What adjuvant systemic therapy would you offer to a healthy elderly woman with a 5mm, node negative, grade 2 HR+HER2+ invasive lobular carcinoma?

Although several studies have clearly indicated a higher risk of recurrence for early stage HER2+ breast cancers, the absolute risk for T1aN0 breast cancers is still quite low. The studies have been limited by small numbers, but there are retrospective series suggesting excellent outcomes without adjuvant chemotherapy or trastuzumab for those with T1a, HR+/HER2+ breast cancer. Vaz-Luis et al in JCO 2014 reported 5 yr estimates: OS 95%, BCSS 99%, and DRFS 96%. Similar excellent outcomes were seen in the report by Fehrenbacher et al JCO 2013. Even when including T1b and HR negative tumors, the Gonzalez-Angulo et al study (JCO 2009) showed a 5 yr RFS rate of 77.1%, and DRFS of 86.4%. Thus, even endocrine therapy alone is reasonable to consider...

I would discuss weekly paclitaxel/trastuzumab followed by AI vs trastuzumab x 12 mos plus AI. The Japanese RESPECT trial randomized 275 women aged 70-80 with mostly stage I (>5mm)-II HER2+ tumors to adjuvant chemo+trastuzumab vs trastuzumab alone. The events were too few to do the planned analysis but the 3-year DFS was 89.2 vs 94.8 p=.35. If she is in good shape and wants to be maximally aggressive for a few percentage points DFS difference, you can try the weekly taxol/tras and stop it early if not well tolerated. Otherwise, I think she would likely do just as well with trastuzumab and AI.

Based on advanced age and a very small tumor, I would use endocrine therapy alone, using an AI like Letrozole.

AI only.