- TABLE OF CONTENTS
- Etiology and Risk Factors
- Genetic Cancer Risk Assessment
- Signs and Symptoms
- Screening and Diagnosis
- Evaluation of a Cystic Mass
- Evaluation of a Solid Mass
- Evaluation of Nonpalpable Mammographic Abnormalities
- Staging and Prognosis
- Suggested Reading
Signs and Symptoms
Increasing numbers of breast malignancies are being discovered in asymptomatic patients through the use of screening mammography. Mammographic features suggestive of malignancy include asymmetry, microcalcifications, a mass, or an architectural distortion.
When these features are identified on a screening mammogram (see Figures 1-5), they should, in most cases, be further evaluated with a diagnostic mammogram (and, in some cases, with a breast ultrasonographic image or, in highly selected cases, with MRI [Figure 6]) prior to determining the need for a tissue diagnosis. Often, pseudolesions, such as those caused by a summation artifact, dust on the mammographic cassettes, and dermal calcifications, are correctly identified in this manner. All mammographic lesions (and the examinations themselves) must be unambiguously categorized according to one of the six Breast Imaging Reporting Data System (BI-RAD) classifications developed by the American College of Radiology (ACR) (Table 4).
When signs or symptoms are present, the most common presenting complaint is a lump within the breast. The incidence of this complaint can range from 65% to 76%, depending on the study.
Inflammatory Breast Cancer
Inflammatory breast cancer is particularly aggressive, although relatively uncommon, accounting for about 5% of all breast cancers. On breast palpation, there often is no definite mass, but the breast appears to be enlarged, with erythema, skin edema (peau d'orange), and skin ridging. A short trial of antibiotics or, on rare occasions, ultrasonography, may be helpful in differentiating mastitis from inflammatory breast cancer. If the problem does not resolve with the antibiotic treatment, a workup and biopsy are necessary.
This condition has been associated with intraductal carcinoma involving the terminal ducts of the breasts and may have an associated invasive component. It presents as an eczematoid change in the nipple, a breast mass, or bloody nipple discharge. Cytology may be helpful in establishing the diagnosis; however, negative cytologic results should not preclude a biopsy.
Other Local Symptoms
Breast pain is the presenting symptom in about 5% of patients; breast enlargement, in 1%; skin or nipple retraction, in about 5%; nipple discharge, in about 2%; and nipple crusting or erosion, in 1%.
The role of breast self-examination is controversial. The American Cancer Society (ACS) no longer recommends monthly self-breast examinations. However, all women should learn about the potential benefits, limitations, and harms (false-positive results) of breast self-examinations. Women should receive instructions regarding proper technique for breast self-exams and then individually may choose to perform them monthly, occasionally, or never. Other groups have suggested that routine breast self-examination may lead to more false-positive results and therefore more benign biopsies. One meta-analysis of 12 studies involving a total of 8,118 patients with breast cancer correlated the performance of breast self-examination with tumor size and regional lymph node status. Women who performed breast self-examination were more likely to have smaller tumors and less likely to have axillary node metastases than those who did not. A multicenter study from Memorial Sloan-Kettering Cancer Center and the University of Virginia attempted to measure the benefits and costs of adding clinical breast exams to yearly screening mammography. These exams detected an additional 14 breast cancers, or 0.02% of the 60,027 exams performed, and the cost for each additional cancer detected was $122,598. Based on this report, the benefit of clinical breast exams appear to be marginal.
A major problem with breast self-examination as a screening technique is that it is rarely performed well. Only 2% to 3% of women do an ideal examination a year after instruction has been provided.
Clinical breast examination
Beginning at age 40, the clinical breast examination should be timed to occur near or prior to screening mammography. If the clinician detects an abnormality, the patient should then undergo diagnostic imaging rather than screening. Clinical breast examination should be performed and a complete breast history obtained when a woman presents for routine health care. The clinical examination should include inspection and palpation of the breast and regional lymph nodes. Between 14% and 21% of breast cancers are detected by clinical breast examination.
Despite conflicting coverage in the lay press, the benefits of screening mammography have been well established by the findings of 11 large-scale evidence-based clinical trials. The ACS, the ACR, and the American Medical Association have updated their guidelines since 1997 and recommend annual mammography beginning at age 40. The National Cancer Institute (NCI) also updated its guidelines in 1997, recommending that women undergo screening mammography every 1 to 2 years beginning in their 40s. In November 2009, the US Preventive Services Task Force (USPSTF) released a comprehensive review of multiple aspects of breast cancer screening. The Task Force issued five controversial recommendations, which would have revolutionized current practices, including recommendations against yearly mammography (at any age), clinical breast exams, and teaching breast self-examinations, as well as mammography starting at age 50 and a mammogram every other year. There is little, if any, support for implementing these wide-ranging recommendations from the medical specialists involved, including strong pushback from the breast imaging community. However, there is evidence that participation in mammographic screening programs dropped nationwide after the release of the Task Force review, perhaps because its credibility was higher among primary care physicians, compared with their breast cancer consultants. The USPSTF has updated its guidelines and now recommends mammography every 2 years, alone or with clinical breast examination, for women aged 50 and older who are at average risk for breast cancer.
Screening mammography is performed in the asymptomatic patient to detect an occult breast cancer. This contrasts with diagnostic mammography, which is performed in a patient with a breast abnormality (palpable mass, bloody nipple discharge, or some other clinical finding) to further identify the etiology of the problem.
Physical examination and mammography are complementary. Mammography has a sensitivity of 85% to 90% and, thus, would miss 10% to 15% of clinically evident tumors while detecting the majority of cases an average of 2 years prior to any perceptible clinical signs or symptoms.
Screening recommendations for average-risk patients. No upper age limit has been suggested, and screening should continue in women who are in good health and would be candidates for breast cancer treatment. The previous recommendation for a "baseline" mammogram between the ages of 35 and 40 has been withdrawn. Thus, both the ACS and the NCCN recommend annual mammography starting at age 40 for women at average risk of breast cancer. The USPSTF currently recommends yearly screening mammograms starting at age 50.
Screening recommendations for high-risk patients. Based on epidemiologic evidence that premenopausal familial breast cancer often presents at similar ages among affected family members, many breast imaging centers recommend that yearly screening for such high-risk individuals begin approximately 10 years prior to the youngest age at which a first-degree relative was diagnosed with breast cancer. For example, according to this algorithm, a woman whose mother developed breast cancer at age 45 could begin yearly screening at age 35, in addition to biannual clinical breast examinations. These commonly used screening algorithms are not based on formal studies but have arisen based on the natural history of the disease. They are, however, in keeping with the recommendations of the NCCN guidelines. Screening for women at genetic risk may begin at age 25. There are numerous studies supporting the use of breast MRI in women at genetic risk, all of which indicated that sensitivity is > 80%.
Digital mammography was approved by the FDA in 2000 and is rapidly being adopted by leading breast cancer centers worldwide. Initial trials indicate a comparable sensitivity to film-based mammography, with the benefit of a reduced risk of women called back from screening for additional workup. The FDA also approved computer-aided detection (CAD)systems for mammography beginning in 2001. Mammograms are scanned by a computer, and possible lesions are marked for further review by a radiologist. A number of studies have shown a reduced risk of "missed cancers" when computer-aided diagnosis is thus employed. Although some physicians are skeptical about the benefits of such CAD systems for mammography, many investigators in the field continue to support its use. For example, Lindfors et al published data showing that these systems increased the effectiveness of mammographic screening by 29%, with a comparable increase in screening cost.
Sensitivity of mammography is diminished when the breast tissue is dense. There have been recent reports in the literature concerning the role of screening breast ultrasonography in women with dense breasts on mammography and normal mammography and clinical breast examination. The results from a multicenter trial of leading breast imagers, ACR Imaging Network (ACRIN) 6666, showed that the addition of ultrasound to mammography increased detection of breast cancer, when compared with mammography alone among women at increased risk of breast cancer who also had dense breast tissue. However, there was also a large increase in the number of benign biopsies.
Pending further investigation, screening ultrasonography of the breast is not sanctioned or approved, and, unlike high-risk MRI screening, it does not constitute the standard of care. However, screening breast ultrasound may have some value in high-risk women with dense breast tissue on mammography, it is currently available at a few institutions and may be offered to selected women who meet the aforementioned criteria. Many leading breast centers do not perform screening ultrasonography, based on the lack of any randomized trials demonstrating population-based benefit and risk.
In August 2012, New York became the fourth state to enact legislation mandating that all breast imagers notify their patients with dense breast parenchyma in writing. There is similar pending legislation in 13 other states, and Representative Rosa DeLauro (D-Connecticut) has introduced HR 3012 in this 112th Congress to extend the mandate nationally. Highly dense breast tissue reduces the sensitivity of routine mammographic screening, and is, in itself, a significant risk factor for breast cancer. The density notification is intended to promote the utilization of "supplemental screening tests" in women with dense breast tissue, which in most cases would be nontargeted ultrasound breast screening. However, there is significant resistance by many in the breast imaging community to using widespread ultrasound screening for the many millions of American women who would become eligible based on this legislation. Ultrasound breast cancer screening has not undergone a single randomized trial of efficacy which uses the gold standard of disease-specific-mortality reduction, and in small-scale trials like ACRIN 6666 (with the participation of the leading experts in breast ultrasound) led to additional cancer detection with a very low positive predictive value (with less than half the specificity of mammography, and thus involving many additional "unnecessary" breast biopsies). This is in contrast to screening mammography, which had demonstrated statistically significant disease-specific mortality reduction in six out of seven randomized large-scale population trials, involving millions of women studied over several decades.
Magnetic resonance imaging
This is a sensitive diagnostic tool for detecting occult breast cancer foci. Owing to its limited specificity and high cost, MRI is not likely to become a screening tool for women at average risk. However, the role of breast MRI screening for detecting breast cancer in very-high-risk women, such as carriers of a BRCA gene mutation, has now been well established. More controversial are guidelines from the ACS, which recommend that a screening breast MRI be performed in women having at least a 20% lifetime risk for breast cancer, including women having a history of radiotherapy when they were 10 to 30 years of age; or harboring a mutation of BRCA1, BRCA2, TP53, or PTEN; or having a first-degree relative who harbors one of these mutations.
Several major studies have demonstrated the increased sensitivity of MRI for detecting cancers in women with inherited susceptibility to breast cancer compared with clinical breast examination, mammography, or ultrasonography. The sensitivity of breast MRI is > 75%; in contrast, the sensitivities of mammography and ultrasonography both are < 40%. The combined sensitivity of MRI plus mammography is about 95%, suggesting that it may be a viable strategy for screening young women at high risk for breast cancer. A recent prospective study documented that the performance of regular breast MRI was associated with earlier stage at breast cancer diagnosis among BRCA carriers.
Digital breast tomosynthesis is a relatively new three-dimensional imaging technology which creates cross-sectional images of the breast. Conventional digital mammography can have low sensitivity rates, particularly for women with dense breast tissue. In addition, the recall rates for screening mammography can be greater than 10%. Overlapping breast tissue is a common reason for recalls with screening mammography and may obscure an underlying breast cancer. Clinical trials are necessary to determine whether this new technology will be helpful in increasing the identification of breast cancer in the screening population and reducing the number of patients who are recalled for additional imaging.
In February 2011, the FDA approved for clinical use the Hologic Selenia Breast Tomosynthesis Mammography system. This new breast imaging modality creates cross-sectional images of the breast, similar to CT slices, from a modified digital mammography unit, utilizing approximately the same x-ray dose as conventional two-dimensional mammography. While there is very limited published clinical experience to date, the early literature reports a significant improvement in the specificity of breast cancer screening with the addition of tomosynthesis to routine screening mammography, reducing the need to recall patients for additional breast imaging following initial screening. There is also growing anecdotal evidence that it may improve the sensitivity of breast cancer detection as well, while adding unknown costs to screening such as reduced patient throughput, additional radiation exposure, and equipment capital expenses. A number of other manufacturers have submitted paperwork on their breast tomosynthesis units for FDA approval. Currently, tomosynthesis is approved for clinical use only as an adjunct to conventional mammography, and thus screening patients must undergo conventional and tomosynthetic imaging concurrently.
When a dominant breast mass is present and the history and physical examination suggest that it is a cyst, the mass can simply be aspirated with a fine needle. Aspiration of a simple benign breast cyst should yield nonbloody fluid and result in complete resolution of the lesion.
Ultrasound examination can also be used to determine whether a mass is solid or cystic and whether a cyst is simple, complicated, or complex. Simple cysts are anechoic and oval, with thin walls; if asymptomatic, a simple cyst may be treated as an incidental finding. Complicated cysts are similar, except that low-level echoes are present in the cyst lumen. In many instances, complicated cysts may be managed conservatively, unless a worrisome feature or history prompts aspiration. To evaluate complex masses (previously termed complex cysts) that demonstrate a mixed cystic and solid lesion and that occasionally have thickened walls or septa, a biopsy (positive predictive value, 25%) is typically necessary.
A biopsy should be considered in the setting of an aspiration that is bloody or for a persistent solid component. Cytologic examination of the fluid is not routinely indicated, as the yield for positive cytology is low. Cystic carcinoma accounts for < 1% of all breast cancers. However, an intraluminal solid mass is a worrisome sign suggesting (intra) cystic carcinoma, and it should be biopsied.
A solid, palpable mass can be evaluated in a variety of ways. The decision to observe a patient with a solid breast mass that appears to be benign should be made only after careful clinical and radiologic examinations. Either FNA for cytology or percutaneous core biopsy should also be performed.
A mammogram is used to assess the radiologic characteristics of the mass and is important for the evaluation of the remainder of the ipsilateral breast as well as the contralateral breast.
This technique is a simple, easy-to-perform method for obtaining material for cytologic examination. The overall incidence of false-positive results ranges from 0% to 2.5% (0.7% when performed by experienced technicians), and the incidence of false-negative results varies from 3% to 27% (ranging from 3% to 9% in experienced hands). Reasons for false-negative readings include less-than-optimal technique in preparing the cytologic material, a missed lesion on aspiration, tumor necrosis, and incorrect cytologic interpretation. FNA is limited in its ability to distinguish invasive from noninvasive cancers. For these reasons, the trend at leading breast centers has been to replace FNA with core biopsy.
In the past, an excisional biopsy of a small breast mass or an incisional biopsy of a larger breast mass was performed to establish a histologic diagnosis of breast cancer. Recently, excisional biopsies for diagnosis have been largely replaced by percutaneous procedures. For a suspected malignancy, core biopsy has become the preferred diagnostic tool. With a core biopsy, the surgeon can plan for the cancer surgery, allowing for definitive surgical management in a single procedure. Core biopsy is also more advantageous than an FNA because it allows evaluation of architectural and cellular characteristics.
Image-guided core biopsy
Ultrasound-guided core biopsies have been shown to offer increased targeting accuracy when compared with freehand core biopsy sampling. In certain limited clinical scenarios, use of vacuum-assisted, large-core needles may help reduce sampling error.
Prior to 1991, almost all nonpalpable mammographic lesions were excised using surgical excision. This technique has become less prevalent with the availability of image-guided percutaneous biopsy techniques.
Stereotactic and ultrasonography-guided core biopsies
These methods have revolutionized the management of nonpalpable breast lesions, and, currently, the majority of biopsies can be performed percutaneously, which is quicker, less invasive, and less expensive than is excisional biopsy. Tissue acquisition is performed with automated core needles or directional vacuum-assisted biopsy probes. Guidance for percutaneous biopsy is usually provided by stereotaxis, ultrasonography, and, more recently, MRI.
Numerous studies comparing the sensitivity and specificity of stereotactic biopsy versus surgical biopsy have consistently found the two procedures to be statistically equivalent. The long-term false-negative rate for stereotactic biopsy is 1.4%, which equals best published results with surgical biopsy.
Up to 80% of patients with nonpalpable mammographic lesions are candidates for stereotactic core biopsy. Lesions near the chest wall or immediately behind the nipple often cannot be reached on the stereotactic table. Diffuse lesions, such as scattered calcifications or a large asymmetric density, are subject to undersampling with the percutaneous approaches. Some patients are unable to lie prone on the stereotactic table for the duration of the examination. Finally, stereotactic units and trained personnel are not universally available.
Ultrasonography-guided core biopsy is another accurate percutaneous technique, useful for lesions best imaged by ultrasonography. Since the biopsy gun is handheld and guided in real time by the ultrasound imager, its use is related to more variability in performance, depending on the experience and skill of the practitioner. The overall reported accuracy rate of ultrasonography-guided biopsy is comparable with rates achieved with stereotactic and surgical biopsies.
Ultrasonography-guided or stereotactic FNA
This biopsy option is somewhat less invasive than core biopsy, but FNA provides only cytologic (not histologic) pathology results. This technique can result in both false-positive and false-negative results, whereas a false-positive result has not been reported to date for core breast biopsies. FNA is most successful in centers that have an experienced cytopathologist, who, ideally, is available on-site to review smears for adequacy during FNA procedures.
This modality is currently used to search for an occult primary tumor in the setting of known metastasis, evaluate the extent of disease in a biopsy-proven breast carcinoma (useful if breast conservation is being considered), and assess lesions in implant-augmented breasts. It is also useful for screening high-risk women, as described previously. Its role in screening women with dense breasts or for evaluating borderline lesions has not been established, and these indications typically are not reimbursable. Breast MRI has a high sensitivity, and clinical developments have improved its specificity. Breast MRI examinations have recently been facilitated by the development of computer-aided detection software, which can help to streamline the interpretation of these images and produce a more uniform result.
Breast surgeons are increasingly using breast MRI for surgical planning. In a study reported by Bedrosian et al (a retrospective review of 267 patients who had preoperative MRI prior to undergoing definitive surgery), preoperative breast MRI changed the planned surgical approach in 26% of cases, including 16.5% of cases of breast conservation switched to mastectomy. Imaging centers across the United States have a varying degree of expertise in performing, interpreting, and providing a standard reporting nomenclature for breast MRI. The ACR has developed an accreditation program in breast MRI (available on their website) to address this issue.
In investigating ultrasonographic features of solid masses that suggest benign or malignant disease, Stavros et al described such factors as sharp margins (benign) and taller-than-wide lesions (malignant). Although these features are useful for clinical decision-making, their utility in increasing the specificity of the breast lesion workup has not been verified.
Molecular breast imaging
Molecular breast imaging has demonstrated excellent specificity and sensitivity in new industry-sponsored trials using high-definition, breast-specific gamma cameras. Both technetium sestamibi–based scanning and breast-specific PET scanning have shown promise. However, their utility has not yet been demonstrated in large-scale clinical trials.