SAN ANTONIO—The first two scientific reports presented here at the CTRC-AACR San Antonio Breast Cancer Symposium (Abstracts S1-1, S1-2) were, in a sense, bookends—one on frontline hormonal therapy with tamoxifen or letrozole, the other dealing with long-term tamoxifen treatment.
This was no coincidence, said Kathy S. Albain, MD, the session's moderator, as well as a member of the program committee that chose the abstracts.
“The two papers were paired because both clearly impact clinical practice, and they both deal with tamoxifen issues,” she said in an interview after the session.
The first paper was from the Breast International Group (BIG) 1-98 trial (page 5), showing letrozole to be more effective than tamoxifen for both progression-free and overall survival in postmenopausal women with ER-positive, HER2-negative classic lobular or ductal carcinoma breast cancer. That study also showed a greater effect of letrozole in women with lobular vs ductal tumors, and a greater effect in luminal B compared with luminal A tumors.
The second study, with final results of the ATLAS trial (page 3), showed that 10 years of tamoxifen has a carryover benefit to at least 15 years after initiation of treatment.
“The BIG 1-98 presentation is giving us more confidence about a frontline tamoxifen approach for certain patients,” said Albain, Professor of Medicine in the Division of Hematology/Oncology at Loyola University Medical Center. “It was paired with the ATLAS presentation because ATLAS is looking at another role for tamoxifen, to see what the benefit of five more years of tamoxifen would be in a very large, prospectively designed trial.”
Both have a message for oncologists, she said. For BIG 1-98, the message is that by histology and intrinsic subtyping, recommendations can be fine-tuned about which women should receive letrozole and which should receive tamoxifen as frontline treatment. And on the other side, ATLAS shows that once on tamoxifen, women can be counseled to continue it for five more years.
“They're obviously different studies, but still addressing the decision-making we face every day in our clinics about adjuvant endocrine therapy,” she said. “Both were very important presentations.”
Getting the Word Out
Breast cancer survivors need to know about the findings, she said. “Women who have recently stopped five years of tamoxifen and may not be going to their oncologists anymore have to know about this; they have to revisit the question with their physicians. And we as oncologists have to devote more time to help patients understand these results.”
Nothing comes without a price, Albain acknowledged—namely, a greater risk of endometrial cancer in the 10 versus five years for women who still have their uterus. But that risk, in her opinion, is counterbalanced by the benefit.
“The other big issue is which is better—five-plus-five a la MA.17, or 10 years of tamoxifen?” she said. “If the patient is postmenopausal, are we all going to jump to giving 10 years of tamoxifen instead of the five-plus-five, or instead of some tamoxifen followed by five years of an AI? I don't think so.”
She said she believes there is still a slightly greater efficacy, based on data from trials that have reported, to having some aromatase inhibitor in the prescription for the patient, especially if their nodes are positive. “But if a patient is not tolerating an AI you can very confidently put her back on tamoxifen. And the patient can be reassured that if she's gotten some of an AI she can now get tamoxifen, that this is very good treatment.”
It has been known for quite a long time, Albain noted, that in patients with estrogen receptor-positive, generally HER2-negative breast cancers, reaching the five year anniversary is not the end of the need for vigilance about recurrences.
“From the original trials of one to two years of tamoxifen versus none, and then five years versus two, we knew that longer was better. Then along came MA.17 [Breast Cancer Res Treat 2007;105(suppl 1): 45-53], which added five years of an aromatase inhibitor after five years of tamoxifen. For node-positive patients there's a survival advantage to that, and for all patients there's a recurrence-free survival advantage for that.”
She said that most oncologists are now offering 10 years of adjuvant endocrine therapy after five years of tamoxifen for postmenopausal patients with a sufficient risk of recurrence.
Meanwhile, ongoing studies are investigating 10 versus five years of an aromatase inhibitor, and also whether patients who receive a few years of tamoxifen should be given a longer or shorter duration of the aromatase inhibitor.
And an ongoing extension of MA.17, called MA.17R, is studying of the effects of 15 years of hormonal therapy versus 10 years.
“I have patients in my own practice still on placebo versus letrozole for that question,” she said.
Into this landscape comes ATLAS, statistically analyzing the carryover benefit of tamoxifen, and showing a remarkable additional utility to this drug. “This is what we really have to help patients see, that after they finish five years of tamoxifen and stop it—which was the standard prescription up until ATLAS—in the next five years, and even the next decade after, that there is still benefit over and above the benefit from the five years. By adding that to the carryover benefit of the first five years, you're essentially halving the deaths from breast cancer.”