Chapter 1

Introduction

In the United States, one in eight women will be diagnosed with breast cancer, accounting for 26% of all cancer cases in women (Jiao, 2014). The standard of care for women over the age of 40 is mammography. It has been shown to increase life expectancy by detecting breast cancer through a quick and easy x-ray. Magnetic resonance imaging, which is more sensitive to breast cancer is costlier and produces more false-positive results, therefore it is not used as often. When mammography is the only test being done, breast cancer is more likely to go undetected in patients with dense breasts and those with small lesions. In high-risk women, MRI has been shown to detect breast cancer in earlier stages than mammography. MRI screening is successfully reported between 77% and 91% (Jiao, 2014). Most detections from MRI are located within axillary lymph nodes during stage 1 breast cancer. A patient may simply refuse yearly mammograms, when she goes five years later breast cancer may be in the final stage whereas MRI could’ve detected it years earlier. Women are recalled more often for additional diagnostic testing when screened less frequently and recalled less often when screened more frequently (Orel, 2005). The American Cancer Society recommends MRI testing for women with the BCRA1 & BCRA 2 genes or a lifetime risk of 20% or greater for breast cancer (Saslow, 2007). Women who inherit the BRCA1 or BRCA2 gene have a 45% to 65% chance of developing breast cancer (Plevritis, 2006). BRCA 1 gene carriers are at a greater risk for developing breast cancer at an aggressive pace. Tumors in women screened with mammography alone are larger and more likely to have metastasized to axillary nodes (Taneja, 2009).

MRI is approximately
ten times more expensive than mammography making its cost effectiveness a
critical consideration (Jiao, 2014). Due to its lower specificity than
mammography increased costs are related to biopsies and additional exams. Estimated
lifetime costs for 10,000 women would be higher by $10.6 million with MRI in
combination with mammography than with mammography alone. In 2009, the costs
billed to Medicare for a bilateral mammography was $49.76 while a bilateral MRI
was $965.57 (Jiao, 2014). The price per quality adjusted life year would be
$310,616 when MRI was performed with mammography (Fieg, 2009). MRI screening is
most cost effective if the cost of MRI decreased or the cost of mammography
decreased, when the risk of breast cancer increases, when mammography performance
worsens, and if greater quality of life is accomplished (Orel, 2005). MRI
becomes cost effective when patients with high-risk profiles are treated. If
cancer was detected early enough, chemotherapy can be reduced. MRI is also
needed for surveillance when breast conserving therapy results in recurrences. MRI
would yield an additional 106 years of life per 10,000 women (Fieg, 2009). Women
with BRCA1 and BRCA2 start mammograms at the age of 25 which makes MRI more
cost effective and would decrease their radiation dose. Given the aggressive
nature of breast cancer, screening with MRI whether alone or with mammography
is cost effective and will prolong life expectancy (Berg, 2012). Contrast
enhanced MRI is proven to detect breast cancer in the earliest stages compared
to ultrasound and mammography.

Statement of the Problem and Professional Significance

Is MRI effective
as screening tool for breast cancer? Which modality is the most effective study
for diagnosing breast cancer? Are imaging modalities other than MRI a waste of
time and money for patients? Mammography is seen as the first step in
preventing breast cancer when a patient turns 40. For some patients, it might
already be too late. Mammography is quick and low cost but does not detect
breast cancer in patients with dense breasts or small lesions. MRI is
considered the gold standard in imaging but is used with fewer women. As the
population grows and rates of cancer increase, patients are demanding precise
diagnosis and early detection for cancer. What factors should stand out to
differentiate who receives MRI vs. mammography? By gathering medical history
and diagnosis from several women receiving breast MRI’s, data will be examined
to determine whether or not breast MRI’s were needed for proper diagnosis and
if testing detected further malignancies.

Research Hypothesis

1. It is hypothesized that MRI will be more
effective in detecting breast abnormalities than Ultrasound or Mammography.
This can be tested by comparing the results of their MRI with results of
previous tests.  

2. It is hypothesized that at least 50% of patients
will feel more confident regarding their diagnosis following a MRI scan. This
can be tested by having patients rank how they felt before and after having the
test and talking with a radiologist on staff (using a scale of 1-10).

3. It is hypothesized that patients will
not have had a mastectomy or received radiation until an MRI is performed. By
surveying patients to determine who was and wasn’t diagnosed prior to MRI and
what measures they took to prevent the malignancy from spreading I can
determine these results.  

4. It is hypothesized that patients
positive for breast cancer will have at least one lesion undetected on
mammography or ultrasound because of its small size or position in the axillary
region.  This can be tested by comparing
MRI test results with other imaging modalities.

5. It is hypothesized that 10% of
participants will have had inconclusive results. This can be determined by
whether the radiologist recommends a breast biopsy. MRI can produce
false-positives, which cause the radiologist to compare results with past
imaging.

6. It is hypothesized that at least 50% of
the participants were recommended to have an MRI after inconclusive testing in
other modalities. This information will be obtained through obtaining previous
medical history in the survey.

Definitions

Breast cancer – Uncontrolled growth of breast cells resulting in a malignant tumor (Medical Dictionary Online, 2018).

Malignant – Cancerous tumor that can spread to other parts of the body.

Benign – Tumor that is not dangerous to health.

Quality adjusted life year – Used to assess the value for money of medical intervention. One QALY = one year of perfect health (Science Direct Online, 2018).

Probabilistic sensitivity analysis – Technique used in economic modeling that allows the modellar to quantify the level of confidence in the output of the analysis (Science Direct Online, 2018).

National comprehensive cancer network – Not-for-profit alliance of leading cancer centers devoted to patient care, research, and education.

BRCA 1 – breast cancer type 1 susceptibility protein- Identified in 1990 and is on chromosome 17, increases likelihood of cervical, uterine, and colon cancer (National Cancer Institute, 2018).

BRCA 2 – breast cancer type 2 susceptibility protein- Identified in 1994 and is on chromosome 13-, increases likelihood of stomach cancer, gallbladder cancer, and melanoma (National Cancer Institute, 2018).

Ultrasound – Imaging test using high frequency sound waves.

MRI – Imaging test that used magnets to generate a detailed picture.

Mammography – Images produced from low dose radiation.

Gadolinium – Chemical element of atomic number 64, injected into patients as contrast during MRI.

Ductal carcinoma in situ (DCIS) – Presence of abnormal cells inside a milk duct in the breast (Medical Dictionary Online, 2018).

Mastectomy – Surgical operation to remove a breast.

Stereotactic biopsy – Procedure that uses mammography to precisely identify and sample an abnormality within the breast.

Limitations and Delimitations

This study will
survey twenty women (all ages) who are scheduled for breast MRI’s at Geisinger
Community Medical Center during September-November 2018. I will conduct surveys
with the patient prior to their MRI. Breast MRI’s will be conducted on a 1.5T,
Siemens machine. All patients will be scanned using the same protocol for
imaging regardless of medical history. External limitations are obtaining a
medical history, incompletion of the patient’s MRI, lack of intravenous access
for contrast, claustrophobia, and no show appointments. I will rely on patients
to give me a detailed, accurate medical history.

Assumptions

During a typical
work day in MRI at Geisinger Hospital a breast MRI is completed once. Within a
typical month at least 20 scans are completed. This should allow me to survey
enough patients over a six-week period. Permission for this study will come
from patients who allow me to ask questions regarding their medical history and
diagnosis. In accordance with HIPAA, I will keep all patient names and
identifying information anonymous.

Chapter 2

Introduction

The purpose of this research project is to determine if MRI is effective as an imaging tool for diagnosing breast cancer. By surveying women, who have been diagnosed or are currently being diagnosed, collecting medical history, and analyzing data, imaging modalities will be examined to determine the most reliable, accurate, and timely way to diagnose breast cancer. If MRI is more efficient than mammography and ultrasound, time and money spent on those modalities could be eliminated. Women can be treated faster, and cancer could be diagnosed earlier when proper testing is ordered. Breast cancer during stage one is treatable, thousands of lives could be changed when it is diagnosed in a timely manner.

Cancer is the
overall most common cause of death in America with breast cancer being the most
common type (Jiao, 2014). One in eight women will be diagnosed with breast
cancer during their lifetime making it a very costly disease. Standard protocols
for screening are determined by the American Cancer Society. Screening
mammography is recommended for women with a 25-30% lifetime risk of breast
cancer (National Cancer Institute, 2018). This includes women treated for
Hodgkin disease and those with a family history of breast or ovarian cancer.
Screening mammography typically starts at age 40 unless preexisting conditions
are present, screening begins at age 25. The Gail, Claus, and Tyrer-Cusick
models are used to estimate breast cancer based on family history. Breast
cancer genes 1 and 2 (BRCA) are found in 1/500-1/1,000 women. Women of Jewish
ethnicity have a 1/50 risk (National Cancer Institute, 2018). Those who test
positive have a 65% chance of breast cancer by 70 years old (Saslow, 2007).

What are American Cancer Society Guidelines?

Recommendations for women at average
risk of breast cancer are women between
40 and 44 have the option to start screening with a mammogram every
year. Women ages 45 to 54 should
get mammograms every year. Women 55 and
older can continue with mammograms every year or switch to having
mammograms every other year (American Cancer Society, 2018). Screening should
continue as long as a woman is in good health and is expected to live 10 more
years or longer. Not all types of breast cancer cause a lump in the breast.
Many breast cancers are found on screening mammograms which can detect cancers
at an earlier stage, before the mass can be felt, and before symptoms develop.
Women who are at high risk for breast cancer based on certain factors should
get and MRI and a mammogram every
year, starting at age 30 (American Cancer Society, 2018). This includes women
who have a lifetime risk of breast cancer of about 20% to 25% or greater, have
a known BRCA1 or BRCA2 gene mutation, have a first-degree relative (parent,
brother, sister, or child) with a BRCA1 or BRCA2 gene mutation, had
radiation therapy to the chest when they were between the ages of 10 and 30
years, or have Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba
syndrome, or have first-degree relatives with one of these syndromes. (American
Cancer Society, 2018). The American Cancer Society recommends against MRI
screening for women whose lifetime risk of breast cancer is less than 15%. MRI
in this case would be less cost-effective and timelier for patients to get
done.

How does MRI detect breast cancer?

There are three imaging modalities that can effectively detect breast cancer. MRI, mammography, and ultrasound are commonly used in different combinations. MRI uses magnetic fields to produce cross-sectional images of breast tissue. Hydrogen atoms in fat and water contribute to the signal that is produced (Pilewskie, 2014). Gadolinium, IV based contrast, is administered to detect lesions and cancer. Subtraction images are obtained to differentiate fat from enhancing lesions. MRI produces high quality imaging from signal to noise ratio and high spatial resolution (Pilewskie, 2014). MRI is safe for all women (unless contraindicated by pregnancy) and doesn’t use radiation. A drawback to MRI is false positives that are produced and additional testing that this creates. On the other hand, additional testing leads to a higher number of cancer detected. The more women who are being closely watched and recommended for further tests, the greater their likelihood of being diagnosed early. In a study in the UK involving high risk populations, 4% found MRI “extremely distressing” and 47% reported having disturbing thoughts about it six weeks after (Saslow, 2007). Due to the psychological distress of MRI, other testing needs to be considered.

Imaging Limitations

Unlike other
imaging tests, MRI candidates need to be screened for metal before considering
the test. Pacemakers, aneurysm clips, specific stents and filters, and
neuro-stimulators are not allowed in the machine. Body habitus and
claustrophobia are also factors to consider. A small, loud environment can
cause emotional distress and anxiety for a patient, some patients will refuse
MRI testing. Breast MRI testing should be completed with and without contrast.
Gadolinium, MRI contrast, can only be injected in patients with a glomerular
filtration rate of >60. Patients on dialysis, with impaired kidney function,
diabetes, high blood pressure, or certain allergies may not be able to receive
contrast, making the test inconclusive.

MRI results can
also be misleading. False-negatives and false-positives occur from technical
limitations, patient characteristics, quality assurance failures, human error,
and heightened medical concern. A false negative exam looks normal even though
the patient has breast cancer. They are more likely to occur in younger
patients with dense breasts. MRI is commonly used for dense tissue to
differentiate benign and malignant lumps. A false positive test looks abnormal
even though the patient doesn’t have cancer. False positives occur in half of
women getting mammograms over a ten-year period (Gillman, 2014). MRI’s and MRI
guided biopsies are usually recommended for more accurate diagnosis. A patient’s
need for definitive findings may increase testing ordered. According to the
American Medical Association, 7% of women are biopsied only because of MRI
findings. The call back and biopsy rates of MRI are higher than mammography in
high risk populations due to the increased sensitivity of MRI (Gillman, 2014).
MRI is also able to obtain images for women with breast implants. 3D and 2D
images are acquired in all planes, whereas mammography could miss an area of
interest and compromise the breast implant.  

Economic Impact

 Cancer treatment can be impacted by lack of insurance, proximity to health care facilities, and availability of services. According to Cancer Facts & Figures 2018, “Uninsured patients and those from many ethnic minority groups are substantially more likely to be diagnosed with cancer at a later stage, when treatment can be more extensive, costlier, and less successful.” (American Cancer Society 2018). Without routine mammograms, breast cancer can go undiagnosed and impose much higher costs when it’s found in a later stage. Early detection can potentially eliminate radiation, chemotherapy, mastectomy, and breast reconstruction.

In 2009, the average Medicare reimbursement for a bilateral mammogram was $49.76, a bilateral MRI $965.57, and mastectomy $13,590.03 (Moore, 2009). These procedures drastically differ in costs therefore insurance companies use cost effectiveness and quantity adjusted life years as means in determining which patient will benefit from costlier studies. MRI screening becomes more cost effective as the cost of MRI decreases or the cost of mammography increases. It is also more cost effective for patients with higher risk profiles such as BRCA1 & BRCA2 genes. MRI combined with mammography would produce 106 years of life per 10,000 women compared with mammography alone (Taneja, 2009). The drawback is that MRI in addition to mammography would increase lifetime health care costs for those 10,000 women by $10,600,000 (Taneja, 2009).

What does insurance cover?

Breast cancer is
the costliest cancer to treat. In 2010, it cost $16.5 billion in the United
States to treat breast cancer. A major concern when ordering breast MRI’s is
that insurance will deny it or charge a high co-pay. MRI’s cost more due to
radiologist, facility, contrast, and technology fees. According to a survey by
the American Cancer Society, many patients are cutting prescriptions, not going
to their doctor, and not getting preventive services due to the high costs.
Yearly mammograms are covered by insurance companies. The average cost of a breast MRI in the United States is
$1,325 with prices ranging from $375 to $2,850. Patients with health insurance are responsible for paying
their deductible, copay, and coinsurance amounts. The amount of each of these
costs depends on their health plan. Patients without health insurance are
responsible for 100% of mammogram and MRI costs.

Case Study

In a study published by the New England Journal of Medicine, titled MRI evaluation of the Contralateral Breast in Women with Recently Diagnosed Breast Cancer, 969 women with a diagnosis of unilateral breast cancer and no abnormalities on mammography went for a breast MRI. MRI detected clinically occult breast cancer in the contralateral breast tissue in 30 women (Lehman, 2007). Biopsies were performed on 121 of the 969 women whose MRI showed breast cancer (Lehman, 2007). Of those 121, 30 were tested positive. MRI was able to detect cancer that was missed by mammography and clinical exam. Within the 969 women, 33 tumors were diagnosed with 30 being from MRI. The three others were diagnosed from a mastectomy specimen before a biopsy could be performed. Those three samples contained ductal carcinomas in situ and measured 1, 3, and 4 mm in diameter. The most common types of invasive cancer found on MRI was ducal carcinoma (67%), invasive lobular carcinoma (22%), and tubular carcinoma (Lehman, 2007). 96.7% of cancer found was stage 0 or 1. The overall high accuracy of MRI is due to technology and interpretation of results. Contrast enhanced MRI aids in distinguishing benign from malignant patterns. This study also showed that screening MRI can improve on mammography by detecting cancer in women at high risk especially those with aggressive cancers.

When ordering MRI, cost effectiveness continues to be a major concern. In the article, American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography, benefits of MRI’s sensitivity in detecting lesions is noted but without data on the recurrence and survival rates, MRI is not recommended as a screening exam. The article compares study results from six published studies, sensitivity for MRI is consistently higher than mammogram and ultrasound while specificity was lower than mammogram and ultrasound. High sensitivity means MRI correctly identifies a patient with cancer. Low specificity means MRI is not able to correctly reject a patient without cancer as accurately as other modalities. MRI has higher error but in calling back more patients and performing more biopsies, it diagnoses cancer more accurately. With this being said, the article does not recommend MRI as a screening tool unless women are at an increased risk of breast cancer, have a family history, or carry the BRCA gene (Stephens, 2011).

Conclusion

Women who
present with signs and symptoms of breast cancer or have a family history
should be screened with MRI in addition to mammography. It is not acceptable to
deny patients imaging studies that can prolong their life. Breast cancer is
100% treatable when caught early. Due to advances in technology and a growing
healthcare system, facilities are more readily available to treat women.
Patients no longer need to wait months for tests or results. Steps should be
taken to reduce anxiety associated with MRI cancer screening and wait time.
Patients should be informed about the likelihood of false-negative and
false-positive findings. Whether or not patients need to go through additional
imaging, the chance of early detection outweighs the stress of additional testing.
MRI is a very useful imaging test that can save lives if performed. Patients
who want to be proactive in their treatment should be encouraged to get routine
imaging tests done and educate themselves on different stages of breast cancer,
so they understand the process they are going through. By creating high
resolution imaging, MRI proves to be the most effective study for diagnosing
breast cancer. MRI is able to detect smaller masses and abnormalities than
other imaging tests miss. Utilization of MRI is crucial for early detection,
with its results breast cancer can be highly treatable and late stages along
with metastases can be stopped. MRI used in screening for women with high risk
factors proves more cost effective than mammography and ultrasound because it
detects cancer in earlier stages which reduces the need for more invasive, long
term care. MRI is also able to cover a larger area including axillary lymph
nodes where cancer is commonly missed on mammograms.

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