Should I take Tamoxifen with Kadcyla or wait until after?

Treatment timing questions like this are really important to discuss thoroughly with your oncology team. Many patients with HER2+ and ER+ breast cancer face similar decisions about combining or sequencing these therapies. Your research shows great advocacy for your own care, and bringing these findings to your doctor can help ensure you're getting the most appropriate treatment plan for your specific situation. Other community members who've navigated similar treatment decisions might have valuable insights to share about their experiences and how they worked through these timing questions with their care teams.

The reference below reports that ER and ET treatments were synergistic in significantly improving Overall Survival and Time to Progression. Of course the side effects may be more but could be worth it. In my Stage 4 breast cancer group several ladies are on treatments that target both ER and HER2 simultaneously. “Combining Endocrine Therapy with Trastuzumab Emtansine Improves Progression-Free Survival and Overall Survival in HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer” Medicina 2024, 60(6), 951. Abstract Background and Objectives: Patients with human epidermal growth factor receptor 2 (HER2) -positive, hormone receptor-positive (HR-positive) metastatic breast cancer (MBC) usually undergo trastuzumab emtansine (T-DM1) therapy in subsequent lines. Combining endocrine therapy (ET) with T-DM1 can improve treatment outcomes in this subtype. Therefore, this study aimed to investigate the benefits of using T-DM1 with ET in HER2-positive and HR-positive MBC. This study was the first to investigate the benefits of combining ET with T-DM1. Material and Methods: This study analyzed the medical records of patients with HER2-positive and HR-positive MBC who were treated with T-DM1 from June 2010 to December 2021. The patients were divided into groups based on whether they received concomitant ET with T-DM1. The primary endpoint was to determine the progression-free survival (PFS), while the secondary endpoints were overall survival (OS), objective response rate, and safety of the treatment. Results: Our analysis examined 88 patients, of whom 32 (36.4%) were treated with T-DM1 in combination with ET. The combination therapy showed a significant improvement in median PFS (15.4 vs. 6.4 months; p = 0.00004) and median OS (35.0 vs. 23.1 months; p = 0.026) compared to T-DM1 alone. The ORR was also higher in the combination group (65.6% vs. 29.3%; p = 0.026). Patients treated with pertuzumab priorly had reduced median PFS on T-DM1 compared to those who were not treated with pertuzumab (11.7 vs. 5.4 months, respectively; p < 0.01). T-DM1 demonstrated better median PFS in HER2 3+ patients compared to HER2 2+ patients, with an amplification ratio of >2.0 (10.8 vs 5.8 months, respectively; p = 0.049). The safety profiles were consistent with previous T-DM1 studies. Conclusions: The combination of T-DM1 with ET can significantly improve PFS and OS in patients with HER2-positive and HR-positive MBC. Our study suggests that prior pertuzumab treatment plus trastuzumab treatment might decrease T-DM1 efficacy. Keywords: metastatic breast cancer; trastuzumab emtansine; endocrine therapy; pertuzumab plus trastuzumab

Thanks @Ana Tuckman, yes I am familiar with this study but there are some facts to consider The study combining endocrine therapy (ET) with Trastuzumab Emtansine (T-DM1) showed great benefit but had drawbacks including its retrospective nature (not a randomized trial), potential lack of long-term follow-up, missing patient-reported outcomes (PROs) for quality of life, and the need to understand if prior anti-HER2 therapy (like pertuzumab) affects T-DM1 efficacy, though it's a strong preliminary finding. Key limitations involve real-world data variability, absence of PROs, and the potential impact of prior treatments (like Pertuzumab) on T-DM1's effectiveness, suggesting future randomized studies are needed. Study-Specific Limitations (Based on the provided snippet/context): Retrospective Design: The study appears to be a retrospective analysis, meaning it looks back at existing patient data, which can be less robust than a prospective randomized controlled trial (RCT). Potential for Bias: Retrospective studies may have selection bias or variations in care, unlike RCTs. Missing Quality of Life Data: The study lacked patient-reported outcomes (PROs), which are crucial for understanding treatment impact on daily life and are vital for long-term metastatic cancer care. Impact of Prior Therapy: An important question is whether prior treatment with drugs like pertuzumab (another anti-HER2 agent) affects T-DM1's effectiveness, a factor needing clearer investigation. General Limitations of T-DM1 & Combination Therapy: Adverse Events: While effective, T-DM1 (Kadcyla) carries risks like liver issues (hepatotoxicity), heart problems (reduced LVEF), interstitial lung disease (ILD), and general side effects (fatigue, nausea, musculoskeletal pain, neuropathy). No Long-Term Follow-up: Like many initial studies, there's a need for longer-term data to understand sustained effectiveness and delayed toxicities. In Summary: The study offers promising insights for combining ET with T-DM1, but its retrospective nature, lack of PROs, and unresolved questions about prior therapies highlight the need for larger, prospective trials to confirm these benefits and fully understand the safety profile.

Ram, all good comments - understand all the cons - just some background on the efficacy. The combination of ET and Her2 therapies appears to be Standard of Care in my Stage 4 support group. These ladies have 4+ years of survival. Maybe you are not Stage 4 since you have limited cycles and Stage 4 treatment is usually forever. None are taking Tamoxifen, either Aromatase Inhibitors, Faslodex or other more recent ET pathway drugs are used more. Sometimes with cyclin inhibitors too.

Thanks Ana - I figured the staging might be a critical factor too - I will share another recent study that was reported in San Antonio by a Dr Nadia Herbek - will share it here for reference and for others in our group who may be interested.