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Breast Diseases

Skin Diseases

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Anti-Infective Agents

Zinc

Iodine

Technetium Tc 99m Sestamibi

Radiopharmaceuticals

Participants underwent conventional mammography and molecular breast imaging after a 740-millibecquerel (mBQ) (8-mCi) Technetium (99mTc) sestamibi injection.

Molecular breast imaging is a new nuclear medicine technique for imaging the breast. It uses small field of view semiconductor-based gamma cameras that use Cadmium Zinc Telluride detectors. These have superior spatial and energy resolution to conventional sodium iodide detectors.

Molecular Breast Imaging

Mammography is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast and is used as a diagnostic and a screening tool.

Conventional Mammography

Technetium (99mTc) sestamibi is a pharmaceutical agent used in nuclear medicine imaging. The drug is a coordination complex consisting of the radioisotope technetium-99m bound to six methoxyisobutylisonitrile (MIBI) ligands.

Technetium (99mTc) sestamibi

Deborah J Rhodes, M.D.

A new test for breast cancer screening, molecular breast imaging (MBI) may be more sensitive than mammography for detecting breast cancer in women with dense breasts. The purpose of this study is to see if MBI using a low dose of gamma radiation can find cancers not seen on mammography.

Hypotheses: 1. Low-Dose MBI has a significantly higher sensitivity and specificity and equal or higher positive predictive value than SM in women age 40 and older with mammographically dense breasts. 2. Low-dose MBI has comparable sensitivity and specificity to that previously achieved with MBI using a higher dose of radiation. 3. MBI produces a low false positive rate (specificity \>90%) that permits its use as a screening tool in this patient population.

A previous study demonstrated that the addition of MBI using 20 mCi Tc-99m sestamibi to screening mammography (SM) increased diagnostic yield for breast cancer in dense breasts (supplemental yield of 7.5/1000 screened). After implementing radiation dose reduction techniques, the performance of incident SM and prevalent screen MBI in women with dense breasts will be compared.

Methods:

Women presenting for SM with heterogeneously or extremely dense breasts on past prior SM were enrolled and underwent digital SM and MBI. Study information was sent to all eligible patients in advance of their scheduled SM explaining the study and offering them participation. Eligible patients who requested to participate were offered an MBI on the same day as their SM or within 21 days of the SM. Participants may have participated in this screening study up to two times provided at least 24 months had elapsed since the initial MBI scan. This time period was selected as the average time for a tumor to double in size is approximately 20 months. Hence a 24 month time interval between MBI studies was to enable detection of interval cancers or cancers that were too small to be detected in the initial MBI scan.

MBI was performed with 8 mCi Tc-99m sestamibi and dual-head cadmium zinc telluride detectors. SMs were read independently; MBIs were read in comparison with SM. MBIs were assigned an assessment score of 1-5 which parallels BI-RADS; scores of 3-5 on MBI were considered positive.

Low Dose Molecular Breast Imaging as a Screening Tool for Women With Dense Breasts

Evaluation of Low-dose Molecular Breast Imaging as a Screening Tool in Women With Mammographically Dense Breasts and Increased Risk of Breast Cancer

The cancer detection rate per 1000 women screened is the estimate of the number of women with positive results from a screening test.

Specificity measures the percentage of negatives which are correctly identified as such.

Sensitivity measures the percentage of actual positives which are correctly identified as such.

Recall rate was defined as the percentage of participants recalled for follow-up studies initiated because of abnormal findings with mammography or MBI.

Biopsy rate = number of participants who had a biopsy/number of number of participants analyzed.

Susan G. Komen Breast Cancer Foundation

Mayo Clinic

Associate Professor of Medicine

Mammography and Molecular Breast Imaging

Participants underwent conventional mammography and molecular breast imaging after a 740-millibecquerel (mBQ) (8-mCi) Technetium (99mTc) sestamibi injection.

Molecular Breast Imaging: Molecular breast imaging is a new nuclear medicine technique for imaging the breast. It uses small field of view semiconductor-based gamma cameras that use Cadmium Zinc Telluride detectors. These have superior spatial and energy resolution to conventional sodium iodide detectors.

Conventional Mammography: Mammography is the process of using low-energy X-rays (usually around 30 kVp) to examine the human breast and is used as a diagnostic and a screening tool.

Technetium (99mTc) sestamibi: Technetium (99mTc) sestamibi is a pharmaceutical agent used in nuclear medicine imaging. The drug is a coordination complex consisting of the radioisotope technetium-99m bound to six methoxyisobutylisonitrile (MIBI) ligands.

At the beginning of the study, the protocol inclusion criteria allowed women aged 25 years and older to participate. Between the dates of 5/11/09 and 4/20/10 there were 13 women under age 40 enrolled. On 4/20/2010 a protocol revision was approved by the Institutional Review Board to allow women aged 40 and older. In the final analyzable dataset of 1585 women who completed the study and had reference standard, 6 women were under age 40.

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Premenopausal

Peri-menopausal

Postmenopausal

Surgical Menopause

Menopausal Status

Almost entirely fat

Scattered fibroglandular densities

Heterogeneously dense

Extremely dense

Eligibility was determined by density assessed on a previous mammogram prior to study entry; mammographic density reported refers to density assessed from the study mammogram.

Mammographic Breast Density

Known mutation in BRCA1 or BRCA2 genes

Chest, mediastinal, or axillary irradiation

Personal history of breast cancer

Prior biopsy showing hyperplasia, etc.

Gail or Claus model lifetime risk ≥ 20%

Gail model 5 year risk ≥ 2.5%

Gail model 5 year risk ≥ 1.7%

1 first-deg relative with history of breast cancer

2 2nd-deg relatives with history of breast cancer

None of the above risk factors

Although participants may have qualified for multiple risk factor categories, they were assigned to only one risk factor category in this table. These risk factors are listed in order of priority. The last two risk factors with respect to first and second-degree relatives with a history of breast cancer refer to subjects who qualified on the basis of family history but did not meet the Gail or Claus model risk threshold levels.

The Gail risk model focuses on nongenetic risk factors, with limited information on family history. The Claus risk model focuses on genetic risk factors.

Risk Factors

< 425 days

425-730 days

>730 days

None

A total of 7 women under the age of 50 with no prior mammogram were enrolled.

Mammogram Prior to Study Entry

415- 730 days

> 730 days

Molecular Breast Imaging Prior to Study Entry

Heterogeneously dense breasts

Participants with Prior Mammogram

Breast Density of Participants with No Prior Mammogram

Dr. Deborah Rhodes

Comparison of the two groups for all densities, significant difference p ≤ 0.05.

Comparison of two groups for all densities; significant difference p ≤ 0.05.

All densities

For this reporting arm, the interpretation and analysis was done with mammography only.

Mammography Only

For this reporting arm, the interpretation and analysis was done with both mammography and MBI together.

Mammography With Adjunct MBI

For this reporting arm, the interpretation and analysis was done with gamma imaging only.

Molecular Breast Imaging Alone

Cancer Detection Rate Per 1000 Women Screened, by Breast Density

The analysis population only included participants with a verified negative cancer status at 12 months after the initial screening (mammography and MBI).

Specificity

The analysis population only included participants with a verified cancer status at 12 months after the initial screening. 21 participants out of the total study population of 1585 were diagnosed with cancer.

Sensitivity for All Cancers Diagnosed

The analysis population only included participants with a verified cancer status at 12 months after the initial screening (mammography and MBI).

Recall Rate

Biopsy Rate

Overall Study

Participants underwent conventional mammography and molecular breast imaging after a 740-millibecquerel (mBQ) (20-mCi) Technetium (99mTc) sestamibi injection.

Deborah J. Rhodes, M.D.

We aim to compare the sensitivity of mammography to the sensitivity of Molecular Breast Imaging (a new gamma-camera based breast imaging technology) in women with dense breast tissue who are at increased risk for breast cancer.

The sensitivity of conventional mammography (MMO) is poor in women with mammographically dense breast parenchyma. We have developed Molecular Breast Imaging (MBI) - a new technique which utilizes a Cadmium-Zinc-Telluride (CZT) gamma camera for scintimammography that has a high sensitivity (\~90%) for the detection of breast cancers independent of breast density.

The aim of this study is to demonstrate the utility of MBI as an adjunct screening modality for the detection of occult breast cancers in women with mammographically dense breast tissue. Initial recruitment will be from the pool of patients awaiting a screening mammogram in the Department of Radiology at Mayo Clinic Rochester. All patients will have a screening MMO and an MBI study. Patients with positive studies (MBI or MMO) will undergo additional diagnostic studies. At 15 months post-recruitment, all patients will be contacted by phone or mail to determine whether subsequent to their study, there has been any change in their breast status.

Molecular Breast Imaging as a Screening Tool for Women With Dense Breasts

Diagnostic yield is the likelihood that a test or procedure will provide the information needed to establish a diagnosis. In this case, it is the proportion of women with positive results of a screening test and positive results with the reference standard (verified cancer status).

Sensitivity measures the proportion of actual positives which are correctly identified as such.

Specificity measures the proportion of negatives which are correctly identified as such.

Recall rate was defined as the percentage of participants recalled for follow-up studies initiated because of abnormal findings with mammography or gamma imaging.

Participants underwent conventional mammography and molecular breast imaging after a 740-millibecquerel (mBQ)(20-mCi) Technetium (99mTc) sestamibi injection.

Participants underwent conventional mammography and molecular breast imaging after a 740-mBQ (20-mCi) Technetium (99mTc) sestamibi injection.

White

Hispanic or Latina

Black or African American

Asian

American Indian or Alaskan Native

Unknown or data missing

Race or ethnicity

Perimenopausal

Postmenopause

Surgical menopause

Menopausal status

Mammographic breast density

Known mutation in BRCA1 or BRCA2 gene

Prior chest, mediastinal, or auxiliary irradiation

Gail model 5 year risk ≥ 1.6%

2 second-deg relatives history of breast cancer

personal history of breast cancer

Risk factors

Dr. Deborah J. Rhodes

Gamma Imaging

For this reporting arm, the interpretation and analysis was done with both mammography and gamma images together.

Both Mammography and Gamma Imaging

The analysis population only included participants with a verified cancer status at 12 months after the initial screening (mammography and gamma imaging).

Diagnostic Yield

For all cancers; significant difference p ≤ 0.05

For invasive cancers; significant difference p ≤ 0.05

For ductal carcinoma in situ; significant difference p ≤ 0.05

All cancers

Invasive cancers

Ductal carcinoma in situ (DCIS)

Sensitivity

Invasive cancer

Number of Participants With Cancer Diagnosis at 12 Months

The analysis population only included participants with a verified cancer status at 12 months after the initial screening (mammography and gamma imaging). The number of participants negative for breast cancer was 936-11 = 925.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Low Dose Molecular Breast Imaging as a Screening Tool for Women With Dense Breasts	NCT01925170	Breast Cancer	Molecular Breas... Conventional Ma... Technetium (99m...	40 Years -	Mayo Clinic
Molecular Breast Imaging as a Screening Tool for Women With Dense Breasts	NCT00620373	Breast Cancer	Molecular Breas... Conventional Ma... Technetium (99m...	25 Years -	Mayo Clinic

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