Rena Kass

Clip migration in stereotactic biopsy

BACKGROUND Needle localization breast biopsy (NLBB) is the standard for removal of breast lesions after vacuum assisted core biopsy (VACB). Disadvantages include a miss rate of 0% to 22%, a positive margin rate of approximately 50%, and vasovagal reactions (approximately 20%). We hypothesized that clip migration after VACB is clinically significant and may contribute to the positive margin rates seen after NLBB. METHODS We performed a retrospective review of postbiopsy films in patients who had undergone VACB with stereotactic clip placement for abnormal mammograms. We measured the distance between the clip and the biopsy site in standard two view mammograms. The location of the biopsy air pocket was confirmed using the prebiopsy calcification site. The Pythagorean Theorem was used to calculate the distance the clip moved within the breast. Pathology reports on NLBB or intraoperative hematoma-directed ultrasound-guided breast biopsy (HUG, which localizes by US the VACB site) were reviewed to assess margin status. RESULTS In all, 165 postbiopsy mammograms on patients who had VACB with clip placement were reviewed. In 93 evaluable cases, the mean distance the clip moved was 13.5 mm +/- 1.6 mm, SEM (95% CI = 10.3 mm to 16.7 mm). Range of migration was 0 to 78.3 mm. The median was 9.5 mm. In 21.5% of patients the clip was more than 20 mm from the targeted site. Migration of the clip did not change with the age of the patient, the size of the breast or location within the breast. In the subgroup of patients with cancer, margin positivity (including those with close margins) after NLBB was 60% versus 0% in the HUG group. CONCLUSIONS Significant clip migration after VACB may contribute to the high positive margin status of standard NLBBs. Surgeons cannot rely on needle localization of the clip alone and must be cognizant of potential clip migration. HUG as an alternative biopsy technique after VACB eliminates operator dependency on clip location and may have superior results in margin status.

Intraoperative Subareolar Radioisotope Injection for Immediate Sentinel Lymph Node Biopsy

Objective:To determine the identification of sentinel lymph node biopsy (SLNB) in breast cancer patients after intraoperative injection of unfiltered technetium-99m sulfur colloid (Tc-99) and blue dye. Background:SLNB guided by a combination of radioisotope and blue dye injection yields the best identification rates in breast cancer patients. Radioisotope is given preoperatively, without local anesthesia, whereas blue dye is given intraoperatively. We hypothesized that, because of the rapid drainage noted with the subareolar injection technique of radioisotope, intraoperative injection would be feasible and less painful for SLN localization in breast cancer patients. Methods:Intraoperative injection of Tc-99 and confirmation blue dye was performed using the subareolar technique for SLNB in patients with operable breast cancer. The time lapse between injection and axillary incision, the background count, the preincision and ex vivo counts of the hot nodes, and the axillary bed counts were documented. The identification rate was recorded. Results:Ninety-six SLNB procedures were done in 88 patients with breast cancer employing intraoperative subareolar injection technique for both radioisotope (all 96 procedures) and blue dye (93 procedures) injections. Ninety-three (97%) procedures had successful identification; all SLNs were hot; 91 (of 93 procedures with blue dye) were blue and hot. The mean time from radioisotope injection to incision was 19.9 minutes (SD 8.5 minutes). The mean highest 10 second count was 88,544 (SD 55,954). Three of 96 (3%) patients with failure of localization had previous excisional biopsies: 1 circumareolar and 2 upper outer quadrant incisions that may have disrupted the lymphatic flow. Conclusion:Intraoperative subareolar injection of radioisotope rapidly drains to the SLNs and allows immediate staging of the axilla, avoiding the need to coordinate diagnostic services and a painful preoperative procedure.

Contralateral Prophylactic Mastectomy (CPM) Consensus Statement from the American Society of Breast Surgeons: Data on CPM Outcomes and Risks.

The American Society of Breast Surgeons (ASBrS) endorses the American Board of Internal Medicine’s Choosing Wisely campaign statement: “Don’t routinely perform a double mastectomy in patients who have a single breast with cancer.”1 However, women with a newly diagnosed unilateral breast cancer are increasingly opting for bilateral mastectomy. This has been seen in patients who are candidates for breast conservation who elect mastectomy as well as those requiring mastectomy for their index breast cancer.2 National rates of contralateral prophylactic mastectomy (CPM) in the United States have been increasing and this trend is continuing.2–4

In vitro induction of tumor-specific HLA class I-restricted CD8+ cytotoxic T lymphocytes from patients with locally advanced breast cancer by tumor antigen-pulsed autologous dendritic cells.

BACKGROUND Early dissemination of treatment-resistant tumor cells remains the major cause of metastatic recurrence and death in breast cancer patients. Dendritic cells (DCs) are the most powerful antigen-presenting cells, and recently DC-based vaccination has shown great promise for the treatment of human malignancies by immunological intervention. MATERIALS AND METHODS CD8+ T lymphocytes derived from peripheral blood mononuclear cells stimulated in vitro with autologous breast tumor antigen-pulsed DCs were tested for their ability to induce a HLA class I restricted cytotoxic T lymphocyte (CTL) response against autologous tumor cells. To correlate cytotoxic activity by CTL with T cell phenotype, two-color flow cytometric analysis of surface markers and intracellular cytokine expression was performed. RESULTS DC pulsed with breast tumor extracts consistently elicited a tumor-specific HLA class I restricted CTL response in vitro in three consecutive patients harboring locally advanced breast cancer. CTL expressed strong cytolytic activity against autologous tumor cells but did not lyse autologous Epstein Barr virus-transformed lymphoblastoid cell lines and showed variable cytotoxicity against the natural killer-sensitive cell line K-562. In all patients, two color flow cytometric analysis of surface markers and intracellular cytokine expression demonstrated that tumor-specific CTL exhibited an heterogeneous CD8+/CD56+ expression and a striking Th1 cytokine bias (IFNgamma(high)/IL-4 (low)). CONCLUSIONS Tumor lysate-pulsed DCs can consistently stimulate specific CD8+ CTLs able to kill autologous tumor cells in patients with locally advanced breast cancer in vitro. Tumor antigen-pulsed DC-based vaccinations may be appropriate for the treatment of residual and/or chemotherapy-resistant breast cancer refractory to standard salvage treatment modalities.

Restoration of tumor-specific HLA class I restricted cytotoxicity in tumor infiltrating lymphocytes of advanced breast cancer patients by in vitro stimulation with tumor antigen-pulsed autologous dendritic cells.

Breast tumor infiltrating lymphocytes (TIL) are enriched in tumor-specific cytotoxic T lymphocytes (CTL), and may represent a superior source of CTL compare to peripheral blood lymphocytes (PBL), for adoptive T cell immunotherapy of breast cancer. However, the immunocompetence of TIL and the possibility to consistently restore their tumor-specific lytic activity in vitro remains an open issue. In this study we evaluated the potential of tumor antigen-pulsed fully mature dendritic cell (DC) stimulation in restoring tumor-specific cytotoxicity in anergic TIL populations from advanced breast cancer patients. In addition we have compared tumor-specific T cell responses induced by tumor antigen-loaded DC stimulation of TIL to responses induced from PBL. Although TIL were consistently non-cytotoxic after isolation or culture in the presence of interleukin-2 (IL-2), in matched experiments from three consecutive patients, tumor-lysate-pulsed DC-stimulated CD8+ T cell derived from TIL were found to be significantly more cytotoxic than PBL (p < 0.05). In addition, cytotoxicity against autologous tumor cells was more significantly inhibited by an anti-HLA class I (W6/32) MAb in TIL compared to PBL (p < 0.05). CTL populations derived from TIL and PBL did not lyse autologous EBV-transformed lymphoblastoid cell lines, and showed negligible cytotoxicity against the NK-sensitive cell line K562. Furthermore, in both CD8+ T cell populations the majority of the tumor-specific CTL exhibited a Th1 cytokine bias (IFN-γhigh/IL-4low). Taken together, these data show that tumor lysate-pulsed mature DC can consistently restore tumor-specific lytic activity in non-cytotoxic breast cancer TIL. These results may have important implications for the treatment of chemotherapy resistant breast cancer with active or adoptive immunotherapy.

Performance and Practice Guideline for the Use of Neoadjuvant Systemic Therapy in the Management of Breast Cancer

PurposeThe American Society of Breast Surgeons (ASBrS) sought to provide an evidence-based guideline on the use of neoadjuvant systemic therapy (NST) in the management of clinical stage II and III invasive breast cancer.MethodsA comprehensive nonsystematic review was performed of selected peer-reviewed literature published since 2000. The Education Committee of the ASBrS convened to develop guideline recommendations.ResultsA performance and practice guideline was prepared to outline the baseline assessment and perioperative management of patients with clinical stage II–III breast cancer under consideration for NST.RecommendationsPreoperative or NST is emerging as an important initial strategy for the management of invasive breast cancer. From the surgeon’s perspective, the primary goal of NST is to increase the resectability of locally advanced breast cancer, increase the feasibility of breast-conserving surgery and sentinel node biopsy, and decrease surgical morbidity. To ensure optimal patient selection and efficient patient care, the guideline recommends: (1) baseline breast and axillary imaging; (2) minimally invasive biopsies of breast and axillary lesions; (3) determination of tumor biomarkers; (4) systemic staging; (5) care coordination, including referrals to medical oncology, radiation oncology, plastic surgery, social work, and genetic counseling, if indicated; (6) initiation of NST; (7) post-NST breast and axillary imaging; and (8) decision for surgery based on extent of disease at presentation, patient choice, clinical response to NST, and genetic testing results, if performed.

Use of breast simulators compared with standardized patients in teaching the clinical breast examination to medical students.

OBJECTIVE Simulators have replaced some standardized patients in medical student teaching, and their use seems to decrease anxiety related to the clinical breast examination (CBE). We compared learning the CBE on a breast palpation simulator with learning on a standardized patient with respect to skill acquisition and comfort level. METHODS At Penn State College of Medicine, the class of 2008 (historical control group, n = 113) learned the CBE on a standardized patient, whereas the class of 2009 (experimental group, n = 131) learned on the breast palpation simulator. We used measures of the process (conducting the CBE) and measures of the outcome (examination scores and detection of abnormal findings). During their third-year surgical clerkship, students in both groups completed a questionnaire reporting the number of CBEs performed and confidence in performing the CBE. The students then performed an observed examination on the simulator, and the number of positive findings detected was recorded. The mean number of positive findings was compared between groups, and an economic analysis was conducted. RESULTS The experimental group had a significantly higher mean examination score than the historical control. In subgroups, this difference was significant for those who reported performing 0-5 clinical examinations but for not those who had performed >6 examinations. On individual items, the experimental group scored significantly higher in examining for neck nodes, nipple retraction, skin changes, and axillary evaluation. The 2 groups did not differ significantly in the mean number of positive findings detected or in ratings of comfort level. CONCLUSIONS Medical students who learned the CBE on breast palpation simulators performed as well or better than those who learned on standardized patients; however, a subgroup analysis revealed that the benefit was limited to students with less clinical experience.

Etiology and Management of Benign Breast Disease

The aberrations of normal development and involution (ANDI) classification of benign breast disorder (BBD) provides an overall framework for benign conditions of the breast that encompasses both pathogenesis and the degree of abnormality. It is a bidirectional framework based on the fact that most BBDs arise from normal physiologic processes: one component defines BBD along a spectrum from normal to mild abnormality (“disorder”) to severe abnormality (“disease”); the other component defines the pathogenesis of the condition. Together these two components provide a comprehensive framework into which most BBDs can be fit. This scheme is based on the recommendations of the international multidisciplinary working group held in 1992.

Breast Cancer Surgery Decision-Making and African-American Women

Prior research has used focus group methodology to investigate cultural factors impacting the breast cancer experience of women of various ethnicities including African-Americans; however, this work has not specifically addressed treatment decision-making. This study identifies key issues faced by African-American women diagnosed with breast cancer regarding treatment decisions. We used an interpretive-descriptive study design based on qualitative data from three focus groups (n = 14) representing a population of African-American women in central Pennsylvania. Participants were asked to think back to when they were diagnosed with breast cancer and their visit with the breast surgeon. Questions were asked about the actual visit, treatment choices offered, sources of information, and whether the women felt prepared for the surgery and subsequent treatments. The prompts triggered memories and encouraged open discussion. The most important themes identified were fear across the breast cancer disease trajectory, a preference for visual information for understanding the diagnosis and surgical treatment, and support systems relying on family and friends, rather than the formal health-care system. Our results have implications for practice strategies and development of educational interventions that will help breast cancer patients better understand their diagnosis and treatment options, encourage their participation in treatment decision-making, and provide psychosocial support for those at high risk for emotional distress.

Breast Physiology: Normal and Abnormal Development and Function

The mammary gland is composed of an epithelial system of ducts and lobuloalveolar secretory units embedded in a mesenchymally derived fat pad. The growth and morphogenesis of the epithelial structures of the breast occur in various stages and are associated with concurrent hormonal changes and affected by genetic mutations. Each stage reflects the effects of systemic hormones on the glandular epithelium as well as the paracrine effects of locally derived growth factors and other regulatory products produced in the stroma. Appreciating the relationship of epithelium to mesenchyme in normal growth is essential for understanding developmental abnormalities and factors that may lead to disease.