Michael Grant

Preliminary Outcome Analysis in Patients With Breast Cancer and a Positive Sentinel Lymph Node Who Declined Axillary Dissection

Background:This retrospective study was designed to provide a preliminary outcome analysis in patients with positive sentinel nodes who declined axillary dissection.Methods:A review was conducted of patients who underwent lumpectomy and sentinel lymph node excision for invasive disease between January 1998 and July 2000. Those who were found to have sentinel lymph node metastasis without completion axillary dissection were selected for evaluation. Follow-up included physical examination and mammography.Results:Thirty-one patients were identified who met inclusion criteria. Primary invasive cell types included infiltrating ductal carcinoma, infiltrating lobular carcinoma, and mixed cellularity. Most primary tumors were T1. Nodal metastases were identified by hematoxylin and eosin stain and immunohistochemistry. Twenty-seven of the metastases were microscopic (<2 mm), and the remaining four were macroscopic. All patients received adjuvant systemic therapy. With a mean follow-up of 30 months, there have been no patients with axillary recurrence on physical examination or mammographic evaluation.Conclusions:We have presented patients with sentinel lymph nodes involved by cancer who did not undergo further axillary resection and remain free of disease at least 1 year later. This preliminary analysis supports the inclusion of patients with subclinical axillary disease in trials that randomize to observation alone.

Circulating Tumor Cells in Patients Undergoing Surgery for Primary Breast Cancer: Preliminary Results of a Pilot Study

IntroductionCirculating tumor cells (CTCs) have recently been shown to be an independent predictor of progression-free and overall survival in patients undergoing treatment for metastatic breast cancer. This study evaluates the presence and significance of CTCs in patient undergoing surgical resection of clinically localized primary breast cancer.MethodsPatients undergoing surgery for clinically localized primary breast cancer were enrolled into a prospective study. Thirty milliliters of blood was drawn and studied using the CellSearch assay.ResultsForty-one patients were enrolled at a single tertiary referral center. Ten patients (24.4%) had detectable CTCs preoperatively (PreOp). Nine (30%) patients were found to have CTCs postoperatively (PostOp). Overall, 16 (39%) were found to have CTCs either PreOp or PostOp. Hormone-negative patients were significantly more likely to have CTCs than hormone-positive patients. No other pathologic factor was predictive of the presence of CTCs.ConclusionCTCs are detectable and quantifiable in breast surgery patients. CTCs were more likely to be found in hormone receptor negative patients. Further study will allow correlation with other pathological variables and clinical outcome.

Sentinel lymph node biopsy followed by delayed mastectomy and reconstruction.

BACKGROUND The role of sentinel lymph node (SLN) biopsy with total mastectomy is evolving. In patients who desire mastectomy with immediate reconstruction, the final pathologic results of the SLN may create unique problems. Specifically, if the SLN is found to be positive on final pathology, the reconstructed patient would generally require a potentially difficult re-operation on the remaining axillary nodes. The purpose of this study was to review the results of patients who underwent an initial SNL biopsy followed by a planned mastectomy and reconstruction. METHODS A chart review of patients who underwent staged SLN biopsy with subsequent definitive procedure between 1997 and 2001 was conducted. These were evaluated with regard to type of tumor, status of sentinel node, and design of subsequent operation. RESULTS There were 40 patients who underwent an initial SLN biopsy followed by a staged mastectomy with reconstruction. Tumors included high-grade carcinoma in situ (n = 4), infiltrating ductal carcinoma (n = 28), invasive lobular carcinoma (n = 4), mucinous carcinoma (n = 1), adenoid cystic carcinoma (n = 1), and mixed ductal and lobular carcinoma (n = 2). Tissue biopsy was obtained by either open (n = 9) or needle (n = 31) technique. Twenty-five patients had a negative SLN biopsy and a delayed total mastectomy with immediate reconstruction. Positive SLNs were identified in 15 patients (37%). Eight patients had macroscopic nodal metastases and underwent a delayed modified radical mastectomy and immediate reconstruction. Seven patients had microscopic nodal metastases and 3 declined further axillary dissection. They proceeded with total mastectomy and immediate reconstruction. CONCLUSIONS These data suggest that a substantial proportion of patients treated with SLN biopsy, simple mastectomy, and reconstruction will have positive sentinel lymph nodes. Thus, the ideal approach for patients who wish to have reconstruction should involve an initial SLN biopsy as a separate procedure. If the SLN is benign, the patient may undergo a total mastectomy with immediate reconstruction. However, a patient with a positive SLN may proceed to a modified radical mastectomy with immediate reconstruction. This treatment algorithm eliminates a potentially difficult reoperation on the axilla following reconstruction.

Survival analysis following sentinel lymph node biopsy: a validation trial demonstrating its accuracy in staging early breast cancer.

Few long-term follow-up studies prove sentinel lymph node biopsy (SLNB) effectively stages breast cancer without the further evaluation of a completion axillary dissection. Our prospective study addressed this issue, enrolling 345 women with clinically node-negative breast cancer who underwent SLNB from October 1997 through December 2000. The median age of the patients in the study was 56.7 years. Average primary tumor size was 1.42 cm. Ninety-three patients had a positive sentinel lymph node (27%); 70 (75.3%) of these patients underwent completion axillary dissection, while 23 patients (24.7%) declined further surgery. Most (91.3%) of the patients who declined further surgery had evidence of micrometastatic disease only. The median follow-up period for all patients was 60 months. No tumor recurrences in the axilla were reported in either sentinel nodenegative or -positive patients. The local and systemic recurrence rates were 3.1% and 4% in node-negative patients and 2.2% and 4.3% in node-positive patients. Two patients (0.9%) in the node-negative group and 6 (6.5%) in the node-positive group died of their disease. Estimated 5-year disease-free survival rates were 96% for node-negative patients and 87% for node-positive patients (P = 0.02). The clinical false-negative rate of the SLNB in this study was 0%. This long-term validation trial proves the accuracy of the SLNB and its extremely low false-negative rate. The findings indicate that patients with a positive SLNB have significantly different survival rates than patients with a negative SLNB.

Predictors for nonsentinel node involvement in breast cancer patients with micrometastases in the sentinel lymph node.

Sentinel lymph node (SLN) biopsy in breast cancer allows for a more thorough pathologic assessment with serial sectioning and cytokeratin staining. This has resulted in increased detection of micrometastatic disease (tumor size <2 mm) in the SLN. Unfortunately, the value of completion axillary dissection after finding micrometastatic disease in the SLN remains poorly defined. Over a 2-year period, a prospective database of 305 patients who underwent SLN biopsy for breast cancer at Baylor University Medical Center was reviewed. Eighty-four (27.5%) of the patients had evidence of metastatic disease in the SLN. Twenty-four of the 41 patients identified as having micrometastatic disease in the SLN underwent completion axillary lymph node dissection. In these patients, all nonsentinel nodes were further studied by serial sectioning and immunohistochemistry. The median age of these 24 patients was 52 years (range, 34–83). Their primary tumor stages were T1a and T1b (n = 5), T1c (n = 15), and T2 (n = 4). A total of 328 nonsentinel lymph nodes were examined, including 225 from patients with infiltrating ductal carcinoma (n = 17) and 103 from patients with infiltrating lobular carcinoma (n = 7). In the patients with infiltrating ductal carcinoma, no additional nodal metastases were identified, while in those with infiltrating lobular carcinoma, additional nodal disease was found in 5 lymph nodes (2 of 12 patients, 17%). Primary tumor characteristics were not predictive of additional nodal disease. These data suggest that patients with micrometastasis in the SLN from infiltrating lobular carcinoma have a significant risk of harboring additional nodal disease and should undergo completion axillary dissection. However, those with micrometastatic disease from infiltrating ductal carcinoma have a very low incidence of additional metastasis and may not need completion axillary dissection.

Galactography in patients with nipple discharge

Nipple discharge is a common presenting symptom of underlying breast pathology. This study examined the impact of galactography on the evaluation of abnormal nipple discharge. Thirty-five women with spontaneous, unilateral nipple discharge who underwent galactography from 1995 to 1997 were retrospectively studied. Their presenting signs as well as mammographic, galactographic, and pathology findings were evaluated. Nipple discharge was bloody (n = 24), clear (n = 7), or serous (n = 4). A palpable mass was found in 5 patients, and discharge was spontaneous in 29 patients (83%). Mammography was normal in 25 patients (71%). Thirty patients (86%) had an abnormal ductogram that was characterized as a filling defect (n = 20), cutoff sign (n = 5), or ductal dilatation (n = 5). The ductogram demonstrated the location and depth of the lesion in 29 patients (97%). Excision was performed in 27 of 30 patients with an abnormal ductogram: 14 received complete subareolar duct excisions; 12, focused excisions; and 1, excision with a vacuum-assisted biopsy device. Pathology included intraductal papilloma (n = 20) and ductal ectasia (n = 7). Follow-up was completed in 24 patients, including 2 postoperative patients who had persistent discharge on manipulation. In conclusion, galactography is accurate in identifying the location of the ductal abnormality. It allows a focused surgical approach to the pathologic lesion in these patients.

Angiosarcoma of the breast: mammographic, clinical, and pathologic correlation.

The Breast Journal, Volume 9, Number 3, 2003 252–253 Address correspondence and reprint requests to: Michael Grant, MD, 3409 Worth St., Suite 300, Dallas, TX 75246, USA. Blackwell Publishing Ltd. Oxford, UK TBJ he Breast Journal 1075-122X 2 03 Blackwel Publishing M y–June 2003 93 riginal Artic e An os rcoma of the Breast fa t et l. Angiosarcoma of the Breast: Mammographic, Clinical, and Pathologic Correlation

Tamoxifen Downregulates Ets Oncogene Family Members ETV4 and ETV5 in Benign Breast Tissue: Implications for Durable Risk Reduction

Five years of tamoxifen reduces breast cancer risk by nearly 50% but is associated with significant side effects and toxicities. A better understanding of the direct and indirect effects of tamoxifen in benign breast tissue could elucidate new mechanisms of breast carcinogenesis, suggest novel chemoprevention targets, and provide relevant early response biomarkers for phase II prevention trials. Seventy-three women at increased risk for breast cancer were randomized to tamoxifen (20 mg daily) or placebo for 3 months. Blood and breast tissue samples were collected at baseline and posttreatment. Sixty-nine women completed all study activities (37 tamoxifen and 32 placebo). The selected biomarkers focused on estradiol and IGFs in the blood; DNA methylation and cytology in random periareolar fine-needle aspirates; and tissue morphometry, proliferation, apoptosis, and gene expression (microarray and reverse transcriptase PCR) in the tissue core samples. Tamoxifen downregulated Ets oncogene transcription factor family members ETV4 and ETV5 and reduced breast epithelial cell proliferation independent of CYP2D6 genotypes or effects on estradiol, ESR1, or IGFs. Reduction in proliferation was correlated with downregulation of ETV4 and DNAJC12. Tamoxifen reduced the expression of ETV4- and ETV5-regulated genes implicated in epithelial-stromal interaction and tissue remodeling. Three months of tamoxifen did not affect breast tissue composition, cytologic atypia, preneoplasia, or apoptosis. A plausible mechanism for the chemopreventive effects of tamoxifen is restriction of lobular expansion into stroma through downregulation of ETV4 and ETV5. The human equivalent of murine multipotential progenitor cap cells of terminal end buds may be the primary target. Cancer Prev Res; 4(11); 1852–62. ©2011 AACR.

A randomized clinical trial investigating the relationship between aprotinin and hypercoagulability in off-pump coronary surgery.

BACKGROUND: Off-pump coronary artery bypass (OPCAB) surgery is associated with a hypercoagulable state in which the platelet thrombin receptor, protease-activated receptor-1 (PAR-1), helps propagate a thrombin burst within saphenous vein grafts. Aprotinin, used in cardiothoracic surgery mainly for its antifibrinolytic properties, also spares platelet PAR-1 activation due to thrombin. We hypothesized that this PAR-1 antagonistic property provides an antithrombotic benefit during OPCAB surgery. METHODS: Patients were randomly assigned to receive saline (n = 38) or a modified full-dose regimen of aprotinin (n = 37) IV during OPCAB surgery. Blood sampled perioperatively from the coronary sinus, skin wounds, and systemic circulation was analyzed to test coagulation and platelet function. Major adverse cardiovascular events were monitored by obtaining troponin I at 24 h (myocardial infarction), predischarge computed tomography angiography (vein graft thrombosis), and by clinical examination for stroke. RESULTS: Coronary sinus blood obtained immediately after OPCAB surgery showed significantly less activation in the aprotinin group, as judged by reduced formation of platelet-leukocyte conjugates (P < 0.02) and platelet-derived microparticles (P < 0.05). The aprotinin group showed inhibition of platelet aggregation induced by thrombin (P = 0.007) but not adenosine diphosphate. Thrombin generation, defined by F1.2 levels, was significantly reduced by aprotinin in the coronary sinus but not in skin wound incisions. Major adverse cardiovascular events were significantly reduced in aprotinin-treated patients (5.4% vs 29.7%, P < 0.05). Aprotinin also demonstrated antifibrinolytic properties through diminished red blood cell transfusion (P < 0.04) and reduced blood loss postoperatively (603 ± 330 vs 810 ± 415 mL, P < 0.004). CONCLUSION: This study demonstrates that aprotinin protects patients undergoing OPCAB surgery from a hypercoagulable state by diminishing thrombin-induced platelet activation and thrombin generation within saphenous vein grafts, while maintaining systemic hemostatic and antifibrinolytic benefits. These results support further investigation of aprotinin and other PAR-1 antagonists in OPCAB surgery.

Cannula-Assisted Flap Elevation (CAFE): A Novel Technique for Developing Flaps During Skin-Sparing Mastectomies

BackgroundOne of the most challenging procedures in breast surgery is the skin-sparing mastectomy (SSM). Various techniques and incisions have evolved that characterize this procedure; however, what is common in all of them is the smaller the incision, the more difficult it is to develop the skin flaps.MethodsA procedure was developed that incorporates the use of liposuction cannulas (without suction) to create the skin flaps. The technique and results are described in this manuscript.ResultsFrom October of 2012 to April 2014, 289 mastectomies (171 patients) were performed using the CAFE procedure on women of all shapes and sizes. Postoperatively, no problems were experienced with flap viability using this technique. The main difference in side effects between the CAFE technique and other standard techniques for developing flaps in SSMs was more bruising than normal, but this resolved rapidly. The results for use of this technique were consistently impressive. The learning curve for this procedure is very short, especially for those who perform SSMs using sharp technique (scissors). Residents and fellows became proficient with the CAFE technique in a relatively short amount of time. Plastic surgeons were pleased with the cosmetic outcomes of their reconstructions that follow this type of mastectomy. Patients were extremely satisfied with their reconstructions as well.ConclusionsIncorporating the use of liposuction cannulas (without suction) makes the creation of flaps for SSM a relatively simple and rapid method. It is especially useful to assist in developing skin flaps with even the smallest of skin incisions.