How would you approach adjuvant treatment for a premenopausal woman with a large, lymph node positive HR+, Her2 negative lobular breast cancer?

In pure or classical estrogen receptor positive lobular breast cancers neoadjuvant chemotherapy works very poorly (3% vs 15% pCR; Cristofanilli et al. J Clin Oncol 2005;23:41-8) and you are not likely to convert mastectomy to lumpectomy. I would strongly consider neoadjuvant endocrine therapy, especially if the tumor is strongly ER positive, using aromatase inhibitor and monthly GnRH agonist. The every 3-month GnRH agonist preparations don't suppress estrogen levels as well as the monthly preparations. There is a large, mostly European literature on neoadjuvant endocrine therapy and it works. Finally, the ongoing Alliance Alternate trial is comparing neoadjuvant anastrozole vs. fulvestrant vs. the combination of anastrozole and fulvestrant....