Male breast cancer: correlation between immunohistochemical subtyping and PAM50 intrinsic subtypes, and the subsequent clinical outcomes.

Male breast cancer is a rare disease that is still poorly understood. It is mainly classified by immunohistochemistry as a luminal disease. In this study, we assess for the first time the correlation between molecular subtypes based on a validated six-marker immunohistochemical panel and PAM50 signature in male breast cancer, and the subsequent clinical outcome of these different subtypes. We collected 67 surgical specimens of invasive male breast cancer from four different Spanish pathology laboratories. Immunohistochemical staining for the six-marker panel was performed on tissue microarrays. PAM50 subtypes were determined in a research-use-only nCounter Analysis System. We explored the association of immunohistochemical and PAM50 subtypes. Overall survival and disease-free survival were analyzed in the different subtypes of each classification. The distribution of tumor molecular subtypes according PAM50 was: 60% luminal B, 30% luminal A and 10% human epidermal growth factor receptor 2 (Her2) enriched. Only one Her2-enriched tumor was also positive by immunohistochemistry and was treated with trastuzumab. None of the tumors were basal-like. Using immunohistochemical surrogates, 51% of the tumors were luminal B, 44% luminal A, 4% triple-negative and 1% Her2-positive. The clinicopathological characteristics did not differ significantly between immunohistochemical and PAM50 subtypes. We found a significant worse overall survival in Her2-enriched compared with luminal tumors. Male breast cancer seems to be mainly a genomic luminal disease with a predominance of the luminal B subtype. In addition, we found a proportion of patients with Her2-negative by immunohistochemistry but Her2-enriched profile by PAM50 tumors with a worse outcome compared with luminal subtypes that may benefit from anti-Her2 therapies.

Role of germline variants in the metastasis of breast carcinomas.

Most cancer-related deaths in breast cancer patients are associated with metastasis, a multistep, intricate process that requires the cooperation of tumour cells, tumour microenvironment and metastasis target tissues. It is accepted that metastasis does not depend on the tumour characteristics but the host's genetic makeup. However, there has been limited success in determining the germline genetic variants that influence metastasis development, mainly because of the limitations of traditional genome-wide association studies to detect the relevant genetic polymorphisms underlying complex phenotypes. In this work, we leveraged the extreme discordant phenotypes approach and the epistasis networks to analyse the genotypes of 97 breast cancer patients. We found that the host's genetic makeup facilitates metastases by the dysregulation of gene expression that can promote the dispersion of metastatic seeds and help establish the metastatic niche-providing a congenial soil for the metastatic seeds.

Serum protein levels following surgery in breast cancer patients: a protein microarray approach.

Surgery is the primary treatment for non-metastatic breast cancer. However, the risk of early recurrence remains after surgical removal of the primary tumor. Recurrence is suggested to result from hidden micrometastatic foci, which are triggered to escape from dormancy by surgical resection of the primary tumor. In this study, we focused on the differential impact of breast surgery on the serum profiles of early breast cancer patients and healthy women. Serum samples from invasive breast cancer patients, in situ carcinoma breast cancer patients and healthy women were analyzed using reverse phase protein array technology. Samples were collected prior to breast surgery and 24 h following breast surgery. Both the expression level and the velocity of 42 serum proteins were quantified and compared among groups. We found that surgery increased the concentration of several proteins (CSF1, THSB2, IL6, IL7, IL16, FasL and VEGF-B) in the overall population. Compared with healthy women and patients with non-invasive tumors, invasive tumor patients exhibited higher preoperative levels of several serum proteins, such as αFP, IFNß1, VEGF-A, IL18, E-cadherin or CD31, and lower postoperative levels of TNFα and IL5. Similarly, we detected significant surgery-induced changes in the velocity of VEGF-A and IL16 accumulation in samples derived from invasive breast cancer patients. In conclusion, breast surgery induced distinct changes in the concentrations and dynamics of serum proteins in invasive breast cancer patients compared with healthy women and non-invasive tumor patients.