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Expert Addresses Controversies in Management of HR+ Early-Stage Breast Cancer

Kristi Rosa
Published: Sunday, Dec 16, 2018

Rachel C. Jankowitz, MD

Rachel C. Jankowitz, MD

Adjuvant endocrine therapy has become the standard treatment for patients with hormone receptor (HR)–positive, HER2-negative breast cancer. However, while therapeutic developments and longer follow-up data have led to a shift to more individualized treatment, a lack of consensus persists.

“Part of the problem centers around the fact that there are so many choices and individual patient factors that you consider when making these decisions in the clinic,” explained Rachel C. Jankowitz, MD.

With the availability of new and effective agents, options for endocrine therapy have expanded, and many have been integrated into the early-stage setting. However, many questions remain regarding timing of ovarian suppression and the optimal use of available agents.

In a recent presentation at the 2018 OncLive® State of the Science Summit™ on Breast Cancer, Jankowitz, assistant professor of medicine at the University of Pittsburgh School of Medicine and the University of Pittsburgh Medical Center Hillman Cancer Center, discussed the range of risk associated with HR-positive, HER2-negative breast cancer, important factors physicians should consider when choosing the appropriate therapy, and the importance of communicating with patients about associated adverse events (AEs).

OncLive: Could you provide an overview of your presentation on adjuvant hormonal therapy in earlystage breast cancer?

Jankowitz: The beginning part of my presentation was an overview of duration of tamoxifen therapy and how we arrived at 10 years of tamoxifen being superior to 5 years in this patient population.

I then discussed the duration of aromatase inhibitors and what we’ve learned, now that trials looking at 10 years of aromatase inhibitor use versus 5 years have started to mature. The final part of my presentation was about ovarian function suppression for premenopausal women with breast cancer.

The overarching theme of my presentation is that there’s a range of risk when it comes to HR-positive/HER2-negative breast cancer, where certain patients are on the lower end of that scale and other patients are on the higher end. We have a number of ways to assess that risk. Generally, we look at factors such as the stage of their disease, but we have also come to look more at quantitative expression of HR status, grade, Ki-67, and gene expression profiles when we’re making decisions about adjuvant endocrine therapy.

The other important thing that we need to consider when talking to our patients about these therapies is tolerance, quality of life, and AEs. Often, more aggressive hormonal therapies are accompanied by AEs. We’re always weighing these incremental gains against how well patients are tolerating these therapies and how high breast cancer risk was to begin with.

Could you explain how 10 years of tamoxifen use proved to be superior to 5 years? What else do we know now about aromatase inhibitors?

The ATLAS and aTTom trials are 2 very large studies that looked at approximately 17,000 women with early-stage breast cancer who were randomized to receive either 10 years or 5 years of tamoxifen. It took a long time to see this, but at about 10 years of follow-up you started to see an improvement in disease-free survival [DFS] with 10 years of tamoxifen use compared with 5 years.

That benefit was apparent regardless of stage, age, and menopausal status—so really, all subsets benefited. Does that mean that every patient needs 10 years of tamoxifen? Not necessarily. Women with stage I cancer who also have low gene expression profiles, for instance, may not do 10 years of tamoxifen, but yes, there is a benefit to receiving it beyond 5 years.

What are the controversies in the management of HR-positive early-stage disease? How do you assess risk for these patients?

In the beginning of my presentation, I highlighted some of the current consensus guidelines from the St. Gallen International Breast Cancer Expert Panel and ASCO, and they don’t always match; they’re not always updated. That, in and of itself, is sometimes confusing to patients and providers.

Also, in terms of how long to give an aromatase inhibitor, there is controversy at face value because 1 large trial showed a DFS advantage with 10 years of aromatase inhibitor use versus 5 years, while another trial did not. However, if you really break down the data and look at the way that they define that endpoint, the data are actually quite similar between the 2 trials; [the problem] was [with the] language they used to define DFS.

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