Optimal Duration of Adjuvant Endocrine Therapy Undecided in ER+ Breast Cancer

Maryann J. Kwa, MD

Further biomarker studies are needed to determine which patients may benefit from extended adjuvant endocrine therapy, in an effort to reconcile the high risk of recurrence in patients with estrogen receptor (ER)-positive breast cancer, said Maryann J. Kwa, MD.

Although the risk of distant recurrence continued up to 20 years after follow-up in a meta-analysis of 62,923 women with early-stage, ER-positive breast cancer—pooled from 88 trials from the Early Breast Cancer Trialists’ Collaborative Group—efforts to establish the optimal duration of adjuvant endocrine therapy have been unsuccessful, said Kwa.

“It's a challenge, because patients are concerned about toxicity and that's something that we try to balance with the efficacy of treatment,” Kwa explained.

OncLive: What does the landscape of early-stage ER-positive breast cancer look like?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Breast Cancer, Kwa, an instructor in the Department of Medicine, NYU Langone’s Perlmutter Cancer Center, discussed the optimal duration of endocrine therapy in the treatment of patients with early-stage ER-positive breast cancer.Kwa: The first part of my presentation focused on a meta-analysis that looked at over 60,000 women with early-stage ER-positive breast cancer who had received an initial 5 years of adjuvant endocrine therapy. They followed these women out for up to 20 years to see what the risk of distant recurrence was. The summary of the meta-analysis was published in the New England Journal of Medicine in 2017, and showed that there was a risk of distant recurrence all the way up to the 20-year mark. The risk of distant recurrence was 13% for small tumors and even greater for large tumors and involved lymph nodes.

Afterwards, I discussed the optimal duration of endocrine therapy and whether there is a role for extended adjuvant endocrine therapy. Results of the ABCSG-16 study was presented at the 2017 San Antonio Breast Cancer Symposium and looked at 2 additional years versus 5 years of an extended aromatase inhibitor (AI). The study was performed in Austria. The results showed that there was no overall difference in disease-free survival (DFS) between 2 and 5 years of additional therapy. However, of note, this was a study that involved patients who had smaller tumors that were lower grade and node negative.

How do you reconcile the high risk of recurrence in ER-positive breast cancer with compliance rates?

I also discussed the highly anticipated, recently reported TAILORx trial. The study was recently discussed at the 2018 ASCO Annual Meeting and looked at intermediate-risk patients who were based on the 21-gene recurrence score. These were patients who had an Oncotype DX Breast Recurrence Score test of 16 to 25. Half of the patients were randomized to receive chemotherapy and endocrine therapy and half were randomized to receive endocrine therapy alone. The study found that there was no difference in DFS between groups. A subgroup analysis looked at women who were 58 years of age or younger and found a small benefit in the women who received both chemotherapy and endocrine therapy.That is a really good question. In one of the studies that I discussed during the presentation, the drop-off rate was much higher in the longer patients who took endocrine therapy versus those who took it for a shorter duration.

Is neoadjuvant endocrine therapy underutilized in the United States?

Could the potential adoption of neoadjuvant endocrine therapy affect the use of adjuvant endocrine therapy?

What is the protocol at NYU Langone’s Perlmutter Cancer Center for neoadjuvant treatment?

What is an area of research you would like to see addressed?

What information do you hope oncologists apply to their practice?

Having discussions with patients in the clinic about the persistent risk of recurrence that goes beyond the initial 5 years of treatment [is important]. It provides additional information for patients to make an informed decision as to whether to stay on treatment or extend therapy beyond 5 years.It is. Right now, it is mostly used in the setting of an older patient. The patient may have comorbidities and can't tolerate chemotherapy to help downstage the tumor before surgery. A meta-analysis published in JAMA Oncology, and some other studies, showed that the response rates for patients who receive neoadjuvant endocrine therapy are similar to those in patients who receive chemotherapy. [Neoadjuvant endocrine therapy] also shows less toxicity.That is a really good question. Potentially, yes. There are no studies that I’m aware of that looked at patients who received [both] neoadjuvant endocrine therapy and adjuvant endocrine therapy. There could be questions with compliance—whether patients who receive neoadjuvant endocrine therapy and experience toxicity would be willing to continue therapy. Older patients tolerate neoadjuvant [endocrine] therapy much better than chemotherapy. It should be offered more in the clinical setting. The tendency is to use neoadjuvant chemotherapy for ER-positive/HER2-negative breast cancer. We do use neoadjuvant endocrine therapy for older patients with comorbidities.We need more biomarker-based studies that may be able to determine which patients will benefit from extended adjuvant therapy with an AI or tamoxifen.The risk of distant recurrence for patients with early-stage, ER-positive breast cancer persists beyond the initial 5 years of treatment with adjuvant endocrine therapy. Right now, the question is what the optimal duration of endocrine therapy is and whether there is a role of extended treatment. There have been many studies that are looking to answer that question.

As of right now, strongly hormone receptor—positive patients with larger and higher-grade tumors with positive lymph nodes may benefit from extended AI therapy.

Based on the results from TAILORx, patients with an intermediate-risk recurrence score based on the 21-gene assay may not benefit from the addition of chemotherapy to endocrine therapy alone.

Lastly, neoadjuvant endocrine therapy is underutilized in the United States. There is ongoing research looking at this modality of treatment in the neoadjuvant setting. We are also looking at biomarkers that can predict which patients will respond to treatment and those who are not going to respond to treatment.

Pan H, Gray R, Braybrooke J, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017;377:1836-1846. doi: 10.1056/NEJMoa1701830.