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In a large population-based case-control study in Germany, including 3,464 breast cancer cases aged 50-74 at diagnosis and 6,657 population based and frequency matched controls, we investigated the effects of menopausal hormone therapy (HT) by type, regimen, timing and progestagenic constituent on postmenopausal breast cancer risk overall and according to histological type. Data were collected by face-to-face interviews. Logistic and polytomous logistic regression analysis were used to estimate odds ratios (OR) and 95%-confidence intervals (95% CI). Risk of invasive breast cancer was significantly elevated in current users (OR, 1.73, 95% CI, 1.55-1.94) and heterogeneous by histological type (p < 0.01), being more than 2-fold higher for lobular and tubular than for ductal cancer. Risks for current users varied significantly by type and regimen of HT, with ORs per year of use of 1.05 (95% CI, 1.04-1.06) for continuous combined estrogen-progestagen, 1.03 (95% CI, 1.02-1.04) for cyclical EP and 1.01 (95% CI, 1.00-1.03) for estrogen-only therapy. No statistically significant increase in risk was observed after 5 years of cessation of HT use for any histological type. Analyses of progestagenic content by regimen revealed a significantly higher risk for continuously administered norethisterone- or levonorgestrel-derived progestagens than for continuously administered progesterone-derived progestagens (OR, 2.27, 95% CI, 1.98-2.62 vs. 1.47, 95% CI, 1.12-1.93, respectively, p = 0.003), which may be explained by dose rather than type of progestagen. These data suggest that the risks associated with menopausal HT differ by type and regimen of HT and histological type of breast cancer and may vary by progestagenic component, depending on the effective dose.

The immaturity of the foetal lung is one of the central problems in obstetrics. In this paper first results are presented to determine the maturity of the foetal lung by sonography. Using the foetal liver as a reference organ we are avoiding the known pitfalls which made it impossible in the past to standardise the foetal lung changes depending upon the age of gestation. We examined 121 patients between week 27 and week 41. In one ultrasound section cut we depicted lung and liver as well. According to the known A-mode we registered frequencies in both organs. The registered frequencies were entered digitally into a computer and checked for f mean, f max and f min. Subsequently we calculated quotients of frequencies of the foetal lung and liver. For all weeks of gestation the mean value and standard deviation were calculated. We found that the liver is an adequate reference organ, since there is no change in the reflection pattern between the different weeks of gestation. We registered significant differences in the quotients of lung and liver between the different weeks of gestation, a cutting line being week 35. A quotient of Q mean lower than 1.1 hints to lung maturity while values over 1.1 point to immaturity.

A retrospective analysis of 78 maternal deaths was performed during 1991-1992 to estimate maternal mortality at the maternity unit of the main tertiary level hospital in The Gambia. The non-abortion maternal mortality ratio (MMR) was 736 per 100 000 live births. Among the direct causes, haemorrhage caused most deaths (24%), followed by hypertensive disorders in pregnancy (HDP) (21%). Sepsis was the main cause of death in 15%. Anaemia led among the indirect causes of death (8%) and was a co-factor in 41% of all deaths. Substandard care factors other than medical causes were determined involving health care facilities, staff, drugs and equipment, and patient-related factors. Well known risk factors of low age (< or = 19 years) and nulliparity were highly represented in the maternal death group, and delivery by Caesarean section occurred more than threefold compared to the overall Caesarean section rate. Taking haemorrhage as an example, it is demonstrated that the way diagnoses are grouped significantly affects the statistical elaboration of maternal deaths.

This is a report on 278 patients who underwent subcutaneous mastectomy (SCM) at the Gynaecological Department of the University Hospital Heidelberg between 1980 and 1996. These operations were indicated either because of diagnostic problems (n = 104), a carcinoma of the contralateral breast (n = 33), non-invasive lobular carcinoma (n = 33), non-invasive ductal carcinoma (n=64), recurrent disease (n=8) or invasive carcinoma (n=36). In the group of patients with diagnostic problems occult lesions were found in 16%. In women with a previously known contralateral carcinoma occult carcinomata were diagnosed in 27%. In cases with a preoperative lobular carcinoma in situ we found ipsilaterally 6% occult invasive carcinoma and in 20% with a preoperatively diagnosed ductal carcinoma in situ. After a median follow up of 16.6 years the local recurrence rate for the invasive carcinoma was 19%, for LCIS was 10% and for DCIS was 3%. The recurrence free survival after 10 years was 91% for DCIS and LCIS and 86% for invasive carcinoma. The overall survival after ten years was 97% for DCIS, 95% for LCIS and 90% for invasive carcinoma. The incidence of invasive breast cancer after prophylactic subcutaneous mastectomy was 1 %. The findings of this study support the use of SCM because of comparable results in local recurrence rates and overall survival with breast conserving therapy and mastectomy, therefore SCM is a further therapeutic option.

Developing primary systemic chemotherapy (PST) regimens that induce higher pathological complete response (pCR) rates remains a challenge in operable breast cancer. We recruited 77 eligible patients into a multicentre phase I/II study to evaluate the maximum tolerated dose (MTD), toxicity and efficacy of preoperative gemcitabine day 1 and 8 (800 mg/m 2 fixed dose), epirubicin and docetaxel on day 1 (doses escalated from 60 mg/m 2 ) (GEDoc), repeated 3-weekly for 6 cycles with filgrastim support. MTD for epirubicin was 90 mg/m 2 and for docetaxel 75 mg/m 2 . Dose-limiting toxicities (DLTs) included febrile neutropenia and grade 3 diarrhoea. Clinical response rate was 92%, pCR rate was 26%. 79% of patients had breast-conserving surgery. Grade 3/4 leucopenia was the main toxicity, occurring in 55 (87%) of 63 patients treated at the MTD. Non-haematological toxicity caused no serious clinical problems. In conclusion, GEDoc is highly active as PST. Efficacy and toxicity compare favourably with other effective combinations.

Purpose: The 6th edition of TNM classification, valid since January 1, 2003, shows important changes in breast cancer classification, especially regarding lymph node status and UICC stage grouping. The effects of the redefinition of the TNM categories on stage and prognosis have not yet been studied in a large cohort of patients. Patients and Methods: We analyzed TNM staging of 5366 breast cancer cases registered at the Gynecological University Hospital Heidelberg (diagnosed from 1985 to 2000) according to the old and the new TNM classification. The effects of the new classification system were examined with regard to stage grouping and survival. Results: One of the most important effects of the 6th TNM edition is that reclassification of patients with nodal stage pN1 (5th edition) are now graded in the new nodal categories pN1, pN2 or pN3 according to the number and the localization of lymph node metastasis. This shifting of cases significantly increases the number of patients in UICC Stage III. Thereby, relative survival rates in the new pN categories 1, 2 and 3 and in the new UICC Stages II and III are visibly improved (so called Will Rogers Phenomenon or stage migration). Apart from that, splitting of the big group of patients with nodal stage pN1 (5th edition) provides a prognostically more meaningful stratification of patients, permitting easier identification of prognostically unfavorable cases. A new division of cases also resulted for patients with nodal stage pN2 (5th edition) according to the number of affected lymph nodes, permitting a better identification of prognostically - more favorable cases in this group. Conclusion: Prognostic data that relate to the 5th edition ofTNM and the tumor stages defined therein are not directly comparable with the 6th edition of TNM. This should be considered when analyzing clinical studies using the new staging system.

Objective: Cytotoxic chemotherapy of advanced breast cancer is frequently complicated by drug resistance. Our goal was to define the role of the apoptosis-regulating receptors Fas (CD95) and CD40 in the chemosensitivity of breast cancer. Methods: The sensitivity of four breast cancer cell lines to paclitaxel and mitoxantrone was evaluated using an ATP-based cell viability assay. After verification of apoptosis by annexin V staining and TUNEL assay, cell lines were characterized regarding their constitutive expression of both surface and soluble (s)Fas (CD95) and Fas ligand (Fas-L). The role of the Fas/Fas-L system and different caspases was assessed by blocking drug-mediated apoptosis with specific antibodies. Finally, the paclitaxel sensitivity of the CD40-negative cell line KS was compared to that of its CD40-positive transfectant KS-CD40. Results and Conclusion: While the cytotoxic effect of mitoxantrone did not correlate with Fas expression, the results presented here suggest some involvement of the Fas/Fas-L system in paclitaxel-induced apoptosis. Cell lines with constitutive expression of Fas/sFas demonstrated a higher sensitivity to paclitaxel than Fas-negative cells. Incubation with paclitaxel led to a measurable downregulation of the expression of both soluble and surface Fas receptor in these cells. Interestingly, stimulation of the CD40 receptor inhibited paclitaxel-induced apoptosis in the transfected cell line KS-CD40, suggesting a role of this receptor in the modulation of chemosensitivity.

Purpose: Neoadjuvant chemotherapy (pCHT) is an established method to reduce tumor size (downstaging) in breast cancer patients before performing breast conserving therapy. The consequences of pCHT on tumor cell dissemination (TCD) in these patients are not known. The aim of this study was to evaluate tumor cell dissemination before and after pCHT in breast cancer patients. In addition, the prognostic value of TCD after pCHT was studied. Patients and Methods: 140 women with non-inflammatory, locally advanced breast cancer (tumor size > 3 cm and an unfavorable relation between breast and tumor size) received neoadjuvant chemotherapy with Epirubicin/Cyclophosphamide (90/ 600 mg/m 2 every 3 weeks for 4 cycles). In all patients bilateral aspiration of bone marrow was performed at the time of surgery (after neoadjuvant chemotherapy). In 42 of the 140 patients additional bone marrow aspirations were taken before neoadjuvant chemotherapy. Results: 68 of 140(49%) breast cancer patients had disseminated tumor cells (TCD) after neoadjuvant chemotherapy. TCD was an independent prognostic factor for disease free intervals (p=0.022, RR=2.63) and overall survival (p=0.032, RR=2.23). 20 of 42 patients had disseminated tumor cells before and after neoadjuvant chemotherapy. In contrast, 18 patients had no tumor cell dissemination during neoadjuvant treatment. Four patients had a change of their bone marrow status. Conclusion: Our results demonstrate that TCD is not influenced by neoadjuvant chemotherapy and remains an independent prognostic factor after pCHT. However, future studies will need to investigate whether neoadjuvant therapy changes the metastatic behaviour of TCD.

Ovarian cancer during pregnancy is rare. We report on a 35-year-old para 3 who showed ascites after an uncomplicated pregnancy and delivery. Sonography showed ovarian masses suspicious for malignancy. Laparotomy confirmed FIGO stage IIIC ovarian cancer. Tumor debulking was performed and combination platinum-based chemotherapy was initiated. We review the diagnostic features and role of ultrasonography in women with possible ovarian cancer during pregnancy.

Follow-up for patients with breast and genital cancers is part of the overall cancer care. Relevant data about early detection, diagnostic procedures and therapies in the adjuvant and palliative setting are available. Information about the value of and the strategies for time intervals and diagnostic procedures during the follow-up interval are up to date not standardized. Large scale data from prospective randomised trials or evidence-based criteria are missing for most procedures applied. As a consequence a clinically orientated follow-up care programme is proposed. This programme encompasses individualisation of care with an informative, detailed and structured talk and a clinically directed exam. The detection of clinical signs and symptoms leads to further diagnostic procedures. 'Talking Care' is the way of personal care for the diseased women. Follow-up care is divided into a general and a specific part. The latter summarizes organ-specific symptoms, frequencies and nature of exams. Early cancer detection for other cancer types has to be integrated. These standards are the summary of the available and evident study data, clinical experiences, the wishes and the demands of the patients and the integration of factors for quality control.

In den letzten Jahren sind zahlreiche Immuntherapien gegen maligne Erkrankungen entwickelt worden. Dies ist darauf zuruckzufuhren, dass durch die wesentlichen Verbesserungen zellularer, biochemischer und molekularer Techniken Immunantworten auf humoraler und zellularer Ebene detaillierter analysiert und verstanden werden konnten. So konnte vor allem die Charakterisierung zahlreicher tumorassoziierter Antigene, die als Zielstrukturen immunologischer Abwehrprozesse dienen konnen, erfolgen. Da beim Mammakarzinom der Zusammenhang zwischen minimaler Resttumorerkrankung und erneutem Auftreten des Tumors erkannt wurde, ist ein wichtiger Aspekt bei der Entwicklung neuer erganzender Therapiekonzepte die Nutzung immunologischer Abwehrprozesse. Dabei ist das Ziel die erfolgreiche systemische Aktivierung tumorspezifischer T-Lymphozyten und die Ausbildung eines immunologischen Gedachtnisses im Patienten. Die Fahigkeit spezifischer T-Zellen zur Zirkulation wurde die Erkennung und Zerstorung von Metastasen und Mikrometastasen ermoglichen, die sich gangigen Therapiekonzepten wie der Chemo- und Radiotherapie entziehen. Auch wenn die Zukunft therapeutischer Vakzinierungen sicher in der Adjuvanz liegen wird, haben erste Erfahrungen bei Melanomen und Nierenzellkarzinomen gezeigt, dass auch Patienten mit relativ hoher Tumorlast von Immuninterventionen profitieren konnen. Diese Ubersicht soll Fortschritte und Moglichkeiten in der Entwicklung verschiedener Vakzinierungsstrategien und deren Verlaufskontrollen verdeutlichen, die sich zumindest teilweise die Kenntnis tumorassoziierter Antigene zu Nutze machen. Dazu zahlt deren direkter Einsatz als Peptidvakzine oder deren Kombinationen mit Adjuvanzien und antigenprasentierenden Zellen. Neben definierten Peptidantigenen wird auch der Tumor selbst haufig als Antigenquelle genutzt, die zwar das gesamte Antigenspektrum eines individuellen Tumors abdeckt, jedoch weitgehend undefiniert ist. Hier werden beispielsweise genetisch modifizierte Tumorzellvarianten eingesetzt, die in der Lage sind tumorspezifische immunologische Toleranz zu durchbrechen und so die Induktion einer Immunabwehr bewirken sollen. Recent advances in tumor immunology - such as the characterization of tumor-associated antigens recognized by cellular effectors of the immune system and the improved understanding of antigen processing and presentation - have opened new perspectives on cancer immunotherapy. The most important new approaches are peptide vaccines and whole-cell vaccines (tumor-cell-based or immune-cell-based). The advantage of tumor-cell-based vaccines is that they comprise the complete antigen pool of an individual tumor for activating polyclonal immune responses. The introduction of genes encoding costimulatory molecules or cytokines aims to confer their immunostimulatory potential. The rationale for fusing tumor cells and antigen-presenting cells is that the hybrid cell will display the antigenicity of the tumor and the immunogenicity of the fusion partner. Since the antigenic repertoire of tumor-cell-based vaccines is usually not fully characterized, it is difficult to estimate their immunostimulatory potential. To be able to assess vaccine-induced immune reactions and clinical responses it will be necessary to at least partially characterize the antgenicity of cellular vaccines and to define surrogate parameters. The continuously increasing number of HLA-restricted tumor antigens - also identified in breast cancer - allowed the development of antigen-defined vaccines. Direct in vivo administration of peptides in combination with adjuvants suitable for establishing effective immune responses or ex vivo loading of dendritic cells with tumor-specific epitopes are target-specific immunation approaches. Cocktails of synthetic peptide epitopes should permit targeting multiple antigens while avoiding the development of antigen-loss variants. Most clinical phase I/II trials to date indicate that cellular or peptide-based vaccines are safe. But the individual studies are heterogenous and based on small numbers of patients. This review describes advances in vaccination strategies and treatment approaches based on tumor-assocated antigens.

Introduction: Substitution of estrogenes and progestins is the most common therapy and prophylaxis for postmenopausal discomforts like hot flushes, osteoporosis, etc. However in the majority of studies long term HRT has been associated with an slightly increased risk of breast cancer. On the other hand patients with preoperative HRT have a lower mortality and a longer overall-survival. Material and Methods: For further investigation we examined 544 patients between 45 and 60 years at time of first diagnosis of breast cancer with and without HRT with regard to the incidence of bone metastases. 154 patients were premenopausal (mean 48.0±2.7 y), 390 were postmenopausal (54.5±3.5 y), 208 of them received HRT (group HRT+) and 182 patients not (group HRT-). Patients of group HRT+ received estrogenes over a minimum of 12 months (mean 5.5 ±4.0y). Results: Although tumor size and grading of group HRT- were significantly higher than in group HRT+ (p = 0.024), nodal status, S-phase fraction, and hormone-receptor status showed no significant differences. Adjuvant treatment in the postmenopausal groups were also not significantly different. In regard to the incidence of metastases patients without HRT have significantly (p

This prospective study was performed to examine the safety and efficacy of a continuous infusion of ceftazidime in patients who developed febrile neutropenia after high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplantation (PBSCT) and to determine if the underlying disease represents a risk factor for infectious complications. From September 1995 to May 2000, 55 patients with breast cancer (BC, group I, 54 females, one male) and 32 patients with multiple myeloma (MM, group II, 10 female, 22 male) were included in this study. The febrile patients received a 2 g intravenous bolus of ceftazidime, followed by a 4 g continuous infusion over 24 h using a portable infusion pump. If the fever persisted for 72 h a glycopeptide antibiotic was added. The median age was 42 years (range 22-59) in group I and 52 years (range 35-63) in group II. Thirty-five BC patients (64%) and 20 MM patients (63%) responded to the monotherapy with ceftazidime. After addition of a glycopeptide antibiotic, an additional 11 BC patients vs 10 MM patients became afebrile. The causes of fever in group I were fever of unknown origin (FUO) in 49 patients, microbiologically documented infection (MDI) in five patients, and clinically documented infection (CDI) in one patient. The causes of fever in group II were FUO in 22 patients, MDI in eight patients and CDI in two patients. Forty-one febrile episodes in BC patients (75%) and 22 episodes in the MM patients (69%) were successfully managed by out-patient treatment, resulting in a saving of an average of 20 days of inpatient care. Significantly more episodes of MDI and CDI occurred in patients with MM (P = 0.05). The results indicate that BC and MM patients with febrile neutropenia after HDCT and PBSCT can be treated as outpatients with close monitoring to ensure safety. This approach represents a better use of health care resources.

Objective: We analyzed the prognostic value of the immunohistochemical factors Ki67, p53, CD31, BCL2 and HER2 in patients with recurrent gynecologic malignancies. Methods: We reviewed 22 patients with advanced pelvic sidewall recurrence of gynecologic cancers treated with surgical debulking and intraoperative radiotherapy (IORT). Patients with peritoneal carcinomatosis were excluded. Ki67, p53, CD31, BCL2, and HER2 were evaluated in histologic specimens from 17 patients. Results: The analyzed tumors showed low expression of HER2 and BCL2 (11% and 18%, respectively). Tumors with a high proliferative index (Ki67 expression >30% of cells) had a worse prognosis than those with a low proliferative index (P = 0.015). High CD31 expression and low p53 expression were also associated with a higher rate of recurrence (P = 0.07 and 0.09, respectively). Tumor-free resection margins were an important prognostic factor (P = 0.004). Conclusion: Immunohistochemical parameters have prognostic relevance in patients with recurrent gynecologic cancer and can be considered when planning treatment. The expression of these factors changes during the progression of the disease. The status of the resection margins remains an important prognostic factor in patients with recurrent disease.

Objective: Aim of this retrospective study was to investigate in which way the spectrum of pelviscopy changed over 12 years of observation. In addition it should be tested, whether the duration of hospitalisation and the number of complications changed. Material and Methods: 12 382 gynecological pelviscopies which were performed during 1986-1998 at two centers were included into the study. The study protocol was designed retrospectively and focussed on time of hospitalisation, indication for pelviscopy and operation performed as well as complications that occurred. Statistical analysis was done by student-t-test. Results: The spectrum of pelviscopic operations changed during the time period investigated. While in 1986 diagnostic procedures were performed in a lot of cases, in 1998 most of the procedures were pelviscopic curative operations with in part rather complex operative procedures. In the same time the time of hospitalisation was reduced significantly as well as the number of secondary laparotomies and complications. Conclusion: Today a lot of - in former times - operations via laparotomy may be now performed via laparoscopy. Even though these laparoscopies are today in a lot of cases complex operations, the number of complications as well the time of hospitalisation has diminished, indicating that this change in operative procedures is accompanied by a benefit for the patient.

Objective: The monopolar, low-energy, high-frequency needle electrode is an innovative tool for electrosurgical dissection at laparoscopy. We reviewed the use of the needle and complications. Methods: A total of 1384 patients underwent laparoscopic operations including the new monopolar needle between 1990 and 1998. We reviewed indications for surgery, the intraoperative and postoperative course, indications for use of the needle, and complications. Results: The monopolar needle electrode was used for a wide range of indications, most commonly adhesiolysis (38.5%) and ovarian cystectomy (13%). Four patients developed superficial skin lesions, which were probably a result of patient positioning. Four patients with extensive adhesiolysis involving bowel developed bowel lesions. One patient developed postoperative bleeding after adnexectomy. Conclusion: The monopolar, low-energy, high-frequency needle electrode is a safe dissecting tool for laparoscopic surgery and has a wide range of indications.

In patients with metastatic breast cancer (MBC), early dose intensification with multiple cycles of peripheral blood stem cell-supported high-dose chemotherapy (HDCT) seems superior to a late dose-intensification strategy. We compared the progression-free survival (PFS) and overall survival (OS) of 20 patients treated with a double (D)-HDCT regimen to 20 patients who received a triple (T)-HDCT, matched by age, estrogen receptor (ER) status, adjuvant chemotherapy, initial disease-free interval, predominant metastatic site, and number of metastatic sites. At a median follow-up of 41.5 months (range, 14-88 months) an intent-to-treat analysis showed no difference in PFS (p = 0.72) and OS (p = 0.93) between the matched patients. For all 76 patients treated within the D- or T-HDCT trial, median PFS and OS was 13 months (range, 2-78 months) and 24.5 months (range, 7-78 months), respectively. In multivariate analysis independent predictors of shorter OS included negative ER (relative risk [RR] = 3.0 [95% confidence interval (CI) 1.5-5.9]; p = 0.002), more than two metastatic sites (RR = 2.4 [95% CI 1.0-5.7]; p = 0.049) and failure to achieve complete remission/no evidence of disease (CR/NED) after HDCT (RR = 4.5 [95% CI 2.0-10.1]; p < 0.0001). These data show that early dose intensification with T-HDCT is not superior to a D-HDCT regimen in patients with MBC. ER-negative tumors, more than two metastatic sites and no CR/NED after HDCT, are associated with inferior outcome.

OBJECTIVE A retrospective comparison of the efficacy and toxicity of docetaxel and paclitaxel in the treatment of metastatic breast cancer (MBC) was conducted based on our institution's experience since 1992. METHODS Two groups of 43 patients who received a similar chemotherapy regimen containing either docetaxel or paclitaxel were matched for the number of prior treatments. RESULTS Toxicity was mild in both groups. Tumour growth control, defined as either objective response or stable disease for at least 6 months, was obtained in a significantly higher proportion of patients treated with docetaxel compared with paclitaxel (67 % vs. 44 %, p = 0.001). Moreover, fewer patients progressed during treatment with docetaxel (28 % vs. 53 %, p < 0.001). At a median follow-up of 17 months there was no significant difference between the groups in median progression-free survival (7 vs. 5 months, p = 0.123) or median overall survival (OS) (12 vs. 11 months, p = 0.211). According to the method of Kaplan and Meier estimated OS rates at 1 year (74 % vs. 62 %) and 2 years (50 % vs. 26 %), however, were in favour of docetaxel. In a multivariate analysis only a positive hormone receptor status was significantly associated with improved OS. CONCLUSION These results suggest that docetaxel may be superior to paclitaxel in the treatment of MBC.

Objective : This study reviewed the results of breast reconstruction with the Fleur de lis-technique of the latissimus dorsi myocutaneous flap. Methods: We reviewed the cosmetic and functional results of 48 patients with breast cancer who underwent immediate or delayed breast reconstruction with the above technique. Results: A total of 44 patients (92%) considered the cosmetic results good or excellent. The surgeon considered the result good in 39 patients (81%). Complications consisted of seromas, wide scars, and dog ears at the donor site. Immediate reconstruction was not associated with increased morbidity. Conclusion: The Fleur de lis-technique of the latissimus dorsi myocutaneous flap is a safe technique with satisfactory cosmetic and functional results for immediate or delayed breast reconstruction.

PURPOSE: We evaluated the effect on future prognosis of an isolated locoregional recurrence (ILRR) after the primary diagnosis of breast cancer. Using data from four prospective studies of the German Breast Cancer Study Group, we investigated factors influencing prognosis after ILRR and defined a simple classification of patients into groups with different prognoses. PATIENTS AND METHODS: From 1983 to 1989, 2,746 patients were recruited into four studies comparing different treatments in primary breast cancer. After a median follow-up time of 8 years, 337 patients developed an ILRR as the first event. The influence of ILRRs on disease progression was examined. The effects of different prognostic factors on progression-free survival (PFS) and overall survival after ILRR were analyzed after a median follow-up time of 4.5 years. RESULTS: ILRRs increased the risk with respect to distant recurrence and death. After ILRR, 185 events occurred with respect to the PFS end point, and 171 patients died. Primary nodal status, tumor grade, estrogen receptor status of the primary tumor, and length of the disease-free interval (DFI) until the time of the ILRR had a significant prognostic impact. CONCLUSION: Determinants of prognosis after the ILRR should be taken into account for designing future risk-adapted clinical studies for these patients. Risk strata can be defined by a simple classification scheme based on primary nodal status and DFI.