Genomic profiling of breast cancer in African-American women using MammaPrint.

Breast cancer in African-American females (AAF) has a less favorable outcome than that in Caucasians. More information is needed regarding its biology. We evaluated gene expression in tumors from AAF presenting with early stage or locally advanced breast cancer using MammaPrint(®), BluePrint (®) (molecular subtype) and TargetPrint (®) [estrogen receptor (ER), progesterone receptor, and Human Epidermal Growth Factor Receptor 2 (HER2) mRNA levels]. Genomic information was correlated with clinical and pathologic characteristics and Oncotype DX(®) Recurrence Score(®) (RS). One hundred Patients were enrolled, 1 not evaluable by BluePrint. The median age was 60 years (range 22-98), and eighty-four (84 %) patients had stage I or II disease. High Risk MammaPrint was present in 66 % of patients and in 52 % of patients with stage I disease. High Risk MammaPrint was associated with young age (p = 0.02), high grade (p < 0.0001), HER2 expression (p = 0.016), and triple-negative phenotype (p < 0.001). Sixty-four tumors (65 %) were Luminal type (47 % of these were classified as High Risk), 26 (26 %) were Basal type, and 9 (9 %) HER2 type. Twenty-two cancers were triple negative (TN) by IHC and 19 (90 %) Basal type. Among the 15 tumors HER2 positive by IHC/FISH, 8 (53 %) were HER2 type by BluePrint. Eleven tumors with ER expression of 1-9 % were ER negative by TargetPrint and none of these was Luminal type. None of the seven tumors HER2 positive by IHC/FISH but negative by TargetPrint was HER type. RS results were available in 29 patients: two had High Risk both by RS and MammaPrint; eight had intermediate RS, with four High Risk by MammaPrint; 19 had a low RS, with eight High Risk by MammaPrint. AAF with stage I to III breast cancer often present with High Risk disease. Molecular heterogeneity is present within TN, HER2-positive, and ER-positive breast cancer. RS and MammaPrint offer different prognostic information.

TARGIT-R (Retrospective): North American Experience with Intraoperative Radiation Using Low-Kilovoltage X-Rays for Breast Cancer.

BACKGROUND: Single-dose intraoperative radiotherapy (IORT) is an emerging treatment for women with early stage breast cancer. The objective of this study was to define the frequency of IORT use, patient selection, and outcomes of patients treated in North America. METHODS: A multi-institutional retrospective registry was created, and 19 institutions using low-kilovoltage IORT for the treatment of breast cancer entered data on patients treated at their institution before July 31, 2013. Patient selection, IORT treatment details, complications, and recurrences were analyzed. RESULTS: From 2007 to July 31, 2013, a total of 935 women were identified and treated with lumpectomy and IORT. A total of 822 patients had at least 6 months' follow-up documented and were included in the analysis. The number of IORT cases performed increased significantly over time (p < 0.001). The median patient age was 66.8 years. Most patients had disease that was <2 cm in size (90 %) and was estrogen positive (91 %); most patients had invasive ductal cancer (68 %). Of those who had a sentinel lymph node procedure performed, 89 % had negative sentinel lymph nodes. The types of IORT performed were primary IORT in 79 %, secondary IORT in 7 %, or planned boost in 14 %. Complications were low. At a median follow-up of 23.3 months, crude in-breast recurrence was 2.3 % for all patients treated. CONCLUSIONS: IORT use for the treatment of breast cancer is significantly increasing in North America, and physicians are selecting low-risk patients for this treatment option. Low complication and local recurrence rates support IORT as a treatment option for selected women with early stage breast cancer.

Postoperative Outcomes following a Multidisciplinary Approach to HIV-positive Breast Cancer Patients.

Improvements in human immunodeficiency virus (HIV) treatment resulted in drastic increases in the lifespan of HIV-positive individuals, resulting in higher rates of non-AIDS-defining cancers. We describe our postoperative outcomes in HIV+ breast cancer (BC) patients, highlighting our multidisciplinary experience with this high-risk population. Methods: A 7-year multi-institutional retrospective review of all HIV+ BC patients who underwent surgical intervention was performed. Patient demographics, therapeutic interventions, and treatment outcomes were collected. Results: Twenty-four patients were identified, including one male patient (4.2%). Most patients were African American (83.3%). Mean age was 52.1 + 9.7 years at the time of diagnosis in HIV+ BC patients. Surgical interventions included lumpectomy (n = 16, 66.7%), simple mastectomy (n = 3, 12.5%), and skin-sparing mastectomy (n = 5. 20.8%). All patients were on antiretroviral therapy, and 81.3% had undetectable viral loads at the time of operation. Seventeen patients (70.8%) underwent breast reconstruction, with three (17.7%) undergoing delayed reconstruction. Thirty-day postoperative complications occurred in three patients (17.6%), including flap necrosis (11.8%), infection (11.8%), dehiscence (5.9%), and return to OR (11.8%). Three patients (12.5%) experienced recurrence at a median of 18 months since operation. Mean follow-up was 51.4 + 33.3 months since BC diagnosis. Conclusions: While postoperative complication rates in HIV+ patients trended higher (17.6%) compared with the existing data on breast reconstruction patients overall (10.1%), HIV+ patients did not exhibit increased risk of BC recurrence (12.5%) compared with BC patients overall (12-27%). This highlights the importance of a combined multidisciplinary approach involving infectious disease, breast surgery, and plastic and reconstructive surgery to optimize surgical and oncologic outcomes in these high-risk patients.

Risk-reducing surgery in PALB2 mutations carriers with breast cancer: a case series and literature review.

Background: Inherited germline mutations in PALB2 are known to predispose patients to a higher risk of breast, ovarian and pancreatic cancer with an estimated risk of developing breast cancer in over half of all affected women by age 80 years. Current guidelines for screening patients with PALB2 mutations include annual mammograms beginning at age 30 years and consideration of breast magnetic resonance imaging (MRI) and tomosynthesis. Existing evidence regarding risk-reducing surgery with mastectomy is insufficient to make a definitive recommendation to patients. In this case series, we describe the presentation and management of 5 patients with unilateral breast cancer and PALB2 mutations. To our knowledge, this is the first reported case series discussing the role of contralateral risk-reducing mastectomy (CRRM) in breast cancer patients with PALB2 mutations. The aim of our study was to evaluate the challenges in managing breast cancer risk in patients with PALB2 pathogenic variants with illustration through real-world clinical cases and a review of the literature. Methods: In this retrospective observational study, we present 5 patients with PALB2 mutations between the ages of 29 and 61 years who were diagnosed with breast cancer and underwent surgical management of their breast cancer at our institution between November 2020 and March 2022. Through their clinical courses and a literature review, we discuss the role of CRRM in breast cancer patients with PALB2 gene mutations. Results: Out of the 5 patients, 3 patients underwent CRRM and 2 patients chose unilateral surgery for their breast cancer and active surveillance for the contralateral breast. Of the 3 patients who underwent CRRM, 1 patient experienced a surgical complication from reconstruction on the prophylactic side. None of the patients developed any recurrences with an average length of follow up of 15.4 months. Conclusions: Based on our experience and the currently available literature, CRRM in patients with a PALB2 mutation should be performed on a case-by-case basis through a shared decision-making process taking into consideration overall risk, family history, patient preference and quality of life.

Immediate reconstruction after mastectomy for breast cancer does not prolong the time to starting adjuvant chemotherapy.

BACKGROUND: Immediate breast reconstruction is often performed after mastectomy for breast cancer. There has been concern that this will result in a delay in initiating chemotherapy and, as a consequence, may adversely impact survival. In this study we sought to determine whether immediate breast reconstruction affects the interval between surgery and adjuvant chemotherapy. METHODS: A single institution retrospective analysis was made using the institutional tumor registry and chart reviews. RESULTS: Forty-nine patients were identified who had undergone mastectomy with immediate reconstruction followed by adjuvant chemotherapy. They were compared with 308 patients undergoing mastectomy without reconstruction. Patients who underwent reconstruction were overall younger (46 versus 55, P <0.001), and had more advanced disease. The time to chemotherapy was significantly longer in the group receiving no reconstruction: 53 versus 41 days (P = 0.039). The type of reconstruction did not affect the time to chemotherapy. CONCLUSIONS: Immediate reconstruction after mastectomy does not increase the time to chemotherapy compared with mastectomy alone.

Bare bones laparoscopy: a randomized prospective trial of cost savings in laparoscopic cholecystectomy.

OBJECTIVE: Rising costs and lowered reimbursements make value essential if laparoscopic cholecystectomy (LC) is to be offered to patients without condemning providers to financial loss. We hypothesize that our protocol increases this value. Once practiced, operative time, complications, and patient satisfaction compare with those of the typical method. METHODS: We prospectively randomized 50 consecutive patients equally to control or experimental LC according to our protocol. Equipment costs, operative time, conversions, complications, pain, and return to work were compared. The student's t test was used for comparisons. RESULTS: Mean disposable equipment costs were 173.00 dollars +/- 43.45 dollars and 434.42 dollars +/- 50.54 dollars for the study and control groups, respectively (P < .0001). Mean operative times were 67.26 +/- 15 and 70.60 +/- 19 minutes, respectively. CONCLUSIONS: The "bare bones" protocol is safe. It has a short learning curve, demonstrates a cost advantage over the common method, and requires no additional operative time. Pain, time to return to work, and satisfaction are equivalent.

Out-of-plane Stokes imaging polarimeter for early skin cancer diagnosis.

Optimal treatment of skin cancer before it metastasizes critically depends on early diagnosis and treatment. Imaging spectroscopy and polarized remittance have been utilized in the past for diagnostic purposes, but valuable information can be also obtained from the analysis of skin roughness. For this purpose, we have developed an out-of-plane hemispherical Stokes imaging polarimeter designed to monitor potential skin neoplasia based on a roughness assessment of the epidermis. The system was utilized to study the rough surface scattering for wax samples and human skin. The scattering by rough skin-simulating phantoms showed behavior that is reasonably described by a facet scattering model. Clinical tests were conducted on patients grouped as follows: benign nevi, melanocytic nevus, melanoma, and normal skin. Images were captured and analyzed, and polarization properties are presented in terms of the principal angle of the polarization ellipse and the degree of polarization. In the former case, there is separation between different groups of patients for some incidence azimuth angles. In the latter, separation between different skin samples for various incidence azimuth angles is observed.

Immunogenicity for CD8+ and CD4+ T cells of 2 formulations of an incomplete freund's adjuvant for multipeptide melanoma vaccines.

An incomplete Freund's adjuvant (IFA) commonly used in experimental cancer vaccines has recently been reformulated. Oleic acid used in the surfactant was purified from a vegetable source (olives, IFA-VG) rather than an animal source (beef tallow, IFA-AN). To provide an insight into the adjuvant properties of the new formulation, we reviewed T-cell responses, by enzyme-linked immunospot assay, to multipeptide vaccines in 2 sequential clinical trials that spanned this transition of adjuvants. Analyses included 194 patients who received either IFA-AN or IFA-VG for all vaccines, and a subset of 93 patients best matched by study arm for vaccine antigens (12 melanoma peptides restricted by major histocompatibility complex class I, 12MP; plus a tetanus helper peptide, tet) administered with IFA but without granulocyte macrophage-colony stimulating factor. Inflammation was observed at vaccine sites clinically for almost all patients, even including ulceration in a subset with each IFA formulation. CD8 T-cell response rates to the 12 melanoma peptides were 53% [95% confidence interval (CI), 44%, 61%)] for IFA-AN and 46% [95% CI, 32%, 59%)] for IFA-VG. In the 93 patient subset, these rates were 73% [95% CI, 61%, 83%)] and 70% [95% CI, 47%, 87%)], respectively. CD4 T-cell responses to tetanus helper peptide were identified in 94% [95% CI, 86%, 98%)] and 96% [95% CI, 78%, 100%)], respectively. Responses to individual human leukocyte antigen (HLA)-A1, A2, and DR associated peptides were largely preserved, but reactivity trended lower for some HLA-A3 associated peptides. Despite the necessarily retrospective nature of the analysis and limitations of multiple comparisons, our summary data support the use of IFA-VG as an adjuvant with multipeptide vaccines in melanoma patients.

Effect of granulocyte/macrophage colony-stimulating factor on circulating CD8+ and CD4+ T-cell responses to a multipeptide melanoma vaccine: outcome of a multicenter randomized trial.

PURPOSE: Granulocyte/macrophage colony-stimulating factor (GM-CSF) administered locally together with vaccines can augment T-cell responses in animal models. Human experience has been limited to small and uncontrolled trials. Thus, a multicenter randomized phase II trial was done to determine whether local administration of GM-CSF augments immunogenicity of a multipeptide vaccine. It also assessed immunogenicity of administration in one versus two vaccine sites. EXPERIMENTAL DESIGN: One hundred twenty-one eligible patients with resected stage IIB to IV melanoma were vaccinated with 12 MHC class I-restricted melanoma peptides to stimulate CD8+ T cells plus a HLA-DR-restricted tetanus helper peptide to stimulate CD4+ T cells, emulsified in incomplete Freund's adjuvant, with or without 110 microg GM-CSF. Among 119 evaluable patients, T-cell responses were assessed by IFN-gamma ELIspot assay and tetramer analysis. Clinical outcomes were recorded. RESULTS: CD8+ T-cell response rates to the 12 MHC class I-restricted melanoma peptides (by day 50) with or without GM-CSF were 34% and 73%, respectively (P < 0.001), by direct ELIspot assay. Tetramer analyses corroborated the functional data. CD4+ T-cell responses to tetanus helper peptide were higher without GM-CSF (95% versus 77%; P = 0.005). There was no significant difference by number of vaccine sites. Three-year overall and disease-free survival estimates (95% confidence interval) were 76% (67-83%) and 52% (43-61%), respectively, with too few events to assess differences by study group. CONCLUSIONS: High immune response rates for this multipeptide vaccine were achieved, but CD8+ and CD4+ T-cell responses were lower when administered with GM-CSF. These data challenge the value of local GM-CSF as a vaccine adjuvant in humans.