Joanne L. Blum, MD
The management of patients with hormone receptor (HR)-positive breast cancer continues to evolve, with phase III studies shedding light on the length of adjuvant antiestrogen therapy, a novel treatment gaining approval, and new trials exploring combination strategies.
With the evolution of treatment under way, OncLive interviewed three world-renowned experts in the field: Joanne L. Blum, MD, PhD, Adam M. Brufsky, MD, PhD, and Harold J. Burstein, MD, PhD.
“We’re now entering the area of truly targeted agents. We have things like palbociclib. We have everolimus. We really have an enormous amount of things,” said Brufsky, co-director of the Comprehensive Breast Cancer Center at the UPMC Cancer Centers and the University of Pittsburgh. “I think that our issue is that, with such a wealth of choices, it really becomes fairly complicated to figure out the right therapy for the right patient.”Adjuvant Therapy Duration Enumerated
Traditionally, a 5-year regimen of adjuvant tamoxifen was utilized following surgery for women with early-stage breast cancer. However, results from the phase III ATLAS and aTTom studies demonstrated that extending the duration of adjuvant tamoxifen therapy from 5 to 10 years further reduced the risk of recurrence and breast cancer mortality.1,2
“There were two trials that came forward in the past couple of years that looked at 10 years versus 5 years,” explained Burstein, a senior physician at the Dana-Farber Cancer Institute and an associate professor at Harvard Medical School. “With a very long follow-up, they showed a small but real survival advantage and a reduction in the chance of breast cancer recurrence with the longer duration.”
In the ATLAS trial, patients who continued tamoxifen for 10 years had a 12.2% risk of dying due to breast cancer versus 15% for those who had 5 years of treatment, and the rate of recurrence was 25% less with the longer course of treatment. In the aTTom study, women continuing tamoxifen for 10 years had a 25% lower recurrence rate and a 23% lower breast cancer mortality rate compared with those who stopped at 5 years.
Based on these studies, ASCO updated its clinical practice guideline to recommend treatment with adjuvant tamoxifen for 10 years in women with stage I-III HR-positive breast cancer. However, there are still many factors to consider when assessing the duration of adjuvant therapy, including tumor burden, tumor biology, comorbidities, and age.
In older patients with small, node-negative disease, it is prudent to administer tamoxifen for 5 years, Brufsky noted. However, in younger patients with several positive nodes, there is an impetus for longer treatment.
“I think it’s important to note that you really have to balance the patient’s risk,” said Brufsky. “What’s really interesting is that there’s a number of genomic assays right now that are coming to the plate that may help us kind of select people based on their prognosis.”
One of the tests available, the Breast Cancer Index, provides a prediction for the risk of recurrence at various time points, noted Brufsky. This tool reports on the probably of early recurrence (0-5 years), late recurrence (5-10 years), and overall recurrence (0-10 years). Additionally, the test provides information on the likelihood of benefit from extended endocrine therapy.
“Tamoxifen isn’t totally benign,” Brufsky added. “There is going to be a certain rate of endometrial cancer, a certain small rate of blood clots. That’s the tradeoff—a lowered risk of recurrence but a slightly increased rates of those two complications.”
Adding to the question of duration, the TEXT and SOFT stud- ies demonstrated that adjuvant ovarian function suppression (OFS) plus exemestane or tamoxifen reduced the relative risk of developing subsequent invasive cancer.
In the SOFT trial, which was presented at the 2014 San Antonio Breast Cancer Symposium (SABCS), adding tamoxifen to OFS reduced the risk of disease recurrence by 22% versus tamoxifen alone (HR = 0.78; 95% CI, 0.60-1.02).3
Further benefit was observed with exemestane, which reduced the risk of recurrence by 35% when combined with OFS versus treatment with standard tamoxifen (HR = 0.65; 95% CI, 0.49-0.87).
Similarly, in a joint analysis of the SOFT and TEXT trials, exemestane plus OFS reduced the relative risk of recurrence by 34% compared with tamoxifen plus OFS, according to findings presented at the 2014 ASCO Annual Meeting.4
Cancer-free survival at 5 years was 91.1% in the exemestane arm compared with 87.3% in the tamoxifen arm. Similar 5-year overall survival rates occurred in both arms, with a 95.9% survival with exemestane compared with 96.9% with tamoxifen.Frontline Therapy for Advanced Disease