Sergio Cifuentes Canaval, Medical Oncologist at Las Américas Auna Clinic, shared a post on LinkedIn about a recent article by Susan M. Domchek published in Journal of Clinical Oncology:

“ER-positive, BRCA-associated early breast cancer: how to apply this evidence in LATAM?

This article addresses one of the most relevant current dilemmas in early breast cancer: how to integrate PARP inhibitors (olaparib) and CDK4/6 inhibitors in ER+/HER2− patients with germline BRCA mutations, in a context of therapeutic de-escalation… but with potentially more aggressive biology.

1. Prediction: Not all ER+ are created equal

The article recalls something key and often ignored in daily practice:

ER+ patients with BRCA1/2 may have a worse prognosis than sporadic ER+ patients, especially BRCA2.

In LATAM, where many decisions are based on stage + receptors, this biological nuance is rarely incorporated into the therapeutic algorithm.

2. Oncotype DX: Really Reliable in BRCA?

Although Oncotype DX is widely used in the region to prevent chemotherapy:

There is no prospective validation of the Oncotype in BRCA carriers
BRCA tumors typically have homologous recombination deficiency (HRD), which is not captured by Oncotype
There are reports of early metastatic relapses in BRCA patients with low-intermediate RS

Involvement in LMICs:
Using Oncotype to de-escalate chemotherapy in BRCA+ ER+ may be risky, especially in young or node-negative patients.

3.Olaparib: who to offer it to when we do not comply with OlympiA ‘to the letter’?

OlympiA demands criteria that are difficult to meet today:
≥4 positive nodes
CPS+EG ≥3 after neoadjuvant

But in modern practice:

We do less and less ALND
It makes no sense to indicate ALND just to ‘count nodes’

The article proposes a pragmatic approach:
Consider olaparib in any BRCA+, ER+, node-positive patient after a risk-benefit discussion.

In LATAM, where access to PARP can be limited, correctly identifying who to really prioritize is key.

4. Olaparib vs CDK4/6: the great dilemma (no comparative trial)
There are no studies that directly compare:
Olaparib vs Abemaciclib / Ribociclib in adjuvant

Some critical points:

In metastatic disease, BRCAs may have less benefit with CDK4/6 (possible loss of RB1)
All OlympiA patients received intensive chemotherapy (anthracyclines + taxanes)

Key message for LMICs:

Giving both treatments for 3–4 years involves:
1. Cumulative toxicity
2. High cost
3. Low sustainability of the system
Selection should be individualized, not automatic.
Therapeutic de-escalation should not be applied blindly in BRCA+ ER+ patients
Oncotype DX is not enough
Olaparib should be considered beyond strict OlympiA criteria
CDK4/6 and PARP are not interchangeable
Shared decision-making is essential.”

Title: Therapeutic Considerations in Early-Stage, Estrogen Receptor–Positive, BRCA-Associated Breast Cancer