Histone acetylation is thought to facilitate binding of transcription factors (TFs) to specific target DNA sequences by destabilizing nucleosomes bound to the promoter region of a target gene. In addition, non-histone proteins including a subset of TFs and co-activators are acetylated by p300/CBP and P/CAF. The regulation of estrogen signaling by direct estrogen receptor alpha (ERα) post-translational modification reveals a novel role for histone acetyltransferase in hormone signaling. ERα is acetylated and phosphorylated and phosphorylation occurs at multiple sites in response to kinase signaling. The finding that mutations with the ERα hinge domain lysine residues enhance hormone sensitivity suggests these residues may be involved in ligand-dependent transcriptional repression or transcriptional attenuation. Phosphorylation and acetylation of the ER regulates hormone signaling and is being assessed for a role in resistance to anti-estrogen therapy of ERα-positive patients.

Chemoprevention with tamoxifen and oophorectomy are thought to be effective in decreasing the incidence of breast cancer in women at increased risk for the disease. There is mounting data supporting the idea that hormonal interventions that reduce estrogen exposure to breast epithelium, such as prophylactic oophorectomy and tamoxifen, are effective in breast cancer prevention in both BRCA1 and BRCA2 mutations carriers. Several recent studies directly address the protective effect of tamoxifen and oophorectomy in BRCA mutation carriers and suggest that these endocrine manipulations decrease the risk of primary and secondary breast cancers. Ongoing studies aim to better define the effect of tamoxifen in these very high-risk women and determining whether factors, such as earlier age of use or prior prophylactic oophorectomy, impact tamoxifen's effect. Based on existing data, we recommend that women with deleterious mutations in BRCA1 or BRCA2 be informed of the beneficial effect of oophorectomy on breast cancer risk and that women who choose breast cancer screening instead of prophylactic mastectomy be offered tamoxifen as a prevention option.

Physicians are testing minimally invasive ablation techniques to determine if they will be acceptable substitutes for surgical removal of primary breast tumors. In radiofrequency ablation (RFA), frictional heating of the tissue is caused by the rapid movement of ions attempting to follow a high frequency alternating current moving between two electrodes. Localization of a small electrode in the tumor is accomplished under ultrasound guidance, and a larger electrode pad is placed on the outside of the body. Five pilot studies have demonstrated that RFA can effectively ablate tumors up to 3 cm in size. In addition to treating small primary tumors, RFA may also be useful for consolidation therapy after lumpectomy, for treatment of inoperable tumors in end-stage patients, for treatment of locally advanced disease as a substitute for neoadjuvant chemotherapy, and for treatment of breast cancer metastases, such as bone, liver, and kidney. Clinical trials are needed to assess treatment outcomes and to monitor the long-term fate of ablated tissue.