Extended Adjuvant Therapy in Breast Cancer Requires Individualized Approach

Paula Klein, MD

De-escalation of adjuvant therapy for patients with early-stage hormone receptor (HR)-positive breast cancer continues to be an area of investigation, said Paula Klein, MD, with the constant goal to avoid overtreatment in this population.

“It’s great that we have this cure rate [for these patients],” Klein explained. “It’s the word of the times: de-escalate. We need to preserve the cure rate or sacrifice very little and avoid the overtreatment of so many patients.”

Specifically in this setting, researchers have been focused on how to best select patients for extended adjuvant therapy beyond 5 years of tamoxifen with additional time on tamoxifen or an aromatase inhibitor (AI). An essential component of this forward way of thinking, Klein added, is to focus on the biology of the disease versus tumor size.

OncLive: There have been discussions on de-escalation of therapy in this breast cancer space. Could you discuss this?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Advanced Breast Cancer, Klein, an associate professor at the Icahn School of Medicine, Mount Sinai Health System, discussed the research surrounding extended adjuvant therapy in early-stage HR-positive breast cancer.Klein: The whole field is trying to de-escalate. We have reached a cure rate that is terrific, but it came with piling on lots of treatment to many, many patients. We know that we are overtreating a good number of patients, and the goal is to find those patients who don’t benefit [from extra therapy] and only get additional toxicity from whatever treatment they do have—whether targeted treatments, antibodies, antiestrogens, etc.

What steps do researchers need to take to get to that point?

One of the big themes in oncology is precision medicine. Is there a wave of this occurring in breast cancer?

What studies did you highlight in your presentation at the State of the Science Summit™?

What is the main message for community physicians about this area?

Therefore, the stage has been set to continue adjuvant therapy beyond the 5 years and there are some hallmark trials that certainly pave the way but, once again, with the full knowledge that we are overtreating patients. There have been some studies looking at less of an extension that seem to be just as good. The goal is to find the high-risk patient who is bound to recur, despite the 5 years of endocrine therapy, and only treat those—that is the holy grail. We are not there.There are 2 ways of looking at HR-positive breast cancer these days, and certainly early-stage ER-positive breast cancer. There are the old-fashioned, clinical pathologic features: how big the tumor is, what the lymph node status is, what the grade is, etc. There is a sort of revolution to look at the biology of each woman’s unique cancer and treat them based on that rather than size. A [poor] biology, despite a small tumor size, triggers aggressive therapy.Precision medicine is a word that is kind of tossed around; it does not necessarily mean what everyone is using it as. Our goal is to treat a patient’s unique biology; it is not just to treat “Mrs. Smith” and “Mrs. Jones” the same way, simply because each of them had a 2-cm tumor without lymph node involvement. Perhaps they are both ER-positive and HER2-negative, but the goal is to drill down. This is where personalized medicine, or the use of genomics [comes in], to evaluate each woman’s individual tumor and try to de-escalate or escalate therapy if we find that is the right path. Precision medicine takes into account a lot of things: who the person is and the biology of the tumor—the newest is what we call next-generation sequencing—is drilling down into the DNA and cancer cell. This is the future.The “grandfather” or “birth” from all of this came from the first adjuvant clinical trial, which was of 5 years of tamoxifen versus [no therapy]. Slowly, we then looked at 5 years of tamoxifen versus 10 years, and 5 years of tamoxifen going onto 5 years of an AI, and then 10 years of an AI versus 5 years of an AI, and the plethora of studies over the last 5 years have been looking at treatment beyond the first 5 years.It is going to come down to where we, honestly, as a community think we should be offering longer duration of therapy. I had one slide [in my presentation at the State of the Science Summit™] of genomic assays that have been looked at to help predict late recurrence, and none of them have gotten near the guidelines. Therefore, we are far away [in that aspect].