Es wurden 177 Patientinnen mit zwischen 1999 und 2005 an der Universitätsfrauenklinik Leipzig operativ therapiertem Mammakarzinom und vorangegangener Stanzbiopsie, für die vollständige Befunde vorlagen und bei denen keine neoadjuvante Chemotherapie stattfand, hinsichtlich der prognostischen und prädiktiven Faktoren und deren Vergleich zwischen Stanzbiopsie und dem endgültigen Tumorexzidat untersucht. Unsere Daten zeigten, dass die Stanzbiopsie in der Einschätzung des Differenzierungsgrades mit einer Konkordanz von 62,9% und der Lymphgefäßinvasion mit einer Konkordanz in 69,8% keine hohe Genauigkeit besitzt. Bezüglich des histologischen Typs mit einer Übereinstimmung von 77%, der Östrogen- und Progesteronrezeptorbestimmung mit Konkordanzen von 87% und 83% sowie hinsichtlich des Her-2/neu-Status mit einer Konkordanz von 79% fand sich eine moderate bis gute Übereinstimmung mit dem Exzidat, wobei zu diskutieren ist, ob bei initial an der Stanzbiopsie negativem Östrogen- und/oder Progesteronrezeptorstatus oder auch bei positivem Progesteronrezeptor- und negativem Östrogenrezeptornachweis eine erneute immunhistochemische Hormonrezeptoruntersuchung am Exzidat erfolgen sollte sowie ob bei einer Konkordanzrate des Her-2/neu von weniger 95% immer eine zweite Bestimmung am Operationspräparat als Basis einer definitiven Therapieplanung durchgeführt werden muß. In 8,5% wurde an der Biopsie keine Malignität festgestellt. Der Vergleich des Malignitätsgrades mit der Tumorkategorie als auch mit dem Lymphknotenstatus zeigte keine signifikante Korrelation. Eine fortgeschrittene Tumorkategorie war mit dem Vorhandensein von Lymphknotenmetastasen korreliert.:1.Einleitung 2 1.1 Epidemiologie des Mammakarzinoms 2 1.2 Ätiologie und Pathogenese des Mammakarzinoms 2 1.2.1 Risikofaktoren des Mammakarzinoms 2 1.2.2 Molekulare Subtypisierung des Mammakarzinoms 4 1.3 Histologische Typen des Mammakarzinoms 6 1.4 Histopathologisches Grading des Mammakarzinoms 8 1.5 Metastasierung des Mammakarzinoms 9 1.6 Hormonrezeptoren und Her-2/neu 11 1.6.1 Östrogen- und Progesteronrezeptoren 11 1.6.2 Her-2/neu-Rezeptor 14 1.7 Prognostische und prädiktive Faktoren 14 1.7.1 Der histologische Typ als prognostischer Faktor 15 1.7.2 Das Grading als prognostischer Faktor 16 1.7.3 Lymphgefäßinvasion als prognostischer Faktor 17 1.7.4 Östrogen- und Progesteronrezeptorstatus als prognostischer und prädiktiver Faktor 18 1.7.5 Her-2/neu als prognostischer und prädiktiver Faktor 19 1.7.6 Tumorgröße und Lymphknotenstatus als prognostische Faktoren 20 1.8 Diagnostik des Mammakarzinoms 21 1.9 Therapie des Mammakarzinoms 24 1.9.1 Operative Therapie 24 1.9.2 Strahlentherapie 25 1.9.3 Adjuvante systemische Therapie 25 1.9.4 Primäre systemische Therapie 26 2. Zielstellung 28 3. Patientinnen, Material und Methoden 30 3.1 Datenerhebung 30 3.2 Histopathologische Aufarbeitung und Befunderhebung 30 3.3 Immunhistochemische Hormonrezeptorbestimmung und Her-2/neu-Analyse 31 3.4 Statistische Auswertung 34 4. Ergebnisse 4.1 Altersverteilung des Patientinnenkollektivs 35 4.2 Vergleich des histologischen Tumortyps zwischen Stanzbiopsie und Exzidat 35 4.3 Vergleich des histopathologischen Malignitätsgrades zwischen Stanzbiopsie und Tumorexzidat 41 4.4Vergleich der Lymphgefäßinvasion zwischen Stanzbiopsie und Tumorexzidat 44 4.5 Vergleich des Östrogen- und Progesteronrezeptorstatus zwischen Stanzbiopsie und Tumorexzidat 46 4.5.1 Östrogenrezeptoren 46 4.5.2 Progesteronrezeptoren 47 4.5.3 Her-2/neu-Rezeptorstatus 48 4.5.4 Vergleichende Darstellung der Östrogen- mit den Progesteronrezeptoren sowie der Hormonrezeptoren mit dem Her-2/neu-Status 51 4.6 Fehlender Nachweis von Malignität an der Stanzbiopsie 55 4.7 Vergleichende Auswertung des histopathologischen Malignitätsgrades und der lokalen Tumorausdehnung (pT) am endgültigen Tumorexzidat 57 4.8 Vergleichende Auswertung des Differenzierungsgrades und des Lymphknotenstatus (pN) zum Zeitpunkt der Operation 58 4.9 Vergleichende Auswertung der lokalen Tumorausdehnung (pT) und des Lymphknotenstatus (pN) zum Zeitpunkt der Operation 60 4.10 Zusammenfassung der Ergebnisse 62 5. Diskussion 63 5.1 Der histologische Typ 63 5.2 Der histologische Malignitätsgrad 65 5.3 Lymphgefäßinvasion 67 5.4 Hormonrezeptorstatus 67 5.5 Her-2/neu-Status 70 5.6 Vergleich des Malignitätsgrades mit der lokalen Tumorausdehnung und dem Lymphknotenstatus 73 6. Zusammenfassung 74 Tabellenverzeichnis 77 Abbildungsverzeichnis 79 Literaturverzeichnis 81 Erklärung 95 Danksagung 96

Skeletal muscle metastasis from breast carcinoma is a relatively rare clinical entity. We report two cases of breast cancer metastatic to the skeletal muscle, diagnosed by ultrasound guided fine needle aspiration (US-FNA) biopsy done by interventional cytopathologists at an outpatient cytopathology center. Our two patients presented with lower anterior neck firmness and chest wall mass, respectively. Ultrasound evaluation of our first case demonstrated hypo-echoic thickened anterior strap muscles while in the second case there was significant distortion of the anatomy from previous surgeries. It was necessary to proceed with FNA biopsy even when their ultrasound findings were equivocal, to establish a definite rapid diagnosis. The immediate onsite evaluation findings were suggestive of malignancy in both cases with subsequent core biopsy confirming the diagnosis of metastatic breast carcinoma. In cytopathology, point-of-care (POC) ultrasound is used as an adjunct tool that offers visual guidance during FNA of nonpalpable masses and enables sampling of lesional “hot” spots to ensure specimen adequacy. Studies have demonstrated a reduction in FNA nondiagnostic rates with the use of ultrasound-guidance consequently reducing health care costs associated with nondiagnostic FNAs. US-FNA also provides adequate samples for cell block preparations. Metastatic lobular carcinoma of the breast has a wide range of clinical presentations and a high level of suspicion is advised. Cytopathologists-performed US-FNA is a proven, less-invasive, cost-effective tool that provides timely cytologic diagnosis.

Introduction: About 5 - 10% of breast carcinomas are caused by genetic mutations. The most common genetic mutation that is involved in the development of this malignancy is a mutation in the tumor suppressor genes BRCA1/2 whose carriers have approximately a 70% lifetime risk of developing breast cancer. The prognosis of patients with BRCA1/2-asociated breast carcinoma, compared to patients with sporadic breast carcinoma is the subject of many studies with ambiguous results. Aim: The aim of the theoretical part of this work was to approach the issue of breast cancer and the most common genetic syndromes associated with it. In the practical part of this work a retrospective study was carried out in order to compare BRCA1/2 mutated breast cancer patients with non-mutated breast cancer patients in the tumor profile, methods of treatment and prognosis. Methods: We retrospectively analyzed the data of 134 patients who were tested for the presence of BRCA1/2 mutation at the Institute of Medical Genetics, University Hospital in Pilsen during the years 2013-2018 and at the same time were treated for early breast cancer at the University Hospital in Pilsen during the years 2000-2020. 32 patients were BRCA1 positive (24%), 10 BRCA2 positive (7%) and 92 without BRCA1/2 mutation (69%). The follow- up time was...

Submitted by LUCIANA GURGEL DA TRINDADE MEIRA HENRIQUES (gustavoluciana@globo.com) on 2016-11-18T17:11:15Z No. of bitstreams: 1 LUCIANA GURGEL TRINDADE HENRIQUES.pdf: 1198247 bytes, checksum: 3ce5ab865cdb5ea1c6e1973bf14b8d1a (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-11-23T19:59:02Z (GMT) No. of bitstreams: 1 henriques_lgtm_dr_bot.pdf: 1198247 bytes, checksum: 3ce5ab865cdb5ea1c6e1973bf14b8d1a (MD5) / Made available in DSpace on 2016-11-23T19:59:02Z (GMT). No. of bitstreams: 1 henriques_lgtm_dr_bot.pdf: 1198247 bytes, checksum: 3ce5ab865cdb5ea1c6e1973bf14b8d1a (MD5) Previous issue date: 2016-09-21 / Introdução: o carcinoma de mama é uma das principais causas de morte no mundo e seu diagnóstico e tratamento precoces tem importante impacto na evolução clínica. A classificação imunoistoquímica (IHQ) determina o prognóstico do carcinoma e qual a melhor forma terapêutica a ser instituída. Autores sugerem que a cintilografia mamária poderia auxiliar a IHQ nessas definições de prognóstico. Casuística e Métodos: este estudo incluiu pacientes portadoras de carcinoma invasivo da mama que tiveram seu diagnóstico no período de 2011 a 2013 no Hospital das Clínicas da Faculdade de Medicina de Botucatu. Em todos os casos foram feitos exames imunoistoquímicos, determinando o índice proliferativo (IP) e a classificação. Associação entre ambos e os achados da cintilografia mamária foram analisadas. Resultados: dos 310 pacientes com carcinoma invasivo de mama diagnosticados no período, 243 tiveram sua classificação e IP definidos pela IHQ. Cintilografia normal está associada a baixo IP e a classificações responsivas à hormonioterapia. As pacientes com cintilografia alterada tiveram mais chance de ter IP maior ou igual a 14%, com alta acurácia, alto valor preditivo positivo e alta sensibilidade, e estão significativamente associadas a formas irresponsivas ao tratamento hormonal. Alterações mais intensas associam-se com formas de pior prognóstico. Conclusão: cintilografia mamária alterada em pacientes com diagnóstico histológico de carcinoma invasivo de mama indicam um pior prognóstico, bem como a normalidade indica a existência de classificação tumoral com melhor resposta à quimioterapia hormonal. Esses achados não permitem que a cintilografia de mama substitua a realização do painel prognóstico imunoistoquímico no tratamento dessa doença, mas sim possa orientar o prognóstico e responsividade a droga. Palavras chaves: carcinoma invasivo de mama; imuno-histoquímica; cintilografia mamária; radioisotopo; medicina nuclear. / Introduction: Breast carcinoma is one of the leading causes of deaths in the world and its early diagnosis and treatment have an important impact in the clinic evolution. The Immunohistochemical (IHC) profile determines the prognosis of the carcinoma and which is the best therapy to be established. Authors suggest that scintimammography could help immunohistochemistry (IHC) in these prognosis definitions. Methods: This study included patients with invasive breast carcinoma who were diagnosed in the period of 2011- 2013 at the Hospital das Clinicas of the Medical School of Botucatu. In all of the cases, IHC exams were performed, determining the proliferative index (PI) and the classification. The association between both results and the scintimammography (SMG) findings were analyzed. Results: of the 310 patients with invasive breast carcinoma diagnosed in the period, 243 had their classification and PI defined by the IHC. Normal SMG is associated to low PI and to hormonal therapy responsive classifications. The patients with altered SMG have had more chances of having a PI greater or equal to 14%, with high accuracy, high positive predictive valor and high sensibility, and are significantly associated to hormonal therapy irresponsive forms. More intense alterations are associated with forms of poor prognosis. Conclusion: altered SMG in patients with histological diagnosis of invasive breast carcinoma indicate a worse prognosis, as well as normaly indicates the existence of tumor classification with better response to hormonal chemotherapy. These findings do not allow the replacement of the immunohistochemistry prognosis profile for the scintimammography in the treatment of this disease, but can guide the prognosis and responsiveness to drug. Key Words: invasive breast carcinoma; immunohistochemistry; scintimammography; radioisotope; nuclear medicine.

Philosophiae Doctor - PhD / Globally, breast cancer is the most common cancer affecting women and it is predicted that in 2030 about 12 million deaths will occur with approximately 21.7 million new cases [2]. Genetic risk factors as well as race and ethnicity, account for about 5-10% of all breast cancer occurrences. Triple negative breast cancer (TNBC), tumors that tested negative for oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), contribute to 10-20% of all breast carcinomas [3,4] and is known to be a more aggressive type of cancer with varying degree of response to chemotherapeutic and radiation therapy [5,6] / 2022-02-24

Protein product tumor suppressor PALB2 gene plays a major role in pathway of DNA repair of double-strand breaks throught the homologous recombination mechanism. Significance of its pathogenic variants in hereditary forms of breast cancer in BRCA1/2- negative patients in families with multiple breast cancers may be in the Czech Republic comparable with the BRCA2 gene. A role of the PALB2 gene in sporadic breast cancer occurence, which represent 90 - 95 % of all cancers, is still unknown. This thesis focuses on inactivation pathway of tumor suppressor PALB2 in the sporadic breast cancer by a mechanism of allelic loss detecting by loss of heterozygosity (LOH) of corresponding microsatellite markers and hypermethylation of promoter region as the most common mechanisms of inactivation tumor suppressors in early tumorigenesis. In a group of 51 nonselected patients with sporadic breast cancer we found four samples with PALB2 locus allelic loss. These samples were analyzed for somatic mutations. No mutation was found. There is no evidence of promotor hypermethylation in any of the samples. Our data suggest a role of the PALB2 gene inactivation in a minority group of sporadic breast cancers.

The thesis "Psychological and social aspects of coping with oncological gynecokogical illnesses (focused on breast cancer)" studies the demands and difficulties which women diagnosed with breast cancer are delaing with. In the theoretical part, attention is given to breast tumor and to the stages of the illness. It shows the needs and problems the women face and the possibilities of psychological help. This part of my thesis also describes different types of cure and its specifics and the changes it brings to the women's life. It is followed by coping strategies and defence mechanisms. In conclusion, the effects of the illness on personal relationships are outlined. In the empirical part, we map supporting psychological and other factors which helped with the treatment and with coping with it. The empirical part comprises 11 individual interviews with women who had breast cancer. The research methodology is supplemented with The Life Satisfaction Inventory. In the interviews we also focused on the factors of health care which were helping and the ones that could be improved. The results of the mapping qualitative study indicated two most important factors which helped the women to cope with this serious illness. It was social support and active coping strategies. In the sphere of health care, the...

Submitted by admin tede (tede@pucgoias.edu.br) on 2018-06-19T18:25:16Z No. of bitstreams: 1 DANIEL RODRIGUES DE BASTOS.pdf: 1922893 bytes, checksum: 51e3aa82ceb630f944c3c65627dcffaa (MD5) / Made available in DSpace on 2018-06-19T18:25:16Z (GMT). No. of bitstreams: 1 DANIEL RODRIGUES DE BASTOS.pdf: 1922893 bytes, checksum: 51e3aa82ceb630f944c3c65627dcffaa (MD5) Previous issue date: 2017-05-04 / Introduction: Breast cancer is the most frequent neoplasm among women worldwide and represents the leading cause of death in this population. Important biomarkers have been studied in order to better define the prognosis of patients affected by this cancer. MicroRNAs are small molecules of non-coding RNAs composed of 21 to 25 nucleotides that play an important role in the post-transcriptional regulation of several genes. Objective: The objective of this study was to evaluate the expression of microRNAs (miRNAs: hsa-miR-7 and hsa-miR-10b) and BRCA1 protein in breast cancer samples, as well as the possible associations between expression of these markers with clinicopathological and prognostic aspects. Method: The study included 92 cases of breast carcinoma from Hospital Araújo Jorge, Associação de Combate ao Câncer em Goiás. Formalin fixed paraphin embedded samples were used for the analisis. MicroRNA was extracted from the samples and used for cDNA synthesis. The cDNA samples were adjusted to the same concentration and submitted to quantitative real-time PCR (qRT-PCR). Samples were further evaluated by immunohistochemistry for BRCA1 expression. Results: From a group of 234 immunohistochemical records, 56 cases of non-triple-negative and 36 triple-negative breast carcinomas were selected. Five-year overall survival was significantly associated to triple negative phenotype (p = 0.044), advanced stages (p = 0.005), lymph node involvement (p = 0.038), presence of distant metastasis (p = 0, 0008) and absence of BRCA1 expression (p = 0.039). Significant associations were demonstrated between the absence of BRCA1 and the triple-negative phenotype (p = 0.0346), as well as the absence of estrogen receptor expression (p = 0.006) and absence of progesterone receptor expression (p = 0.0163). The analysis by qRTPCR demonstrated different levels of miR-10b and miR-7 expression in the tumors, with significant associations with triple-negative phenotype (p = 0.021, p = 0.042) and the absence of BRCA1 (p = 0.039, p = 0.006). The comparison between absence and presence of human epidermal growth factor receptor expression showed a significant difference for miR-7 (p = 0.031), and the expression of miR-10b in these cases was not statistically different (p = 0.926). Conclusion: Significant associations were demonstrated between the absence of BRCA1 and the triple-negative phenotype. Five-year overall survival was reduced for the triple-negative phenotype patients, clinical stages III and IV, the presence of lymph node metastasis, the presence of distant metastasis and the absence of BRCA1 expression. This study also demonstrated that hsa-miR-7 and hsa-miR-10b are significantly associated with the absence of BRCA1 expression and triple-negative phenotype, with poorer survival in these patient profiles. Studies with more cases and with cell lines should be performed in order to confirm the role of hsa-miR-7 and hsa-miR-10b in the modulation of BRCA1 expression. / Introdução: O câncer de mama é a neoplasia mais frequente entre as mulheres de todo o mundo e representa a principal causa de morte nesta população. Importantes biomarcadores têm sido estudados, a fim de definir melhor o prognóstico de pacientes acometidas por esta doença. Os microRNAs são pequenas moléculas de RNAs não codificantes, compostos por 21 a 25 nucleotídeos e desempenham importante papel na regulação pós-transcricional de diversos genes. Objetivo: O objetivo do estudo foi avaliar a expressão de microRNAs (miRNAs: hsa-miR-7 e hsamiR- 10b) e da proteína BRCA1 em amostras de câncer de mama, bem como as possíveis associações entre a expressão desses marcadores e os aspectos clinicopatológicos e prognósticos. Método: O estudo foi composto por 92 casos de carcinoma de mama, provenientes do Hospital Araújo Jorge, da Associação de Combate ao Câncer em Goiás. Foram utilizados fragmentos de tumores incluídos em parafina. A extração de microRNA das amostras foi realizada e o produto gerado foi utilizado para a síntese de cDNA. As amostras de cDNA foram ajustadas para igual concentração e submetidas à PCR quantitativa em tempo real (qRT-PCR). As amostras foram avaliadas ainda por meio de imuno-histoquímica para expressão de BRCA1. Resultados: Um total de 234 registros de imuno-histoquímica foi avaliado, resultando em 56 casos de carcinomas de mama apresentando fenótipo não triplonegativo e 36 com fenótipo triplo-negativo. A sobrevida das pacientes em função das características clinicopatológicas demonstrou associações com os casos triplonegativos (p=0,044), estádios mais avançados (p=0,005), acometimento linfonodal (p=0,038), presença de metástase à distância (p=0,0008) e ausência da expressão de BRCA1 (p=0,039). Associações significativas foram demonstradas entre a ausência de BRCA1 e o fenótipo triplo-negativo (p=0,0346), entre a ausência da expressão do receptor de estrógeno e ausência da expressão de BRCA1 (p=0,006), e entre o receptor de progesterona e a ausência da expressão de BRCA1 (p=0,0163). A análise por qRT-PCR demonstrou diferentes níveis de expressão de miR-10b e de miR-7, com associações significativas ao fenótipo triplo-negativo (p=0,021; p=0,042) e à ausência de BRCA1 (p=0,039; p=0,006). A comparação entre ausência e presença da expressão do receptor do fator de crescimento epidérmico humano demonstrou diferença significativa para miR-7 (p=0,031), sendo que a expressão de miR-10b nestes casos não foi estatisticamente diferente (p=0,926). Conclusão: Associações significativas foram demonstradas entre a ausência de BRCA1 e o fenótipo triplo-negativo. A sobrevida em cinco anos foi inversamente associada ao fenótipo triplo-negativo, aos estádios clínicos III e IV, à presença de metástase linfonodal, à presença de metástase à distância e à ausência da expressão de BRCA1. Este estudo demonstrou ainda que hsa-miR-7 e hsa-miR- 10b estão significativamente associados à ausência da expressão de BRCA1 e ao fenótipo triplo-negativo, sendo observada pior sobrevida nestes perfis de pacientes. Estudos com maior número de casos e com linhagens celulares devem ser realizados para constatar o papel de hsa-miR-7 e hsa-miR-10b na modulação da expressão de BRCA1.

<p>The incidence of breast cancer is rising steadily in Sweden and the proportion of carcinoma in situ (CIS) has increased appreciably, most likely due to mammography screening. The aim of this study was twofold: (1) to examine risk factors for subsequent invasive breast carcinoma and breast cancer death after primary ductal carcinoma in situ (DCIS) and (2) to study the biology in the progress between in situ and invasive carcinoma.</p><p> In a cohort-study based on 3,398 women with a primary CIS reported to the Swedish Cancer Registry (SCR) 1980-1992, women diagnosed in 1989-1992 ran a relative risk of 0.1 (CI 95%, 0.0-0.9) from dying of breast cancer as compared with women diagnosed in 1980-1982. Women in counties with mammography screening ran a relative risk of 0.2 (CI 95%, 0.0-2.1) for breast cancer death in comparison with women in non-screening counties.</p><p> In a case-control study derived from all 4,661 women with primary CIS reported to the SCR 1960-1992, we investigated risk factors for subsequent invasive breast carcinoma (n=118) and breast cancer death (n=39). Large size and multifocality were found to increase the risk for breast cancer death. Postoperative radiotherapy and mastectomy lowered the risk for ipsilateral invasive cancer.</p><p> The standardised incidence rates (SIR) for invasive breast cancer were estimated in the cohort from 1980-1992. The SIR after primary DCIS and primary lobular carcinoma in situ (LCIS) was 4.5 (CI 95%, 3.7-5.5) and 4.0 (CI 95%, 2.1-7.5), respectively.</p><p> New histopathological classification systems for DCIS were evaluated in 195 women consecutively diagnosed with primary DCIS between 1986-1994. One group with highly differentiated lesions was defined with the EORTC classification system and had an excellent prognosis.</p><p> Histopathological grade and expression of p53, c-erbB-2, Ki 67, hormone receptors, Bcl-2 and angiogenesis were compared in 626 women with either a pure DCIS, a small invasive carcinoma or a lesion with both an invasive and in situ component. When grade was taken into account, no change in tumour markers could be detected that signalled the progression from an in situ stage to invasiveness. All tumour markers correlated to grade and their distribution was very similar in the two components of mixed lesions.</p>

The incidence of breast cancer is rising steadily in Sweden and the proportion of carcinoma in situ (CIS) has increased appreciably, most likely due to mammography screening. The aim of this study was twofold: (1) to examine risk factors for subsequent invasive breast carcinoma and breast cancer death after primary ductal carcinoma in situ (DCIS) and (2) to study the biology in the progress between in situ and invasive carcinoma. In a cohort-study based on 3,398 women with a primary CIS reported to the Swedish Cancer Registry (SCR) 1980-1992, women diagnosed in 1989-1992 ran a relative risk of 0.1 (CI 95%, 0.0-0.9) from dying of breast cancer as compared with women diagnosed in 1980-1982. Women in counties with mammography screening ran a relative risk of 0.2 (CI 95%, 0.0-2.1) for breast cancer death in comparison with women in non-screening counties. In a case-control study derived from all 4,661 women with primary CIS reported to the SCR 1960-1992, we investigated risk factors for subsequent invasive breast carcinoma (n=118) and breast cancer death (n=39). Large size and multifocality were found to increase the risk for breast cancer death. Postoperative radiotherapy and mastectomy lowered the risk for ipsilateral invasive cancer. The standardised incidence rates (SIR) for invasive breast cancer were estimated in the cohort from 1980-1992. The SIR after primary DCIS and primary lobular carcinoma in situ (LCIS) was 4.5 (CI 95%, 3.7-5.5) and 4.0 (CI 95%, 2.1-7.5), respectively. New histopathological classification systems for DCIS were evaluated in 195 women consecutively diagnosed with primary DCIS between 1986-1994. One group with highly differentiated lesions was defined with the EORTC classification system and had an excellent prognosis. Histopathological grade and expression of p53, c-erbB-2, Ki 67, hormone receptors, Bcl-2 and angiogenesis were compared in 626 women with either a pure DCIS, a small invasive carcinoma or a lesion with both an invasive and in situ component. When grade was taken into account, no change in tumour markers could be detected that signalled the progression from an in situ stage to invasiveness. All tumour markers correlated to grade and their distribution was very similar in the two components of mixed lesions.