Mammography has been the study of choice for breast cancer screening since the 1950's. Although it is universally accepted that it has saved lives, its low sensitivity and specificity also puts women at increased risk. Balancing the need for screening and the risk of current screening methods, different organizations have differing opinions on what the best course of action is. Recent studies in magnetic resonance imaging and ultrasound provide hope for better screening methods in the future.
BREAST CANCER SCREENING
Breast cancer is the most common form of cancer in women second leading cause of cancer deaths according to the latest data (Bandi, Brinton, Buchet, Cokkinides, & Cowens-Alavardo, 2009). As a result, significant effort has been made to research the disease and find ways to prevent its occurrence, detect its presence early on in the disease process and cure it when malignancies are found. Government, professional, and many non-profit organizations champion this terrible disease and make it a priority to inform the public of its risks, prevalence, prevention and treatment options available.
In 2002 as part of the Putting Prevention into Practice movement, the United States Preventive Services Task Force (USPSTF) published its recommendations on the screening of breast cancer (Humphrey, Helfand, Chan, & Woolf, 2002). These recommendations were widely adopted by the medical community and the public over the last several years. On November 17, 2009, the USPSTF published an updated recommendation statement in Annals of Internal Medicine dramatically altering some of its recommendations. In the past year since this publication, medical professional organizations have either agreed or disagreed with these recommendations leaving the public to wonder what is in their best interest for screening and what it is they need to do in order to lengthen and improve their quality of life. The recommendation most in debate is that women not start mammography screening until the age of 50 (Calonge, et al., 2009); a change from its prior recommendation which was at 40 years old (Berg, Allan, Frame, Homer, & Johnson, 2002).
Although X-ray mammography has been around for years as well as being the imaging study of choice, advances in magnetic resonance imaging and ultrasound have made significant headway in screening of breast tumors and their results indicate a potential to ultimately replace mammography as the study of choice and therefore eliminating this controversy. Although breast exams and mammography have been the imaging studies of choice over the past fifty years, recent research demonstrates its significant limitations making magnetic resonance imaging and ultrasound the future of breast cancer screening.
The prevalence of breast cancer sheds light on the seriousness of this disease. Statistical information demonstrates the significance of this disease in American society. The National Cancer Institute's 2010 estimate for invasive breast cancer is 207,090 diagnoses adding to the already 2,591,855 (based on 2007 data) women already have a history of malignant breast tumors. In addition, the National Cancer Institute estimates 29,840 will die of breast cancer this year (Alekruse, et al., 2010). Of the new cases of breast cancer diagnosed between 2002 and 2006, 95% were over the age of 40 with the median age of diagnosis of 61 years old (Alekruse, et al., 2010; Bandi, et al., 2009). Incidence rates in 2007 show that the highest age group is those women aged 65 to 74 years old at 413.5 per 100,000 (CI 95%) and the lowest in women aged 20 to 49 at 70.4 per 100,000 (CI 95%)(Alekruse, et al., 2010). Based on these numbers about twelve out of every thousand women currently have invasive breast malignancies making its prevalence deserving of the level of screening it receives.
Based on the above figures, it is understandable why so many people are concerned about this disease and organizations like the American Cancer Society inform the public of the dangers and need for aggressive screening. It is also reasonable to understand organizations such as the USPSTS and the American Cancer Society publish recommendations they deem necessary to find these cancers early and treat them, but also not put unwarranted anxiety on women who are at low risk of developing breast malignancies.
The goal of screening is to find cancer as early as possible in order to remove it and prolong life. A stressful and sometimes painful part in that process is performing a biopsy if a suspicious lesion is found. This inherently causes the patient a great deal of distress due to the discomfort of the procedure as well as the anxiety waiting for the results. This procedure does not come inexpensively either ranging from 1,000 to $5,000 a procedure (Imaginis, 2010). In addition, this puts the patient at risk for infection. Reducing this procedure has to be a goal. In order to do this, better screening tools must be developed that will make it easier to rule out the likelihood of cancer in the least invasive, and cost effective way. Currently, the main tools used to screen are self and clinical breast exams, mammography (film and digital), magnetic resonance imaging (MRI) and ultrasound (Calonge, et al., 2009). Each has its own benefits and disadvantages associated with them. These recommendations form the basis of breast cancer screening and the means to which biopsies are either indicated or not.
The simplest, most widely available and least expensive of these methods is the breast exam. Performed either by the individual patient or the physician, it serves as the foundation of all screening of breast cancer despite its low sensitivities and specificities (Calonge, et al., 2009). Women who wish to perform self breast exams are encouraged to seek the guidance of her health care provider before beginning the procedure in order to give her a better idea on how to perform the exam. This will also educate her on how different masses feel like and their significance. In the procedure, the breasts and axilla are visually inspected making note of symmetry, texture, contour and discoloration. Dimpling, redness, abnormal growths and a skin condition known as peau d'Orange are all signs of possible tumors. Following the visual inspection, the breasts are palpated using the tips of the fingers on the naked breast. The breast is gently palpated looking for lumps or other abnormalities over the entire breast tissue as well as the axillary lymph nodes (Bandi, et al., 2009). This simple, inexpensive procedure is easily taught and with training, can be easily replicated.
The efficacy of these exams is often put into question and recent data has caused certain groups to soften their stances on the procedure (Bandi, et al., 2009; Calonge, et al., 2009). This is most true with the breast self exam. Based on a randomised trial studies done in China and Russia, breast self exams (BSE) showed no additional benefit in survivability in women who did monthly breast exams compared to those who did not (Semiglazov, Manikaha, Moiseenko, Protsenko, Kharikova, & Seleznev, 2003; Thomas, et al., 2002). The results of this study changed both the ACS and USPSTF recommendations for SBEs and no longer promote regular breast self exams. However, the ACS still has the opinion that physicians need to inform women on the advantages and disadvantages of doing routine breast self exams (Bandi, et al., 2009; Calonge, et al., 2009).
Clinical breast exams (CBE) have a more favorable interpretation from both the ACS and USPSTF despite not providing any convincing data to support their recommendations. This is due to little data on the potential harms of CBEs being available for interpretation (Calonge, et al., 2009). Based on this, the USPSTF makes no recommendation for or against CBEs while the ACS continues to recommend CBEs in all women over the age of 20 (Calonge, et al., 2009). The ACS bases this recommendation primarily on anecdotal information and the idea that a clinician will have a better skill at the exam and a better understanding of what masses are concerning (Bandi, et al., 2009).
X-ray mammography (originally called Roentgenography) has been used since the 1950's and continues to be the standard imaging study to screen breast cancer in women (Bandi, et al., 2009; Calonge, et al., 2009; Sklaroff, Berger, & Moore, 1959). The procedure utilizes a specialized X-ray machine to take radiographs of each breast by compressing each breast in the machine. A radiologist is then able to read the resulting films and determine if there is no evidence of masses or if the findings support additional tests, most often a biopsy. This tool serves both as a diagnostic tool and as a screening tool. In both instances, a clinical breast exam is performed prior to mammography and the results from this test determines the type of mammography performed. Either way, the process of imaging the breast is the same.
Over the last fifty years, hundreds of thousands of women have been tracked in several randomized trials have been performed in order to validate this screening tool. With so much time and effort to study this, it is quite interesting that there is still as much controversy in the medical community and society as a whole as to its effectiveness. The reason can be summed up in the fact that data, especially data from recent studies show that this test, although better than nothing, is not all that good (Welch, 2010). Furthermore, in some instances, the benefits of screening mammography may not outweigh its risks (Calonge, et al., 2009). Looking at some of these recent studies and the risks they identify will demonstrate this.
The first risk is the amount of false negative screens done by mammography. Screening tests that have high sensitivities reduce the amount of false negative tests result by as many of the true positive findings. Therefore it is best to have a screening test that is very sensitive to what one is looking for. Recent studies show mammography sensitivity to be between 81.2% and 82.3% with no significant variations among different social groups (Goldman, Walker, Miglioretti, Smith-Bindman, & Kerlilowske, 2010; Taplin, et al., 2010). Since the purpose of screening is to have as few false negative screens as possible, this shows how ineffective mammography is at identifying cancers in women. As a result of this, many women who have breast cancer will go undiagnosed even with mammography.
Another way mammography puts women at risk is its high number of false positives they produce. These findings result in expensive biopsies. The specificity of a test tries to reduce the amount of these false positive test results. Although various studies put the specificity of mammography is ranges from 91.9% to 96.8%, the lack of sensitivity puts many healthy women through painful and expensive procedures and puts them in unnecessary worry (Goldman, et al., 2010; Kuhl, et al., 2005; Taplin, et al., 2010). An additional study confirms these findings citing the over-diagnosis of breast cancer was 10% between the ages of 55-69 years after 15 years of follow-up (Zackrisson, Andersson, Janzon, Manjer, & Garne, 2006). In another study the rate of over diagnoses was one in three (Jørgensen & Gøtzsche, 2009). Although this result seems as a bit of an outlier as compared with the previous mentioned studies, it is hard to argue that the specificity of mammography is questionable.
Of even more significance is that mammography becomes less sensitive and specific when a woman has a previous benign biopsy result. This puts these women at even greater risk of having an undiagnosed cancer. A prospective study demonstrates this by showing a 2.70 difference in sensitivity and a 2.30 difference in specificity compared to women who have not had a previous breast biopsy. (Taplin, et al., 2010). Putting women at risk who already had to go through a stressful biopsy was surely not the intended purpose of mammograhy.
Age also plays a role in the sensitivity of screening mammography. Women who are younger have denser breast parenchyma resulting in more difficult to read mammograms (Pediconi, et al., 2009). This denser tissue accounted for 79% of the lowered tumor detection by mammography in women aged 40-49 years making x-ray mammography significantly less sensitive in this age group compared to women aged 50-69 years. (Bailey, Sigal, & Plevritis, 2010). This confirms previous study data putting mammography's senstivity and specificity of identifying malignant masses in dense tissue at 72.7% and 45.2% respectfully (Pediconi, et al., 2009). Studies such as these prompted the USPSTF to update its recommendations in 2009 and bring its stance on mammography screening in line with other countries (Calonge, et al., 2009).
The type of health care system also has influence on how well any screening method works to include mammography. A recent published study compared the 2002 USPSTF screening recommendations to that of Norway to see if there was any significance. The relevence to this is that Norway's screening criteria is very similar to the 2009 USPSTF recommendations (Calonge, et al., 2009; Hofvind, Vacek, Skelly, Weaver, & Geller, 2008). The results showed that screening at age 50 bianually had no significant impact on the rate nor stage of cancer as compared to the 2002 USPSTF screening criteria. Additionally, the subjects in Norway needed fewer adjunctive studies such as MRI and ultrasound as compared to the U.S. group. (Hofvind, et al., 2008). This gives credence to the USPSTF's 2009 change to its mammograhy screening recommendations.
Despite its flaws, mammograhy has saved countless lives in its fifty year history. The question remains though how significant of an impact did it make. Anctedoteically one can argue that it has made a large impact. In just awareness alone, the advent of screening mammography has made an enoumous impcact. Organizations such as the Susan G. Komen Foundation and even the National Football League have made breast cancer awareness one of, if not the most talked about cancers in U.S. society. All these organizations use their influence to advocate for regular screening of breast cancer to include mammography. At the very least, the amount of awarness brought about from mammography has had impact on breast cancer survival.
Awareness alone does nothing to save lives. Mammograhy must provide substantial improvement in the mortality and morbidity that inherently comes with a disease as prevalent and as deadly as breast cancer. A recent study out of Norway puts questions the overall benefit mammography has on women's quality and longevity of life. This study looked at two population groups over a nine year span. One group received regular mammography screenings and the other did not. These two groups were then compared to historical data. The data reported showed a relative reduction in the mortality due to breast cancer of 10% which is less than the 25% reported by the World Health Organization in 2002. (Kalager, Zelen, Frøydis, & Adami, 2010).
This recent study out of Norway brings into question the need of screening mammography at all. Making the assumption that the ten percent reduction in death is due to mammography alone, the current rate of 4 deaths per 1000 women would rise to 4.4 deaths per 1000 (Alekruse, et al., 2010). In other words 2500 women would need to have screening mammograms over the next ten years in order to save a single life. In addition, nearly 1000 of these women would require at least one needless biopsy due to a false positive mammogram thus putting the patient through potential anxiety and fear (Welch, 2010). The potential of benefit for one does not seem to outweigh the potential harms to many others with the use of screening mammography.
Despite these recent findings, it is unquestioned the use of screening mammography has been extremely valuable in preventing needless deaths from breast cancer (Bandi, et al., 2009). And despite its flaws, mammography is poised to continue to be the imaging of choice for the screening of breast cancer. However, as technology evolves, exploration has begun to expand the playing field and new players have emerged as potential rivals to x-ray mammography. Of note is MRI and ultrasound. Both come with the inherit advantage of not exposing women to potentially cancer causing radiation, but neither have yet developed in such a way as to gain wide-spread support (Bandi, et al., 2009; Calonge, et al., 2009). Arguments such as cost, availability, and reproducibility have overshadowed the studies that show potentially higher sensitivity and specificity over mammography. These potential replacement modalities will now be discussed.
Magnetic Resonance Imaging currently is used as a screening tool for women at high risk for breast cancer and it also has potential for more wide-spread use (Calonge, et al., 2009; Kuhl, et al., 2005; Pediconi, et al., 2009). This is primarily due to its superior sensitivity, especially in regards to positively identifying masses in dense breast tissue. MRI as the sole imaging modality allows physicians to diagnose malignant tumors in women who hold the breast cancer susceptability gene (BRCA) far better than with x-ray mammography (Kuhl, et al., 2005). The study by Pediconi, et al. confirms this notion by reporting a sensitivity of 98.2% and a specificity of 95.2% vastly outperforming mammography in the same study (2009). Clearly, MRI holds merit in breast cancer screening.
As good as MRI is at identifying masses, it is also far more expensive than traditional x-ray mammography making it impracticle for wide-spread screening of women at low risk. Comparing the cost in the ten most populous cities in the U.S. MRI averaged $2,855 where mammography was more than one tenth the cost at $268 (New Choice Health, 2010). With incidence rates in the U.S. at 122.9 per 100,000 the cost of MRI far exceeds its benefits except in cases where women are at high risk (Alekruse, et al., 2010).
Ultrasound has also been studied as a method to screen breast tissue for tumors. This nonevasive, painless and simple proceedure uses sound waves that penetrate tissue and reflect back to a transducer. This information is then projected onto a display that a provider can view in real-time NEED CITATION. As a matter of cost, it is comprable with mammography at an average of $359 in the top ten metropolitan areas in the country (New Choice Health, 2010).
Despite these advantages, significant issues in sensitivity and specificity in regards to cancer identification exist as shown in a study sponsored by the German Cancer Aid (Deutsche Krebshilfe). The study's authors reported the sensitivity at 39.5%. This is only slightly better than the 32.6% for mammography reported by the same study. Ultrasound's ultimate shortcomings are in specificity and positive predictive value; both are lower than mammography and far lower than MRI (Kuhl, et al., 2005).
Although ultrasound has its drawbacks in identifying malignant masses in breasts, recent new methods may change that and potentially eliminate the need for other screening methods all together. The new ultrasound technique is called the elastrographic technique (EI). Initially developed in 1991, this technique uses ultrasound to measure the elasticity of tissue (Ophir, Cespedes, & Ponnekanti, 1991).
A recent study published by Richard G. Barr, MD, PhD used this technique and applied it to the screening of breast tissue to determine if it was capable of detecting breast masses and if it could differentiate between benign and malignant masses. This revolutionary imaging modality utilizes new software that simultaneously projects B-mode with elasticity images (2010). Based on Dr. Barr's observations, malignant tumors have a larger image on the elasticity view than on the B-mode. Using the measurements from the largest diameter of the two views, a simple ratio is created (EI/B-mode) and this ratio determines the character of the tumor. An EI/B-mode ratio greater than one indicates a malignant tumor whereas a ration less than one identifies the mass as benign (Barr, 2010).
This initial study gives strong indication for real-time ultrasound elasticity imaging's future inclusion in identification of not only breast tumors, but other soft tissue masses. Out of the 251 lesions biopsied, they correctly identified all fifty-four cancers giving it 100% sensitivity. Of the 197 benign masses, this imaging modality identified 184 with an EI/B-mode ration less than 1 giving it 95% specificity. This correlates to positive and negative predictive values of 84% and 100% respectfully (Barr, 2010).
This study shows great promise for the future, but this was an initial report and therefore more work is needed in order to be of clinical benefit. In order for it to be used for screening and/or diagnostic imaging, at least two major issues must first be addressed. Most critical is the elasticity view bases its results on the relative stiffness of the tissues in the view field which may distort or mask masses. Additionally, if a lesion is identified on the elasticity view and not on the B-mode view, there is no way to determine if the mass is malignant or not. Dr. Barr proposes that instead of using the relative stiffness of a tissue to use a standard, such as fat, that can be used to compare any mass to. If this modification is possible, Dr. Barr indicates that this may be a powerful tool to reduce the number of benign mass biopsies and perhaps a future screening tool (Barr, 2010).
Despite mammography's 50 plus history as the imaging study of choice for screening breast cancer, its limitations and the strides of MRI and ultrasound are rendering it obsolete. Studies have shown that the low sensitivity and specificity of mammography results in a significant false positive rate. The consequence of this is an increase of unnecessary biopsies. The benign biopsy further increases a woman's chance of getting cancer in the future. Although MRI has better sensitivity and specificity in breast cancer screening, its expense precludes it from being the study of choice. MRI, however, has a very necessary niche in screening women who are at much higher risk of getting breast cancer as in those who have the BRCA gene. Ultrasound is an inexpensive alternative, but plain ultrasound lacks the sensitivity and specificity needed to replace mammography. New advances in ultrasound techniques, such as elasticity imaging, provide hope that future screening tests will be inexpensive enough and sensitive enough to replace mammography. Further study is needed in order for real-time elasticity ultrasound to take fruition. Until this happens, controversy will continue on when it is best to start mammography screening. Ultimately, this decision rests in the individual woman. It is therefore, paramount that the scientific community, healthcare professionals, and advocate groups continue to provide patients the risks and benefits of these different imaging modalities so the patients are better equipped to make a choice that serves their best interests.
