Notes: Abstract: Axillary nodal status is the most significant prognosticator for predicting survival and guiding adjuvant therapy in breast cancer patients. Sentinel lymph node biopsy (SLNB) represents a minimally invasive procedure with low morbidity for staging axillary nodal status. In this article we review and report our experiences in patients with early breast cancer who underwent SLNB at the Revlon/UCLA Breast Center. Between September 1998 and May 2000, a total 83 SLNBs were performed in 81 patients with proven breast cancer and negative axillary examination who elected to have SLNB as the first step of nodal staging. Two patients had bilateral breast cancer. SLNB was localized by using both 99Tc sulfur colloid (83 cases) and isosulfan blue dye (75 cases). Data of these patients were prospectively collected and analyzed. The clinical and pathologic characteristics of women with positive and negative sentinel lymph nodes (SLNs) were compared to identify features predictive of SLN metastasis. Of the 83 cases, the SLN was successfully localized in 82 (98.8%). Sixty-three percent of patients had SLNs found in level I only, 18.3% in both level I and II, and 4.9% in level II alone. The vast majority (84.3%) of these cases had T1 breast cancer with an average size of 1.55 cm for the entire series. Twenty-three patients (28%) had positive SLNs, with an average of 1.5 positive SLNs per patient. Fifteen had metastases detected by hematoxylin and eosin staining and 8 had micrometastases detected by immunohistochemistry (IHC) using anticytokeratin antibodies. Ten of the former group agreed to and 2 of the latter group opted for full axillary lymph node dissection (ALND). An average of 17.5 lymph nodes were removed from each ALND procedure. Additional metastases or micrometastases were found in seven patients (in a total of 28 lymph nodes). Three patients with completely negative SLNs experienced additional axillary lymph node removal due to their election of free flap reconstruction. None had metastases detected in these lymph nodes. The absence of estrogen and progesterone receptors (ER/PR) by IHC (p = 0.036) and the presence of lymphatic/vascular invasion (LVI) (p = 0.002) predicted positive SLNs in patients with early breast cancer in a univariate analysis; in a multivariate analysis only LVI was predictive (p = 0.0125). Histologic type, nuclear grade, tumor differentiation, HER-2/neu and p53 status, S-phase fraction, and DNA ploidy did not predict SLN status. Immediate postoperative complications were uncommon and delayed complications completely absent. Because of the high detection rate, accurate staging, and minimal morbidity, SLNB should be offered as a choice to women with small breast cancers and clinically negative nodes. Because positive LVI and negative ER/PR status are highly predictive of pathologically positive SLNs in small breast cancers, women whose cancers meet these criteria should be advised preoperatively about their risk of having a positive SLN and may benefit from intraoperative assessment (frozen section and/or touch preparation) of their SLNs.

Notes: Abstract: Breast-conserving surgery is the preferred operation for the majority of women with stage I or II breast cancer. It consists of the removal of primary breast cancer with a rim of adjacent normal tissues and the axillary dissection. The goal of breast-conserving surgery is to control the local-regional disease without removing the entire breast and to provide an accurate pathologic staging of the tumor (T) and draining nodes (N). The primary outcomes of breast-conserving surgery in treating women with invasive breast cancer are measured by the survival rate, local disease control and cosmetic results. The consideration of the factors that have major impacts on the outcomes of this form of treatment are discussed. This article provides a framework for considering and performing breast-conserving surgery and for critically evaluating the literature dealing with the various issues involved in the treatment of women with early breast cancer.

Notes: Abstract: A 53-year-old white female on mammography had “suspicious” microcalcifications. Upon excision, these turned out to be pseudomicrocalcifications created by the intraductal cellular proliferations of atypical ductal hyperplasia so dense as to create radiodensities. 

Notes: Abstract: It has been shown that early detection of breast cancer saves lives. Recently there has been increasing interest in nipple aspirate fluid as a potential avenue for breast cancer diagnosis. One major challenge regarding studies of nipple aspirate fluid is the ability to obtain adequate samples. Here we describe the use of nasal oxytocin in a group of volunteer women in order to increase the yield of nipple aspirate fluid. 

Notes: Abstract:  The HER-2/neu gene is a proto-oncogene that is amplified in 10–30% of breast cancers. New drugs for targeted therapy, such as Herceptin, are effective for patients with HER-2/neu-positive tumors, making it necessary to have a noncostly and accurate method to assess HER-2/neu status. We studied the correlation of findings made by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) staining and the possibility of combining IHC and other clinicopathologic characteristics of breast tumors to predict FISH-determined HER-2/neu status. The clinicopathologic characteristics analyzed were the size of the tumor, p53, lymph-vascular invasion, estrogen/progesterone receptors (ER/PR), tumor grade, axillary lymph node status, and patient age. A total of 199 cases of invasive breast cancer studied at the UCLA Pathology Laboratory during 2003 were included in this study. Tumors with IHC 0, 1+, 2+, and 3+ scores were found to be FISH positive in 3.5%, 6.4%, 25.7%, and 81.5% of the respective groups. Our study showed a strong association between the FISH-negative and IHC scored 0 and 1+ tumors, suggesting that the FISH test may not be necessary in these cases (p 〈 0.0001). Although the concordance between IHC 3+ and FISH positive is high, 18% of the patients with overexpression of HER-2/neu fail to show gene amplification by FISH. HER-2/neu positivity was found to be proportionally associated with increasing grade in infiltrating ductal carcinoma (p 〈 0.0001). p53-positive tumors are more likely to be HER-2/neu amplified (p = 0.0003). Tumors that are negative for ER/PR are also associated with HER-2/neu positivity by FISH (31.15%, p = 0.0016). FISH-determined HER-2/neu status is not associated with histologic type, tumor size, nodal status, lymph-vascular invasion, or patient age.

Notes: Abstract The treatment of extremity soft tissue sarcoma is now directed at limb preservation with the addition of various adjuvant therapies to improve treatment results. To achieve this goal, a knowledge of prognostic factors for extremity soft tissue sarcoma becomes increasingly critical. The object of this study was to analyze prognostic factors for survival in patients with extremity liposarcoma. Eighty-three patients with primary localized extremity liposarcoma, admitted from 1968 to 1978, were retrospectively reviewed. Surgical resection was the primary mode of treatment. Eleven prognostic factors were analyzed. Tumor factors included: histologic subtype, tumor grade, size, depth, invasion of vital structures, and site; operative factors included: type of operation, and surgical margins; and patient factors included: symptoms, age at diagnosis, and sex. Kaplan-Meier survival curves, and univariate and stratified log-rank tests of association were performed. Independent factors for predicting survival were identified using the Cox model stepwise regression technique. In univariate analysis of the entire group of patients, 5 factors were significant for tumor mortality: tumor grade (p=0.00005), histologie subtype (p=0.00025), tumor size s≥5 cm (p=0.005), type of surgery/ margin (p=0.0001), and invasion of vital structures (p=0.008). When associations among all factors were analyzed, it was found that many factors were interdependent. The independent prognosticators were, therefore, determined according to the Cox model technique. For the multivariate analysis, well-differentiated and lipoblastic liposarcomas were excluded because of lack of survival variation within each group. The former group had no tumor-related deaths and the latter group showed 80% tumor mortality. The remaining patients with myxoid, high-grade fibroblastic and pleomorphic liposarcoma were subjected to multivariate analysis. Three factors emerged as independent prognostic predictors: high-grade tumor (p=0.013), inadequate resection/amputation (p=0.003), and tumor≥cm (p=0.04).

Notes: Abstract PURPOSE: Human monoclonal antibody (HuMAb) SK1, a human monoclonal IgM, has previously been shown to react selectively with a wide range of human carcinomas. In this study, the complement-dependent cytotoxicity (CDC) mediated by the HuMAb SK1 was investigated. METHODS: The presence of AgSK1 on the two studied cell lines, HT29 and PANC-1, was evaluated by the immunocytochemical staining. The intracellular and surface locations of the targeting antigen of HuMAb SK1 were further characterized by the study of flow cytometry. The specific lysis of target cells by the HuMAb SK1 in the CDC assay was studied. RESULTS: In the presence of human complement, the HuMAb SK1 was shown to be effective in the lysis of cultured human gastrointestinal cancer cells as well as the fresh colon cancer cells derived from the patient's specimens. In addition, our data suggested that HuMAb SK1 activated the mouse complement in a similar magnitude. CONCLUSIONS: We concluded that HuMAb SK1 showed some promise for future clinical trials. The in vitro CDC effect of HuMAb SK1 with mouse complement suggested that the antitumor effect of HuMAb SK1 might be successfully studied in the nude mouse model bearing xenografts of human colon cancer as a part of the preclinical evaluation.

Notes: Abstract Background: The roles of breast conservation and surgical evaluation of the contralateral breast in the treatment of lobular carcinoma of the breast remain unclear. The aim of this study was to compare local recurrence, 5-year survival, and incidence of contralateral breast cancer in women with lobular carcinoma to that in women with infiltrating ductal carcinoma. Methods: Women with infiltrating ductal carcinoma (IDC) and invasive lobular breast carcinoma (ILC) diagnosed during the years 1984 to 1994 were identified through a statewide tumor registry. The women were divided into groups based on their histology and treatment (breast conservation or modified radical mastectomy). The incidences of contralateral breast cancer, local recurrence, and 5-year survival were compared within each histologic group and treatment category. Results: During the period 1984 to 1994, 4886 women were diagnosed with invasive lobular or ductal breast carcinoma. Of these, 316 (6.5%) had infiltrating lobular cancer. The 5-year survival rates were 68% and 71% for ILC and IDC, respectively (p=0.5). The local recurrence rates were 2.8% and 4.3% for ILC treated with lumpectomy and axillary nodal dissection (LAND) and modified radical mastectomy (MRM), respectively, which were not significantly different from that obtained with IDC (LAND=2.5%, MRM=2.1%). The incidence of contralateral breast cancer during the period was 6.6% and 6.5% for ILC and IDC, respectively. Conclusions: Invasive lobular carcinoma can be safely treated with breast conservation with no difference in local recurrence or survival. In the absence of a suspicious finding on clinical or radiologic examination, routine contralateral breast intervention is not recommended.

Notes: Abstract Background: Nonhuman monoclonal antibodies (MoAbs) of desired specificities have been studied in cancer treatment and tumor targeting with minimal success. Attempts of using humanized chimeric antibodies have not improved significantly their clinical applications. We have engaged in the development of human MoAbs by incorporating the in vitro immunization protocols to the nodal lymphocytes of cancer patients. Three human MoAbs thus generated were found to be strongly reactive with various human malignancies. The antigens recognized by the three antibodies were selected for immunochemical and biochemical characterizations. Methods: The antigens investigated were AgSK1, PA 1-2 and PA 3-1. The patterns of each antigen expression in various human cancer cell lines were studied by the immunocytochemical staining technique. The expression of AgSK1 in association with cellular proliferation was examined by the flow cytometry analysis. In studying the biochemical natures of these antigens, their sensitivies toward various chemical and physical treatments were determined. The antigens that were shown to be proteins were subjected to SDS-PAGE and Western blot for estimations of molecular weights. Results: The AgSK1 was detected in 10 human carcinoma cell lines but in none of the melanoma cell lines. This suggests that SK1 may be an epithelial or carcinoma marker. The phenotypic expressions of AgSK1 were shown to be associated with proliferation of carcinoma cells. Biochemically AgSK1 was a sialophycoprotein with an estimated molecular weight of 42–44 kilodaltons (kDa). HuMAb PA1-2 demonstrated a unique staining pattern at both the cytoplasmic and intercellular interface. The stained filamentlike structures extending from cell to cell indicated that Ag PA1-2 might play a role in cellular interactions. Biochemically, Ag PA1-2 appeared to be an asialocarbohydrate. The Ag PA3-1 was a cytoplasmic glycoprotein expressed by all 13 cell lines. The estimated molecular weights of PA3-1 were 164, 104, and 40 kDa. Conclusions: Tumor-associated antigens recognized by the human MoAbs may be more relevant clinically than those recognized by the mouse immune system. Carcinoma-specific human MoAbs are desirable for cancer treatment and tumor localization.

Notes: A method involving short pulses of 5-bromodeoxyuridine (brUdRib) followed by irraidation with 313 nm light was used to locate the time of replication of certain genes during the cell cycle of two cell lines, AF8 and AL106. AF8, a temperature-sensitive mutant of BHK21/13 cells, grows at 33°C but not at 39.5°C. AL106, a hybrid clone of tsAF8 and SV-40 transformed Lesch-Nyhan fibroblasts (LNSV), which retains all hamster chromosomes and one human chromosome (No. 3), has the ability to grow at 39.5°C. AF8 and AL106 cells synchronized at the G1-S boundary were released from their block and pulsed with brUdRib for 2-hour periods during the S phase. The cells were subsequently irradiated with 313 nm light. Colony-forming efficiency and revertants frequency were studied. Incorporation of brUdRib during the early S phase (0-4 hours from the begining of S), decreased the colony-forming efficiency of AL106 cells both at 33°C and 39.5°C, and also of AF8 cells at 33°C. No AF8 colonies grew at the nonpermissive temperature regardless of the treatment. Thus the time of replication of genes responsible for colony-forming ability was the same in tsAF8 at the permissive temperature and in AL106 at both temperatures. The time of replication of the genes responsible for the ts function in AF8 cells was located by determining the revertants frequency in synchronized AF8 cells pulsed with brUdRib and irradiated during 1- to 2-hour periods of the S phase. Back-mutants were scored by counting the number of clones capable of growing at 39.5°C (nonpermissive for AF8 cells). The highest frequency of induced back-mutations occurred in synchronized AF8 cells pulsed with brUdRib (and irradiated) between two to four hours from the begining of the S phase. Exposure to brUdRib during other periods of the S phase or during G1 had no effect on the reversion rate.This method can be used to locate the time of replication (in S) of ts genes in other temperature-sensitive mutants or of other specific genes in other conditional mutants.