Pilot Study of the Mechanism of Action of Preoperative Trastuzumab in Patients with Primary Operable Breast Tumors Overexpressing HER2

Abstract Purpose: To elucidate the mechanism by which trastuzumab, a humanized monoclonal antibody against HER2 with proven survival benefit in women with HER2-positive metastatic breast cancer, mediates its antitumor activity. Experimental Design: A pilot study including 11 patients with HER2-positive tumors treated in a neo-adjuvant setting with trastuzumab was performed. Trastuzumab was administered i.v. at a dose of 4 mg/kg followed by three weekly i.v. doses of 2 mg/kg. The primary tumor was surgically removed 7 days after the last treatment. Surgical samples, tumor biopsies, and lymphocytes from these patients were collected for biological studies. Result: Clinical data indicated one complete pathological remission and four partial remissions using RECIST (Response Evaluation Criteria in Solid Tumors). Trastuzumab was well tolerated and neither serious adverse events nor changes in cardiac function were observed during this short-term treatment and after surgery. The biological data showed that, independent of response, (a) all patients showed high levels of circulating trastuzumab; (b) saturating level of trastuzumab was present in all of the tumors; (c) no down-modulation of HER2 was observed in any tumors; (d) no changes in vessel diameter was observed in any tumors; (e) no changes in proliferation was observed in any tumors; and (f) a strong infiltration by lymphoid cells was observed in all cases. Patients with complete remission or partial remission were found to have a higher in situ infiltration of leukocytes and a higher capability to mediate in vitro antibody-dependent cellular cytotoxicity activity. Conclusions: The results of this pilot study argue against trastuzumab activity in patients through down-modulation of HER2 but in favor of antibody-dependent cellular cytotoxicity guiding efforts to optimize the use of trastuzumab in breast cancer patients

immediate breast reconstruction after mastectomy

Summary Aims There is a general agreement for immediate breast reconstruction in case of in situ tumors, while the reconstruction is often still delayed in cases of invasive cancers or not performed in the elderly cohort. Aim of this review is to investigate the safety of immediate postmastectomy reconstruction for invasive cancers and in the elderly population. Methods and results We reviewed our series and the recent literature on this topic. While there is a general consensus that advanced age is not a contraindication to immediate reconstruction and breast reconstruction can be successfully performed on well-selected elderly patients, many oncologists in Europe do not prefer immediate reconstruction for invasive carcinoma, advocating the risk of delay of the medical adjuvant treatment in case of complications due to the reconstructive procedure. Our experience and a lot of studies suggest that immediate breast reconstruction is a safe and reliable treatment option in case of invasive cancers. However, if postmastectomy irradiation is necessary on the basis of the final pathological finding, this is associated with a high rate of surgical complications and implant loss among patients who underwent immediate reconstruction with prostheses. Moreover, current evidence suggests that postmastectomy radiation therapy also adversely affects autologous tissue reconstruction. Conclusions Immediate breast reconstruction after mastectomy is an integral part of the complete management of breast cancer. Determining the risk of postmastectomy irradiation prior to definitive resection and reconstructive operations may reduce complications and improve aesthetic outcomes by guiding surgical decision making

Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (TAXIS): study protocol for a multicenter, randomized phase-III trial

Abstract Background Complete lymph node removal through conventional axillary dissection (ALND) has been standard treatment for breast cancer patients for almost a century. In the 1990s, however, and in parallel with the advent of the sentinel lymph node (SLN) procedure, ALND came under increasing scrutiny due to its association with significant patient morbidity. Several studies have since provided evidence to suggest omission of ALND, often in favor of axillary radiation, in selected clinically node-negative, SLN-positive patients, thus supporting the current trend in clinical practice. Clinically node-positive patients, by contrast, continue to undergo ALND in many cases, if only for the lack of studies re-assessing the indication for ALND in these patients. Hence, there is a need for a clinical trial to evaluate the optimal treatment for clinically node-positive breast cancer patients in terms of surgery and radiotherapy. The TAXIS trial is designed to fill this gap by examining in particular the value of tailored axillary surgery (TAS), a new technique for selectively removing positive lymph nodes. Methods In this international, multicenter, phase-III, non-inferiority, randomized controlled trial (RCT), including 34 study sites from four different countries, we plan to randomize 1500 patients to either receive TAS followed by ALND and regional nodal irradiation excluding the dissected axilla, or receive TAS followed by regional nodal irradiation including the full axilla. All patients undergo adjuvant whole-breast irradiation after breast-conserving surgery and chest-wall irradiation after mastectomy. The main objective of the trial is to test the hypothesis that treatment with TAS and axillary radiotherapy is non-inferior to ALND in terms of disease-free survival of clinically node-positive breast cancer patients in the era of effective systemic therapy and extended regional nodal irradiation. The trial was activated on 31 July 2018 and the first patient was randomized on 7 August 2018. Discussion Designed to test the hypothesis that TAS is non-inferior to ALND in terms of curing patients and preventing recurrences, yet is significantly superior in reducing patient morbidity, this trial may establish a new worldwide treatment standard in breast cancer surgery. If found to be non-inferior to standard treatment, TAS may significantly contribute to reduce morbidity in breast cancer patients by avoiding surgical overtreatment. Trial registration ClinicalTrials.gov, ID: NCT03513614. Registered on 1 May 2018. www.kofam.ch, ID: NCT03513614. Registered on 17 June 2018. EudraCT No.: 2018–000372-14

Results of the ECHO (Eating habits CHanges in Oncologic patients) Survey: An Italian Cross-Sectional Multicentric Study to Explore Dietary Changes and Dietary Supplement Use, in Breast Cancer Survivors

none21no: The role of a healthy diet in cancer prevention is well recognized. Recent data indicate that following the same advices can also improve cancer survivors' quality of life. Breast cancer (BC) patients are commonly concerned about diet and nutrition and frequently express the need to obtain health-related information and the will to change their diet and lifestyle. Hence, be aware of survivors' dietary changes and information needs is crucial for healthcare professionals to guide them toward optimal lifestyle choices. In order to investigate eating habits changes in a BC survivors' population, we conceived the cross-sectional multicentric study ECHO (Eating habits CHanges in Oncologic patients) Survey. Data were collected from 684 patients, diagnosed with invasive breast cancer, in order to investigate their changes in food consumption, use of supplements, or the beginning of a specific diet, after BC diagnosis. We also examined the sources of information used and if any modification in their diets was reported to the oncologist. We primarily observed that patients increased their consumption of vegetables, pulses, nuts, fruits, wholemeal bread/pasta, grains and fish; while decreasing red and processed meat, refined bread/pasta, baked good and animal fat consumption. Survivors also reported the use of dietary supplements, mainly vitamins, aimed at counteracting therapies' side effects. Changes in nutritional habits were often adopted without asking or informing the oncologist. Despite BC survivors made some positive changes in their nutritional habits, those modifications were mostly pursued by less than half of them, while the majority of patients consumed nutritional supplements after diagnosis. These results, as well as the failure to communicate with the physicians, reinforce the need to both improve the patient-healthcare professional relationship and to develop tailored nutrition counselling and intervention programs for cancer survivors.noneCaprara, Greta; Tieri, Maria; Fabi, Alessandra; Guarneri, Valentina; Falci, Cristina; Dieci, Maria Vittoria; Turazza, Monica; Ballardini, Bettina; Bin, Alessandra; Cinieri, Saverio; Vici, Patrizia; Montagna, Emilia; Zamagni, Claudio; Mazzi, Cristina; Modena, Alessandra; Marchetti, Fabiana; Verzè, Matteo; Ghelfi, Francesca; Titta, Lucilla; Nicolis, Fabrizio; Gori, StefaniaCaprara, Greta; Tieri, Maria; Fabi, Alessandra; Guarneri, Valentina; Falci, Cristina; Dieci, Maria Vittoria; Turazza, Monica; Ballardini, Bettina; Bin, Alessandra; Cinieri, Saverio; Vici, Patrizia; Montagna, Emilia; Zamagni, Claudio; Mazzi, Cristina; Modena, Alessandra; Marchetti, Fabiana; Verzè, Matteo; Ghelfi, Francesca; Titta, Lucilla; Nicolis, Fabrizio; Gori, Stefani