Study: Does extending hormonal therapy impact risk of breast cancer recurrence?
|At a glance
|Questions for your doctor
This study is about:
- Identifying which patients with ER-positive breast cancer could safely stop endocrine (hormonal) therapy (thereby avoiding the side effects) after 5 years because their risk for long-term distant recurrence was "so small”
- Factors that may influence whether or not to extend hormonal therapy beyond 5 years for women with estrogen receptor- (ER-) positive breast cancer.
Why is this study important?
Standard treatment for breast cancer often includes 5 years of endocrine-based (hormonal) treatments such as tamoxifen or aromatase inhibitors (both are pills that are taken daily). The aim of this study was to learn which patients could stop hormonal therapy after 5 years because their risk of recurrence would be very small. However, this study found that even for women believed to be at low risk of recurrence, breast cancer recurrences continued steadily for up to 20 years after diagnosis. This study identified which features of a patient’s original cancer influence long-term risk of recurrence. These findings may help guide the decision of whether or not to extend standard hormonal therapy beyond 5 years.
In women diagnosed with ER-positive breast cancer who stopped endocrine therapy after the standard 5 years of treatment, breast cancer recurrence occurred at a steady rate from 5 to 20 years. Over the study period, risk of recurrence was strongly linked to the original cancer's size and to the number of positive at the time of diagnosis.
- Among women with T1(2 cm or less) breast cancer, risk of recurrence was:
- 13% for those with no positive
- 20% for those with 1 to 3 positive
- 34% for those with 4 to 9 positive
- Among women with T2 (larger than 2 cm but less than 5 cm) breast cancer, risk of recurrence was:
- 19% for those with no positive
- 26% for those with 1 to 3 positive
- 41% for those with 4 to 9 positive
What does this mean for me?
The results of this study may help identify which ER-positive breast cancer patients would most benefit from extending hormonal therapy beyond the standard 5 years of treatment. However, the benefits of extending endocrine therapy must be weight against side effects. The findings of this study underline the need to help women who are receiving endocrine therapy to discover whether any side effect symptoms are actually caused or made worse by therapy.
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This article is relevant for:
Women with early-stage ER-positive breast cancer
This article is also relevant for:
people with ER/PR + cancer
people with a genetic mutation linked to cancer risk
people with breast cancer
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IN-DEPTH REVIEW OF RESEARCH
Researchers of this study attempted to identify women whose long-term risk of recurrence was so small that any additional benefit from extended therapy would not be outweighed by added side effects. Hongchao Pan, PhD, and colleagues conducted a of 88 trials involving 62,923 women with ER-positive breast cancer who were disease free after 5 years of endocrine therapy. They used data on recurrence, tumor diameter and nodal status (TN), tumor grade and other factors during 5 to 20 years after standard endocrine therapy ended. Results were published in the November 9, 2017 edition of the New England Journal of Medicine.
Researchers of this study wanted to know:
Whether they could identify women with , ER-positive breast cancer who were disease free following 5 years of standard endocrine therapy for whom additional benefit from extended therapy would not outweigh added side effects. However, they revealed factors that may help to guide patients and healthcare providers when considering who would benefit from extended hormonal therapy.
Population(s) looked at in the study:
Researchers analyzed data from 88 clinical trials involving 62,923 women with ER-positive breast cancer.
- All of the women received endocrine therapy for 5 years and were free of cancer when therapy ended.
- Half of the women received a diagnosis of breast cancer before 2000 (from 1976 to 2011).
- Data was available on:
- Age, tumor size and nodal status for all the women
- Tumor grade for 43,590 (69%) of the patients
- Progesterone-receptor status for 54,115 (86%)
- HER-2 status for 24,145 (38%)
- A tumor marker called Ki-67—a protein that is a marker for cell division—status for 7692 (12%)
The cumulative risk and annual rates of distant recurrence and death from breast cancer in each 5-year period from year 0 to year 20, was subdivided according to lymph node status at the time of diagnosis. In each category, distant recurrence occurred steadily throughout the 20-year period. Annual risk was strongly related to nodal status.
- The 20-year risk of distant recurrence was:
- 22% in those with no positive nodes
- 31% in those with 1 to 3 positive nodes
- 52% in those with 4 to 9 positive nodes
The annual rates of death from breast cancer, as would be predicted in a population that was disease free following 5 years of endocrine therapy, was low during the first 5 years. However, starting at year 5, the annual rates of death increased. These risks were not significantly lower than the 20-year risk of distant recurrence.
- The 20 year risks of death from breast cancer were:
- 15% in women with no positive nodes
- 28% in women with 1 to 3 positive nodes
- 49% in women with 4 to 9 positive nodes
However, even women with small, node-negative (T1N0) low-grade tumors had risk of distant recurrence. For these women (T1N0) risk of recurrence was:
- 10% for patients with low-grade disease
- 13% for patients with moderate-grade disease
- 17% for patients with high-grade disease
The corresponding risk of any recurrence or for these women (T1N0) was:
- 17% for patients with low-grade disease
- 22% for patients with moderate-grade disease
- 26%for patients with high-grade disease
When other factors were taken into account, tumor grade and Ki-67 status were moderate independent predictive indicators for recurrence. Progesterone receptor and receptor status did not predict recurrence.
- Noncompliance (patients stopping medications early) is a big concern with long-term hormonal treatment due to side effects. The recurrence rates reported here are among women who were scheduled to receive 5 years of hormonal therapy, not in those who actually completed 5 years of treatment.
- Researchers could not reliably look at the effect of chemotherapy after year 5, since the extent of lymph node involvement differed between women who received chemotherapy and those who did not.
- The analysis included a significant number of patients who were diagnosed before the year 2000, and therefore may not be completely relevant to today’s population that has better screening, diagnostic methods, and .
The risk for recurrence steadily rose among women who were diagnosed with ER-positive breast cancer, received 5 years of hormonal therapy and were disease-free when their therapy ended. Risk of recurrence was strongly associated with the original size of the tumor and the patient’s nodal status at the time of diagnosis. These findings impact long-term follow-up strategies and the need for new approaches to reduce the long-term risk of recurrence. For some patients, risk may be reduced by extending the duration of hormonal therapy; however, additional side effects of extended therapy must be taken into consideration. Tumor size and lymph node involvement at the time of diagnosis may help to identify those who would benefit the most from extended endocrine therapy.
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Pan H, Gray R, Braybrooke J, et al. “20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.” New England Journal of Medicine 2017;377:1836-46.
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In 2019, the American Society of Clinical Oncology (ASCO) published updated guidelines on endocrine treatment (hormonal therapy) for women with breast cancer. The guidelines recommended:
- Women with node-positive breast cancer receive extended therapy, including an aromatase inhibitor, for up to a total of 10 years of endocrine treatment.
- Many women with node-negative breast cancer should consider extended therapy for up to a total of 10 years of endocrine treatment based on considerations of recurrence risk.
- The decision about extending hormone therapy should be a shared decision between doctors and patients based on discussions that weighs the benefits in lowering the risk for breast cancer recurrence, the benefits of prevention of second breast cancers versus the negative impact of side effects of treatment.
The Panel noted that the benefits in of reduction were small and that a substantial portion of the benefit for extended aromatase inhibitor therapy came from prevention of a new breast cancer diagnosis.
- Would I benefit from extending hormonal therapy beyond the standard 5 years?
- What are the side effects and of hormonal therapies like tamoxifen?
- What are the side effects and of aromatase inhibitors?
- What are the added side effects of extending hormonal therapy beyond 5 years?
The following are studies enrolling people with early ER-positive, breast cancer.
- NCT03053193: MammaPrint, BluePrint, and Full-genome Data Linked With Clinical Data to Evaluate New Gene EXpression Profiles (FLEX). The FLEX Registry is a large-scale, population based, registry. All patients with I to III breast cancer who receive MammaPrint® and BluePrint testing on a primary breast tumor are eligible for entry into the FLEX Registry.
- NCT05607004: (Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer (EVANGELINE). This study is looking at drug called (Z)-endoxifen as a possible treatment for pre-menopausal women with ER+/HER2- breast cancer. (Z)-endoxifen is a type of hormone therapy that blocks the body's natural from binding to cancer cells.
- NCT04584255: Treating HER2-Negative Breast Cancer with a () and (Dostarlimab) in People with a or Mutation. This study will look at how well the drugs (a ) and Dostarlimab (an ) treat breast cancer in people with an inherited , or mutation.
- NCT03749421: Prosigna Assay on Clinical Decision-making in Women With HR+/Her2- Breast Cancer. This research study is evaluating a genomic analysis called Predictor Analysis of Microarray 50 (PAM50, by Prosigna®) as a tool to possibly guide the participant and the treating physician to choose the most personalized pre-operative treatment for breast cancer.
- NCT04567420: DNA-Guided Second Line Therapy For High Residual Risk, II-III, Hormone Receptor Positive, Negative Breast Cancer. This study will monitor people with , high-risk breast cancer for possible recurrence using a test called circulating tumor (). People who test positive for but who have no other signs of recurrence, will receive either the drugs palbociclib combined with fulvestrant or standard-of-care hormone therapy.
NCT04852887: De-Escalation of Breast Radiation Trial for Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer (DEBRA). This study evaluates whether breast conservation surgery and endocrine therapy results in a non-inferior rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation with breast radiation and endocrine therapy.
A number of other clinical trials for patients with breast cancer can be found here.
The following organizations offer peer support services for people with, or at high risk for breast cancer:
- FORCE peer support:
- Our Message Boards allow people to connect with others who share their situation. Once you register, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Our Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Connect online with our Private Facebook Group.
- Join our virtual and in-person support meetings.
- Other organizations that offer breast cancer support:
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