Triple-negative breast cancer: a new risk category identified

The results of the study led by a research team from the University of Padua, published in Nature Communications: two accessible markers can be used to individualise the monitoring of patients with triple-negative breast cancer after treatment and to guide future research.

Triple-negative breast cancer accounts for approximately 10–15% of breast cancers. Studying the rarer subgroups of patients requires volumes of data that a single hospital cannot guarantee. GAMBIT is an international research network on triple-negative breast cancer, promoted and coordinated by the Department of Surgical, Oncological and Gastroenterological Sciences of the University of Padua, under the leadership of Professor Maria Vittoria Dieci, as part of the research activities of the Oncology group directed by Professor Valentina Guarneri. The research, supported by Fondazione AIRC per la Ricerca sul Cancro as regards Professor Dieci’s studies, was created precisely to overcome this limitation and lay the foundations for new research projects. GAMBIT involves 42 institutions in Italy, France, Belgium, the Netherlands, Sweden, Poland, Austria and Japan, and gathers data relating to more than 3,000 patients, pooling evidence from clinical practice and multidisciplinary expertise.

The network’s first article has been published in Nature Communications, with Davide Massa of the University of Padua research group as first author. In the study, the cases of 2,457 patients treated in 18 European centres belonging to the GAMBIT network were analysed retrospectively, identifying a subgroup of patients previously considered cured, but who instead proved to have a clinically relevant residual risk of recurrence.

In early-stage triple-negative breast cancer, therapy is generally started before surgery. When, at the time of the operation, no residual invasive disease is found either in the breast or in the lymph nodes, this is referred to as a pathological complete response. Patients who achieve this have very low recurrence rates, which means that, with excellent probability, the tumour will not return. For this reason, achieving a pathological complete response is currently one of the main criteria used in the design of clinical trials evaluating new therapeutic and monitoring strategies.

However, a minority of these patients may develop a recurrence even after a complete response. In the study carried out by the group, the researchers therefore sought to understand whether, in this case series, it was possible to identify the patients at greater risk of recurrence by studying two markers: involvement of the axillary lymph nodes and the quantity of tumour-infiltrating lymphocytes.

By combining these two pieces of information available at diagnosis, the researchers, led by Professor Maria Vittoria Dieci, identified differences in risk not previously described within the group of patients with a pathological complete response. In particular, patients with axillary lymph nodes involved by the tumour and a low quantity of tumour-infiltrating lymphocytes showed a higher risk of recurrence than other patients with different characteristics. In this subgroup, five-year distant recurrence-free survival was in fact 83.4%, whereas in the others it exceeded 95%. Moreover, when this recurrence occurred, there was one preferred site: the central nervous system.

«GAMBIT’s strength lies not only in the numbers,” says Professor Maria Vittoria Dieci of the University of Padua and Principal Investigator of GAMBIT, “but in its ability to bring together centres and different expertise around concrete clinical questions. In this study, we observed that pathological complete response, while remaining a strongly favourable outcome, is not sufficient to identify a completely homogeneous population with a favourable prognosis.”

The study results made it possible to identify a population of patients in whom therapeutic or surveillance strategies adapted to the risk of recurrence could be assessed prospectively, opening up avenues for future research. The data collected also showed the value of the GAMBIT network in generating, through collaboration among many centres, sufficiently robust data to study subgroups of patients that would otherwise be difficult to analyse because of their limited numbers.

In practical terms, the two parameters used – lymph node status and the quantity of lymphocytes infiltrating the tumour – do not require advanced or expensive technologies. Lymph node involvement is defined during the normal diagnostic pathway, after biopsy and surgery, while the quantity of tumour-infiltrating lymphocytes can be assessed on the histological slides from the biopsy itself, at no additional cost.

«This study shows that clinical research arising from collaboration among centres can be translated into concrete tools already available in everyday clinical practice,” emphasises Professor Valentina Guarneri, Professor of Oncology at the University of Padua and Director of the Department of Oncology at the Istituto Oncologico Veneto. “This result does not change patient care today, but it indicates more precisely where we should focus future research, working to ensure that it always remains at the service of patients.”

The next step will be to confirm the data obtained through prospective studies, especially in populations treated with the most recent regimens including immunotherapy, and then to use them to design more precise and targeted clinical studies, with which to assess strategies genuinely proportionate to the risk of recurrence, so as to administer the right treatments to the right patients at the right time.