Researchers also found that molecular and genetic analysis of tumor cells can identify which patients do better in the long run with different estrogen-blocking drugs.
The research was conducted at the Karolinska Institutet in Stockholm, Sweden, and the University of California, San Francisco, using data from women treated in Sweden. It was published in the Journal of Clinical Oncology.
Why Endocrine Therapy Helps Estrogen Receptor-Positive Breast Cancer
Estrogen receptor-positive breast cancer is a type of breast cancer with cells fueled by estrogen. After their cancer is treated with chemotherapy, radiation, surgery, or a combination of these methods, estrogen receptor-positive patients are usually given endocrine therapy, also called hormone therapy, to reduce the risk of the cancer recurring.
Endocrine therapy uses drugs that suppress estrogen from the ovaries that fuels the cancer cells. These types of drugs include tamoxifen, goserelin, and other hormonal therapies. About 80% of breast cancers are sensitive to estrogen.
Over 30 Years of Research
The new study’s findings came from follow-up and analysis of data from an earlier clinical trial. That trial, which took place between 1990 and 1997, assigned 584 premenopausal women to two years of treatment with either goserelin, tamoxifen, a combination of goserelin and tamoxifen, or no endocrine therapy after they received chemotherapy for their breast cancer.
In 2020, researchers conducted molecular and genetic profiles of tumor cells from 463 of the patients, who were then identified as being either at low risk or high risk of developing tumors later in other parts of the body.
The researchers found that goserelin, tamoxifen, and the combination of both significantly improved the long-term risk of recurrence compared to not receiving endocrine therapy. The combination of goserelin and tamoxifen was no better than either drug alone.
A major finding is that there was a difference between patients who were at high risk compared to those at low risk, study co-author Laura Esserman, MD, told Verywell in an email. Esserman is a professor of surgery and radiology at the University of California, San Francisco.
“Women with molecularly high-risk disease benefited from ovarian suppression, and very interestingly, tamoxifen plus goserelin did away with the benefit of goserelin,” she said. “For women with molecularly low-risk disease, tamoxifen was better than goserelin.”
This differentiation means that endocrine treatment for breast cancer must be individualized to the patient, as well as the molecular and genetic profile of the cancer, she Esserman emphasized.
Another important finding? People with molecularly high-risk tumors have a higher risk of cancer recurrence in the first five years after treatment. Low-risk tumors are more likely to have a risk at a later time after treatment.
According to Esserman, the study shows “the incredible importance of long-term follow up, especially for the lower-risk patients” whose risk of recurrence lasts for years.
“Sweden is unique in its ability to track patients for long periods of time,” she said. “This is unfortunately rare, but here, the investment the Swedes have benefited us all.”
Why a Lasting Benefit Matters
Being able to tell patients that endocrine treatment has a benefit for at least 20 years will have an impact on discussions of the advantages and disadvantages of hormone therapy, said Kathy D. Miller, MD, professor of oncology at the Indiana University School of Medicine in Hematology/Oncology Division.
“None of our therapies are without any potential toxicity or downsides, and patients have to balance that with the potential benefits of therapy,” Miller told Verywell. “To still see an improvement in overall survival in the number of women who are alive 20 years later from just two years of anti-estrogen therapy really highlights the power of anti-estrogen therapy in this disease.”
The length of the follow-up for the endocrine treatment is impressive, said Miller, who is a member of an advisory group to the Susan G. Komen breast cancer organization and was not involved with the study.
“As people get older, it becomes harder and harder to show an improvement in overall survival from a cancer-directed therapy,” she said.
Even Just 2 Years Is Beneficial
Most oncologists prescribe tamoxifen or goserelin for at least five years and for up to 10 years, Miller pointed out. But many women struggle with side effects of hormone therapy and want to cut the treatment short.
“Some patients struggle so much with the side effects of therapy that they need to stop. I think it’s helpful to reassure patients that there was benefit from two years, and we saw that benefit all the way up to 20 years of follow up,” she said. “It still doesn’t let me tell them what additional benefit you might be leaving on the table by stopping at two or three years compared to going longer, but it does reassure them that the time was not for nothing.”
