Study: Can tumor tests identify more breast cancer patients who can safely skip chemotherapy?
Summary
Two studies presented at the December 2020 San Antonio Breast Cancer Symposium looked at how tumor testing can identify patients who may benefit the most and the least from chemotherapy. (3/4/21)
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Relevance
This article is most relevant for Women with breast cancer
Relevance: Medium-High
Strength of Science: High
Research Timeline: Post Approval
Media Ratings
Who covered this study?
verywellhealth
Chemotherapy may not be necessary for certain breast cancers, study finds
This article rates 5.0 out of 5 stars
Cancer Therapy Advisor
Adjuvant endocrine therapy alone judged suitable for certain breast cancer patients
This article rates 4.0 out of 5 stars
Contents
| At a glance | Clinical trials |
| Study findings | Guidelines |
| What does this mean for me? | Questions for your doctor |
| In-depth | Resources |
UPDATE AT A GLANCE
What are these studies about?
These studies are about whether tumor tests can identify which breast cancer patients with cancer that has spread to their can safely skip chemotherapy and which patients are most likely to benefit from chemotherapy.
Why are these studies important?
Chemotherapy has long been a part of breast cancer treatment. For many patients, it can have serious and/or long-lasting side effects. These studies looked at how some tumor tests may better identify breast cancer patients who can safely skip chemotherapy (without an increased chance of cancer coming back or recurring) and patients who can benefit from chemotherapy.
Oncotype Dx
Oncotype DX is a type of tumor test. It looks at which genes are active in cancer cells compared to healthy cells. The test assigns scores ranging from 0 to 100. A score of 25 or below suggests that there is a low risk of breast cancer coming back.
Oncotype DX risk scores are used to identify women with hormone-positive, , node-negative breast cancer who would benefit from chemotherapy. The TAILORx study showed that women with this type of breast cancer and an Oncotype DX recurrence score of 25 or lower did as well on hormone therapy alone as those who were given hormone therapy plus chemotherapy.
The results of TAILORx left an important question unanswered: What is the best way to treat women with breast cancer that has spread to the ? Two recent studies, RxPONDER and ADAPT studied this question in different ways.
Can even more women safely skip chemotherapy?
The RxPONDER study looked at the benefit of chemotherapy in women with breast cancer that had spread to one to three . About 5,000 patients were randomly assigned to receive hormone therapy alone or hormone therapy plus several months of chemotherapy. Each of these participants had all of the following:
- hormone-positive, breast cancer.
- 1-3 positive .
- an Oncotype Dx score of 25 or less.
Early (five year) results of the RxPONDER study presented at the 2020 San Antonio Breast Cancer Symposium showed that:
- no association was found between recurrence score and chemotherapy benefit. In other words, patients with higher recurrence scores (e.g., up to 25) did not have greater benefit from chemotherapy than those with lower scores (e.g., 4, 5, 6).
- Among premenopausal women, those who received chemotherapy were more likely to be disease-free 5 years later than premenopausal women who received hormone therapy only.
- Among postmenopausal women, there was no difference in disease-free survival whether or not they had chemotherapy.
Based on these findings, many postmenopausal women may be able to safely skip chemotherapy. However, it is important to note that this study showed that there is benefit from combination chemotherapy and hormone therapy for premenopausal women.
Questions remain
Researchers will continue to follow patients for a total of 15 years. This will allow them to collect more data and get a better understanding of how these patients fare over time.
While the results of RxPONDER confirm earlier research that showed chemotherapy benefits premenopausal women, why that is so is unknown. One possible explanation is that chemotherapy can induce menopause, which in turn can starve Hormone-positive breast cancer cells of the they need to grow.
Additional research is needed to see if premenopausal women who are given menopause-inducing medications plus hormone therapy would respond more like the postmenopausal women in this study who did not benefit from chemotherapy.
The ADAPT study findings
Like the RxPONDER trial, researchers of the ADAPT trial wanted to know whether women with breast cancer that has spread to the would benefit from chemotherapy.
The ADAPT study looked at whether combining two tests, Oncotype Dx and a tumor marker called Ki-67 could help identify women who are most likely to benefit from chemotherapy and those who may safely skip chemotherapy.
Participants in the ADAPT study had hormone receptor-positive, breast cancer with zero or up to three positive . Unlike the RxPONDER study, all patients in this study received three weeks of hormone therapy after their initial biopsy and before surgery to remove their tumor.
Biopsy tissue was used to get an Oncotype Dx score and a first Ki-67 score. Tumor tissue removed at the time of surgery was used to get a second Ki-67 score.
Researchers used Oncotype DX scores and changes in Ki-67 scores (at biopsy and after surgery) to decide who should receive chemotherapy with hormone therapy and who could receive hormone therapy alone after surgery.
People with Oncotype Dx scores of 12 or higher and Ki-67 scores of 10 percent or higher after three weeks of hormone therapy were given chemotherapy along with hormone therapy after surgery. The results of this group were presented in another presentation and are not included here.
The ADAPT study presents the results for the remaining 2,290 participants who were separated into two groups:
- Those with an Oncotype Dx score of 0 to 11 and 0 to 3 positive .
- Those with an Oncotype Dx score of 12 to 25, 0 to 3 positive and a second Ki-67 score of 10% or less at the time of surgery.
People in these two groups received hormone therapy alone (no chemotherapy).
After five years, in the two groups that received hormone therapy alone:
- the overall survival rate was excellent and similar for both groups.
- survival rates did not differ by age or menopausal status.
- survival rates did not differ for people with 0 to 2 positive .
- people with 3 positive were more likely to have their cancer come back within 5 years (24%) compared to people with 0 positive (3%), 1 positive lymph node (5%) or 2 positive (8%).
This part of the ADAPT study showed that together, a patient’s Oncotype Dx score, Ki-67 scores and lymph node status may help identify women with up to three positive who can safely skip chemotherapy. Based on the results of the ADAPT study the following patients can be safely treated by hormone therapy alone:
- Patients treated with a short course of hormone therapy prior to surgery,0 to 3 positive and Oncotype Dx scores of 0 to 11.
- Patients treated with a short course of hormone therapy prior to surgery, 0 to 2 positive , an Oncotype DX score of 12 to 25 and a Ki-67 tumor score of less than 10% at the time of surgery.
However, patients with hormone receptor-positive, breast cancer, Oncotype Dx scores between 12 to 25 and a Ki-67 score of 10 percent or less with three or more positive may not be good candidates for hormone therapy alone and may benefit from chemotherapy.
Strengths and limitations
- RxPONDER and ADAPT are both very large , studies.
- Follow-up for both studies has been limited. Data will continue to be collected and results may change.
What does this mean for me?
These results are likely to provide more clarity and guidance to doctors who recommend treatment for breast cancer patients who may be able to safely avoid chemotherapy. Many experts believe that national treatment guidelines may change based on the results of these studies.
If you are a premenopausal woman with receptor-positive, breast cancer, you should speak with your doctor about the possible benefits of chemotherapy. If you are a post-menopausal woman with estrogen-receptor-positive, breast cancer and have zero to three positive , an Oncotype DX test together with Ki-67 tests may help your doctor determine whether or not you will benefit from chemotherapy.
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posted 3/4/21
References
Kalinsky K, Barlow WE, Meric-Bernstam F, et al. Abstract GS3-00. First results from a phase III of standard endocrine therapy (ET) +/- chemotherapy (CT) in patients (pts) with 1-3 positive nodes, hormone receptor-positive (HR+) and (HER2-) breast cancer Presented at San Antonio Breast Cancer Symposium (virtual meeting); Dec. 8-11, 2020.
Harbeck N, Gluz O, Kuemmel S, et al. Abstract GS4-04. Endocrine therapy alone in patients with intermediate or high-risk luminal early breast cancer (0-3 ), Recurrence Score <26 and Ki67 response after preoperative endocrine therapy: First efficacy results from the ADAPT HR+/HER2- Presented at 2020 Virtual San Antonio Breast Cancer Symposium; December 8-11, 2020.
Disclosure
FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board before publication to assure scientific integrity.
This article is relevant for:
Women with breast cancer
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IN-DEPTH REVIEW OF RESEARCH
Study background
Historically, most patients with breast cancer who were hormone receptor-positive and node-negative received chemotherapy, but many may not have benefited from it. Tumor tests that may help predict an individual’s risk of recurrence and indicate those who would most benefit from chemotherapy are now available.
Oncotype DX is a test to predict whether chemotherapy will benefit a patient with hormone receptor-positive breast cancer. Recurrence scores are based on RNA expression of 21 genes. Recurrence scores range from 0 to 100.
The results of the TAILORx trial, the largest breast cancer treatment trial ever conducted, suggest that the Oncotype DX tumor test could identify up to 85 percent of women with early breast cancer who can forego . This applies especially to women older than 50 who have a recurrence score of 25 or less and women 50 years of age or younger with a recurrence score of 15 or less. This trial was previously discussed in an XRAY review here.
While the TAILORx trial was groundbreaking, more studies were needed to clarify which women need more of some therapies and less of others. For example, it was uncertain which if any women with node-positive breast cancer could safely forgo chemotherapy.
Two studies presented at the 2020 San Antonio Breast Cancer Symposium attempted to answer this important question.
Researchers of these studies wanted to know if tumor tests could be used to identify more women who can safely forgo chemotherapy. Specifically, are there women with hormone receptor-positive, breast cancer who are candidates for chemotherapy by standard criteria who can safely be treated with hormone therapy alone?
The RxPONDER trial
Populations looked at in this study
RxPONDER is a , trial of hormone therapy versus chemotherapy combined with hormone therapy in women with one t three positive and an Oncotype Dx score below 25. Eligible participants were women over 18 years of age with hormone receptor-positive, breast cancer with one to three positive .
Study design
A total of 9,383 women with , breast cancer and one to three positive were screened to identify those with Oncotype Dx recurrences scores of 25 or less. Among those identified, 5,083 patients were randomly assigned to receive hormone therapy alone or hormone therapy plus several months of intravenous chemotherapy with taxane and/or anthracyclines. These chemotherapy drugs are considered to be standard treatments for this type of cancer.
The primary goal of the study was to determine the effect of chemotherapy on disease-free survival and whether the effect depended on Oncotype Dx scores. All women were monitored for about five years to assess invasive disease-free survival, or IDFS, a measure that counts which patients develop cancer that spreads outside of the breast, develop a new tumor inside a breast or die from any cause. Overall survival was a secondary assessment.
Study findings
As a data and safety monitoring committee began reviewing the trial results, they noticed a surprising pattern—one that was clear enough for them to recommend that the findings be reported publicly before the final analysis was complete.
Data from 5,015 participants were used in the early five-year analysis.
- Among postmenopausal women:
- The five-year disease-free survival rate was 91.6% for the chemotherapy-plus-hormone therapy group and 91.9% for the hormone therapy-only group.
- Among premenopausal women:
- The five-year disease-free survival rate was 94.2% for the chemotherapy-and-hormone therapy group, compared to 89.0% for the hormone therapy-only group.
- Premenopausal women also had an overall survival benefit from chemotherapy.
- At five years, the overall survival rate was 98.6% for those receiving chemotherapy plus hormone therapy and 97.3% for women in the hormone therapy-only group.
The ADAPT trial
Populations looked at in this study
Among the 5,625 registered participants, 2,290 women with hormone receptor-positive, breast cancer who were candidates for chemotherapy by standard criteria were studied in the ADAPT hormone therapy arm.
Study design
The ADAPT trial looked at combining two tumor scores, Oncotype Dx and a tumor marker called Ki-67, to see if combining these scores could identify women with up to three positive who were most likely to benefit from chemotherapy. The study was done as follows:
- All patients had a biopsy.
- Biopsy tissued was tested by Oncotype Dx to generate a recurrence score and tested to see what percentage of tumor cells had the Ki-67 tumor marker.
- All patients had a short course (about 3 weeks) of hormone therapy before surgery.
- After surgery, patients’ tumors were again scored for Ki-67.
- If the second Ki67 score was less than 10% (less than 10% of tumor cells had the Ki-67 tumor marker), the researchers used that as an indication that patients were responding to hormone therapy.
- Researchers grouped patients by Oncotype Dx and their second Ki-67 score. The two groups that received hormone therapy alone were:
- those who had an Oncotype Dx score of 0 to 11 (868 participants) and had a Ki-67 score of less than 10% at the time of surgery.
- those who had an Oncotype Dx score of 12 to 25 (1,422 participants) and had a Ki-67 score of less than 10% at the time of surgery.
- Women with Oncotype Dx scores of 12 or higher and Ki67 scores of 10% or higher after 3 weeks of hormone therapy were given chemotherapy with hormone therapy after surgery. The results of this group were presented in another presentation and are not included here.
Study findings
After 5 years:
- The overall survival rate was excellent and similar for both groups.
- Patients with Oncotype Dx scores of 0 to 11 had a 5-year survival rate of 98%.
- Patients with Oncotype Dx scores of 12 to 25 who were responding to hormone therapy had a 5-year survival rate of 97%.
- Survival rates did not differ by subgroup such as age or how many positive a patient had except for one subgroup of women with 3 positive .
- Patients in this subgroup with recurrence scores of 12 to 25 who responded to pre-surgery hormone therapy had a significantly lower 5-year disease-free survival rate of 76% compared to patients with no positive (97%), 1 positive lymph node (95%) or 2 positive (92%).
- The ADAPT study showed that regardless of age, the following patients can be safely treated by hormone therapy alone:
- Patients with 0 to 3 positive and Oncotype Dx scores of 0 to 11.
- Patients with 0 to 2 positive and Oncotype DX scores of 12 to 25 who are responding to hormone therapy based on Ki-67 tumor scores of 10% or lower.
- The ADAPT study also suggests that patients with 3 positive who had Oncotype Dx scores of 12 to 25 and responded to hormone therapy based on Ki-67 tumor scores may not be good candidates for hormone therapy alone and may benefit from chemotherapy.
Looking at Oncotype Dx scores score together with Ki-67 scores may help identify women who can safely skip chemotherapy.
Why are study results different?
The results of RxPONDER and the ADAPT studies seem to be different based on menopausal status and the number of positive .
- RxPONDER showed that postmenopausal women with up to 3 positive do not benefit from chemotherapy.
- ADAPT showed that regardless of menopausal status, women with 3 positive likely benefit from chemotherapy.
These differences are likely due to how the two studies were conducted. Both studies looked at Oncotype Dx scores in patients with early breast cancer and 0 to 3 positive .
However, patients in the ADAPT study had:
- a short course of hormone therapy before surgery (patients in the RxPONDER study did not).
- a Ki-67 tumor score at biopsy and at surgery. This score was used to identify patients for whom hormone therapy seemed to be working. (Ki-67 scores were not used in RxPONDER so researchers did not identify which patients might not respond to hormone therapy.)
Strengths and limitations
Strengths
- RxPONDER and ADAPT are both very large , studies.
Limitations
- To date, follow-up for both studies is limited. Data will continue to be collected and results may change.
Context
The side effects of chemotherapy can be devastating. While some resolve quickly, others may last months, years or even a lifetime. The results of the RxPONDER and ADAPT studies are likely to be useful in the clinic and expand the number of patients who can safely forgo chemotherapy.
Conclusions
These studies represent important steps towards the goal of more . By matching patients to the treatments that will likely benefit them, doctors can also identify patients which are unlikely to benefit from treatments.
Share your thoughts on this XRAYS article by taking our brief survey.
posted 3/4/21
Expert Guidelines
The National Comprehensive Cancer Network (NCCN) guidelines recommend the following for tumor testing in , , ER-positive breast cancer:
Premenopausal women:
Oncotype Dx testing and the following treatments are recommended:
- no positive and tumors greater than 0.5 cm:
- for people with an Oncotype Dx recurrence score of 15 or lower:
- recommend hormone therapy.
- consider medications to suppress ovaries.
- consider 3-5 years of bisphosphonate therapy
- for people with an Oncotype Dx recurrence score of 16-25:
- recommend either hormone therapy plus medications to suppress ovaries or chemotherapy followed by hormone therapy.
- consider 3-5 years of bisphosphonate therapy.
- for people with an Oncotype Dx recurrence score of 26 or higher:
- recommend chemotherapy followed by hormone therapy
- consider 3-5 years of bisphosphonate therapy
- for people with an Oncotype Dx recurrence score of 15 or lower:
- micrometastasis to of 2 mm or smaller or 1-3 positive lymph nodes:
- if candidate for chemotherapy, consider Oncotype Dx testing.
- recommend either hormone therapy plus medications to suppress ovaries or chemotherapy followed by hormone therapy.
- consider 3-5 years of bisphosphonate therapy.
NCCN notes that data are limited with regards to the use of Oncotype Dx in men. Available data suggest that the test provides prognostic information for men.
Updated: 11/13/2023
Questions To Ask Your Doctor
- What tumor tests have I had?
- How are my tumor test results being used to guide my treatment?
- Can I safely skip chemotherapy?
- With my tumor test results, what are the chances that my cancer will come back?
Open Clinical Trials
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.
Updated: 02/01/2024
Related Resources
The following organizations have resources related to breast cancer.
- FORCE related resources:
- Information: Breast cancer screening and prevention
- Information: Breast cancer treatment
- Personalized portal: Breast cancer
- XRAY category: Breast cancer
- XRAY category: breast cancer
- Video playlist: Breast cancer
- Blogs: Breast cancer
- General breast cancer resources:
- breast cancer resources:
- Male breast cancer resources:
- Resources for Black, Indigenous and People of Color:
Updated: 06/28/2023
Who covered this study?
verywellhealth
Chemotherapy may not be necessary for certain breast cancers, study finds
This article rates 5.0 out of 5 stars
Cancer Therapy Advisor
Adjuvant endocrine therapy alone judged suitable for certain breast cancer patients
This article rates 4.0 out of 5 stars
Medscape
RxPONDER: Chemo 'no longer a mandate' for some with breast cancer 
This article rates 3.5 out of 5 stars