The molecular profile of breast cancer patients according to the presence of HER2 overexpression.

197 Background: There is a wide variation of compliance with National Comprehensive Cancer Network (NCCN) guidelines for diagnosis and treatment. Overutilization of preoperative testing and underutilization of adjuvant treatments have been documented. The former is associated with higher costs of care; the latter with poor patient outcomes. Prior reports of adherence to NCCN Guidelines contain methodological limitations due to lack of contemporary review and incomplete listing of reasons for non-compliance. This limits the “real time” analysis of breast cancer quality and delays action plans to address quality and cost issues of care. Methods: NCCN Guideline compliance was recorded prospectively by use of electronic synoptic templates for all newly diagnosed breast cancer patients treated at a single institution between January 2010 and December 2011. A retrospective review of the synoptic templates was then conducted. Accuracy of the synoptic auditing method was assessed as well as NCCN compliance and reasons for non-compliance. Results: A total of 312 new breast cancer patients who underwent surgery as initial treatment were identified. Compliance with NCCN Guidelines for preoperative testing, breast surgery and lymph node surgery was 98% (306/312), 99.7% (311/312) and 93% (290/312) respectively. Reasons for non-compliance include patient refusal, comorbidities, advanced age and overutilization of systemic imaging. There was 100% compliance to College of American Pathologist (CAP) molecular profile documentation for all breast cancer cases. There were two discrepancies noted between the prospective template reporting and medical record review. The average time needed to populate data into synoptic templates was less than 2 minutes per patient. Conclusions: Prospective auditing of adherence to NCCN Guidelines with electronic synoptic templates is accurate and time efficient. High compliance rates with NCCN Guidelines were demonstrated. Electronic synoptic NCCN templates potentially facilitate early recognition of quality gaps in compliance and provide a framework for peer performance comparison.

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Mutational status and thromboembolic risk in lung, gastrointestinal and breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e23147 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e23147-e23147

Author(s):

Marco Platania ◽

Federico Nichetti ◽

Filippo G. De Braud

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Clinical Manifestations ◽

Gene Mutations ◽

Molecular Profile ◽

Breast Cancer Patients ◽

Vein Thrombosis ◽

Mutational Status ◽

Cancer Associated Thrombosis ◽

Low Prevalence

e23147 Background: Cancer-Associated Thrombosis (CAT) is one of the most threatening complications of cancer. Recent evidences suggested a link between the molecular profile of solid tumors and the incidence of CAT. The aim of this study was to explore the relationship between the mutational status of breast, lung and gastrointestinal cancer patients and the risk of CAT. Methods: We retrospectively evaluated the molecular profile, analysed as per clinical practice, of all consecutive patients hospitalized at the National Cancer Institute’s Department in Milan from October 2017 to November 2018. Patients with previous thromboembolic events and patients under anticoagulant therapy at cancer diagnosis were excluded. Due to death as competing risk, the Fine and Gray proportional regression model was used to detect statistical association and estimate relative risk. Results: The resulting cohort consisted of 484 patients, of whom 47% had gastrointestinal cancers, 18% had lung cancer and 15% had breast cancer. Molecular investigations were available for 375 (77%) patients; in particular, a 50-gene Next Generation Sequencing (NGS) panel was performed on 148 (31%) patients. After a median follow up of 17 months, 118 patients (24%) exhibited clinical manifestations of thrombosis (i.e. deep vein thrombosis, pulmonary thromboembolism, splanchnic thrombosis, disseminated intravascular coagulation, arterial thrombosis) and 117 (24%) patients deceased without thrombotic events. A statistically significant association was observed between incidence of CAT and presence of TP53 (HR 0.50, p = 0.04), c-KIT (HR 4.30, p = 0.041), and SMAD4 (HR 3.19, p = 0.029) mutations. No significant association was detected for KRAS and MET gene mutations, even if HRs were >2. Conclusions: In this study, the mutational status of TP53, SMAD4 and c-KIT genes was statistically associated to the risk of thrombosis. Due to methodological limits and low prevalence of mutations, large prospective studies are warranted, with the aim of better defining the role of oncogenes in CAT risk.

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Postmastectomy radiotherapy after neoadjuvant chemotherapy in cT1-2N+ breast cancer patients: a single center experience and review of current literature

10.21203/rs.3.rs-1201823/v1 ◽

2022 ◽

Author(s):

Meng Luo ◽

Huihui Chen ◽

Hao Deng ◽

Yao Jin ◽

Gui Wang ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Cox Regression ◽

Medical Center ◽

Clinical Stage ◽

Disease Free Survival ◽

Her2 Overexpression ◽

Breast Cancer Patients ◽

Significant Difference

Abstract PurposePostmastectomy radiotherapy (PMRT) after NAC in breast cancer patients with initial clinical stage cT1−2N+, especially for those who achieved ypT1−2N0, is still controversial. This study was to evaluate the survival prognosis of cT1−2N+ patients after NAC with or without PMRT, and to discuss the selection of patients who may omit PMRT.Patients and MethodsFrom January 2005 to December 2017, 3055 female breast cancer patients underwent mastectomy in our medical center, among whom 215 patients of cT1−2N+ stage, receiving neoadjuvant chemotherapy (NAC) with or without PMRT were finally analyzed. The median follow-up duration was 72.6 months. The primary endpoint was overall survival, and the secondary endpoint was disease-free survival. Comparison was conducted between PMRT and non-PMRT subgroups.ResultsOf the 215 eligible patients, 35.8% (77/215) cT1−2N+ patients achieved ypT0−2N0 after NAC while 64.2% (138/215) of the patients remained nodal positive (ypT0−2N+). The 5-year DFS of ypT0−2N0 non-PMRT was 79.5% (95% confidence interval [CI] 63.4-95.6%). No statistically significant difference was observed between the ypT0−2N0 PMRT and non-PMRT subgroups for the 5-year DFS (78.5% vs 79.5%, p = 0.673) and OS (88.8% vs 90.8%, p = 0.721). The 5-years DFS didn’t obviously differ between the ypT0−2N0 non-PMRT subgroup and cT1−2N0 subgroup (79.5% vs 93.3%, p = 0.070). By using Cox regression model in multivariate analyses of prognosis in ypT0−2N+ PMRT subgroup, HER2 overexpression and triple-negative breast cancer were significantly poor predictors of DFS and OS, while ypN stage was significant independent predictors of OS.ConclusionAn excellent response to NAC (ypT0−2N0) indicates a sufficiently favorable prognosis, and PMRT might be omitted for cT1−2N+ breast cancer patients with ypT0−2N0 after NAC.

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2026849118 ◽

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.

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Correlation of HER2 overexpression evaluated by fluorescence in situ hybridization with response to docetaxel-based first-line chemotherapy in advanced breast cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.1124 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 1124-1124

Author(s):

A. Cavazzana ◽

A. Camerini ◽

R. Prosperi Porta ◽

F. De Luca ◽

N. Decarli ◽

...

Keyword(s):

Breast Cancer ◽

In Situ Hybridization ◽

Advanced Breast Cancer ◽

Fluorescence In Situ Hybridization ◽

Cancer Patients ◽

Her2 Overexpression ◽

Breast Cancer Patients ◽

First Line ◽

Line Chemotherapy

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Morphological pattern of MR mammography in breast cancer patients with HER2 overexpression.

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.15_suppl.e11038 ◽

2010 ◽

Vol 28 (15_suppl) ◽

pp. e11038-e11038

Author(s):

A. Artmann ◽

N. A. Boehm ◽

I. Laemmer-Skarke ◽

K. Annecke ◽

M. Settles ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Her2 Overexpression ◽

Mr Mammography ◽

Breast Cancer Patients ◽

Morphological Pattern

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Limitations in assessment of ER, PR, and HER2 status of breast cancer patients: Yangon experience.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e11078 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e11078-e11078

Author(s):

Yin Yin Mon

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Advanced Technology ◽

Molecular Profile ◽

Molecular Testing ◽

Breast Cancer Patients ◽

Financial Problem ◽

Lack Of Information ◽

Number Of Patients ◽

Her 2

e11078 Background: Management of breast cancer become individualized nowadays especially in developed countries. Molecular profile of breast cancer is essential to have this management. However, there are still limitations to examine such molecular profile in developing countries like Myanmar. Our aim in this study is to know the number of patients who underwent ER, PR and HER 2 status assessment among breast cancer patients in Myanmar and to analyze types of limitations for the molecular assessment in management of breast cancer. Methods: Total number of 823 breast cancer patients who registered from January 2009 to December 2011 at Medical Oncology Unit of Yangon General Hospital and two private oncology clinics were studied. Results: The age range from 19-80 years and mean age of 44.36 years. Among 823 breast cancer patients, ER, PR and HER 2 status were done in 134 patients (16.28% ) whereas 689 patients( 83.71% ) were not. 604 (87.66%) out of 689 patients who did not undergo profiling were due to financial problem. 60 patients (8.70 %) were found to have lack of information about molecular profiling although they were affordable . 25 patients (3.62 %) lost their tissue due to technological limitation Conclusions: Financial problem is the major limitation to get molecular profile for breast cancer patients in Myanmar. Patients need self expense to do advanced technology examinations in different health care system of our country. In this study we also found out that there was lack of information which leads not to undergo further investigations to some well to do patients. Overall, we believe that molecular technology support with reduced expense will help more patients in future to get better management in breast cancer in Myanmar. Besides, we need to provide update information about molecular testing in breast cancer to not only patients but also health professionals in our country.

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