusions: These results show that combination treatment induces adaptive immunity to antigens released by tumor and that metastatic patients remain capable of responding immunologically to their cancer. Thus, in metastatic breast cancer patients, combination trastuzumab and chemotherapy may behave as a vaccine.

Antibodies reactive with the mouse mammary tumor virus in sera of breast cancer patients

1980 ◽  
Vol 25 (6) ◽  
pp. 721-725 ◽  
Author(s):  
Steven S. Witkin ◽  
Nurul H. Sarkar ◽  
David W. Kinne ◽  
Robert A. Good ◽  
Noorbibi K. Day
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Mammary Tumor ◽  
Mouse Mammary Tumor Virus ◽  
Breast Cancer Patients ◽  
Mammary Tumor Virus ◽  
Mouse Mammary Tumor ◽  
Tumor Virus

scholarly journals Heterogeneity of genomic profile in patients with HER2-positive breast cancer

2020 ◽  
Vol 27 (3) ◽  
pp. 153-162 ◽  
Author(s):  
Bo Chen ◽  
Guochun Zhang ◽  
Guangnan Wei ◽  
Yulei Wang ◽  
Liping Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Somatic Mutation ◽  
Breast Tumors ◽  
Molecular Heterogeneity ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Mutation Profile ◽  
Positive Breast Cancer

HER2-positive breast cancer is a biologically and clinically heterogeneous disease. Based on the expression of hormone receptors (HR), breast tumors can be further categorized into HR positive and HR negative. Here, we elucidated the comprehensive somatic mutation profile of HR+ and HR− HER2-positive breast tumors to understand their molecular heterogeneity. In this study, 64 HR+/HER2+ and 43 HR-/HER2+ stage I-III breast cancer patients were included. Capture-based targeted sequencing was performed using a panel consisting of 520 cancer-related genes, spanning 1.64 megabases of the human genome. A total of 1119 mutations were detected among the 107 HER2-positive patients. TP53, CDK12 and PIK3CA were the most frequently mutated, with mutation rates of 76, 61 and 49, respectively. HR+/HER2+ tumors had more gene amplification, splice site and frameshift mutations and a smaller number of missense, nonsense and insertion-deletion mutations than HR-/HER2+ tumors. In KEGG analysis, HR+/HER2+ tumors had more mutations in genes involved in homologous recombination (P = 0.004), TGF-beta (P = 0.007) and WNT (P = 0.002) signaling pathways than HR-/HER2+ tumors. Moreover, comparative analysis of our cohort with datasets from The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium revealed the distinct somatic mutation profile of Chinese HER2-positive breast cancer patients. Our study revealed the heterogeneity of somatic mutations between HR+/HER2+ and HR-/HER2+ in Chinese breast cancer patients. The distinct mutation profile and related pathways are potentially relevant in the development of optimal treatment strategies for this subset of patients.

The Effect of Biology in the Treatment of Small Breast Tumors

2013 ◽  
pp. 25-31
Author(s):  
Jose Perez-Garcia ◽  
Eva Muñoz-Couselo ◽  
Javier Cortes
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Breast Tumors ◽  
Molecular Characteristics ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Node Negative ◽  
Screening Programs ◽  
Small Breast ◽  
Number Of Patients

Although the outcome of small (T1a/b) node-negative breast tumors is generally excellent, in the absence of prospective clinical trials, we are limited to data derived from retrospective analyses. Overall, the 10-year overall mortality rate is approximately 20%, while the 10-year breast cancer-specific mortality is in the range of 4% to 8% among this population in the absence of systemic therapy. This clearly reflects that many patients die of causes not related to breast cancer. Due in large part to breast cancer screening programs, the incidence of small tumors is increasing. There is consequently a growing interest in identifying factors that negatively affect the prognosis of these patients. Several studies have shown that patients with triple-negative and HER2+ tumors have a worse prognosis compared with hormone-receptor–positive, HER2- small breast cancers. However, the recent explosion of knowledge of the molecular characteristics of tumors is opening a new way to address cancer. Different genomic assays are currently available to help better predict the outcome of breast cancer patients. However, none of these techniques have been specifically evaluated in patients with small (T1a/b) node-negative tumors, and only a small number of patients with these tumors were included in those studies. In addition, very limited data are available about the role of these assays in patients with triple-negative or HER2-positive cancers. Although a chemotherapy-based strategy might be useful for triple-negative or HER2-positive T1b tumors, more information is urgently needed in order to optimize the treatment of our patients.

Quantitative HER2 levels and steroid receptor expression in primary breast cancers and in matched brain metastases.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 603-603 ◽  
Author(s):  
Wojciech Biernat ◽  
Renata Duchnowska ◽  
Tomasz Trojanowski ◽  
Tomasz Mandat ◽  
Anna Kowalczyk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Breast Tumors ◽  
Steroid Receptor ◽  
Receptor Expression ◽  
Nuclear Staining ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Primary Tumors

603 Background: Breast cancer patients with HER2-positive tumors are at high risk for brain metastases. In the current study we examined expression of ER, PR and HER2 in primary breast tumors and in matched brain metastases, as changes of their levels might reflect modes of escape from therapy. Methods: Fifty-three pairs of matched formalin-fixed paraffin-embedded samples from primary breast cancers and brain metastases were assayed for ER and PR status by immuno-histochemistry, whereas HER2 expression was quantified using the novel HERmark assay. Nuclear staining of ER and PR >10%, and relative fluorescence of HER2 >17.8/mm2 were considered as positive results. Results: HER2 levels in brain metastases were generally higher than in the primary tumors (p = 3e-6), with a median increase of 1.9-fold (range 0.08 to 199-fold). There were also substantial differences in ER and PR status between primary tumors and brain metastases. Loss of steroid receptor positivity in brain metastases was more frequent than its gain (ER: 46% vs. 26%; p = 0.16; PR: 57% vs. 23%; p = 0.044). These changes resulted in a net increase in the number of HER2-positive/ER-negative brain metastases, which more than doubled the proportion of primary breast tumors with this phenotype (26% vs. 11%, respectively; p = 0.08). Additionally, HER2 levels in the primary tumors significantly correlated with overall survival when stratified by ER status (p = 0.011). Conclusions: Brain metastases of breast cancer show significant changes in steroid receptor status and in quantitative HER2 levels compared to matched primary tumors. These data provide a rationale for future studies and may help in designing treatment strategies that target the most likely escape pathways of breast cancer.

Nine-weeks of adjuvant trastuzumab in HER2-positive breast cancer: A single center experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11080-e11080
Author(s):  
Cemal Kizilarslanoglu ◽  
Ibrahim Petekkaya ◽  
Taner Babacan ◽  
Kadri Altundag
Keyword(s):  
Breast Cancer ◽  
Survival Data ◽  
Ductal Carcinoma ◽  
Breast Cancer Patients ◽  
Survival Times ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Trastuzumab Therapy ◽  
One Year ◽  
Positive Breast Cancer

e11080 Background: Trastuzumab is an effective adjuvant targeted therapy in patients with HER-2 positive breast cancer. However, effect of this therapy on survival is not well described in literature. In this study, we aimed to show characteristics of patients treated with nine week trastuzumab therapy for breast cancer and survival analysis. Methods: We analyzed the data of 2.218 breast cancer patients treated and followed up in our medical oncology department. There were 165 patients treated with 9 weeks of adjuvant trastuzumab therapy in this cohort. Patients’ characteristics, prognostic factors, and survival data were analyzed by using SPSS 18.0 version. Results: The mean age of the patients at the time of diagnosis of breast cancer was 47.3 ± 10.0 years. Sixty two (37.6%) patients were postmenopausal, eighty two patients (49.7%) were premenopausal and twenty patients (12.1%) were peri-menopausal. Invasive ductal carcinoma was the most common pathological type and was observed in 87.9% of the patients. ER and PR was positive in 49.1% of the patients and 54.5 % of the patients, respectively. Percentage of stage of the patients was 10.9 in stage I, 21.1 in stage IIA, 17.6 in stage IIB, 21.2 in stage IIIA, 0.6 in stage IIIB, 23.6 in stage IIIC. Mean follow up time of the patients was 30.9 ± 13.4 months. Numbers of the patients with progression were eighteen (10.9%). Eight (4.8%) patients died due to disease progression. Two-year survival rate was 98.3%. Disease free, progression free and overall survival times could not be obtained due to inadequate number of events. Conclusions: The superiority of nine weeks of adjuvant trastuzumab therapy to standard one year regimen of adjuvant trastuzumab is not well described in literature. The studies comparing 9-weeks and one year of adjuvant trastuzumab use with large numbers of patients are needed to show which regimen is superior.

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