Breast Cancer Following Radiation for Hodgkin Lymphoma: Clinical Scenarios and Risk-Reducing Strategies.

Since most patients with Hodgkin lymphoma survive their disease, long-term issues such as development of second primary malignancies arise, especially in patients treated with multimodal therapy including radiation therapy plus chemotherapy. The risk of breast cancer is significantly elevated in women exposed to high-dose ionizing radiation to the chest before age 40. The case of a 48-year-old patient with a lump in her right breast is presented as a clinical scenario in this article. We review available strategies for screening and risk reduction through chemoprevention or risk-reducing surgery, as well as challenges for management of breast cancer in patients with prior exposure to radiation for Hodgkin lymphoma. The Children's Oncology Group clinical practice guidelines for long-term follow-up care of pediatric cancer survivors provide recommendations that have been endorsed by American and European oncologists.

Hepatic complications of breast cancer.

Hepatic disease associated with breast cancer is common and can result from metastatic spread of the tumour to the liver, or can be caused by systemic treatment with chemotherapeutic or antiendocrine agents. Metastatic disease to the liver can present clinically and pathologically in various ways. Little is known as to why breast cancer can sometimes present as liver dominant disease or with liver involvement as a late event in the disease course. However, there are many postulations involving metastasis organotropism, which might offer future insight. The mainstay of treatment for hepatic metastases continues to be systemic therapy, but several locoregional adjunct therapies exist. Despite these therapies, liver metastasis from breast cancer is associated with a poor prognosis. Ongoing research of the mechanisms and tropism of liver metastasis from breast cancer will hopefully result in improved targeted therapies to reduce their incidence and improve outcomes when they arise.

Early-stage BRCA2-linked breast cancer diagnosed in the first trimester of pregnancy associated with a hypercoagulable state.

This patient was found to have a BRCA2 gene mutation. She underwent lumpectomy and axillary lymph node dissection without any evidence of lymph node metastasis. Systemic chemotherapy with doxorubicin and cyclophosphamide for four cycles was administered beginning in the second trimester. She was treated with prophylactic LMWH until delivery and then for 6 weeks postpartum. She delivered a healthy baby boy and, after a period of breast-feeding, underwent bilateral mastectomy with immediate reconstruction. She remains well and is expecting her second child. Prophylactic oophorectomy is planned after completion of this pregnancy.

Immunomodulatory therapy in multiple sclerosis and breast cancer risk: a case report and literature review.

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system frequently complicated by devastating neurologic symptoms and progressive disability. Much progress has been made in the development of immunomodulating drugs to help fight the progression of MS. These drugs are believed to work by interacting with various immune system components to reduce the amount of autoimmune destruction to the nervous system. We report 2 cases of women with MS on immunomodulatory therapy who presented with locally advanced breast cancer with aggressive biologic phenotypes and exceptionally poor outcomes. We consider the potential for an increased risk of developing a poorer-prognosis breast cancer as a result of concomitant immunomodulatory effects of the previous MS treatment, particularly the effects the drugs are reported to have on regulatory T cells, and therefore present these cases and a review of the current literature. Current data in the literature reflect the need for further study in ascertaining the risk of biologically poor-prognosis breast cancer development in patients with MS treated with immunomodulatory therapy.

Expression of vascular endothelial growth factor and proliferation marker MIB1 are influenced by neoadjuvant chemotherapy in locally advanced breast cancer.

Neoadjuvant chemotherapy (NACT) has become the standard of care for patients with locally advanced breast cancer (LABC). This was a retrospective review of 21 consecutive women who received NACT as initial treatment of LABC, followed by surgical excision. The pre- and post-treatment breast specimens and post-treatment axillary lymph nodes with metastases were immunostained to evaluate for proliferative index (PI) (MIB-1 Immunotech) and vascular endothelial growth factor (VEGF) expression (Santa Cruz, CA, clone A-20). Thirteen of the 21 patients (62%) had more than 50% tumor shrinkage following NACT. The breast's mean PI decreased from 47.86% to 23.95% after treatment (P = 0.005). The mean PI in the post-treatment lymph nodes was 24.47%. A nodal post-NACT PI of less than 10% and progesterone receptor-positive tumor status were associated with better survival, as all such patients are alive. A high PI after NACT was associated with recurrence or death. All of the patients who showed an excellent clinical response had either a decrease in the PI or an absence of a high level of VEGF after NACT. Most patients exhibited persistent expression of VEGF after NACT. Pathologic response in the primary tumor did not correlate with the response in the lymph nodes or with overall survival. NACT reduces the size and PI of the primary breast tumor independent of the patient's node status. The PI may be an early means by which to identify tumors most likely to reduce in size with chemotherapy. A low PI after NACT is associated with better survival. There is persistent expression of VEGF in post-NACT residual breast carcinoma. Thus, anti-VEGF drugs after conventional chemotherapy may benefit patients with residual carcinoma.

Enhanced insulin signaling via Shc in human breast cancer.

Insulin is a mild mitogen and has been shown to potentiate mitogenic influence of other growth factors. Because hyperinsulinemia and/or overexpression of insulin receptors have been linked to development, progression, and outcome of breast cancer, we attempted to evaluate the mechanism of these associations. We have compared the expression of insulin receptors and the magnitude of insulin signaling in breast tumors and adjacent normal mammary tissue samples obtained from 20 patients. We observed that insulin binding more than doubled in the tumors as compared with the normal tissue (P <.01 by paired t test). Insulin signaling to Shc, judged by the magnitude of its phosphorylation, was also significantly enhanced in the tumors. In contrast, the phosphorylation of the insulin-receptor substrate-1 (IRS-1), Akt, and mitogen-activated protein (MAP) kinase were identical in the tumorous and normal mammary tissues. Finally, tumors displayed significantly increased amounts of farnesylated p21 Ras and geranylgeranylated Rho-A (P <.01), consistent with Shc-dependent activation of farnesyl (FTase) and geranylgeranyl transferases (GGTase) in the tumor tissue. We conclude that the mechanism of the mitogenic influence of insulin in breast cancer may include increased expression of insulin receptors, preferential hyperphosphorylation of Shc, and increased amounts of prenylated p21 Ras and Rho-A in tumor tissue as compared with adjacent normal mammary tissue.

Urachal carcinoma: key points for the general surgeon.

Urachal carcinoma is a rare neoplasm with the majority of cases reported in the urologic literature. Because of its presentation as an intra-abdominal mass with involvement of adjacent structures the general surgeon may be consulted early in the diagnostic evaluation. One should be aware of this entity as early recognition and appropriate surgery provides the best opportunity for long-term survival. Herein we describe a typical case, appropriate evaluation, and review of the literature.