https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(06)68226-3.pdf

Male breast cancer

The anti–human epidermal growth factor receptor 2 (HER2/neu) antibody trastuzumab is administered to patients with HER2/neu-overexpressing breast cancer. Whole-body noninvasive HER2/neu scintigraphy could help to assess and quantify the HER2/neu expression of all lesions, including nonaccessible metastases. The aims of this study were to develop clinical-grade radiolabeled trastuzumab for clinical HER2/neu immunoPET scintigraphy, to improve diagnostic imaging, to guide antibody-based therapy, and to support early antibody development. The PET radiopharmaceutical 89Zr-trastuzumab was compared with the SPECT tracer 111In-trastuzumab, which we have tested in the clinic already. Methods: Trastuzumab was labeled with 89Zr and (for comparison) with 111In. The minimal dose of trastuzumab required for optimal small-animal PET imaging and biodistribution was determined with human HER2/neu-positive or -negative tumor xenograft–bearing mice. Results: Trastuzumab was efficiently radiolabeled with 89Zr at a high radiochemical purity and specific activity. The antigen-binding capacity was preserved, and the radiopharmaceutical proved to be stable for up to 7 d in solvent and human serum. Of the tested protein doses, the minimal dose of trastuzumab (100 μg) proved to be optimal for imaging. The comparative biodistribution study showed a higher level of 89Zr-trastuzumab in HER2/neu-positive tumors than in HER2/neu-negative tumors, especially at day 6 (33.4 ± 7.6 [mean ± SEM] vs. 7.1 ± 0.7 percentage injected dose per gram of tissue). There were good correlations between the small-animal PET images and the biodistribution data and between 89Zr-trastuzumab and 111In-trastuzumab uptake in tumors (R2 = 0.972). Conclusion: Clinical-grade 89Zr-trastuzumab showed high and HER2/neu-specific tumor uptake at a good resolution.

https://jnm.snmjournals.org/content/jnumed/50/6/974.full.pdf

Development and characterization of clinical-grade 89Zr-trastuzumab for HER2/neu immunoPET imaging.

Trastuzumab is a monoclonal antibody used for the treatment of metastatic breast carcinoma in women whose tumors overexpress the HER2 protein. Cardiotoxicity has been reported to occur with trastuzumab when administered alone and in combination with antineoplastic agents, particularly anthracyclines. The risk of cardiotoxicity with trastuzumab has been reported to be 4% with monotherapy and 27% when administered in combination with an anthracycline and cyclophosphamide, but to the author's knowledge severe outcomes, such as death or permanent disability, are uncommon. The majority of reported cardiac effects are mild to moderate, nonspecific, and medically manageable. Signs and symptoms are similar to those observed in patients who develop anthracycline-induced cardiomyopathy and include tachycardia, palpitations, and exertional dyspnea, which may progress to congestive heart failure. The pathogenesis and histologic changes responsible for trastuzumab-associated cardiotoxicity currently are under investigation. Unlike anthracycline-induced toxicity, trastuzumab-associated toxicity usually responds to standard treatment or the discontinuation of trastuzumab, and there is no evidence that the toxicity is dose related. Current methods for the early detection of cardiotoxicity in trastuzumab-treated patients are similar to those used in anthracycline-treated patients. Cardiac function is established at baseline and monitored regularly during treatment by physical examination and measurement of left ventricular ejection fraction. The majority of patients improve with proper treatment, and some are able to continue to receive trastuzumab.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.10854

Trastuzumab‐associated cardiotoxicity

The clinical utility of a human epidermal growth factor receptor 2 (HER2)-targeting Affibody molecule for detection and characterization of HER2-positive lesions was investigated in patients with r ...

https://jnm.snmjournals.org/content/jnumed/51/6/892.full.pdf

Molecular Imaging of HER2-Expressing Malignant Tumors in Breast Cancer Patients Using Synthetic 111In- or 68Ga-Labeled Affibody Molecules

Male breast cancer incidence is 1% of all breast cancers and is increasing. We aim to present an overview of male breast cancer with particular emphasis on clinical management. Studies were identified by an online search of literature in the MEDLINE database till June 2006 followed by an extensive review of bibliographies. Increased risk factors include genetic predisposition as in BRCA2 families; testicular dysfunction due to chromosomal abnormality such as Klinefelter’s syndrome or environmental factors such as chronic heat exposure and radiation. Clinical assessment with biopsy is the hallmark of diagnosis. Earlier presentations are becoming commoner but there are wide geographical differences. Surgical treatment involves simple or modified radical mastectomy along with surgical assessment of the axilla, either via sentinel node biopsy in clinically node-negative disease or axillary sampling/clearance in node-positive disease. Reconstructions for restoring body image have been recently reported. Indications for adjuvant therapies are similar to that in women. For metastatic disease, tamoxifen is still the mainstay for oestrogen receptor positive disease. For oestrogen receptor negative disease, doxorubicin based chemotherapy regimens are used. In addition, the oft neglected psychological aspects of men having a “cancer of women” are increasingly being recognised. There is, thus, need for further increasing awareness among men to reduce stigma associated with presentation of symptoms related to breast. This should be in addition to stressing to clinicians the ways of earlier detection and tailor-made “gender oriented” treatment of breast cancer in men.

Male breast cancer: a review of clinical management

Trastuzumab and breast cancer.

Novel mouse models of Myd88-driven DLBCL serve as preclinical platforms to evaluate combined BTK/BCL2 inhibition and immune-therapeutic approaches.

https://doi.org/10.1158/2643-3230.bcd-22-0007

Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies

MammaPrint® 10-Year Follow Up Results from a German Breast Cancer Cohort Study

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Trastuzumab and breast cancer.

Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies

MammaPrint® 10-Year Follow Up Results from a German Breast Cancer Cohort Study