What is your approach to adjuvant endocrine therapy in high-risk premenopausal women with ER/PR+ Her2+ breast cancer?

There are no large scale modern era assessing the role of adjuvant hormonal therapy in patients with HER2+ and hormone receptor positive breast cancer. Data from metastatic trials and cohort studies do suggest that there is an interaction with concurrent hormonal and HER2-targeted therapy and the two together are beneficial. However, the impact of hormonal therapy in the longer term is not as clearly known. I tend to be a "lumper" rather than a "splitter", so I currently do apply principles from SOFT/TEXT for these patients and do recommend ovarian suppression and aromatase inhibitor therapy for premenopausal patients at high risk. Note that receipt of chemotherapy does not automatically make them high risk since many patients receive weekl...

As a follow up to this question, I wanted to share some points from the planned update after 9 years median follow-up of the combined analysis of TEXT and SOFT presented by Dr. Pagani at SABCS 2017. This joint analysis included 4690 premenopausal ER/PR+ patients, of whom 12% were HER2+. Among the subgroup of patients who received chemotherapy (N=2694), which had a benefit from exemestane plus ovarian function suppression (OFS) over tamoxifen plus OFS, between 17-20% were HER2+. Although a sustained 4% absolute improvement in the 8-year DFS was reported for the group who received exemestane plus OFS, a subset analysis for the HER2+ patients was not shown. As recommended by Dr. Pagani, the results for the HER2+ subgroup require further invest...

In the subset analysis for patients on SOFT with HER2+ breast cancer, tamoxifen in addition to LHRH agonist vs exemestane actually had an advantage. It is important to remember that tamoxifen is more preserving than full on estrogen deprivation and that you save more bone and joints, and perhaps cardiovascular risk that way.

For patients with ER+/HER2+ breast cancer who are on adjuvant trastuzumab after chemotherapy, whether premenopausal or postmenopausal, my practice is to give them tamoxifen instead of an AI during that time, because of the potential for interaction between the two targeted strategies, and to get more preservation of bone/joint, quality of life for as long as possible. Remember that in ER+/HER2+ breast cancer, events sti...

The young patients (<35) and those with HER2 positive tumors had the most benefit from complete hormonal blockade in the soft/text trials - however this is often very toxic for young patients and has long term effects on quality of life - so it really becomes a discussion about the risks and benefits. I often suggest patients try OFS and an AI - and if they can not tolerate it to switch to tamoxifen. The important thing is that they not discontinue hormonal therapy early. In addition, some of these patients may be getting neratinib following herceptin, so adherence to the oral therapies needs to be monitored.