A new position paper on predictive BRCA genetic testing for breast cancer, recently published in Cancer Treatment Reviews, represents the Italian multidisciplinary consensus on the indications and operational methods for this test, placing it at the centre of a shared diagnostic therapeutic care pathway (PDTA).

Eight societies were included in the work that led to the final document, representing various professional groups involved in managing these cases: medical oncologists (Italian Association for Medical Oncology), radiation oncologists (Italian Association of Radiotherapy and Medical Oncology), breast surgeons (Italian Association of Breast Surgeons), anatomical pathologists (Italian Society of Anatomical Pathology and Diagnostic Cytology, Italian Association of Pathologists), surgical oncologists (Italian Society of Surgical Oncology), geneticists (Italian Society of Human Genetics), GPs (Italian College of General Practitioners), and medical and interventional radiology (Italian Society of Medical and Interventional Radiology).

“This document was developed to address the lack of consensus in Italy on standard pathways for accessing and managing BRCA testing, made urgent by the introduction of targeted therapies such as PARP inhibitors.”

“A multidisciplinary approach is crucial to integrating every aspect of this pathway,” said Alberto Zambelli, MD, professor of oncology at the University of Milano-Bicocca in Milan, Italy, and director of oncology at ASST Papa Giovanni XXIII in Bergamo, Italy, in an interview with Univadis Italy, part of the Medscape Professional Network. 

The experts who participated in drafting this position paper highlighted several unmet needs in this context, including regional disparities in access to testing and long waiting times for genetic counselling. “Patients risk not having timely access to testing or targeted therapy if pathways are not rapid and uniform,” he said.

Genetic Counselling

In an increasingly genetics-driven oncology setting, tests that assess the presence of pathogenic variants in specific genes may be both preventative (such as risk screening in healthy family members of variant carriers) and predictive and designed to guide treatment.

The introduction of PARPi has changed these needs, increased the importance of testing and prompting new approaches to genetic counselling.

This led to the development of Mainstreaming Cancer Genetics, a model that allows medical oncologists and other specialists involved in breast cancer diagnosis and treatment to directly refer patients for BRCA genetic testing when it has therapeutic implications.

However, using this approach and implementing it in daily practice is not easy from an organizational perspective. The main obstacles include a shortage of geneticists and genetic counsellors, inconsistent oncologist training in cancer genetics, and the need for shared pathways within defined timeframes in the PDTA.

“It is necessary to strengthen integrated training programs and opportunities for discussion between geneticists and oncologists. Furthermore, we propose adopting PDTAs with shared pathways, defined timeframes, targeted training, and strengthened referral centres,” Zambelli said.

He emphasised the urgent need to reinforce genetic counselling services through investment and integrated training to ensure equitable access to genetic testing and treatment.

Summary

The recommendations presented in this position paper are the final products of research and discussion by 33 clinicians representing the aforementioned Italian scientific societies. The document addresses key topics, such as eligibility criteria for oncology genetic counselling, the role of contralateral prophylactic mastectomy (CPM) in individuals carrying germline pathogenic variants (gPV) of the BRCA1 or BRCA2 genes, and the appropriate positioning of BRCA1 or BRCA2 predictive testing.

Regarding eligibility for oncogenetic counselling, the experts provided recommendations to distinguish between the three groups of individuals as follows:

1. those with clinical characteristics associated with an increased likelihood of BRCA1 or BRCA2 gPV, regardless of the family history
2. those without such clinical characteristics but who may be eligible for specific treatments if a gPV is detected
3. those with a family history suggest a high likelihood of carrying BRCA1 or BRCA2 gPV

The text also included a conditional recommendation in favour of CPM in individuals with a history of surgically treated breast cancer and a BRCA gPV and proposed specific multidisciplinary pathways for BRCA testing for individuals with hormone receptor-positive (HR-positive) or HER2-negative triple negative breast cancer.

These are recommendations for the present. However, what the future holds for these recommendations is unclear.

“Evolution aims to integrate somatic and germline molecular data (genotype) and clinical pathological characteristics (phenotype), along with the use of artificial intelligence algorithms (digital pathology) capable of stratifying risk for and predicting response to treatment.” Zambelli concluded.

He believes that in this evolving scenario, the BRCA test will remain a fundamental theragnostic biomarker for individual therapy and family prevention.

Zambelli is a member of advisory boards for Roche, Pfizer, Lilly, Novartis, AstraZeneca, Gilead, Daiichi Sankyo, MSD, Menarini Stemline, Exact Sciences, and Ipsen. 

This story was translated from Univadis Italy.