Breast cancer, the duration of therapy is written in a gene

Breast cancer, the duration of therapy is written in a gene

The genome is something complex, but with current technologies we are able to read important information in it that can change breast cancer treatment. The latest discovery comes from an Italian study lasting 15 years and coordinated by the IRCCS Policlinico San Martino Hospital in Genoa: three mutations of a gene have been identified – or, more precisely, three variants – which, if present, indicate a greater benefit from prolonged therapy, with a lower risk of side effects.

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What a gene can tell us

The gene is the one that codes for the aromatase enzyme and the three variants are associated, on the one hand, with an increased probability of relapses and metastases, and on the other with a lower incidence of adverse events, in particular osteoporosis and cardiovascular diseases. In the future, therefore, by analyzing the gene in each patient, we may be able to better balance the duration of precautionary (adjuvant) treatments, which have the precise objective of reducing the risk of the disease returning, but which also involve side effects for the bones and heart.

The role of the aromatase enzyme in breast cancer

The aromatase enzyme is involved in the production of estrogen and is the target of some drugs called aromatase inhibitors. Among these is the letrozole: “Aromatase inhibitors represent the standard adjuvant anti-hormonal therapy – he explains Lucia Del Mastrooncologist and director of the Medical Oncology Clinic of the IRCCS Policlinico San Martino Hospital, responsible for the study – In fact, they prevent androgens from transforming into estrogens, the ‘fuel’ for hormone-sensitive breast cancer, which represents approximately 70% of 55,000 breast cancers diagnosed every year in our country”.

They are called hormone-sensitive tumors precisely because their growth is stimulated by estrogen and/or progesterone. For this reason, after surgery, patients with early breast cancer are prescribed anti-hormonal therapy capable of blocking what fuels tumor growth, thus reducing the risk of relapse. Blocking estrogen, however, is associated with a greater likelihood of side effects such as osteoporosis and cardiovascular disease.

The Italian study

The research, published on Clinical Cancer Research and financed by the Ministry of Health, started in 2005: it involved 35 oncology centers throughout Italy, for a total of 886 women with estrogen receptor-positive breast cancer who, after surgery, received letrozole as therapy hormonal adjuvant.

For each, the genetic profile was analyzed to understand if and how it influenced clinical outcomes in the years following the intervention. “The results made it possible to identify three gene variants that are decisive for therapy – he says Benedetta Conteoncologist of the breast unit of the San Martino Polyclinic Hospital and currently researcher of the Translational Genomics and Targeted Therapies in Solid Tumors of the IDIBAPS of the University of Barcelona and first author of the study – The three variants are associated with a greater cumulative risk of tumor recurrence and metastasis after years and with a greater mortality, but also with a lower cumulative incidence of side effects such as fractures or cardiovascular events within ten years. These results lead us to hypothesize that patients with these genetic variants physiologically produce a greater quantity of estrogen which, on the one hand, reduces the effectiveness of hormonal therapy, leading to a higher risk of recurrence, and on the other, also reduces the serious side effects of such therapy, such as osteoporosis fractures”.

Possible clinical applications

The results could have important clinical implications, through an analysis – nowadays relatively simple – of the gene: “Today, patients operated for breast cancer positive for hormone receptors receive adjuvant hormonal treatment for a period of up to 7-8 years – concludes Del Mastro, already coordinator of other studies on the optimal duration of anti-hormonal therapy – Evaluating the presence or absence of these three genetic variants could open the way to personalizing the duration of this treatment based on the risk of relapses and side effects of each patient, to minimize the dangers and optimize the benefits”.

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