ADAPT - Chemotherapy-Free Treatment

In Germany, approximately 70,000 women are diagnosed with breast cancer each year. Of these, 44,000 have hormone receptor-positive breast cancer.

Until now, it was common practice for patients at high risk of recurrence to receive chemotherapy in addition to hormonal therapy (tamoxifen or aromatase inhibitors). Patients at low risk received only endocrine therapy.

The challenge lay in selecting the optimal therapy for patients with moderate risk of recurrence, who make up about half of all patients with hormone receptor-positive tumors. It was particularly difficult to predict which women in this group would benefit from chemotherapy.

To answer this question, the ADAPT studies were conducted. They included:

• Patients aged 18-75
• Hormone receptor-positive tumors, HER2-negative
• T1 to T4c, N1-3, M0

After tumor biopsy, patients had their Ki67 level and recurrence risk determined using the OncotypeDX test. They were then categorized into three risk groups: high, intermediate, and low.

Patients with up to three affected lymph nodes also had their Ki67 level and recurrence risk assessed using the OncotypeDX test. These patients received 3 weeks of induction endocrine therapy, followed by a repeat biopsy or surgery.

Patients with N0-N1, Ki67 below 10%, and an OncotypeDX recurrence risk score below 12 received tamoxifen or aromatase inhibitor therapy. If Ki67 remained high or OncotypeDX was greater than 25 after induction endocrine therapy, patients received chemotherapy in addition to endocrine therapy.

To emphasize once again, after the initial biopsy, patients underwent 3 weeks of endocrine therapy. Then, a repeat biopsy was performed, and if there was a favorable response to endocrine therapy, further treatment consisted ONLY of endocrine drugs. This is a very progressive approach!

The results showed that women in the intermediate-risk group, with Ki67 reduced to 10% or lower after induction therapy, achieved similar results in terms of recurrence-free survival and overall survival as patients with low risk at the initial biopsy.

Furthermore, there was a high-risk group with subdivision into groups receiving paclitaxel and nab-paclitaxel. In this case, nab-paclitaxel demonstrated an effectiveness rate 2 times higher than the complete pathological response rate - from 10% to 20%.

The research is ongoing as there are still interesting questions to be answered:

• What about women with 4 or more affected lymph nodes?
• How should women with a good response to endocrine therapy but a poor response to chemotherapy be managed?
• Can these women benefit from intensified endocrine therapy?

These questions are currently being investigated in the ADAPT-cycle study, and we are eagerly awaiting the results, hoping that this group of patients can be treated without chemotherapy with equally good outcomes!