Biomedical subjects

P Kenemans

Publications and source records attributed to P Kenemans.

At least 91 records · Page 5Linked to original sources

PubMed1998

Biodistribution of 111In-labelled engineered human antibody CTM01 (hCTM01) in ovarian cancer patients: influence of prior administration of unlabelled hCTM01.

mAb hCTM01 binds a carcinoma-associated antigen, the MUC1 gene product. The antigen is also present in the circulation, and administration of 111In-labelled hCTM01 results in the formation of immune complexes with enhanced accumulation in the liver. To avoid the unwanted effect of circulating radioactive immune complexes, a strategy to remove the circulating antigen was investigated using a split-dosage schedule. Eleven patients suspected of having ovarian carcinoma were injected with 1 mg/kg unlabelled hCTM01, 1 h before receiving 0.1 mg/kg 111In-labelled hCTM01 (100 M Bq). The amount of radioactivity was determined in resected tumour tissue, various normal tissues and blood samples obtained at laparotomy 6 days postinjection (p.i.). In all patients, the circulating antigen decreased to its nadir after the unlabelled antibody infusion and immune complex formation was demonstrated. Uptake in tumour deposits 6 days p.i. was 11.1 times higher than in normal tissues (P < 0.0001) and 5.9 times higher than in blood (P < 0.0001). 111In activity in liver tissue was comparable to 111In uptake in tumour tissue, and considerably lower than previously reported in patients not pretreated with unlabelled antibody. The split-dosing strategy would appear to be advantageous for use of hCTM01 as a specific carrier for the delivery of cytotoxic agents to patients with ovarian cancer.

Adult↗

PubMed1998

Postmenopausal oral 17beta-estradiol continuously combined with dydrogesterone reduces fasting serum homocysteine levels.

OBJECTIVE: To investigate the effects of oral 17beta-estradiol administration continuously combined with dydrogesterone on fasting serum total homocysteine levels in postmenopausal women. DESIGN: Randomized, double-blind study. SETTING: Gynecologic outpatient department of a university hospital. PATIENT(S): One hundred thirty-five healthy, nonhysterectomized postmenopausal women. INTERVENTION(S): Oral micronized 17beta-estradiol (2 mg/d) continuously combined with one of four dosages of dydrogesterone (2.5 mg [n = 41], 5 mg [n = 38], 10 mg [n = 37], or 15 mg [n = 19]) was given for 6 months. MAIN OUTCOME MEASURE(S): Fasting serum total homocysteine concentrations. RESULT(S): The mean fasting serum total homocysteine concentrations in the overall study population decreased significantly (by 13.5%) after the first 3 months of treatment and remained unchanged thereafter. No influence of dydrogesterone dosage was found. The greatest reduction in total homocysteine concentration was obtained in women with the highest baseline levels. CONCLUSION(S): Continuously combined hormone replacement therapy lowers fasting serum total homocysteine levels significantly in postmenopausal women. This decrease may be one of the mechanisms that underlie the cardioprotective effects of postmenopausal hormone replacement therapy.

Administration, Oral↗

PubMed1998

Randomized, double-blind, placebo-controlled study of the effects of raloxifene and conjugated equine estrogen on plasma homocysteine levels in healthy postmenopausal women.

OBJECTIVE: To investigate the long-term effects of raloxifene on fasting plasma homocysteine levels in postmenopausal women compared with conjugated equine estrogen (CEE). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Outpatient department of a university hospital. PATIENT(S): Fifty-two hysterectomized, healthy postmenopausal women. INTERVENTION(S): Oral raloxifene in two dosages (60 mg/d [n=13] and 150 mg/d [n=13]), oral CEE (0.625 mg/d [n=13], and placebo (n=13) were given for 24 months. MAIN OUTCOME MEASURE(S): Fasting plasma homocysteine concentrations. RESULT(S): Plasma homocysteine levels were not altered in the placebo group. After 12 months, a significant reduction versus baseline in the mean plasma homocysteine level (-16%) was found only in the raloxifene 150-mg group. The mean change in plasma homocysteine levels within this group also was significantly different from the changes versus baseline found in the placebo group (+2%) and the raloxifene 60-mg group (-2%), but not different from those found in the CEE group (-8%). After 24 months, plasma homocysteine levels were decreased significantly in the raloxifene 150-mg and CEE groups compared with both baseline (-13% and -10%, respectively) and placebo values (-15% and -11%, respectively). No significant change in plasma homocysteine levels was observed in the raloxifene 60-mg group. CONCLUSION(S): Raloxifene has a favorable, dose-related effect on plasma homocysteine levels in postmenopausal women.

Administration, Oral↗

PubMed1998

A randomized controlled study of the effects of 17beta-estradiol-dydrogesterone on plasma homocysteine in postmenopausal women.

OBJECTIVE: To investigate the effects of oral 17beta-estradiol (E2) -dydrogesterone on fasting plasma homocysteine concentrations in healthy postmenopausal women. METHODS: We studied 27 postmenopausal women who were assigned randomly to either a treatment group (n = 14) or a control group (n = 13). During the first 12 months of the study, treatment consisted of oral E2, 1 mg daily, combined sequentially with dydrogesterone 5 or 10 mg (14 days per 28-day treatment cycle). Thereafter, women were treated with oral E2, 2 mg daily, combined sequentially with dydrogesterone, 10 mg daily (14 days per 28-day treatment cycle) for a period of 3 months. The control group received no treatment. Fasting plasma total homocysteine concentrations were determined at baseline and 3, 12, and 15 months after study entry. RESULTS: At baseline, plasma homocysteine levels did not differ between the groups. After 15 months of hormone treatment mean plasma homocysteine concentration was lowered by 12.6% compared with baseline (P < .001; analysis of variance for repeated measures). Plasma homocysteine levels were not altered in the control group. The interaction between treatment and time for homocysteine levels was significantly different between the groups (P < .001; analysis of variance for repeated measures). The decrease in plasma homocysteine levels correlated inversely with the increase in serum E2 levels after 3 and 12 months of hormone treatment (r = -.54, P < .05 and r = -.56, P < .05, respectively). CONCLUSION: Plasma fasting homocysteine concentrations are lowered by E2-dydrogesterone therapy in postmenopausal women.

Dydrogesterone↗

PubMed1998

Digital color imaging colposcopy: a matter of choice.

OBJECTIVE: To describe the technical performance of a digital color imaging colposcopy (DCIC) system. STUDY DESIGN: A videocamera has been selected on the basis of physical size and technical performance. Four digitizer boards with different analogue input signals and different digitizing properties, have been tested with a video test image. The technical performance of a DCIC-system has been analyzed. RESULTS: A 3-CCD color videocamera gives the best analogue registration. Signal transfer by RGB-videosignal gives superior color and spatial resolution when compared to Y/C in composite videotransfer. Digitalization of the analogue videoimage with less than 24-bit resolution digitizer boards resulted in unwanted side effects that were related to the color measurement accuracy. CONCLUSIONS: Digital imaging colposcopy requires a 3-CCD videocamera of which the videosignal is transferred as an RGB-signal to a digitizerboard with 24-bit resolution that provides 16 million different colors. To store the image a large medium that is easily accessible is needed.

Colposcopy↗

PubMed1998

Ambulatory--not office--blood pressures decline during hormone replacement therapy in healthy postmenopausal women.

Hormone replacement therapy (HRT, estrogen plus progestagen) in postmenopausal women has beneficial effects on the cardiovascular system. However, effects on blood pressure, determined with office measurements, remain controversial. We studied the effects of HRT in 29 healthy normotensive postmenopausal women (mean age 52.3 [3.8] years, median duration of amenorrhea 34.5 months), using ambulatory blood pressure monitoring at baseline and at 3 and 12 months of follow-up. Women were randomized to two groups: an HRT group (N = 14), treated with 1 mg 17beta-estradiol once daily and 5 or 10 mg dydrogesterone once daily during the third and fourth week of every 4 weeks; and a control group (C-group, N = 15), which did not receive therapy. Blood pressures did not differ between the groups at baseline (HRT group 117.1 (9.2)/74.4 (6.6) mm Hg, C-group 113.8 (11.2)/71.3 (7.4) mm Hg). During the follow-up period, changes from baseline of office blood pressures did not differ significantly between the groups. However, changes (95% CI) of mean 24-h blood pressures differed significantly between the two groups after 1 year of follow-up: a decrease of blood pressures was observed in the HRT group (delta systolic/delta diastolic = -5.54 [-8.86 to -2.21]/-4.23 [-6.66 to -1.80] mm Hg), whereas an increase was found in the C-group (+3.33 [-0.69 to +7.35]/+1.67 [-1.75 to +5.09] mm Hg; P [HRT v control group] = .001/.005). We conclude that HRT may have blood pressure lowering properties in healthy, normotensive postmenopausal women.

Analysis of Variance↗

PubMed1998

Postmenopausal hormone replacement therapy and cancer of the female genital tract and breast.

Taking into account data from recent case-control and cohort studies, this review addresses anew the controversial issue of a possible relationship between hormone replacement therapy and an increased risk of female cancer. The adequate addition of a progestogen reduces considerably the significantly increased risk of endometrial cancer seen in current and in past long-term estrogen replacement therapy (ERT) users. However, a small risk increase might still be present with combined estrogen-progestogen replacement therapy (EPRT), and with low-dose continuous combined treatment. Whether long-term hormone replacement therapy increases the risk of breast cancer remains controversial. All four recent case-control studies report a small, marginally significant risk increase of about 20-30%, while two recent cohort studies are very reassuring. Sequential addition of a progestogen does not seem to influence breast cancer risk. Unfortunately, no data are available on the both practically and theoretically interesting option of continuous combined hormone replacement therapy. It can be concluded from the present data that hormone replacement therapy can be safely prescribed for periods of less than five years to women with climacteric symptoms. Short-term hormone replacement therapy for climacteric complaints in women who have been treated for the above-mentioned cancers should not be considered to be absolutely contraindicated as the available but scanty new data do not indicate any detrimental effect in such women.

Breast Neoplasms↗

PubMed1998

Positive predictive rate of colposcopic examination of the cervix uteri: an overview of literature.

Study of literature revealed that the positive predictive rate of the colposcopic impression is better as the cervical lesion is more severe. When directed biopsies are taken, the positive predictive rate of colposcopy increases considerably. For microinvasive disease, the positive predictive rate is quite poor, probably because of the absence of characteristic features. Large loop biopsies diagnosed all cases of microinvasive disease missed by directed biopsies, but this technique has the disadvantage of considerable "overtreatment" when integrated in the management of all patients with abnormal cytology. The restrictions of colposcopy are the invisibility of the squamocolumnar junction and observer variability in the assessment of the impression. The levels of agreement among experienced colposcopists are in the same range as those in cytological and histopathological diagnosis. It is concluded that colposcopy is an indispensable tool in the management of premalignant cervical disease, as long as the restrictions of the technique are kept in mind by the colposcopist.

Adolescent↗

PubMed1998

An enzyme-linked immunosorbent assay for the measurement of circulating antibodies to polymorphic epithelial mucin (MUC1).

INTRODUCTION: About one-third of breast and ovarian carcinoma patients have circulating antibodies reactive with polymorphic epithelial mucin (MUC1), either free or bound to immune complexes. While the presence of these immune complexes has prognostic significance in breast cancer patients, the significance of free MUC1 antibodies is less clear. The objective of this study was to develop a reliable assay for the accurate determination of circulating free antibodies to MUC1. MATERIAL AND METHODS: We developed an enzyme-linked immunosorbent assay (ELISA) (PEM.CIg) employing a 60 mer peptide (a triple tandem repeat sequence of the MUC1 peptide core) conjugated to bovine serum albumin and peroxidase-labeled antihuman immunoglobulin G or M antibodies. The assay was standardized and its analytical performance evaluated. A total of 492 serum samples were obtained from 40 healthy men, from 201 healthy women (including 55 women without a history of pregnancy and 45 pregnant women), and (before primary treatment) from 62 benign breast tumor patients and 190 breast cancer patients. MUC1 serum levels were determined with commercial CA 15-3 tests. RESULTS: Circulating antibodies to MUC1 are present both in healthy subjects and in breast cancer patients. The within- and between-assay coefficients of variation were, respectively, 2 and 12% for the IgG determinations and 1.2 and 3% for the IgM determinations. Correlation coefficients for serially diluted serum samples ranged from 0.9998 to 0.9920 for IgG and from 0.9996 to 0.9818 for IgM determinations. The reactivity of serum samples was partially blocked by the addition of various MUC1 peptides and by MUC1 mucin. The inhibiting effect of modified 60 mer peptides suggests the presence of antibodies directed to more than one epitope. CONCLUSIONS: The PEM. CIg assay is a reliable ELISA for measuring free MUC1 antibodies in serum. We are in the process of relating the results obtained in the breast cancer group to disease outcome to evaluate its prognostic significance. In addition, the assay may become a useful tool for vaccine therapy monitoring.

Autoantibodies↗

PubMed1998

Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1 mucin. San Diego, Calif., November 17-23, 1996.

Sixteen research groups participated in the ISOBM TD-4 Workshop in which the reactivity and specificity of 56 monoclonal antibodies against the MUC1 mucin was investigated using a diverse panel of target antigens and MUC1 mucin-related synthetic peptides and glycopeptides. The majority of antibodies (34/56) defined epitopes located within the 20-amino acid tandem repeat sequence of the MUC1 mucin protein core. Of the remaining 22 antibodies, there was evidence for the involvement of carbohydrate residues in the epitopes for 16 antibodies. There was no obvious relationship between the type of immunogen and the specificity of each antibody. Synthetic peptides and glycopeptides were analyzed for their reactivity with each antibody either by assay of direct binding (e.g. by ELISA or BiaCore) or by determining the capacity of synthetic ligands to inhibit antibody binding interactions. There was good concordance between the research groups in identifying antibodies reactive with peptide epitopes within the MUC1 protein core. Epitope mapping tests were performed using the Pepscan analysis for antibody reactivity against overlapping synthetic peptides, and results were largely consistent between research groups. The dominant feature of epitopes within the MUC1 protein core was the presence, in full or part, of the hydrophilic sequence of PDTRAPAP. Carbohydrate epitopes were less easily characterized and the most useful reagents in this respect were defined oligosaccharides, rather than purified mucin preparations enriched in particular carbohydrate moieties. It was evident that carbohydrate residues were involved in many epitopes, by regulating epitope accessibility or masking determinants, or by stabilizing preferred conformations of peptide epitopes within the MUC1 protein core. Overall, the studies, highlight concordance between groups rather than exposing inconsistencies which gives added confidence to the results of analyses of the specificity of antimucin monoclonal antibodies.

Amino Acid Sequence↗

PubMed1998

'Epitope fingerprinting' using overlapping 20-mer peptides of the MUC1 tandem repeat sequence.

The ISOBM TD-4 Workshop antibodies 122-177 were tested for reactivity with 20 overlapping MUC1 tandem repeat 20-mer peptides by an ELISA, in order to determine the complete amino acid sequences of the epitopes. Of the 56 antibodies studied, 30 showed specific binding and thus the epitopes were characterized. The epitopes appear to be 'broader' when compared to those deduced from studies using smaller peptides. Interassay variation is remarkably small, allowing for precise grouping of clusters with very similar epitope patterns. Five groups of antibodies show remarkable similarity: BC3 and VU-4-H5; BC4W154, C595 and Mc5; MF06 and B27.29; VU-11-D1 and VU-11-E2; Ma552, VU-3-C6, 7540MR and BC4E549. We have used the term 'epitope fingerprinting' to refer to the 'fine structure' of the epitope with all its essential and flanking amino acids. We believe this method is more precise than the usual epitope mapping with short peptides.

Amino Acid Sequence↗

PubMed1998

Comparison of seven immunoassays for the quantification of CA 125 antigen in serum.

Seven CA 125 immunoassays were compared for their clinical performance. CA 125 concentrations were determined in 289 serum samples obtained from women with benign pelvic tumors (samples from 98 patients) and patients with various cancers (samples from 111 patients). In the range of 0-1000 kilounits/L, all assays tested were linearly correlated, with correlation coefficients ranging from 0.89 to 0.99. In relation to the original Centocor CA 125 assay, there was an overall tendency to measure higher absolute values in the lower CA 125 value range. This was not seen in relation to the Centocor CA 125 II assay. ROC curves (benign vs pretreatment ovarian cancer patients) were nearly identical for all assays, and the areas under the ROC curves were not markedly different. We conclude that the CA 125 assays tested are strongly related to each other and are clinically reliable for the quantification of serum CA 125 and that none of the assays offers higher diagnostic accuracy or better discrimination between patient groups, especially not in the lower ranges.

Adenocarcinoma↗

PubMed1997

Escalating protein doses of chimeric monoclonal antibody MOv18 immunoglobulin G in ovarian carcinoma patients: a phase I study.

BACKGROUND: Successful first-line treatment of ovarian cancer does not incite cure. Recurrent disease often shows an increased resistance to chemotherapeutic agents. Therefore, other treatment modalities, like (radio)immunotherapy using tumor-associated monoclonal antibodies, should be considered. Chimeric MOv18 (c-MOv18) localizes well in ovarian carcinoma tissue. We investigated the safety of a single intravenous (i.v.) infusion of increasing doses of c-MOv18 in ovarian carcinoma patients. METHODS: Fifteen patients received c-MOv18 (from 5 mg to 75 mg). Safety was determined by recording vital signs; by hematological, biochemical, and urinary analyses; and by the human-antichimeric antibody (HACA) response. Five patients received c-MOv18 labeled with a tracer dose of iodine-131 to analyze the pharmacokinetics and biodistribution in blood, urine, and tissue biopsies at surgery. RESULTS: Administration of c-MOv18 IgG was uneventful. No significant changes in hematological, biochemical, or urine profiles were noted at any time postinjection (p.i). Starting with a dose of 50 mg, all patients experienced side effects, like fever, headache, and nausea/vomiting, maximally Grade II (World Health Organization toxicity scale). No HACA response was found up to 12 weeks p.i. The mean elimination half-life after infusion of 30-75 mg c-MOv18 was significantly higher compared with infusion of 1 mg. Absolute amount of c-MOv18 in carcinoma tissue increased with increasing c-MOv18 doses. CONCLUSIONS: Intravenous administration of c-MOv18 IgG in a dose up to 75 mg is safe, inducing only minor side effects at doses of 50 mg or higher. In view of the characteristics of c-MOv18, this antibody might be applicable as an unmodified antibody or as an immunoconjugate in the treatment of ovarian carcinomas.

Adult↗

PubMed1997

Continuously combined hormone replacement therapy and bone turnover: the influence of dydrogesterone dose, smoking and initial degree of bone turnover.

In this study we examined whether the effect of continuously combined hormone replacement therapy (HRT) on bone metabolism is influenced by dydrogesterone dose, smoking and initial degree of bone turnover. In a double-blind randomized study, 123 healthy postmenopausal women (mean age 51.7 years; range 30-61 years) received 17 beta-estradiol, 2 mg orally per day, continuously combined with either 2.5, 5, 10 or 15 mg of dydrogesterone daily. At baseline and at 3 and 6 months of therapy, bone formation was assessed by determining total alkaline phosphatase (TAP), bone-derived alkaline phosphatase (BAP), and the carboxy-terminal propeptide of collagen type I (PICP) in serum; bone resorption was assessed by the calcium/creatinine (Ca/Creat) and hydroxyproline/creatinine (Hp/Creat) ratio in 2-h fasting urine, and the serum carboxy-terminal pyridinolyne cross-linked telopeptide of collagen type I (ICTP). Dydrogesterone dose did not influence the effect of HRT on any of the bone markers. Combining the data of the four treatment groups, the decrease in each marker, compared to baseline values, was significant. However, in non-smokers, compared to smokers, after 6 months of therapy the decline in BAP and TAP was significantly more pronounced and the plasma estradiol level was significantly higher. For each bonemarker at baseline, women in the highest quartile, compared to women in the lowest quartile, showed a significantly stronger decrease in this marker in response to HRT. We conclude that dydrogesterone dose does not modify the effectiveness of replacement therapy. However, smoking and a low bone turnover at baseline may diminish its beneficial effect on bone.

Adult↗

PubMed1997

Foscan-mediated photodynamic therapy for a peritoneal-cancer model: drug distribution and efficacy studies.

Distribution of the photosensitizer Foscan (meta-tetrahydroxyphenylchlorin, mTHPC), after i.v. or i.p. injection, was investigated in Wag/Rij rats bearing i.p. tumours. These results were compared with the efficacy of mTHPC-mediated photodynamic therapy for illumination intervals of 4 hr to 3 days. For the distribution experiments a single tumour (CC53I colon carcinoma) was implanted intra-abdominally in a fat pad, or a cell suspension (1 x 10(6) CC531 cells) was injected into the peritoneal cavity, which results in a dissemination of tumour nodules on the peritoneum. 14C-mTHPC was not selectively taken up in the single-tumour model after i.v. or i.p. injection, but higher concentrations were achieved for i.p. administration. For this tumour model the concentration ratios between tumour and normal tissue never exceeded a value of 3. In the disseminated-tumour model, an uptake of up to 40% of the injected dose was found per gram tumour at 4 hr after an i.p. injection and this resulted in very high (> 14) concentration ratios of tumour to normal tissues. Low uptake was found after the i.v. injection route (1% of the injected dose per gram tumour) with lower tumour/normal tissue ratios (<8). The efficacy of i.p. photodynamic therapy (IPPDT) was evaluated using the single-tumour model only. The lower abdomen was illuminated at 4 hr to 3 days after mTHPC, and tumour size was repeatedly measured via a small laparoscopy. Significant delay in tumour regrowth was achieved for 6 J x cm-2 at 1 day after i.v., or at 4 hr after i.p. mTHPC (p values 0.019 and 0.045 respectively). Response to PDT, of tumours implanted in the fat pad, was not greater for i.p. administration of the photosensitizer and there was a poor correlation between times of maximum drug uptake in tumours and optimal illumination times for PDT efficacy.

Adipose Tissue↗

PubMed1997

Tumor eradication by wild-type p53-specific cytotoxic T lymphocytes.

The tumor suppressor protein p53 is overexpressed in close to 50% of all human malignancies. The p53 protein is therefore an attractive target for immunotherapy. Cytotoxic T lymphocytes (CTLs) recognizing a murine wild-type p53 peptide, presented by the major histocompatibility complex class I molecule H-2Kb, were generated by immunizing p53 gene deficient (p53 -/-) C57BL/6 mice with syngeneic p53-overexpressing tumor cells. Adoptive transfer of these CTLs into tumor-bearing p53 +/+ nude mice caused complete and permanent tumor eradication. Importantly, this occurred in the absence of any demonstrable damage to normal tissue. When transferred into p53 +/+ immunocompetent C57BL/6 mice, the CTLs persisted for weeks in the absence of immunopathology and were capable of preventing tumor outgrowth. Wild-type p53-specific CTLs can apparently discriminate between p53-overexpressing tumor cells and normal tissue, indicating that widely expressed autologous molecules such as p53 can serve as a target for CTL-mediated immunotherapy of tumors.

Adoptive Transfer↗

PubMed1997

Autoantibodies to p53 in ovarian cancer patients and healthy women: a comparison between whole p53 protein and 18-mer peptides for screening purposes.

Autoantibodies against complete p53 protein and 18-mer peptides of p53 in ovarian cancer patients and healthy women were examined. Sera from 9% (4/46) of ovarian cancer patients but none (0/51) of healthy women recognized complete p53 protein. The antibodies were mainly of the IgG1 isotype. Two patients had also IgG2 antibodies. Sera from 28% (13/46) of cancer patients and 21% (11/52) of healthy women contained either IgM, or IgM plus IgG2 antibodies against 18-mer p53 peptides. Screening against complete p53 protein instead of peptides seems necessary for identifying patients with tumor-related antibodies. IgG2 antibodies against p53 suggest p53-specific CD4+ T helper 1 cell activity in some of the ovarian cancer patients.

Autoantibodies↗

PubMed1997

[Postmenopausal hormone replacement therapy and cancer of the female genitalia and breast].

Oestrogen replacement therapy (ORT) significantly increases the relative risk (RR) of endometrial cancer, especially long-term oestrogen use (RR: 9.5; 95% confidence interval (CI): 7.4-12.3). Addition of a progestin to ORT reduces this increased risk completely or largely. The risk of breast cancer is increased after ORT of 5 years or longer (RR: 1.23; 95% CI: 1.08-1.40). Addition of a progestin does not reduce this increased risk. The possibility cannot be excluded that long-term ORT increases the risk of epithelial ovarian cancer. No significant association between ORT and cervical cancer has been demonstrated. It is safe to prescribe ORT for a period shorter than 5 years for women with menopausal symptoms. Addition of a progestin is indicated when the uterus is in situ. Hormonal supplementation therapy is to be discouraged in women treated for breast cancer, may be considered in young women previously treated for endometrial or ovarian cancer with a good prognosis and severe menopausal symptoms and is justified in women previously treated for cervical cancer.

Aged↗