Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE.

BACKGROUND: In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses. PATIENTS AND METHODS: KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/axilla at surgery after NACT containing a taxane (± anthracycline, ± platinum) and trastuzumab (± pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS). RESULTS: The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (∼65% versus ∼82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the T-DM1 arm (13.5% versus 3.8%), but there was no grade ≥3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT [hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67], non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.22-0.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence. CONCLUSIONS: T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.

[Is preoperative bone scintigraphy in early stage of breast cancer T1N0 indicated and meaningful?]. / Je predoperacní scintigrafie skeletu v casném stadiu karcinomu prsu T1N0 indikovaná a smysluplná?

In the Czech Republic bone scintigraphy has still been performed routinely as a part of preoperative staging examinations of early breast carcinomas, which had been in 42% diagnosed in the national breast cancer screening program. The incidence of synchronnous distant metastases was analysed for a subgroup of T1N0 breast carcinomas using the database of the Czech National Cancer Registry. Out of 21,675 women with T1N0 breast carcinomas diagnosed in the decade of 2001-2010 the potential occurence of various distant metastases (M1) was estimated in 147 cases (0,68%). Since only approximately 40% of all distant metastases were skeletal (M1 OSS), the pro-bability of bone metastases in T1N0 breast cancer does not exceed 0,3-0,4%. Distant metastases were present in 0,5% in a subgroup of well and moderately differentiated carcinomas and up to 1,2% in poorly differentiated and anaplastic tumors, however, only a minor part (0,2% and 0,5%, respectively) involved bones. We conclude that preoperative bone scintigraphy is overused and undue in more than 99% of Czech women with early breast cancer T1N0. Skeletal scintigraphy as a staging procedure for small breast carcinoma T1N0 may perhaps be recommended only postoperatively and very selectively with regards to individual risk factors and symptomatology.

[Breast reconstruction by autologous fat transfer]. / Rekonstrukce prsu prenosem autologního tuku.

INTRODUCTION: Autologous fat tissue transfer has recently become extremely popular in the field of plastic and reconstructive surgery. Fat represents a filling material with ideal properties - it naturally incorporates into tissues and it is autologous, and therefore 100% biocompatible. An increasing number of publications describe the regenerative properties of autologous fat tissue, especially when used in soft tissue with post-radiation damage. The aim of this article is to describe our experience with fat grafting in breasts. MATERIALS AND METHODS: An autologous fat grafting operation consists in 3 phases - harvesting of fat tissue, its processing, and application of the graft. Fat harvesting is similar to classic liposuction. Common methods of fat tissue processing are centrifugation and the use of the PureGraft filter bags. The most important precondition for a favourable result of the operation is the correct graft application. RESULTS: In the period between March 2011 and January 2012, we used this fagrafting to perform surgical breast reconstruction in 15 patients; 8 patients with a breast deformity after partial mastectomy and radiation, 2 patients after complete mastectomy, 2 patients after complete mastectomy reconstructed with the additional use of external expansion, 2 patients after implant reconstruction presenting with subsequent deformity and 1 patient with pectus excavatum. The patients were followed up for 3-12 months. Long-term retention of the graft was considered good. CONCLUSION: By use of fatgrafting, we can achieve excellent results with minimal risk of complications in reconstructive breast surgery. Autologous fat has plenty of advantages when compared to other biomaterials. It is absolutely biocompatible and able to regenerate the surrounding tissue.

[Outcomes of complex therapy in female patients after breast-saving surgery for breast carcinoma at the 1st Surgical Department 1st Faculty of Medicine, Charles University and General University Hospital in Prague during a ten-year follow up period]. / Výsledky komplexní terapie u pacientek s provedeným prs setrícím výkonem pro karcinom prsu operovaných na I. chirurgické klinice 1. LF UK a VFN.

INTRODUCTION: Good longterm outcomes of complex therapy in operable breast cancer can be achieved mainly due to early diagnosis of the tumor, adequate radicality of surgery and adequate oncotherapy. The following outcome criteria are considered significant: long-term survival rate in complete remission, a number of locoregional recurrences and a number of reoperations or mastectomies required by results of final histological examination, patient satisfaction with a cosmetic result of their breast- saving surgery. Comparison of complex treatment results collected from patients who underwent breast-saving procedures performed for breast cancer at our department of surgery with data reported in literature. MATERIAL AND METHODS: Retrospective analysis of data collected from 106 female patients suffering from invasive breast cancer and ductal carcinoma in situ operated at our surgery department from 1998 until mid-2002. The sample included nine patients who underwent surgery after neoadjuvant oncotherapy. The median follow-up time after surgery was 10 years and 7 months. Reresection was indicated based on the following criteria, set up by the authors: outline margin of less than 1 mm in invasive tumors, and in cases of ductal carcinomas in situ and carcinomatous lymphangiopathy their presence directly within the resection line. RESULTS: The patient group included 13 (12.3%) patients with early reoperations. During the follow up period, locoregional recurrence was recorded in 3 (2.8%) patients. A total of 12 (11.3%) patients with generalized breast carcinoma died, their median survival was 6 years and 4 months. A total of 90 (84.9%) patients are surviving with complete remission of the disease. Thecosmetic outcome was evaluated by patients according to a five-point scale. Out of the total of 77 surviving patients who underwent breast-saving procedures, the authors personally contacted 52 subjects (67.5 %). Out of the total, 45 (86.5 %) subjects evaluated the cosmetic outcome as excellent or very good. CONCLUSION: The survival rate with complete remission and satisfactory cosmetic results is considered to be comparable with the data presented in literature. Considering a small number of early reresections or mastectomis and locoregional recurrences our clinic achieved good outcomes.

Comparative analysis of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in colorectal cancer and surrounding normal tissue.

Thymidylate synthase [TS], thymidine phosphorylase [TP] and dihydropyrimidine dehydrogenase [DPD] play the essential role in the activation and catabolism of the fluoropyrimidines used in cancer therapy. Its expression may influence the antitumor activity or toxicity of these drugs. We studied the expression levels of selected enzymes in colorectal tumors and adjacent normal mucosa. The analysis of TS, TP and DPD gene expression was performed using quantitative Real time PCR technique (Roche) in 15 (TS), 64 (TP) and 12 (DPD) of 64 colorectal cancer patients. The mean gene expression of TS, TP and DPD was found to be 3.29; 3.79 and 8.24 in tumors and 1.88; 3.80 and 19.69 in normal mucosa. The corresponding median gene expression was 1.87; 2.32 and 4.50 for tumors and 2.14; 2.63 and 11.64 for normal tissue. We did not find any significant differences in TS, TP and DPD gene expression between colorectal tumor and surrounding mucosa.