Treatment of HER2 positive stage 4 breast cancer: When to stop anti-HER2 agents.

person Yoshihiko Kamada Nahanishi Clinic, Naha, Japan info_outline Yoshihiko Kamada, Naoko Takigami, Kanou Uehara, Kentaro Tamaki, Nobumitsu Tamaki

Authors person Yoshihiko Kamada Nahanishi Clinic, Naha, Japan info_outline Yoshihiko Kamada, Naoko Takigami, Kanou Uehara, Kentaro Tamaki, Nobumitsu Tamaki Organizations Nahanishi Clinic, Naha, Japan Abstract Disclosures Research Funding No funding sources reported Background: The goal of treatment of stage 4 breast cancer has been prolongation of live without compromising the quality of life of the patient and family. However, with the incorporation of anti-HER2 agents in the treatment of HER2 positive primary breast cancer, stage 4 disease of this subtype has become potentially curable. The issue is when or by what criteria anti-HER2 drugs can be discontinued, since continuation of expensive medication post cure could be considered to be financial toxicity, but then premature discontinuation might jeopardize a previously unattainable condition of cure. We endeavor to address this issue. Methods: The treatment and survival of 110 cases of Stage 4 primary breast cancer treated between April 2011 to December 2023 (i.e. 12-year period) in our institution was evaluated retrospectively. Results: The subtype by immuno-histiochemistry of the 110 cases is as follows; Luminal A - 17 cases, Luminal B - 23 cases, HER2-enriched - 13 cases, Luminal-HER2 - 17 cases, Triple negative - 6 cases. The 5 and 10 year survival rates according to subtype is as shown in the table. Of the surviving 25 HER2 positive (Luminal and Enriched) cases, 16 cases are still on anti-HER2 therapy, while 6 cases have discontinued. 3 cases have been lost to follow-up. The metastatic site/duration (months) of anti-HER2 therapy/observation time (months) post anti-HER2 therapy of the 6 cases are, ..... case 1: bone & distant lymph-nodes / 19.0 / 11.2, ..... case 2: bone / 52.7 / 6.8, ..... case 3: bone / 76.2 / 2.1, ..... case 4: liver & distant lymph-nodes / 80.8 / 19.3, ..... case 5: liver 6 bone / 103.8 / 24.9, and ..... case 6: lung / 120.0 / 11.4. The cCR status by imaging modalities of all 6 cases were confirmed by 6 months after initiation of anti-HER2 therapy. Case 5, who continued hormonal therapy (i.e. tamoxifen) for an additional 22 months, terminated anti-HER2 therapy after testing negative for ERBB2 related genes on liquid biopsy. Conclusions: This observational study suggests that in stage 4 HER2 positive primary breast cancer patients in which cCR is achieved within 6 months of initiation of anti-HER2 therapy, the treatment might safety be concluded after an additional 2 to 3 years of anti-HER2 therapy. Liquid biopsy for tumor related genes (e.g. ctDNA, miRNA) might facilitate decision making. Subtype Luminal A Luminal B Her2-enriched Luminal HER2 Triple Negative 5 year survival rate 74.0% 52.4% 53.5% 76.0% 0% 10 year survival rate not assessable 52.4% 53.5% 60.8% not assessable