Tomosynthesis Mammographic Imaging Screening Trial (TMIST)

Study Status: Recruiting

Do you want to help doctors develop ways to personalize breast cancer screening for women in the future?

Primary Contact: Research Staff BC Women’s Hospital and Health Centre

TMIST@cw.bc.ca | Contact Phone Number: 604-875-2424 ext. 5534

About the study

TMIST (Tomosynthesis Mammographic Imaging Screening Trial) is a research study that will help researchers learn about the best way to find breast cancer in women who have no symptoms. This is a randomized breast cancer screening study that compares two types of digital mammograms for their ability to reduce advanced breast cancer. Each woman will be randomized either into a group that receives the standard digital mammogram (2-D) or a newer technology called tomosynthesis mammogram, which has 3-dimensional capability.The 2-D mammograms take pictures from two sides of the breast to create a flat image. The 3-D mammogram images are taken from different angles around the breast and then built into a 3-D-like image.

About 129,000 people from Canada, the United States and Argentina will take part in this study. This research is part of a multicentre study sponsored and coordinated by the Canadian Cancer Trials Group in Canada as well as sponsored by ECOG-ACRIN in the United States.

Why is this research important?

The goal of breast cancer screening is to find life-threatening breast cancer early, when it may be easier to treat, and reduce the chance that someone will die from it. Researchers are doing this trial because they do not know if 3-D mammograms are better than 2-D mammograms for breast cancer screening.

Therefore, the main goal of TMIST is to compare 2-D mammograms with 3-D mammograms to see which one is better at reducing advanced breast cancer. If one type of mammogram is better at finding life-threatening breast cancers early, then fewer people screened with that type of mammogram should go on to develop advanced breast cancer.

The researchers are also looking at whether 3-D mammograms might help certain groups of women. Questions they are trying to answer include:

Among the women who receive 3-D mammograms, will fewer advanced cancers be diagnosed in certain groups, such as

women with dense breasts
different racial and ethnic groups
premenopausal women
women who are taking hormone replacement therapy

Will there be fewer false-positive test results in the entire study group or among certain groups?
Is there a link between certain findings on mammograms and development of the most aggressive breast cancers?
Are some types of cancers more common between recommended screening intervals?

Another important aspect of the trial is to build a tissue bank for future research. Everyone who joins the trial will be offered the option to submit tissue samples, such as blood and swabs of cells from inside their mouths. Researchers hope that the information from these tissue samples will help personalize the way we screen for breast cancer in the future by taking a person’s genetics and other personal risk factors into account.

Who can participate?

Women between 45-74 years of age, who are eligible for mammography screening at the Screening Mammography Program of British Columbia, and can return to the original screening site (X-Ray 505) for further mammograms during the study.

What happens once I enroll in TMIST

TMIST will last for 5 years. Once enrolled, you will be randomly assigned by a computer to have either a 3-D or 2-D screening mammogram. You will have that kind of mammogram every year or every other year for 5 years. How often you have a mammogram during these 5 years will be based on your

age
breast density
family history of breast cancer
use of hormone replacement therapy
menopausal status

How often you have a mammogram during the 5 years of the study may change if your risk changes. Risk changes might include new genetic testing findings, changes in family history, or changes in hormone replacement therapy use.

During the study, the results of every mammogram from every participant will be collected. Information will also be recorded about any medical follow-up tests, such as more imaging or a biopsy, breast cancer diagnoses, treatment, and how people responded to treatment. Results will also be sent to your referring doctor or nurse practitioner as per standard clinical care.

After you complete 5 years on the study receiving the type of mammogram that was assigned, the research team will follow you for another 3 years. During the 3-year follow-up period you can get either type of mammogram.

Frequently Asked Questions

What is the study about?

TMIST (Tomosynthesis Mammographic Imaging Screening Trial) is a breast cancer screening trial that compares two mammography screening technologies, conventional, standard digital mammography (DM) and tomosynthesis (TM), and their ability to reduce advanced breast cancer in the screened population.
What is tomosynthesis?

Tomosynthesis is a new type of mammography imaging that allows the radiologist to evaluate your breast health in more detail. Tomosynthesis mammography images are taken from different angles around the breast and then built into a 3-D-like image by a computer.
What does the study involve?

Being part of the study means that you will be randomly assigned to either Group 1 which uses conventional, standard 2D mammography or to Group 2 which uses a combination of the standard 2D mammography plus tomosynthesis which takes 3D images. You will have 3-5 screening mammograms during the first 5 years of the study. After that the researcher will follow up once a year by phone or email to check how you are doing.
Is tomosynthesis safe?

Yes, the radiation with a tomosynthesis mammogram remains within national accreditation guidelines in Canada. The radiation you are exposed to for 2D mammography is approximately 1.2 mSv while the amount from the tomo 3D plus 2D mammograms is 2.7 mSv. This, ‘double’ dose is just slightly more that the dose of a film mammogram which was used in BC before the introduction of digital mammography in 2012. This is about the amount of radiation you would be exposed to flying from New York to California on a jet airplane.
What are the screening arms, and how many women will be enrolled?

TMIST will randomize women to either the 2D (DM) or 3D (TM) arm. Each woman will get screened either annually or biennially, depending on certain breast cancer risk factors. The accrual goal is 128,905 women in approximately 130 sites.
What is the population for this trial?

The TMIST population is women 45 to 74 years old who present for screening mammography at participating centers. This is a study of screening for breast cancer, intended for women with no symptoms. It is not a study of a treatment for women who have breast cancer.
Who is not eligible to participate in TMIST?

Women may not participate if they are symptomatic for breast disease, have new breast complaints (i.e., lump or nipple discharge), had a screening mammogram within the last 11 months, previously had breast cancer, have breast enhancements, or are pregnant or lactating. Women with mild breast pain are eligible to participate.
What determines if I’ll have screening mammograms done once every year or once every other year?

Most women in the trial will get annual screening. The frequency of screening mammograms will depend on your age and certain risk factors.
Annual screening in the trial is for women who are:
1. Premenopausal, or
2. Postmenopausal, age 45 to 69 with any of the following risk factors: have dense breasts (BIRADS category c–heterogeneously dense, or d–extremely dense), be a known breast cancer deleterious mutation carrier, have a first-degree relative with breast cancer, or currently on hormone replacement therapy, or
3. Postmenopausal, age 70 to 74 and have dense breasts (BIRADS category c or d, or
4. 4) Postmenopausal, age 70 to 74 and currently taking hormone replacement therapy.
Additionally, postmenopausal women age 45 to 74 are eligible for annual screening if they have had at least one benign breast biopsy with a diagnosis of LCIS or atypia of any kind (atypical ductal hyperplasia, atypical lobular hyperplasia, atypical hyperplasia NOS, or intraductal papilloma with atypia).
How does the trial define “postmenopausal”?

The trial defines postmenopausal women as those who had their last menstrual period more than 12 months before study entry or who no longer have menses due to bilateral oophorectomy with either hysterectomy or endometrial ablation. Women who had either hysterectomy or endometrial ablation who have at least one ovary will be considered premenopausal until age 52, and postmenopausal thereafter.
Who is eligible to participate in the biennial screening cohort of TMIST?

All postmenopausal women not meeting eligibility for the annual screening cohort are eligible for the biennial screening.
Is the procedure for mammograms within the study different from what I’m used to with regular screening?
No, all screening mammography exams will be conducted in the same way as per standard of care within the Screening Mammography Program of BC. The experience will be almost identical whether you have the regular mammogram or both the mammogram and tomosynthesis. The same positions and compression are required for tomosynthesis so the technologist will just take the pictures at the same time as your 2D mammogram. This takes an extra 4 seconds per picture in the tomo group.
What is the duration of follow-up for this trial?
The screening examinations that are part of the screening period in TMIST occur within the first 5 years after randomization. The site trial team will collect clinical and imaging data regarding the screening, diagnosis, and treatment of breast cancer during this period. After the study-specific screening mammograms are completed, there is a long-term follow-up period to monitor women for the diagnosis of breast cancer. All participants will be followed for at least 3 and up to 8 years after study entry. The site trial team will conduct surveys to determine breast cancer status, either when the participant returns to the clinic for standard-of-care follow-up and routine breast cancer screening, or through telephone surveys, chart reviews, and/or death and tumor registries.
How much time will participation in the study take?
For the first visit we will need you to schedule an extra 50-60 minutes phone call to go over the intake questions and consent forms. At the following visits you will spend approximately 20 minutes extra to complete the yearly visit questions in person or by phone.
How is the trial being funded?
This trial is being funded by the National Cancer Institute through the National Community Oncology Research Program or National Clinical Trials Network funding mechanisms based on your institution’s NCI affiliation. To learn more, visit the EA1151 page at www.ctsu.org and click on the Funding Information tab.
What happens if a woman has a positive screen?
She will undergo the usual standard-of-care diagnostic workup, which may include additional imaging and/or biopsy. She remains in the trial, but the results of the downstream exams and/or procedures will dictate whether she remains in the screening population and continues with study screening rounds. For women who are clinically recommended for short- term follow-up or biopsy, we will follow clinical care as it is performed for the duration of the trial.
What happens if a woman is diagnosed with breast cancer?
On detection and confirmation of breast cancer, participants will cease protocol screening and begin annual follow-up. This includes the collection of reports for all procedures and treatments (eg, imaging, biopsy, surgery, chemotherapy, and radiation therapy). These women will be followed by the site trial team for progression, recurrence, and vital status, either when they return to the clinic for standard-of-care follow-up or through telephone surveys, chart reviews, and/or death and tumor registries.
Will this change how my results are sent to me?
No, you will still receive your results in the same way according to the BC Cancer procedures.
Who do I contact about the study?
You can email TMIST@cw.bc.ca for further information.

Principal Investigator: Dr. Paula Gordon

Sponsored by: Canadian Cancer Trials Group

Partners: BC Women’s Hospital + Health Centre, BC Cancer Agency, Screening Mammography Program of BC, American College of Radiology (ACR), American College of Radiology Imaging Network (ACRIN)