Pink is good
by Ivan De Stefano
Fondazione Umberto Veronesi with the project “Pink is Good” supports many researchers who deal with research against breast cancer. During the year 2016 the foundation has supported these three researchers with high scientific profile:
Nicoletta Tomasi Cont
Born in Courgné (Turin) in 1983
Degree in Medicine and Surgery , University of Turin
Specialization in Gynecology and Obstetrics, University of Turin
Where she developed the project: Fondazione del Piemonte per l’Oncologia di Candiolo (Turin)
Partial chest wall irradiation after nipple-areola sparing mastectomy for breast cancer patients at increased risk of local recurrence
Mastectomy with the preservation of the nipple-areola complex (NAC sparing mastectomy) has been introduced in early-stage breast cancer patients who undergo immediate reconstruction. Postmastectomy radiotherapy is delivered to selected patients at high risk for recurrence, but is associated with significant complications and unfavourable cosmesis after implant-based breast reconstruction. Most local recurrences after breast conserving surgery occur in the quadrant where the
original tumor was located (ingex quadrant). In selected patients, partial breast radiotherapy delivered to the index quadrant is associated with similar recurrence rates as compared to whole breast radiotherapy. Accordingly, in our series of over 500 NAC sparing mastectomies virtually all chest wall recurrences occurred in the subdermal tissue of the index quadrant. Therefore, we hypothesize that partial chest wall irradiation in selected patients may be equivalent to whole chest wall irradiation in terms of local control, while being associated with lower complication rates ad better cosmetic results. A protocol of accelerated partial chest wall irradiation will be submitted to the Ethical Commitee. All patients undergoing to NAC sparing mastectomy and immediate reconstruction for whom the indication to partial chest wall irradiation is uncertain will be enrolled. The feasibility of partial chest wall irradiation and its interaction with the reconstructive plan will be assessed. Outcome measures will include quality control of dose distribution and homogeneity, success rate and time to complete breast reconstruction. Toxicities, complication rates and final cosmetic results will be recorded.
The objective is to validate whether partial chest wall irradiation may be associated with decreased toxicitiy and improved cosmetic results in selected patients submitted to NAC sparing mastectomy and immediate reconstruction.
Maria del Pilar Camacho-Leal
Born in Mexico City in 1974
Degree in Biology, University of Mexico City
PhD Biochemistry at McGill University in Montreal
Where she developed the project: University of Turin
In vivo and in vitro therapeutic activity of micro RNA-23b against ErbB2/p130Cas/Blimp1-dependent breast cancer invasion
Understanding transcriptional changes during cancer progression is of crucial importance to develop new and more efficacious diagnostic and therapeutic approaches. ErbB2 protein is overexpressed in about 25% of human invasive breast cancers. In the past we have demonstrated that p130Cas overexpression synergizes with ErbB2 in mammary cell transformation and promotes ErbB2-dependent invasion in 3-dimensional cultures of human mammary epithelial cells. In addition, our recent data (funded by the Fondazione Umberto Veronesi Post-Doctoral Fellowship 2015) established PRDM1 (Blimp1) as new regulator of p130Cas-ErbB2 mediated breast cancer invasion. In particular, the previous study established Blimp1 as putative target of microRNA-23b. In invasive breast cancer cells both a tumor suppressive activity and an oncogenic role of microRNA-23b has been described. Interestingly, we observed that in MCF10A.B2 cells, Blimp1 protein expression inversely correlate with microRNA-23b expression. Analysis of the functional relevance of microRNA-23b in vitro in p130Cas-ErbB2 acini revealed that in Cas/ErbB2 cells, invasion impairment observed upon microRNA-23b overexpression does not occur upon overexpression of Blimp1. Thus, Blimp1 over-expression overcomes microRNA-23b effects on cell invasion. Altogether this data suggest that microRNA-23b is an important regulator in p130Cas- ErbB2 mammary carcinoma.
In this context, the main goals of this work are 1) to evaluate the activity of encapsulated
microRNA-23b in stable nucleid acid lipid particles in 3D and 2D cultures. 2) to evaluate the activity of this particles on breast cancer cells.
Born in Genova in 1973
Degree in Chemistry, University of Genoa
PhD Technology and Chemical Processes, University of Genoa
Where she developed the project: Medical University of South Carolina di Charleston (USA)
Breast cancer proteomics: new insights in sub-typing and progression using innovative MALDI Imaging Mass Spectrometry
Breast cancer is the most common form of cancer among women worldwide. Currently the treatments are based on tumor staging/grading and molecular biomarkers. However, the response to the treatment, the disease free and overall survival, are not the same for all patients with similar tumor histological characteristics. The proteomic profile, allowing the evaluation of proteins effectively expressed in the tissue, could provide a better tool to characterize breast carcinoma. The goal of this project is to determine differences in the proteomic profile of formalin fixed paraffin embedded breast cancer tissues using MALDI Imaging Mass Spectrometry. This technique provides the determination of the “molecular signature” of the tumor through the detection and the localization of proteins directly on the tissue section. Preliminary experiments, conducted in collaboration with the Medical University of South Carolina Proteomics Center(USA), on 30 samples, added new insights for a better classification in risk categories. These results should be confirmed on a larger data set. Moreover, an open issue in the treatment of the metastatic patients consists in evaluation of the variation of the biological characteristics between primary tumors and metastasis, useful to be taken into account for determining the best therapy.
This project aims to: a)Evaluate the heterogeneity in proteomic expression of G2 ER+ HER2- breast carcinoma, considered at intermediate risk of recurrence, in order to identify retrospectively prognostic/ predictive biomarker candidates. Develop and validate a classifier that could divide samples in risk categories. b)Determine differences in the proteomic profile between primary tumor and associated metastasis and correlate these variations with the immunohistochemical expression of ER, PgR and HER2 markers.
The results of this study will produce new data for better defining breast cancer subtypes and will help in understanding tumor progression mechanisms.