Cutaneous adverse effects of hormonal adjuvant therapy for breast cancer: a case of localised urticarial vasculitis following anastrozole therapy and a review of the literature.

Hormonal therapy with either tamoxifen or aromatase inhibitors is commonly used to treat women with breast cancer in both the adjuvant and recurrent disease setting. Cutaneous adverse reactions to these drugs have been rarely reported in the literature. We report an unusual case of urticarial vasculitis following the aromatase inhibitor anastrozole that localised to the unilateral trunk and mastectomy scar, and review the literature on the cutaneous adverse effects of hormonal therapy for breast cancer.

Hotspot mutation of Brahma in non-melanoma skin cancer.

Mammalian SWItch/sucrose non fermentable (SWI/SNF) remodeling of chromatin modulates transcription and DNA repair. The Brahma (BRM) catalytic subunit of the SWI/SNF complex is one of two mutually exclusive subunits that provide energy for remodeling. BRM has been identified as an important cancer susceptibility locus; however, to date no mutations have been identified in the BRM gene. We performed genetic analysis of BRM in human non-melanoma skin cancers, precancerous lesions, and normal skin revealing a common nonsynonymous point mutation present in one of ten squamous cell and two of six basal cell carcinoma of the skin. This hotspot was not present in germ-line DNA from the same patients, nor in epithelial precancerous lesions. The observed G:C to T:A transversion is typical of mutations occurring following oxidative damage, such as that caused by UVA radiation. This previously unreported hotspot mutation occurs in a highly conserved region of the BRM gene.

SWI/SNF: a chromatin-remodelling complex with a role in carcinogenesis.

SWI/SNF is a chromatin-remodelling complex that makes DNA that has been compacted into nucleosomes accessible to transcription factors and repair enzymes. It does this by displacing DNA from the core histone surface. SWI/SNF consists of at least nine subunits, including one of two alternative ATPase subunits, BRM or BRG-1, that provide the energy for remodelling. As it regulates access to DNA it controls many aspects of normal cellular function. Limited studies have recently linked loss of function of SWI/SNF subunits to cancer development, suggesting that it may be a tumor suppressor complex. As epigenetic repression regulates SWI/SNF component expression at least in some cases, restoration of function is therapeutically promising for cancer treatment. Considerably more research is required into deregulation of SWI/SNF in cancer and determination of how this affects tumor development. This is an exciting but poorly understood molecule that may have a role in carcinogenesis.