Bone marrow micrometastases do not impact disease-free and overall survival in early stage sentinel lymph node-negative breast cancer patients.

BACKGROUND: The presence of lymph node metastases is the most important prognostic factor in early stage breast cancer. Whether bone marrow micrometastases (BMM) impact the prognosis in sentinel lymph node (SLN)-negative breast cancer patients remains a matter of debate. Therefore, the objective of this study was to assess the impact of BMM on 5-year disease-free and overall survival among those patients. METHODS: We analyzed 410 patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, cN0) who were prospectively enrolled into the Swiss Multicenter Sentinel Lymph Node Study in Breast Cancer between January 2000 and December 2003. All patients underwent bone marrow aspiration followed by SLN biopsy. All SLN were stained with hematoxylin and eosin and immunohistochemistry (Lu-5, CK-22). Cancer cells in the bone marrow were identified after staining with monoclonal antibodies A45-B/B3 against CK-8, -18, and -19. RESULTS: Negative SLN were found in 67.6% (277 of 410) of the enrolled patients. Of those, BMM status was negative in 75.8% (210 of 277) and positive in 24.2% (67 of 277) patients. Median follow-up was 61 (range 11-96) months. Five-year disease-free survival was 93.6% (95% confidence interval [CI] 89.1-96.0) in BMM-negative and 92.2% (95% CI 82.5-96.2) in BMM-positive patients (p = 0.50). Five-year overall survival was 92.7% (95% CI 87.9-95.8) for the BMM-negative and 92.5% (95% CI 83.4-96.2) for the BMM-positive group (p = 0.85). CONCLUSIONS: This is one of the first prospective studies to examine 5-year disease-free and overall survivals in SLN-negative patients in correlation to their BMM status. Although BMM are identified in one of four SLN-negative patients, they do not impact disease-free and overall survival.

Endometrial Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry Number 032/034-OL, September 2022). Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer, Geriatric Assessment and Supply Structures.

Summary The S3-guideline on endometrial cancer, first published in April 2018, was reviewed in its entirety between April 2020 and January 2022 and updated. The review was carried out at the request of German Cancer Aid as part of the Oncology Guidelines Program and the lead coordinators were the German Society for Gynecology and Obstetrics (DGGG), the Gynecology Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Cancer Aid (DKH). The guideline update was based on a systematic search and assessment of the literature published between 2016 and 2020. All statements, recommendations and background texts were reviewed and either confirmed or amended. New statements and recommendations were included where necessary. Aim The use of evidence-based risk-adapted therapies to treat women with endometrial cancer of low risk prevents unnecessarily radical surgery and avoids non-beneficial adjuvant radiation therapy and/or chemotherapy. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimum level of radical surgery and indicates whether chemotherapy and/or adjuvant radiation therapy is necessary. This should improve the survival rates and quality of life of these patients. The S3-guideline on endometrial cancer and the quality indicators based on the guideline aim to provide the basis for the work of certified gynecological cancer centers. Methods The guideline was first compiled in 2018 in accordance with the requirements for S3-level guidelines and was updated in 2022. The update included an adaptation of the source guidelines identified using the German Instrument for Methodological Guideline Appraisal (DELBI). The update also used evidence reviews which were created based on selected literature obtained from systematic searches in selected literature databases using the PICO process. The Clinical Guidelines Service Group was tasked with carrying out a systematic search and assessment of the literature. Their results were used by interdisciplinary working groups as a basis for developing suggestions for recommendations and statements which were then modified during structured online consensus conferences and/or additionally amended online using the DELPHI process to achieve a consensus. Recommendations Part 1 of this short version of the guideline provides recommendations on epidemiology, screening, diagnosis, and hereditary factors. The epidemiology of endometrial cancer and the risk factors for developing endometrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer. The use of geriatric assessment is considered and existing structures of care are presented.

Accuracy of urethral swab and urine analysis for the detection of Mycoplasma hominis and Ureaplasma urealyticum in women with lower urinary tract symptoms.

OBJECTIVES: Our objective was to evaluate and compare the accuracy of urethral swabs and urine specimens in the detection of Mycoplasmas in women with lower urinary tract symptoms (LUTS). METHODS: During a urogynecological work-up, including cystometry, we obtained first-void urine, urethral and vaginal swabs in 207 consecutive women at our urogynecological division. Mycoplasma hominis and Ureaplasma urealyticum as well as other microorganisms were detected by standard culture methods. RESULTS: 131 of 207 women reported LUTS. The other 76 formed the controls. Of 207 women 50 (24.2%) had positive cultures for Mycoplasmas. The prevalence of Mycoplasmas in women with LUTS (30.3%) was statistically significant and higher in the group without LUTS (14.5%) (p = 0.011). The detection of M. hominis was most accurate using urethral swab (Specificity 99.9%, PPV 99.6%) compared to the urine specimen (96%, 75%) and vaginal swab (95.1%, 67%). Similar results could be achieved for U. urealyticum (urethral swab: specificity 98.7%, PPV 96.3%; urine specimen: 86.8%, 72%; vaginal swab: 80.5%, 65.2%). CONCLUSION: In the subgroup of women less than 50 years an (detectable) infection due to Mycoplasma or Ureaplasma leads typically to LUTS with normal filling cystometry, whereas no such findings were relevant for the elderly women.

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) - Part 2 with Recommendations on Psycho-oncology, Rehabilitation, Follow-up, Recurrence, Palliative Therapy and Healthcare Facilities.

Aim This is an update of the interdisciplinary S3-guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL), published in March 2021. The work on the updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process used to update the 2014 S3-guideline was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on the consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which would take account of more recently published literature and the recent appraisal of new evidence. Recommendations The short version of this guideline consists of recommendations and statements on palliative therapy and follow-up of patients with cervical cancer. The most important aspects included in this updated guideline are the new FIGO classification published in 2018, the radical open surgery approach used to treat cervical cancer up to FIGO stage IB1, and the use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) - Part 1 with Recommendations on Epidemiology, Screening, Diagnostics and Therapy.

Aim This update of the interdisciplinary S3 guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL) was published in March 2021. This updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process of updating the S3 guideline dating from 2014 was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on a consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which took account of more recently published literature and the appraisal of the new evidence. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, screening, diagnostic workup and therapy of patients with cervical cancer. The most important new aspects included in this updated guideline include the newly published FIGO classification of 2018, the radical open surgery approach for cervical cancers up to FIGO stage IB1, and use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.

Prognostic impact and therapeutic implications of sentinel lymph node micro-metastases in early-stage breast cancer patients.

The prognostic value of sentinel lymph node (SLN) micro-metastases and the question whether patients with SLN micro-metastases should undergo axillary lymph node dissection remain a matter of great debate. Based on the current literature and on our own data, we provide suggestive evidence that SLN micro-metastases in early stage breast cancer patients appear to have prognostic value and should impact the decision-making regarding adjuvant therapy, however, do not necessarily require further surgical treatment.

Bilateral papillary cystadenoma of the mesosalpinx: a rare manifestation of Von Hippel-Lindau disease.

We report a rare case of a woman with bilateral papillary cystadenomata of the broad ligament with von Hippel-Lindau disease (VHL) (other manifestations: capillary hemangioblastomas of the spinal cord). Patient surveillance is important, because in the course of VHL-associated tumors malignant lesions may arise that are relevant for the prognosis.

Is the current concept of recurrent ovarian carcinoma as a chronic disease also applicable in platinum resistant patients?

PURPOSE: The treatment of recurrent ovarian carcinoma (ROC) has become increasingly oriented according to the therapy principles of a chronic disease. We evaluated whether it is justifiable to also apply this concept to the treatment of platinum resistant patients with their known poor prognosis and short overall survival (OS). METHODS: We analyzed the overall courses of 85 unselected ROC patients and defined the following groups: A, platinum resistant patients (n=39); subgroup A.1, those who received no or at maximum one line of palliative chemotherapy (n=15, 38.5%); subgroup A.2, those who received>or=two therapy lines (n=24, 61.5%); B, platinum sensitive patients, n=46. RESULTS: Group A had significantly lower OS than group B (median: 16 vs. 25 months; p=0.019). Group A.1 had significantly worse outcome compared to group A.2 (median: 5 vs. 21.5 months; p<0.001). The comparison between study group A.2 and group B showed comparable survival rates (p=0.738). Considering only the patients who had completed treatment courses, the median number of therapy lines administered was higher in group A.2 than in group B (4 vs. 3; p=0.008). CONCLUSIONS: There is not only the known dichotomy between platinum sensitive and resistant ROC patients, but rather also within the platinum resistant subgroup itself. There is a considerably large subgroup of platinum resistant patients who will subsequently enter a phase where multiple treatment programs will be considered and administered. These patients have similar survival rates compared to those from the platinum sensitive patient group and the therapy principles of a chronic disease are applicable.

Levels of plasma circulating cell free nuclear and mitochondrial DNA as potential biomarkers for breast tumors.

BACKGROUND: With the aim to simplify cancer management, cancer research lately dedicated itself more and more to discover and develop non-invasive biomarkers. In this connection, circulating cell-free DNA (ccf DNA) seems to be a promising candidate. Altered levels of ccf nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) have been found in several cancer types and might have a diagnostic value. METHODS: Using multiplex real-time PCR we investigated the levels of ccf nDNA and mtDNA in plasma samples from patients with malignant and benign breast tumors, and from healthy controls. To evaluate the applicability of plasma ccf nDNA and mtDNA as a biomarker for distinguishing between the three study-groups we performed ROC (Receiver Operating Characteristic) curve analysis. We also compared the levels of both species in the cancer group with clinicopathological parameters. RESULTS: While the levels of ccf nDNA in the cancer group were significantly higher in comparison with the benign tumor group (P < 0.001) and the healthy control group (P < 0.001), the level of ccf mtDNA was found to be significantly lower in the two tumor-groups (benign: P < 0.001; malignant: P = 0.022). The level of ccf nDNA was also associated with tumor-size (<2 cm vs. >2 cm<5 cm; 2250 vs. 6658; Mann-Whitney-U-Test: P = 0.034). Using ROC curve analysis, we were able to distinguish between the breast cancer cases and the healthy controls using ccf nDNA as marker (cut-off: 1866 GE/ml; sensitivity: 81%; specificity: 69%; P < 0.001) and between the tumor group and the healthy controls using ccf mtDNA as marker (cut-off: 463282 GE/ml; sensitivity: 53%; specificity: 87%; P < 0.001). CONCLUSION: Our data suggests that nuclear and mitochondrial ccf DNA have potential as biomarkers in breast tumor management. However, ccf nDNA shows greater promise regarding sensitivity and specificity.

Three-dimensional pathological size assessment in primary breast carcinoma.

Maximal tumor diameter (MD) is traditionally an important prognostic factor in breast cancer. It must be questioned, however, how well a one-dimensional parameter alone can represent the actual morphologic condition of a three-dimensional body. Along with the pathologically assessed MD and two perpendicular diameters (PDs) of a lesion, eccentricity (EF) and the three-dimensional parameters tumor volume (TV) and surface area (TSA) of 395 ductal invasive breast carcinomas of limited size (10-40 mm) were calculated. The dependent prognostic variable was axillary lymph node involvement (ALNI). MD, TV and TSA area were highly significant predictors of ALNI; these variables had similar levels of prediction accuracy (univariate analyses: MD: P = 0.0003, TV: P = 0.0009, TSA: P < 0.0001; multivariate analyses: MD: P = 0.0018, TV: P = 0.0109, TSA: P = 0.0009; pseudo R-squared values: MD: 0.42, TV: 0.39, TSA: 0.39). Despite certain variations in tumor shape, TV and TSA with similar MD, there is no evidence that three-dimensional pathologic measurements (TV/TSA) are more precise prognostic predictors of ALNI compared to the one-dimensional measurement alone.

Accuracy of frozen section of sentinel lymph nodes: a prospective analysis of 659 breast cancer patients of the Swiss multicenter study.

OBJECTIVE: To assess the accuracy of sentinel lymph node (SLN) frozen section in a prospective multicenter study of early-stage breast cancer patients. SUMMARY BACKGROUND DATA: The decision to perform an immediate completion axillary node dissection (ALND) is based on results of SLN frozen section. However, SLN frozen sections are not routinely performed in all centers. Moreover, the accuracy of SLN frozen section remains a matter of great debate. METHODS: Prospective multicenter trial analyzing 659 early stage breast cancer patients (pT1 and pT2

Axillary lymph node dissection for sentinel lymph node micrometastases may be safely omitted in early-stage breast cancer patients: long-term outcomes of a prospective study.

OBJECTIVES: To evaluate the long-term disease-free and overall survival of patients with sentinel lymph node (SLN) micrometastases, in whom a completion axillary lymph node dissection (ALND) was systematically omitted. BACKGROUND: The use of step sectioning and immunohistochemistry for SLN analysis results in a more accurate histopathologic examination and a higher detection rate of micrometastases. However, the clinical relevance and therapeutic implications of SLN micrometastases remain a matter of debate. METHODS: In this prospective study, 236 SLN biopsies were performed in 234 consecutive early-stage breast cancer patients (T1, T2 .2 mm to

Systemic therapy of metastatic breast cancer: the truth beyond the clinical trials.

OBJECTIVE: To depict a clear and coherent picture of the overall course of palliative treatment in an unselected study cohort over the course of time. METHODS: We compared therapy type and course of 242 women whose distant metastatic disease was diagnosed from 1990 to 2006 and who ultimately died of the disease. We divided the patients into two subgroups depending on the year of diagnosis of metastases (group A: 1998-2006 vs. group B: 1990-1997). RESULTS: In both subgroups, there were no significant differences in the general type of treatment and the number of administered therapy lines (no systemic therapy: 12.9 vs.13.7%, p = 0.848; endocrine therapy only: 20.4 vs. 25.2%, p = 0.430; chemotherapy only: 18.4 vs.16.9%, p = 0.735; sequential combination regimen including endocrine therapy/chemotherapy/trastuzumab: 46.9 vs. 44.2%, p = 0.694; median: 2 lines). In the cases where chemotherapy was administered, there were no differences between the number of lines among older and younger patients (median: two lines; >or=70 years vs. <70 years: p = 0.269). The median metastatic disease-specific survival increased from 16 months in the period from 1990 to 1997, to 21 months in the period from 1998 to 2000 (p = 0.062). CONCLUSION: The number of patients who died from metastatic breast cancer without receiving any antineoplastic therapy was surprisingly high. The use of newer agents and regimens in the treatment of metastatic breast cancer was associated with an improved survival over time. Chemotherapy is a feasible option also among older patients.

Systemic therapy developments and their effects regarding the current concept of recurrent ovarian carcinoma as a chronic disease.

PURPOSE: To demonstrate how the current concept of recurrent ovarian carcinoma (ROC) as a chronic disease resulted in developments in the systemic treatment strategies and outcome over time. METHODS: We compared therapy type and course of a population-based cohort whose recurrent disease was diagnosed from 1990 to 2006. We divided the patients into two subgroups depending on the year of diagnosis of ROC (group A 1990-1997, n = 70; group B 1998-2006, n = 63). RESULTS: Both study groups showed similar results in survival (median recurrent disease-specific survival-A 18 months vs. B 19 months; P = 0.549). In group B, the patients had significantly fewer combination therapies administered [12.0% vs. 24.1%; odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.81; P = 0.0057], received more therapy lines (> or =3 lines 56.1% vs. 31.1%; OR 3.10; 95% CI 1.37-7.17; P = 0.005) and had significantly longer times of treatment (TT) in relation to the survival time (ST; mean TT/ST-ratio 57.5% vs. 47.5%; difference of the mean values B-A = -10.02; 95%CI -17.99 to -2.05; P = 0.014). CONCLUSIONS: The finding that survival of ROC patients could not be improved over time should not necessarily be viewed with undue pessimism regarding the general therapy situation. In the more recent study period, a similar outcome could be achieved with less aggressive treatment regimens, i.e., with fewer combination therapies and with longer treatment periods using less toxic agents. When a disease which requires periodic chemotherapy to control progressive course is increasingly treated with a strategy that permits stabilization with limited cumulative toxicity, then the requirements of a chronic disease management have been fulfilled.

Sexual dysfunction after premenopausal stage I and II breast cancer: do androgens play a role?

INTRODUCTION: Sexual dysfunction after breast cancer has been attributed to a variety of treatment associated and psychological factors. Data on the role of a treatment-induced decrease of testosterone for the development of sexual problems in breast cancer survivors have remained inconclusive. However, androgen metabolites constitute a more reliable measure for total androgen activity. AIM: To measure levels of total androgen activity in breast cancer patients and to investigate relevant predictors of sexual dysfunction after breast cancer. METHODS: Twenty-nine patients with a premenopausal diagnosis of Stage I or II breast cancer and terminated adjuvant treatment, completed questionnaires on sexuality, quality of relationship, body image, and depression. In addition, blood samples were taken for the analysis of sex steroids. MAIN OUTCOME MEASURES: Female Sexual Function Index (FSFI), Relationship (PFB), Beck Depression Inventory, and European Organization for Research and Treatment of Cancer quality of life questionnaire. Analysis of dihydroepiandrosterone, dihydroepiandrosterone-sulfate, androstenedione, 17beta-diol, testosterone, dihydrotestosterone, androsterone, and ADT-G, 3-alpha-diol-3G, 3-alpha-diol-17G. RESULTS: Low levels of sex steroids reflected the medication-induced postmenopausal status independent of the type of chemotherapy treatment. Sexual dysfunction was present in 68% of the study group. Women with a history of chemotherapy were more affected in all of the FSFI-domains. The only predictor for desire was quality of relationship, while chemotherapy was predictive for problems with arousal, lubrication, orgasm, and sexual pain. Sexual satisfaction and higher FSFI sum scores were predicted by better quality of relationship and no history of chemotherapy, together explaining 54.2% and 49.7% of the variance. CONCLUSIONS: Sexual dysfunction after breast cancer is common and women should be informed properly at an early stage of treatment. Specific interventions have to be offered considering person-related preexisting factors and couples at risk should be supported in the transition to sexual life after breast cancer.

Positive correlation of cell-free DNA in plasma/serum in patients with malignant and benign breast disease.

BACKGROUND: Circulating cell-free (ccf) DNA is measurable in healthy individuals and in higher concentration in patients with benign and malignant breast disease (BD). PATIENTS AND METHODS: In paired plasma and serum samples ccf DNA was extracted and quantified by real-time quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. RESULTS: The concentration of ccf DNA in serum was higher in patients with benign and malignant BD (p = 0.023/p = 0.001) compared to healthy controls, whereas ccf DNA in plasma was higher in patients with malignant BD compared to patients with benign BD or healthy controls (p = 0.012/0.007). The ccf DNA correlated significantly between plasma and serum samples in patients with benign (p = 0.01; R: 0.677) as well as malignant BD (p = 0.01; R:0.713). CONCLUSION: The positive correlation between ccf DNA in plasma and serum in patients with benign as well as malignant BD, might have a diagnostic value for discriminating between malignant and benign BD.

[Pregnancy-associated breast cancer]. / Schwangerschaftsassoziiertes Mammakarzinom.

Pregnancy-associated breast cancer is a rare disease with an incidence of 1:3000. There is no indication anymore to terminate the pregnancy since the maternal prognosis will not be influenced. Due to physiologic pregnancy-related changes in the breast, the interpretation of clinical findings, breast ultrasound and mammography is more demanding. There is often a diagnostic delay in detecting pregnancy-associated breast cancer. Mastectomy and axillary lymphonodectomy compose the surgical therapy. In the third trimester, breast conserving surgery and radiotherapy postpartum is an option. Chemotherapy can be administered relatively safe in the second and third trimester. Radiotherapy, hormonal therapy and trastuzumab are contraindicated during pregnancy. Patients with pregnancy-associated breast cancer should be seen and treated in an interdisciplinary setting, preferably in a specialized centre.

Expression of peroxisome proliferator activated receptor gamma and cyclo-oxygenase 2 in primary and recurrent ovarian carcinoma.

AIM: Peroxisome proliferator-activated receptor gamma (PPARgamma) has emerged as a potential therapeutic target in several types of cancer. In ovarian carcinomas, limited and conflicting data on PPARgamma protein expression have been reported. METHODS: The immunoexpression of PPARgamma and its putative target cyclo-oxygenase 2 (COX2) was investigated in tumour tissues from 80 patients with primary and corresponding recurrent ovarian serous carcinomas after conventional platinum-based chemotherapy. RESULTS: PPARgamma expression was observed in 29% of primary and recurrent carcinomas. In the recurrent tumours, PPARgamma expression inversely correlated with COX2 overexpression in both chemosensitive (p = 0.02) and chemoresistant (p = 0.04) carcinomas. CONCLUSIONS: The data indicate that PPARgamma may represent a potential target for second-line treatment in ovarian cancers.

T4 breast cancer under closer inspection: a case for revision of the TNM classification.

The presence of skin involvement in breast cancer results in the classification of the tumor into the highest tumor category, and accordingly into the highest non-metastatic disease stage (current TNM classification: T4/stage III). This traditional view is no longer justifiable, as tumors that show non-inflammatory skin involvement (T4b) make up a considerably heterogeneous group with a high percentage of small-sized tumors. Classifying all lesions demonstrating this feature together results in the combination of tumors with widely differing prognostic and therapeutic implications into a single group. This violates the basic principle of the TNM concept in that only tumors exhibiting similar extension and prognosis should be grouped into one category/stage. Furthermore, the currently valid definitions of non-inflammatory skin involvement are misconceived for the substantial group of small tumors which often have ambiguous morphologic findings: the clinical classification depends on the subjective perception of the individual observer, and the pathologic staging considers histologic criteria that are not justifiable from a functional-morphological point of view. For these reasons, we strongly feel that there is a need to revise the current T4 category. We recommend that breast carcinomas currently classified as T4a-c should be eliminated from the T4 category and classified simply according to their tumor size (T1-3). The prognostically very unfavorable inflammatory carcinoma (T4d) should be maintained as the only clinicopathologic entity in the T4 category. This proposal, which will also lead to a revision of the stage III group, adheres more closely to the goals and principles of the TNM classification than do the current classification guidelines. Through the revision of the T4 category, the definitions and guidelines of inflammatory breast carcinoma should be adapted to the internationally accepted nomenclature.

Comparison of gene expression profiles in core biopsies and corresponding surgical breast cancer samples.

INTRODUCTION: Gene expression profiling has been successfully used to classify breast cancer into clinically distinct subtypes, and to predict the risk of recurrence and treatment response. The aim of this study was to investigate whether the gene expression profile (GEP) detected in a core biopsy (CB) is representative for the entire tumor, since CB is an important tool in breast cancer diagnosis. Moreover, we investigated whether performing CBs prior to the surgical excision could influence the GEP of the respective tumor. METHODS: We quantified the RNA expression of 60 relevant genes by quantitative real-time PCR in paired CBs and surgical specimens from 22 untreated primary breast cancer patients. Subsequently, expression data were compared with independent GEPs obtained from tumors of 317 patients without preceding CB. RESULTS: In 82% of the cases the GEP detected in the CB correlated very well with the corresponding profile in the surgical sample (rs > or = 0.95, p < 0.001). Gene-by-gene analysis revealed four genes significantly elevated in the surgical sample compared to the CB; these comprised genes mainly involved in inflammation and the wound repair process as well as in tumor invasion and metastasis. CONCLUSION: A GEP detected in a CB are representative for the entire tumor and is, therefore, of clinical relevance. The observed alterations of individual genes after performance of CB deserve attention since they might impact the clinical interpretation with respect to prognosis and therapy prediction of the GEP as detected in the surgical specimen following CB performance.