Society of Surgical Oncology Breast Disease Site Working Group Statement on Bilateral Risk-Reducing Mastectomy: Indications, Outcomes, and Risks.

Bilateral risk-reducing mastectomy (BRRM) is the surgical removal of both breasts to reduce the risk of cancer. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, outcomes, and risks of BRRM to update the society's 2017 statement. We held a virtual meeting to outline key topics and conducted a literature search using PubMed to identify relevant articles.

The Trimeric Autotransporter Adhesin EmaA and Infective Endocarditis.

Infective endocarditis (IE), a disease of the endocardial surface of the heart, is usually of bacterial origin and disproportionally affects individuals with underlying structural heart disease. Although IE is typically associated with Gram-positive bacteria, a minority of cases are caused by a group of Gram-negative species referred to as the HACEK group. These species, classically associated with the oral cavity, consist of bacteria from the genera (excluding ), , , , and .

Dual function of the O-antigen WaaL ligase of Aggregatibacter actinomycetemcomitans.

Protein glycosylation is critical to the quaternary structure and collagen-binding activity of the extracellular matrix protein adhesin A (EmaA) associated with Aggregatibacter actinomycetemcomitans. The glycosylation of this large, trimeric autotransporter adhesin is postulated to be mediated by WaaL, an enzyme with the canonical function to ligate the O-polysaccharide (O-PS) antigen with a terminal sugar of the lipid A-core oligosaccharide of lipopolysaccharide (LPS). In this study, we have determined that the Escherichia coli waaL ortholog (rflA) does not restore collagen binding of a waaL mutant strain of A.

Regulation of adhesin synthesis in Aggregatibacter actinomycetemcomitans.

Aggregatibacter actinomycetemcomitans is a gram-negative bacterium associated with periodontal disease and a variety of disseminated extra-oral infections. Tissue colonization is mediated by fimbriae and non-fimbriae adhesins resulting in the formation of a sessile bacterial community or biofilm, which confers enhanced resistance to antibiotics and mechanical removal. The environmental changes experienced by A.

The serotype a-EmaA adhesin of does not require O-PS synthesis for collagen binding activity.

, a causative agent of periodontitis and non-oral diseases, synthesizes a trimeric extracellular matrix protein adhesin A (EmaA) that mediates collagen binding and biofilm formation. EmaA is found as two molecular forms, which correlate with the serotype of the bacterium. The canonical protein (b-EmaA), associated with serotypes b and c, has a monomeric molecular mass of 202 kDa.

Impact of Prior Treatment on the Efficacy of Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma.

Purpose: Adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes (TIL) can mediate durable responses in patients with metastatic melanoma. This retrospective analysis provides long-term follow-up and describes the effect of prior therapy on outcomes after ACT-TIL.

Patients And Methods: Patients with metastatic melanoma underwent surgical resection of a tumor for generation of TILs and were treated with a lymphodepleting preparative regimen followed by adoptive transfer of TILs and intravenous IL2.

The Role of Chronic Inflammation in the Development of Breast Cancer.

Chronic inflammation contributes to the malignant transformation of several malignancies and is an important component of breast cancer. The role of chronic inflammation in the initiation and development of breast cancer from normal breast tissue, however, is unclear and needs to be clarified. A review of the literature was conducted to define the chronic inflammatory processes in normal breast tissue at risk for breast cancer and in breast cancer, including the role of lymphocyte and macrophage infiltrates, chronic active adipocytes and fibroblasts, and processes that may promote chronic inflammation including the microbiome and factors related to genomic abnormalities and cellular injury.

Contribution of adhesion proteins to Aggregatibacter actinomycetemcomitans biofilm formation.

Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium associated with periodontal disease and multiple disseminated extra-oral infections. Colonization of these distinct physiological niches is contingent on the expression of specific surface proteins during the initiation of developing biofilms. In this investigation, we studied fimbriae and three well-characterized nonfimbrial surface proteins (EmaA, Aae, and ApiA/Omp100) for their contribution to biofilm formation.

The Role of Immune Cells in Breast Tissue and Immunotherapy for the Treatment of Breast Cancer.

Immune cells are present in normal breast tissue and in breast carcinoma. The nature and distribution of the immune cell subtypes in these tissues are reviewed to promote a better understanding of their important role in breast cancer prevention and treatment. We conducted a review of the literature to define the type, location, distribution, and role of immune cells in normal breast tissue and in in situ and invasive breast cancer.

Characteristics of Breast Ducts in Normal-Risk and High-risk Women and Their Relationship to Ductal Cytologic Atypia.

Breast ductal cytologic atypia is an important risk factor for sporadic breast cancer. Characterization of the associated normal breast tissue is needed to develop additional methods of risk assessment and new targets for breast cancer prevention. We conducted a prospective clinical trial evaluating women at normal-risk or at high-risk for sporadic breast cancer.

Twenty-five-Year Follow-up of a Prospective Randomized Trial Comparing Preoperative Versus Postoperative FLAC/Granulocyte Colony-Stimulating Factor Chemotherapy for Stage II Breast Cancer.

Background: Preoperative chemotherapy is important in the management of women with breast cancer, with the ability to downstage the breast primary tumor and axillary lymph nodes. Long-term studies are needed to identify late toxicities, recurrence patterns, and equivalency with postoperative chemotherapy for recurrence-free survival (RFS) and overall survival (OS).

Patients And Methods: We conducted a single-institution prospective randomized control trial comparing preoperative or postoperative fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamides/granulocyte colony-stimulating factor chemotherapy for women with untreated clinical stage II (T1N1, T2N0, and T2N1) breast cancer.

A Nonfimbrial Adhesin of Mediates Biofilm Biogenesis.

Periodontitis is an inflammatory disease caused by polymicrobial biofilms. The periodontal pathogen displays two proteinaceous surface structures, the fimbriae and the nonfimbrial extracellular matrix binding protein A (EmaA), as observed by electron microscopy. Fimbriae participate in biofilm biogenesis and the EmaA adhesins mediate collagen binding.

T-cell Responses to "Hotspot" Mutations and Unique Neoantigens Expressed by Human Ovarian Cancers.

This was a study prospectively evaluating intratumoral T-cell responses to autologous somatic mutated neoepitopes expressed by human metastatic ovarian cancers. Tumor-infiltrating lymphocytes (TIL) were expanded from resected ovarian cancer metastases, which were analyzed by whole-exome and transcriptome sequencing to identify autologous somatic mutations. All mutated neoepitopes, independent of prediction algorithms, were expressed in autologous antigen-presenting cells and then cocultured with TIL fragment cultures.

Molecular profile of atypical hyperplasia of the breast.

Purpose: Atypical ductal and atypical lobular hyperplasia (AH) of the breast are important proliferative lesions which are associated with a significantly increased risk for breast cancer. The breast cancer which develops in association with AH may occur synchronously, representing local progression, or metachronously at a later date in either the ipsilateral or contralateral breast. These high-risk characteristics of AH suggest they contain significant genomic changes.

Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study.

Background: Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours.

Genomic Changes in Normal Breast Tissue in Women at Normal Risk or at High Risk for Breast Cancer.

Sporadic breast cancer develops through the accumulation of molecular abnormalities in normal breast tissue, resulting from exposure to estrogens and other carcinogens beginning at adolescence and continuing throughout life. These molecular changes may take a variety of forms, including numerical and structural chromosomal abnormalities, epigenetic changes, and gene expression alterations. To characterize these abnormalities, a review of the literature has been conducted to define the molecular changes in each of the above major genomic categories in normal breast tissue considered to be either at normal risk or at high risk for sporadic breast cancer.

Randomized, Prospective Evaluation Comparing Intensity of Lymphodepletion Before Adoptive Transfer of Tumor-Infiltrating Lymphocytes for Patients With Metastatic Melanoma.

Purpose: Adoptive cell transfer, the infusion of large numbers of activated autologous lymphocytes, can mediate objective tumor regression in a majority of patients with metastatic melanoma (52 of 93; 56%). Addition and intensification of total body irradiation (TBI) to the preparative lymphodepleting chemotherapy regimen in sequential trials improved objective partial and complete response (CR) rates. Here, we evaluated the importance of adding TBI to the adoptive transfer of tumor-infiltrating lymphocytes (TIL) in a randomized fashion.

An Improved Breast Epithelial Sampling Method for Molecular Profiling and Biomarker Analysis in Women at Risk for Breast Cancer.

Background: There is a strong need to define the molecular changes in normal at-risk breast epithelium to identify biomarkers and new targets for breast cancer prevention and to develop a molecular signature for risk assessment. Improved methods of breast epithelial sampling are needed to promote whole-genome molecular profiling, increase ductal epithelial cell yield, and reduce sample cell heterogeneity.

Methods: We developed an improved method of breast ductal sampling with ductal lavage through a 22-gauge catheter and collection of ductal samples with a microaspirator.

Appendicitis secondary to metastatic melanoma: review of the National Institutes of Health experience.

Importance: Malignant melanoma has an unusual propensity to metastasize to the small bowel; however, malignant melanoma with metastatic spread to the appendix presenting as acute appendicitis has rarely been reported. We describe cases of melanoma of the appendix presenting with appendicitis and review our institutional experience with this entity.

Observations: Medical records were reviewed in patients with melanoma at the National Cancer Institute between January 1, 1953, and December 31, 2010, who underwent appendectomy.

Commentary on the Canadian National Breast Screening study.

In the setting of the 25-year follow-up of the Canadian National Breast Screening Study, the Society of Surgical Oncology continues to endorse mammographic screening for women beginning at 40 years of age, while acknowledging that mammography has both risks and benefits. Further investigation is warranted to develop better screening methods and to determine optimal screening schedules for women based on their risk of future breast cancer and their imaging characteristics.

Disparities in breast cancer outcomes between Caucasian and African American women: a model for describing the relationship of biological and nonbiological factors.

Breast cancer is the most common malignancy in women in the United States but significant disparities exist for African American women compared to Caucasian women. African American women present with breast cancer at a younger age and with a greater incidence under the age of 50 years, develop histologically more aggressive tumors that are at a more advanced stage at presentation, and have a worse disease-free and overall survival than Caucasian women. The biological characteristics of the primary tumor play an important role in determining the outcome of the disparity, and significant differences have been identified between African American and Caucasian breast cancer in steroid receptor and growth factor receptor content, mutations in cell cycle components, chromosomal abnormalities, and tumor suppressor and other cancer genes.

Twenty-five year results of the national cancer institute randomized breast conservation trial.

Breast conservation therapy (BCT) consisting of lumpectomy and postoperative radiation has become an accepted alternative to mastectomy (MRM) for the treatment of early stage breast cancer. We currently report the 25 year outcomes of a single institution, prospective, randomized clinical trial at the National Cancer Institute. 237 women with pathologically confirmed invasive breast tumors 5 cm or less were accrued between 1979 and 1987 and randomized to receive either BCT or MRM.

Selective release of microRNA species from normal and malignant mammary epithelial cells.

MicroRNAs (miRNAs) in body fluids are candidate diagnostics for a variety of conditions and diseases, including breast cancer. One premise for using extracellular miRNAs to diagnose disease is the notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells causing the disease. As a result, the search for such diagnostics in body fluids has focused on miRNAs that are abundant in the cells of origin.