Financial difficulties in breast cancer survivors with and without migration background in Germany-results from the prospective multicentre cohort study BRENDA II.

PURPOSE: We aimed to explore the trajectory of financial difficulties among breast cancer survivors in the German health system and its association with migration background. METHODS: In a multicentre prospective study, breast cancer survivors were approached four times (before surgery, before and after adjuvant therapy, five years after surgery) and asked about their migration history and financial difficulties. Migrants were defined as born/resided outside Germany or having citizenship/nationality other than German. Financial difficulties were ascertained with the financial difficulties item of the European Organisation for Research and Treatment of Cancer Core Instrument (EORTC QLQ-C30) at each time-point (cut-off > 17). Financial difficulties were classified in trajectories: always (every time-point), never (no time-point), initial (first, not fourth), delayed (only fourth), and acquired (second and/or third, not first). A logistic regression was conducted with the trajectories of financial difficulties as outcome and migration background as exposure. Age, trends in partnership status, and educational level were considered as confounders. RESULTS: Of the 363 participants included, 49% reported financial difficulties at at least one time-point. Financial difficulties were reported always by 7% of the participants, initially by 5%, delayed by 10%, and acquired by 21%. Migrants were almost four times more likely to report delayed (odds ratio [OR] = 3.7; 95% confidence interval [CI] 1.3, 10.5) or acquired (OR = 3.6; 95% CI 1.6, 8.4) financial difficulties compared to non-migrant participants. CONCLUSION: Survivors with a migration background are more likely to suffer from financial difficulties, especially in later stages of the follow-up. A linguistically/culturally competent active enquiry about financial difficulties and information material regarding supporting services/insurances should be considered.

To which extent do breast cancer survivors feel well informed about disease and treatment 5 years after diagnosis?

OBJECTIVE: In this study, we investigated to which extent patients feel well informed about their disease and treatment, which areas they wish more or less information and which variables are associated with a need for information about the disease, medical tests and treatment. METHODS: In a German multi-centre prospective study, we enrolled 759 female breast cancer patients at the time of cancer diagnosis (baseline). Data on information were captured at 5 years after diagnosis with the European Organisation for Research and Treatment of Cancer (EORTC) Information Module (EORTC QLQ-INFO24). Good information predictors were analysed using linear regression models. RESULTS: There were 456 patients who participated at the 5-year follow-up. They reported to feel well informed about medical tests (mean score 78.5) and the disease itself (69.3) but relatively poorly about other services (44.3) and about different places of care (31.3). The survivors expressed a need for more information concerning: side effects and long-term consequences of therapy, more information in general, information about aftercare, prognosis, complementary medicine, disease and therapy. Patients with higher incomes were better informed about medical tests (ß 0.26, p 0.04) and worse informed with increasing levels of fear of treatment (ß - 0.11, p 0.02). Information about treatment was reported to be worse by survivors > 70 years old (ß -0.34, p 0.03) and by immigrants (ß -0.11, p 0.02). Survivors who had received additional written information felt better informed about disease, medical tests, treatment and other services (ß 0.19/0.19/0.20/0.25; each p < 0.01). CONCLUSION: Health care providers have to reconsider how and what kind of information they provide. Providing written information, in addition to oral information, may improve meeting those information needs.

Sensor-controlled scalp cooling to prevent chemotherapy-induced alopecia in female cancer patients.

BACKGROUND: Scalp cooling has been used since the 1970s to prevent chemotherapy-induced alopecia, one of the most common and psychologically troubling side effects of chemotherapy. Currently available scalp cooling systems demonstrate varying results in terms of effectiveness and tolerability. METHODS: For the present prospective study, 55 women receiving neoadjuvant, adjuvant, or palliative chemotherapy were enrolled. The aim was to assess the effectiveness of a sensor-controlled scalp cooling system (DigniCap: Sysmex Europe GmbH, Norderstedt, Germany) to prevent chemotherapy-induced alopecia in breast or gynecologic cancer patients receiving 1 of 7 regimens. Clinical assessments, satisfaction questionnaires, and alopecia evaluations [World Health Organization (who) grading for toxicity] were completed at baseline, at each cycle, and at completion of chemotherapy. RESULTS: Of the 55 patients, 78% underwent scalp cooling until completion of chemotherapy. In multivariate analysis, younger women and those receiving paclitaxel weekly or paclitaxel-carboplatin experienced less alopecia. The compound successful outcome ("no head covering" plus "who grade 0/1") was observed in all patients 50 years of age and younger receiving 4 cycles of docetaxel-cyclophosphamide or 6 cycles of paclitaxel-carboplatin. Conversely, alopecia was experienced by all women receiving triplet polychemotherapy (6 cycles of docetaxel-doxorubicin-cyclophosphamide). For women receiving sequential polychemotherapy regimens (3 cycles of fluorouracil-epirubicin-cyclophosphamide followed by 3 cycles of docetaxel or 4 cycles of doxorubicin-cyclophosphamide followed by 4 cycles of docetaxel), the subgroup 50 years of age and younger experienced a 43% success rate compared with a 10% rate for the subgroup pf older women receiving the same regimens. CONCLUSIONS: The ability of scalp cooling to prevent chemotherapy-induced alopecia varies with the chemotherapy regimen and the age of the patient. Use of a compound endpoint with subjective and objective measures provides insightful and practical information when counselling patients.

Assisted reproductive technology in Europe, 2004: results generated from European registers by ESHRE.

BACKGROUND: European results of assisted reproductive techniques from treatments initiated during 2004 are presented in this eighth report. METHODS: Data were mainly collected from existing national registers. From 29 countries, 785 clinics reported 367,066 treatment cycles including: IVF (114,672), ICSI (167,192), frozen embryo replacement (FER, 71,997), egg donation (ED, 10 334), preimplantation genetic diagnosis/screening (PGD/PGS, 2701) and in vitro maturation (IVM, 170). Overall, this represents only a marginal increase since 2003, due to a huge reduction in treatments in Germany. European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 20 countries. A total of 115,980 cycles (IUI-H, 98,388; IUI-D, 17,592) were included. RESULTS: In 14 countries where all clinics reported to the IVF register, a total of 248,937 ART cycles were performed in a population of 261.6 million, corresponding to 1095 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 26.6% and 30.1%, respectively. For ICSI, the corresponding rates were 27.1% and 29.8%. After IUI-H, the clinical pregnancy rate was 12.6% in women below 40. After IVF and ICSI, the distribution of transfer of 1, 2, 3 and 4 or more embryos was 19.2%, 55.3%, 22.1% and 3.3%, respectively. Compared with 2003, fewer embryos were transferred, but huge differences still existed between countries. The distribution of singleton, twin and triplet deliveries after IVF and ICSI combined was 77.2%, 21.7% and 1.0%, respectively. This gives a total multiple delivery rate of 22.7% compared with 23.1% in 2003 and 24.5% in 2002. After IUI-H in women below 40 years of age, 11.9% were twin and 1.3% triplet gestations. CONCLUSIONS: Compared with earlier years, the reported number of ART cycles in Europe increased and the pregnancy rates increased marginally, even though fewer embryos were transferred and the multiple delivery rates were reduced.

Assisted reproductive technology in Europe, 2003. Results generated from European registers by ESHRE.

BACKGROUND: European results of assisted reproductive techniques (ARTs) from treatments initiated during 2003 are presented in this seventh report. METHODS: Data were mainly collected from already existing national registers. From 28 countries, 725 clinics reported 365 103 treatment cycles with: IVF 132 932, ICSI 162 149, frozen embryo replacement (FER) 60 412, oocyte donation (OD) 7548, PGD/PGS 1956 and IVM 109. Overall, this represents a 13% increase since 2002. For the third time, results on European data on intrauterine inseminations (IUIs) were reported from 19 countries. A total of 99 577 cycles (IUI-H, 82 834; IUI-D, 16 743) were included. RESULTS: In those 15 countries where all clinics reported to the register, a total of 284 765 cycles were performed in a population of 278.7 million, corresponding to 1022 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 26.1 and 29.6%, respectively. For ICSI, the corresponding rates were 26.5 and 28.7%. After IUI-H, the clinical pregnancy rate was 12.2% in women below 40 years and 8.8% in women > or =40 years. After IVF and ICSI, the distribution of transfer of one, two, three and four or more embryos was 15.7, 55.9, 24.9 and 3.5%, respectively. Compared to the year 2002, fewer embryos were transferred, but huge differences still exist between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 76.7, 22.0 and 1.1%, respectively. This gives a total multiple delivery rate of 23.1% compared with 24.5% in 2002. The range of triplet deliveries after IVF and ICSI varied from 0.0 to 4.4% between countries. After IUI-H in women below 40 years of age, 11.4% were twin and 2.2% triplet gestations.

Cytokine and hormonal profile in blood serum and follicular fluids during ovarian stimulation with the multidose antagonist or the long agonist protocol.

BACKGROUND: The aim of our study was to explore cytokine and hormonal profiles in blood and follicular fluids from normal women stimulated with either the multidose antagonist or the long agonist protocol. METHODS: Fifty-six patients were stimulated with the multidose antagonist protocol and 12 with the long agonist protocol. Interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha (TNFalpha), leptin, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), estradiol (E(2)), progesterone and testosterone levels were measured in serum and follicular fluids by immunoassays. RESULTS: The two treatment groups had similar cytokine concentrations in serum. The intrafollicular concentrations of IL-1beta, IL-6, VEGF and leptin were also similar in the two groups. The concentrations of bFGF in follicular fluids from the antagonist group (169.5 +/- 113.2 ng/ml) were lower than those from the agonist group (249.7 +/- 119.8 ng/ml). bFGF concentrations were correlated with the amount of administered gonadotrophins (R = 0.364, P < 0.01) which was significantly lower in the antagonist group (antagonist group: 2037.7 +/- 725.8 IU; agonist group: 2836.4 +/- 1163.5 IU). CONCLUSIONS: Normal women stimulated with either the multidose antagonist or the long agonist protocol generally have similar cytokine profiles in serum and follicular fluids. The intrafollicular levels of bFGF tend to be lower in antagonist cycles because of the lower amount of administered gonadotrophins.

GnRH agonists and antagonists in assisted reproduction: pregnancy rate.

Although gonadotrophin-releasing hormone (GnRH) antagonists offer many advantages when used in ovarian stimulation, their popularity is lower than expected. GnRH protocols are suspected to yield lower pregnancy rates compared with the long agonist protocol. In the current study, subgroup analyses from the German IVF registry (DIR) were performed to evaluate the hypothesis that GnRH antagonists are often used as second-line medication in patients with difficult medical conditions, and thus pregnancy rates may be biased. Consequently, pregnancy rates in the first six stimulation cycles (low rank cycles) were more favourable in the group treated according to the long protocol, while in the patient group requiring more stimulation cycles (high rank cycles; 7, 9 and 10), numerically higher pregnancy rates were achieved with GnRH antagonist protocols. On the other hand, in a patient collective with equal demographic and clinical features (<35 years, tubal infertility), the long and the GnRH antagonist protocols resulted in similar pregnancy rates, supporting the hypothesis that both stimulation protocols lead to equal results.

Assisted reproductive technology in Europe, 2002. Results generated from European registers by ESHRE.

European results of assisted reproductive techniques (ART) from treatments initiated during 2002 are presented in this sixth report. Data was mainly collected from already existing national registers. From 25 countries, 631 clinics reported 324,238 treatment cycles with: IVF 122,634, ICSI 135,048, frozen embryo replacement (FER) 57 162, egg donation (ED) 7677, preimplantation genetic diagnosis/screening (PGD/PGS) 1563 and in vitro maturation (IVM) 154. Overall this represents a 12% increase since year 2001. For the second time, results on European data on intrauterine inseminations were reported from 17 countries. A total of 93,284 cycles [IUI-husband/partner (H), 78 505 and IUI-donor (D), 14,779] were included. In 13 countries where all clinics reported to the register, a total of 177,429 cycles were performed in a population of 193.7 million, corresponding to 916 cycles per million inhabitants. For IVF the clinical pregnancy rate per aspiration and per transfer was 26.0 and 29.5%, respectively. For ICSI the corresponding rates were 27.2 and 29.4%. These figures are marginally better than in 2001. After IUI-H the clinical pregnancy rate was 11.6% in women below 40 and 7.8% in women>or=40 years of age. After IVF and ICSI the distribution of transfer of 1, 2, 3 and 4 or more embryos was 13.7, 54.8, 26.9 and 4.7%, respectively. Compared with year 2001, less embryos were transferred, but huge differences existed between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 75.5, 23.2 and 1.3%, respectively. This gives a total multiple delivery rate of 24.5%, compared with 25.5% in year 2001. The range of triplet deliveries after IVF and ICSI varied from 0.0 to 5.2% between countries. After IUI-H in women below 40 years of age, 10.2% were twin and 1.3% triplet gestations.

Why do couples refuse or discontinue ART?

The first child born after in-vitro fertilisation, (IVF)-treatment, just passed its 26th birthday in July 2004. Since that birth-assisted reproduction techniques (ART) became a practicable technology, they had been used all over the world, and more than 2 million children were born after IVF-treatment. Despite all success in this field, ART is neither accepted nor used for all infertile couples, although this might be the only possibility of becoming pregnant. Two different kinds of ART refusal are distinguishable: the primary refusal being for financial, psychosocial, moral, ethical and medical reasons including the risk of severe ovarian hyperstimulation syndrome, the risk of multiple pregnancies and the risk of malformations. The secondary refusal includes dropouts after one or more unsuccessful IVF-treatments mainly influenced by the outcome of previous cycles (prognostic factors: oocyte and embryo count, embryo quality, females age) associated with psychological and emotional aspects. However, financial factors seem to be the most potent reasons for ART-refusal.

Recombinant luteinizing hormone supplementation to recombinant follicle-stimulating hormone induced ovarian hyperstimulation in the GnRH-antagonist multiple-dose protocol.

BACKGROUND: Suppression of endogenous LH production by mid-follicular phase GnRH-antagonist administration in controlled ovarian hyperstimulation protocol using recombinant (rec) FSH preparations void of LH activity may potentially affect ovarian response and the outcome of IVF treatment. The present study prospectively assessed the effect of using a combination of recFSH and recLH on ovarian stimulation parameters and treatment outcome in a fixed GnRH-antagonist multiple dose protocol. METHODS: 127 infertile patients with an indication for IVF or ICSI were recruited and randomized (using sealed envelopes) to receive a starting dose of either 150 IU recFSH (follitropin alpha) or 150 IU recFSH plus 75 IU recLH (lutropin alpha) for ovarian hyperstimulation. GnRH-antagonist (Cetrorelix) 0.25 mg was administered daily from stimulation day 6 onwards up to and including the day of the administration of recombinant HCG (chorion gonadotropin alpha). Gonadotropin dose adjustments were allowed from stimulation day 6 onwards, HCG was administered as soon as three follicles > or =18 mm were present. The primary outcome parameter was treatment duration until administration of HCG. RESULTS: Exogenous LH did not shorten the time necessary to reach ovulation induction criteria. Serum estradiol (E(2)) and LH levels were significantly higher on the day of HCG administration in the recLH-supplemented group (1924.7 +/- 1256.4 vs 1488.3 +/- 824.0 pg/ml, P < 0.03), and 2.1 +/- 1.4 vs 1.4 +/- 1.5 IU/l, P < 0.01, respectively). CONCLUSIONS: Except for higher E(2) and LH levels on the day of HCG administration, no positive trend in favour of additional LH was found as defined by treatment outcome parameters.

Assisted reproductive technology in Europe, 2001. Results generated from European registers by ESHRE.

European results of assisted reproductive techniques from treatments initiated during 2001 are presented in this fifth report. Data were collected mainly from already existing national registers. From 23 countries, 579 clinics reported 289 690 cycles with: IVF 120 946, ICSI 114 378, frozen embryo transfer (FER) 47 195 and egg donation (ED) 7171. Overall this represents a 4% increase since the year 2000. For the first time, results on European data on intra-uterine inseminations (IUIs) were reported from 15 countries. A total of 67 124 cycles [IUI husband'sperm (IUI-H) 52 949 and IUI donor sperm (IUI-D) 14 185] were included. In 12 countries where all clinics reported to the register, a total of 108 910 cycles were performed in a population of 131.4 million, corresponding to 829 cycles per million inhabitants. For IVF, the clinical pregnancy rate per aspiration and per transfer was 25.1 and 29.0%, respectively. For ICSI, the corresponding rates were 26.2 and 28.3%. These figures are similar to the results from 2000. After IUI-H, the clinical pregnancy rate was 12.8% in women <40 and 9.7% in women > or =40 years of age. After IVF and ICSI, the distribution of transfer of one, two, three and > or =4 embryos was 12.0, 51.7, 30.8 and 5.5%, respectively. Compared with the year 2000, fewer embryos were transferred, but huge differences existed between countries. The distribution of singleton, twin and triplet deliveries for IVF and ICSI combined was 74.5, 24.0 and 1.5%, respectively. This gives a total multiple delivery rate of 25.5%, compared with 26.9% in the year 2000. The range of triplet deliveries after IVF and ICSI differed from 0.0 to 8.2% between countries. After IUI-H in women <40 years of age, 10.2% were twin and 1.1% were triplet gestations.

FSH time-concentration profiles before and after administration of 0.25 mg cetrorelix in the gnRH-antagonist multiple-dose protocol for ovarian hyperstimulation.

PURPOSE: To determine FSH concentration behavior before and after cetrorelix 0.25 mg administration in the GnRH-antagonist multiple-dose protocol on day 6 of ovarian stimulation with 150-300 IU daily recombinant FSH. METHODS: Blood samples for FSH measurements were drawn from seven women every 15 min from 8 h prior to the first cetrorelix administration in the GnRH-antagonist multiple-dose protocol until 15-32 h thereafter. RESULTS: No significant change of FSH concentration was observed. CONCLUSIONS: This observation indicates that no rationale exists of increasing the daily FSH dosage concomitantly to the GnRH-antagonist administration to compensate for a drop of endogenous FSH.

Taxanes in the first-line chemotherapy of metastatic breast cancer: review.

Taxanes belong to the most effective agents in the treatment of advanced and non-hormone responsive breast cancer. Several recently published phase III studies have examined the role of taxane-anthracycline combinations in the first line treatment of metastatic breast cancer. Especially, patients with symptomatic visceral spread seem to benefit from taxanes containing polychemotherapy that is adequately dosed. Polychemotherapy with taxanes appears to be more effective than monotherapy. But at present, there are no adequate data concerning the comparison of taxane-monotherapy and anthracycline-containing polychemotherapy. New hopeful results with respect to efficacy and toxicity are reported from the docetaxel-capecitabine polychemotherapy. Thus, the combination of anthracyclines (adriamycin, doxorubicin) and taxanes (docetaxel, paclitaxel) is a promising tool in the treatment of metastatic breast cancer. New interesting combinations are under investigation.

Previous miscarriages influence IVF and intracytoplasmatic sperm injection pregnancy outcome.

Previous conceptions are one predictor for the outcome of assisted reproductive technology procedures. Approximately 18-34% of clinical pregnancies following assisted reproduction procedures result in spontaneous abortion. The risk of such pregnancy loss is believed to increase with women's age, previous miscarriages and use of frozen-thawed embryos. This study analyses German IVF Registry data to examine the impact of previous miscarriages on the outcome of assisted reproduction procedures. The data set consists of a total of 174,909 assisted reproduction procedures performed between January 1998 and December 2000. Multiple logistic regression is used to assess the correlation between women's age, spousal/partner change, and infertility diagnosis. It is demonstrated that any previous miscarriage will increase the treatment-dependent miscarriage rate in assisted reproduction procedures. A significantly higher impact is shown for one previous miscarriage achieved by assisted reproduction procedures compared with spontaneous conception. Partner change is shown to have no specific impact on the treatment dependent miscarriage rate, whereas a statistically significant increase in miscarriages in all assisted reproduction procedures was found among women older than 34 years of age. Overall, the highest rate of treatment-dependent miscarriages was seen in assisted reproduction procedures with cryopreserved embryo transfer.

[Cumulus cell apoptosis as a predictor for oocyte quality in artificial reproduction technique]. / Die Apoptoseaktivität in Cumuluszellen als ein Indikator der Eizellqualität in der Assistierten Reproduktion.

OBJECTIVE: To be able to predict the success of ART reliable tests for determining the quality of the oocytes are necessary. Apart from a vague morphologic assessment via microscopy a direct analysis of the oocyte quality is not possible. Because of the very close relation between the oocyte and the cumulus cells the analysis of the cumulus cells might give sufficient information on the oocyte quality. In this study we correlate the apoptotic activity of cumulus cells to the outcome of fertilized oocytes after Intracytoplasmic Sperm Injection (ICSI). MATERIAL AND METHODS: 246 cumulus-oocyte-complexes from patients undergoing infertility treatment with the ICSI procedure were individually collected. The comet assay was used to determine the proportion of apoptotic cells within the cumulus population of each oocyte and correlated with oocyte fertilization and oocyte quality as well as with pregnancy outcome in 86 patients. RESULTS: We were able to show that high quality embryos correlate to a low rate of apoptotic cells in their corresponding cumuli. Differences regarding the pregnancy outcome were statistically not significant. CONCLUSIONS: Our results on cumulus cell apoptosis and embryo quality confirm other publications. To arrive at statistically proven criteria for the further development of single oocytes an increase in the number of analyzed patients is necessary.

Safety and efficacy of a 3 mg dose of the GnRH antagonist cetrorelix in preventing premature LH surges: report of two large multicentre, multinational, phase IIIb clinical experiences.

Gonadotrophin-releasing hormone antagonists are effective and safe in preventing premature LH surges, a leading cause of cycle cancellation or failure during assisted conception. Two studies assessed two administration regimens for cetrorelix (as Cetrotide): the multiple-dose (MD, 0.25 mg/day, n = 1066) and single-dose (SD, 3 mg, n = 541) protocols. Patient outcomes were very similar: >90% reached criteria for human chorionic gonadotrophin (HCG) administration and underwent oocyte retrieval; embryo transfer was performed in 83-84%; failure to retrieve oocytes was rare (0.8%); on average, 11 follicles > or =10 mm in diameter were seen on the day of HCG administration. The SD protocol was associated with higher numbers of oocytes retrieved and available for insemination, although the numbers of embryos obtained or transferred were comparable. A total of 251 and 121 pregnancies were reported in the MD and SD groups respectively. Pregnancy rates per embryo transfer were 27 and 28% respectively. Severe ovarian hyperstimulation syndrome (OHSS) occurred in <1% of cycles. Twelve per cent of patients reported local reactions to injections in the MD group, compared with 8% in the SD group; none was serious or led to discontinuation. Seventy-three per cent of patients in the SD group received only one injection. These two studies therefore show that the single-dose cetrorelix protocol offers equal efficacy and safety to the MD regimen, while having the advantage of requiring only one injection in most patients.

[Enhanced liposomal transfection through the application of sex steroids in gynecological cancer cells]. / Die Sexualsteroid-vermittelte Verstärkung liposomaler Transfektion gynäkologischer Krebszellen--Ein neuer Ansatz für ein selektives Targeting in der Gentherapie?

OBJECTIVE: Liposomal transfection in gene therapeutic application against gynecological malignoma does not reach satisfying efficacy. A desirable goal would be the specific intensification of transfection in these kind of cells. Steroids have successfully been used in other systems to increase liposomal transfection and hopefully there might be a specific impact of sexual steroids in cells from high sex steroid receptor expressing malignoma, like some mamma- and endometrium cancer. MATERIAL AND METHODS: The mamma carcinoma cell line T-47D was transfected with the transfection agent DOTAP and cyclodextrin solubilized steroids and cholesterol were co-applied. The efficiency of transfection was followed by luciferase activity resulting from the transfected reporter gene. RESULTS: Like cholesterol, which is already established as transfection co-agent, also the steroids progesterone, estrogen, testosterone and hydrocortisone provoked a clear increase in transfection efficiency shown in a dose dependent manner. CONCLUSIONS: These results indicate the usefulness of steroids as additives for liposomal transfection procedures in gene therapeutic application. As sexual steroid receptors migrate into the nucleus of a cell after binding its specific ligand a targeted enhancement of transfection is supposable in malignoma overexpressing steroid receptors. There is evidence that plasmid DNA can be co-transported with nuclear proteins into the nucleus.

Ductal carcinoma in situ of the breast: diagnosis and management.

Currently, no precise morphologic or biologic prognostic factors reliably identify patients with ductal carcinoma in situ (DCIS) who are at high risk of disease progression. DCIS is a disease with an extremely favorable prognosis and a small likelihood of dying from breast cancer, regardless of what type of treatment is received. No retrospective or prospective study to date has demonstrated a significant difference in breast cancer specific mortality regardless of treatment. The similarities between DCIS and invasive cancer suggest that an important area for future research should be elucidating the processes that can either unleash or contain the invasive potential of DCIS cells. Thus, an understanding of the biology of DCIS can assist in the prevention, the assessment, and the diagnosis of invasive breast cancer.

Use of GnRH antagonists in the treatment of endometriosis.

Endometriosis is an oestrogen-dependent disease that is treatable by oestrogen withdrawal, a therapy that has been effectively provided by the use of a gonadotrophin-releasing hormone (GnRH) agonist. Complete oestrogen withdrawal results in unacceptable side-effects, in particular in accelerated bone density loss. This problem has been effectively overcome with 'add-back therapy' using low-dose oestrogens and progestins in combination with a GnRH agonist to limit these side-effects, while still allowing regression of endometriotic lesions. The aim of this study was to determine the feasibility of using a subcutaneous injection of GnRH antagonist in the treatment of endometriosis. All patients (15/15; 100%) reported a symptom-free period during GnRH antagonist treatment, including mood changes, hot flushes, loss of libido, vaginal dryness and other symptoms. Serum oestradiol oscillated around a mean concentration of 50 pg/ml during therapy. Diagnostic laparoscopy before GnRH antagonist administration showed a mean stage III of disease. Regression occurred in 60% of cases (9/15) and the degree of endometriosis declined to stage II. Sequential administration of the GnRH antagonist cetrorelix (Cetrotide) in a 3 mg dosage once weekly over 8 weeks creates a new opportunity for medical treatment of symptomatic endometriosis. Preserving basic oestrogen production during the course of treatment apparently does not influence regression of disease, and has no major side-effects.