Kelly K. Hunt, MD, MD Anderson Cancer Center, Houston, Texas, discusses findings following, "Neoadjuvant Endocrine Therapy: Optimal Strategies and Impact on Surgical Outcomes", presented at the 2021 Miami Breast Cancer Conference. 
 

Transcript

Hi, I am Kelly Hunt, and I am the chair of Breast Surgical Oncology at the MD Anderson Cancer Center in Houston, Texas. What I am speaking about is neoadjuvant endocrine therapy. This is a topic that has been evolving over the last 10 years.

It is known that about 2/3 of women who develop breast cancer will have hormone receptor-positive disease, and endocrine therapy is a big component of their treatment.

For those that have more advanced disease at presentation, neoadjuvant chemotherapy has been utilized in order to downstage the primary tumor to allow for reduction in mastectomies and increased rates of breast-conserving surgery. We also know that neoadjuvant chemotherapy can reduce the incidents of nodal metastases that are found at surgery.

Also, an important thing is that improved outcome has been associated with pathologic complete response associated with neoadjuvant chemotherapy. In hormone receptor-positive disease, patients that have strongly estrogen receptor-positive tumors, we do not see these dramatic responses with neoadjuvant chemotherapy.

We see less down-staging of the primary tumor and we see less reduction in the incidents of nodal metastasis when we compare that with other subtypes. Many have looked at the role of neoadjuvant endocrine therapy before surgery to see if that improves rates of breast conservation and allows for less aggressive surgical approaches in those patients who initially present with larger tumors.

There was a randomized trial comparing neoadjuvant endocrine therapy to neoadjuvant chemotherapy in patients with advanced-stage disease and estrogen receptor-positive tumors that was published in 2007. This showed that the rates of pathologic complete response were the same.

Whether patients received chemotherapy or endocrine therapy, it was quite low. Less than 10 percent of patients achieved path CR. They did find that there was a higher rate of breast-conserving surgery in those patients that received neoadjuvant endocrine therapy.

Now that we have aromatase inhibitors well-established in postmenopausal women that have estrogen receptor-positive breast cancers, we have data from the ACOSOG Z1031 trial that compared three aromatase inhibitors for 16 weeks prior to surgery.

What we saw is that the three different aromatase inhibitors performed similarly, in that clinical response rates were the same no matter which AI the patients received. We did find in that study that surgical outcomes were improved, in terms of patients that were thought to be marginal candidates for breast conservation.

80% of them were able to have breast conservation with negative margins. Those that were thought to require mastectomy at presentation, 50% were able to have breast conservation after only 16 weeks of neoadjuvant AI. Ki67 was shown to be a useful biomarker to assess treatment response.

We also looked at the Preoperative Endocrine Prognostic Index, which is also known as the PEPI score. This looks at tumor size, nodal status, Ki67 level, and ER Allred score after neoadjuvant endocrine therapy.

We know that a PEPI 0 status is associated with improved survival outcome. In the Z1031 trial, patients who achieved a PEPI 0 status had improved recurrence-free survival when looking at the entire patient population and in those patients who received chemotherapy.

The question remains in the field, how can we increase the PEPI 0 rate in patients that are getting neoadjuvant endocrine therapy? It is probably going to be through combination treatment strategies. Just using AI alone is probably not sufficient.

We also know that treatment duration plays a role. Longer duration of endocrine therapy does result in a better PEPI 0 score or an increased PEPI 0 score. Also, we can use genomic tools for patient selection.

There are several trials that are ongoing looking at other endocrine therapies besides just AI. There are also multiple pathways that we know are involved in endocrine therapy resistance. Some of the combination treatment strategies are looking at targeting these pathways. Thank you.