Frequently asked questions
We hope that these common questions and answers help you decide whether the I-SPY 2 Trial is right for you. The resources on the EXPERTS EXPLAIN page may also help you decide. You can use the National Cancer Institute dictionary at the bottom of the page to find the meanings of terms that are not familiar to you.
Deciding whether to participate
What is a clinical trial and why should I consider participating in a cancer clinical trial?
- Clinical trials are studies that test whether a new investigational drug, combination of drugs or medical procedure improves health or extends life and is safe for patients. Here’s a helpful National Cancer Institute (NCI) booklet about clinical trials that you can download.
- Clinical trials are required before any new drug can be approved for use by patients. All modern currently available drugs have been tested in clinical trials and are available because patients volunteered to participate in a clinical trial.
- As part of a clinical trial, you could receive the 1) standard treatment for your cancer or 2) a new treatment that is being tested or 3) both of these treatments combined.
- Clinical trials often require additional tests beyond what you would receive with standard treatment. The additional test results may help you and your doctor decide what treatment is best for you. The trial covers the cost of these additional tests. Be sure to check with your insurance company to find out exactly what tests they will pay for and what, if any costs, you will be responsible for covering.
- Clinical trials require more time from you because you are followed more closely than if you were receiving standard treatment outside of a trial.
- Clinical trials offer you an opportunity to contribute to medical science and help others.
- You can download this list of questions you may want to ask the study team before volunteering to participate in a clinical trial.
- Participating in a clinical trial is completely voluntary and you can stop participating at any time.
What is the I-SPY 2 Trial?
Who is eligible to participate?
How does the trial work? What are the screening criteria?
For patients enrolled before June 23, 2022
The Screening Phase is when your tumor and overall health (heart, kidney, and liver function) are assessed to determine if you qualify to participate in the trial. You will have a biopsy of the tumor, which is evaluated by a molecular test called MammaPrint®. MammaPrint determines if a tumor has a high risk of recurrence if it is treated with surgery alone and not treated with chemotherapy.
There are 3 phases to the I-SPY 2 trial:
The Screening Phase is when your tumor and overall health (heart, kidney, and liver function) are assessed to determine if you qualify to participate in the trial. You will have a biopsy of the tumor, which is evaluated by a molecular test called MammaPrint®. MammaPrint determines if a tumor has a high risk of recurrence if it is treated with surgery alone and not treated with chemotherapy. If your tumor is MammaPrint high-risk or you have HER2+ or triple negative breast cancer, you qualify for chemotherapy treatment. If your tumor is ER+ HER2- and MammaPrint low-risk you qualify for endocrine therapy. Again, the majority of people screened for the trial meet the screening criteria.
The Treatment Phase is when you will receive your assigned drug treatment. Chemotherapy treatment will be either 12 weeks of:
- standard treatment chemotherapy called paclitaxel or
- paclitaxel and an investigational drug or drug combination or
- an investigational drug or drug combination without paclitaxel.
If your tumor is HER2 positive you will also receive a HER2 targeted standard treatment (traztuzumab and pertuzumab).
Next, you will receive 4 doses of the drugs Adriamycin and cyclophosphamide (called AC, for short), over the next 12 weeks, which is standard treatment.
If your tumor has completely responded to your first 12 weeks of treatment, as seen on an MRI and through a biopsy, you and your doctor may decide that Adriamycin and cyclophosphamide (AC) treatment is not necessary before surgery.
For the Endocrine Therapy Treatment Phase patients are randomly assigned to receive either an investigational oral SERD (Amcenestrant) alone or in combination with another investigational targeted drug (Letrozole (AI) or Abemaciclib) for 6 months.
Response to your treatment will be monitored by MRI (Magnetic Resonance Imaging) to see any change in your tumor size. Blood and breast tissue samples are collected to use for research at several times during the trial. Following treatment, you will have surgery to remove any remaining tumor. Any additional treatment after surgery, if needed, will be decided by you and your study doctor.
During the Follow-Up Phase a member of your study care team will check on your health once every six months for ten years and do a blood draw for research once a year for at least five years.
For patients who enrolled on or after June 23, 2022 or who are interested in learning more about the trial
There are 3 phases to the I-SPY 2 trial:
The Screening Phase is when your tumor and overall health (heart, kidney, and liver function) are assessed to determine if you meet the criteria to participate in the trial. You will have a biopsy of the tumor, which is evaluated by a molecular test called MammaPrint®. MammaPrint determines if a tumor has a high risk of recurrence if it is treated with surgery alone and not treated with chemotherapy.
- If your tumor is MammaPrint high-risk or you have HER2+ or triple negative breast cancer, you qualify for chemotherapy treatment.
- If your tumor is ER+ HER2- and MammaPrint low-risk or MammaPrint high risk and clinical stage II, you meet the criteria for endocrine therapy.
- If your tumor is MammaPrint high risk, RPS negative and SET high (see below for explanation), you may choose either the novel targeted chemotherapy treatment or the endocrine treatment.
- MammaPrint high risk means that a tumor has a risk of recurring with surgery only.
- Response Predictive Subtype (RPS) is an I-SPY 2 classification system that matches a tumor to the investigational treatment that is most likely to be effective. RPS negative means we don’t have evidence that a tumor will respond to one of the investigational chemotherapy treatments.
- SET (Sensitivity to Endocrine Therapy) is a test that predicts if a tumor will respond to endocrine therapy. A SET high score means a tumor is predicted to respond to endocrine therapy.
The Treatment Phase is when you will receive your assigned drug treatment. Chemotherapy treatment will range from 12 to 36 weeks of:
- Standard treatment chemotherapy
- An investigational drug with or without standard chemotherapy
If your tumor is HER2 positive you will also receive a HER2 targeted standard treatment (traztuzumab and pertuzumab).
Next, you may receive 4 doses of the drugs Adriamycin and cyclophosphamide (called AC, for short), over the next 12 weeks, which is standard treatment.
If your tumor has completely responded to your first 12 weeks of treatment, as seen on an MRI and through a biopsy, you and your doctor may decide that Adriamycin and cyclophosphamide (AC) treatment is not necessary before surgery.
The treatment phase is divided into three different treatments as noted below:
Treatment A will be 12 weeks of a novel treatment targeted to your tumor’s Response Predictive Subtype.
If your tumor responds completely to Treatment A as seen on an MRI and through a biopsy, you and your doctor may decide that Treatment B is not necessary. You will be given the option to go directly to surgery. If your tumor is showing minimal response to treatment A, you will move onto Treatment B early.
If there is no Treatment A option for your tumor type when you join the trial, you will start with Treatment B.
Treatment B will be 12 to 18 weeks of standard treatment chemotherapy.
If your tumor is HER2 positive you may also receive a HER2 targeted standard treatment (traztuzumab and pertuzumab).
If your tumor responds completely to Treatment B you will be given the option to go to surgery early. If your tumor shows only minimal response to Treatment B, you will move to Treatment C.
Treatment C will be 8 to 12 weeks of:1) Adriamycin and cyclophosphamide (called AC, for short).
After you have completed Treatment C you will have surgery.
For the Endocrine Therapy Treatment Phase patients are randomly assigned to receive either an investigational oral SERD (Selective Estrogen Receptor Degrader) drug (Amcenestrant) alone or in combination with another investigational targeted drug (Letrozole (AI) or Abemaciclib) for 6 months.
Response to your treatment will be monitored by MRI (Magnetic Resonance Imaging) to see any change in your tumor size. Blood and breast tissue samples are collected to use for research at several times during the trial. Following treatment, you will have surgery to remove any remaining tumor. Any additional treatment after surgery, if needed, will be decided by you and your study doctor.
During the Follow-Up Phase a member of your study care team will check on your health after 6 months and then annually for ten years. They will do a blood draw for research once a year for at least five years.
What else should I know as I consider whether to join the I-SPY 2 Trial?
- Gives drug therapy before surgery (neoadjuvant therapy).
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- Neoadjuvant therapy combined with imaging your tumor by MRI (Magnetic Resonance Imaging) allows your doctor to see if your tumor is responding to treatment.
- Neoadjuvant therapy also offers the possibility of less extensive surgery if the drug treatment is effective and the tumor shrinks.
- If neoadjuvant therapy is not completely effective, studies have shown that additional treatment after surgery reduces the risk of the cancer spreading. Neoadjuvant therapy allows you and your doctor to know if additional treatment is needed.
- Has shown that patients who chose to join the trial have a greater chance of being free of cancer in the breast when they go to surgery, than those who did not join the I-SPY 2 trial. When there is no breast cancer at surgery, it is called “pathological complete response” (pCR). In the I-SPY 2 trial pCR is predictive of a higher likelihood that there will not be a breast cancer recurrence within 5 years. As the trial continues, this follow up data will be extended.
- Gives patients a chance to receive a cutting-edge investigational drug. The investigation drugs have all shown promise in effectiveness and safety in earlier studies in cancer patients, and often in patients with breast cancer. The investigational drugs may be better than, worse than, or no different from standard chemotherapy. The goal of the I-SPY 2 Trial is to give patients a greater chance of achieving a pathological complete response (pCR), that is, being cancer free in the breast before going to surgery.
- Focuses on finding treatments to test in the trial that are more effective, less toxic, or both.
- Offers more opportunities to be seen by your care team as well as to get additional MRI scans, biopsies and blood draws to follow your progress. A patient on a clinical trial is generally watched more closely than one not on a clinical trial.
- Enables you to participate in research that is advancing drug development and treatment to help women and men who will have breast cancer in the future.
- Is a trial that continually learns from each patient so it can zero in on patients for whom a drug is appropriate. So, if you join the trial and are randomized to a treatment based on your tumor’s Response Predictive Subtype, you may have a higher likelihood of receiving a drug that has the greatest chance of reducing or eliminating your tumor because the trial has “learned” from previous patients. This is called adaptive randomization.
- Covers costs of the investigational drug as well as the cost for additional tests beyond what you would get if you were not in the trial. Be sure to check with your insurance company to see if they have any concerns about your participation in the trial. Find out exactly what tests they will pay for and what, if any costs, you will be responsible for covering.
Who may I speak with if I have more questions about the trial?
The Study Coordinator at the clinical trial site nearest you will be able to answer your questions as you are deciding whether to participate. If you decide to join the I-SPY 2 Trial, all questions should be directed to your clinical care team at your clinical trial site.
When did the trial start and what have we learned so far?
- The I-SPY 2 Trial began enrolling patients in 2010.
- One goal of the I-SPY 2 Trial is to more quickly test which investigational drugs benefit patients. Another goal is to find tumor characteristics (biomarkers) that can be used to match future patients with the best drug for their tumor.
- The I-SPY 2 Trial has developed a new tumor classification system, called Response Predictive Subtypes (RPS), to tailor treatment to the biology of the tumor.
- The I-SPY 2 Trial has already tested more than 20 investigational drugs. More than a dozen of these drugs were more beneficial for patients than standard therapy.
- One of the investigational drugs tested in I-SPY 2 was pembrolizumab, also known as Keytruda®, a new type of cancer drug that helps the immune system attack cancer cells. A large follow-up Phase 3 neoadjuvant study has confirmed I-SPY 2’s results that this drug is among the most effective treatments currently available for patients with triple negative breast cancer (TNBC).
- Due to efforts of the I-SPY team and its patient partners, the FDA introduced a quicker drug approval process for neoadjuvant breast cancer therapy, called accelerated approval. This allows highly effective new drug therapies to be used for specific types of breast cancer, several years earlier than before the I-SPY trials.
How does my participation in the I-SPY 2 Trial help other patients?
- The I-SPY 2 Trial uses a neoadjuvant approach to drug therapy, in which chemotherapy is given to patients prior to surgery. A patient’s response to treatment is determined both by measuring the size of the tumor with MRI over the course of treatment and by measuring the amount of tumor left at the time of surgery. The I-SPY 2 Trial is designed to learn from every patient as they complete the treatment phase of the trial. How each patient responds to the treatment she or he receives impacts which study treatment future patients will be assigned if they join the trial.
- By participating in this trial, you are helping to advance the development of effective and safe drugs more quickly so they can be evaluated and, hopefully, be approved by the U.S. FDA (Federal Drug Administration). Following approval, they can be used to treat more patients with breast cancer.
Why is the trial called the I-SPY 2 Trial?
Timing
If I join the I-SPY 2 Trial, how soon will I be able to start my treatment?
If I join the I-SPY 2 Trial, how long will I be in the study?
- If you are eligible and join the study, the Treatment Phase will last about 6 months. Then you will have surgery.
- After your surgery, you and your doctors will choose what further treatment (adjuvant therapy), if any, you will receive.
- The Follow Up Phase will last for at least five years and up to ten years during which your health will continue to be monitored.
- If you are eligible and join the study, the Treatment Phase may last from 3 to 9 months, depending on your tumor’s response to therapy. You may be eligible to have surgery before completing all 3 study treatments.
- After your surgery, you and your doctors will choose what further treatment (adjuvant therapy), if any, you will receive.
- The Follow Up Phase will last for at least five years and up to ten years during which your health will continue to be monitored.
Does taking the extra time to treat the tumor before surgery (neoadjuvant therapy) pose any risk to me?
Drug Treatment, Drug Assignments, and Side Effects
What investigational drugs are being tested in the trial?
- The investigational drugs being tested change over time. After a drug’s I-SPY 2 evaluation is complete it either “graduates” to be tested in a Phase 3 study (larger study) or gets removed from the trial because it did not reach the goal for safety and effectiveness.
- Drugs that have already been tested in I-SPY 2 include immune modulators such as pembrolizumab, (Keytruda®), PARP inhibitors such as talazoparib and anti-HER 2 drugs such as pertuzumab.
- The drugs to be tested in I-SPY 2, are carefully selected by a team of I-SPY 2 doctors, researchers, and patient advocates, as having shown promise of effectiveness and safety in earlier studies with cancer patients, and often in patients with breast cancer.
How likely am I to receive one of the investigational drugs on the I-SPY 2 Trial?
For patients enrolled before June 23, 2022
who enrolled on or after June 23, 2022 or who are interested in learning more about the trial
How does the I-SPY 2 Trial assign which treatment I receive?
For patients enrolled before June 23, 2022
If you are eligible for chemotherapy treatment, a computer will randomize you (assign you to a treatment group by chance), while taking into account your tumor’s biomarkers and study data from prior patients with tumors similar to yours. This is called adaptive randomization. Adaptive randomization gives you a greater chance of receiving treatment that is the most effective for your particular type of tumor.
- The tumor biomarkers used in the I-SPY 2 Trial are Estrogen Receptor (ER) status, Progesterone Receptor (PR) status, and HER2 receptor status, along with your MammaPrint risk score.
- If you are eligible for treatment with endocrine therapy, you will be randomly assigned to receive one of the three investigational drugs or drug combinations.
who enrolled on or after June 23, 2022 or who are interested in learning more about the trial
- If you are eligible for chemotherapy treatment, you will be assigned a Treatment A that is predicted to be most effective for your tumor based on tumor biomarkers.
- The tumor biomarkers used in the I-SPY 2 Trial are Estrogen Receptor (ER) status, Progesterone Receptor (PR) status, and HER2 receptor status, Responsive Predictive Subtype (RPS), along with your MammaPrint risk score.
- For Treatment B, a computer will randomize you (assign you to a treatment group by chance), while taking into account your tumor’s biomarkers and study data from prior patients with tumors similar to yours. This is called adaptive randomization. Adaptive randomization gives you a greater chance of receiving treatment that is the most effective for your particular type of tumor.
- If you are eligible for treatment with endocrine therapy you will be randomly assigned to receive one of the three investigational drugs or drug combinations.
What are the possible side effects of treatment?
- The side effects vary according to the drug or drug combination you are taking. Side effects may be more or less than those of standard treatment.
- Once you are placed in a study group to receive a specific drug, your doctor will explain the possible side effects to you and give you a consent form that lists all the known side effects. After asking questions, you can choose whether you want to start this treatment and participate in the study.
- You will be carefully monitored for side effects. If you experience any side effects it is important that you tell your study doctor as soon as possible so your study team can provide help to manage them.
Can I choose which treatment I receive?
- A computer will randomize you (assign you to a treatment group by chance), while taking into account your tumor’s biomarkers or characteristics.
- Once you are placed in a treatment group, you can decide if you want to participate in the Treatment Phase of the trial.
Can I switch investigational drugs during the Treatment Phase of the I-SPY 2 Trial?
For patients enrolled before June 23, 2022
- No. After you have been randomized to a treatment group, you will not be allowed to switch to another study treatment group.
- If you or your doctor feels that it is not in your best interest to continue on the Treatment Phase of the trial, you can stop participating in the trial at any time. Your participation in this and all clinical trials is always voluntary.
For patients who enrolled on or after June 23, 2022 or who are interested in learning more about the trial
- Yes. After you have been assigned or randomized to a treatment your tumor’s response will be evaluated. At each treatment decision point, you and your doctor will meet to review your results and together decide the next steps in treatment. Depending on your tumor’s response, you may have the opportunity to skip additional treatment and have surgery or move to the next treatment that is designed for your tumor’s Response Predictive Subtype.
- If you or your doctor feels that it is not in your best interest to continue on the Treatment Phase of the trial, you can stop participating in the trial at any time. Your participation in this and all clinical trials is always voluntary.
Are there any investigational drugs being tested specifically for patients with HR+/HER2- MammaPrint low risk breast cancer?
Yes, patients with HR+/HER2-, whose breast cancer has a low risk of recurrence according to the MammaPrint test (MP low risk), are eligible to receive endocrine therapy. These patients will be randomly assigned to receive either an investigational oral selective estrogen receptor degrader (SERD) alone or in combination with another investigational targeted agent for 6 months prior to their surgery.
Testing Procedures and Access to Results
How many times will tissue be collected, and how will the tissue be collected?
For patients enrolled before June 23, 2022
If you are eligible for chemotherapy treatment, a computer will randomize you (assign you to a treatment group by chance), while taking into account your tumor’s biomarkers and study data from prior patients with tumors similar to yours. This is called adaptive randomization. Adaptive randomization gives you a greater chance of receiving treatment that is the most effective for your particular type of tumor.
- The tumor biomarkers used in the I-SPY 2 Trial are Estrogen Receptor (ER) status, Progesterone Receptor (PR) status, and HER2 receptor status, along with your MammaPrint risk score.
- If you are eligible for treatment with endocrine therapy, you will be randomly assigned to receive one of the three investigational drugs or drug combinations.
who enrolled on or after June 23, 2022 or who are interested in learning more about the trial
- If you are eligible for chemotherapy treatment, you will be assigned a Treatment A that is predicted to be most effective for your tumor based on tumor biomarkers.
- The tumor biomarkers used in the I-SPY 2 Trial are Estrogen Receptor (ER) status, Progesterone Receptor (PR) status, and HER2 receptor status, Responsive Predictive Subtype (RPS), along with your MammaPrint risk score.
- For Treatment B, a computer will randomize you (assign you to a treatment group by chance), while taking into account your tumor’s biomarkers and study data from prior patients with tumors similar to yours. This is called adaptive randomization. Adaptive randomization gives you a greater chance of receiving treatment that is the most effective for your particular type of tumor.
- If you are eligible for treatment with endocrine therapy you will be randomly assigned to receive one of the three investigational drugs or drug combinations.
What tests will be run on my tumor tissue and blood samples and will I know the results?
- Your study doctor will receive a report to share with you that has information about the standard biomarkers in your tumor: Estrogen Receptor (ER), Progesterone Receptor (PR), and HER2 receptor.
- A portion of the tissue collected during the Screening Phase will be used to run the MammaPrint/BluePrint test. These test results will be provided to your study doctor and also will be shared with you. The biomarkers identified through these tests will be used to give you a greater chance of receiving treatment that targets your specific type of tumor.
- The I-SPY 2 Trial is committed to sharing your test results with you. Your doctor will meet with your regularly to share results. They will discuss how your treatment could be tailored based on the tumor’s response.
- Other tests will be run on your tissue and blood samples that are collected for research purposes only. Information from these tests will not be provided to you or your doctor and will not affect the care that you receive. This is because the study does not yet know what the results of these research tests mean. We hope to learn this information through the trial to help breast cancer patients in the future.
How many times will my blood be collected?
For patients enrolled before June 23, 2022
If you are eligible for chemotherapy treatment, a computer will randomize you (assign you to a treatment group by chance), while taking into account your tumor’s biomarkers and study data from prior patients with tumors similar to yours. This is called adaptive randomization. Adaptive randomization gives you a greater chance of receiving treatment that is the most effective for your particular type of tumor.
- The tumor biomarkers used in the I-SPY 2 Trial are Estrogen Receptor (ER) status, Progesterone Receptor (PR) status, and HER2 receptor status, along with your MammaPrint risk score.
- If you are eligible for treatment with endocrine therapy, you will be randomly assigned to receive one of the three investigational drugs or drug combinations.
who enrolled on or after June 23, 2022 or who are interested in learning more about the trial
- If you are eligible for chemotherapy treatment, you will be assigned a Treatment A that is predicted to be most effective for your tumor based on tumor biomarkers.
- The tumor biomarkers used in the I-SPY 2 Trial are Estrogen Receptor (ER) status, Progesterone Receptor (PR) status, and HER2 receptor status, Responsive Predictive Subtype (RPS), along with your MammaPrint risk score.
- For Treatment B, a computer will randomize you (assign you to a treatment group by chance), while taking into account your tumor’s biomarkers and study data from prior patients with tumors similar to yours. This is called adaptive randomization. Adaptive randomization gives you a greater chance of receiving treatment that is the most effective for your particular type of tumor.
- If you are eligible for treatment with endocrine therapy you will be randomly assigned to receive one of the three investigational drugs or drug combinations.
How can we tell if the drug is working to shrink my tumor?
- The I-SPY 2 Trial uses Magnetic Resonance Imaging * (MRI) to monitor and measure how your tumor is responding to your treatment.
- MRI is a non-invasive technique used to see inside the body. MRI does not use x-rays so there is no risk from radiation. However, it does use strong magnets so patients with metal implants like a heart pacemaker, insulin pump, or surgical pins are not eligible to join I-SPY 2.
If I join the I-SPY 2 Trial, how many MRI scans will I have and will I know the results?
- A computer will randomize you (assign you to a treatment group by chance), while taking into account your tumor’s biomarkers or characteristics.
- Once you are placed in a treatment group, you can decide if you want to participate in the Treatment Phase of the trial.
