Antonio Marra, MD, European Institute of Oncology, Milan, Italy, discusses a study investigating the impact of germline BRCA status on distant relapse-free survival and invasive disease-free survival among patients with early hormone receptor (HR)-positive, HER2-negative breast cancer.

According to this analysis, patients who were carriers for germline BRCA alterations had a significantly increased risk of recurrence. Dr Marra concluded, "germline BRCA1/BRCA2-altered, early stage hormone receptor-positive, HER2-negative breast cancer is a population that need to be investigated in new trials. testing novel drugs"

These data were first presented at the 2025 American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:

I am Antonio Marra. I'm medical oncologist at European Institute of Oncology in Milan, Italy. And this year at ASCO, we presented a study aimed at evaluating the role of germline BRCA1/BRCA2 alterations in patients with hormone receptor-positive, HER2-negative early breast cancer.

We know that hormone receptor-positive, HER2-negative breast cancer is the most commonly diagnosed breast cancer subtype in the world. And in this patient population, the role of germline BRCA1/BRCA2 in determining the prognosis is not well characterized. Using an institutional database with about 15 to 20 years of follow-up, we studied the incidents and prognostic role of germline BRCA1, BRCA2, and PALB2 genetic alterations. We had a matched population of wild-type tumors to be the control group, and we analyzed all the clinical, pathological, physical, and treatment information that were available. The primary aims of the study were to evaluate the impact of germline status on invasive disease-free survival and distant relapse-free trial.

In this patient population, we found that patients with germline BRCA-altered tumors have higher disease stage and high advanced grade at baseline compared to non-carrier controls. When we look at the treatment, consistently we found that these patients had an advanced stage. Patients receive more commonly neoadjuvant chemotherapy and adjuvant chemotherapy compared to the non-carriers. No differences were found in the type of adjuvant treatment that was prescribed. As per clinical practice, all patients that were premenopausal at diagnosis had received ovarian function suppression.

The main findings were that germline BRCA1, BRC2, and PALB2 status was independently associated with the reduced distant relapse-free interval and invasive disease-free survival in this patient population. This statistical significant difference was maintained even in the multivariate analysis adjusted for multiple covariates. As additional analyses and exploratory analyses, we try to understand which part of this patient population is currently eligible for adjuvant treatment with PARP inhibitors based on the OlympiA criteria. And surprisingly, we found that only 20% of these patients are currently eligible for treatment with adjuvant olaparib. Despite, as we clearly show in the main analysis, that this patient population is associated with reduced long-term outcomes and that improved risk of disease relapse.

The main conclusion is that this patient population, especially in the one carrying BRCA2 germline alteration, should be investigated in further clinical trials to understand whether an escalation of adjuvant treatment, including PARP inhibitors, novel DDR agents alone or in combination with novel agents for endocrine therapy, can improve the outcome of the population. In conclusion, I'd say that germline BRCA1/BRCA2 altered, early stage hormone receptor-positive, HER2-negative breast cancer is a population that need to be investigated in new trials. testing novel drugs.

Source:

Marra A, Perazzo S, Martino E, et al. Impact of germline BRCA status on clinical outcomes of patients with HR+/HER2- early breast cancer. Presented at the 2025 ASCO Annual Meeting. May 30-June 4, 2025; Chicago, IL. Abstract #559