Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06261918 |
| Other study ID # |
6269 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2024 |
| Est. completion date |
July 1, 2026 |
Study information
| Verified date |
February 2024 |
| Source |
Fondazione Policlinico Universitario Agostino Gemelli IRCCS |
| Contact |
Alessandra Fabi |
| Phone |
0630153773 |
| Email |
alessandra.fabi[@]policlinicogemelli.it |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
This prospective pilot study of biological specimens aims to identify new prognostic and
predictive biomarkers of response to standard therapy for local advanced BC, as well as to
identify new targets for the development of immuno- therapeutic protocols. First aim is
therefore to expand our knowledge to increase the response to preoperative treatment,
intensify treatment patterns, and select patients based on clinical parameters. In this
regard, it appears imperative to investigate yet under-investigated factors that might impair
the response to standard therapy for local advanced BC including association to metabolic
syndrome and analysis of tumoral and stromal features supporting a tumor microenvironment
impenetrable to both drugs and immune system cells.
Description:
Breast cancer (BC) represents the most common cancer disease among women. In Italy, according
to the Aiom-Airtum Report "Cancer Numbers 2020," there are an estimated 54,976 new cases in
the female population, which represents 30.3 % of all cancers. Although adherence to
screening programs has improved in recent years, the diagnosis of locally advanced BC
accounts for about 30% of new diagnoses.
Neo-adjuvant therapy (NCT), which is the administration of chemotherapy drugs combined with
biologic therapies if indicated, is the gold-standard in the setting of patients with locally
advanced BC (1). It allows down-staging of the primary neoplasm so that conservative rather
than demolitive surgical treatment can be performed. NCT also allows prognostic evaluation
based on the response obtained to the treatment itself. Noteworthy, a large meta-analysis
conducted on 11955 patients enrolled in 12 different clinical trials reported a significant
correlation between obtaining a pathological complete response (pathological complete
response, pCR, i.e., absence of invasive disease in both breast and lymph nodes) and both
event-free survival (EFS) and overall survival (OS) in all tumor subtypes, albeit more
pronounced for HER-2 positive neoplasms (EFS: HR 0. 39, CI 95% 0.31-0.50; OS: HR 0.34, CI 95%
0.24-0.47) or triple negative (EFS: HR 0.24, CI 95% 0.18-0.33; OS: HR 0.16, CI 95% 0.11-0.25)
(2). To date, about 30% of BC patients go on to pCR following NCT (2), thus highlighting the
need for further investigation to expand the proportion of these patients who may benefit
from long-lasting clinical responses following such therapy. The consideration of a
preexisting history of metabolic syndrome might open new avenues in therapeutic and
prognostic perspectives.
Despite the numerous drugs currently available for the NCT, classic chemotherapy (CT)
represents the most widely used class of drugs. Growing pieces of evidence show that the
efficacy of CT depends not only on its ability to directly inhibit or kill malignant cells,
but also on features of the tumor microenvironment in term of metabolic alterations, which
might influence the anti-tumoral response (3). Specifically, tumor cell death promoted by
cytotoxic drugs causes the release of cancer-associated antigens that, in turn, activate and
recruit immune cells within the tumor (4). A recent Italian phase 2 study, the GIADA trial,
showed that the number of tumor-infiltrating lymphocytes is significantly associated with pCR
and that anthracycline-based chemotherapy treatment results in the establishment of a more
immunogenic tumor microenvironment (5). Early results show that despite an improvement in
pCR, a considerable number of treated individuals still do not respond or lack long-term
responses (6). This evidence suggests that such combinatorial regimens often fail to
neutralize all of the immunosuppressive activities that BC enacts to resist CT, evade the
anti-tumor immune response, and progress (7). To date, the identification of a system that
can predict responses to NCT and the delineation of mechanisms of immunosuppressive
resistance in patients with BC unresponsive to NCT remain unresolved issues.
The complex network of interactions between immune cells and other components of the tumor
microenvironment results in significant heterogeneity in clinical practice to the response to
precision medicine therapeutic options. Consequently, it will be increasingly important to
decipher the functional status of the metabolic status of the tumor microenvironment in each
patient in order to move from standardized therapy to individualized treatment that in the
future could increase survival and improve the quality of life of a greater numbers of BC
patients.
