The Clinical Research Group on Breast Cancer of the Oncology 2 Unit is mainly focused on the development of new tailored treatment strategies and the identification of prognostic and predictive biomarkers to guide treatment personalization for breast cancer patients.

The Clinical Research Breast Cancer Group at IOV IRCCS has coordinated and coordinates the conduction of several multicentric investigator-driven clinical trials and participates to several national and international trials for breast cancer patients. The results of these studies have been presented at the most important national and international conferences and published by peer-review journals.

The researchers of the group are active members of the Associations of Medical Oncology AIOM, European Society of Medical Oncology ESMO and American Society of Clinical Oncology ASCO.

Research activity

Tailoring the treatment in early breast cancer

Breast cancers represent a heterogeneous spectrum of diseases and the use of the right treatment for the right patient avoiding potential overtreatment in patients at good prognosis remains a challenge. In early-stage breast cancer, an important question for researchers and clinician is how to identify which patients would benefit from a more intensive treatment versus those who could spare it, in order to avoid over- and under-treatment.

In this context, the Clinical Research Group on Breast Cancer of the Oncology 2 Unit has conducted two trials, the ShortHER and the PerElisa trials, that evaluated de-escalated treatments for patients with early-stage breast cancer overexpressing the HER2 protein.
The introduction of the monoclonal antibody trastuzumab has in fact dramatically increased the prognosis of early HER2-positive breast cancer patients. However, the current standard duration of adjuvant trastuzumab has been established conventionally at one year. Considering the potential cardiac toxicity of such treatment, efforts have been made to understand whether some patients could benefit from a shorter treatment.

The ShortHER trial randomized 1253 patients with early HER2-positive breast cancer to receive adjuvant trastuzumab for 9 weeks or 1 year in combination with adjuvant chemotherapy. Even if non-inferiority of 9 weeks trastuzumab could not be claimed, this trial showed that shorter trastuzumab administration could be an option for those patients who experience cardiac events and for those with a low risk of relapse. Moreover, this regimen might facilitate the access to trastuzumab to patients living in countries with limited resources. In addition, this trial is also the basis for several translational studies aiming to identify prognostic and predictive biomarkers to tailor the adjuvant treatment of early HER2-breast cancer.

In the neoadjuvant setting, the Per-Elisa trial evaluated a preoperative chemotherapy-free treatment (including two monoclonal anti-HER2 antibodies – trastuzumab and pertuzumab – and endocrine therapy) for patients with HER2-positive and hormone-receptor positive breast cancer who were classified as “molecular responders” on the basis of the reduction in proliferation index evaluated with a tumor biopsy after two weeks of endocrine treatment alone (letrozole). This trial showed that a meaningful pCR rate can be achieved without chemotherapy in patients with triple-positive breast cancer and that intrinsic subtyping by PAM50 can further refine our ability to identify a subset of patients for whom chemotherapy might be spared.

On the other side, the group is also involved in several multicenter trials exploring intensification of neo/adjuvant treatment for early breast cancer patients at high-risk of relapse (post-neoadjuvant T-DM1, adjuvant CdK inhibitors, addition of immunotherapy to neo/adjuvant chemotherapy).

Immunotherapy in breast cancer

The last years have seen the rise of immunotherapy as a new efficient treatment strategy in several solid tumors. In the field of breast cancer, the addition of an immune checkpoint inhibitor to chemotherapy has recently shown activity in a selected population of metastatic breast cancer patients with triple-negative PD-L1 positive disease. Moreover, the addition of an immune checkpoint inhibitor to neoadjuvant chemotherapy has also been reported to increase pathologic complete response rates in early triple-negative breast cancer.

The Clinical Research Group on Breast Cancer of the Oncology 2 Unit is currently coordinating two prospective trials exploring immunotherapy strategies for early breast cancer patients. The A-BRAVE trial is a randomized phase III trial ongoing in more than 60 centers in Italy and UK, which is evaluating the efficacy of adjuvant immunotherapy with the anti-PD-L1 avelumab for one year for patients with high-risk triple negative breast cancer who completed the standard treatment with curative intent, including surgery and chemotherapy.

The GIADA phase II study, an Italian multicentric study coordinated by IOV, tested the efficacy of a preoperative sequence of anthracycline-based chemotherapy followed by immunotherapy with the anti-PD 1 nivolumab and endocrine treatment for patients with a specific subtype of hormone-receptor positive breast cancer (Luminal B).

Moreover, the Clinical Research Group on Breast Cancer is also involved in several multicenter trials exploring the use of immunotherapy, both in the early and in the advanced setting.

Identifying prognostic and predictive biomarkers in breast cancer

Breast cancer is a very heterogeneous disease, with a broad spectrum of morphological entities that reflect the complex genetic landscape of this disease and the presence of inter/intra-tumor heterogeneity.
The Clinical Research Group on Breast Cancer is involved in several translational studies aiming to identify potential biomarkers that can predict clinical outcome and response to treatments.

For example, the role of PI3K/Akt/mTOR pathway, which is frequently de-regulated in breast cancer and is related to anti-HER2 therapies sensitivity, and the role of gene-expression biomarkers such as PAM50 intrinsic subtyping has been studied by the Clinical Research Group on Breast Cancer in the context of the PER-Elisa trial and the ShortHER trial.

Moreover, as analysis of tumor tissue is not able to capture the whole intra-tumor heterogeneity and temporal evolution under exposure to specific treatments and liquid biopsy offers an interesting tool to assess molecular tumor characteristics in a non-invasive way, the Clinical Research Group on Breast Cancer is also conducting a pilot study to fine-tune the analysis of ESR1 and PIK3CA mutations in ctDNA in a prospective cohort of metastatic breast cancer patients, evaluate its concordance with tumor tissue and prospectively describe the dynamic evolution of these mutations.

The Clinical Research Group on Breast Cancer is also actively involved in several projects meant to extensively characterize immune biomarkers in early and advanced breast cancer. In particular, the group demonstrated the prognostic role of high levels of tumor infiltrating lymphocytes in metastatic breast cancer patients and in early HER2-positive patients enrolled in the ShortHER trial. Moreover, the pilot prospective MOON study is exploring the role of gut microbiome composition as a potential biomarker of treatment response in early triple-negative breast cancer patients.

Team members

Clinical Researchers

Fellows – Specializing in Oncology, University of Padua

  • Federica Miglietta, MD
  • Elisa Genovesi, MD
  • Enrico Cumerlato, MD
  • Michele Bottosso, MD

Research Nurses

  • Daniela Grosso, RNs’ coordinator
  • Giulia Pauletti, NS
  • Ilenia Gazzetta, NS
  • Annalisa Tocco, NS

Study Coordinator

  • Maria Concetta Falcone

Internal Collaborations at IOV-IRCCS

External Collaborations

  • Pathology Unit, Azienda Ospedale – University of Padova
  • Clinica Chirurgica 1, Azienda Ospedale – University of Padova

International and National Collaborations

  • International Immuno-Oncology Biomarker Working Group on Breast Cancer
  • Gruppo Italiano Mammella (GIM)
  • Translational Genomics and Targeted Therapeutics in Solid Tumors Laboratory – IDIBAPS August Pi i Sunyer Biomedical Research Institute
  • AIRC (Italian Association for Cancer Research)
  • IFOM (Istituto FIRC di Oncologia Molecolare)
  • ASTRO (Association Translation Research Oncology)
  • European Society of Medical Oncology (ESMO) – Faculty
  • TRIO (Translational Research in Oncology) – Scientific Committee
  • Fondazione Periplo Onlus