In the group that is arguably the best among these women—those presenting with T1N0 tumors—we see a steady increase in the [event] line, and it doesn’t seem to waver in any fashion.

— Nancy E. Davidson, MD

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Nancy E. Davidson, MD, the Hillman Professor of Oncology and Director of the University of Pittsburgh Cancer Institute in Philadelphia, was the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) study’s formal discussant. With this analysis, she noted, the EBCTCG has “reinforced the long natural history of estrogen receptor–positive breast cancer.”

Referring to the event curve, Dr. Davidson observed: “In the group that is arguably the best among these women—those presenting with T1N0 tumors—we see a steady increase in the [event] line, and it doesn’t seem to waver in any fashion.” The 21% recurrence rate at year 20, in this best-prognosis group, is a consequence of a 14% rate of distant recurrences and a 7% rate of local recurrence or contralateral breast cancers, although information on mortality risk would also be helpful, she added.

“Knowing this relentless increase in recurrence, there are strategies we might consider to improve outcomes in hormone-responsive early breast cancer,” Dr. Davidson said. Such strategies are growing in number and diversity to include extended endocrine therapy; combinations with novel agents; and unconventional nontargeted agents, such as metformin, bisphosphonates, and even aspirin, which are investigational in the setting of adjuvant breast therapy.

More on Extended Adjuvant Therapy

At the ASCO Plenary Session, the results of the MA.17R trial were reported (see the June 10, 2016, issue of The ASCO Post for further details), showing substantial benefits—but not overall survival—for extended treatment with letrozole on recurrences and contralateral breasts cancers,¹ she said.

Aside from prolonged endocrine therapy, based on encouraging results in the metastatic setting, palbociclib (Ibrance) and everolimus (Afinitor) are now being evaluated in the adjuvant setting. In similar populations—early-stage hormone receptor–positive, HER2-negative women treated for at least 5 years with endocrine therapy—the PALLAS trial (N = 4,600) will evaluate 2 years of palbociclib, and the S1207 trial will evaluate 1 year of everolimus. The primary endpoint for both studies is invasive disease–free survival.

Regarding the need for tailored assessment of risk, “an area of active research,” Dr. Davidson observed that the EBCTCG analysis “showed a range of recurrence based on tumor size and nodal status” and also included information related to Ki67 expression and grade. The aim is to “move beyond conventional histopathology,” perhaps with multigene testing, she added. “Increasingly, we hope these tests will be able to help us predict response to targeted therapy and to gauge the role of extended adjuvant endocrine therapy.” ■

Disclosure: Dr. Davidson reported no potential conflicts of interest.

Reference

1. Goss PE, Ingle JN, Pritchard KI, et al: A randomized trial (MA.17R) of extending adjuvant letrozole for 5 years after completing an initial 5 years of aromatase inhibitor therapy alone or preceded by tamoxifen in postmenopausal women with early-stage breast cancer. 2016 ASCO Annual Meeting. Abstract LBA1. Presented June 5, 2016.