Strontium-89 for palliation of pain from bone metastases in patients with prostate and breast cancer

We have used strontium-89 chloride (89Sr) for the palliative treatment of metastatic bone pain. Seventy-six patients (50 males with prostate carcinoma and 26 females with breast cancer) were treated with 148 MBq of 89Sr. Sixteen patients were retreated, receiving two or three doses; the total number of injected doses was consequently 95. The Karnofsky performance status was assessed and pain and analgesia were scored on scales of 9 and 5 points, respectively. The efficacy of 89Sr was evaluated at 3 months of treatment. Three levels of response were considered: good - when there was an increase in the Karnofsky status and a decrease in the pain score (equal to or higher than 4) or analgesic score (equal to or higher than 1); partial - when there was an increase in the Karnofsky status and a decrease in the pain score (2 or 3 points) without significant changes in the analgesic score; no response - if no variation or deterioration in these parameters was observed. In prostate cancer patients, the response was good in 64% of cases and partial in 25%, and there was no response in the remaining 11%. In breast cancer patients, the response was good in 62% of cases and partial in 31%, and there was no response in the remaining 8%. Duration of the response ranged from 3 to 12 months (mean 6 months). In the patients who were retreated the effectiveness was as good as after the first dose of 89Sr. A decrease in the initial leucocyte and platelet counts was observed after the 1st month of treatment, with a gradual partial to complete recovery within 6 months. It is concluded that 89Sr is an effective agent in palliative therapy for metastatic bone pain in patients with prostate or breast carcinoma. If required, retreatment can be administered safely and with the same efficacy as is achieved by the first dose.     

High prevalence of the 999del5 mutation in icelandic breast and ovarian cancer patients

Studies on Icelandic breast cancer families have shown that most of them segregate a 999del5 BRCA2 mutation. Here, we report the frequency of the 999del5 BRCA2 mutation in an Icelandic control population and four different groups of cancer patients diagnosed with (a) breast cancer; (b) ovarian cancer; (c) prostate cancer (patients younger than 65 years); and (d) other cancer types. The proportions of individuals carrying the mutation were 0.4% in the control population and in the patient groups 8.5%, 7.9%, 2.7%, and 1.0%, respectively. Our results indicate that BRCA2 confers a very high risk of breast cancer and is responsible for a substantial fraction of breast and ovarian cancer in Iceland, but only a small proportion of other cancers.     

The quality of life of prostatic cancer patients

A questionnaire was used to assess the quality of life (QOL) of forty-two outpatients with prostate cancer. Most of the patients were old, so reduced physical comfort was correlated with bodily factors other than those caused by prostate cancer. Many patients with progressive disease reported disease--and treatment--related physical problems that tended to be correlated to the extent of the disease. Many patients treated with female hormones complained of breast induration or discomfort. Patient's sexual life was impaired remarkably. Our treatment for cancer pain would be especially inadequate to cancer pain relief. We must give positive aid to cancer pain relief from now on. Most patients lost sexual interest after developing prostate cancer. Only three of the patients were able to have sexual intercourse. Some of the patients who underwent radical prostatectomy suffered from urinary incontinence after the operation. Thus, the patients' social life was remarkably affected for relative good performance status. Many patients lived only with other elderly individuals. Therefore, it is also important to manage patients in the light of their living environment.     

Keratinocyte differentiation is stimulated by activators of the nuclear hormone receptor PPARalpha

BACKGROUND: A patient's likelihood of dying from breast cancer or another cause can be assessed with competing risks analyses. METHODS: Data for a cohort of 678 patients with primary invasive breast cancer accrued from 1971 to 1990, updated to 1995, included cause of death (e.g., breast cancer vs. other cause). We investigated the effects of age, tumor size, nodal status, ER, PgR, and adjuvant therapy (hormones, chemotherapy, radiotherapy) on type of death and time to death for patients of all ages and for those over the age of 65 years. RESULTS: Although there were no significant univariate differences in breast cancer death rates by age group (P=0.94), more patients over the age of 65 years died from other causes (41/207 [20%] of those older than 65 years vs. 16/471 [3%] of those younger than 65 years; P <.001). In competing risks analyses, older age was associated with non-breast cancer death, whereas larger tumor size was associated with breast cancer death. PgR was positively, and nodal status negatively, associated with survival, regardless of type. In the older patient group, the competing risks analyses identified similar effects for age and tumor size; in addition, higher ER assay values were less likely to be associated with breast cancer death. CONCLUSIONS: With increased lifespan, there will be more breast cancer cases in women older than 65 years; we have shown that women in this group have more non-breast cancer deaths. It becomes important, then, to delineate differential effects of prognostic factors on competing causes of death.     

Cost benefit of emerging technology in localized carcinoma of the prostate

PURPOSE: In a health care environment strongly concerned with cost containment, cost-benefit studies of new technology must include analyses of loco-regional tumor control, morbidity, impact on quality of life, and financial considerations. METHODS AND MATERIALS: This nonrandomized study analyzes 124 patients treated with three-dimensional conformal radiation therapy (3D CRT) and 153 with standard irradiation (SRT) between January 1992 and December 1995, for histologically proven adenocarcinoma of prostate, clinical Stage T1 or T2. Mean follow-up is 1.4 years. Three-dimensional CRT consisted of six or seven coplanar oblique and lateral and, in some patients, AP fields designed to treat the prostate with a 1 to 1.7 cm margin. SRT consisted of 120 degrees bilateral arc rotation. Total doses to prostate were 67 to 70 Gy when pelvic lymph nodes were irradiated or 68.4 to 73.8 Gy when prostatic volume only was treated; dose per fraction was 1.8 Gy. Patients were interviewed weekly for severity of 12 acute intestinal and urinary pelvic irradiation side effects (0 to 4+ grading). Time and effort for 3D RTP and daily treatment with 3D CRT and SRT were recorded. Dose-volume histograms (DVHs) were calculated for gross tumor volume, planning target volume, bladder, and rectum. Actual reimbursement to the hospital and university was determined for 41 3D CRT, 43 SRT, and 40 radical prostatectomy patients treated during the same period. RESULTS: Average treatment planning times (in minutes) were: 101 for 3D conformal therapy simulation, 66 for contouring of target volume and sensitive structures, 55 for virtual simulation, 39 for plan preparation and documentation, 65 for physical simulation, and 20 for approval of treatment plan. Daily mean treatment times were 19 min for 3D CRT with Cerrobend blocking, 16 with multileaf collimation, and 10 with bilateral arc rotation. Dosimetric analysis (DVHs) showed a reduction of 50% in volume of bladder or rectum receiving doses higher than 65 Gy. Acute side effects included dysuria, moderate difficulty in urinating, and nocturia in 25-39% of both SRT and CRT patients; loose stools or diarrhea in 5-12% of 3D CRT and 16-22% of SRT patients; moderate proctitis in 3% of 3D CRT and 12% of SRT patients (p = 0.01). Chemical disease-free survival (prostate-specific antigen < or =2 ng/ml) at 3 years was 90% with 3D CRT and 80% with SRT (p = 0.01). Average initial treatment reimbursements were $13,823 (3D CRT), $10,864 (SRT), and $12,250 (radical prostatectomy). Average total treatment reimbursement and projected cost of management of initial therapy failures per patients were $15,173, $16,264, and $16,405, respectively. CONCLUSIONS: Three-dimensional CRT irradiated less bladder and rectum volume than SRT; CRT initial reimbursement was 28% higher than SRT and 12% higher than radical prostatectomy. Because of projected better local tumor control, average total cost of treating a patient with 3D CRT or radical prostatectomy is equivalent to cost of SRT. Treatment morbidity was lower with 3D CRT. Our findings reflect an overall benefit with 3D CRT as a new promising technology in treatment of localized prostate cancer. Dose-escalation studies may enhance its efficacy and cost benefit.     

Urinary symptoms, potency, and quality of life in patients with localized prostate cancer followed up with deferred treatment

OBJECTIVES: To evaluate urinary symptoms, potency, and quality of life in a group of patients with prostate cancer followed up with deferred treatment. METHODS: A self-administered questionnaire was mailed to patients with localized prostate cancer who were followed up with deferred treatment. Data regarding clinical stage, pathologic grade, and treatment after diagnosis were obtained from patient files. RESULTS: A total of 71 consecutive patients (age 79 years or less) were included. Of the 52 patients (73%) who responded, 31% had undergone transurethral resection of the prostate, 8% underwent radiation therapy, and 44% underwent hormonal deprivation during the follow-up period. With respect to incontinence, 21% were using pads and 37% leaked urine daily; in 21% of the patients, urine dripping or leaking was a substantial problem. Before the diagnosis of their prostate cancer, 81% stated they were able to have an erection. At the time of the questionnaire, 77% stated that their ability to have erections was reduced and only 29% had had an erection after the prostate cancer was diagnosed. For 12%, impotence was a problem. With respect to quality of life, 52% of the patients rated their health as excellent or good and 61% would be happy to spend the rest of their life feeling the way they did at the time of the questionnaire. Eighty-five percent were satisfied with the treatment policy for their prostate cancer, and 96% would choose deferred treatment again if faced with the decision. CONCLUSIONS: By use of a self-administered questionnaire, a high frequency of incontinence and impotence was found in a group of patients with prostate cancer followed up with deferred treatment. Despite these problems, more than half of the patients rated their health as good and would undergo expectant management again if faced with the decision.     

Treatment of prostate cancer in patients aged 75 or older

In view of the increasing incidence and mortality rate of prostate cancer in Japan, the management of elderly patients with prostate cancer is an important issue now. We therefore analyzed the clinicopathological features and long-term outcomes of 182 patients with prostate cancer, aged 75 or older, in order to establish the treatment strategy for this age group of patients. There were more patients with advanced disease (stage C-D) than those with localized disease (stage A2-B), and the patients with moderate to poorly differentiated tumors were more numerous than those with well-differentiated tumors. The overall survival curve of the patients with localized prostate cancer was in line with the age-matched expected survival curve, while that with advanced prostate cancer was far below the expected survival curve. These results demonstrated that advanced prostate cancer in elderly patients is as harmful as in younger patients, indicating the necessity for early detection and treatment of prostate cancer among the younger generation. On the other hand, localized prostate cancer in elderly patients should be treated less invasively to maintain their quality of life.     

Treatment of metastatic prostate cancer: certainty and doubts

HIGH MORTALITY: Despite progress in early diagnosis, mainly due to prostate specific antigen (PSA) assay, metastasic cancer of the prostate remains an important health problem; more than 40,000 men died from prostate cancer in 1996 in the USA. More than 50 years after the hormone sensitivity of prostate cancer, antiandrogen therapy remains the cornerstone of treatment protocols. Although this is only a palliative therapy, it does delay disease progression for several years before the tumor inevitably escapes from hormone control. STAGE D1 DISEASE: In patients with microscopic nodal metastases (stage D1) it is classical to propose early or delayed hormone therapy which gives a 5-year survival rate in the 77-85% range. Certain teams also associate radical treatment (radical prostatectomy or pelvic prostate radiotherapy) with the hormone therapy, basically with the aim of better local control despite the lack of proven gain in survival rate. STAGE D2 DISEASE: Medical or surgical castration is the gold standard when the disease reaches stage D2. Specific treatments for urinary, neurological or bone complications may also be associated. Median survival is approximately 3 years. ASYMPTOMATIC PATIENTS: There remains a certain controversy about the best time to initiate treatment. Some advocate treatment immediately upon diagnosis while others propose delaying treatment until the onset of symptoms. There is a trend towards early treatment, but the beneficial effect in terms of survival and quality of life has not been proven. STAGE D3 DISEASE: When the tumor escapes hormone control (stage D3) mean survival is less than one year. Castration should be maintained and antiandrogens, which may have been given initially in combination with castration to achieve total androgen blockade, should be withdrawn (antiandrogen withdrawal syndrome) before assessing the need for second intention hormonal or other treatment. Such second intention regimens usually have a temporary and symptomatic effect. Their indication depends on side effects which may have a deleterious effect on quality of life. Symptomatic treatment plays a predominant role at this stage, combining analgesics, external or metabolic radiotherapy for bone pain, transurethral excision and/or urinary tract derivations for neurological or urological complications, and psychological care which requires the combined efforts of the radiotherapist, oncologist, urologist, and general practitioner.     

The effect of repeated strontium-89 chloride therapy on bone pain palliation in patients with skeletal cancer metastases

One hundred and eighteen patients with painful skeletal metastases of malignant diseases (predominantly prostate, breast and lung cancer) were treated with 150 MBq of strontium-89 chloride (Metastron, Amersham, UK) intravenously. The results were evaluated according to a score considering pain relief, mobility, analgesic intake and general feeling. In only five patients (4.2%) was no improvement observed; mild improvement was noted in 48 (40.7%), and substantial or complete improvement in 56 (47.5%) and 9 (7.6%), respectively. The mean painless period after a single 89SrCl dose was 3.3 +/- 2.28 months (in patients with prostate, lung, breast and other types of cancer it was 3.65 +/- 2.11, 3.29 +/- 1.27, 3.08 +/- 0.48 and 3.44 +/- 1.36 months, respectively). During a 3-year study, 89SrCl treatment was successively repeated up to 5 times in some patients (total number of Metastron applications was 256) who benefited from the first Metastron administration and did not show signs of myelosuppression. Even after repeated treatment, relief was consistent and the duration of the period without pain increased (in particular in patients with breast cancer, in whom the period of relief was prolonged from 3.08 +/- 0.48 months after the first dose to 5.33 +/- 2.36 months after the fifth 89SrCl administration). The increased painless period was not observed after repeated treatment in the patient group comprising miscellaneous types of cancer, and the degree of improvement was less apparent. During the course of successive 89SrCl treatments, transient signs of myelosuppression indicated by a decrease in white cell and thrombocyte counts of at least 25% were observed 10 times after Metastron administration (twice in two patients), i.e. in 3.9% of all 89SrCl administrations; these transient haematological changes of moderate grade were closely connected with Metastron administration. Palliative treatment of metastatic skeletal pain with 89SrCl improves the quality of life in most patients suffering from prostate, lung and breast cancer and may be safely repeated with the same benefit and without significant myelosuppression. The beneficial effect of 89SrCl treatment seems to be less pronounced in other types of cancer with painful skeletal metastases.     

Sexuality and quality of life. Results from the quality of life-study of 4,626 Danes aged 31-33 years born at Rigshospitalet 1959-1961

From a cohort of 7222 31-33-year-olds we obtained answers to a 317-item quality-of-life questionnaire that included five questions on sexuality from 4626 respondents, giving a response rate of 64.1%. Among the women, 1.6% said they were bisexual and 1.4% homosexual; the corresponding figures for men were 1.3% and 1.1% respectively. The quality of life of bisexual persons was somewhat lower than the cohort mean (W: 15.6% lower, M: 19.1% lower), and that of homosexual persons was a little lower than the cohort mean (W: 8.5% lower, M: 3.7% lower). About a quarter of all respondents said they had sexual problems. Most frequent among the women were reduced sexual desire (17.0%) and the absence of a suitable sex partner (7.6%), and among the men, the absence of a suitable sex partner (12.5%) and premature ejaculation (5.5%). The quality of life of persons with sexual problems was measured to be from 7.0% to 24.2% lower than the cohort mean (as expressed in terms of this mean). The intermediate-sized relationship between sexual problems and quality of life suggests that such problems can be symptoms of reduced quality of life, rather than medical problems to be tackled as such. Implications for quality life-sensitive clinical practice are discussed.     

Prostate cancer patients' utilities for health states: how it looks depends on where you stand

Two versions of the time-tradeoff (TTO) method were compared. In the personal TTO version, 31 prostate cancer patients decided whether they personally would give up some longevity to have perfect health rather than a longer life in a state of poor health associated with prostate cancer. In the impersonal version, 28 patients compared two hypothetical friends, one of whom has perfect health but will live less time than the other who is in poor health, and decided which person they would rather be. All patients evaluated three hypothetical health states. The two TTO methods were assessed by examining 1) how well they distinguished three health states of varying degrees of dysfunction and 2) patients' willingness to trade time for quality of life. Patients using the impersonal TTO version were more likely than those using the personal version to order the three health states appropriately (68% vs 16%, p < 0.0001) and were more willing to trade off length of life for quality of life (p < 0.05).     

The presence of atopy does not determine the type of cellular infiltrate in nasal polyps

Prostate cancer screening with DRE, TRUS, and PSA testing was offered to 2,400 randomly selected men 55-70 years old. Among 1,782 examined, 65 (3.6%) men with prostate cancer were diagnosed. The PSA results were correlated to the diagnosis, the men's age, and the prostate volume. Least square regression analysis was used to calculate the 95% upper confidence intervals for PSA in each year of age in men without prostate cancer. The PPV was calculated for: (i) PSA > 4 ng/ml, (ii) PSAD > 0.15, (iii) PSAD > 0.20 and (iv) age-adjusted PSA reference values. A significant correlation was found between PSA and prostate volume, between PSA and age, and between the prostate volume and age. The calculated annual growth of the prostate was 1.6% and the annual increase in PSA was 2.4%. The age-adjusted upper PSA reference values for the three age categories studied (55-59, 60-64 and 65-70 years) were 5.2, 5.8, and 6.7 ng/ml, respectively. The PPVs for PSA > 4 ng/ml, PSAD > 0.15, PSAD > 0.20, and the age-adjusted PSA reference values were 17%, 14%, 22%, and 27%, respectively. Age-adjusted PSA or PSAD may increase the PPV compared to PSA > 4 ng/ml. The detection rate is, however, inadequate. A PSA cut-off at 4 ng/ml could therefore be maintained in men 55-70 years old. The median PSA values and median prostate volumes calculated for men with benign findings may serve as a reference in future studies.     

Transcranial magnetic-stimulation mapping of the cortical topography of the human masseter muscle

BACKGROUND: Population-based screening for prostate cancer is currently being evaluated in randomized clinical trials in the United States and in Europe. Side effects arising from the process of screening and from the earlier treatment of screen-detected prostate cancer may be important factors in the evaluation. To examine health-related quality of life (or health status) among men screened for prostate cancer, we conducted a longitudinal study of 626 attenders to the Rotterdam (The Netherlands) prostate cancer screening program and of 500 nonparticipants. METHODS: Attenders of the screening program and nonparticipants completed self-assessment questionnaires (SF-36 [i.e., Medical Outcomes Study 36-Item Short-Form Health Survey] and EQ-5D [i.e., EuroQol measure for health-related quality of life] health surveys) to measure generic health status, as well as an additional questionnaire for anxiety and items relating to prostate cancer screening. RESULTS: Physical discomfort during digital rectal examination and during transrectal ultrasound was reported by 181 (37%) of 491 men and by 139 (29%) of 487 men, respectively; discomfort during prostate biopsy was reported by 64 (55%) of 116 men. Mean scores for health status and anxiety indicated that the participants did not experience relevant changes in physical, psychological, and social functioning during the screening procedure. However, high levels of anxiety were observed throughout the screening process among men with a high predisposition to anxiety. Similar scores for anxiety predisposition were observed among attenders and nonparticipants. CONCLUSIONS: At the group level, we did not find evidence that prostate cancer screening induced important short-term health-status effects, despite the short-lasting side effects related to the biopsy procedure. However, subgroups may experience high levels of anxiety. The implication is that unfavorable health-status effects of prostate cancer screening occur mainly in the treatment phase.     

Normative values for the Beck Anxiety Inventory, Fear Questionnaire, Penn State Worry Questionnaire, and Social Phobia and Anxiety Inventory.

Community norms are reported for the Beck Anxiety Inventory (BAI; A. T. Beck, N. Epstein, G. Brown, & R. A. Steer, 1988), Fear Questionnaire (FQ; I. M. Marks & A. Mathews, 1979), Penn State Worry Questionnaire (PSWQ; T. J. Meyer, M. L. Miller, R. L. Metzger, & T. D. Borkovec, 1990), and Social Phobia and Anxiety Inventory (SPAI; S. M. Turner, D. C. Beidel, C. V. Dancu, & M. A. Stanley, 1989). The demographic profile of the samples closely matched the 1990 U.S. national census. On the SPAI, women scored higher than men on the Agoraphobia subscale, and the lowest income group scored higher than higher income participants on the Difference and Social Phobia subscales. Participants under 45 years of age exceeded those aged 45–65 on the BAI, the PSWQ, and FQ Social Phobia, Blood/Injury, and Total Phobia scores. Percentile scores are provided for all measures, as well as discussion of their usefulness for assessing clinical significance of therapy outcomes. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Correlation between mannose-6-phosphate/IGFII receptor and cathepsin D RNA levels by in situ hybridization in benign and malignant mammary tumors

We evaluated levels of mannose-6-phosphate/insulin growth factor-II receptor (M6P/IGFII-R) RNA in 37 breast cancer tumors by quantitative in situ hybridization using a computer-aided image analyzer and compared them to cathepsin D RNA and protein levels in the same tissues. Breast cancer cells expressed more cathepsin D and M6P/IGFII-R RNA than fibroblasts in the same tumors. We found a significant increase of cathepsin D RNA (P = 1 x 10(-5)) and M6P/IGFII-R RNA (P = 0.02) in breast cancer cells compared to epithelial cells of benign mastopathies. There was a positive correlation (r = 0.65; P = 1 x 10(-5)) between M6P/IGFII-R and cathepsin D RNA levels measured on serial sections. This contrasted with the inverse relationship of these 2 RNA species in breast cancer cell lines where estrogen down-regulates M6P/IGFII receptor RNA levels. Moreover, in vivo we found no correlation between the M6P/IGFII-R RNA level and menopausal or estrogen receptor status, suggesting that the in vivo regulation of M6P/IGFII-R RNA differs from its in vitro regulation in cell lines. The M6P/IGFII-R RNA level was not correlated with cathepsin D status, histological grade, and tumor size but was significantly higher in lymph node-positive tumors (P = 0.047). The M6P/IGFII-R could therefore be an additional parameter to predict aggressive breast cancers, complementing cathepsin D assays and other more classical prognostic parameters.     

Chinese MMPI profiles among neurotic patients.

The Chinese Minnesota Multiphasic Personality Inventory (MMPI) profiles of 1,112 neurotic patients were scored with the Chinese norm, the original MMPI norm, and the MMPI—2 Uniform T scores. In comparison with the Chinese normative sample, the neurotic profiles were elevated on all the clinical scales except Scale 5 (Mf). The neurotic patients also scored higher than schizophrenic patients on Scales 1 (Hs), 2 (D), 3 (Hy), 7 (Pt), 8 (Sc), and 0 (Si). The Chinese normative profiles produced typical neurotic code types of 12/21, 13/31, 23/32, and 27/72. However, the overall T score elevations of the clinical scales were much lower than those found on the American norms. Profiles based on the 3 American norms bore the characteristic peaks on Scales 2 and 8 found among Chinese samples. The authors recommend using both the Chinese and the American norms in the interpretation of the Chinese MMPI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hormone replacement therapy after treatment of breast carcinoma

A correct Hormone Replacement Therapy (HRT) guarantees a successful treatment of subjective symptoms of oestrogen deficiency and an efficient prevention of postmenopausal osteoporosis, of cardiovascular diseases and of M. Alzheimer. In non-substituted postmenopausal women, the risk to die from a myocardial infarction is ten times higher than the risk to die from a carcinoma of the breast or the consequences of a fracture of the femoral neck. In spite of this observation, the acceptance is still insufficient because of an unjustified fear of hormone-induced carcinomas. The incidence of a carcinoma of the breast is not higher in women profiting of a HRT by a correct combination of an oestrogen and a progestogen administered up to 5 years than in untreated controls. Although some but not all authors suspect a slight increase of the relative risk of a carcinoma of the breast to approximately 1.5 after > or = 10 years of HRT, the overall mortality of substituted women is clearly inferior to the one of a non-substituted population. However, the final goal of HRT is not prolongation of life, but a better quality of life. Quality of life is often miserable in women treated for breast cancer. The final answer to the question if women after treatment of breast cancer should be allowed to profit of HRT is still open because formal evidence is missing. However, a woman should not be denied HRT if she lived two years without relapse since her primary cancer and if she does not belong to the subgroup where adjuvant treatment by tamoxifen is appropriate. In the future, selective oestrogen receptor modulators may be used in women after breast cancer.     

The effects of preoperative therapy with angiotensin-converting enzyme inhibitors on clinical outcome after cardiovascular surgery

PURPOSE: Quality of life of breast cancer survivors 8 years after diagnosis was compared with that among similarly aged women who had never confronted cancer (controls). METHODS: Survivors of a consecutive series of 227 breast cancer patients first treated in 1984 were approached for this study. Random-digit dialing was used to identify controls with the same age and residential distribution as the survivors. Quality of life was assessed in terms of physical health, functional status, psychologic distress, and social functioning. RESULTS: Participation was obtained from 96% (n = 124) of 129 eligible survivors and 61% (n = 262) of 427 potentially eligible controls. Consistently smaller proportions of survivors reported positive quality-of-life outcomes compared with controls, but these differences were generally small and nonsignificant statistically. When limited to women who remained free of disease over the entire follow-up period (n = 98), survivors' quality of life was similar to that among controls, with the exception of arm problems and sexual satisfaction for those women who lived with a partner. In contrast, survivors who developed recurrence or new primary breast cancer (n = 26) experienced a worse quality of life in all domains except social functioning. CONCLUSION: In most domains and for women without further disease events after diagnosis, quality of life does not seem to be permanently and globally impaired by breast cancer. Consequently, breast cancer survivors who remain free of disease probably do not need organized late psychosocial follow-up to improve quality of life. However, arm problems and sexuality are two areas in which additional effort may be still needed to improve quality of life of long-term survivors.     

Expression in human prostate of drug- and carcinogen-metabolizing enzymes: association with prostate cancer risk

The role of two common polymorphisms of enzymes involved in the metabolism of drugs and carcinogens was studied in relation to prostate cancer. The gene encoding one of these enzymes (NAT2) is located in an area where frequent allelic loss occurs in prostate cancer. Mutations at the genes CYP2D6 and NAT2 were analysed by allele-specific polymerase chain reaction and restriction mapping in DNA from 94 subjects with prostate cancer and 160 male healthy control subjects. Eleven prostate specimens were analysed for genotype and enzymatic activities NAT2, CYP2D6 and CYP3A by using the enzyme-specific substrates sulphamethazine and dextromethorphan. Enzyme activities with substrate specificities corresponding to NAT2, CYP2D6 and CYP3A are present in human prostate tissue, with mean +/-s.d. activities of 4.8+/-4.4 pmol min(-1) mg(-1) protein, 156+/-91 and 112+/-72 nmol min(-1) mg(-1) protein respectively. The Km values for the prostate CYP2D6 and CYP3A enzyme activities corresponded to that of liver CYP2D6 and CYP3A activities, and the CYP2D6 enzyme activity is related to the CYP2D6 genotype. The N-acetyltransferase, in contrast, had a higher Km than NAT2 and was independent of the NAT2 genotype. The CYP2D6 and CYP3A enzymes, and an N-acetyltransferase activity that is independent of the regulation of the NAT2 gene, are expressed in human prostate tissue. The presence of carcinogen-metabolizing enzymes in human prostate with a high interindividual variability may be involved in the regulation of local levels of carcinogens and mutagens and may underlie interindividual differences in cancer susceptibility.