Adjuvant AI Tx Extended to 10 Years for HR+ Breast Cancer

Postmenopausal women with node-positive, hormone receptor-positive (HR-positive) breast cancer should have the option to continue adjuvant endocrine therapy, including an aromatase inhibitor (AI), for 10 years, according to an updated clinical guideline.

Selected patients with high-risk node-negative disease should discuss the pros and cons of extended-duration endocrine therapy with their doctors and then decide how to proceed, according to the focused update from the American Society of Clinical Oncology (ASCO).

The update took into account data from recent clinical trials of extended-duration therapy with AIs in postmenopausal patients, as reported in the Journal of Clinical Oncology.

“One of the strengths of this update is that there have been multiple studies, and by pooling that data and seeing the patterns and similarities that emerged from all the work,” said guideline co-author Harold Burstein, MD, PhD, an ASCO clinical expert. “The study that probably came closest to mirroring most women in America is the NSABP B-42 trial. The patients were largely postmenopausal, might have had tamoxifen for a couple of years or an aromatase inhibitor; they got to year 5 and then the question came up about whether they should continue an aromatase inhibitor.”

The focused update honed recommendations for postmenopausal women with HR-positive breast cancer. An update published in 2014 recommended that patients who completed 5 years of adjuvant tamoxifen should be offered an additional 5 years of tamoxifen (pre- and perimenopausal patients) or offered the option to continue tamoxifen for 5 more years or switch to an AI (postmenopausal patients).

The 2014 update did not distinguish between node-positive and node-negative patients — but discussed nodal status as a prognostic factor — and placed a 5-year limit on total duration of AI therapy. At the time, no available data supported the safety and efficacy of AI therapy beyond 5 years.

The 2018 update (published in 2019) gave an unqualified recommendation that node-positive postmenopausal patients should be offered extended-duration endocrine therapy with an AI for a total of 10 years but no more than 10 years. Burstein and colleagues also concluded that many women with node-negative disease warrant consideration of extended AI therapy if they have high-risk disease, as defined by established prognostic factors.

“However, as the recurrence risk is lower, the benefits are likely narrower for such patients,” the authors noted.

Extended endocrine therapy should not be offered routinely to women with low-risk node-negative disease.

The guideline panel highlighted three “preferred options” for extended-duration endocrine therapy for postmenopausal patients:

• 10 years with an AI
• 2-3 years of tamoxifen followed by 7-8 years with an AI
• 5 years of tamoxifen followed by 5 years with an AI

The recommendation for premenopausal patients remained unchanged: 10 years of tamoxifen. Postmenopausal patients may also continue tamoxifen for 10 years if they cannot tolerate an AI or prefer tamoxifen over an AI.

The authors qualified the recommendations by pointing out that none of the studies reported to date showed an improvement in overall survival with longer-duration AI therapy. Instead, the recommendations are based on evidence that extended AI therapy reduces the risk of distant recurrence and second breast cancers.

The impetus for evaluation of extended-duration endocrine therapy came from evidence that the risk of disease recurrence in HR-positive breast cancer continues beyond 5 years. Contemporary studies showed that more recurrences happened after 5 years than in the first 5 years after diagnosis. Extended endocrine therapy emerged as a strategy to reduce the risk of late recurrence.

The guideline authors noted several well-established prognostic factors for late recurrence, including tumor size, nodal status, higher tumor grade, and lower estrogen-receptor expression. Additionally, higher scores on genomic assays have proved to be prognostic for late recurrence.

“We’ve been using hormonal therapy for 40-something years in the prevention of breast cancer,” said Burstein, of Dana-Farber Cancer Institute in Boston. “Having worked on these guidelines, what’s incredible to me is that we’re still learning how to do it better. This guideline talks about longer duration of therapy, which will help reduce recurrences for thousands and thousands of women in the U.S. and around the world.”

As another example of the evolution, a focused update published in 2016 addressed ovarian suppression to optimize the benefits of endocrine therapy for premenopausal women, he added.