"It is not easy to demonstrate overall survival (OS) improvement in early breast cancer patients. However, patients with BRCA mutations experience faster and more aggressive disease progression compared to the general patient population, which made it possible to observe OS differences within a relatively short period. This is the clinical significance of the Lynparza OlympiA study."
Lynparza (ingredient: olaparib) is the first PARP (Poly ADP-ribose polymerase) inhibitor to demonstrate OS improvement in patients with gBRCA-mutated, HER2-negative, high-risk early breast cancer. After initially receiving approval for the treatment of adult patients with gBRCA-mutated, HER2-negative metastatic breast cancer who had prior chemotherapy, its indication was expanded to adjuvant treatment for adult patients with gBRCA-mutated, HER2-negative, high-risk early breast cancer who received neoadjuvant or adjuvant chemotherapy.
With this, Lynparza has been expanding its clinical application as an early treatment option for breast cancer patients with gBRCA mutations. The OlympiA trial, which provided this evidence, was presented at the San Antonio Breast Cancer Symposium (SABCS 2024) in December 2024 and drew significant attention.
In this context, Korea Biomedical Review spoke with Professor Kim Ji-hyung of the Department of Medical Oncology at Gangnam Severance Hospital about the clinical value of Lynparza in gBRCA-mutated early breast cancer and triple-negative breast cancer.
Question: Based on BRCA mutations, what is the current treatment environment for early breast cancer and triple-negative breast cancer (TNBC)?
Answer: In early breast cancer, the first step is to check for BRCA mutations. If a mutation is found and the patient is considered high-risk, then after neoadjuvant chemotherapy before surgery or adjuvant chemotherapy after surgery, a BRCA-targeted therapy is used as an adjuvant treatment.
The current standard applies to HER2-negative early breast cancer patients, which includes both triple-negative breast cancer (TNBC) and HR-positive breast cancer. In general, high-risk early breast cancer—whether TNBC or HR-positive—receives neoadjuvant chemotherapy before surgery.
After surgery, the standard treatment for HR-positive breast cancer patients is hormone therapy—endocrine therapy—for five years. For TNBC patients, the post-surgery approach depends on whether or not they achieved a pathological complete response (pCR).
If a pCR is not achieved, additional adjuvant chemotherapy is given after surgery. Even for patients who achieve pCR, if a BRCA mutation is present, adjuvant therapy may still be considered.
Q: In early breast cancer, not only Lynparza but also CDK4/6 inhibitors have recently been approved. What are the characteristics of the patient groups that receive these drugs, including Lynparza?
A: Lynparza applies to both HR-positive and triple-negative breast cancers, and in some patients, the indications overlap with CDK4/6 inhibitors. For example, if an HR-positive breast cancer patient has a BRCA mutation, both CDK4/6 inhibitors and PARP inhibitors like Lynparza may be options. However, patients who use both drugs are extremely rare in practice—perhaps one or two cases a year.
Both CDK4/6 inhibitors and PARP inhibitors can be prescribed for these high-risk patients. However, there is no definitive answer yet on which treatment to prioritize when both options are available. Discussions on this issue are ongoing not only in Korea but also globally at academic meetings. Still, no prospective trials are being conducted, and it is not easy to establish strong clinical evidence in this area.
For now, decisions must be made based on the existing data. The key is to weigh which strategy may improve survival, which drug has fewer side effects, the cost of treatment, and each patient’s underlying conditions to determine the best choice.
Q: Which patients would need to use both CDK4/6 inhibitors and PARP inhibitors?
A: A representative case would be HR-positive breast cancer patients who, despite receiving six months of neoadjuvant chemotherapy, showed little reduction in tumor size after surgery and still had more than 10 axillary lymph node metastases. These belong to the subgroup of early breast cancer patients at very high risk of recurrence.
In such cases, if a CDK4/6 inhibitor and Lynparza can be prescribed because of a BRCA mutation, we explain the available treatment options to patients. But due to economic considerations and safety concerns, the two drugs are not used simultaneously.
When given this explanation, most patients ask how they should be treated. From the doctor’s perspective, the advice is to choose the drug that has demonstrated an OS benefit. At present, the only drug that has shown such evidence is Lynparza.
Academic societies have also reached a consensus that since Lynparza has proven an OS benefit, it should be prioritized in such cases. However, this is merely a consensus, not an established definitive guideline.
Q: TNBC is known to have a poor prognosis and high recurrence risk compared to other breast cancers.
A: In stage 0 or stage 1 TNBC, survival rates are not particularly worse than in other breast cancers. However, from stage 2 onward, the situation changes. Prognosis becomes as poor as that of late stage 3 HER2-positive breast cancer, with rapid recurrence and high aggressiveness.
Especially in stage 2 or 3 high-risk groups, recurrence rates are high, and survival after recurrence is markedly lower. In Korea, TNBC is often diagnosed in younger patients, and the younger the patient, the faster and more aggressive the disease tends to be, making strategies to prevent recurrence and metastasis all the more crucial.
Thus, in high-risk early breast cancer patients, the strategy is to shrink the tumor with neoadjuvant chemotherapy before surgery. The goal after surgery is to leave no residual cancer cells in the tissue—this is called pathological complete response (pCR). Whether pCR is achieved is a critical factor determining prognosis in TNBC patients.
Among patients who achieved pCR with standard treatment, about 95 percent did not relapse. However, those who failed to achieve pCR still face high recurrence risk, requiring additional treatment strategies. Currently, there is no clear solution, but participation in new clinical trials can be considered, and for patients with BRCA mutations, targeted therapies may be applied.
TNBC patients may receive pembrolizumab (brand name: Keytruda) as neoadjuvant and adjuvant therapy. If a BRCA mutation is present, Lynparza may be combined with pembrolizumab, or used sequentially after pembrolizumab therapy. The choice depends on the patient’s condition and circumstances.
On the other hand, in patients without BRCA mutations who did not achieve pCR, the recommendation is to continue existing standard therapies or to participate in clinical trials for new drugs.