Hung T. Khong, MD
Neoadjuvant endocrine therapy is well utilized in Europe but underutilized in the United States, says Hung T. Khong, MD. Many factors are at play, but they can be boiled down to physicians’ familiarity with chemotherapy in the treatment of patients with estrogen receptor (ER)-positive breast cancer.
“Now, we know that many patients may not need chemotherapy, so we’re trying to promote the use of upfront endocrine therapy,” says Khong, a medical oncologist at Moffitt Cancer Center.
The results of numerous clinical trials demonstrate neoadjuvant endocrine therapy’s effectiveness in practice. A phase II study of 239 postmenopausal women with ER-positive and/or progesterone receptor–positive breast cancer were randomized to chemotherapy with doxorubicin and paclitaxel every 3 weeks for 4 cycles, or to 25 mg exemestane daily or 1 mg anastrozole daily for 3 months.
Both the endocrine therapy and chemotherapy arms showed a 64% clinical objective response; however, there was an absolute difference of 9% with breast-conserving surgery in the endocrine versus chemotherapy group at 33% and 24%, respectively (P
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Breast Cancer, Khong expanded on the benefits of neoadjuvant endocrine therapy and addressed the use of adjuvant endocrine therapy in ER-positive breast cancer.
OncLive: What is the benefit of neoadjuvant endocrine therapy?
: Neoadjuvant endocrine therapy is usually used to downstage tumors so that surgery can be optimally performed. In patients who [would otherwise] require a mastectomy, downstaging the tumor can enable a lumpectomy, conserving the breast. The use of neoadjuvant endocrine therapy can also convert an unresectable tumor to a resectable tumor. In addition, it can confer long-term survival benefit. The adverse events (AEs) are very minimal compared with those seen in chemotherapy. The benefit is very similar to, and in some cases better than, chemotherapy. It’s important to note that the benefit of neoadjuvant endocrine therapy is not inferior to chemotherapy.
Are patients hesitant about undergoing neoadjuvant chemotherapy?
Patients want a quick means of treatment, so that they can proceed to surgery sooner rather than later. They don’t like the mental image of having a tumor in their breast. Neoadjuvant endocrine therapy is usually done for 4 to 6 months; I prefer 6 months minimum. A lot of patients don’t understand why they would wait 6 months before proceeding to surgery. They also can’t fathom that such a little pill with so few AEs can benefit them. It’s just a misconception that patients have.
Does the optimal duration vary across endocrine therapies?
For postmenopausal women, we recommend 6 months [of therapy] regardless. We’ll usually use an aromatase inhibitor (AI), which are shown to be superior to tamoxifen for premenopausal women. Therefore, I usually consider chemotherapy for premenopausal women because we don’t have a lot of data aside from patients who enter studies of endocrine therapy, tamoxifen, or another combination.
Can targeted agents enhance the efficacy of neoadjuvant endocrine therapy?
Absolutely. Several ongoing studies are using CDK 4/6 inhibitors that have been shown to be beneficial to patients in the metastatic setting. Right now, we’re trying to use them more in the early-stage setting. There was a study that combined CDK 4/6 inhibitors with AI. We don’t have a lot of data, but the data that we do have show more benefit.
Should patients receive 2 or 5 years of additional adjuvant endocrine therapy?
The study that compared 2 years with 5 years of additional adjuvant endocrine therapy with the AI anastrozole showed no difference between 2 and 5 years of additional therapy. The problem is that a study like this is usually focused on low-stage disease—patients with stage I and possibly stage II disease.