Online Calculator Helps Predict Risk of Hormone-Receptor-Positive Breast Cancer Returning Elsewhere in the Body
The CTS5 calculator can help predict the late distant recurrence risk of hormone-receptor-positive disease.
One of the goals of breast cancer treatment, especially treatments that are given after surgery (called adjuvant treatments), is to reduce the risk of the cancer coming back (recurrence).
Studies have shown that estrogen-receptor-positive breast cancer has a more drawn-out risk of recurrence compared to estrogen-receptor-negative disease. About 50% of estrogen-receptor-positive breast cancer recurrences happen 5 or more years after the initial diagnosis. Most estrogen-receptor-negative disease recurrences happen within the first 5 years after initial diagnosis.
Researchers have developed an online tool called Clinical Treatment Score post-5 years (CTS5) to help doctors better predict the risk of late distant recurrence of hormone-receptor-positive breast cancer. Late distant recurrence is breast cancer that comes back in a part of the body away from the breast more than 5 years after initial diagnosis.
The study was published in the July 1, 2018 issue of the Journal of Clinical Oncology. Read the abstract of “Integration of Clinical Variables for the Prediction of Late Distant Recurrence in Patients With Estrogen Receptor-Positive Breast Cancer Treated With 5 Years of Endocrine Therapy: CTS5.”
How long should I take hormonal therapy?
After surgery, most women diagnosed with estrogen-receptor-positive breast cancer take hormonal therapy medicine to reduce the risk of recurrence.
There are several types of hormonal therapy medicines. Tamoxifen, a selective estrogen receptor modulator (SERM), is one of the most well-known. Tamoxifen can be used to treat both premenopausal and postmenopausal women. The aromatase inhibitors:
- Arimidex (chemical name: anastrozole)
- Aromasin (chemical name: exemestane)
- Femara (chemical name: letrozole)
have been shown to be more effective at reducing recurrence risk in postmenopausal women and are used more often than tamoxifen to treat women who’ve gone through menopause.
Until 2012, most women took hormonal therapy for 5 years after surgery. Then large studies found that 10 years of tamoxifen was better than 5 because it reduced the risk of recurrence even more. Other studies have suggested that extending aromatase inhibitor treatment for 2 to 5 more years after the initial 5 years of treatment -- for a total of 7 to 10 years of hormonal therapy -- could offer more risk reduction benefits.
Taking hormonal therapy for more than 5 years is called extended hormonal therapy.
Making sure the benefits outweigh the risks
Still, both tamoxifen and the aromatase inhibitors can cause side effects. Tamoxifen may cause hot flashes and increase the risk of blood clots and stroke. Aromatase inhibitors may cause muscle and joint aches and pains. Less common but more severe side effects of aromatase inhibitors are heart problems, osteoporosis, and broken bones. Research has shown that about 25% of women who are prescribed hormonal therapy to reduce the risk of recurrence after breast cancer surgery either don’t start taking the medicine or stop taking it early. In many cases, this is because of side effects.
If doctors knew a woman’s risk of late distant recurrence, they could recommend extended hormonal therapy only for women who would benefit from it.
Currently there are several genomic tests available that analyze the genes in a breast cancer tumor to help predict the risk of estrogen-receptor-positive disease coming back within 10 years after diagnosis. Still, these tests can be expensive and may not be covered by all insurance companies.
The doctors who did this study wanted to develop an easy-to-use online tool that would calculate the risk of late distant recurrence for women with early-stage, estrogen-receptor-positive disease based on the clinical and pathological characteristics of the cancer.
To create the CTS5 tool, the researchers used information from 4,735 postmenopausal women diagnosed with early-stage, estrogen-receptor-positive breast cancer who were part of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) study. The women were randomly assigned to receive Arimidex alone or tamoxifen alone and had no distant recurrence after 5 years of follow-up.
The researchers included the following cancer characteristics in the tool to calculate the risk of late distant recurrence:
- number of lymph nodes with cancer in them
- tumor size
- cancer grade
- a woman’s age at the start of hormonal therapy
The researchers then tested the CTS5 tool against information from 6,711 women who were part of the Breast International Group (BIG) 1-98 study. In the BIG 1-98 study, postmenopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer were randomly assigned to receive either 5 years of Femara or 5 years of tamoxifen. Later in the study, some women were also randomly assigned to 2 years of Femara followed by 3 years of tamoxifen or 3 years of tamoxifen followed by 2 years of Femara.
CTS5 was able to accurately separate the women into groups of low, intermediate, or high risk of late distant recurrence after 5 years of hormonal therapy. The tool found 42% of the women had low late distant recurrence risk, so the risks of extended hormonal therapy outweighed the benefits for these women.
“What we have developed could improve clinical practice, benefiting breast cancer patients by avoiding potentially unnecessary extended treatment,” said Mitch Dowsett, professor of biochemical endocrinology at the Institute of Cancer Research in London, U.K., and co-leader of the study. “Clinicians require expertise and the best tools to help them make crucial decisions on treatment for patients, decisions that can make a difference to patients' quality of life.”
“Hormone-sensitive breast cancer is one of the few cancers where late recurrence is common, and predicting who is at high risk is particularly important so that they can continue hormone treatment,” said Jack Cuzick, director of the Wolfson Institute of Preventive Medicine and Head of the Centre for Cancer Prevention at Queen Mary University of London and another co-leader of the study. “While our ability to predict this type of cancer is highly likely to improve in the future, we're providing a simple tool which is available now, and is easily used and well-tested.”
The CTS5 calculator is available online. The tool is meant to be used by doctors. Anyone using the tool should always interpret the results in partnership with her/his doctor.
Staying on track with hormonal therapy treatment
If you’ve been diagnosed with early-stage, hormone-receptor-positive breast cancer, it’s likely that you’ll be prescribed at least 5 years of hormonal therapy after surgery. After those initial 5 years, you and your doctor will decide if extended hormonal therapy treatment makes sense for your unique situation, based on your risk of late distant recurrence. Your doctor may use the CTS5 calculator, as well as the results of genomic tests, to help make decisions about extended hormonal therapy.
No matter how long you’re taking hormonal therapy, it’s very important that you take the medicine for as long as it’s prescribed and at the dose at which it is prescribed. Hormone-receptor-positive breast cancer can come back -- even after 5 or 10 years -- and hormonal therapy after surgery reduces that risk. You must remember that.
Side effects caused by hormonal therapy can be very troublesome for many women. It’s important to talk to your doctor as soon as you start having any side effects, including hot flashes, joint pain, blood clots, trouble sleeping, fatigue, or difficulty concentrating. Don’t wait until the symptoms are intolerable and you have to stop taking the medicine. There are steps you can take to ease these side effects, including switching to a different type of hormonal therapy.
For more information, visit the Breastcancer.org pages on Staying on Track With Treatment. You can read about why it’s so important to stick to your treatment plan, as well as ways to manage side effects after radiation, chemotherapy, and hormonal therapy. If you’re taking hormonal therapy now, stick with it as prescribed. If you’re thinking of stopping early, talk to your doctor first. Together, you can find a solution that is best for you.
To discuss your hormonal therapy experience with others and share ways to help you stick with your treatment plan, join the Breastcancer.org Discussion Board forum Hormonal Therapy -- Before, During, and After.
— Last updated on February 22, 2022, 10:00 PM
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