NGS, essential tool for breast cancer treatment, but Korea’s reimbursement barriers stall progress

Just over a decade ago, doctors relied on biopsy results and a few clinical indicators to develop treatment plans for breast cancer. At the time, pathology reports documented the tumor's size, cell type, and hormone receptor status, and doctors used this information to combine hormone therapy, chemotherapy, and radiation therapy.

However, today's clinics look completely different. Doctors analyze patients' tumors in detail, including genetic mutations, protein expression patterns, and treatment resistance signals, and use the results to adjust the type and sequence of drugs in real time. This change shows that treatment strategies are no longer static but dynamic, like a car navigation system that reflects real-time traffic conditions.

At the center of this innovation is next-generation sequencing (NGS). NGS goes beyond its previous role as a one-time map needed at the start of treatment and now serves as a precise dashboard that tells us when to change drugs throughout the treatment process. In the field of breast cancer, NGS is no longer a simple “test” but has become a core pillar of treatment strategies.

NGS is not an option but the first step toward treatment

Approximately half of patients with hormone receptor (HR)-positive breast cancer have mutations in the PIK3CA, PTEN, and AKT genes. These mutations are the primary targets of targeted therapies, such as alpelisib, inavolisib, and capivasertib.

The only method capable of accurately identifying all three of these mutations simultaneously is NGS. Conducting individual gene tests sequentially would require excessive time and costs, potentially causing patients to miss treatment opportunities. Additionally, considering the possibility of concurrent or overlapping mutations, NGS is the only option capable of providing an integrated analysis.

Therefore, NGS is not an option but a necessity for HR+ breast cancer patients, serving as the first step in determining treatment direction. Starting treatment without NGS is akin to entering a maze without a map. In the era of personalized medicine, the absence of NGS directly translates to treatment delays and worsened outcomes.

NGS redesigns the patient's treatment pathway in real time

That's not all. NGS is now moving beyond the traditional concept of a “one-time test before treatment.” A prime example of this is the SERENA-6 study presented at the ASCO 2025 Plenary Session in June.

The SERENA-6 study included patients with HR+/HER2– advanced breast cancer. The research team initiated standard treatment with aromatase inhibitors (AI) and CDK4/6 inhibitors for all patients. During treatment, if the “ESR1 mutation” was newly detected in blood ctDNA analysis, the existing AI was switched to “camizestrant,” an oral selective estrogen receptor degrader (SERD), before the disease worsened on imaging tests.

The results showed that the early switching group had a 56 percent reduced risk of disease progression and death compared to the group that continued with the original AI therapy (HR 0.44). This is the first phase 3 clinical trial to demonstrate that changing treatment strategies based solely on blood-based genetic signals can improve patient outcomes.

The SERENA-6 study raises challenging questions within the current regulatory and reimbursement framework. Traditionally, NGS testing has been performed only once before treatment initiation. However, ctDNA-based NGS allows for repeated measurements not only before treatment but also during and after treatment.

This represents an evolution from a simple map to real-time navigation that continuously guides the treatment process. The SERENA-6 study demonstrated through a phase 3 clinical trial that this monitoring strategy can improve patient survival.

NGS has now advanced beyond a one-time tool for selecting drugs to become a core device that guides patients throughout their entire treatment journey. As a result, treatment is no longer a fixed course but a customized path that responds immediately to changes in the patient's condition.

Precision medicine is ‘accelerating’ while Korea's reimbursement policy is ‘going backward’

What is the situation in Korea? While the world is rapidly advancing toward precision medicine based on NGS, Korea's reimbursement policies are moving in the opposite direction.

In 2017, Korea introduced selective reimbursement for NGS, setting the patient copayment rate at 50 percent. However, in late 2023, the copayment rate was increased to 80 percent (excluding lung cancer). This decision has significantly increased the cost burden for cancer patients and noticeably worsened access to testing.

In this situation, Korean breast cancer experts have recently been calling for a reduction in the copayment rate for NGS screening from the current 80 percent to 50 percent for patients with stage 3 or 4 breast cancer. In March this year, the Korean Cancer Association and the Korean Cancer Study Group held a policy discussion forum at the National Assembly to formally convey this request to the government.

At the forum, Professor Im Seock-ah of the Department of Hematology-Oncology at Seoul National University Hospital presented the keynote speech, highlighting the necessity of NGS by presenting the results of genetic panel test analyses conducted over the past seven years at Seoul National University Hospital. Professor Im revealed that more than half of patients with locally advanced or metastatic breast cancer harbor treatable mutations. She also introduced findings showing that when these patients received treatment with approved targeted therapies or experimental drugs, their average survival period was extended from two years to a maximum of five years.

This analysis was published in the international academic journal “Cancer Research and Treatment (CRT)” issued by the Korean Cancer Association in August 2023 and is considered evidence that NGS-based personalized treatment can substantially improve patient survival rates.

Delays in drug reimbursement are another barrier to precision medicine

Korea faces another barrier in the form of limited access to treatment. Even if the door to diagnosis is open, precision medicine cannot function if the door to drug reimbursement is closed. Currently, the second door is particularly tightly closed in Korea.

Alpelisib, inavolisib, and capivasertib, mentioned earlier, are currently not reimbursed in Korea. These three drugs are targeted therapies for half of HR+ breast cancer patients. In other words, even if half of HR+ breast cancer patients are diagnosed with a treatable target, they cannot receive treatment covered by insurance. Among these, alpelisib, the first to be introduced in Korea, received approval from the Ministry of Food and Drug Safety (MFDS) in May 2021 and has undergone multiple reimbursement applications, but remains non-reimbursed four years later.

Patients newly identified as HER2-low, who are now considered eligible for targeted therapy, face the same situation. This patient group, previously classified as HER2-negative, was excluded from targeted therapy in the past. However, the global academic community has recently recognized that Enhertu could become a new standard treatment for these patients. Notably, the DESTINY-Breast04 study presented at the 2022 American Society of Clinical Oncology (ASCO) annual meeting demonstrated that Enhertu significantly extended overall survival compared to existing treatments in HER2-low patients, receiving standing ovations. However, three years after the presentation, HER2-low patients in Korea still cannot access Enhertu through insurance coverage. Compared to major countries that have already adopted this treatment as standard, Korean patients remain excluded from clinically proven treatment benefits.

The situation is even more urgent for patients with triple-negative breast cancer (TNBC) who are PD-L1-positive (CPS≥10). This type of breast cancer does not express hormone receptors or HER2, limiting treatment options. Global treatment guidelines recommend the combination of chemotherapy and immunotherapy as the standard first-line treatment, with Keytruda (pembrolizumab) being the most commonly used drug. However, Keytruda remains non-reimbursed in Korea, and the Health Insurance Review and Assessment Service (HIRA) has been reviewing its reimbursement status for over two years. As a result, both patients and medical professionals are unable to predict when this drug will become available as a standard treatment in Korea.

When either diagnosis or treatment is hindered, patients lose the opportunity to receive optimal treatment. The current situation in Korea is like a bicycle with both wheels malfunctioning. In this state, it is impossible to reach the destination of precision medicine.

How to turn ‘happy dilemmas’ into reality

The “happy dilemmas” mentioned by Professor Im Seock-ah, where there are so many drugs to choose from, are the aspirations of both doctors and patients. However, for this aspiration to become a reality, certain prerequisites must be met.

The doors to diagnosis and treatment must be fully open. Currently, both doors in Korea are heavily closed, leaving patients stranded at the entrance, missing out on treatment opportunities.

Diagnosis and treatment are like interlocking gears that turn together. If one stops, the other stops, and the entire precision medicine system grinds to a halt. Only when the simultaneity and indispensability of these two pillars are fulfilled can breast cancer patients in Korea receive timely and appropriate treatment.

To avoid falling behind in the upcoming wave of treatment innovations, the government and the medical community must work together to find solutions that improve both diagnostic and treatment environments. Only then will “happy dilemmas” become a reality for both patients and medical staff in breast cancer clinics.