Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation.

BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy. METHODS: Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years. RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women. CONCLUSIONS: The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue.

Local recurrence of breast cancer in the stereotactic core needle biopsy site: case reports and review of the literature.

Early mammographic detection of nonpalpable breast lesions has led to the increasing use of stereotactic core biopsies for tissue diagnosis. Tumor seeding the needle tract is a theorectical concern; the incidence and clinical significance of this potential complication are unknown. We report three cases of subcutaneous breast cancer recurrence at the stereotactic biopsy site after definitive treatment of the primary breast tumor. Two cases were clinically evident and relevant; the third was detected in the preclinical, microscopic state. All three patients underwent multiple passes during stereotactic large-core biopsies (14 gauge needle) followed by modified radical mastectomy. Two patients developed a subcutaneous recurrence at the site of the previous biopsy 12 and 17 months later; one had excision of the skin and dermis at the time of mastectomy revealing tumor cells locally. In summary, clinically relevant recurrence from tumor cells seeding the needle tract is reported in two patients after definitive surgical therapy (without adjuvant radiation therapy). Often, the biopsy site is outside the boundaries of surgical resection. Since the core needle biopsy exit site represents a potential area of malignant seeding and subsequent tumor recurrence, we recommend excising the stereotactic core biopsy tract at the time of definitive surgical resection of the primary tumor.

Phase I trial of TALL-104 cells in patients with refractory metastatic breast cancer.

The human cytotoxic T-cell line TALL-104 displays antitumor effects in animals with implanted and spontaneous malignancies. A Phase I trial was conducted to determine toxicity of TALL-104 cell therapy in women with metastatic refractory breast cancer. Fifteen patients with metastatic infiltrating ductal (n = 12), lobular (n = 2), or medullary (n = 1) carcinoma received escalating doses of lethally irradiated TALL-104 cells (three patients/group received 10(6), 3 x 10(6), 10(7), 3 x 10(7), and 10(8) cells/kg) for 5 consecutive days (induction course). Patients without progressive disease received monthly maintenance 2-day infusions at the same dose level. Mild grade I/II toxicity developed in 11 patients regardless of cell dose. One grade IV toxicity consequent to hepatic tumor necrosis occurred in a patient given 10(8) cells/kg, 3 weeks after the induction course. Nine patients progressed within 1 month from induction, and five patients had stable disease for 2-6 months. One patient (at 3 x 10(7)/kg) had improvement of liver metastases and ascites, and a second patient (at 10(6)/kg) experienced a dramatic relief in bone pain. Increases in blood natural killer cell activity and levels of IFN-gamma, interleukin-10, and activation markers (soluble interleukin-2 receptor and soluble intercellular adhesion molecule-1) were often seen. Only one patient developed anti-HLA class I antibody responses against TALL-104 cells; specific CTL activity developed in three patients during induction and in four patients during the maintenance boosts. In conclusion, TALL-104 cells were well tolerated by patients with metastatic breast cancer at the doses and regimen tested. The clinical responses observed in this preliminary trial demonstrate that further investigation of TALL-104 cell therapy is warranted.

Pancreatic carcinoma deemed unresectable at exploration may be resected for cure: an institutional experience.

Only a minority of patients with a diagnosis of pancreatic adenocarcinoma (PA) have disease amenable to curative resection. Between April 1987 and March 1999, 40 patients with pancreatic adenocarcinoma deemed unresectable at exploration at other institutions were considered for neoadjuvant treatments and then re-evaluated for possible re-exploration. We retrospectively compared the clinical outcomes, including overall survival (OS), among three groups: Group A, 22 previously unresectable patients who were subsequently successfully resected, 20 after induction therapy; Group B, 31 patients who received preoperative chemoradiotherapy before their only operation; and Group C, 33 patients who were primarily resected, 27 of whom were then treated with adjuvant therapy. Of those resectable from Group A, 5 required portal venorrhaphy and 3 had hepatic artery reconstruction. Eighteen of the 40 patients were unresectable because of progression of disease with a mean OS of 8 months; 12 were assessed at second laparotomy; 6 were excluded from second operation on the basis of preoperative imaging studies. Kaplan-Meier curves showed no differences in OS among the three groups: OS in Group A was 34 months; Group B, 21; and Group C, 13 (P = 0.15). Margin status was comparable in all three groups (P = 0.52). As expected, nodal positivity was greatest in Group C (P = 0.001). There were no operative mortalities in Group A, and the morbidity rate was comparable with that of Groups B and C. Upon re-evaluation, many tumors (54%) previously deemed "unresectable" were surgically extirpated for cure with a median survival comparable with that of patients who did not undergo previous exploration.

Should internal mammary lymph nodes in breast cancer be a target for the radiation oncologist?

PURPOSE: The elective treatment of internal mammary lymph nodes (++IMNs) in breast cancer is controversial. Previous randomized trials have not shown a benefit to the extended radical mastectomy or elective IMN irradiation overall, but a survival benefit has been suggested by some for subgroups of patients with medial tumors and positive axillary lymph nodes. The advent of effective systemic chemotherapy and potential for serious cardiac morbidity have also been factors leading to the decreased use of IMN irradiation during the past decade. The recent publishing of positive trials testing postmastectomy radiation that had included regional IMN irradiation has renewed interest in their elective treatment. The purpose of this study is to critically review historical and new data regarding IMNs in breast cancer. METHODS AND MATERIALS: The historical incidence of occult IMN positivity in operable breast cancer is reviewed, and the new information provided by sentinel lymph node studies also discussed. The results of published randomized prospective trials testing the value of elective IMN dissection and/or radiation are analyzed. The data regarding patterns of failure following elective IMN treatment is studied to determine its impact on local-regional control, distant metastases, and survival. A conclusion is drawn regarding the merits of elective IMN treatment based on this review of the literature. RESULTS: Although controversial, the existing data from prospective, randomized trials of IMN treatment do not seem to support their elective dissection or irradiation. While it has not been shown to contribute to a survival benefit, the IMN irradiation increases the risk of cardiac toxicity that has effaced the value of radiation of the chest wall in reducing breast cancer deaths in previous randomized studies and meta-analyses. Sentinel lymph node mapping provides an opportunity to further evaluate the IMN chain in early stage breast cancer. Biopsy of "hot" nodes may be considered in the future to select patients who are most likely to benefit from additional regional therapy to these nodes. CONCLUSIONS: Irradiation of the IMN chain in conjunction with the chest wall and supraclavicular region should be considered only for those with pathologically proven IMNs with the goal of improving tumor regional control.

Perioperative nutrition support for patients undergoing gastrointestinal surgery: critical analysis and recommendations.

There is a high incidence of malnutrition in hospitalized patients undergoing gastrointestinal surgery. Malnutrition is clearly associated with increased morbidity and mortality after major gastrointestinal surgery. The efficacy of perioperative nutrition support to reduce surgical complications and mortality significantly has been an area of active clinical investigation over the past three decades. From multiple prospective, randomized trials, significant benefit from perioperative nutritional support has been demonstrated in severely malnourished patients undergoing major surgery. Results of the prospective, randomized trials studying the effects of perioperative nutrition support on patients undergoing gastrointestinal surgery are reviewed and critically analyzed.

A simplified procedure for creating a urinary conduit in patients with a colostomy.

A simplified procedure for constructing a urinary conduit is described in patients who have already undergone fecal diversion with colostomy. Two patients are described in whom this method was utilized to create a urinary conduit without the need for an intestinal anastomosis. This procedure is especially suited to high-risk surgical candidates with comorbid medical conditions, multiple previous surgical procedures or prior pelvic radiotherapy in whom avoiding an intestinal anastomosis can significantly reduce postoperative morbidity. This simplified method for creating a urinary conduit is described in two patients and discussed as related to alternative methods for establishing supravesicular urinary diversion.

Correlation of lesion appearance and histologic findings for the nodes of a breast MR imaging interpretation model.

An interpretation model for evaluating magnetic resonance (MR) images of the breast was constructed that allowed differentiation of benign from malignant palpable or mammographically visible abnormalities. Architectural features define each node of the model. Investigation was subsequently made of the histologic findings in individuals within each node and of the frequency with which each histologic finding manifested as a particular architectural feature to determine whether nodal location and specific histologic findings are mutually predictive. The strongest associations were found between fibrocystic change and smooth masses, fibroadenoma and lobulated masses with nonenhancing internal septations, invasive ductal carcinoma (with or without ductal carcinoma in situ [DCIS]) and enhancing irregular or spiculated masses, invasive tubular carcinoma or radial scar and spiculated masses, medullary or colloid carcinoma and enhancing lobulated masses, invasive lobular carcinoma and the absence of a focal mass, DCIS and ductal enhancement, and DCIS (with or without invasive ductal carcinoma) and regional enhancement. Nodal location and histologic findings proved to be mutually predictive within the model; that is, the nodal location of MR imaging features within the model can be used to predict histologic findings and vice versa.

Spontaneous pelvic hematoma simulating neoplasm: case report and literature review.

Spontaneous hematomas are rare and can present with acute or chronic symptoms. Our patient presented with deep vein thrombosis of the lower extremity associated with a spontaneous pelvic hematoma. This lesion was radiologically and clinically indistinguishable from a soft-tissue neoplasm. The case of a spontaneous pelvic neoplasm in an otherwise healthy young man is presented and the literature reviewed regarding issues of differential diagnosis and clinical management.

Unique presentation of a granular cell tumor as a paratracheal mass.

An unusual presentation of a granular cell tumor is reported with a review of the natural history and pathologic characteristics of this tumor. Our patient was asymptomatic and presented with a mass in the inferior right neck on routine physical examination. Preoperative radiologic evaluation suggested a parathyroid adenoma but the normal parathormone level was inconsistent with this diagnosis. At surgery, a firm mass was identified inferior to the right lobe of the thyroid gland and was found to represent a granular cell tumor densely adherent to the trachea. This case demonstrates a unique presentation for this relatively rare neoplasm which was treated with complete surgical resection.

Evidence for selective use of bone scans in early stage breast cancer.

To determine the usefulness of bone scans in detecting metastatic disease in women with early stage breast cancer, records of 193 patients who had bone scans preformed and underwent breast conservation therapy at a single institution were reviewed. Patients with invasive T1 or T2 breast carcinomas were eligible for this study; patients with a true positive bone scan were excluded from conservation therapy and, thus, were excluded from this study. The incidence of false positive bone scans in this study population was 32.6% (63/193 patients). Patients over 50 years of age had a significantly greater incidence of false positive bone scans (p<0. 05). In the 63 patients with false positive bone scans, 101 radiographs were performed to exclude metastatic disease in areas of increased uptake identified on bone scan. No significant difference in the rate of false positive bone scans was seen in relation to tumor size, pathologic or clinical nodal status or hormone receptor activity of the primary tumor. Thus, selective use of bone scans is advocated in patients with early stage (T1 or T2) breast cancer.

Growth characteristics and metastatic properties of human breast cancer xenografts in immunodeficient mice.

We evaluated the growth and metastatic potential of two human breast cancer cell lines and 16 patient-derived biopsy specimens, representing the most common histological types of breast carcinomas, upon subcutaneous implantation into severe combined immunodeficient (SCID) mice. The method of engraftment we used, based on implantation of intact tissue specimens and complete immunosuppression of the host, provided an easier system to grow human breast carcinoma specimens in mouse models and resulted in a 50% success rate of tumor take. No correlation was found between growth in SCID mice and pathological diagnosis, grading, or estrogen/progesterone receptor expression by the tumor biopsy specimen. Serial passage of the tumor fragments in SCID mice resulted in increased metastasis rates and more rapid emergence of a palpable tumor mass. A tumor from a patient with infiltrating ductal carcinoma, which grew aggressively and metastasized in 100% of the female SCID mice, was also successfully engrafted in 100% of nonobese diabetic (NOD)/SCID female mice, but systemic spread was minimal. Fragments of the same tumor grew in only 33% of male SCID mice with very limited metastases. A strong correlation (r = 0.997) was observed between tumor burden and the presence of soluble (serum) interleukin-2 receptor, a marker associated with a subset of human breast tumors. All together, these data indicate the usefulness of SCID/human breast tumor xenografts for measuring tumor progression and evaluating novel therapeutic approaches to breast cancer.

Myofibroblastoma associated with bilateral gynecomastia: a case report and literature review.

Myofibroblastoma of the breast is a recently recognized benign mesenchymal mammary tumor that typically occurs as a unilateral, solitary lesion. Myofibroblastomas are well-circumscribed, unencapsulated tumors characterized by spindle cells in fascicles which exhibit varying degrees of myogenic and fibroblastic differentiation. Our case reports a mammary myofibroblastoma occurring in an 82-year-old male with gynecomastia and reviews the reported incidence of this benign spindle cell tumor in the world literature.

Catamenial mononeuropathy and radiculopathy: a treatable neuropathic disorder.

OBJECT: The aim of this study was to investigate the indications and treatment options in patients with lower-extremity neuropathies and radiculopathies caused by endometriosis. METHODS: The authors identified five patients whose symptoms included catamenial pain, weakness, and sensory loss involving the sciatic and femoral nerves and multiple lumbosacral nerve roots. Radiographic studies supported the diagnosis of catamenial neuropathy or radiculopathy, but definitive diagnosis depended on surgical and pathological examination. Treatment of symptoms, including physical therapy and a course of antiinflammatory or analgesic medication, was not helpful. Patients responded favorably to hormonal therapy. Laparoscopy or open exploration for extrapelvic lesions was performed for diagnosis or for treatment when hormone therapy failed. Pain and sensory symptoms responded well to therapy. Weakness improved, but never recovered completely. CONCLUSIONS: Catamenial neuropathy or radiculopathy should be considered when evaluating reproductive-age women with recurring focal neuropathic leg pain, weakness, and sensory loss.

Diagnostic performance characteristics of architectural features revealed by high spatial-resolution MR imaging of the breast.

OBJECTIVE: Our objective was twofold: to determine which architectural features revealed by high spatial-resolution MR imaging of the breast contribute to diagnostic accuracy and to evaluate the diagnostic performance characteristics of those architectural features. MATERIALS AND METHODS: Eligible patients with suspicious mammographic or palpable findings or both underwent MR imaging. Ninety-three patients whose MR images revealed lesions that corresponded to the mammographically visible or palpable findings were included in the study. Patients were examined with sagittal T1-weighted spin-echo MR imaging, fat-saturated T2-weighted fast spin-echo MR imaging, and dynamically enhanced fat-saturated fast gradient-echo MR imaging. All patients underwent subsequent excisional biopsy or cyst aspiration. Lesions were identified initially by an experienced radiologist who was aware of the patient's clinical or mammographic information. Two radiologists who were unaware of the patients' histories and who had less experience in MR imaging of the breast then independently evaluated each lesion for the architectural-features and predicted each lesion's potential for malignancy. RESULTS: Architectural features that were highly predictive of benign disease included smooth or lobulated borders (97-100%), the absence of mass enhancement (100%), and enhancement that was less than the enhancement of surrounding breast fibroglandular tissue (93-100%). Nonenhancing internal septations were specific for the diagnosis of fibroadenoma. Architectural features that were highly predictive of malignant disease included spiculated borders (76-88%) and peripheral rim enhancement in the presence of central lesion enhancement (79-92%). CONCLUSION: Architectural features revealed by high spatial-resolution MR imaging of the breast can help distinguish benign from malignant disease.

Breast MR imaging: interpretation model.

PURPOSE: To develop an interpretation model based on architectural features of suspicious breast findings on magnetic resonance (MR) images. MATERIALS AND METHODS: One hundred ninety-two patients with mammographically visible or palpable findings underwent T1- and fat-saturated T2-weighted spin-echo and contrast agent-enhanced fat-saturated gradient-echo MR imaging. Patients underwent subsequent excisional biopsy for histopathologic confirmation. An interpretation model was constructed by using 98 cases and was tested prospectively and expanded by using 94 different cases. Sensitivity, specificity, predictive values, and receiver operating characteristic curves were computed for all models. RESULTS: Individual features with high predictive values were MR visibility, enhancement degree and pattern, focal mass border characteristics, and focal mass internal septations. Feature combinations with high negative predictive values for malignancy were absence of an MR-visible abnormality, focal masses with smooth borders, lobulated or irregular masses with nonenhancing internal septations, and focal masses with no (or minimal) enhancement. The validated- and revised-model performance characteristics were, respectively, as follows: sensitivity, 100% and 96%; specificity, 69% and 79%; positive predictive value, 75% and 76%; negative predictive value, 100% and 97%; and overall accuracy, 83% and 86%. CONCLUSION: An interpretation model that incorporates breast MR architectural features can achieve high sensitivity and improve specificity for diagnosing breast cancer.

Cell therapy of a highly invasive human breast carcinoma implanted in immunodeficient (SCID) mice.

Although enormous progress has been made in the detection and treatment of localized (nonmetastatic) breast cancer, there has been relatively moderate progress toward the effective treatment of advanced disease. This study investigates the antitumor efficacy of a potent MHC nonrestricted cytotoxic human T cell line (TALL-104) upon transfer into a clinically relevant mouse model of metastatic breast cancer. Fragments from a surgical specimen of a patient with infiltrating ductal carcinoma were implanted s.c. in the flank region of severe combined immunodeficient (SCID) mice. One hundred % of the animals developed a local tumor mass that metastasized to subaxillary and inguinal lymph nodes, bones, lungs, liver, kidneys, ovaries, and brain, very closely mimicking the human disease. Multiple i.p. transfers of gamma-irradiated (nonproliferating) TALL-104 cells into mice bearing low tumor burden (the primary tumor mass weighed only 150 mg) completely arrested local tumor growth and prevented systemic spread into local lymph nodes and distant organs. Remarkably, cell therapy administered in an advanced disease stage (when the tumor weighed 2 g) induced a significant or total regression of established metastasis with no obvious effects on the primary tumor mass. Profound antitumor effects against both local and systemic disease were instead seen in mice that received cell therapy after surgical excision of the primary tumor. The implications of these data in adjuvant breast cancer therapy are discussed.

Effect of protein intake on tumor growth and cell cycle kinetics.

Previous research has documented significant acceleration of tumor growth in animals receiving short-term parenteral nutrition. This study was performed to determine the effect of long-term enteral protein intake on tumor cell cycle kinetics in the tumor-bearing host. Fifty Lewis/Wistar rats with subcutaneous mammary tumor implants (AC-33) were randomized to receive a standard protein diet (22.0% protein; 4.20 kcal/g) or protein-depleted diet (0.03% protein; 4.27 kcal/g). Animals were sacrificed after 7 or 14 days on each diet and tumor cytokinetics determined by flow cytometry. Tumor volume was significantly reduced in animals receiving the protein-depleted versus standard protein diet after 14 days (P < 0.01). No difference was found in tumor cell cycle kinetics (% G0/G1, S, or G2/M populations) or tumor growth fraction (S + G2/M) in animals receiving standard or protein-depleted diet after 7 or 14 days. These results suggest that reduced tumor growth with prolonged protein depletion in this model occurs by either (a) movement of tumor cells from the active cell cycle to the dormant G0 state or (b) uniform increase of cell cycle duration without changing the relative proportion of cells throughout the cell cycle. The potential therapeutic implications of nutrient-induced alterations in tumor growth are discussed.

Staging of suspected breast cancer: effect of MR imaging and MR-guided biopsy.

PURPOSE: To investigate the effect of contrast material-enhanced magnetic resonance (MR) imaging on staging of breast cancer in patients with mammographically or clinically suspected tumor. MATERIALS AND METHODS: One hundred seventy-six patients underwent breast MR imaging at 1.5 T before excisional biopsy of a suspicious mammographic or palpable abnormality. Diagnostic imaging studies in patients with biopsy-proved or presumed breast carcinoma were reviewed. RESULTS: Sixty-four patients met the study criteria. MR imaging enabled detection of all 57 invasive breast cancers and nine of 15 in situ cancers. In 22 patients (34%), MR imaging depicted one or more cancers not visible at mammography, 13 (20%) of which were unsuspected multifocal or diffuse disease. As a result of the increased sensitivity of MR imaging compared with that of mammography, clinical staging and subsequent treatment were altered in seven patients (11%). CONCLUSION: MR imaging allows detection of mammographically and clinically occult foci of carcinoma in patients with suspected breast cancer.