A double-blind, placebo-controlled randomized trial of creatine for the cancer anorexia/weight loss syndrome (N02C4): an Alliance trial.

BACKGROUND: Multiple pilot studies, including one in colorectal cancer patients, suggest that creatine, an amino acid derivative, augments muscle, improves strength, and thereby could palliate the cancer anorexia/weight loss syndrome. PATIENTS AND METHODS: In this randomized, double-blind, placebo-controlled trial, incurable patients with this syndrome were assigned creatine (20 g/day load×5 days followed by 2 g/day orally) versus identical placebo. Patients were weighed once a week for 1 month and then monthly. Patients were also assessed over 1 month for appetite and quality of life (validated questionnaires), fist grip strength, body composition (bioelectrical impedance), and adverse events. The primary endpoint was 10% or greater weight gain from baseline during the first month. RESULTS: Within this combined cohort of 263 evaluable patients (134 received creatine and 129 placebo), only 3 gained ≥10% of their baseline weight by 1 month: two creatine-treated and the other placebo-exposed (P = 1.00). Questionnaire data on appetite, quality of life, and activities of daily living showed no statistically significant differences between groups. Similarly, no statistically significant differences between groups were observed for fist-grip strength or body composition. Rates and severity of adverse events were comparable between groups. Finally, a median survival of 230 and 239 days were observed in the creatine and placebo groups, respectively (P = 0.70). CONCLUSION: Creatine, as prescribed in this trial, had no effect on the cancer anorexia/weight loss syndrome.

Risk of acute myeloid leukemia and myelodysplastic syndrome among older women receiving anthracycline-based adjuvant chemotherapy for breast cancer on Modern Cooperative Group Trials (Alliance A151511).

PURPOSE: We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with >90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines. METHODS: We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (≥65 vs. <65 years; separately for ≥70 vs. <70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS. RESULTS: On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age ≥65 and 7% were ≥70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age ≥65 and ≥70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age <65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age ≥65 [vs. <65] = 3.13, 95% confidence interval [CI] 1.18-8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47-18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS. CONCLUSIONS: We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients.

A phase II study (ARCHER 1042) to evaluate prophylactic treatment of dacomitinib-induced dermatologic and gastrointestinal adverse events in advanced non-small-cell lung cancer.

BACKGROUND: ARCHER 1042, a randomized phase II trial, explored the impact of prophylactic treatment on select dermatologic adverse events of interest (SDAEI), diarrhea, and mucositis associated with dacomitinib, an oral irreversible pan-human epidermal growth factor receptor (HER) inhibitor, in development for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC treated with dacomitinib were enrolled in two cohorts. Cohort I patients were randomized 1:1 to receive oral doxycycline or placebo (4 weeks). Cohort II patients received oral VSL#3 probiotic plus topical alclometasone. Primary end points for Cohorts I and II were incidence of all grade and grade ≥2 SDAEI in the first 8 weeks of treatment and quality of life (QoL) assessed by the Skindex-16 survey. Additional primary end points for Cohort II were incidence of all grade and grade ≥2 diarrhea and mucositis in the first 8 weeks of treatment; QoL regarding diarrhea and mucositis incidence was assessed by the modified-Oral Mucositis Daily Questionnaire. RESULTS: Cohort I randomized 114 evaluable patients: 56 in the doxycycline arm, 58 in the placebo arm. Cohort II enrolled 59 evaluable patients. Doxycycline significantly reduced the incidence of grade ≥2 SDAEI by 50% (P = 0.016) compared with placebo. The incidence of all grade SDAEI was lower with doxycycline than with placebo but did not reach statistical significance. Doxycycline was associated with less deterioration in QoL compared with placebo. Alclometasone was associated with less deterioration in QoL compared with placebo but did not statistically significantly reduce the incidence of all grade or grade ≥2 SDAEI. VSL#3 did not reduce the incidence of all grade or grade ≥2 diarrhea and did not impact mucositis scores. CONCLUSIONS: Doxycycline was effective as a prophylactic treatment for dacomitinib-induced grade ≥2 SDAEI. Both doxycycline and alclometasone reduced the negative impact in patient-reported dermatologic AEs. The probiotic was not effective for preventing diarrhea or mucositis.

Disease-free ovarian cancer patients report severe pain and fatigue over time: prospective quality of life assessment in a consecutive series.

UNLABELLED: objective: Among ovarian cancer patients, cancer treatment is aggressive and yet survival is often so limited; hence, this study sought to measure quality of life with the ultimate goal of identifying ways of improving it over the duration of these patients' lives. MATERIALS AND METHODS: The medical records of all ovarian cancer patients who received some/all of their initial chemotherapy at the Mayo Clinic in Rochester, Minnesota from late 2010 through 2012 were reviewed. Patient-reported quality of life was derived from the following ten-point linear analogue scale questions which had been administered to all patients: 1) How would you describe your degree of pain, on average? 2) How would you describe your level of fatigue, on average? 3) How would you describe your overall quality of life? Quality of life data were censored upon cancer recurrence. RESULTS: Among 59 eligible patients, the median cumulative interval during which quality of life was serially assessed was 1.15 years (range: three months, 3.2 years). Area under the curve for pain, fatigue, and global quality of life showed no statistically significant differences between patients treated with dose-dense chemotherapy with carboplatin/paclitaxel (n = 10) versus three-week chemotherapy with carboplatin/paclitaxel (n = 36) versus other (n = 13). Although pain, fatigue, and global quality of life improved over time, 35 of 59 (59%) patients reported grade 4 or worse pain during follow up, and 47 of 59 (80%) reported grade 4 or worse fatigue (higher scores denote worse pain or fatigue). After completion of cancer treatment, 30 (51%) described grade 4 or worse pain or fatigue. The most common pain site was the abdomen/pelvis, followed by the back, followed by the hands, feet, fingers, and toes. CONCLUSION: In ovarian cancer patients who remain cancer-free, severe pain and fatigue occur years after cancer treatment. Further research should focus on how best to address these symptoms.

Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a European School of Oncology Task Force.

BACKGROUND: Weight loss and cachexia are common, reduce tolerance of cancer treatment and the likelihood of response, and independently predict poor outcome. METHODS: A group of experts met under the auspices of the European School of Oncology to review the literature and-on the basis of the limited evidence at present-make recommendations for malnutrition and cachexia management and future research. CONCLUSIONS: Our focus should move from end-stage wasting to supporting patients' nutritional and functional state throughout the increasingly complex and prolonged course of anti-cancer treatment. When inadequate nutrient intake predominates (malnutrition), this can be managed by conventional nutritional support. In the presence of systemic inflammation/altered metabolism (cachexia), a multi-modal approach including novel therapeutic agents is required. For all patients, oncologists should consider three supportive care issues: ensuring sufficient energy and protein intake, maintaining physical activity to maintain muscle mass and (if present) reducing systemic inflammation. The results of phase II/III trials based on novel drug targets (e.g. cytokines, ghrelin receptor, androgen receptor, myostatin) are expected in the next 2 years. If effective therapies emerge, early detection of malnutrition and cachexia will be increasingly important in the hope that timely intervention can improve both patient-centered and oncology outcomes.

Ostomies in rectal cancer patients: what is their psychosocial impact?

The resection of a low-lying rectal cancer can lead to the creation of an ostomy to discharge fecal material. In view of this reconfiguration of anatomy and life-changing modification of daily bodily functions, it is not surprising that a rapidly growing literature has examined ostomy patients' psychosocial challenges. The current study was designed (1) to systematically review the published literature on these psychosocial challenges and (2) to explore, in a single-institution setting, whether medical oncologists appear to acknowledge the existence of an ostomy during their post-operative evaluations of rectal cancer patients. This systematic review identified that social isolation, sleep deprivation; financial concerns; sexual inhibition; and other such issues are common among patients. Surprisingly, however, in our review of 66 consecutive rectal cancer patients, in 17%, the ostomy was not mentioned at all in the medical record during the first medical oncology visit; and, in one patient, it was never mentioned at all during months of adjuvant chemotherapy. Even in the setting of ostomy complications, the ostomy was not always mentioned. This study underscores the major psychosocial issues cancer patients confront after an ostomy and suggests that healthcare providers of all disciplines should work to remain sensitive to such issues.

Overall survival and self-reported fatigue in patients with esophageal cancer.

PURPOSE: A prospective cohort study was conducted to analyze whether self-reported fatigue predicts overall survival in patients with esophageal cancer. METHODS: Patients enrolled in the Mayo Clinic Esophageal Adenocarcinoma and Barrett's Esophagus Registry between September 2001 and January 2009 who completed a baseline quality of life instrument were eligible for evaluation. The fatigue component was scored on a 0-10 scale, with 0 as extreme fatigue. Patients were categorized as having a decreased energy level if they reported a score of ≤ 5. Fatigue scores ≥ 6 reflect normal levels of energy. RESULTS: Data from a total of 659 enrolled patients were analyzed. A total of 392 (59 %) and 267 (41 %) patients reported decreased and normal energy, respectively. Univariate analysis indicates patients with normal energy had improved 5-year survival compared to patients with decreased energy (37 vs 28 %, hazard ratio (HR) 0.74, p = 0.006). Among the patients with locally advanced disease, the same relationship was seen (28 vs 17 %, HR = 0.67, p = 0.003); this remained significant on multivariate analysis (HR = 0.71, p = 0.015). CONCLUSIONS: A decreased energy level is associated with poor survival in patients with esophageal cancer. Thus, patients with high levels of fatigue should be referred for psychological support and be considered for therapy aimed at amelioration of fatigue symptoms.

Bone pain from granulocyte colony stimulating factor: does clinical trial sponsorship by a pharmaceutical company influence its reporting?

It is alleged that pharmaceutical companies sometimes unfairly present clinical trial results. To our knowledge, studies have not explored whether such alleged unfair reporting also occurs in the testing of palliative care agents in cancer patients, a particularly vulnerable group. Therefore, a systematic search was conducted to retrieve all published, prospective clinical trials that used granulocyte colony stimulating factor starting in 2003. Because granulocyte colony stimulating factor can cause severe bone pain - a concerning but historically under-reported symptom in cancer patients - this symptom was assessed to determine whether differences in reporting occurred based on pharmaceutical company-sponsorship. A total of 239 published clinical trials met the present study's eligibility criteria and were retrievable. Within this entire group of studies, 65 (27%) were pharmaceutical company-sponsored, and only 31 (13%) reported on bone pain. However, pharmaceutical company-sponsored trials reported on bone pain at a higher rate compared with other studies: 23% versus 9% (P= 0.005), and this conclusion did not change after adjusting for dose, use of the slow release formulation and year of publication. The reporting of adverse events from cancer symptom control and palliative care interventions should be improved - especially in trials not sponsored by pharmaceutical companies.

A phase II study of cetuximab and radiation in elderly and/or poor performance status patients with locally advanced non-small-cell lung cancer (N0422).

BACKGROUND: Non-small-cell lung cancer (NSCLC) is a disease of the elderly. Seeking a tolerable but effective regimen, we tested cetuximab + radiation in elderly and/or poor performance status patients with locally advanced NSCLC. PATIENTS AND METHODS: Older patients [≥ 65 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2] or younger patients (performance status of 2) received cetuximab 400 mg/m(2) i.v. on day 1 followed by weekly cetuximab 250 mg/m(2) i.v. with concomitant radiation of 6000 cGy in 30 fractions. The primary end point was the percentage who lived 11+ months. RESULTS: This 57-patient cohort had a median age (range) of 77 years (60-87), and 12 (21%) had a performance status of 2. Forty of 57 (70%) lived 11+ months, thus exceeding the anticipated survival rate of 50%. The median survival was 15.1 months [95% confidence interval (CI) 13.1-19.3 months], and the median time to cancer progression was 7.2 months (95% CI 5.8-8.6 months). No treatment-related deaths occurred, but 31 patients experienced grade 3+ adverse events, most commonly fatigue, anorexia, dyspnea, rash, and dysphagia, each of which occurred in <10% of patients. CONCLUSION: This combination merits further study in this group of patients.

Bioavailability of phylloquinone from an intravenous lipid emulsion.

This randomized, controlled study evaluated the bioavailability of phylloquinone from an intravenous lipid emulsion. A mild vitamin K deficiency was induced in 12 healthy adult men and women by dietary restriction of phylloquinone (40 microg/d, days 1-11) and by administration of warfarin (1.0 mg/d, days 5-11). On day 11, subjects received a 500-mL intravenous solution of either lipid or saline, both of which contained 154 microg phylloquinone. Bioavailability was assessed by serial measurements of plasma phylloquinone, vitamin K1-2,3-epoxide. PIVKA-II (proteins induced by vitamin K absence or antagonists-II), and percentage undercarboxylated osteocalcin. As a result of vitamin K deficiency and minidose warfarin, vitamin K1-2,3-epoxide, PIVKA-II, and percentage undercarboxylated osteocalcin increased significantly between days 1 and 11 (P = 0.05, 0.016, and 0.001, respectively). With the infusions, plasma phylloquinone increased in both groups (P = 0.001). After the infusions vitamin K,-2,3-epoxide decreased in both groups (P = 0.002). Changes in plasma phylloquinone and vitamin K1-2,3-epoxide were no different in the two groups (mean areas under the curves +/- SEM: 116+/-13 nmol x h/L for the saline group and 102+/-20 nmol x h/L for the lipid group for phylloquinone; 38.6+/-7.5 nmol x h/L for the saline group and 31.3+/-9.0 nmol x h/L for the lipid group for vitamin K1-2,3-epoxide). PIVKA-II decreased significantly from baseline values (P = 0.005) in both groups after the infusions. Intravenous lipid reversed the effects of minidose warfarin and of dietary restriction of phylloquinone on hemostasis and vitamin K nutritional status. This reversal was no different from that seen with the infusion of phylloquinone in a saline solution.

The prognostic effect of increased resting energy expenditure prior to treatment for lung cancer.

OBJECTIVE: Increased resting energy expenditure (REE) is thought to confer a poor prognosis in patients with non-small cell lung cancer (NSCLC). However, no study has validated this hypothesis to date. This study's objective was to examine the prognostic significance of REE in NSCLC. METHODS: Seventeen patients with NSCLC (stages IA-IIIB) underwent measurement of REE with indirect calorimetry before the initiation of cancer treatment. Similar measurements were performed in 17 control subjects, each of whom was matched to a cancer patient by age ( +/-5 years), sex and body mass index ( +/-3 kg/m2). Patients were classified as hypermetabolic or hypometabolic based on a direct comparison of measured REE between cancer patients and their matched controls. After cancer treatment, these 17 patients were followed for evidence of metastatic disease for up to 32 months. RESULTS: Six patients developed metastatic disease. The eight hypometabolic cancer patients had a significantly shorter mean disease-free survival compared to the nine hypermetabolic cancer patients: 19 months (95% confidence interval (CI) 12, 26) versus 29 months (95% CI 24, 34), respectively (P < 0.05 by log-rank test). In contrast, Cox regression showed no relationship between disease-free survival and differences in REE between cancer patients and their matched controls (P = 0.20). CONCLUSIONS: These results suggest that hypermetabolism may predict a longer disease-free survival in NSCLC patients. This finding differs from the prevailing hypothesis that hypometabolic patients with NSCLC survive longer, and deserves further investigation.

Environmental tobacco smoke exposure in women with lung cancer.

BACKGROUND: Investigations on environmental tobacco smoke (ETS) exposure that include source intensity, childhood exposure, and association with histologic subtypes among never smoking lung cancer cases are limited. We report the patterns of ETS exposure history in a clinical cohort of women with newly diagnosed lung cancer. METHODS: From 1997 to 2001, 810 women with lung cancer were interviewed to obtain data including the source, intensity, and duration of ETS exposure. In this descriptive study, relationships between smoking history, ETS exposure, and lung cancer histologic subtypes were analyzed. RESULTS: Among the 810 patients, 773 (95.4%) reported personal smoking or ETS exposure including 170 of 207 (82%) never smokers. Among the never smokers with a history of ETS exposure, the mean years of exposure were 27 from a smoking spouse, 19 from parents, and 15 from co-workers. For each major subtype of lung cancer (adenocarcinoma, squamous cell, unclassified non-small cell lung cancer, small cell, or carcinoids) among never smokers, 75-100% of patients had ETS exposure. Trends for adenocarcinoma, squamous, and small cell carcinoma are statistically significant using the Cochran-Armitage Test for Trend (P<0.001) among never smokers without ETS exposure, never smokers with ETS exposure, former smokers, and current smokers. CONCLUSIONS: Over 95% of women with lung cancer in our study were exposed to tobacco smoke through a personal smoking history or ETS. The cumulative amount of tobacco smoke exposure may be significantly underestimated if only personal smoking history is considered. Our results add to the public health implications of exposure to tobacco smoke and highlight the importance of eliminating tobacco smoking in public and private settings.

Parosteal osteosarcoma from a rib.

Comprising 1.6% of primary bone malignancies, parosteal osteosarcomas are rare. Rib parosteal osteosarcomas are even rarer, with only 2 cases in the literature. We report a third such case, with a 32-month disease-free survival. Issues relevant to the management of rib parosteal osteosarcomas are discussed.

Do patients with nonmetastatic non-small cell lung cancer demonstrate altered resting energy expenditure?

BACKGROUND: The cancer cachexia syndrome occurs in patients with non-small cell lung cancer (NSCLC) and includes elevated resting energy expenditure (REE). This increase in REE leads to weight loss, which in turn confers a poor prognosis. This study was undertaken to determine whether the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC. METHODS: In this case-control study, 18 patients with nonmetastatic NSCLC (stages IA to IIIB) were matched to healthy controls on age (+/- 5 years), gender, and body mass index (+/- 3 kg/m2). Only 4 cancer patients had experienced > 5% weight loss. Cancer patients and controls were compared on the basis of: (1) unadjusted REE, as measured by indirect calorimetry; (2) REE adjusted for lean body mass, as measured by dual x-ray absorptiometry; (3) REE adjusted for body cell mass, as measured by potassium-40 measurement; and (4) REE adjusted for total body water, as measured by tritiated water dilution. RESULTS: We observed no significant difference in unadjusted REE or in REE adjusted for total body water. However, with separate adjustments for lean body mass and body cell mass, cancer patients manifested an increase in REE: mean difference +/- standard error of the mean: 140+/-35 kcal/day (p = 0.001) and 173+/-65 kcal/day (p = 0.032), respectively. Further adjustment for weight loss yielded similarly significant results. CONCLUSIONS: These results suggest that the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC and raise the question of whether clinical trials that target cancer cachexia should be initiated before weight loss.

Current management of cancer-associated anorexia and weight loss.

Loss of appetite and weight predict a poor prognosis for cancer patients. Although caloric supplementation might benefit subgroups of patients--specifically, perioperative, severely malnourished cancer patients, stem cell and bone marrow transplant patients and head and neck cancer patients--its use remains controversial and is not recommended for the majority of patients with cancer-associated weight loss. Most patients with advanced cancer, anorexia, and/or weight loss do not appear to benefit from nutritional supplementation. Instead, discussions with patients and families about realistic eating goals ans, at time armacologic interventions with progestational agents or corticosteroids--both of which are aimed at palliating anorexia--provide clinical benefit. Other phamalogic interventions such as eicosapentaenoic acid, thalidomide (Thalomid), adenosine triphosphate and nonsteriodal anti-inflammatory agents focus on the fact that cancer-assciated weight loss is an enitty dintinct for simple starvation These interventions promise to replenish lean tissue but require further investigation before they can be recommndedas standard clinical practice.

Protein-calorie malnutrition does not predict subtle vitamin K depletion in hospitalized patients.

OBJECTIVE: Recent studies suggest that subtle vitamin K depletion has far-reaching consequences. As this entity is not associated with prothrombin time elevation, it is important to determine whether alternate methods can help identify it. We investigated subtle vitamin K depletion in a hospital setting and determined whether protein calorie malnutrition predicts its presence. DESIGN, SETTING, SUBJECTS: Using a high-pressure liquid chromatography (HPLC) assay of plasma phylloquinone and a food frequency questionnaire for phylloquinone intake, we examined the phylloquinone status of 27 hospitalized patients with normal coagulation parameters, no liver disease, and no recent warfarin use. We assessed protein-calorie nutritional status with Reilly's criteria and anthropometrics. RESULTS: 51% of patients (95% CI = 31% to 70%) had evidence of subtle vitamin K depletion as defined by a subnormal plasma phylloquinone concentration. Patients whose phylloquinone intake was less than the Recommended Daily Allowance (RDA) over the preceding year had lower plasma phylloquinone concentrations when compared to other patients: median (range) 0.106 nmol/l (0.022-0.461) versus 0.301 nmol/l (0.067-3.928), respectively (P = 0.023). Plasma phylloquinone concentrations were no different, however, between well-nourished and malnourished patients: median (range) 0.245 nmol/l (0.022-0.522) versus 0.188 nmol/l (0.067-3.928), respectively (P=0.782). CONCLUSIONS: Subtle vitamin K depletion is common among hospitalized patients and protein-calorie malnutrition does not predict its presence.

Nutritional determinants of survival among patients with breast cancer.

Recent data leave little doubt that nutritional factors modulate the growth of breast cancer cells. Nonetheless, the question of what type of diet is best for patients with a history of early-stage breast cancer or for patients with metastatic breast cancer continues to loom despite a growing number of studies on nutrition and cancer. Recommendations for the general population from the American Cancer Society and the Dietary Guidelines for Americans outline 25% of calories from fat, multiple servings of fruits and vegetables, and an emphasis on eating a variety of different foods. Although these recommendations likely constitute prudent advice for patients with breast cancer who have completed treatment for early-stage disease, they remain unproved. Specific, beneficial recommendations for patients currently receiving adjuvant chemotherapy or for patients with metastatic disease may well differ from those for the general population. Future clinical trials will play an important role in clarifying such issues.

A prospective survey for central line skin-site colonization by the pathogen Malassezia furfur among hospitalized adults receiving total parenteral nutrition.

BACKGROUND: Over 50 case reports suggest that Malassezia furfur is an emerging systemic pathogen in neonates who receive IV lipid emulsions. Because isolation of this fungus requires special culture techniques, which are not routinely used, the authors of many case reports of M. furfur infections in adults question whether infections caused by this organism are being underdiagnosed in older patients. METHODS: Catheter insertion site colonization rates in adults receiving total parenteral nutrition (TPN) were prospectively evaluated in 149 hospitalized patients with 928 cultures handled specifically for M. furfur detection. Positive control samples consisted of M. furfur cultures in neonates and in adults, who had not been enrolled in the study, and of a separate positive culture obtained from a skin site inoculated with M. furfur. RESULTS: M. furfur was not cultured from any of the 928 study samples (95% confidence interval [CI] -0.4% to +0.4%). CONCLUSIONS: These results suggest that M. furfur is less of a threat to hospitalized adults receiving TPN than has been otherwise postulated. These data do not support the inclusion of special cultures for M. furfur in routine skin-site surveillance programs among hospitalized adults receiving TPN.

Prognostic variables in male breast cancer.

The prognostic role of ploidy status, S phase fraction, estrogen and progesterone receptor status, and the expression of p53 and erbB-2 protein in male breast carcinoma (MBC) remains controversial. The primary objective of this study was to determine which of the common prognostic factors for female breast cancer predict prognosis in MBC. A secondary objective was to assess the impact of comorbid illnesses on survival. A retrospective review of demographic data, surgical treatment, pathological staging, adjuvant treatment and follow-up was completed for 16 patients with MBC (1 intraductal and 15 invasive). Formalin-fixed, paraffin-embedded tissue was processed for ploidy, S phase fraction, and immunohistochemical detection of estrogen and progesterone receptors plus expression of p53 and erbB-2 protein. Six of 15 patients with infiltrating ductal carcinoma are currently alive without evidence of disease and a median survival of 61 months. Nine patients died after a median survival of 52 months, with 6 patients having no evidence of recurrent breast cancer. Two of 3 deaths secondary to advanced breast cancer occurred in patients who initially presented with T4 lesions and were staged IIIB. Two of 15 tumors were erbB-2 positive, whereas only 1 tested weakly positive for p53 protein. We observed that MBCs express erbB-2 and p53 proteins infrequently. Neither ploidy status, S phase fraction, nor erbB-2/p53 status provided any apparent improvement in establishing prognosis beyond routine pathological staging. Advanced TNM stage was associated with diminished survival. The majority of MBCs express estrogen and progesterone receptors. Survivals in MBC were reduced in association with comorbid medical conditions.