Biopsy of liver metastasis for women with breast cancer: Impact on survival

Abstract Background Biopsy of metastatic site of disease can influence treatment decisions, but its impact on survival remains uncertain. Patients and methods One-hundred patients with first metachronous liver metastases (LM) from breast cancer (BC) who underwent liver biopsy between 1999 and 2009 were identified. One-hundred matched control patients with LM from BC and no biopsy were selected. Results Liver biopsy had no statistically significant impact on survival when comparing biopsied patients to controls [HR 0.82 (95% CI 0.58–1.16)]. Patients with early metastasis (within 3 years) undergoing liver biopsy had a better survival [HR 0.60 (95% CI 0.38–0.97)] compared to those who did not. Liver biopsy had no statistically significant impact on survival in patients with late LM (after 3 years) [HR 1.09 (95% CI 0.69–1.74)]. We observed that 18 out of 100 biopsied patients (18.0%) had a conversion of predictive factors which allowed adjusting for therapy, specifically new expression of ER ( n = 5), overexpression of HER2 ( n = 12) or both ( n = 1). Fourteen out of 18 (77.8%) received anti-HER2 treatment for the first time at the time of metastasis and 3 others (16.7%) received hormone therapy. Those 18 patients showed a better survival compared to the other 82 biopsied patients [HR 0.55 (95% CI 0.28–1.10)] and compared to the 13 biopsied patients with disappearance of features which predicted responsiveness to a given treatment [HR 0.19 (95% CI 0.06–0.62)]. Conclusions Liver biopsy can impact survival of patients with early metastases from BC. Discordance between primary and distant lesions can offer the patients new treatment options

Hormonal Therapy and Chemoprevention.

Hormone replacement therapy (HRT) can increase the quality as well as the length of life, but a prolonged use can also increase the risk of breast cancer. The combination of HRT and a selective estrogen receptor modulator (SERM) such as tamoxifen may retain the benefits while reducing the risks of either agent. A post hoc analysis of the Italian Tamoxifen Prevention Study showed a borderline significant reduction of breast cancer among women who were on HRT continuously and tamoxifen as compared with continuous HRT users who received placebo. Recent studies suggest that the standard dose of tamoxifen may be reduced to one-quarter (i.e., 10 mg every other day) without loss of its beneficial biological effects. Since the endometrial effect of tamoxifen seems to be both dose and time dependent, a dose reduction could substantially reduce the risk of endometrial cancer while retaining its preventive efficacy. On the other hand, the addition of HRT containing progestins could also minimize the risk of endometrial cancer associated with tamoxifen. Moreover, estrogen should reduce the incidence of vasomotor and urogenital symptoms, which are a major reason for tamoxifen withdrawal in prevention studies. Notably, in the National Surgical Adjuvant Breast Project (NSABP) P-1 trial, women ages 50 or younger had no increased incidence of adverse events, including endometrial cancer and venous thromboembolic events. One possible explanation for the lack of toxicity in premenopause is the presence of adequate circulating estrogen levels which prevent tamoxifen to act as an estrogen agonist at these target tissues. Moreover, data from the current Italian tamoxifen prevention trial indicate that the compliance was substantially higher for de novo and current HRT users as compared to women who never received HRT during the study. The combination of HRT and tamoxifen at low doses could thus reduce the risks and side effects while retaining the benefits of either agent

LETTER TO THE EDITOR

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local therapy for breast cancer in malignant lymphoma survivors

Summary Aims: Breast cancer is the most frequent secondary tumor in young women previously treated with mantle radiation for Hodgkin's disease. Prior therapeutic radiation to the breast region is considered an absolute contraindication to breast conservative surgery, and mastectomy is considered the treatment of choice. We performed a retrospective review to assess the potential of performing breast conservative surgery and intraoperative radiotherapy with electrons (ELIOT), in these patients. Methods and results: Forty-three patients affected by early breast cancer, previously treated with mantle radiation for malignant lymphoma, who underwent breast conservative surgery and ELIOT, were identified in our institution. Median age at diagnosis of lymphoma was 26 years (49% were less than 25). Median interval between lymphoma and breast cancer occurrence was 19 years. A total dose of 21 Gy (prescribed at 90% isodose) in 39 patients (91%), of 17 Gy (prescribed at 100% isodose) in 1 patient and 18 Gy (prescribed at 90% isodose), was delivered. ELIOT was well tolerated in all patients without any unusual acute or late reactions. After a median follow-up of 52 months, local recurrence occurred in 9% of the patients and metastases in 7% patients. Conclusion: In patients previously treated for lymphoma, partial breast irradiation, and in particular ELIOT, permits breast conservative surgery without acute local complications, decreasing the number of avoidable mastectomies

Pathological features and survival outcomes of very young patients with early breast cancer: How much is "very young"?

Abstract We collected information on 497 consecutive breast cancer patients aged less than 35 years operated at the European Institute of Oncology. The main aim of the study is to compare biological and clinical features dividing the population by age: Patients aged p = 0.79) and overall survival ( p = 0.99) between the three age groups. This latter findings was confirmed using age as a continuous variable assuming a linear association between age and the outcomes considered, too. In conclusion, our data indicate that the group of patients with breast cancer below 35 years is essentially a homogenous group when classical clinical and immunohistochemical features were considered

breast conserving surgery in 201 very young patients 35 years

Abstract Introduction Surgical treatment of breast cancer in very young patients ( Patients and Methods We retrospectively evaluated outcome and prognostic factors of 201 consecutive patients treated with breast conservation followed by whole breast irradiation between 1997 and 2004 with special attention paid to local control. The average follow up was 72 months (range 13–133 months). Results The mean age was 32 years (Range 20–34). Invasive ductal carcinoma was found in 175 (87.1%) patients. Two (1%) patients had invasive lobular carcinoma. One-hundred and eighteen patients (58.7%) had tumors of 2 cm or smaller. Sentinel lymph node biopsy was performed in 105 (52.2%) patients. One-hundred and ten (54.7%) patients had node-negative disease, 68 (33.8%) patients had 1–3 positive nodes and 23 (11.4%) +4 positive nodes. Eighteen patients (9.0%) developed a local recurrence, 25 (12.5%) developed distant metastases and 23 patients (11.4%) died during follow up. The 5- and 10-year cumulative incidence of local events were 8.2% and 12,3% respectively. The univariate analysis did not identify any variables affecting local disease-free survival. Conclusions Breast conservation in very young patients achieves an acceptable local control rate. No prognostic factors were associated with local events

is 18f fluorodeoxyglucose uptake by the primary tumor a prognostic factor in breast cancer

Abstract Background We retrospectively investigated 18F-FDG uptake by the primary breast tumor as a predictor for relapse and survival. Patients and methods We studied 203 patients with cT1-T3N0 breast cancer. Standardized uptake value (SUVmax), was measured on the primary tumor. After a median follow-up of 68 months (range 22–80), the relation between SUVmax and tumor factors, disease free-survival (DFS) and overall survival (OS) was investigated. Results In the PET-positive patients, the median FDG uptake by the tumor was 4.7. FDG uptake was significantly related to tumor size, number of involved axillary nodes, grade, negative ER, high Ki-67 and HER2 overexpression. No distant metastases or deaths occurred in the PET-negative group. Five-year DFS was 97% and 83%, respectively in the PET-negative and PET-positive groups (P = 0.096). At univariate analysis, DFS was significantly lower in patients with SUVmax >4.7 compared to the patients with negative PET (P = 0.042), but not to the patients with SUVmax ≤4.7 (P = 0.106). At multivariable analysis, among PET-positive patients, SUVmax was not an independent prognostic factor for DFS (HR>4.7 vs ≤4.7: 1.02 (95% CI 0.45–2.31)). Five-year OS was 100% and 93%, respectively, in the PET-negative and PET-positive groups (P = 0.126). Conclusion FDG uptake by the primary lesion was significantly associated with several prognostic variables, but it was not an independent prognostic factor

Erratum to: Oncoplastic Breast-Conserving Surgery for Tumors Larger than 2 Centimeters: Is it Oncologically Safe? A Matched-Cohort Analysis

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Approaches to interim analysis of cancer randomised clinical trials with time to event endpoints: A survey from the Italian National Monitoring Centre for Clinical Trials

<p>Abstract</p> <p>Background</p> <p>Although interim analysis approaches in clinical trials are widely known, information on current practice of planned monitoring is still scarce. Reports of studies rarely include details on the strategies for both data monitoring and interim analysis. The aim of this project is to investigate the forms of monitoring used in cancer clinical trials and in particular to gather information on the role of interim analyses in the data monitoring process of a clinical trial. This study focused on the prevalence of different types of interim analyses and data monitoring in cancer clinical trials.</p> <p>Methods</p> <p>Source of investigation were the protocols of cancer clinical trials included in the Italian registry of clinical trials from 2000 to 2005. Evaluation was restricted to protocols of randomised studies with a time to event endpoint, such as overall survival (OS) or progression free survival (PFS). A template data extraction form was developed and tested in a pilot phase. Selection of relevant protocols and data extraction were performed independently by two evaluators, with differences in the data assessment resolved by consensus with a third reviewer, referring back to the original protocol. Information was obtained on a) general characteristics of the protocol b) disease localization and patient setting; c) study design d) interim analyses; e) DSMC.</p> <p>Results</p> <p>The analysis of the collected protocols reveals that 70.7% of the protocols incorporate statistical interim analysis plans, but only 56% have also a DSMC and be considered adequately planned. The most concerning cases are related to lack of any form of monitoring (20.0% of the protocols), and the planning of interim analysis, without DSMC (14.7%).</p> <p>Conclusion</p> <p>The results indicate that there is still insufficient attention paid to the implementation of interim analysis.</p

Evaluating the ability of an artificial-intelligence cloud-based platform designed to provide information prior to locoregional therapy for breast cancer in improving patient's satisfaction with therapy: the CINDERELLA trial

Background: Breast cancer therapy improved significantly, allowing for different surgical approaches for the same disease stage, therefore offering patients different aesthetic outcomes with similar locoregional control. The purpose of the CINDERELLA trial is to evaluate an artificial-intelligence (AI) cloud-based platform (CINDERELLA platform) vs the standard approach for patient education prior to therapy. Methods: A prospective randomized international multicentre trial comparing two methods for patient education prior to therapy. After institutional ethics approval and a written informed consent, patients planned for locoregional treatment will be randomized to the intervention (CINDERELLA platform) or controls. The patients in the intervention arm will use the newly designed web-application (CINDERELLA platform, CINDERELLA APProach) to access the information related to surgery and/or radiotherapy. Using an AI system, the platform will provide the patient with a picture of her own aesthetic outcome resulting from the surgical procedure she chooses, and an objective evaluation of this aesthetic outcome (e.g., good/fair). The control group will have access to the standard approach. The primary objectives of the trial will be i) to examine the differences between the treatment arms with regards to patients' pre-treatment expectations and the final aesthetic outcomes and ii) in the experimental arm only, the agreement of the pre-treatment AI-evaluation (output) and patient's post-therapy self-evaluation. Discussion: The project aims to develop an easy-to-use cost-effective AI-powered tool that improves shared decision-making processes. We assume that the CINDERELLA APProach will lead to higher satisfaction, better psychosocial status, and wellbeing of breast cancer patients, and reduce the need for additional surgeries to improve aesthetic outcome