Currently, women diagnosed with estrogen-sensitive breast cancer undergo anti-hormonal therapy. A recent study reveals that postmenopausal women with low-risk tumors can expect lasting benefits for at least 20 years. In contrast, younger women with similar tumors who haven’t reached menopause experience benefits that are more short-lived. These findings are published in the Journal of the National Cancer Institute (JNCI).
Each year in Sweden, around 9,000 women are diagnosed with breast cancer, with hormone-sensitive breast cancer representing about 75 percent of these cases. For those with hormone-sensitive tumors, growth is largely fueled by estrogen, leading to treatment with drugs that suppress estrogen, commonly tamoxifen. However, this treatment can negatively impact quality of life, prompting the need to understand its long-term effectiveness against recurrence. Approximately one-third of breast cancer patients are premenopausal and face a higher likelihood of recurrence.
“Younger women typically have a greater chance of recurrence compared to older, postmenopausal women, yet most studies involving anti-hormonal therapy primarily focus on postmenopausal subjects. We aimed to evaluate the lasting advantages of the treatment across both demographics,” explains Linda Lindström, associate professor and research leader in the Department of Oncology-Pathology at Karolinska Institutet, who spearheaded the study.
The study analyzed over 1,200 women diagnosed with hormone-dependent breast cancer between 1976 and 1997, nearly 400 of whom were premenopausal. At the study’s inception, the benefits of anti-hormonal treatments were unclear, leading to the random allocation of women to receive tamoxifen for at least two years or to act as a control group with no treatment. The main focus was on instances of breast cancer metastasis or distant recurrence, with follow-up data now exceeding 20 years since their initial diagnosis.
“The regional breast cancer registry provides us with nearly complete follow-up data for all patients. This, paired with a control group that did not receive anti-hormonal therapy, makes our research stand out. Additionally, we have comprehensive information regarding the menopausal status of each woman at the time of diagnosis, which is usually only inferred from age,” states Annelie Johansson, a researcher from the same department and the study’s lead author.
The tumors were categorized as either low- or high-risk based on commonly utilized clinical markers. Low-risk characteristics included a tumor size of two centimeters or smaller, no lymph node involvement, a low tumor grade, positivity for the progesterone receptor, and a low genomic risk indicated by a molecular signature assessing the expression of 70 genes.
Women with high-risk tumors, regardless of menopausal status, showed reduced benefits in terms of distant recurrence. Those with low-risk tumors after menopause, however, exhibited long-term benefits lasting 20 years or beyond. Unfortunately, for younger women diagnosed before menopause, the predictive value of clinical markers for long-term benefits remains unclear. Therefore, researchers emphasize the need for new markers.
“Further investigation is essential to determine which tumor characteristics affect the long-term risk of recurrence and benefits for younger patients. We strive for treatments that provide advantages for the duration of elevated recurrence risk,” asserts Linda Lindström.
In future research, the team aims to connect more intricate tumor characteristics with the extended risk and benefits of anti-hormonal therapy, tailoring treatment to patients who stand to gain the most from it.
“For instance, we intend to conduct multi-protein assessments and utilize machine learning for image analysis of breast cancer tumors to gain insights into tumor heterogeneity — the variations between and within tumors — and how it influences risk and treatment outcomes,” adds Linda Lindström.
This study is funded by the Swedish Research Council, the Swedish Cancer Society, the Stockholm Cancer Society, ALF medicin, and the Gösta Milton Foundation. Researchers affiliated with Karolinska Institutet declare no conflicts of interest; other relevant conflicts are fully disclosed in the study.
