Metastatic lobular carcinoma of the breast: patterns of spread in the chest, abdomen, and pelvis on CT.

OBJECTIVE: We determined the pattern of spread of metastatic lobular carcinoma in the chest, abdomen, and pelvis on CT. MATERIALS AND METHODS: We identified 57 women (age range, 30-79 years; mean age, 57 years) with metastatic lobular carcinoma of the breast who underwent CT of the chest, abdomen, or pelvis between 1995 and 1998. Then two experienced oncology radiologists retrospectively reviewed 78 CT examinations of those patients to identify sites of metastatic disease and to identify complications caused by metastases. RESULTS: Metastases were identified in bone in 46 patients (81%), lymph nodes in 27 patients (47%), lung in 19 patients (33%), liver in 18 patients (32%), peritoneum in 17 patients (30%), colon in 15 patients (26%), pleura in 13 patients (23%), adnexa in 12 patients (21%), stomach in nine patients (16%), retroperitoneum in nine patients (16%), and small bowel in six patients (11%). Eighteen patients (32%) had gastrointestinal tract involvement that manifested as bowel wall thickening. Hydronephrosis was present in six patients (11%). CONCLUSION: Although lobular carcinoma metastasized to common metastatic sites of infiltrating ductal carcinoma, lobular carcinoma frequently metastasized to unusual sites, including the gastrointestinal tract, peritoneum, and adnexa. Gastrointestinal tract involvement was as frequent as liver involvement, appearing as bowel wall thickening on CT. Hydronephrosis was a complication of metastatic lobular carcinoma.

Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer.

The HER2/neu proto-oncogene is overexpressed in 25% to 30% of patients with breast cancer. Trastuzumab (Herceptin; Genentech, San Francisco, CA), a recombinant humanized monoclonal antibody with high affinity for the HER2 protein, inhibits the growth of breast cancer cells overexpressing HER2. In this phase II study the efficacy and toxicity of weekly administration of trastuzumab was evaluated in 46 patients with metastatic breast cancer whose tumors overexpressed HER2. A loading dose of 250 mg trastuzumab was administered intravenously, which was followed by 10 weekly doses of 100 mg each. Upon completion of this treatment period, patients with no disease progression could receive a weekly maintenance dose of 100 mg. Patients in this trial had extensive metastatic disease, and most had received prior anticancer therapy. Ninety percent of patients achieved adequate serum levels of trastuzumab. Toxicity was minimal, and no antibodies against trastuzumab could be detected. Objective responses were observed in 5 of the 43 evaluable patients, which included 1 complete remission and 4 partial remissions, for an overall response rate of 11.6%. Responses were seen in mediastinum, lymph nodes, liver, and chest wall lesions. Minor responses (seen in 2 patients) and stable disease (14 patients) lasted for a median of 5.1 months. These results demonstrate that trastuzumab is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers who have received extensive prior therapy. The regression of human cancer through the targeting of putative growth factor receptors such as HER2 warrants further evaluation of trastuzumab in the treatment of breast cancer.

A phase I trial and pharmacokinetic evaluation of CI-980 in patients with advanced solid tumors.

CI-980 is a synthetic mitotic inhibitor that binds to the colchicine binding site of tubulin. It demonstrates broad activity against human and murine tumor models and shows no cross resistance with tumor models whose mechanism of resistance is mediated by P-glycoprotein (MDR-1). A phase I study was completed in 25 patients with solid tumors using a 24-hour infusion schedule, with courses repeated every 3 weeks. Eight dose levels were tested between 1.2 and 15.6 mg/m2. The maximum tolerated dose was 14.4 mg/m2. Neutropenia was dose-related but not dose-limiting; thrombocytopenia was infrequent. CNS toxicities were dose-limiting and consisted of dizziness, headache, loss of coordination, loss of consciousness, nervousness, and other symptoms. These events occurred near the end of the infusion and were reversible, usually within 24 hours. One patient who was to be treated at dose level 8 (intended dose was 19.2 mg/m2; actual dose was 15.6 mg/m2) became encephalopathic prior to completion of the infusion. Other adverse events included gastrointestinal toxicities (nausea, vomiting, anorexia, constipation, stomatitis, dyspepsia, bleeding, cheilitis), IV site erythema, fever, and fatigue. A partial response was observed in one patient with colon cancer and reductions in CA-125 levels were observed in 2 patients with ovarian cancer. Pharmacokinetics were linear and dose-proportional. Results indicate high systemic clearance and wide tissue distribution. Mean pharmacokinetic parameter values: T1/2 = 5.52 hours, plasma clearance 1163 mL/min/m2, and Vdss 376 L/m2.

Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer.

PURPOSE: Breast cancer frequently overexpresses the product of the HER2 proto-oncogene, a 185-kd growth factor receptor (p185HER2). The recombinant humanized monoclonal antibody (rhuMAb) HER2 has high affinity for p185HER2 and inhibits the growth of breast cancer cells that overexpress HER2. We evaluated the efficacy and toxicity of weekly intravenous administration of rhuMAb HER2 in patients with HER2-overexpressing metastatic breast cancer. PATIENTS AND METHODS: We treated 46 patients with metastatic breast carcinomas that overexpressed HER2. Patients received a loading dose of 250 mg of intravenous rhuMAb HER2, then 10 weekly doses of 100 mg each. Patients with no disease progression at the completion of this treatment period were offered a maintenance phase of 100 mg/wk. RESULTS: Study patients had extensive metastatic disease, and most had received extensive prior anticancer therapy. Adequate pharmacokinetic levels of rhuMAb HER2 were obtained in 90% of the patients. Toxicity was minimal and no antibodies against rhuMAb HER2 were detected in any patients. Objective responses were seen in five of 43 assessable patients, and included one complete remission and four partial remissions (overall response rate, 11.6%; 95% confidence interval, 4.36 to 25.9). Responses were observed in liver, mediastinum, lymph nodes, and chest wall lesions. Minor responses, seen in two patients, and stable disease, which occurred in 14 patients, lasted for a median of 5.1 months. CONCLUSION: rhuMAb HER2 is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers that had received extensive prior therapy. This is evidence that targeting growth factor receptors can cause regression of human cancer and justifies further evaluation of this agent.

Sources of anticipatory emotional distress in women receiving chemotherapy for breast cancer.

BACKGROUND: The contribution of classical conditioning processes to patients' distress before chemotherapy infusions (anticipatory distress) was compared to other potential sources of distress (e.g., trait anxiety). We hypothesized that posttreatment distress (putative unconditioned response) would become a stronger predictor of anticipatory distress as patients underwent more treatment infusions (putative conditioning trials). MATERIALS AND METHODS: Fifty women with early stage breast cancer, undergoing standard chemotherapy, completed questionnaires in the clinic prior to each of eight consecutive treatment infusions, as well as telephone interviews to assess side effects following infusions. RESULTS: Consistent with the conditioning hypothesis, posttreatment distress became significantly related to anticipatory distress at the fourth infusion and became the strongest predictor by the sixth. Path analysis indicated that posttreatment distress had a direct influence on anticipatory distress, and that trait anxiety had an indirect influence by influencing apprehension about chemotherapy which, in turn, directly predicted anticipatory distress. CONCLUSIONS: The results of the present study contribute to an emerging view of anticipatory distress as a conditioned response in chemotherapy patients. Results demonstrate that conditioning factors may be one of the strongest predictors of anticipatory distress in the later phases of chemotherapy treatment.

Spontaneous recurrent tumor lysis syndrome in breast cancer.

A case of spontaneous recurrent acute tumor lysis syndrome is presented in a woman with inflammatory breast cancer. The occurrence of tumor lysis syndrome in solid tumors is unusual, and spontaneous cases are rare. This and other unusual aspects of this case are discussed.

Adjuvant radiotherapy for breast cancer as a risk factor for the development of lung cancer.

Women diagnosed with primary breast or lung cancer and recorded between 1972 and 1989 in our tumor registry were identified. Of 4,123 lung cancer patients and 3,537 breast cancer patients, 42 patients with both diagnoses were identified. The two malignancies were diagnosed simultaneously in five patients, lung cancer was diagnosed first in six patients and breast cancer was diagnosed first in 31 (p < 0.001). Nineteen of those 31 patients received adjuvant radiotherapy for breast cancer and developed lung cancer a median of 17 years later. Of the 19 irradiated patients who subsequently developed lung cancer, 15 did so in the ipsilateral lung and only four had lung cancer contralateral to the previously irradiated site (p < 0.001). Adjuvant radiotherapy for breast cancer as delivered decades ago may be an etiologic factor for lung cancer.

Metastatic placental lymphoma associated with maternal human immunodeficiency virus infection.

BACKGROUND: Pregnancy complicated by maternal human immunodeficiency virus (HIV) infection is increasing in frequency. This report describes a maternal malignancy associated with HIV infection that may complicate pregnancy. CASE: A 33-year-old primigravida was delivered by cesarean. Histologic examination of the placenta revealed the presence of metastatic non-Hodgkin lymphoma of B-cell origin. The patient was then found to be infected with HIV. Nine months postpartum, she was diagnosed with immunoblastic lymphoma. She is currently undergoing chemotherapy. CONCLUSION: Non-Hodgkin lymphoma of B-cell origin is an indication of AIDS. Pregnancies associated with maternal HIV infection may be complicated by this malignancy, which may metastasize to the products of conception. Careful examination of the placenta can detect metastases in women with non-Hodgkin B-cell lymphoma.

A phase II trial of CI-921 in advanced malignancies.

CI-921, (9-[[2-methoxy-4-[(methylsulfonyl)amino]phenyl]amino]- N,5-dimethyl-4-acridinecarboxamide 2-hydroxyethanesulfonate (1:1)), an anilinoacridine derivative with activity in experimental solid tumors was studied in a multicenter phase II trial in patients with solid tumors. Eligible tumor types included cancers of the breast, stomach, pancreas, nonsmall cell lung, small cell lung, colon, head and neck area, and melanoma. Prestudy requirements included an ECOG performance status of < or = 2, no CNS metastases, and measurable disease. CI-921 was administered intravenously over 1-2 hours on days 1, 8, and 15 of a 35-day course at an initial dose of 270 mg/M2, with modification in subsequent courses based upon tolerance. Principal toxicities included leukopenia, marked phlebitis, and mild nausea and vomiting. One hundred fifty patients were entered of whom 132 were evaluable for response. There was one complete and one partial response among 19 patients with breast cancer, and two partial responses, one each among 14 head and neck and 36 nonsmall cell lung cancer patients.

Lymphomas following cardiac transplantation. Case report and review of the literature.

The success of allogeneic organ transplantation is in great part due to pharmacologic advances in the area of immunosuppressive therapy. However, this achievement has been attained at the price of an unexpectedly high incidence of malignancies in this transplant population. Lymphoid malignancies predominate in this and other immunodeficiency states. There is some controversy in the literature over the clonal or malignant nature of these proliferations. This paper presents a case of Burkitt-like lymphoma occurring after cardiac transplantation. The role of Epstein-Barr virus in the pathogenesis of this disorder is reviewed as are multidisciplinary approaches to its management.

Augmentation of activity of cis-diamminedichloroplatinum(II) and mitomycin C by interferon in human malignant mesothelioma xenografts in nude mice.

Two human mesothelioma xenograft lines, BG and ES, serially passaged in athymic mice, were studied to determine the efficacy of alpha-interferon in this type of tumor. Treatment began after progressive tumor growth was established. Recombinant human alpha-interferon-2a (Roferon- A) was given by s.c. injection, at a site distant from the tumor, at a dose of 2 x 10(5) IU 5 days per wk for 5 wk. Mild inhibitory activity was noted in both lines with interferon alone. cis-Diamminedichloroplatinum(II) (CDDP) (4 mg/kg) weekly x 5 was effective in line BG, while mitomycin C (1.5 mg/kg) weekly x 3 was effective in line ES. CDDP was not as effective in line ES. The moderate activity of CDDP in line BG and of mitomycin C in line ES was markedly increased by the addition of alpha-interferon. The combination of mitomycin C and alpha-interferon was as effective as mitomycin C and CDDP. No additional toxicity was noted by the addition of alpha-interferon. The combination of recombinant human alpha-interferon-2a and active chemotherapeutic agents is effective in mesothelioma xenografts.