Distant Recurrence Risk of Hormone-Receptor-Positive Breast Cancer Steady 20 Years After Initial Diagnosis
After 5 years of hormonal therapy, the risk of distant recurrence is still sizable, even 20 years after the initial diagnosis, and the risk of distant recurrence is strongly linked to cancer size and number of positive lymph nodes.
After surgery, women diagnosed with early-stage, hormone-receptor-positive breast cancer usually take hormonal therapy medicine to reduce the risk of the cancer coming back (recurrence). Recurrence can be local (the cancer coming back in the breast area), regional (coming back in the chest wall or area near the breast), or distant/metastatic (the cancer coming back in a part of the body away from the breast, such as the bones or liver).
Hormonal therapy given after surgery is called adjuvant hormonal therapy.
Hormonal therapy medicines work in two ways:
- by lowering the amount of estrogen in the body
- by blocking the action of estrogen on breast cancer cells
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 now used more often than tamoxifen to treat women who’ve gone through menopause.
For many years, the standard of care was for a woman to take hormonal therapy for 5 years after breast cancer surgery. In 2012 and 2013, large studies found that 10 years of tamoxifen was better than 5 because it:
- lowered the incidence of breast cancer recurrence
- reduced the number of deaths from breast cancer
- improved overall survival
Some research has suggested that taking Femara for 10 years instead of 5 may offer some benefits, but only for very specific women. Taking an aromatase inhibitor for 10 years isn’t the standard of care yet.
While taking tamoxifen for 10 years instead of 5 offers more benefits, tamoxifen does cause side effects, some of them serious. Hot flashes and night sweats are common tamoxifen side effects. In rare cases, tamoxifen can cause dangerous blood clots. Tamoxifen also may increase the risk of endometrial cancer in some women. So the benefits of taking tamoxifen for 10 years have to be weighed against 10 years of possible side effects.
If doctors knew the specific risk of distant recurrence of a breast cancer after 5 years of hormonal therapy, it could help decide whether to extend hormonal therapy to 10 years.
A study suggests that after 5 years of hormonal therapy, the risk of distant recurrence is still sizable, even 20 years after the initial diagnosis. The risk of distant recurrence is strongly linked to the characteristics of the cancer, including cancer size and number of positive lymph nodes.
The research was published in the Nov. 9, 2017 issue of the New England Journal of Medicine. Read the abstract of “20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.”
This study was a meta-analysis, which means the researchers analyzed results from previously published studies. In this case, the researchers looked at 88 studies involving 62,923 women diagnosed with early-stage, hormone-receptor-positive breast cancer who had no evidence of disease after 5 years of hormonal therapy after surgery.
The women were all younger than 75 when they were first diagnosed, and all were diagnosed between 1976 and 2011.
All the breast cancers were classified as either:
- T1: 2 cm or smaller in size
- T2: 2.1 cm to 5 cm in size
and had fewer than 10 positive lymph nodes.
None of the cancers were metastatic.
About half the women had lumpectomy and half the women had mastectomy to remove the cancer. Approximately 74% of the women who had positive lymph nodes were treated with chemotherapy. Only about 25% of the women diagnosed with HER2-positive disease were scheduled to be treated with Herceptin (chemical name: trastuzumab).
All the women were scheduled to take hormonal therapy for 5 years and then stop.
The researchers looked at the rates of distant recurrence up to 20 years after diagnosis, grouping the women by number of positive lymph nodes. They also looked at rates of death from breast cancer. The researchers then used statistical analysis to see if there were links between the characteristics of the cancer and the rates of distant recurrence.
Within each group of women, distant recurrences occurred steadily during the 20 years after diagnosis. Specific 20-year risks of distant recurrence were:
- 22% for women with zero positive lymph nodes
- 31% for women with one to three positive lymph nodes
- 52% for women with four to nine positive lymph nodes
As the researchers expected, the annual rates of death from breast cancer were low during the first 5 years after initial diagnosis. But after year 5, the annual rates of death from breast cancer and distant recurrence were similar. Specific 20-year risks of death from breast cancer were:
- 15% for women with zero positive lymph nodes
- 28% for women with one to three positive lymph nodes
- 49% for women with four to nine positive lymph nodes
The researchers then looked at the cumulative risk of distant recurrence and the cumulative risk of death from breast cancer from 5 to 20 years after diagnosis based on the classification and lymph node status of the cancer. Cumulative risk is the total risk that something will happen over time. For example, women diagnosed with T1 cancer with zero positive lymph nodes had less than a 1% risk of distant recurrence per year for 5 to 20 years after diagnosis. This works out to be a cumulative risk of distant recurrence of 13% 20 years after diagnosis.
Cumulative risk of distant recurrence at 20 years was:
- 13% for T1 cancer with zero positive lymph nodes
- 20% for T1 cancer with one to three positive lymph nodes
- 34% for T1 cancer with four to nine positive lymph nodes
- 19% for T2 cancer with zero positive lymph nodes
- 26% for T2 cancer with one to three positive lymph nodes
- 41% for T2 cancer with four to nine positive lymph nodes
The cumulative risk of distant recurrence was strongly related to the original classification and lymph node status of the cancer.
Cumulative risk of death from breast cancer at 20 years was:
- 7% for T1 cancer with zero positive lymph nodes
- 13% for T1 cancer with one to three positive lymph nodes
- 22% for T1 cancer with four to nine positive lymph nodes
- 13% for T2 cancer with zero positive lymph nodes
- 20% for T2 cancer with one to three positive lymph nodes
- 29% for T2 cancer with four to nine positive lymph nodes
As with distant recurrence, the cumulative risk of death from breast cancer was strongly related to the original classification and lymph node status of the cancer.
"Even though these women remained free of recurrence in the first 5 years, the risk of having the cancer recur elsewhere (for example in the bone, liver, or lung) from years 5 to 20 remained constant," said senior study author Daniel F. Hayes, M.D., Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Comprehensive Cancer Center.
"It is remarkable that breast cancer can remain dormant for so long and then spread many years later with this risk remaining the same year after year and still strongly related to the size of the original cancer and whether it had spread to the nodes," said Hongchao Pan, Ph.D., M.Sc., lead author from the University of Oxford.
While these risk numbers seem concerning, we know that the risk of recurrence doesn’t ever go down to zero.
"The article doesn't tell the breast cancer community anything they didn't already know, which is that cancer risk doesn't go down to zero for patients with hormone-receptor-positive breast cancer," said Jennifer Litton, M.D., of the University of Texas MD Anderson Cancer Center, who was not involved in the analysis, in an interview. "I wouldn't want women to panic when they see this. This is what was happening 20 years ago, and we know women are living longer, decade by decade when they are diagnosed.
"It confirms that there is a lifelong risk,” she continued. “We still need to do better with our chemotherapy, we need to do better with our anti-estrogen therapies. A lot of people are looking into different combinations in clinical trials, as far as the length of time that women are on these therapies."
It’s important to know that the women in this analysis were diagnosed up to 30 years ago. Breast cancer treatment has improved dramatically in that time, so women who have been diagnosed more recently will have a lower risk of distant recurrence.
Also, not all the women in the studies analyzed completed the full 5 years of hormonal therapy. Up to 31% of the women in some of the studies didn’t complete treatment, which may have led to higher rates of distant recurrence.
If you’ve been diagnosed with hormone-receptor-positive breast cancer and will be taking hormonal therapy after surgery and other treatments, 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, 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, such as 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 Hormonal Therapy. You can read about why it’s so important to stick to your treatment plan, as well as ways to manage side effects. If you’re taking hormonal therapy after surgery 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.
— Last updated on July 31, 2022, 10:42 PM
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