ESR1 and p53 interactome alteration defines mechanisms of tamoxifen response in luminal breast cancer.

The canonical mechanism behind tamoxifen's therapeutic effect on estrogen receptor α/ESR1+ breast cancers is inhibition of ESR1-dependent estrogen signaling. Although ESR1+ tumors expressing wild-type p53 were reported to be more responsive to tamoxifen (Tam) therapy, p53 has not been factored into choice of this therapy and the mechanism underlying the role of p53 in Tam response remains unclear. In a window-of-opportunity trial on patients with newly diagnosed stage I-III ESR1+/HER2/wild-type p53 breast cancer who were randomized to arms with or without Tam prior to surgery, we reveal that the ESR1-p53 interaction in tumors was inhibited by Tam. This resulted in functional reactivation of p53 leading to transcriptional reprogramming that favors tumor-suppressive signaling, as well as downregulation of oncogenic pathways. These findings illustrating the convergence of ESR1 and p53 signaling during Tam therapy enrich mechanistic understanding of the impact of p53 on the response to Tam therapy.

Syringomatous Tumor of the Nipple.

Syringomatous tumor of the nipple (SyT), previously known as syringomatous adenoma of the nipple (SAN) was originally described in 1983 as a rare benign tumor of the sweat duct. It is a rare benign tumor arising from the skin adnexal eccrine glands that can be misdiagnosed as invasive carcinoma due to its infiltrative nature, resulting in overtreatment. We report clinical, histopathologic, and surgical findings of a case of infiltrating syringomatous adenoma in a 40-year-old female as well as a literature review of previous cases. A high index of suspicion is required to make the diagnosis of SyT and prevent overtreatment.

A Presurgical-Window Intervention Trial of Isothiocyanate-Rich Broccoli Sprout Extract in Patients with Breast Cancer.

SCOPE: Dietary isothiocyanates (ITCs) from cruciferous vegetables have shown potent anti-breast cancer activities in preclinical models, but their anticancer effects in vivo in breast cancer patients remain elusive. A proof-of-principle, presurgical window of opportunity trial is conducted to assess the anticancer effects of dietary ITCs in breast cancer patients. METHODS AND RESULTS: Thirty postmenopausal breast cancer patients are randomly assigned to receive ITC-rich broccoli sprout extract (BSE) (200 µmol ITC per day) or a placebo for 2 weeks. Expression of biomarkers related to ITCs functions are measured in breast cancer tissue specimens at pre- and post-interventions using immunohistochemistry staining. First morning urine samples are collected at both timepoints for proteomic analysis. Overall, the study shows high compliance (100%) and low toxicity (no grade 4 adverse event). Trends of increase in cleaved caspase 3 and tumor-infiltrating lymphocytes (TILs) and trends of decrease in Ki-67 and nuclear to cytoplasm ratio of estrogen receptor (ER)-α are observed in the BSE arm only, consistent with the significantly altered signaling pathways identified in urinary proteomic analysis. CONCLUSIONS: Anticancer activities of ITCs are observed in breast cancer patients, supporting the potential beneficial roles of ITC-containing cruciferous vegetables in breast cancer prognosis.

Breast Implant-Associated Anaplastic Large Cell Lymphoma (ALCL): A Case Report.

BACKGROUND Anaplastic large cell lymphomas (ALCL) are a rare type of primary breast lymphoma. The association between breast implants and ALCL was first described in 1997 and since then 34-173 cases have been presented. The annual incidence of breast implant-associated ALCL (BI-ALCL) is 0.1-0.3 per 100 000 women who undergo breast reconstruction, and cases are often underreported due to the rarity of these tumors. BI-ALCL arises from the inflammatory T cells surrounding the fibrous capsule, and most tumors are in situ. CASE REPORT Here, we present the case of a 51-year-old woman with ALCL following bilateral silicone breast implants. The patient presented with breast enlargement and tenderness 9 years following reconstructive surgery. Imagining studies showed fluid collection surrounding the affected breast implant. Staging studies and histocytopathology examination confirmed the presence BI-ALCL without capsular invasion or metastasis. Complete surgical excision was performed. The patient continues to be in complete remission. CONCLUSIONS Due to the rarity of these tumors, establishing the diagnosis of BI-ALCL can be challenging and requires a multidisciplinary approach. Clinicians should be aware of the relationship between breast implants and BI-ALCL.

Systemic Hypothermia as Treatment for an Acute Cervical Spinal Cord Injury in a Professional Football Player: 9-Year Follow-Up.

The following report provides clinical follow-up on a National Football League player who sustained a complete cervical spinal cord injury (SCI) while tackling an opposing player in 2007. He received prompt medical and surgical care based on then-current recommendations, but was also treated with systemic hypothermia soon after his injury, which was controversial at the time. Since then, smaller randomized human studies have described the tolerable safety profile, efficacy, and potential benefits of this intervention in acute SCI in humans. Now, modest systemic hypothermia can be one of many tools considered in the treatment of acute SCI. Before it can become the standard of care, however, additional larger prospective randomized studies need to be completed. The patient described in this article had long-term excellent clinical results, with residual deficits of occasional tingling in fingertips and toe tips, although the patient continues to slowly improve.

Impact of American College of Surgeons Oncology Group Z11 on surgical training at an academic cancer center.

BACKGROUND: The application of the American College of Surgeons Oncology Group Z0011 trial (Z11) has resulted in fewer completion axillary lymph node dissections (ALNDs) for select patients. We hypothesize that the application of Z11 may result in fewer ALND cases for surgeons in training. METHODS: In the setting of an academic cancer center incorporating Z11 into routine practice, we compared the total number of ALND performed in a pre-Z11 period (January 2007-April 2011, 52 mo) and post-Z11 period (April 2011-February 2014, 34 mo). We also identified the number of patients in the post-Z11 era in whom ALND was omitted as a result of Z11. Clinical and pathologic characteristics among these groups were analyzed. RESULTS: A total of 279 and 191 ALNDs were performed in the pre-Z11 and post-Z11 groups, respectively. Variables were similar among these groups with respect to demographics, tumor characteristics, and surgeries performed. There was no difference in the monthly rates of ALND between groups-5.37 cases/mo (pre-Z11) and 5.62 cases/mo (post-Z11), P = 0.52. We identified a total of 53 patients for whom ALND was omitted due to Z11 application in the post-Z11 period, representing a potential 21.7% decrease (53/191 + 53) in the number of ALNDs in this period. CONCLUSIONS: Although the application of Z11 could potentially impact surgical training with a 21.7% decrease in ALND cases (53/191 + 53), the surgical case volume at an academic cancer center absorbs this decrease and maintains consistent levels of training for ALND.

Systemic hypothermia for the treatment of acute cervical spinal cord injury in sports.

Spinal cord injury is a devastating condition that affects approximately 12,000 patients each year in the United States. Major causes for spinal cord injury include motor vehicle accidents, sports-related injuries, and direct trauma. Moderate hypothermia has gained attention as a potential therapy due to recent experimental and clinical studies and the use of modest systemic hypothermia (MSH) in high profile case of spinal cord injury in a National Football League (NFL) player. In experimental models of spinal cord injury, moderate hypothermia has been shown to improve functional recovery and reduce overall structural damage. In a recent Phase I clinical trial, systemic hypothermia has been shown to be safe and provide some encouraging results in terms of functional recovery. This review will summarize recent preclinical data, as well as clinical findings that support the continued investigations for the use of hypothermia in severe cervical spinal cord injury.

The use of systemic hypothermia for the treatment of an acute cervical spinal cord injury in a professional football player.

STUDY DESIGN: Case Report. OBJECTIVE: We will describe the injury and clinical course of an NFL Football player who sustained a complete spinal cord injury and was treated with conventional care in addition to modest systemic hypothermia. SUMMARY OF BACKGROUND DATA: Systemically induced moderate hypothermia is a potentially neuroprotective intervention in acute spinal cord injury. However, case descriptions of human patients receiving systemic hypothermia after spinal cord injuries are lacking in the literature. METHODS: Here, we present the case of a National Football League player who sustained a complete (ASIA A) spinal cord injury from a C3/4 fracture dislocation. Moderate systemic hypothermia was instituted immediately after his injury, in addition to standard medical/surgical treatment, including, surgical decompression and intravenous methylprednisolone. RESULTS: The patient experienced significant and rapid neurologic improvement, and within weeks of his injury was walking with harness assistance. Since that time, the patient has continued to make significant progress in his rehabilitation (now ASIA D). CONCLUSION: The extent to which this hypothermia contributed to his neurologic recovery is difficult to determine. It is hoped that this case will draw attention to the need for further preclinical and clinical studies to elucidate the role of hypothermia in acute spinal cord injury. Until these studies are completed, it is impossible to advocate for systemic hypothermia as a standard of care.