Abstract Background Comparative studies on the use of meshes and acellular dermal matrices (ADM) in implant-based breast reconstruction (IBBR) have not yet been performed. Methods This prospective, ...randomized, controlled, multicenter pilot study was performed at four Austrian breast cancer centers. Fifty patients with oncologic or prophylactic indication for mastectomy and IBBR were randomized to immediate IBBR with either an ADM (Protexa® ) or a titanized mesh (TiLOOP® Bra). Complications, failed reconstruction, cosmetic outcome, patients' quality of life and the thickness of the overlying tissue were recorded immediately postoperatively and 3 and 6 months after surgery. Results 48 patients participated in the study (Protexa® group: 23; TiLOOP® Bra group: 25 patients). The overall complication rate was 31.25% with similar rates in both groups (Protexa® group: 9 versus TiLOOP® Bra group: 6; p = 0.188). There was a higher incidence of severe complications leading to failed reconstructions with implant loss in the Protexa® group than in the TiLOOP® Bra group (7 versus 2; p < 0.0001). An inverted T-incision technique led to significantly more complications and reconstructive failure with Protexa® (p = 0.037, p = 0.012, respectively). There were no significant differences in patients' satisfaction with cosmetic results (p = 0.632), but surgeons and external specialists graded significantly better outcomes with TiLOOP® Bra (p = 0.034, p = 0.032). Conclusion This pilot study showed use of TiLOOP® Bra or Protexa® in IBBR is feasible leading to good cosmetic outcomes and high patient satisfaction. To validate the higher failure rates in the Protexa® group, data from a larger trial are required. NCT02562170
Objective Aromatase inhibitors are essential as endocrine treatment for hormone receptor-positive postmenopausal breast cancer patients. Menopausal symptoms are often aggravated during endocrine ...treatment. We investigated whether vaginal estriol is a safe therapeutic option to overcome the urogenital side-effects of aromatase inhibitors. Serum hormone levels were used as the surrogate parameter for safety.
Methods Fasting serum hormone levels of ten postmenopausal breast cancer patients receiving aromatase inhibitors were prospectively measured by electro-chemiluminescence immunoassays and gas chromatography/mass spectrometry before and 2 weeks after daily application of 0.5 mg vaginal estriol (Ovestin® ovula), respectively.
Results Two weeks of daily vaginal estriol treatment did not change serum estradiol or estriol levels. However, significant decreases in levels of serum follicle stimulating hormone (p = 0.01) and luteinizing hormone (p = 0.02) were observed. Five out of six breast cancer patients noticed an improvement in vaginal dryness and/or dyspareunia.
Conclusions The significant decline in gonadotropin levels, indicating systemic effects, has to be kept in mind when offering vaginal estriol to breast cancer patients receiving an aromatase inhibitor.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The objective of this study was to describe the experience of genetic testing in Austrian women with a BRCA1 or BRCA2 mutation in terms of preventive measures taken and incident cancers diagnosed. We ...collected clinical information on 246 Austrian women with a BRCA1 or BRCA2 mutation tested between 1995 and 2012 and followed 182 of them for an average of 6.5 years. Of the 90 women who were cancer‐free at baseline, 21.4% underwent preventive bilateral mastectomy, 46.1% had preventive bilateral salpingo‐oophorectomy, and 1 took tamoxifen; 58.8% of the at‐risk women underwent at least one screening breast magnetic resonance imaging (MRI). Of the 85 women with breast cancer, 69.4% had a unilateral mastectomy or lumpectomy and 30.6% had a contralateral mastectomy. In the follow‐up period, 14 new invasive breast cancers (6 first primary and 8 contralateral), 1 ductal carcinoma in situ case, 2 incident ovarian cancer cases, and 1 peritoneal cancer were diagnosed. In Austria, the majority of healthy women with a BRCA1 or BRCA2 mutation opt for preventive oophorectomy and MRI screening to manage their breast cancer risk; few have preventive mastectomy or take tamoxifen.
BRCA1/2 mutations predispose to early onset breast and ovarian cancers. The phenotypic expression of mutant alleles, however, is thought to be modified by factors that are also involved in the ...pathogenesis of sporadic breast cancer. One such protein is IGF-I, one of the strongest mitogens to breast cancer cells in vitro. We have utilized immunohistochemistry to compare the intratumoral IGF-I and IGF-I receptor (IGF-IR) protein expression in 57 BRCA1/2 mutation carriers and 102 matched breast cancer patients without a family history in a nested case–control study. BRCA1 silencing by siRNA was used to investigate the effect of BRCA mutations on IGF-I protein expression. IGF-I protein expression was detected in tumoral epithelium and surrounding stroma, and was significantly upregulated in tumors of BRCA mutation carriers when compared with matched sporadic tumors (epithelial: 87.7% vs 61.8%, P=0.001; stromal: 73.7% vs 34.3%, P<0.001). By contrast, IGF-IR protein expression was confined to malignant epithelium and was unchanged in mutation carriers (52.6% vs 39.2%, P=0.310). While in mutation carriers IGF-IR protein expression was significantly correlated with both epithelial (P=0.003) and stromal IGF-I (P=0.02), this association was less pronounced in sporadic breast cancer (P=0.02 respectively). siRNA-mediated downregulation of BRCA1 in primary human mammary gland cells triggered upregulation of endogenous intracellular IGF-I in vitro. The increased intratumoral IGF-I protein expression in BRCA mutation carriers suggests an involvement of the IGF-I/IGF-IR axis in the biological behavior of breast cancers in this population and could define a potential therapeutic target.
Endometriosis is an estrogen-dependent gynecological disease causing pelvic pain and infertility. Impaired estrogen metabolism is thought to play a pivotal role in the pathogenesis of the disease. ...While there is some information on factors involved in the synthesis of E2, information on E2-deactivating enzymes is still very limited. To elucidate the intracrinology of endometriotic tissues, the authors analyze the expression of aromatase and E2-inactivating estrogen sulfotransferase (EST) in paired biopsies obtained simultaneously from the endometrium and from endometrial lesions of each of 35 patients with peritoneal or ovarian endometriosis and in cycling endometria from 33 women without endometriosis. Protein localization was demonstrated by immunohistochemistry. Aromatase expression was found in endometriotic glands in 32 of 35 cases and was elevated in comparison to corresponding uterine endometria (25 of 35 cases, P = .021, chi(2) test). The difference was even more pronounced when uterine endometria from endometriosis patients were compared with that of healthy controls (8 of 33 cases, P < .001, chi(2) test). The EST levels were essentially unchanged. The elevated expression of aromatase in eutopic and ectopic endometrium from patients with endometriosis in the presence of comparable EST provides further evidence for unopposed local biosynthesis of estrogens in endometriosis.
The human papillomavirus (HPV) plays an important role in the progression of cervical carcinoma. High-risk (HR) HPV types have been mainly identified in cytologic high-grade squamous intraepithelial ...lesions (HSILs) and histologic invasive carcinoma of the cervix. We examined cervical swabs of patients with abnormal Papanicolaou (Pap) smears, diagnosed as low-grade squamous intraepithelial lesions (LSILs) including atypical squamous cells of uncertain significance or HSILs. Low-risk (LR) HPV and HR-HPV types were identified by the Digene Hybrid Capture II test. Two-dimensional (2D) gel electrophoresis was used to specify the physical state of HPV DNA sequences. Expression of E6/E7 messenger RNA (mRNA) transcripts was analyzed by reverse transcriptase-polymerase chain reaction. Histopathologic results were correlated to the patients' physical status and HPV DNA mRNA transcripts. Pap smears with HPV infections of LR and HR types were correlated to the degree of squamous intraepithelial lesions (SILs). Comparing the physical states of HPV DNA sequences with the expression of HPV E6/E7 mRNA transcripts, all types were identified only as extrachromosomal in benign cervical smears, cervical intraepithelial neoplasia (CIN) I and II. HPV16 showed all physical states in CIN III/carcinoma in situ (CIS), whereas HPV18 only existed in mixed and integrated forms. HPV31/33/52b/58 appeared in all stages of lesions most commonly in extrachromosomal form; in integrated form, they were present only in CIN III/CIS. Although integration of some HR-HPV types is not always necessary for progression of SILs, the above-mentioned method is useful to analyze the physical state of HPV DNA sequences and predict the progression of SILs.
BRCA-1/2 germline mutations are responsible for early onset breast cancer and familial association. The underlying causes of the characteristic phenotypic behavior are not completely understood, but ...mammary stem cells appear to have a key role in this process.
We have investigated the presence of mammary stem / progenitor cells in normal tissues and in tumor tissues obtained from women with and without BRCA1/2 germline mutations by utilizing ALDH-1 immunohistochemistry.
Isolated ALDH-1 positive cells were found in 15/28 (54%) of breast cancer samples from women with BRCA 1 or 2 mutations and in 33 /51 (65%) of matched sporadic breast cancer cases (p=0.5949, Chi Square test). While mammary stem cells were also detected in non-malignant breast lesions, only 41% of the tissues contained ALDH-1 positive cells (p=0.0371, Chi Square test). In patients with BRCA germline mutations ALDH-1 positive cells were more common in p53 positive (p=0.0028, Chi Square test) tumors, in high grade (p=0.0796), and in larger tumors (p=0.0604), while no such association was seen in sporadic cancer cases. In our patients, the expression of ALDH-1 positive cells in breast cancer was neither associated with disease-free and overall survival, nor time to metastasis.
Breast cancers from BRCA mutation carriers do not harbor more ALHD-1 positive cells than sporadic tumors, and their more aggressive phenotype can thus not be explained by an increased stem cell pool. The presence of ALDH-1 in normal breast tissue suggests that additional factors determine the biological behavior of mammary stem cells.
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