Research

Breast cancer

Overview of the research lines

Adjuvant treatment of HER2+ and Triple Negative early breast cancer

There is an urgent need for effective therapies for triple negative breast cancer patients. Triple negative breast cancer represents the subtype with the poorest prognosis. Recent works have suggested that the immune system can play a major role in this breast cancer subtype. In particular, the presence of a tumor infiltration by lymphocytes has been described as a strong and independent prognostic factor especially for triple negative disease . On these premises, immunotherapies hold great promises in this subset of high-risk patients for whom, in current clinical practice, chemotherapy represents the only possible systemic treatment.

5 Publications

Loss of HER2 positivity and prognosis after neoadjuvant therapy in HER2-positive breast cancer patients. Guarneri V, Dieci MV, Barbieri E, Piacentini F, Omarini C, Ficarra G, Bettelli S, Conte P. Ann Onc, 2990-2994, 2013

Relapsed Triple-Negative Breast Cancer: Challenges and Treatment Strategies. Guarneri V, Dieci MV, Conte P. Drugs, 3:1257-1265, 2013

Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study Dieci MV, Criscitiello C, Goubar A, Viale G, Conte P, Guarneri V, Ficarra G, Mathieu MC, Delaloge S, Curigliano G, Andre F. Ann Oncol, 25:611-618, 2014

Prospective biomarker analysis of the randomized CHER-LOB study evaluating the dual anti-HER2 treatment with trastuzumab and lapatinib plus chemotherapy as neoadjuvant therapy for HER2-positive breast cancer. Guarneri V, Dieci MV, Frassoldati A, Maiorana A, Ficarra, G, Bettelli S, Tagliafico E, Bicciato S, Generali DG, Cagossi K, Bisagni G, Sarti S, Musolino A, Ellis C, Crescenzo R, Conte P. Oncol, 20:1001-1010, 2015

Integrated evaluation of PAM50 subtypes and immune modulation of pCR in HER2-positive breast cancer patients treated with chemotherapy and HER2-targeted agents in the CherLOB trial. Dieci M V, Prat A, Tagliafico E, Paré L, Ficarra G, Bisagni G, Piacentini F, Generali D G, Conte P, Guarneri V. Annals Of Oncology, vol. 27, pp. 1867-1873, 2016

Funding

Short-HER: multicentric randomised phase 3 trial of adjuvant chemotherapy plus 3 vs 12 months of trastuzumab in breast cancer patients with HER2 positive disease
A-BRAVE trial: A phase III randomized trial.
Ministero della Salute: Challenging the role of chemotherapy in HER2 positive early breast cancer.
AIRC: PIK3CA mutations/PTEN loss and infiltrating tumor lymphocytes to personalize therapy in HER2+ early breast cancer.
5x100: Oncologia traslazionale - Progetto SHORT-HER.

Treatment optimization of advanced HR+ breast cancer

In June 2005, interim analyses of phase III randomized trials (HERA, Joint Analysis B31-N9831, N9831) showed the superiority of combining Trastuzumab to adjuvant chemotherapy for HER2+ EBC. Trastuzumab granted accelerated approval as adjuvant therapy for HER2+ EBC. Rationale for the Short-HER study: Empirical basis to select 1 year duration of Trastuzumab administration. Synergism of Trastuzumab when combined with chemotherapy 2. Hypothesis: a shorter duration of Trastuzumab administered concomitantly with chemotherapy might produce comparable efficacy with significantly lower toxicities and costs.

5 Publications

Ribociclib as first-line therapy for HR-positive, advanced breast cancer. Hortobagyi G.N, Stemmer S.M., Burris H.A., Yap Y.-S., Sonke G.S., Paluch-Shimon S., Campone M., Blackwell K.L., Andre F., Winer E.P., Janni W., Verma S., Conte P., Arteaga C.L., Cameron D.A., Petrakova K., Hart L.L., Villanueva C., Chan A., Jakobsen E., Nusch A., Burdaeva O., Grischke E.-M., Alba E., Wist E., Marschner N., Favret A.M., Yardley D., Bachelot T., Tseng L.-M., Blau S., Xuan F., Souami F., Miller M., Germa C., Hirawat S., O'Shaughnessy J. New England Journal Of Medicine, vol. 375(18), pp. 1738-1748, 2016

Tumor-infiltrating lymphocytes and molecular response after neoadjuvant therapy for HR+/HER2-breast cancer: results from two prospective trials. Dieci Maria Vittoria, Frassoldati,A., Generali,D., Bisagni,G., Piacentini,F., Cavanna,L., Cagossi,K., Puglisi, F., Michelotti,A., Berardi,R., Banna,G., Goubar,A., Ficarra,G., Griguolo G., Conte P, Guarneri V. Breast Cancer Research And Treatment, 163- 2:295-302, 2017

Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2 advanced breast cancer in the randomized MONALEESA-2 trial. O’Shaughnessy J, Petrakova K, Sonke GS, Conte P, Arteaga CL, Cameron DA, Hart LL, Villanueva C, Jakobsen E, Beck JT, Lindquist D, Souami F, Mondal S, Germa C, Hortobagy, GN. Breast Cancer Research and Treatment, pp. 1-8, 2017

Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2− advanced breast cancer in the randomized MONALEESA-2 trial. Pasello G., Zago G., Lunardi F., Urso L., Kern I., Vlacic G., Grosso F., Mencoboni M., Ceresoli G.L., Schiavon M., Pezzuto F., Pavan A., Vuljan S.E., Del Bianco P., Conte P., Rea F., Calabrese F. Annals of Oncology, vol. 29(5), pp. 1258-1265, 2018

Funding

MAINtenance Afinitor (MAIN-A): A randimized trial comparing maintenance Aromatase Inhibitors AIs) + everolimus (Afinitor) vs. AIs in patients with HR+ metastatic breast cancer with disease control after first line chemotherapy
Ministero della Salute: ricerca corrente 2014
Ministero della Salute: ricerca corrente 2015
Protocollo UNIMORE-SMECHIMAI "Caratterizz. biologica carcinoma mammario”

Molecular characterization of Early Breast Cancer

5 Publications

Discordance in receptor status between primary and recurrent breast cancer has a prognostic impact: a single Institution analysis.Dieci MV, Barbieri E, Piacentini F, Ficarra G, Bettelli S, Dominici M, Conte P, Guarneri V. Ann Oncol, 24:101-108, 2013

Interpreting cancer biology: refining our therapeutic algorithm in breast cancer. Hortobágyi G, Conte P. Oncologist, 18:8-10, 2013

Rare breast cancer subtypes: histological, molecular, and clinical peculiarities. Dieci MV, Orvieto E, Dominici M, Conte P., Guarneri V. Oncologist, vol. 19(8), pp. 805-813, 2014

PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer: pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab. Loibl S, Majewski I, Guarneri V, Nekljudova V, Holmes E, Bria E, Denkert C, Schem C, Sotiriou C, Loi S, Untch M, Conte P, Bernards R, Piccart M, von Minckwitz G, Baselga J. Annals Of Oncology, vol. 27(8), pp. 1519-1525, 2016

First Prospective Multicenter Italian Study on the Impact of the 21-Gene Recurrence Score in Adjuvant Clinical Decisions for Patients with ER Positive/HER2 Negative Breast Cancer. Dieci MV, Guarneri V, Giarratano T, Mion M, Tortora, Giampaolo, De Rossi C, Gori, Stefania, Oliani C, Merlini L, Pasini F, Bonciarelli G, Griguolo G, Orvieto E, Michieletto S, Saibene T, Del Bianco P, De Salvo GL, Conte P. The Oncologist, vol. 23(3), pp. 297-305, 2017

Funding

Ministero della Salute: Challenging the role of chemotherapy in HER2 positive early breast cancer
AIRC: PIK3CA mutations/PTEN loss and infiltrating tumor lymphocytes to personalize therapy in HER2+ early breast cancer
Ministero della Salute: ricerca corrente 2014
Ministero della Salute: ricerca corrente 2015

People involved:

Conte Pierfranco, Full Professor
Guarneri Valentina, Associated Professor
Dieci Maria Vittoria, Assistant Professor

Group members

Griguolo Gaia, Rumanò Laura, Giarratano Tommaso,Tasca Giulia (PhD), McMahon Laura, Tsvetkova Vassilena, Di Liso Elisabetta (Fellow), Falci Cristina, Ghiotto Cristina, Bozza Fernando, De Salvo Gianluca (Medical Doctor)