Distinct Neoadjuvant Chemotherapy Response and 5-Year Outcome in Patients With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Tumors That Reclassify as Basal-Type by the 80-Gene Signature.

Purpose: The 80-gene molecular subtyping signature (80-GS) reclassifies a proportion of immunohistochemistry (IHC)-defined luminal breast cancers (estrogen receptor-positive [ER+], human epidermal growth factor receptor 2-negative [HER2-]) as Basal-Type. We report the association of 80-GS reclassification with neoadjuvant treatment response and 5-year outcome in patients with breast cancer.

Methods: Neoadjuvant Breast Registry Symphony Trial (NBRST; NCT01479101) is an observational, prospective study that included 1,069 patients with early-stage breast cancer age 18-90 years who received neoadjuvant therapy.

Age-Independent Preoperative Chemosensitivity and 5-Year Outcome Determined by Combined 70- and 80-Gene Signature in a Prospective Trial in Early-Stage Breast Cancer.

Background: The Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status.

Methods: The observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18-90 years who received neoadjuvant chemotherapy and had clinical and genomic data available.

Addition of chemotherapy to local therapy in women aged 70 years or older with triple-negative breast cancer: a propensity-matched analysis.

Background: There is a scarcity of data exploring the benefits of adjuvant or neoadjuvant chemotherapy in the treatment of breast cancer in older women. We aimed to explore the effect of adding chemotherapy to local therapy on overall survival in older women with triple-negative breast cancer.

Methods: For this propensity-matched analysis, we used data from the National Cancer Database, a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society.

A structured step-by-step program to increase scholarly activity.

Objectives: Development and maintenance of scholarly activity is a challenge for small community-based surgical training programs. The current Accreditation Council for Graduate Medical Education Program Requirements in General Surgery states that, "Residents should participate in scholarly activity," and "The sponsoring institution and program should allocate adequate educational resources to facilitate resident involvement in scholarly activities." We adopted a program designed to improve the quality of research projects pursued by surgical residents and to increase the number of projects submitted for both presentation and publication.

For-profit hospital ownership status and use of brachytherapy after breast-conserving surgery.

Background: Little is known about the relationship between operative care for breast cancer at for-profit hospitals and subsequent use of adjuvant radiation therapy (RT). Among Medicare beneficiaries, we examined whether hospital ownership status is associated with the use of breast brachytherapy--a newer and more expensive modality--as well as overall RT.

Methods: We conducted a retrospective study of female Medicare beneficiaries who received breast-conserving surgery for invasive breast cancer in 2008 and 2009.

Patterns of use and short-term complications of breast brachytherapy in the national medicare population from 2008-2009.

Purpose: Brachytherapy has disseminated into clinical practice as an alternative to whole-breast irradiation (WBI) for early-stage breast cancer; however, current national treatment patterns and associated complications remain unknown.

Patients And Methods: We constructed a national sample of Medicare beneficiaries ages 66 to 94 years who underwent breast-conserving surgery from 2008 to 2009 and were treated with brachytherapy or WBI. We used hospital referral regions (HRRs) to assess national treatment variation and an instrumental variable analysis to compare complication rates between treatment groups, adjusting for patient and clinical characteristics.

Pretraining and posttraining assessment of residents' performance in the fourth accreditation council for graduate medical education competency: patient communication skills.

Hypothesis: Structured communication curricula will improve surgical residents' ability to communicate effectively with patients.

Design And Setting: A prospective study approved by the institutional review board involved 44 University of Connecticut general surgery residents. Residents initially completed a written baseline survey to assess general communication skills awareness.

Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer.

The purpose of this study is to determine the biologic impact of short-term lipophilic statin exposure on in situ and invasive breast cancer through paired tissue, blood and imaging-based biomarkers. A perioperative window trial of fluvastatin was conducted in women with a diagnosis of DCIS or stage 1 breast cancer. Patients were randomized to high dose (80 mg/day) or low dose (20 mg/day) fluvastatin for 3-6 weeks before surgery.

Do sentinel node micrometastases predict recurrence risk in ductal carcinoma in situ and ductal carcinoma in situ with microinvasion?

Background: Because the implications of micrometastases found on sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) or ductal carcinoma in situ with microinvasion (DCISM) are largely unknown, we wished to determine if SNB pathology predicted recurrence risk in DCIS/DCISM.

Methods: Retrospective chart review identified patients with DCIS/DCISM who underwent SNB. SNB findings and all local and distant recurrences were determined.

Sentinel node biopsy is important in mastectomy for ductal carcinoma in situ.

Background: There is uncertainty about the utility of sentinel node biopsy (SNB) for ductal carcinoma in situ (DCIS) and its potential to avoid axillary lymph node dissection (ALND) in patients undergoing mastectomy for DCIS.

Methods: A review was conducted of 179 patients who underwent mastectomy with sentinel node biopsy for DCIS without invasion or microinvasion on premastectomy pathology review.

Results: The sentinel node identification rate was 98.

Predictors of resistance to preoperative trastuzumab and vinorelbine for HER2-positive early breast cancer.

Purpose: To assess pathologic complete response (pCR), clinical response, feasibility, safety, and potential predictors of response to preoperative trastuzumab plus vinorelbine in patients with operable, human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Experimental Design: Forty-eight patients received preoperative trastuzumab and vinorelbine weekly for 12 weeks. Single and multigene biomarker studies were done in an attempt to identify predictors of response.

A comparison of sentinel node biopsy before and after neoadjuvant chemotherapy: timing is important.

Background: Because neoadjuvant chemotherapy is being used more frequently, the optimal timing of sentinel node biopsy (SNB) remains controversial. We previously evaluated the predictive value of SNB before neoadjuvant chemotherapy in clinically node-negative breast cancer. Our identification rate of the sentinel node among 52 patients before chemotherapy with a mean tumor size of 4 cm was 100%.

Treatment of breast cancer during pregnancy.

The management of breast cancer during pregnancy is one of the great clinical challenges in oncology. Patients are best served by care provided through a multidisciplinary team including surgeons, oncologists, obstetricians and genetics counsellors with experience in caring for similar women. The risks of diagnostic and therapeutic interventions can be mitigated by the consideration of known side effects of therapy on the fetus and the mother.

A comparison of ink-directed and traditional whole-cavity re-excision for breast lumpectomy specimens with positive margins.

Background: Excising a breast tumor with negative margins minimizes local recurrence. With a positive margin, the standard re-excision consists of excising the whole cavity and all surrounding breast tissue. By marking the sides of the lumpectomy specimen with six different colored inks, the surgeon can limit the re-excision to the involved margin.

Xenogeneic endothelial cells activate human prothrombin.

Background: Delayed xenograft rejection is characterized by platelet activation and fibrin deposition and is thought to occur independently of complement activation. We have therefore investigated the potential for xenogeneic endothelial cells (EC) to regulate the conversion of prothrombin to thrombin, a central component of the final common pathway of coagulation and an important platelet agonist.

Methods And Results: Quiescent porcine aortic EC (PAEC) were found to convert high levels of human prothrombin to thrombin (0.

Effect of repetitive high-dose treatment with soluble complement receptor type 1 and cobra venom factor on discordant xenograft survival.

Hyperacute xenograft rejection may be modified by the activation and depletion of complement (C) using cobra venom factor (CVF). This method of prolonging xenograft survival is toxic and associated with systemic inflammation, which may potentially contribute to the pathologic features of delayed xenograft rejection. Soluble complement receptor type 1 (sCR1) inhibits both the classical and alternative C pathways and thus limits the production of proinflammatory products such as the anaphylatoxins.

Inhibition of platelet integrin GPIIbIIIa prolongs survival of discordant cardiac xenografts.

The integrin GPIIbIIIa is known to be crucial to the formation of platelet aggregates and potentiates adhesion to subendothelial matrices via fibrin(ogen), von Willebrand factor, and vitronectin. Given the demonstration by us and others of widespread platelet aggregation during xenograft rejection, we hypothesized that platelet thrombi might contribute to graft dysfunction during development of hyperacute rejection (HAR), as well as during what we have termed delayed xenograft rejection (DXR), e.g.

Thrombin inhibition in an ex vivo model of porcine heart xenograft hyperacute rejection.

Prominent components of vascularized xenograft rejection such as platelet activation and microvascular thrombosis may be dependent upon thrombin generation in vivo. To study potential therapeutic benefits of a synthetic low-molecular-weight thrombin inhibitor, SDZ MTH 958, in hyperacute porcine heart rejection by human blood ex vivo, a working model of hyperacute rejection of porcine by fresh, heparinized (6 microM/ml) human blood with or without 1 microM SDZ MTH 958 was used. Thrombin-antithrombin complexes (TAT) and prothrombin fragment F1.