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

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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Importance of confirming HER2 overexpression of recurrence lesion in breast cancer patients

Breast Cancer ◽

10.1007/s12282-012-0341-6 ◽

2012 ◽

Vol 20 (4) ◽

pp. 336-341 ◽

Cited By ~ 17

Author(s):

Rikiya Nakamura ◽

Naohito Yamamoto ◽

Yasuhide Onai ◽

Yoshihiro Watanabe ◽

Hidetada Kawana ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Her2 Overexpression ◽

Breast Cancer Patients

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Outcomes of HER2-positive nonmetastatic breast cancer patients with or without deleterious BRCA mutations after trastuzumab treatment.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e12550 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e12550-e12550

Author(s):

Aimaz Afrough ◽

Heather Lin ◽

Angelica M. Gutierrez-Barrera ◽

Jennifer Keating Litton ◽

Vicente Valero ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Brca Mutation ◽

Disease Free Survival ◽

Metastatic Breast ◽

Her2 Overexpression ◽

Breast Cancer Patients ◽

Her2 Positive ◽

Brca Mutations ◽

Her2 Breast Cancer

e12550 Background: Human epidermal growth factor receptor (HER2) overexpression or amplification occurs in 20–25% of all breast cancers and is associated with an aggressive form of the disease with reduced disease-free survival (DFS) and overall survival (OS). However, the outcome of patients with HER2+ tumor and BRCA mutation is poorly described. The purpose of this analysis was to analyze the clinical and pathological features and outcomes of patients with HER2+ breast cancer regards to their BRCA status. Methods: Patients who were referred for genetic counseling between 2004-2012 and who had a HER2+ breast cancer treated with trastuzumab were included in our analysis. Patients were considered Her2+ if immunohistochemistry was 3+ or had a ratio of ≥2 by FISH. Patients with metastatic breast cancer at diagnosis were excluded. Clinical and pathological and outcome data was extracted from a prospectively maintained research data base after IRB approval was obtained. Results: Ninety-four patients were identified. The median age at diagnosis was 39 years (range 21 – 58). The majority of the patients were White (76%). Tumors were invasive ductal carcinoma in 89% and had nuclear grading of 3 in 76% of patients. Hormone receptors were positive in 66% and BRCA 1 or 2 mutations were positive in 16% (N=15). The majority of the patients were treated with a combination of Anthracyclines plus Taxanes (76%). All patients received trastuzumab in the neoadjuvant or adjuvant setting. After a median follow-up of 4.4 years, OS and DFS in all patients were 97% and 88%, respectively. Three HER2-positive breast cancer patients had died (3.2 %). Recurrence had occurred in 11 patients; all of these patients were BRCA negative. OS and DFS of patients with BRCA mutations were then compared with OS and DFS of patients without BRCA mutation (both 100% vs. 96% and 81.9%, respectively). There was no statistically significant survival difference in BRCA mutation carriers compared with non-carriers (p=0.362). Conclusions: The presence of a BRCA mutation does not seem to offer prognostic information in this population. Further investigation with larger cohort are needed for confirmation.

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