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1.
Arch Gynecol Obstet ; 308(3): 935-940, 2023 09.
Article in English | MEDLINE | ID: mdl-36872392

ABSTRACT

PURPOSE: Breast surgery is usually performed under general anesthesia. Tumescent local anesthesia (TLA) offers the possibility to anesthetize large areas with highly diluted local anesthetic. METHODS: In this paper, the implementation, and experiences with TLA in the field of breast surgery are discussed. CONCLUSION: For carefully selected indications, breast surgery in TLA represents an alternative to ITN.


Subject(s)
Anesthesia, Local , Breast Neoplasms , Humans , Female , Anesthetics, Local , Mastectomy , Breast Neoplasms/surgery
2.
Urologe A ; 60(9): 1159-1166, 2021 Sep.
Article in German | MEDLINE | ID: mdl-34255127

ABSTRACT

In the context of cancer surgery, there is always a trade-off between oncological safety and preservation of function. This is especially true in pelvic surgery due to the close relationship to the pelvic floor muscles, blood supply and nerves. Currently, risk models, preoperative imaging, the surgeon's assessment, and the intraoperative frozen section serve as the basis for decision-making. New imaging techniques and standardization in frozen section have significantly improved this in recent years. However, limitations remain due to time delays as well as more difficult correct anatomical assignment in the follow-up. Alternative intraoperative techniques may overcome this limitation in the future. Patient-derived organoids have emerged as an important new research vehicle in recent years. They are based on tumor stem cells that, under special culture conditions, form three-dimensional replicas of the original tissue. This makes them ideally suited for testing individual system therapies but also as a validation technique for new intraoperative diagnostic procedures. The Research Training Group 2543/I, which is funded by the German Research Foundation, is researching the potential of new diagnostic methods in an interdisciplinary team regarding validation in addition to intraoperative frozen sections.


Subject(s)
Frozen Sections , Organoids , Humans , Pelvis
3.
Arch Gynecol Obstet ; 303(1): 181-188, 2021 01.
Article in English | MEDLINE | ID: mdl-33146769

ABSTRACT

PURPOSE: Postoperative seromas are a problem in the surgical treatment of breast cancer. The aim of the study was to evaluate whether the lysine-urethane-based tissue adhesive TissuGlu® without drainage is equal/ non-inferior to standard mastecomy with drainage. METHODS: The study was designed as a prospective, randomized, multicentre non-inferiority study comparing the use of TissuGlu® without drainage with standard wound care with a drain insertion in ablative breast procedures. The number of clinical interventions, quality of life and wound complications were followed-up for 90 days in both groups. RESULTS: Although the statistical power was not reached, twice as many clinical interventions were performed in the TissuGlu® group than in the drainage group, especially aspirations of clinically relevant seromas (p = 0.014). The TissuGlu® group produced overall less wound fluid, but developed a clinically relevant seroma (100% vs. 63%) which made an intervention necessary. Less hospitalisation time was observed in the TissuGlu® group, but the complication rate was higher. There was no significant difference in regards to postoperative pain. In summary the non-inferiority of TissuGlu® compared to standard drainage couldn't be reached. DISCUSSION: The present evaluation shows no advantage of the tissue adhesive TissuGlu® in terms of seroma formation and frequency of intervention compared to a standard drainage for mastectomies, but the shorter inpatient stay certainly has a positive effect on the quality of life.


Subject(s)
Breast Neoplasms/surgery , Mastectomy/methods , Plastic Surgery Procedures/adverse effects , Seroma/prevention & control , Surgical Tape , Suture Techniques/adverse effects , Tissue Adhesives/therapeutic use , Adult , Breast Neoplasms/pathology , Drainage/methods , Female , Humans , Lysine/chemistry , Middle Aged , Postoperative Complications/prevention & control , Prospective Studies , Quality of Life , Seroma/epidemiology , Seroma/etiology , Tissue Adhesions , Tissue Adhesives/chemistry , Treatment Outcome , Urethane/chemistry
4.
Breast ; 50: 11-18, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31958661

ABSTRACT

BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.


Subject(s)
Aromatase Inhibitors/adverse effects , Breast Neoplasms/drug therapy , Complementary Therapies , Letrozole/adverse effects , Musculoskeletal Pain/chemically induced , Aged , Arthralgia/chemically induced , Female , Germany/epidemiology , Humans , Middle Aged , Myalgia/chemically induced , Postmenopause
5.
Facts Views Vis Obgyn ; 11(2): 121-126, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31824633

ABSTRACT

Congenital uterine aplasia, also known as Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a condition associated to a non-functional uterus in the presence of functional ovaries. In a setting where surrogacy is illegal (or not accepted) and adoption is the only alternative, neovaginoplasty and subsequent uterus transplantation (UTx) can provide a route to motherhood for women with MRKHS. This review article describes a multistep process by which patients with MRKHS can achieve motherhood with their own biological child. This process involving a careful clinical diagnosis, psychological counselling, assessment of eligibility for neovagina creation and UTx, the surgical treatment, fertility treatment, and long-term follow-up was developed at the Tübingen University Hospital and in close collaboration with Sahlgrenska Academy, University of Gothenburg, Sweden, where the basic experimental and clinical groundwork for UTx was laid and the first-ever UTx procedure was performed.

6.
Arch Gynecol Obstet ; 300(4): 1029-1043, 2019 10.
Article in English | MEDLINE | ID: mdl-31529365

ABSTRACT

PURPOSE: Rare minimal deviation adenocarcinoma (MDA) diagnosed postoperatively as incidental finding of a suspicious cervical lesion at laparoscopy, emphasizing it represents a diagnostic challenge mimicking both benign and malignant cervical lesions with often overlapping imaging characteristics-case report and literature review. CASE PRESENTATION: 35-year-old Gravida with primary infertility presented with a suspicious cervical lesion and complained about menorrhagia, hyper-/dysmenorrhea. Clinical examination was unremarkable, transvaginal scan presented a 42 × 38 × 28 mm sized cervical lesion (i.e. fibroid) without hypervascularization. Unexpectedly, the diagnosis of minimal deviation adenocarcinoma in tissue sample taken from suspicious cervical lesion at laparoscopy was revealed in final pathological report. According to suspected early stage of MDA a radical abdominal hysterectomy (PIVER III/IV), bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic lymphadenectomy was scheduled. Final histology report confirmed: "MDA", G2, FIGO pT1b1, pN0 (0/23 LN) L0 V0 Pn0 R0. RESULTS: Ultrasonography may indicate MDA throughout the examination of vascularization/echogenicity with possibility of mimicking benign lesions with similar characteristics. Magnetic resonance imaging shows no pathognomonic signs for MDA. Subsequently, a review of literature was conducted and main factors affecting the prognosis of MDA considering diagnostic tools, clinical stage, histopathological results and surgical protocols were analyzed. CONCLUSIONS: Minimal deviation adenocarcinoma represents one of rare cervical adenocarcinomas without HPV-association. While it is crucial to differentiate benign from malignant lesions in this subtype, imaging characteristics often overlap and may not provide a specific diagnosis. Therefore, it should be considered in suspicious multicystic cervical lesions and inconclusive PAP-smear. Definitive diagnosis of this subtype should be based on cervical biopsy.


Subject(s)
Adenocarcinoma/pathology , Cervix Uteri/pathology , Uterine Cervical Neoplasms/pathology , Adenocarcinoma/surgery , Adult , Diagnosis, Differential , Female , Humans , Hysterectomy , Lymph Node Excision , Magnetic Resonance Imaging , Postoperative Period , Prognosis , Uterine Cervical Neoplasms/surgery , Vaginal Smears
7.
BJOG ; 126(11): 1328-1335, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31338951

ABSTRACT

Congenital uterovaginal aplasia commonly occurs in Mayer-Rokitansky-Küster-Hauser syndrome. Various methods of neovagina creation exist, including nonsurgical self-dilation, surgical dilation, and surgical procedures involving skin or intestinal transplants. Subsequent uterus transplantation is necessary to enable pregnancy. We review the main characteristics, advantages, and disadvantages of established neovagina creation methods and discuss their suitability regarding subsequent uterus transplantation. Suitability criteria include sufficient vaginal length, absence of previous major intra-abdominal surgery, a natural vaginal axis, and a natural vaginal epithelium. In conclusion, Vecchietti-based laparoscopically assisted neovagina creation provides ideal functional conditions for uterus transplantation. Nonsurgical self-dilation and Wharton-Sheares-George vaginoplasty may also be suitable. TWEETABLE ABSTRACT: This review discusses the main advantages and disadvantages of neovagina creation methods with regard to subsequent uterus transplantation.


Subject(s)
46, XX Disorders of Sex Development/surgery , Congenital Abnormalities/surgery , Gynecologic Surgical Procedures/methods , Mullerian Ducts/abnormalities , Preoperative Care/methods , Transplants , Uterus/transplantation , 46, XX Disorders of Sex Development/physiopathology , Congenital Abnormalities/physiopathology , Female , Humans , Mullerian Ducts/physiopathology , Mullerian Ducts/surgery , Patient Selection , Surgically-Created Structures , Treatment Outcome , Vagina/surgery
8.
Arch Gynecol Obstet ; 299(3): 835-840, 2019 03.
Article in English | MEDLINE | ID: mdl-30607596

ABSTRACT

PURPOSE: This article investigates the qualities and thermal effects of a novel electrosurgical device (PT) which has been designed by ERBE Elektromedizin GmbH, Germany, for the preparation of critical locations such as in skin-sparing or nipple-sparing techniques and compares it to a standard device (SD) in a porcine ex vivo breast model using an heat map generated by infrared thermography. METHODS: In total, 42 abdominal wall specimens of porcine tissue consisting of the skin and the underlying subcutaneous and muscle layer were alternately dissected using one of the devices and pre-settings. During the preparation with the two devices, the epicutaneous temperature was measured by an infrared camera (VarioCam, Jenoptik, Germany) and the maximum temperature as well as the slope of the temperature rise was analysed. RESULTS: The use of PT shows significantly lower values for [Formula: see text] compared to SD. This effect was independent from the chosen mode. Using the same instrument in different modes, the use of AutoCut mode showed a significant reduction of [Formula: see text] at all indicated time points (SD: p < 0.0001 and PT: p < 0.0001). In summary, the combination of AutoCut + PT showed the lowest rise in temperature, whereas the combination of DryCut + SD led to the highest rise in temperature. The temperature difference between these two settings was 13.84 °C, which means a possible temperature reduction of 67% can be achieved by the right choice of device and its tailored mode. CONCLUSIONS: The novel PT shows a significant reduction in epicutaneous temperature and a significant reduction of the slope of temperature rise most probably by a more focused application of energy compared to SD.


Subject(s)
Breast/surgery , Electrosurgery/methods , Thermography/methods , Animals , Breast/pathology , Disease Models, Animal , Female , Swine
9.
Gynecol Oncol ; 153(1): 49-54, 2019 04.
Article in English | MEDLINE | ID: mdl-30635214

ABSTRACT

OBJECTIVE: Hysterectomy is a frequently used therapeutic option for benign gynecological conditions. The purpose of this study was to investigate the incidence and characteristics of unforeseen malignant pathologies of the uterine corpus in a large population-based, single center cohort. METHODS: Patients who underwent hysterectomy for presumed benign conditions between 2003 and 2016 were identified. In cases of unexpected malignancies of the uterine corpus (UUM), available tissue samples were collected and a specialized gynecopathological review was performed. RESULTS: A total of 10,756 patients underwent hysterectomy for benign indications. After chart and gynecopathological review, 45/10,756 (0.42%) cases of unexpected uterine malignancies were confirmed. 33/45 (73.3%) were endometrial carcinomas (UEC) and 12/45 (26.7%) were uterine sarcomas (UUS). 27/33 (81.8%) UEC were FIGO IA, 5/33 (15.2%) FIGO IB and 1/33 (3%) FIGO stage II disease. Endometrioid and serous histotype were present in 31/33 (93.9%) and in 2/33 (6.1%) cases, respectively. 8/12 (66.7%) USS were early stage (FIGO IA or IB); only 3/12 (25.0%) were diagnosed at an advanced stage (≥FIGO II). Fatal outcome was observed in 1 patient diagnosed with UEC and 3 patients diagnosed with UUS. CONCLUSION: Our study shows that diagnosis of UUM is rare (0.42%). The majority of UUM tend to be early stage, making preoperative diagnosis difficult. In case of UEC, patient outcome is generally favorable. Nevertheless, the appropriate surgical approach for hysterectomy for a benign indication should be chosen carefully, taking all preoperative findings into account. Patients should always be informed about the residual risk of UUM.


Subject(s)
Uterine Diseases/diagnosis , Uterine Diseases/surgery , Uterine Neoplasms/diagnosis , Uterine Neoplasms/surgery , Diagnosis, Differential , Female , Germany/epidemiology , Humans , Hysterectomy/statistics & numerical data , Incidence , Neoplasm Staging , Uterine Diseases/epidemiology , Uterine Diseases/pathology , Uterine Neoplasms/epidemiology , Uterine Neoplasms/pathology
10.
BJOG ; 126(1): 65-72, 2019 Jan.
Article in English | MEDLINE | ID: mdl-29992731

ABSTRACT

OBJECTIVE: To study vaginal as opposed to cervical human papillomavirus (HPV) acquisition with regard to true prevalence, HPV types, and the role of co-factors in virgins and after their sexual debut. DESIGN: Prospective epidemiological observational study. SETTING: University hospital specialised in genital malformations. POPULATION: Women diagnosed with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) and undergoing neovaginoplasty between November 2011 and July 2017. METHODS: This is a prospective study including 186 women with MRKHS before and after sexual debut. MAIN OUTCOME MEASURES: Conventional vaginal cytology and different HPV tests were performed at surgery and during routine gynaecological follow-up 1, 3, 6 and ≥ 11 months after surgery and risk factors were documented. RESULTS: The mean age of all women at surgery was 20.1 years (SD 5.4), mean body mass index (BMI) was 22.1 kg/m2 (SD 4.6). In 83 vaginal samples from 41 different women at least one of the HPV tests was positive. Thirty-three different HPV types were detected. The prevalence of 41/186 = 22.0% as well as type distribution are comparable with those found in a young German female population. The overall rate of acquisition was clearly associated with sexual activity and smoking habits. Out of 367 Papanicolaou smears only six were abnormal with Pap IIID (MN II) and no obvious vaginal lesion was detected. CONCLUSIONS: Vaginal HPV prevalence and HPV types in previously virgin women after creation of a neovagina are not different from the acquisition of cervical infections in the general population and is clearly associated with sexual activity and with smoking habits. However, abnormal Papanicolaou smears are rarely seen. TWEETABLE ABSTRACT: Vaginal HPV prevalence after creation of a neovagina is similar to that on the cervix in the general population.


Subject(s)
Papillomavirus Infections/epidemiology , 46, XX Disorders of Sex Development/complications , 46, XX Disorders of Sex Development/surgery , Adolescent , Adult , Congenital Abnormalities/surgery , Female , Humans , Mullerian Ducts/abnormalities , Mullerian Ducts/surgery , Papanicolaou Test/statistics & numerical data , Papillomavirus Infections/diagnosis , Prevalence , Plastic Surgery Procedures , Risk Factors , Sexual Behavior/statistics & numerical data , Smoking/epidemiology , Vagina/surgery , Young Adult
11.
Hum Reprod ; 34(1): 69-78, 2019 Jan 01.
Article in English | MEDLINE | ID: mdl-30428062

ABSTRACT

STUDY QUESTION: Does incisional endometriosis (IE) harbor somatic cancer-driver mutations? SUMMARY ANSWER: We found that approximately one-quarter of IE cases harbor somatic-cancer mutations, which commonly affect components of the MAPK/RAS or PI3K-Akt-mTor signaling pathways. WHAT IS KNOWN ALREADY: Despite the classification of endometriosis as a benign gynecological disease, it shares key features with cancers such as resistance to apoptosis and stimulation of angiogenesis and is well-established as the precursor of clear cell and endometrioid ovarian carcinomas. Our group has recently shown that deep infiltrating endometriosis (DE), a form of endometriosis that rarely undergoes malignant transformation, harbors recurrent somatic mutations. STUDY DESIGN, SIZE, DURATION: In a retrospective study comparing iatrogenically induced and endogenously occurring forms of endometriosis unlikely to progress to cancer, we examined endometriosis specimens from 40 women with IE and 36 women with DE. Specimens were collected between 2004 and 2017 from five hospital sites in either Canada, Germany or the Netherlands. IE and DE cohorts were age-matched and all women presented with histologically typical endometriosis without known history of malignancy. PARTICIPANTS/MATERIALS, SETTING, METHODS: Archival tissue specimens containing endometriotic lesions were macrodissected and/or laser-capture microdissected to enrich endometriotic stroma and epithelium and a hypersensitive cancer hotspot sequencing panel was used to assess for presence of somatic mutations. Mutations were subsequently validated using droplet digital PCR. PTEN and ARID1A immunohistochemistry (IHC) were performed as surrogates for somatic events resulting in functional loss of respective proteins. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, we detected somatic cancer-driver events in 11 of 40 (27.5%) IE cases and 13 of 36 (36.1%) DE cases, including hotspot mutations in KRAS, ERBB2, PIK3CA and CTNNB1. Heterogeneous PTEN loss occurred at similar rates in IE and DE (7/40 vs 5/36, respectively), whereas ARID1A loss only occurred in a single case of DE. While rates of detectable somatic cancer-driver events between IE and DE are not statistically significant (P > 0.05), KRAS activating mutations were more prevalent in DE. LIMITATIONS, REASONS FOR CAUTION: Detection of somatic cancer-driver events were limited to hotspots analyzed in our panel-based sequencing assay and loss of protein expression by IHC from archival tissue. Whole genome or exome sequencing, or epigenetic analysis may uncover additional somatic alterations. Moreover, because of the descriptive nature of this study, the functional roles of identified mutations within the context of endometriosis remain unclear and causality cannot be established. WIDER IMPLICATIONS OF THE FINDINGS: The alterations we report may be important in driving the growth and survival of endometriosis in ectopic regions of the body. Given the frequency of mutation in surgically displaced endometrium (IE), examination of similar somatic events in eutopic endometrium, as well as clinically annotated cases of other forms of endometriosis, in particular endometriomas that are most commonly linked to malignancy, is warranted. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by a Canadian Cancer Society Impact Grant [701603, PI Huntsman], Canadian Institutes of Health Research Transitional Open Operating Grant [MOP-142273, PI Yong], the Canadian Institutes of Health Research Foundation Grant [FDN-154290, PI Huntsman], the Canadian Institutes of Health Research Project Grant [PJT-156084, PIs Yong and Anglesio], and the Janet D. Cottrelle Foundation through the BC Cancer Foundation [PI Huntsman]. D.G. Huntsman is a co-founder and shareholder of Contextual Genomics Inc., a for profit company that provides clinical reporting to assist in cancer patient treatment. R. Aguirre-Hernandez, J. Khattra and L.M. Prentice have a patent MOLECULAR QUALITY ASSURANCE METHODS FOR USE IN SEQUENCING pending and are current (or former) employees of Contextual Genomics Inc. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.


Subject(s)
Biomarkers, Tumor/genetics , Carcinogenesis/genetics , Endometriosis/pathology , Gynecologic Surgical Procedures/adverse effects , Neoplasms/genetics , Adult , Biomarkers, Tumor/metabolism , Canada , Disease Progression , Endometriosis/etiology , Endometrium/pathology , Endometrium/surgery , Female , Germany , Humans , Iatrogenic Disease , Middle Aged , Mutation , Neoplasms/pathology , Netherlands , Retrospective Studies , Signal Transduction/genetics
12.
Int J Hyperthermia ; 35(1): 463-470, 2018.
Article in English | MEDLINE | ID: mdl-30204024

ABSTRACT

PURPOSE: The aim of the study was to evaluate the efficacy of high intensity focused ultrasound (HIFU) in the treatment of symptomatic breast fibroadenomas (FA) after 6 and 12 months. MATERIALS AND METHODS: Between December 2013 and November 2014, 27 patients with histologically confirmed FA received one application of HIFU under local anesthesia (NCT02011919). Follow-up visits occurred after 6 and 12 months measuring the FA volume and clinical symptoms. A volume reduction of more than 65% was defined as success. Core needle biopsy (CNB) was offered after 12 months if indistinct residuals were visible on ultrasound (US). RESULTS: A successful reduction in FA volume after 12 months was achieved in 24/27 patients (89%). At baseline 16 patients (59%) had pain, which was resolved in 63% (10/16). All patients were satisfied with the cosmetic related outcome. Twenty-four patients (89%) would repeat the procedure. After 12 months 21 patients with sonographically indistinct residuals underwent a CNB. There were no vital cells in 86%. Three cases showed vital cells of FA. Retrospectively possible reasons in these three cases were an insufficient treatment due to bad visibility and insufficient fixation of the FA during HIFU and/or a too short follow-up time. CONCLUSION: US-guided HIFU is an effective procedure and a minimally invasive alternative for the treatment of breast FA.


Subject(s)
Fibroadenoma/diagnostic imaging , Fibroadenoma/therapy , High-Intensity Focused Ultrasound Ablation/methods , Adolescent , Adult , Female , Fibroadenoma/pathology , Humans , Middle Aged , Treatment Outcome , Young Adult
14.
Eur J Cancer ; 96: 82-90, 2018 06.
Article in English | MEDLINE | ID: mdl-29679775

ABSTRACT

BACKGROUND: Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. PATIENTS AND METHODS: Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. RESULTS: Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84). CONCLUSIONS: These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. CLINICAL TRIALS NUMBER: CFEM345DDE19.


Subject(s)
Antineoplastic Agents/adverse effects , Aromatase Inhibitors/adverse effects , Breast Neoplasms/drug therapy , Letrozole/adverse effects , Medication Adherence , Postmenopause , Aged , Breast Neoplasms/pathology , Female , Germany , Humans , Middle Aged , Prospective Studies , Risk Factors , Time Factors , Treatment Outcome
15.
Ann Oncol ; 29(5): 1180-1188, 2018 05 01.
Article in English | MEDLINE | ID: mdl-29432521

ABSTRACT

Background: We have previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Inspired by the Cancer Genome Atlas, ProMisE identifies four prognostically distinct molecular subtypes and can be applied to diagnostic specimens (biopsy/curettings) enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier before clinical application. Patients and methods: We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003 and 2013. Primary outcomes of overall, disease-specific, and progression-free survival were evaluated for clinical, pathological, and molecular features. Results: Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 to 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB [89 (19.7%)], stage II [26 (5.8%)], and stage III/IV [61 (13.5%)]. ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognostic marker for progression-free (P = 0.001) and disease-specific (P = 0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, κ 0.88. Discussion: We have developed, confirmed, and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.


Subject(s)
Biomarkers, Tumor/analysis , Endometrial Neoplasms/pathology , Endometrium/pathology , Molecular Diagnostic Techniques/methods , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Biopsy , Disease-Free Survival , Endometrial Neoplasms/genetics , Endometrial Neoplasms/mortality , Female , Humans , Middle Aged , Predictive Value of Tests , Prognosis , Progression-Free Survival , Retrospective Studies , Risk Factors , Survival Analysis
17.
Ann Oncol ; 29(1): 186-192, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29045642

ABSTRACT

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.


Subject(s)
Breast Neoplasms/drug therapy , Letrozole/administration & dosage , Medication Adherence , Aged , Antineoplastic Agents/administration & dosage , Aromatase Inhibitors/administration & dosage , Breast Neoplasms/pathology , Breast Neoplasms/psychology , Chemotherapy, Adjuvant , Female , Humans , Middle Aged , Postmenopause , Prospective Studies
18.
Ann Oncol ; 28(8): 1700-1712, 2017 08 01.
Article in English | MEDLINE | ID: mdl-28838210

ABSTRACT

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.


Subject(s)
Breast Neoplasms/therapy , Adjuvants, Immunologic/therapeutic use , Antineoplastic Agents/therapeutic use , Austria , Breast Neoplasms/pathology , Combined Modality Therapy , Early Diagnosis , Female , Humans , Neoadjuvant Therapy , Radiotherapy , Surgical Procedures, Operative
19.
Eur J Radiol ; 94: 148-153, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28712698

ABSTRACT

PURPOSE: The impact of preoperative MRI on re-excisions and mastectomy rate is discussed controversially in the literature. Aim of this study was to evaluate the effect of preoperative breast MRI on the surgical procedure and rate of repeated surgeries. MATERIAL AND METHODS: A total of 991 consecutive patients in the years 2009 and 2010 with 1036 primary breast cancers were retrospectively analyzed. Sixty percent (599 patients with 626 cancers) received preoperative breast MRI. Planned surgical procedures before and after MRI and numbers of repeated surgeries in patients with (MR+ ) and without preoperative MRI (MR-) were compared. RESULTS: The result of preoperative MRI changed the surgical procedure in 25% (157/626) of the cases. In 81% (127/157), MRI was beneficial for the patients, as otherwise occult carcinomas were removed (n=122) or further biopsy could be prevented (n=5). Mastectomy rates did not differ between MR+ and MR- group (39% vs. 39%). On multiple regression analysis, the MR+ group had a lower chance for repeated surgery (p<0.05). CONCLUSION: Preoperative MRI could lower the chance for repeated surgery in patients with primary breast cancer. The rate of mastectomy did not differ between patients undergoing preoperative MRI and those who did not.


Subject(s)
Breast Neoplasms/pathology , Breast/pathology , Magnetic Resonance Imaging , Mastectomy/statistics & numerical data , Preoperative Care , Reoperation/statistics & numerical data , Adult , Aged , Aged, 80 and over , Breast Neoplasms/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Multivariate Analysis , Neoplasm Staging , Predictive Value of Tests , Retrospective Studies , Unnecessary Procedures , Young Adult
20.
Geburtshilfe Frauenheilkd ; 76(10): 1065-1073, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27761027

ABSTRACT

Introduction: When cancer patients have advanced disease and a primary cure is no longer possible, the focus is on maintaining the patient's quality of life. Recent therapeutic advances in breast cancer treatment mean that even patients with metastatic disease can remain stable for long periods of time. The aim of this study was to look at the health-related quality of life (HRQL) of these patients and compare it with data for the general population and to show the differences in outcomes for different survey instruments used to measure quality of life. Material and Methods: A total of 96 breast cancer patients with metastatic disesae or receiving adjuvant therapy were questioned about their quality of life. Patients were investigated using the established survey instruments EORTC QLQ-C30, EORTC QLQ-BR23, EQ-5D-5L and EQ VAS. All patients filled out questionnaires. Statistical analysis was done using MS Excel and SPSS. Results: Although the questionnaires were completed at the same time, the different questionnaires showed significant differences with regard to the level of stress experienced by the patient. When the EQ VAS questionnaire was used, the patient's current state of health was assessed as significantly better than with the EORTC QLQ-C30. Overall, all aspects of patients' quality of life were found to be in need of optimization and HRQL of patients was significantly poorer in all areas compared to the reference population. Conclusion: To improve the quality of life of patients with metastatic disease, it is necessary to continuously monitor the success of therapy. The choice of survey tools is highly relevant as assessments differ considerably depending on the choice of questionnaire.

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