Multicenter trial of sentinel node biopsy for breast cancer using both technetium sulfur colloid and isosulfan blue dye.

OBJECTIVE: To determine the factors associated with false-negative results on sentinel node biopsy and sentinel node localization (identification rate) in patients with breast cancer enrolled in a multicenter trial using a combination technique of isosulfan blue with technetium sulfur colloid (Tc99). SUMMARY BACKGROUND DATA: Sentinel node biopsy is a diagnostic test used to detect breast cancer metastases. To test the reliability of this method, a complete lymph node dissection must be performed to determine the false-negative rate. Single-institution series have reported excellent results, although one multicenter trial reported a false-negative rate as high as 29% using radioisotope alone. A multicenter trial was initiated to test combined use of Tc99 and isosulfan blue. METHODS: Investigators (both private-practice and academic surgeons) were recruited after attending a course on the technique of sentinel node biopsy. No investigator participated in a learning trial before entering patients. Tc99 and isosulfan blue were injected into the peritumoral region. RESULTS: Five hundred twenty-nine patients underwent 535 sentinel node biopsy procedures for an overall identification rate in finding a sentinel node of 87% and a false-negative rate of 13%. The identification rate increased and the false-negative rate decreased to 90% and 4.3%, respectively, after investigators had performed more than 30 cases. Univariate analysis of tumor showed the poorest success rate with older patients and inexperienced surgeons. Multivariate analysis identified both age and experience as independent predictors of failure. However, with older patients, inexperienced surgeons, and patients with five or more metastatic axillary nodes, the false-negative rate was consistently greater. CONCLUSIONS: This multicenter trial, from both private practice and academic institutions, is an excellent indicator of the general utility of sentinel node biopsy. It establishes the factors that play an important role (patient age, surgical experience, tumor location) and those that are irrelevant (prior surgery, tumor size, Tc99 timing). This widens the applicability of the technique and identifies factors that require further investigation.

Multiple ectopic parathyroid glands.

Parathyroid surgery to correct primary hyperparathyroidism is successful in 80 to 97 per cent of initial explorations. Failures are often linked to inability to locate ectopic parathyroid glands. Although ectopic parathyroid glands are relatively common (15%) multiple ectopic glands are rarely reported. We describe a case of multiple ectopic parathyroid glands and the intraoperative approach to their localization and review the anatomy and embryology of ectopic parathyroid glands. A 39-year-old woman presented with fatigue, lethargy, and depression. On biochemical evaluation she was noted to be hypercalcemic and hyperparathyroid. Preoperative parathyroid localization failed to identify abnormal parathyroid glands. At exploration three of four parathyroid glands, including an adenoma, were located in ectopic positions by a meticulous and systematic dissection. A careful exploration coupled with a thorough knowledge of parathyroid anatomy and embryology will produce successful surgical correction of primary hyperparathyroidism in greater than 95 per cent of patients even in the few patients with multiple ectopic parathyroid glands.

Parameters that predict nipple involvement in breast cancer.

BACKGROUND: Breast conservation therapy has been shown to produce survival rates equivalent to those seen with modified radical mastectomy. Synchronous occult neoplastic involvement of the nipple may lead to incomplete excision of the tumor in patients undergoing breast conservation therapy, possibly leading to recurrence. STUDY DESIGN: The charts of 803 breast cancer patients treated between 1990 and 1995 at two teaching hospitals were retrospectively reviewed. The patients were divided into three groups: nipple-positive for malignancy (n = 54), nipple-negative for malignancy (n = 404), and nipple-not-removed (n = 345). Ten different clinical and tumor parameters including age, race, primary tumor location, histologic grade, primary tumor size, nodal involvement, TNM stage, estrogen receptor status, DNA ploidy, and S-phase were examined for the ability to predict cancerous nipple involvement. RESULTS: Overall, the rate of nipple positivity was 12%. In univariate analysis pathologic stage, tumor size, lymph node status, histologic grade, and tumor location were significant predictors of positive nipple involvement. Patients with tumors that were stage III or higher were nearly ten times (odds ratio [OR] = 9.8, 95% confidence interval [CI] = 5.5 to 17.7) more likely to have nipple involvement than patients with early-stage tumors. Patients with a tumor size of 4 cm or greater were nearly eight times (OR = 7.8, 95% CI = 4.2 to 14.5) more likely to have nipple involvement than patients with tumor size less than 4 cm. Patients with positive lymph nodes were five times (OR = 5.0, 95% CI = 2.7 to 9.1) more likely to have nipple involvement than patients with negative lymph nodes. Patients with tumors in a central location or that overlapped quadrants were nearly four times (OR = 3.8, 95% CI = 2.2 to 6.8) more likely to have nipple involvement than patients with tumors in other locations. Patients with grade 3 or undifferentiated tumors were three times (OR = 3.0, 95% CI = 1.4 to 6.4) more likely to have nipple involvement than patients with lower grade tumors. In multivariable analysis, stage > or = 3 (OR = 9.2, 95% CI = 4.2 to 20.3) central/ overlap location (OR = 4.1, 95% CI = 2.0 to 8.7) and grade 3 or undifferentiated (OR = 3.1, 95% CI = 1.3 to 7.5) were the only variables that remained significant predictors of nipple involvement. CONCLUSIONS: The decision to perform breast conservation surgical procedures with nipple preservation can be difficult, particularly in patients with larger, more centrally located tumors. The multivariable model developed in this study may be useful in predicting the risk of cancerous nipple involvement and selecting appropriate breast conservation patients for nipple preservation.

Relationship between colorectal cancer glutathione levels and patient survival: early results.

PURPOSE: Elevated glutathione is a cause of resistance to anticancer agents and x-rays. The purpose of this study was to determine the frequency and clinical significance of glutathione elevation in human colorectal cancer. METHODS: Glutathione levels were measured in 41 colon cancers, 24 rectal cancers, and corresponding normal tissues. The patients were then followed up prospectively for tumor recurrence and survival. Survival was analyzed by the Kaplan-Meir method and Cox proportional hazards regression. RESULTS: Glutathione levels in primary colorectal cancers were significantly higher than in the corresponding normal tissues. Elevated glutathione levels had a significant negative effect on survival in patients with colorectal cancer, whether based on the mean (P = 0.02) or median (P = 0.04) normal tissue levels. A negative effect of glutathione levels on survival was apparent in patients with colorectal cancer, whether or not they were treated with postoperative therapy. The larger the ratio of tumor glutathione to normal tissue glutathione, the poorer the prognosis. When adjusted for other covariates, glutathione was still a significant predictor of survival. CONCLUSIONS: An elevated tumor glutathione level at the time of diagnosis appears to confer a poor prognosis in patients with colorectal cancer. Longer-term study using a larger number of patients will be required to confirm these findings. Knowledge of tumor glutathione content may help identify patients requiring more intensive therapy.

The importance of DT-diaphorase in mitomycin C resistance in human colon cancer cell lines.

BACKGROUND: Prior studies have suggested the multifactorial nature of mitomycin C (MMC) resistance. However, the relative importance of the different resistance mechanisms is unknown. MATERIALS AND METHODS: A panel of colon cancer cell lines with levels of MMC resistance from 2- to 15-fold compared to the parent line HT-29 was produced by repeated MMC exposure. Cell survival was measured using clonogenic assay. Glutathione and related enzymes and DT-diaphorase were measured using biochemical assays. P-glycoprotein expression was measured using flow cytometry. Topoisomerase II activity was measured using the pBR322 DNA relaxation assay. RESULTS: Multiple drug resistance mechanisms were altered in the resistant cell lines (glutathione reductase, glutathione peroxidase, topoisomerase II). However, the level of DT-diaphorase correlated best with the degree of MMC resistance. The importance of DT-diaphorase was confirmed by using BMY 25282, an MMC analogue which is less dependent on DT-diaphorase for activation. Resistance in the HT-29R54 cell line was 15-fold with MMC compared to 5-fold with BMY 25282. P-glycoprotein-mediated resistance does not appear important in this model. CONCLUSIONS: Although MMC resistance appears to be multifactorial, the results of this study strongly suggest that DT-diaphorase is the major contributor to MMC resistance under aerobic conditions. Strategies to enhance drug activation may therefore be useful for reversing MMC resistance.

Antiproliferative and antiinvasive effects of carboxyamido-triazole on breast cancer cell lines.

BACKGROUND: Basement membrane invasion is one of the critical components of the metastatic cascade. The antiproliferative and antiinvasive activity of carboxyamido-triazole (CAI), a calcium influx inhibitor, was studied in five human breast cancer cell lines (MCF-7, MCF-7/ADRR, MDA-231, MDA-231R44, and BT-474). METHODS: Sensitivity of the cell lines to CAI was measured with a microculture tetrazolium assay. The Boyden chamber Matrigel chemoinvasion assay was used to measure the antiinvasive activity of CAI. Matrix metalloproteinase activity was analyzed by gelatin zymography. RESULTS: The 50% inhibitory concentrations of CAI were cell line dependent and ranged from 7.49 +/- 4.05 mumol/L to 46.1 +/- 8.6 mumol/L. CAI at a low, minimally toxic concentration (5 mumol/L) inhibited invasion by greater than 75% in the four invasive cell lines (MCF-7/ADRR, MDA-231, MDA-231R44, and BT-474) regardless of estrogen receptor or p-glycoprotein status (p < 0.01). CAI treatment also reduced matrix metalloproteinase activity in conditioned media from three of the four invasive lines (p < 0.05). CONCLUSIONS: CAI at clinically achievable concentrations is an effective antiproliferative and antiinvasive agent against human breast cancer cell lines regardless of estrogen receptor or p-glycoprotein status. Reduction in matrix metalloproteinase activity may be partially responsible for CAI inhibition of invasion.

Managed health care: a concept not understood by rural Oklahomans.

OBJECTIVE: The purpose of the study was to find out what people in rural Oklahoma know and understand about managed care. METHODS: A fourteen-statement survey instrument was developed. A panel of managed care professionals were asked to participate to provide a "standard" to compare the responses of the general public. The survey was administered to the general public in five rural communities and to recipients of the Oklahoma AHEC Newsletter. RESULTS: Overall, the panel tended to agree and created an industry profile useful in comparison to the responses of the general public: (1) 55-65% of the respondents answered I Don't Know or Neither Agree nor Disagree to statements using the term "managed care" and only 15-20% of the public respondents answered I Don't Know to statements not including the term, "managed care." (2) 25-30% of the general public answered in accordance with the managed care panel. (3) Over 50% of the public respondents Agreed that changes are necessary in the health sector. CONCLUSIONS: The results of this survey suggest that rural Oklahomans are uninformed about the concept of managed care and need to become better informed.

Treatment and prognosis of primary malignant small bowel tumors.

Primary malignant tumors of the small bowel are a heterogeneous group of tumors and are uncommon compared to tumors in other locations of the gastrointestinal tract. These tumors have been traditionally associated with a poor prognosis. The charts of 53 patients with primary malignant small bowel tumors at major Eastern Virginia Medical School teaching hospitals were retrospectively reviewed. Patient characteristics and presenting symptoms and signs were nonspecific. No single radiographic or endoscopic procedure was performed on every patient, and the diagnosis was suspected preoperatively in only 50 per cent of the patients. Tumors were most common in the ileum, and the most common histologic types were adenocarcinoma (53 per cent) and carcinoid (32 per cent). In univariate analysis, factors determining survival included histologic type, location of tumor, and stage. There was also a trend toward worse survival in patients receiving chemotherapy or radiation therapy, possibly due to patient selection factors. In multivariate analysis, only histology and stage significantly influenced survival. The overall 10-year survival of the entire group was 44 per cent. Small bowel tumors have a variable prognosis. A high index of suspicion and more frequent use of enteroclysis may lead to earlier detection and improved survival.

Effect of acute and chronic intermittent hypoxia on DNA topoisomerase II alpha expression and mitomycin C-induced DNA damage and cytotoxicity in human colon cancer cells.

Recently, we reported that alterations in topoisomerase II (topo II) activity appear to contribute to mitomycin C (MMC) resistance in HT-29R13 human colon cancer cells under aerobic conditions. In this study, the expression of topo II alpha and topo II beta in parent HT-29 and MMC resistant variant HT-29R13 cells was investigated under aerobic, acute hypoxic (after 4 hr in 95% N2, 5% CO2 < 0.01% O2), and chronic intermittent hypoxic (after 4 hr hypoxia/day x 7 days) conditions. Acute hypoxia induced topo II alpha mRNA and protein, effects that were more pronounced in HT-29 cells. Chronic intermittent hypoxia caused a decrease in topo alpha mRNA and protein, changes that were again more pronounced in HT-29 cells. The observed changes in topo II alpha protein were associated with parallel changes in topo II activity under all conditions tested. Topo II beta mRNA was expressed at a very low level in both cell lines under aerobic and hypoxic conditions. Compared with cells under aerobic conditions, HT-29 cells were more sensitive to MMC under acute hypoxia but more resistant under chronic intermittent hypoxia. In contrast, the senstivity of HT-29R13 cells was unchanged under acute hypoxia, but the cells were more resistant under chronic intermittent hypoxia. Under all conditions tested, the degree of cytotoxicity corresponded to the frequency of MMC-induced DNA cross-links and topo II alpha protein levels and activity. Our results demonstrated that MMC cytotoxicity in hypoxic cells is highly dependent upon the type of hypoxia and the cell type. Hypoxia has significant effects on topo II alpha expression in HT-29 and HT-29R13 cells which correlate with MMC cytotoxicity.

Role of c-myc in tamoxifen-induced apoptosis estrogen-independent breast cancer cells.

BACKGROUND: The antiestrogen tamoxifen (TAM) is effective in the treatment of estrogen receptor (ER)-positive as well as some ER-negative breast cancers. However, the precise mechanism of action of TAM, especially in estrogen-independent cells, remains unclear. Previous work by our laboratory has demonstrated that TAM induces the morphologic and biochemical changes that are characteristic of apoptosis in both ER-positive and ER-negative cells. PURPOSE: We compared the effect of TAM at a clinically achievable concentration on cell growth and apoptosis with the effect of TAM on c-myc (also known as C-MYC) messenger RNA (mRNA) and protein expression in ER-negative MDA-231 cells. METHODS: MDA-231 cells were treated for up to 72 hours with 1.0 microM TAM alone or in the presence of 50 microM c-myc antisense or nonsense oligonucleotides. c-myc mRNA expression was determined by northern blot analysis, protein expression by western blot analysis, cell growth inhibition counts, and DNA cleavage by agarose gel electrophoretic analysis. Differences between the mean values from different treatment groups were compared with the use of the two-sided Wilcoxon Ranksum test. RESULTS: TAM treatment for 72 hours increased c-myc mRNA five-fold (from a relative radiolabeled hybridization signal intensity of 17 +/- 4 up to 93 +/- 10; P<.05) and c-MYC protein threefold (from a relative immunofluorescence signal intensity of 28 +/- 7 up to 83+/-21; P< .05). The induction of c-myc by TAM was accompanied by internucleosomal DNA cleavage characteristic of apoptotic cell death. Addition of c-myc antisense oligonucleotide (5'CACGTTGAGGGGCAT-3') to MDA-231 cells resulted in a nearly twofold decrease of basal c-myc mRNA (P< .05) and a sevenfold decrease of basal c-Myc protein (P< .05) expression. Addition of c-myc antisense oligomer also antagonized the TAM-induced increase in c-myc mRNA (P< .05) and protein expression (P< .05) and inhibited TAM-induced cytostasis (P< .01) and apoptosis. In parallel experiments, addition of the nonsense oligomer had no effect on any of the measured parameters. CONCLUSIONS: These results indicate that the effects of TAM on ER-negative MDA-231 cells may be mediated through c-myc overexpression. c-myc may play a critical role in the growth and progression of MDA-231 breast cancer cells.

Pathologic fracture secondary to subungual melanoma.

Subungual melanoma is uncommon, and delays in diagnosis and misdiagnosis occur frequently. We describe a 61-year-old black male who presented with a non-healing area in his left thumb nailbed with many of the features of subungual melanoma. However, the patient also had a pathologic fracture of the distal phalanx, leading to some initial confusion about the diagnosis. Despite aggressive multimodality therapy, the disease rapidly progressed, resulting in the patient's death. Pathologic fracture due to subungual melanoma may indicate a particularly poor prognosis.

p-Glycoprotein expression as a predictor of breast cancer recurrence.

BACKGROUND: Many new prognostic factors for breast cancer have been described, and yet the ability to predict patient outcomes remains poor. Overexpression of p-glycoprotein (p-gp), the multidrug resistance efflux pump, confers a worse prognosis to patients with certain leukemias and other tumors. The purpose of this study was to analyze the potential usefulness of p-gp expression as a prognostic factor in patients with breast cancer. METHODS: Paraffin blocks were obtained from 55 previously untreated patients who underwent surgery between 1987 and 1988. To determine p-gp expression, tumor cell suspensions were incubated with the p-gp-specific C219 monoclonal antibody and analyzed using an indirect immunofluorescent flow cytometric assay. RESULTS: Twenty-four (44%) of the tumors were p-gp positive and 31 (56%) were p-gp negative. Among the p-gp positive patients, 65% had recurrence of their disease, whereas only 13% of the p-gp negative patients experienced recurrence (p = 0.0001). The 5-year disease-free rate for p-gp positive patients was 39% compared with 83% for p-gp negative patients (p = 0.0001). In univariate analysis examining 10 different variables, significant predictors of recurrence were p-gp, stage, and tumor size. Multivariate analysis using Cox Proportional Hazards regression showed that only p-gp and stage were significant independent predictors of recurrence (p = 0.0002). CONCLUSIONS: p-gp is frequently expressed in patients with untreated breast cancer, with p-gp-positive patients being at significantly greater risk for disease recurrence. p-gp appears to be a useful prognostic factor in breast cancer and could potentially help guide management.

Endocrine tumors of the gastrointestinal tract.

Endocrine tumors of the gastrointestinal tract produce a variety of secretory products that cause unique clinical syndromes. Diagnosis, which is often delayed, requires a strong index of suspicion and must be confirmed by biochemical tests. Precisely where these tumors originate remains a topic of controversy. However, several growth factors that may be involved in tumor development have been identified, and genetic abnormalities in patients with multiple endocrine neoplasia have been described. New pre- and intraoperative localization techniques have greatly increased the ability to identify and resect these tumors. The long-acting somatostatin analogue octreotide is frequently useful as a tracer to localize tumors and as symptomatic therapy for limiting release of secretory products produced by the tumors. In some instances it may also have direct anti-tumor activity.

Relationship between tamoxifen-induced transforming growth factor beta 1 expression, cytostasis and apoptosis in human breast cancer cells.

Previously we have shown that tamoxifen (TAM) induces morphological and biochemical changes typical of apoptosis in oestrogen receptor (ER)-positive MCF-7 or ER-negative MDA-231 human breast cancer cells. In this study the effects of TAM on expression of transforming growth factor beta 1 (TGF-beta 1) were correlated with the effects on cell cycle kinetics and apoptosis. TAM had similar biphasic effects on both cell lines. Short-term (< 6 h) TAM incubation resulted in a slight decrease in TGF-beta 1 protein despite an increase in TGF-beta 1 mRNA and was associated with an increase in cells in S-phase. No apoptotic effects were noted. Longer (> or = 12 h) TAM incubation induced TGF-beta 1 protein (about 3-fold) and mRNA expression (about 2-fold) in both cell lines, and was associated with G1/G0 blockade and induction of apoptosis. The accumulation of TAM-induced TGF-beta 1 mRNA was increased by cycloheximide, but was not affected by 17 beta-oestradiol. Long-term incubation with TAM had no significant effect on TGF-beta 1 gene copy number. TAM-induced internucleosomal DNA cleavage was inhibited in both cell lines by the addition of an anti-TGF-beta 1 antibody. TAM has dose- and time-dependent effects on TGF-beta 1 expression associated with changes in cell cycle kinetics. These effects are independent of ER status and may be the result of a direct regulatory effect of TAM on TGF-beta 1 transcription. It also appears that induction of TGF-beta 1 plays an important role in TAM-induced apoptosis in breast cancer cells.

Clinical review 72: diagnosis and management of functioning islet cell tumors.

Functional islet cell tumors cause recognizable clinical syndromes based on the peptide products they secrete (Table 1). Frequently, the diagnosis of these tumors is delayed. A high index of suspicion coupled with the use of appropriate biochemical and provocative tests should lead to earlier diagnosis. A suggested management plan for patients suspected of having an islet cell tumor is shown in Fig. 1. Earlier diagnosis coupled with advances in preoperative and intraoperative localization techniques have resulted in an increased number of patients being cured.

Management and prognosis of adenocarcinoma of the appendix.

PURPOSE: Adenocarcinoma of the appendix is a rare neoplasm, and controversies persist regarding management. The purpose of this study was to identify prognostic factors and define management strategies for patients with adenocarcinoma of the appendix. METHODS: A retrospective case series was conducted at three medical school teaching hospitals over a 20-year period from 1972 to 1992. Overall survival was determined by the actuarial life table method. Comparisons of prognostic factors were made using exact nonparametric log-rank tests. RESULTS: Thirteen patients were diagnosed during the study period. Median age was 62 years. There were five males and eight females. The disease was not suspected in any patient preoperatively. Seventy-seven percent of patients had metastatic disease at presentation. Second primary malignancies were found in 15 percent of patients. Thirty-eight percent of female patients had synchronous ovarian lesions. Median survival was 22 months, with an estimated five-year survival of 43 percent (95 percent confidence interval, 22-84 percent). Patients with colonic histology had significantly worse survival than patients with mucinous histology (P = 0.0093). Patients with carcinomatosis had a significantly worse survival than noncarcinomatosis patients (P = 0.0078). Patients who underwent right hemicolectomy had a better prognosis for survival than appendectomy patients, but the difference was not statistically significant. CONCLUSIONS: Carcinoma of the appendix is very difficult to diagnose preoperatively, and most patients are not identified until disease is advanced. Good prognostic factors include mucinous histology and the absence of carcinomatosis. Right hemicolectomy appears to be a reasonable option, although its superiority to appendectomy alone has not been definitively proven. High frequency of ovarian metastases in women suggests a role for bilateral oophorectomy. In addition, a complete work-up of the patient for a synchronous malignancy, especially in the gastrointestinal tract, should be considered.

Effects of tamoxifen on growth and apoptosis of estrogen-dependent and -independent human breast cancer cells.

BACKGROUND: Apoptosis ("programmed cell death") is an active process characterized by prominent nuclear changes and DNA cleavage, which distinguishes it from cellular necrosis. In this study we investigated whether tamoxifen (TAM) treatment of estrogen receptor ER(+) MCF-7 and ER(-) MDA-231 human breast cancer cells resulted in cytotoxicity and cellular changes typical of apoptosis. METHODS: Cytotoxicity was measured using a tetrazolium assay. Cellular morphologic changes were observed using transmission electron microscopy. DNA cleavage was assessed using 1.6% agarose gel electrophoresis and was also quantitated biochemically. RESULTS: Exposure of cells to TAM for 24 h resulted in dose-dependent cytotoxicity, and MCF-7 cells were somewhat more sensitive to TAM. TAM induced chromatin condensation around the nuclear periphery in both cell lines, changes typical of apoptosis. TAM-induced cytotoxicity correlated with dose-dependent DNA cleavage, which showed the characteristic "internucleosomal ladder." DNA cleavage occurred at a slightly lower TAM dose and occurred somewhat sooner in MCF-7 cells. TAM-induced DNA cleavage in MCF-7 cells was inhibited by the protein synthesis inhibitor cycloheximide, the RNA synthesis inhibitor actinomycin D, and by 17 beta-estradiol. However, in MDA-231 cells, DNA cleavage was inhibited by cycloheximide, partially but not significantly inhibited by actinomycin D, and not inhibited by 17 beta-estradiol. CONCLUSIONS: TAM induces typical apoptosis in ER(+) or ER(-) human breast cancer cells. TAM induction of apoptosis in MCF-7 cells involves the estrogen receptor, and requires the synthesis of new protein and mRNA. TAM induction of apoptosis in MDA-231 cells depends primarily on protein synthesis. TAM-induced cytotoxicity and DNA damage appear to be explained in part by the induction of apoptosis.

Cancer of the male breast.

A retrospective review of 28 male breast cancer patients at Eastern Virginia Medical School and affiliated hospitals was performed to learn about patient characteristics, treatment, and outcome. The mean age of the patients was 64 years, and 60 per cent of patients were obese. The most common presenting symptoms were mass in 79 per cent and nipple discharge in 29 per cent. The median duration of symptoms was 3.3 months. All patients except two underwent mastectomy, and most tumors were early stage (0, I, or II). Many patients, particularly those with advanced disease, were also treated with chemotherapy, radiation therapy, and/or endocrine therapy. At a median follow-up of 29 months, the actuarial 5-year survival was 43 per cent, somewhat worse than the survival of female breast cancer patients in the literature. Male breast cancer patients are treated in a similar fashion to female patients. Aggressive systemic treatment should be considered for patients with poor prognosis disease. The high frequency of estrogen receptor positivity suggests tamoxifen may prove to be particularly useful in these patients.