Stephanie L. Graff, MD
Recent studies have demonstrated that escalation and de-escalation approaches, with chemotherapy, endocrine therapy, and CDK4/6 inhibitors, are areas of research moving to the forefront in hormone receptor (HR)–positive breast cancer, explained Stephanie L. Graff, MD.
For example, data from the phase III TAILORx trial demonstrated that adjuvant endocrine therapy had noninferior outcomes compared with adjuvant chemoendocrine therapy in patients with HR-positive/HER2-negative, node-negative early-stage breast cancer who have an intermediate risk of distant recurrence based on their Oncotype DX Breast Recurrence Score (HR, 1.08; 95% CI, 0.94-1.24; P = .26).1
More recently, at the 2018 San Antonio Breast Cancer Symposium (SABCS), results were presented for the phase III TAM-01 trial, which examined the efficacy of low-dose tamoxifen at 5 mg versus placebo in patients with atypical ductal carcinoma (ADH), lobular carcinoma in situ (LCIS), and estrogen receptor (ER)–positive or ductal carcinoma in situ (DCIS) of unknown origin. Data showed that the addition of low-dose tamoxifen significantly reduced the risk of new and recurrent disease after surgery.2
Additionally, the CDK4/6 inhibitors abemaciclib (Verzenio), ribociclib (Kisqali), and palbociclib (Ibrance), which are all approved by the FDA in the metastatic breast cancer setting, are now being evaluated in the high-risk adjuvant setting in the monarchE (NCT03155997), NATALEE (NCT03701334), and PALLAS (NCT02513394) studies, respectively.
“There are a lot of interesting opportunities around the idea of escalation and de-escalation of care,” said Graff, director of the Breast Program at the Sarah Cannon Cancer Institute of HCA Midwest Health, and associate director of the Breast Cancer Research Program at Sarah Cannon Research Institute.
In an interview during the 2019 OncLive® State of the Science SummitTM on Breast Cancer, Graff discussed the latest updates on escalation and de-escalation of therapy in patients with HR-positive breast cancer.
OncLive: What are the updates in escalation and de-escalation of care for patients with HR-positive breast cancer?
Graff: On the heels of the TAILORx trial, which we saw at the 2018 ASCO Annual Meeting, we saw that a lot of women won’t need chemotherapy to treat their breast cancer—which is a huge opportunity for us to de-escalate care. That is also going on in the background with lots of discussion around what the right length of adjuvant endocrine therapy is. Should we take it for 5 years? Should we take it for 2 years? Does it matter if patients receive 10 years of an aromatase inhibitor (AI) or 5 years of tamoxifen followed by 5 years of an AI? There is a lot of interesting thought happening.
Then, there are some emerging clinical trials of the CDK4/6 inhibitors in the adjuvant setting for patients with locally advanced HR-positive breast cancer. We are moving those drugs out of the metastatic setting and into the earlier-stage setting.
Were there any updates from the 2018 SABCS related to these strategies?
One of the things that really interested me at the 2018 SABCS was data looking at the use of tamoxifen for women with DCIS or the higher-risk, precancerous lesions—such as LCIS or atypical ductal hyperplasia. It asks the question of tamoxifen at 5 mg versus no therapy; again, this was almost a prevention sort of thing. The standard dose of tamoxifen has been 20 mg, but we know this comes with a lot of side effects that can be kind of scary, such as thromboembolic disease and uterine carcinoma. Looking at this 5 mg dose, we saw a big benefit compared with nothing. It gives us, again, an opportunity to de-escalate where something is better than nothing, in those patients with stage 0 DCIS who perhaps are worried about side effects. This gives us a real opportunity to still offer something.
What factors are you looking at to determine the optimal dosage and length of treatment for a patient with DCIS?
All sorts of things are going to factor into our decision around what the right dose of tamoxifen is for women with DCIS. Of course, the trial was not randomized to the standard dose versus 5 mg; it was 5 mg versus nothing. Often in DCIS, we’ll now use the AIs, which we know are a little bit better than tamoxifen.