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Background: As androgen deprivation therapy (ADT) becomes a standard of treatment for men with recurrent or metastatic prostate cancer, evaluation of adverse effects associated with this treatment is needed. In this study, the authors evaluated the effect of ADT administered as monotherapy and in combination with local treatment on physical well-being in a longitudinal sample of men with prostate cancer., Methods: Exposure to ADT was defined by 3 groups: local (local treatment only), combination (local treatment with adjuvant and/or neoadjuvant ADT), and primary ADT. Associations between exposure to ADT and physical well-being measured by self-reported health-related quality of life outcomes over time were evaluated by repeated measures analysis using mixed modeling. Estimates adjusted for various clinical and demographic variables are reported., Results: A total of 2922 men, who completed both pretreatment and follow-up health-related quality of life assessment, were identified from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry. During 24 months of follow-up, exposure to ADT was associated with worse physical well-being compared with local treatment at all time points (P < .001). Being exposed to ADT as primary therapy was associated with more severe declines compared with combination therapy., Conclusions: The potential consequence of decline in physical well-being in patients exposed to ADT has to be included in treatment decision making., (Copyright © 2011 American Cancer Society.)

Background: Breast cancer in men is rare, so clinical trials are not practical. Recommendations suggest treating men who are diagnosed with breast cancer using the guidelines for postmenopausal women; however, to date, no population-based studies have evaluated patterns of care., Methods: To examine characteristics, treatment, and survival among men with newly diagnosed breast cancer, in 2003 and 2004, 512 men were identified from the Surveillance, Epidemiology and End Results Program. Data were reabstracted and therapy was verified through the patients' treating physicians., Results: The majority of men (79%) were diagnosed through discovery of a breast lump or other signs/symptoms. Among men who had invasive disease, 86% underwent mastectomy, 37% received chemotherapy, and 58% received hormone therapy. In multivariate analysis, tumor size (P=.01) and positive lymph node status (P<.0001) were associated positively with the use of chemotherapy, whereas age group (P<.0001) and current unmarried status (P=.01) had negative associations. Among men who had invasive, estrogen receptor (ER)-positive/borderline tumors, the use of tamoxifen or aromatase inhibitors (AIs) was associated with age group (P=.05). Among men who had invasive disease, cancer mortality was associated with tumor size (P<.0001). Among men with ER-positive/borderline disease, increased cancer mortality was associated with tumor size (P<.0001), current unmarried status (P=.04), and decreased mortality with tamoxifen (P=.04)., Conclusions: Tumor characteristics and marital status were the primary predictors of therapy and cancer mortality among men with breast cancer. Although AIs are not currently recommended, they are commonly prescribed. However, their use did not result in a decrease in cancer mortality. Research must examine the efficacy of AIs with and without gonadotropin-releasing hormone analogues., (Copyright (c) 2010 American Cancer Society.)

Background: African-American women have increased breast cancer mortality compared with white women. Diagnostic and treatment gaps may contribute to this disparity., Methods: In this retrospective, longitudinal cohort study, Southern US health plan claims data and linked medical charts were used to identify racial disparities in the diagnoses, treatment, and mortality of commercially insured women with newly diagnosed breast cancer. White women (n = 476) and African-American women (n = 99) with newly diagnosed breast cancer were identified by breast cancer claims codes (International Classification of Diseases, Ninth Revision, Clinical Modification codes 174, 233.0, 238.3, and 239.3) between January 2000 and December 2004. Race, diagnoses (breast cancer stage, estrogen/progesterone receptor [ER/PR]-positive status), treatment (breast-conserving surgery, antiestrogen therapy, and chemotherapy interruption or reduction), and all-cause mortality were assessed from medical charts. Multivariate regression analyses were adjusted for age, geography, and socioeconomic status to test the association of race with diagnoses/treatment., Results: White women were older (P < .001) and had higher rates of diagnosis at stage 0/I (55.2% vs 38.4%; P < .05) than African-American women. More white women had positive ER/PR status (75% vs 56% African-American; P = .001) and received antiestrogen therapy if they were positive (37.2% vs 27.3% African-American; P < .001). White women received slightly more breast-conserving surgery and chemotherapy dose modification than African-American women (P value nonsignificant). African-American women had a higher mortality rate (8.1%) than white women (3.6%; P = .06). In adjusted analyses, African-American women were diagnosed at later stages (odds ratio, 1.71; P = .02), and white women received more antiestrogen therapy (odds ratio, 2.1; P = .03)., Conclusions: Disparities in medical care among patients with newly diagnosed breast cancer were evident between African-American women and white women despite health plan insurance coverage. Interventions that address the gaps identified are needed., (Copyright 2010 American Cancer Society.)

Background: To help oncologists and breast cancer patients make informed decisions about adjuvant therapies, online tools such as Adjuvant! provide tailored estimates of mortality and recurrence risks. However, the graphical format used to display these results (a set of 4 horizontal stacked bars) may be suboptimal. The authors tested whether using simpler formats would improve comprehension of the relevant risk statistics., Methods: A total of 1,619 women, aged 40-74 years, completed an Internet-administered survey vignette about adjuvant therapy decisions for a patient with an estrogen receptor-positive tumor. Participants were randomized to view 1 of 4 risk graphics, a base version that mirrored the Adjuvant! format, an alternate graph that showed only 2 options (those that included hormonal therapy), a graph that used a pictograph format, or a graph that included both changes. Outcome measures included comprehension of key statistics, time required to complete the task, and graph-perception ratings., Results: The simplifying format changes significantly improved comprehension, especially when both changes were implemented together. Compared with participants who viewed the base 4-option bar graph, respondents who, instead, viewed a 2-option pictograph version were more accurate when they reported the incremental risk reduction achievable from adding chemotherapy to hormonal therapy (77% vs 51%; P< .001), answered that question more quickly (median time, 28 seconds vs 42 seconds; P< .001), and liked the graph more (mean, 7.67 vs 6.88; P< .001)., Conclusions: Although most patients will only view risk calculators such as Adjuvant! in consultation with their clinicians, simplifying design graphics could significantly improve patients' comprehension of statistics essential for informed decision making about adjuvant therapies.

Background: Observational data are used increasingly to assess the effectiveness of therapies. However, selection biases are likely to have an impact on results and threaten the validity of these studies., Methods: The primary objective of the current study was to explore the effect of selection biases in observational studies of treatment effectiveness in cancer care. Patients were identified from the Surveillance, Epidemiology, and End Results-Medicare linked database. The following groups of patients were included: 5245 men treated with and without androgen deprivation for locally advanced prostate cancer, 43,847 men with active treatment versus observation for low- and intermediate-risk prostate cancer, and 4860 patients with lymph node-positive colon cancer who were treated with and without fluorouracil chemotherapy. Patients were compared by therapy for the outcomes of cancer-specific mortality, other-cause mortality, and overall mortality., Results: In all comparisons, the observational data produced improbable results. For example, when evaluating outcomes of men who were treated with and without androgen deprivation for locally advanced prostate cancer, men who underwent androgen deprivation had higher prostate cancer mortality (hazard ratio, 1.5; 95% confidence interval, 1.29-1.92) despite clinical trial evidence that this treatment improves cancer mortality. Controlling for comorbidity, extent of disease, and other characteristics by multivariate analyses or by propensity analyses had remarkably small impact on these improbable results., Conclusions: The current results suggested that the results from observational studies of treatment outcomes should be viewed with caution., ((c) 2008 American Cancer Society.)

Background: The current study was conducted to develop a prognostic model of event-free survival (EFS) in men with androgen-independent prostate carcinoma (AIPC)., Methods: Data from 160 patients diagnosed with AIPC between 1989-2002 were reviewed. No patient had received cytotoxic chemotherapy. A univariate Cox proportional hazards model identified significant predictors of EFS. Recursive partitioning analysis divided these significant variables into prognostic risk groups. The final prognostic model was tested with a Cox proportional hazards model., Results: The final prognostic risk model included the presence of metastatic disease at the time of androgen-independent disease progression (P = 0.040), time to prostate-specific antigen (PSA) recurrence (P = 0.043), and PSA doubling time (P < 0.01). Three highly independent risk groups were identified. The observed median EFSs were 6.1 months (95% confidence interval [95= CI], 3.4-8.8 months), 33.6 months (95= CI, 25.3-41.9 months), and 96.1 months (95= CI, 57.9-134.3 months) for the low-risk, intermediate-risk, and high-risk groups, respectively. Each risk group was found to be independently predictive of EFS (P < 0.01). Patients who died of prostate carcinoma experienced significantly more clinical events than those who died of other causes (P < 0.01)., Conclusions: The prognostic model in the current study stratified patients into three highly significant and independent risk groups for EFS. A detailed PSA history and knowledge of metastatic disease are sufficient to risk-stratify patients with AIPC. One very unique aspect of this model was that it was developed from a patient cohort that never received chemotherapy.

Background: The objectives of the current study were to determine the maximum tolerated dose and to evaluate the efficacy of gemcitabine given in combination with strontium-89 to patients with androgen independent prostate carcinoma., Methods: Patients with androgen-independent prostate carcinoma and painful osteoblastic bone metastases were eligible. On a 12-week course, patients received gemcitabine (600 mg/m(2) or 800 mg/m(2)) on Days 1, 8, 15, 43, 50, and 57. A single dose of strontium-89 (55 microCi/kg) was administered on Day 8., Results: Fifteen patients were registered, and all were assessable for response and toxicity. Four patients were treated at Dose Level 1 (gemcitabine 600 mg/m(2)) without dose-limiting toxicity. Eleven patients received a total of 13 courses at Dose Level 2 (gemcitabine 800 mg/m(2)). Platelet nadirs of 25000-50000 platelets per microL were common at Dose Level 2, and 1 patient had Grade 4 thrombocytopenia that was dose-limiting. Granulocyte nadirs up to < 500 granulocytes per microL occurred in 4 patients at Dose Level 2 and were reversible. There were no responses, as measured by prostate specific antigen concentration, although 6 patients (40%) had stable disease., Conclusions: The authors concluded that 800 mg/m(2) gemcitabine was the maximum tolerated dose for the combination. The study was terminated on the basis that an overall response rate > than 10% was unlikely. Further study at this dose level and schedule is not warranted. ., (Copyright 2003 American Cancer Society.)

Background: Poor prognosis of Stage IV breast cancer patients have at best a 10% 3-year survival rate with conventional chemotherapy. Dose-intensive chemotherapy improved survival rates for some of these patients., Methods: All patients were Stage IV estrogen receptor-negative or estrogen receptor-positive hormonal refractory and received conventional chemotherapy (induction phase) to the point of achieving maximal response; if disease was stable or the patients responded, they entered high-dose chemotherapy (intensive phase). Seventy-six percent of the patients received two high-dose treatments with cyclophosphamide (4.5-6.0 g/m2), etoposide (750-1500 mg/m2), and cisplatin (120-180 mg/m2). Patients were randomized to receive or not receive autologous marrow. To identify prognostic factors for survival, univariate statistical analysis and multivariate models were applied to patient subsets., Results: Univariate analysis identified a number of factors whose presence indicates improvement in overall survival rates. These include: (1) absence of liver relapse (P = 0.001); (2) absence of soft tissue relapse (P = 0.001); (3) a smaller number of metastatic sites at the time of detecting Stage IV disease (P = 0.026); and (4) disease-free interval greater than 1 year from initial diagnosis to Stage IV disease (P = 0.011). Multivariate models were fitted to the data, and three variables were identified as independent negative predictors for overall survival: (1) liver site (P = 0.001); (2) soft tissue site (P = 0.039); and (3) prior adjuvant chemotherapy (P = 0.028)., Conclusions: Shorter survival after high-dose chemotherapy is predicted independently by patients pretreated with adjuvant chemotherapy, by disease distributed to the liver or the soft tissue.

Background: In the early 1940s, when it was established that most prostatic cancers were androgen dependent and could be controlled by androgen withdrawal, little was known about the mechanism of androgen action. Measurements of hormones, both in the circulation and in the tissue, were not available, nor were measurements of androgen receptors known at that time., Methods: Since that time, a large body of information has been published regarding the mechanism of androgen-mediated action. With the understanding of androgen-mediated action has come the opportunity to develop drugs targeted to block specific steps in the sequence of androgen action, beginning in the hypothalamus-pituitary area and extending down to the intracellular processes of enzymatic reduction, receptor binding, and nuclear translocation of the hormone receptor complexes. The major focus in prostate cancer therapy currently is the role of the adrenal androgens., Results: It was established in the 1970s that, after castration, there was a 75% reduction in the dihydrotestosterone (DHT) present in prostate tissue. This observation contrasted with the finding that there was a greater than 90% reduction in circulating testosterone levels in the plasma after castration. Based on this important observation regarding tissue DHT concentrations after castration, attempts were made in the 1980s to block androgen totally using simultaneous gonadal and adrenal suppression. Dramatic results were reported after this type of therapy in the early uncontrolled studies. A luteinizing hormone-releasing hormone agonist plus flutamide was used for total androgen blockade. Other techniques for such blockade were available using megestrol acetate in combination with 17-beta-estradiol. One of the key issues has been whether the 25% residual DHT after castration provides a sufficient stimulus to growth of residual prostate tumor cells. The best evidence for the importance of the role of adrenal androgens came from clinical studies in which objective clinical responses were found in patients treated with various inhibitors of androgen action after relapse and castration. If "objectively stable" is included as a category after treatment, then approximately 33% of patients who have relapses after castration can be shown to have an additional response, albeit short, to adrenal androgen withdrawal., Conclusions: Thus, the control of the relatively small amounts of DHT remaining after castration became a major focus for therapy in metastatic prostate cancer.

Background: The role and benefit of adjuvant radiation therapy after radical prostatectomy is unclear. This role was evaluated in 58 patients who, after undergoing radical prostatectomy for prostate carcinoma, had local extension of disease beyond the prostate or positive surgical margins. Thirty-nine patients treated surgically alone were compared with 19 patients who received adjuvant postoperative radiation therapy. All patients were followed for at least 5 years, and 50 patients had 10-year follow-ups., Results: At 10 years, the actuarial local failure rate was 31% for patients treated with prostatectomy alone versus 6% for the group receiving postoperative radiation therapy (P less than 0.05). The actuarial survival and metastasis-free survival were similar for both groups. When patients with involved lymph nodes were excluded from analysis, the addition of radiation therapy resulted in improved recurrence-free survival (91% versus 46% at 10 years, P = 0.04) and in a trend toward improved metastasis-free survival (91% versus 55%, P = 0.08). Complications occurred in similar frequencies in both groups., Conclusions: In patients with local disease extension or positive surgical margins after radical prostatectomy, adjuvant radiation therapy improved local control and was administered with acceptable side effects.

Cancer of the prostate gland is the most frequently occurring malignant lesion in men. Because most prostate cells depend on androgen for growth, removal of testosterone by either orchiectomy or medical castration using diethylstilbestrol or a luteinizing hormone-releasing hormone (LHRH) analogue is first-line treatment for patients with symptomatic Stage D2 disease. The trend in hormonal therapy has been toward long-acting minimal-dosing high-compliance regimens, capitalizing on the recent availability of the long-acting LHRH analogues, which require only monthly injections to maintain castration levels of testosterone, and the nonsteroidal antiandrogen ICI 176,334, which (in early clinical trials) appears to block intracellular testosterone activity with a once-a-day oral regimen. To eliminate the rapid LH increase that can occur during early agonist therapy, combinations of LHRH analogues and antiandrogens (total androgen blockade) have been tested and appear promising. The effects of hormonal treatment in patients with symptomatic Stage D2 prostate cancer have been studied extensively and are relatively well understood. By contrast, hormonal treatment has not been explored in contemporary randomized Phase III trials of asymptomatic Stage D2, D1, or C disease, localized Stage B or A disease, or before prostate surgery or radiation treatment. Research must continue to determine the optimal regimen that suppresses testosterone activity with the least amount of toxicity.

The value of the addition of a pure antiandrogen to castration in advanced prostate cancer will be evaluated by an overview of all randomized studies addressing this question. This overview is currently being organized. Care is taken on identifying all randomized studies, published or unpublished, to avoid publication bias. Already 15 studies possibly related to the question are under investigation. Principal investigators of each relevant study are invited to participate in the overview. The principal end points of the study are overall and cause-specific mortality. The first report of results is planned for the end of 1991.

Prostate cancer is the most common neoplasm in the American male. More than 50% of patients present with locally advanced or metastatic disease and are not curable with local therapies such as radical prostatectomy or radiation therapy. This cancer is hormonally dependent, and methods that interrupt the hypothalamus-pituitary-testicular axis have been used to treat and control the disease effectively. The role of neutralizing the adrenal androgens is controversial. Combined androgen blockade refers to treatment modalities that lower circulating serum testosterone such as bilateral orchiectomy or an LH-RH agonist and combining it with an antiandrogen. The issue at hand is to review current clinical trials addressing the concept of combined androgen blockade and to determine the feasibility of a meta-analysis.

The stimulation of RNA synthesis induced by estradiol has been studied on 60 breast cancers in short-term cultures. In the same tumors the estrogen receptor (ER) assay was carried out. In 35% of the cases studied the stimulating effect by estradiol in vitro was observed. The frequency of response to in vitro hormone treatment was higher (42%) in ER+ cancers and lower (25%) in ER- cancers. The specificity of the in vitro test was assessed by the use of tamoxifen.

Stage, estrogen receptor status, treatment and survival of 29 men with breast cancer attending the Breast Clinic of the Johannesburg Hospital between 1976 and 1985 are reviewed. Most patients had locoregionally advanced disease at presentation. Estrogen receptors (ER) were detected in significant concentration in 15/23 (65%). Local control was achieved in the majority, 19/26 (73%), by either surgery or radiation therapy alone or by combined modality treatment. Fifteen of 23 patients tested (65%) were ER-positive (greater than 10 fmol/mg protein). For patients with metastatic disease hormone receptor status was predictive of response to hormonal manipulation. Tamoxifen was the most acceptable and frequently used form of hormone therapy with 7/12 patients responding. Combination chemotherapy gave a response rate comparable to that seen in women with breast cancer.

The effectiveness of hypophysectomy and tamoxifen in treating advanced breast cancer was compared in a randomized study of 26 patients who had responded to prior oophorectomy or additive hormonal therapy. When patients failed to respond or relapsed from tamoxifen or hypophysectomy, the therapy was crossed over. In this designed sequence, the rate and duration of response observed with tamoxifen or hypophysectomy used as the first regimen were comparable. The results suggest that tamoxifen is effective in the posthypophysectomy phase and the sequence or hypophysectomy followed by tamoxifen in hormone-dependent breast cancer is preferable to achieve a maximal control of the disease.

Biopsy material from primary prostatic carcinoma from 25 patients was analyzed with regard to cytosol content of methyltrienolone (a synthetic androgen) binding sites and the receptor content has been correlated to the clinical response to endocrine therapy. A dextran-coated charcoal technique was used and binding data were calculated from Scatchard plots. In 20 of the tumors detectable levels of methyltrienolone receptor were noted. One of the receptor-positive patients died during radiation therapy before onset of hormonal treatment, and a second patient, who had a highly differentiated carcinoma, so far has not received any endocrine therapy. Of the remaining 18 patients 15 responded well to castration, treatment with estrogens, or Estracyt (approximately 80%). The biopsies from two of the three receptor-positive non-responders contained the lowest measurable receptor levels. Five specimens lacked detectable amounts of methyltrienolone receptor. Four of these patients did not respond to therapy (approximately 80%), but one was "false" negative. Our data indicate that steroid receptor analysis may become an important tool in predicting the value of endocrine therapy in human prostatic carcinoma.

Estrogen receptor (ER) analyses are widely used in the management of patients with breast cancer. Few data are available concerning variations in ER as a function of time and therapy. We examined patients in whom multiple biopsies and receptor analyses were either performed simultaneously or over time with or without intervening chemotherapy or endocrine therapy. In 27 patients with simultaneous assays from different metastatic sites, concordant results were obtained in 23 (85%) with respect to classifying a tumor as ER+ or ER-. In 34 patients, multiple assays were performed over time. The receptor concentrations were concordant in patients receiving no intervening therapy. In 10 patients receiving hormonal therapy, the median receptor concentration changed from 66 femtomoles per mg cytoplasmic protein pretherapy to 8 femtomoles post therapy (P less than 0.05). This change suggested that hormonal therapy selectively eliminates ER+ cells. In 19 patients receiving intervening chemotherapy, the median receptor concentrations pre and post therapy were similar. We conclude that simultaneous assays from multiple metastatic sites are highly concordant and unlikely to change over time without intervening therapy, but marked changes occur following therapy with a decrease in receptor concentration after endocrine therapy.