New research has shown that postmenopausal women with low-risk tumors have a long-term benefit for at least 20 years, whereas the benefit was more short-term for younger women with similar tumor characteristics who had not yet gone through menopause. The results were reported in the Journal of the National Cancer Institute.
In Sweden, 9 000 women are diagnosed with breast cancer each year, with hormone-sensitive breast cancer accounting for about 75% of women diagnosed with the disease. In patients with hormone-sensitive breast cancer, tumor growth is mainly driven by estrogen, and patients are therefore treated with estrogen-suppressing drugs, often tamoxifen. However, antihormonal treatment reduces quality of life, and questions have remained about the long-term benefit against recurrence. About one-third of women diagnosed with breast cancer are younger and premenopausal, and they are known to have an increased risk of recurrence.
Linda Lindström, MSc, PhD
“Younger women generally have a higher risk of recurrence than older postmenopausal women, but most studies on antihormonal therapy have mainly included postmenopausal women. We therefore wanted to compare the long-term benefit from the treatment in both groups,” said Linda Lindström, MSc, PhD, Associate Professor and Research Group Leader at the Department of Oncology-Pathology, Karolinska Institutet, Solna, Sweden, who led the study.
Study Details
The study included more than 1,200 women diagnosed with hormone-dependent breast cancer between 1976 and 1997, of which almost 400 were premenopausal. Women were randomly assigned to treatment with tamoxifen for at least 2 years or no antihormonal treatment. The outcome of interest was breast cancer metastasis or distant recurrence, and more than 20 years of follow-up data are now available.
“From the regional breast cancer registry, we have an almost complete follow-up on all patients and this together with a control group who did not receive antihormonal treatment makes the study unique. There is also complete data on whether the women were pre- or postmenopausal at diagnosis, which is otherwise often estimated based on age,” said Annelie Johansson, MSc, PhD, another researcher at the Karolinska Institutet.
The women's tumors were classified as low or high risk based on clinical markers. Low-risk tumor characteristics were defined as a tumor size ≤ 2 cm in diameter, no lymph node spread, low tumor grade, positivity for the progesterone receptor, and a low genomic risk, which was determined by a molecular signature that measures the expression of 70 different genes.
Key Findings and Next Steps
Women with high-risk tumors had less benefit against distant recurrence, whether they had gone through menopause or not. Women with low-risk tumors after menopause had a long-term benefit of 20 years or more. For younger women who had not gone through menopause at diagnosis, a long-term benefit could not be predicted using the clinically used markers. Therefore, new markers are needed, the researchers say.
“We need to work further to understand which tumor characteristics influence the long-term risk of recurrence and benefit in younger patients. We want patients to benefit from their treatment for as long as the risk of recurrence is elevated,” said Dr. Lindström.
In the next step, the researchers want to be able to link more complex tumor characteristics to the long-term risk and benefit of antihormonal therapy, in order to individualize treatment to the patients who benefit from it.
“For example, we plan to perform multiprotein analyses and use machine learning for image analysis of breast cancer tumors to understand more about tumor heterogeneity—ie, differences between and within tumors—and how it affects risk and treatment benefit,” said Dr. Lindström.
Disclosure: The study was funded by the Swedish Research Council, the Swedish Cancer Society, the Stockholm Cancer Society, ALF Medicin and the Gösta Milton Foundation. For full disclosures of the study authors, visit academic.oup.com.
