Landscape of HER2-low metastatic breast cancer (MBC): results from the Austrian AGMT_MBC-Registry.

BACKGROUND: About 50% of all primary breast cancers show a low-level expression of HER2 (HER2-low), defined as immunohistochemically 1+ or 2+ and lack of HER2 gene amplification measured by in situ hybridization. This low HER2 expression is a promising new target for antibody-drug conjugates (ADCs) currently under investigation. Until now, little is known about the frequency and the prognostic value of low HER2-expression in metastatic breast cancer (MBC). PATIENTS AND METHODS: The MBC-Registry of the Austrian Study Group of Medical Tumor Therapy (AGMT) is a multicenter nationwide ongoing registry for MBC patients in Austria. Unadjusted, univariate survival probabilities of progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method and compared by the log-rank test. Multivariable adjusted hazard ratios were estimated by Cox regression models. In this analysis, only patients with known HER2 status and available survival data were included. RESULTS: As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry. Out of 1,729 evaluable patients, 351 (20.3%) were HER2-positive, 608 (35.2%) were HER2-low and 770 (44.5%) were completely HER2-negative (HER2-0). Low HER2-expression was markedly more frequent in the hormone-receptor(HR)+ subgroup compared to the triple-negative subgroup (40% vs. 23%). In multivariable analysis, low HER2 expression did not significantly influence OS neither in the HR+ (HR 0.89; 95% CI 0.74-1.05; P = 0.171) nor in the triple-negative subgroup (HR 0.92; 95% CI 0.68-1.25; P = 0.585), when compared to completely HER2-negative disease. Similar results were observed when HER2 IHC 2+ patients were compared to IHC 1+ or 0 patients. CONCLUSION: Low-HER2 expression did not have any impact on prognosis of metastatic breast cancer in this real-world population.

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.

Clinicopathologic profile of gestational trophoblastic disease.

Much debate exists on factors predicting the development of persistent gestational trophoblastic disease (pGTD). Diagnosis is still limited by following persistently elevated or rising postevacutation beta-human chorionic gonadotropin (beta-hCG) titers. The aim of the present work was to evaluate the hypothesis that the presence of c-erbB-2 oncogene amplification and expression, in combination with parameters such as DNA-content and karyotype of the sex chromosomes, confer an increased risk of developing pGTD. Clinicopathological characteristics were evaluated in 36 cases of gestational trophoblastic diseases (GTD) and analyzed for c-erbB-2 amplification and protein p185 expression using differential polymerase chain reaction (DPCR) and immunohistochemical (IHC) techniques. The DNA-content was determined by image analysis on Feulgen stained nuclear cell preparations and karyotyping for XY chromosomes was performed by fluorescence in situ hybridization (FISH). The data was correlated with histopathological characteristics of GTD. Seventy-five percent (n = 27) of the examined cases showed spontaneous regression after evacuation, including 2 patients who received additional chemotherapy. Twenty-five percent (n = 9) resulted in a persistent or metastatic disease. The median time between antecedent pregnancy and GTD was 45.4 months. Complete remission was achieved in all patients with pGTD after administration of chemotherapeutic agents or adjuvant surgical procedures. Cases with cerbB-2 amplification and expression in combination with DNA hyperploidy showed higher proliferation and more aggressive behavior (2 complete hydatidiform moles with lung and liver metastases, 2 invasive moles and 1 choriocarcinoma). XY karyotype was evident in the choriocarcinoma and in 2 complete hydatidiform moles with advanced stage and DNA hyperploidy. From these results we conclude that c-erbB-2 amplification and/or protein expression in combination with DNA-content show a significant correlation with the proliferative and aggressive potential of GTD, suggesting their combined use as a possible marker for pGTD.