Liver function indicators in patients with breast cancer before and after detection of hepatic metastases-a retrospective study.

BACKGROUND: Liver metastases are common in patients with breast cancer, and determining the factors associated with such metastases may improve both their early detection and treatment. Given that liver function protein level changes in these patients have not been determined, the aim of our study was to investigate liver function protein level changes over time, spanning 6 months before the detection of liver metastasis to 12 months after. METHODS: We retrospectively studied 104 patients with hepatic metastasis from breast cancer who were treated at the Departments of Internal Medicine I and the Department of Obstetrics and Gynecology at the Medical University of Vienna between 1980 and 2019. Data were extracted from patient records. RESULTS: Aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, lactate dehydrogenase and alkaline phosphatase were significantly elevated when compared to normal range 6 months before the detection of liver metastases (p<0.001) Albumin was decreased (p<0.001). The values of aspartate aminotransferase, gamma-glutamyltransferase, and lactate dehydrogenase were significantly increased at the time of diagnosis compared to 6 months prior (p<0.001). Patient- and tumor-specific parameters had no influence on these liver function indicators. Elevated aspartate aminotransferase (p = 0.002) and reduced albumin (p = 0.002) levels at the time of diagnosis were associated with shorter overall survival. CONCLUSION: Liver function protein levels should be considered as potential indicators when screening for liver metastasis in patients with breast cancer. With the new treatment options available, it could lead to prolonged life.

Residual fibroglandular breast tissue after mastectomy is associated with an increased risk of a local recurrence or a new primary breast cancer".

BACKGROUND: Residual fibroglandular breast tissue (RFGT) following a mastectomy has been claimed to be associated with the occurrence of an in-breast local recurrence (IBLR) or new primary tumor (NP). Yet, scientific evidence proving this assumption is lacking. The primary aim of the study was to verify whether RFGT following a mastectomy is a risk factor for an IBLR or NP. METHODS: This retrospective analysis included all patients that underwent a mastectomy and were followed up at the Department of Obstetrics and Gynecology of the Medical University of Vienna between 01.01.2015 and 26.02.2020. RFGT volume (assessed on magnetic resonance imaging) was correlated with the prevalence of an IBLR and a NP. RESULTS: A total of 105 patients (126 breasts) following a therapeutic mastectomy were included. After a mean follow-up of 46.0 months an IBLR had occurred in 17 breasts and a NP in 1 breast. A significant difference in RFGT volume was observed between the disease-free cohort and the subgroup with an IBLR or NP (p = .017). A RFGT volume of ≥ 1153 mm3 increased the risk by the factor 3.57 [95%CI 1.27; 10.03]. CONCLUSIONS: RFGT volume is associated with an increased risk for an IBLR or NP.

Atezolizumab plus nab-paclitaxel for unresectable, locally advanced or metastatic breast cancer: real-world results from a single academic center in Austria.

PURPOSE: IMpassion130 led to the approval of atezolizumab plus nab-paclitaxel as first-line treatment for patients with unresectable locally advanced or metastatic triple-negative, PD-L1 immune-cell positive breast cancer (BC) by the European Medicines Agency (EMA). The objective of the present study was to investigate the implementation, safety and efficacy of this combination in the initial phase after approval. METHODS: A retrospective data analysis including all BC patients who received atezolizumab and nab-paclitaxel between 1.1.2019 and 31.10.2020 at the Department of Obstetrics and Gynecology and the Department of Medicine 1, respectively, at the Medical University of Vienna, Austria, was performed. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Maier product-limit method. Owing to the retrospective nature of this study, all statistics must be considered exploratory. RESULTS: In total 20 patients were included in the study. Median follow-up was 7.1 months (IQR 5.2-9.1). Median PFS was 3.0 months (SE = .24; 95% CI [2.5; 3.5]). Median OS was 8.94 months (SE = 2.34, 95%CI [4.35; 13.53]). No new safety signals were observed. CONCLUSION: The present study showed a considerably shorter PFS (3.0 vs. 7.5 months) and OS (8.94 vs. 25.0 months) than IMpassion130 putatively owing to the use of atezolizumab in later treatment lines, more aggressive tumors and a study population with higher morbidity compared to the pivotal trial.

Altered Expression of RB and pRB in Tissue Arrays of Primary Breast Cancers and Matched Axillary Lymph Node Metastases.

Objectives: The retinoblastoma (RB) pathway is crucial in the development and progression of many cancers. To better understand the biology of progressive breast cancer (BC), we examined protein expression of the RB pathway in primary BCs and matched axillary lymph node metastases (LM). Methods: Immunohistochemistry was used to evaluate cyclin D1, CDK4/6, RB, phosphorylated RB (pRB), and E2F1 expression in tissue arrays containing cores of 50 primary BCs and matched LM. The number of positive tumor cells and staining intensity were scored. Results: The proteins were localized in the nucleus, while CDK6 was detected in the cytoplasm and CDK4 was found in both. pRB and E2F1 showed higher expression in matched LM than in primary tumors. Expression of these proteins differed significantly by the percentage of positive tumor cells, while proteins in the proximal portion of the RB pathway showed no significant differences. The main path of alteration consisted of high pRB in primary BC, remaining pRB high in the majority of LM, variations occurring in fewer cases. All matched LM of the few primary tumors that had unaltered RB and pRB expression showed changes in RB or pRB expression. Conclusion: Expression of pRB and E2F1 was significantly higher in LM than in primary BC. A majority of cancers with LM showed altered RB or pRB expression, suggesting that proteins downstream in the RB pathway play a critical role in metastatic BC and disease progression. So looking at the RB pathway could be an option for chemotherapy decisions in patients with only few LM.

Patient satisfaction after breast cancer surgery : A prospective clinical trial.

BACKGROUND: This study investigated the impact of curative breast cancer surgery on patient satisfaction concerning cosmetic results and quality of life (QoL). METHODS: In this study 61 participants completed questionnaires to evaluate their QoL and patient satisfaction with cosmetic results following breast cancer surgery. Cosmetic outcomes were evaluated by the breast surgeon and an independent breast specialist using the Harris scale and the breast analyzing tool (BAT). RESULTS: Of the participants 71% completed all 4 follow-up visits, 38 (62%) patients received breast-conserving therapy (BCT) and 23 (38%) received a mastectomy. Surgery-associated complications arose in 2.6% of the patients who received BCT and 17.4% of patients who received a mastectomy. No significant differences in QoL between BCT patients and mastectomy patients were observed immediately after surgery, or after 6 and 12 months. Breast asymmetry, measured using the BAT score, and QoL scores were worst immediately after surgery. The surgeon rated the cosmetic results as better compared to the independent breast expert (p = 0.001). Furthermore, patients aged over 60 years old were less satisfied with the cosmetic outcome compared to younger patients at the time of discharge (p = 0.024). Patients who received a mastectomy were less satisfied when the resected volume was higher. CONCLUSION: Patient satisfaction was lowest immediately after surgery but improved during the following months, despite continued breast asymmetry. For mastectomy patients, a lower resected volume led to a higher satisfaction with cosmetic results. Satisfaction is subjective and cannot be determined from the esthetic satisfaction of the surgeon or using an objective tool measuring breast asymmetry.

Parental feeding practices and the relationship with parents in female adolescents and young adults with eating disorders: A case control study.

OBJECTIVE: Perceived parental influence on diet in early adolescence in the context of the parental relationship had previously not been studied in a clinical sample. The aim of this study was to investigate a possible association between eating disorders and characteristics of the relationship with parents and the parental feeding practices in early adolescence. METHODS: 21 female adolescents and young adults with an eating disorder (ED)-bulimia nervosa or anorexia nervosa-and 22 females without eating disorder (healthy control; HC), aged between 16 and 26, were assessed via self-report questionnaires for problematic eating behaviour, relationship with parents, perceptions of parent's feeding practices at the age of 10-13 years and personality. Statistical evaluation was performed by means of group comparisons, effect sizes, regression analyses and mediator analyses. RESULTS: Adolescent and young adult females with ED reported more fears/overprotection and rejection/neglect by their mothers and less self-responsibility in terms of eating behaviour during adolescence than did the HC. The relationship with the fathers did not differ significantly. Females who perceived more cohesion, rejection/neglect and fears/overprotection by the mother were more likely to suffer from an ED. Rejection/neglect by both parents were associated with less self-acceptance of the young females with even stronger effect sizes for the fathers than the mothers. Harm prevention in the young females was a partial mediator between fears/overprotection and the drive for thinness. CONCLUSIONS: The parental relationship is partly reflected in the self-acceptance and self-responsibility in eating of the adolescent and young females, both of them are particularly affected in EDs. Stressors in the parent-child relationship should be targeted in treatment of eating disorders. Nutritional counselling for parents might be useful in early adolescence.

Complication rates among women undergoing preventive mastectomy: An Austrian registry.

Germline variations in the BRCA-1 and BRCA-2 genes are associated with an increased risk of breast cancer. These variants are found in 5% of all breast cancer cases. Prophylactic mastectomy is the most effective risk-reducing method and shows high rates of patient satisfaction and acceptance. We established a registry of Austrian BRCA-1 and BRCA-2 mutation carriers who had undergone mastectomy for oncologic or prophylactic reasons. Data were collected on the type of operation, complications, and type of reconstructive surgery for patients between 2014 and 2017. The complication rate in patients with nipple-sparing mastectomy was significantly lower (23.1%) than in those with other types of mastectomies (60.7%; P = .005). In patients with implant-based breast reconstruction, subpectoral placement was associated with a significantly higher rate of complications than prepectoral placement (P = .025). Median implant volume was 350 cc (range: 155-650 cc), and a 100-cc increase was associated with doubling of the odds of a complication (regression coefficient = 0.007); based on this finding, some surgeons may decide on using smaller implants. In summary, we identified significant associations between the risk of complications and surgical characteristics, and found host factors like diabetes, BMI, and smoking among Austrian patients with BRCA-1 and BRCA-2 variants.

Receptor Discordance of Metastatic Breast Cancer Depending on the Molecular Subtype.

INTRODUCTION: Almost 30% of all women with early-stage breast cancer develop metastases. Treatment of metastatic disease is often based on the immunohistochemical information of the primary tumor, despite possible discordance of the hormone and Her2 receptor status. OBJECTIVES: The aim of this study was to compare the receptor status of the primary tumor with the metastasis, and to evaluate for receptor discordance with regard to the molecular subtype, receptor status, and the localization of the metastases. METHODS: We retrospectively analyzed the data of all consecutive women with metastatic breast cancer, who underwent treatment at the Medical University Vienna between 2009 and 2016. Associations were calculated using the χ2or Fisher's exact test; years from primary diagnosis to metastatic disease were calculated using the Kaplan-Meier method. RESULTS: We identified 213 metastatic breast cancer patients, of whom 67 (31.5%) showed a discordant receptor status. Out of 32 patients with luminal A subtype, 14 (43.8%) had a switch of at least one receptor; 27 of 53 patients (50.9%) with luminal B subtype and 21 of 32 patients (65.6%) with Her2+ subtype showed receptor discordance; for triple-negative disease, 5 of 19 patients (36.3%) had a switch of at least one receptor. In 63 samples of bone metastases, 13 (20.6%) had discordant estrogen receptor status (p = 0.04). In 55 samples of bone metastases, 35 (63.3%) had discordant Her2 status (p = 0.002). CONCLUSIONS: Our data show high rates of receptor discordance in metastatic breast cancer. Apart from the primary tumor, the immunohistochemical receptor status of the metastasis needs to be verified. This can lead to a change in treatment and prognosis.

Direct-to-implant breast reconstruction: Higher complication rate vs cosmetic benefits.

BACKGROUND: Since skin- and nipple-sparing mastectomies (SSM/NSM) are now considered oncologically safe options, the number of immediate implant-based breast reconstructions (IBBR) has increased. We present our experience with different techniques of immediate and delayed IBBR over a period of 5 years. METHODS: A single center, retrospective, cohort study was performed from January 2008 to January 2013. Complications, reconstructive failure, contralateral adjustment, cosmetic outcome, patient's quality of life, and the thickness of the overlying tissue were compared between different techniques of immediate and delayed IBBR. RESULTS: A total of 180 patients who underwent immediate (n = 148, 82.2%) or delayed (n = 32, 17.8%) IBBR after SSM (n = 62, 34.4%), NSM (n = 21, 11.7%), or total mastectomy (n = 97, 53.9%) were included. The mean follow-up was 46 months. Immediate IBBR was associated with better cosmetic outcomes (P = 0.026), fewer surgical interventions (P = 0.017), and better quality of life (P = 0.004). Patients with NSM showed the best quality of life results (P =< 0.001) and the best cosmetic outcome (P = 0.001). While immediate IBBR with direct-to-implant procedures achieved a trend toward best cosmetic outcomes (P = 0.66), it was associated with the highest complication rate (37.1%) compared to permanent expanders (10.5%) and a two-stage expander-to-implant procedure (22.9%; P = 0.013) without a significant difference in the rate of implant loss (P = 0.51). CONCLUSION: Whenever oncologically feasible, immediate IBBR should be offered to the patient. The advantages of immediate IBBR with a direct-to-implant procedure such as better cosmetic outcome and fewer surgical interventions should be weighed up against the relatively high overall complication rate associated with this procedure.

PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic breast cancer.

BACKGROUND: Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN). This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients. METHODS: Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution. We analyzed PTEN status by immunohistochemistry of 115 available tumor tissues and analyzed associations with other histopathological parameters, response rate, progression free survival (PFS) and overall survival (OS) with a median follow-up of 60 months. RESULTS: Eighty patients were PTEN positive (69.6%) and 35 patients PTEN negative (30.4%). We found a significant association of the expression of PTEN and p53 (p = 0.041), while there was no association with grading, hormone receptor status, IGFR or MIB. We found significantly more cases with progressive disease under trastuzumab-based therapy in patients with PTEN positive breast cancers (p = 0.018), while there was no significant correlation with PFS or OS. CONCLUSION: In Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS.