An analysis of male and female breast cancer treatment and survival among demographically identical pairs of patients.

BACKGROUND: Male breast cancer is rare, and there are no large comparative studies to guide treatment. We used National Cancer Data Base data on 4755 men and 624,174 women who had breast cancer (1985-1994) to identify equivalent groups of male and female breast cancer patients. METHODS: For each man with breast cancer, the next woman treated at the same hospital was sought who matched the man's age (within 5 years), ethnicity, income category, and stage. We identified 3627 closely matched pairs of male and female patients with breast cancer. RESULTS: Men were more likely to be treated with mastectomy (modified radical, 65% of men versus 55.1% of women; radical, 2.5% of men versus 0.9% of women; simple, 7.6% of men versus 3.4% of women; P <.001), and more likely to receive radiation therapy after mastectomy (men, 29%; women, 11%; P <.001). Men treated with lumpectomy were less likely to receive radiation therapy (men, 54%; women, 68%; P <. 001). Men were also less likely to receive chemotherapy (26.7% of men versus 40.6% of women; P <. 001) after any surgical treatment. CONCLUSIONS: This large comparative study is the first to detail stage-specific differences in contemporary treatment strategies for highly comparable groups of men and women treated for breast cancer. Further studies of male breast cancer should focus on identifying prognostic factors and defining optimal therapy.

Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22.

PURPOSE: The National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial (B-22) to determine if intensifying but maintaining the total dose of cyclophosphamide (Cytoxan, Bristol-Myers Squibb Oncology, Princeton, NJ) in a doxorubicin (Adriamycin, Pharmacia, Kalamazoo, MI)-cyclophosphamide combination (AC), or if intensifying and increasing the total dose of cyclophosphamide improves the outcome of women with primary breast cancer and positive axillary nodes. PATIENTS AND METHODS: Patients (N = 2,305) were randomized to receive either four courses of standard AC therapy (group 1); intensified therapy, in which the same total dose of cyclophosphamide was administered in two courses (group 2); or intensified and increased therapy, in which the total dose of cyclophosphamide was doubled (group 3). The dose and intensity of doxorubicin were similar in all groups. Disease-free survival (DFS) and overall survival were determined using life-table estimates. RESULTS: There was no significant difference in DFS (P = .30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in group 1 was similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to that of women in group 3 (62% v 64%, respectively; P = .59). The 5-year survival of women in group 1 was similar to that of women in group 2 (78% v 77%, respectively; P = .86) and to that of women in group 3 (78% v 77%, respectively; P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a difference in outcome among the groups was unrelated to either differences in amount and intensity of cyclophosphamide or to dose delays and intervals between courses of therapy. CONCLUSION: Intensifying or intensifying and increasing the total dose of cyclophosphamide failed to significantly improve either DFS or overall survival in any group. It was concluded that, outside of a clinical trial, dose-intensification of cyclophosphamide in an AC combination represents inappropriate therapy for women with primary breast cancer.

Peritoneal venous shunting for the treatment of lymphatic ascites following retroperitoneal lymph node dissection.

We report a case of refractory lymphatic ascites following retroperitoneal lymph node dissection and venacavectomy. Placement of a Denver peritoneal venous shunt resulted in resolution of the ascites and marked improvement in the patient's nutritional parameters. Shunt occlusion 2 months following placement demonstrated no recurrence of the ascites. This technique may prove useful in the management of lymphatic ascites associated with radical retroperitoneal surgery.

Radiolabeled antibody imaging of patients with potentially resectable colorectal adenocarcinoma.

Thirty-two patients with potentially resectable recurrent colorectal adenocarcinoma were imaged with the radioimmunoconjugate 111In-satumomab pendetide to determine whether imaging supplies clinically relevant information relating to the extent of disease in patients with different presenting characteristics. Patients included 12 with increasing carcinoembryonic antigen (CEA) without anatomical evidence of recurrence, 13 with radiological abnormalities consistent with apparently isolated metastases, and 7 with recurrence and anatomical abnormalities of unclear significance. 111In-satumomab pendetide imaging detected extrahepatic abdominal and pelvic disease in 16 subjects. Imaging was most informative in patients with recurrent disease and anatomical abnormalities of unclear significance, but imaging of the liver was suboptimal owing to high levels of nonspecific uptake. We conclude 111In-satumomab pendetide imaging can supply clinically relevant information relating to the extent and location of recurrent colorectal adenocarcinoma in patients with extrahepatic abdominal and pelvic radiological abnormalities of unclear significance and in radiologically normal patients with high CEA levels.

Handling of cytotoxic drugs by healthcare workers. A review of the risks of exposure.

Increasing utilisation of chemotherapeutic agents in treating patients with malignancy has led to the potential for widespread exposure of healthcare workers who come into contact with patients or these agents in the work place. Unfortunately, these drugs are toxic to both the abnormal and normal somatic cell. This occurs in the patient, and is also likely to affect any individual exposed. There appear to be widely divergent opinions concerning the extent of hazard of coming into contact with these agents, in spite of which caution and minimising exposure risk seems only prudent and appropriate.

Diet intervention methods to reduce fat intake: nutrient and food group composition of self-selected low-fat diets.

A multicentered pilot study was conducted to test an intervention protocol designed to reduce fat intake to 15% of energy intake. Eligible subjects were postmenopausal women with stage II breast cancer whose baseline fat intake was more than 30% of energy intake. The low-fat diet intervention protocol consisted of bi-weekly individual counseling sessions with emphasis on substitution of lower-fat foods for high-fat foods and maintenance of nutritional adequacy. Nutrient intakes were calculated from 4-day food records collected at baseline and after 3 months of diet intervention. Mean daily fat intake for the 17 patients on the low-fat diet dropped significantly from 38.4 +/- 4.3% of energy intake at baseline to 22.8 +/- 7.8% at 3 months (p less than .001). A 25% reduction in mean energy intake, from 1,840 +/- 419 kcal at baseline to 1,365 +/- 291 kcal at 3 months, was accompanied by significant increases in protein and carbohydrate as percent of energy intake. A mean weight loss of 2.8 kg and a 7.7% reduction in serum cholesterol were observed; both changes were significant at the p less than .01 level. Absolute intakes of zinc and magnesium were significantly reduced. However, mean intake on the low-fat diet for 14 vitamins and minerals, including zinc and magnesium, exceeded two-thirds of the 1989 Recommended Dietary Allowances (RDAs). When expressed as nutrient density (i.e., amount of nutrient per 1,000 kcal), increases were observed for all micronutrients. These results support the hypothesis that a nutritionally adequate low-fat diet can be successfully implemented in a highly motivated, free-living population.

Unpublished Data Summaries and the design and conduct of clinical trials. The Nutrition Adjuvant Study experience and commentary.

A trend in cancer clinical investigation has been the application of new analytic techniques and reporting forums to summarize developing trial results. Examples include: Consensus Conferences, Meta-Analyses, and most recently (in the breast cancer area), the "Clinical Alert." These Unpublished Data Summaries have been widely disseminated in lay and scientific communities and have frequently engendered debate conducted in the absence of primary information. We now report the impact of this process on a national, cooperative group effort (the Nutrition Adjuvant Study [NAS] ) designed to test a novel hypothesis involving dietary fat reduction as potential adjuvant breast cancer treatment. It is clear that these Unpublished Data Summaries in the breast cancer area directly resulted in changes in the NAS protocol design and may have influenced patient accrual. The challenge for clinical investigators and governmental agencies is to integrate the positive aspects of the new information forums with those of traditional "peer-review" publication into a system where the conduct of clinical investigation in a timely manner can be facilitated.

Doxorubicin-containing regimens for the treatment of stage II breast cancer: The National Surgical Adjuvant Breast and Bowel Project experience.

Despite numerous reports of findings obtained following the use of doxorubicin (Adriamycin [A]; Adria Laboratories, Columbus, OH) for the postoperative treatment of patients with primary breast cancer and positive axillary nodes, no clear consensus exists regarding its worth when used in that setting. In June 1981, the National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented two randomized clinical trials aimed at evaluating the worth of doxorubicin when administered in conjunction with melphalan (L-PAM) and fluorouracil (5-FU) (PF). A prior NSABP study identified cohorts of patients who did or did not benefit from tamoxifen (TAM, T) when used with chemotherapy. That information was employed in the design of the present studies. Women considered responsive to TAM (1,106) were randomized between PFT and PAFT, and those nonresponsive to TAM (707) were randomized between PF and PAF. Findings through 6 years of follow-up (mean duration of potential time on study, 64 months and 63 months, respectively) indicate that non-TAM-responsive patients who received PAF had a significantly better disease-free survival (DFS) (P = .003) and survival (P = .05) than did those receiving PF. By contrast, there was no significant difference in DFS (P = .6) or survival (P = .7) between PFT- and PAFT-treated patients. No disparity in the amount of drug received, whether related to the median amount or to dose-intensity, is present to account for the difference in findings between the studies. Aside from alopecia and emesis, the toxicity from the doxorubicin-containing regimens was similar to those in which doxorubicin was omitted. Cardiomyopathy was not a significant finding; there were no deaths from cardiac toxicity. The incidence of arterial and venous complications in patients receiving TAM was less than reported by others.

[Lymphoepithelial hyperplasia of the tonsil at the base of the tongue]. / Lymphoepitheliale Hyperplasie der Zungengrundtonsille.

A case report is communicated on lymphoepithelial hyperplasia of the tonsil at the base of the tongue. This may be demonstrated during radiological double contrast examination of the oesophagus as a protrusion of the mucosa of the hypopharynx with smooth or nodular relief pattern. Differential diagnosis is necessary especially against malignant neoplasms.

Preparation and administration of chemotherapy. Haematological consequences for hospital-based nurses.

This study examined the question of whether previous exposure to cytostatic drugs by oncology nurses was sufficient to lead to haematological phenotypical subclinical abnormalities which had previously been identified in a population of patients who had received chemotherapy as an adjuvant to breast surgery. A comparison of baseline haematological parameters, and the results of a prednisolone stimulation test, was made between nurses regularly coming into contact with such agents and age-adjusted group of nurses who had not been exposed. Although there is a persistent trend toward lower neutrophils, platelets, monocytes and neutrophil reserves in the nurses who handled antineoplastic agents, a statistically significant decrement in these parameters was not identified. Such a finding should help to reassure individuals who have had similar exposure, but does not negate the importance of following published recommended guidelines for the handling and dispensing of antineoplastic agents.

A breast cancer Nutrition Adjuvant Study (NAS): protocol design and initial patient adherence.

To evaluate the feasibility of using a reduction in dietary fat intake as a component of treatment regimens for patients with resected breast cancer, a multi-disciplinary cooperative group protocol was developed. Females 50 to 75 years of age with stage II breast cancer who completed primary local therapy were eligible for randomization to a Control Dietary Group in which dietary fat intake was to remain unchanged from baseline level (at approximately 38% of calories derived from fat) and an Intensive Intervention Dietary Group designed to reduce dietary fat intake. Both Dietary Groups were given tamoxifen 20 mg/day. To facilitate early experience with dietary regimen delivery, patients entered during an initial pilot phase could receive any chemotherapy and/or hormonal treatment. A prerandomization nutrition 'run-in' of clinically eligible patients assessed adherence to nutrition data collection procedures and screened patients for nutrition eligibility criteria. Of 59 patients beginning 'run-in', 49 were randomized and, at present, 32 have completed at least three months follow-up. The change in dietary fat intake (as assessed by Four Day Food Records) seen in both arms is outlined below. Formula see table. The 56% reduction in total daily fat gram intake achieved in the Intensive Intervention Dietary Group suggests that protocols designed to reduce dietary fat intake in an adjuvant treatment setting can be developed and implemented using a multi-institutional, cooperative group approach.

B16 melanoma in hairless mice: a model for thermographic research.

Little is understood concerning the mechanism of tumor-induced thermographic abnormalities observed in man. An ideal animal model is lacking. In an effort to create such a model we have worked with hairless mice, subcutaneously inoculated with B16 melanoma cells. This report documents the progress of that work and the subsequent development of a totally satisfactory system for the study of such tumors in a hairless animal.

Malignant melanoma in childhood and adolescence.

A retrospective chart review of 25 patients under the age of 20 years with malignant melanoma, diagnosed between the years 1938 and 1984 at the University of Iowa Hospitals and Clinics, was conducted. Nine of the patients were under the age of 14 years, and 18 patients were females. There appeared to be a frequent delay in diagnosis of the primary lesion, occasionally incorrect initial diagnosis, and under-treatment in these young patients. Primary treatment varied from limited excision of the lesion to wide excision and regional lymph node dissection. Females appeared to have a better prognosis than males, and wide local excision with or without regional lymph node dissection was associated with the most favorable outcome. Overall 10-year survival in this group of patients was 56 per cent, a rate that compares well to the overall survival in adult patients with malignant melanoma.

Sister chromatid exchange analysis in nurses handling antineoplastic drugs.

Sister chromatid exchange (SCE) analyses were carried out in hospital nurses to determine whether an increased frequency of SCE may be used as an indicator of occupational exposure to potentially harmful antineoplastic drugs. In our study of 18 oncology nurses who handled these agents for an average of three days per week, we found no increase in mean SCE frequency (9.3 +/- 1.7 SCEs/cell) and no difference in the distribution of individual mean SCE frequencies compared to a group of 18 nurses who did not handle these drugs (9.5 +/- 1.5 SCEs/cell). There was a great deal of individual variation in mean SCE frequency as well as in SCE values in individual cells. No relationship with SCE frequency was found in terms of a subject's age, or the number of days of exposure to the drugs. Since conflicting results have been reported in persons handling antineoplastic drugs, SCE analysis alone is probably not a reliable indicator of exposure to possible mutagenic/carcinogenic effects of these drugs. SCE analysis may be helpful in conjunction with other studies, such as an analysis of urinary mutagens, or in studies of occupational exposure to agents other than antineoplastic drugs which may have a more noticeable effect on SCE frequency.

Neurosarcomatous malignant melanoma arising in a neuroid giant congenital melanocytic nevus.

We report a case of neuroid giant congenital melanocytic nevus (GCMN) in which a malignant schwannomalike tumor developed. Literature review reveals that neurosarcomatous differentiation occurs among malignant tumors arising in GCMNs, apparently with greater incidence in those GCMNs showing benign neuroid differentiation. Although the differences between neuroid melanocytes and Schwann's cells may be more conceptual than real, we believe that the current tumor arising within a melanocytic nevus is likely of neuroid melanocytic origin and best designated as neurosarcomatous malignant melanoma.

Chemotherapeutic toxicity--the relationship between patients' pretreatment expectations and posttreatment results.

Patients receiving the same cancer chemotherapy regimens exhibit a highly variable incidence of toxic side effects. We studied 56 patients about to receive chemotherapy for the first time to determine whether their expectations of individual side effects were associated with the frequency and severity of the toxicity that they subsequently experienced. Patients completed a self-report questionnaire containing a list of 16 potential toxicities, asking them to indicate how certain they were of experiencing or not experiencing each. Prior to their third treatment, patients again completed a self-report scale indicating the incidence and severity of each side effect experienced. The frequency of actual side effects was much greater than patients anticipated. The most commonly reported side effects were tiredness, changes in appetite or taste, nervousness, and nausea. Patients' expectations failed to predict the occurrence or severity of the experience of common side effects. Anxiety levels and meaning attributed to side effects also were not associated with side effects experienced. Although psychological factors may play a role, it is likely that unique physiologic parameters account primarily for the variable and unpredictable relationship between chemotherapeutic agents and the side effects they induce.

Temperature over tumors in hairless mice.

The question of whether tumors are warmer or colder than surrounding tissue is considered in these experiments which use a highly suitable animal model, the hairless mouse. Temperatures of skin over induced growing subdermal tumors in these mice were monitored by AGA 680 Color Thermovision. The skin over the tumors does not cool over time but on the contrary becomes warmer. This is probably due to an increase in vascularization rather than increased metabolic rate.

Phase II study of dibromodulcitol and BCNU in metastatic malignant melanoma.

Dibromodulcitol (DBD) and BCNU were administered to 20 patients with metastatic malignant melanoma who had not received prior chemotherapy. One complete and three partial responses were noted; duration of response was short. Dose limiting toxicity was thrombocytopenia. DBD and BCNU do not appear to improve response over single agent therapy for disseminated melanoma.