The long-term benefits of endocrine therapy in premenopausal breast cancer appear to differ according to whether patients are categorized as high or low molecular risk using the 70-gene signature (MammaPrint).
Based upon data from patients who had participated in the Stockholm tamoxifen (STO-5) trial, high-risk patients significantly benefited from goserelin treatment, whereas low-risk patients benefited more from tamoxifen treatment when compared with no endocrine therapy.
“Goserelin, tamoxifen, and the combination of the two, reduced the 20-year risk of distant occurrences and fatal breast cancer, compared to no endocrine therapy,” Annelie Johansson, MSc, said at the European Society for Medical Oncology: Breast Cancer virtual meeting.
“Our findings indicate that the long-term endocrine therapy benefit in premenopausal patients is influenced by molecular risk classification and thus tumor characteristics,” she added.
Ms. Johansson, a postdoctoral researcher in genomic breast cancer at the Karolinska Institutet in Stockholm, reported the results of the analysis as a late-breaking abstract at the meeting.
“I think this is an innovative translational study trying to use the multigene assay results to look at differential endocrine therapy effects,” said Prudence Francis, MD, the invited discussant for study.
However, there are relatively few patients in the various subgroups being tested, she added. “We’ve also got short duration of tamoxifen, only 2 years, we’ve got prior chemotherapy in some patients and absence of HER2 therapy, all of which might influence outcomes.”
As a result, Dr. Francis, who is head of medical oncology at the Peter MacCallum Cancer Centre and a consultant Medical Oncologist at St. Vincent’s Hospital Melbourne, called the findings purely “hypothesis generating.”
Study details and results
The analysis was based on data from the STO-5 trial, which had recruited just over 900 patients between 1990 and 1997. Patients were stratified according to their lymph node status and some received chemotherapy with or without locoregional radiotherapy before being randomized to one of four study arms: goserelin alone, tamoxifen alone, the combination of the two, or no endocrine therapy.
Ms. Johansson noted that they were able to obtain the primary tumor blocks from 729 patients in the past year, of whom 610 were estrogen receptor positive. The analysis according to the 70-gene signature was then based on data from 465 patients: 131 had been treated with goserelin, 105 with tamoxifen, 120 with both, and 109 had received no endocrine treatment.
We have complete 20-year follow-up from high-quality Swedish National registries,” Ms. Johansson said, observing that the median age in the trial was 46 years.
Before stratifying patients into high and low risk using the 70-gene signature, the risk for having a distant recurrence, compared with no endocrine therapy was reduced by 52% with goserelin (hazard ratio, .48), 41% with tamoxifen (HR, 0.59), and 33% with both in combination (HR, 0.67).
After stratification, however, goserelin was associated with a 78% reduction of distant recurrence versus no endocrine treatment in high-risk patients (HR, 0.22) and a 20% reduction in low-risk patients (HR, 0.80).
Results in high- and low-risk patients with tamoxifen versus no endocrine treatment were a respective 31% reduction (HR, 0.69) and 62% reduction (HR, 0.38), and a respective 36% (HR, 0.64) and 28% (HR, 0.72) for the combination.
A further analysis was performed to compare between the active treatment arms, and this suggested a greater benefit of goserelin in patients at high risk when compared with both tamoxifen (HR, 0.30) and the combination (HR, 0.33).
Dr. Francis commented: “it is a bit surprising to find that goserelin appeared to be also better than the combination,” and it is something that the research team is looking into.
“One hypothesis might be if you look how the different treatments are working,” Ms. Johansson said. “Goserelin is very efficient in lowering the estrogen levels in premenopausal patients, suppressing the ovarian production of estrogen whereas tamoxifen can act both as an antagonist and agonist.
“So, we are thinking that maybe the addition of tamoxifen, with the agonistic properties of tamoxifen, might then make the goserelin not as efficient. But that’s of course, just a hypothesis right now and we need to look into this further,” she said.
The work was funded by The Swedish Research Council (Vetenskapsrådet), The Swedish Research Council for Health, Working life and Welfare, and the Swedish Cancer Society (Cancerfonden). Ms. Johansson had no personal disclosures; one of the coauthors was a coinventor of MammaPrint. Dr. Francis disclosed receiving travel support for overseas lectures from Ipsen and Novartis and acting as a medical oncology editor for Elsevier.