Gynecology_Novak

Gynecology_Novak. Palpation While the patient is seated, each breast should be palpated methodically. Some physicians recommend palpating the breast in long strips, but the exact palpation technique used is probably not as important as the thoroughness of its application over the entire breast. One very effective method is to palpate the breast in enlarging concentric circles until the entire breast is covered. A pendulous breast can be palpated by placing one hand between the breast and the chest wall and gently palpating the breast between both examining hands. The axillary and supraclavicular areas should be palpated for enlarged lymph nodes. The entire axilla, the upper outer quadrant of the breast, and the axillary tail of Spence are palpated for possible masses. While the patient is supine with one arm over her head, the ipsilateral breast is again methodically palpated from the clavicle to the costal margin and from the sternum to the latissimus dorsi laterally. If the breast is large, a pillow


Gynecology_Novak

Gynecology_Novak. over her head, the ipsilateral breast is again methodically palpated from the clavicle to the costal margin and from the sternum to the latissimus dorsi laterally. If the breast is large, a pillow or towel may be placed beneath the scapula to elevate the side being examined; otherwise, the breast tends to fall to the side, making palpation of the lateral hemisphere more difficult. The major features to be identified on palpation of the breast are temperature, texture and thickness of skin, generalized or focal tenderness, nodularity, density, asymmetry, dominant masses, and nipple discharge. Most premenopausal patients have normally nodular breast parenchyma. The nodularity is diffuse but predominantly in the upper outer quadrants, where there is more breast tissue. These benign parenchymal nodules are small, similar in size, and indistinct. By comparison, breast cancer usually occurs in the form of a nontender, firm mass with irregular margins. A cancerous mass feels distinctly


Gynecology_Novak

Gynecology_Novak. nodules are small, similar in size, and indistinct. By comparison, breast cancer usually occurs in the form of a nontender, firm mass with irregular margins. A cancerous mass feels distinctly different from the surrounding nodularity. A malignant mass may be fixed to the skin or to the underlying fascia. A suspicious mass is usually unilateral. Similar findings in both breasts are unlikely to represent malignant disease (6).


Gynecology_Novak

Gynecology_Novak. Breast Self-Examination There is controversy about recommending breast self-examination (BSE). There is no evidence that doing BSE improves survival rates from breast cancer (7). Staunch opponents of BSE argue that it doubles a woman’s risk of undergoing a breast biopsy for benign pathology (8). BSE increases breast health awareness and helps promote early detection of cancer (9–11). Most breast cancers are detected by women themselves (48%), followed by breast imaging (41%), and by physician clinical examination in only 11% (12). Although young women have a low incidence of breast cancer, it is important to teach BSE early so it becomes habitual. Organizations such as the American Cancer Society sponsor courses in BSE. Reassurance, support, and patient education may encourage women to overcome psychological barriers to routine BSE (13). Such instruction is available through electronic resources (14). The following seven “P”s represent the essential components of breast examination:


Gynecology_Novak

Gynecology_Novak. The following seven “P”s represent the essential components of breast examination: Pads of fingers for palpation Pattern of search


Gynecology_Novak

Gynecology_Novak. The woman should inspect her breasts while standing or sitting before a mirror, looking for any asymmetry, skin dimpling, or nipple retraction. Elevating her arms over her head or pressing her hands against her hips to contract the pectoralis muscles will highlight any skin dimpling. Finally, the woman should examine her breasts while bending over and leaning forward. While standing or sitting, she should carefully palpate her breasts with the fingers of the opposite hand. She should lie down and again palpate each quadrant of the breast as well as the axilla using the pads of the three middle fingers with three pressures—light, medium, and deep—covering the entire breast from the clavicle to the inframammary fold, from sternum to latissimus dorsi laterally. The area within the perimeter of the breast should be palpated, preferably using an up-and-down method called vertical stripe, rather than the concentric circular or radial methods, in which the edges of the breast tissue often


Gynecology_Novak

Gynecology_Novak. of the breast should be palpated, preferably using an up-and-down method called vertical stripe, rather than the concentric circular or radial methods, in which the edges of the breast tissue often are omitted. Many women feel anxious about performing breast examination. The examination may be performed while showering; soap and water may increase the sensitivity of palpation, and the privacy of the shower may provide a less anxiety-provoking environment.


Gynecology_Novak

Gynecology_Novak. It is helpful for all women to examine their breasts at the same time each month to develop a routine. Premenopausal women should examine their breasts monthly 7 to 10 days after the onset of the menstrual cycle. For postmenopausal women, selection of a specific calendar date is a helpful way to remember to perform a monthly BSE. Women should be instructed to report any abnormalities or changes to their physicians. If the physician cannot confirm the patient’s findings, the examination should be repeated in 1 month or after her next menstrual period.


Gynecology_Novak

Gynecology_Novak. Mammography Screen-film mammography was considered the best method for imaging the breast (15). Full-field digital mammography, which records mammographic images on a computer, is a modification of screen-film mammography (16). Some advantages of digital mammography include lower radiation exposure, ability to manipulate a computerized image for optimal viewing, and access to distance consultations through telemammography (17). Studies comparing the sensitivity of full-field digital mammography with screen-film mammography in detecting cancer had mixed results. The Digital Mammographic Imaging Screening Trial (DMIST) consisted of 49,528 asymptomatic women presenting for screening mammography, who underwent both digital and film mammography. Results suggested that while the overall accuracy of digital and film mammography for screening breast cancer is similar, digital mammography may be more accurate in women under the age of 50 years, women with radiographically dense breast, and


Gynecology_Novak

Gynecology_Novak. of digital and film mammography for screening breast cancer is similar, digital mammography may be more accurate in women under the age of 50 years, women with radiographically dense breast, and premenopausal or perimenopausal women (18).


Gynecology_Novak

Gynecology_Novak. Slow-growing breast cancers can be identified by mammography at least 2 years before the mass reaches a size detectable by palpation. These tumors have a less aggressive biologic behavior than interval breast cancers (19–21). Mammography is the only reproducible method of detecting nonpalpable breast cancer, but its use depends on the availability of state-of-the-art equipment and a dedicated breast radiologist. Compression of the breast is necessary to obtain good images, and patients should be forewarned that breast compression is uncomfortable. With good technique and well-maintained modern equipment, exposure to radiation can be limited. Full-field digital mammography (FFDM) has a 22% lower mean glandular radiation dose than film-screen mammography per acquired view. FFDM delivers 1.86 mGy average breast radiation dose per view compared to 2.37 mGy for film screen (22). The indications for mammography are as follows: 1.


Gynecology_Novak

Gynecology_Novak. The indications for mammography are as follows: 1. To screen, at regular intervals, women who are at high risk for developing breast cancer. About one-third of the abnormalities detected on screening mammography prove malignant when biopsy is performed (23). 2. To evaluate a questionable or ill-defined breast mass or other suspicious change in the breast that is detected by clinical breast examination. 3. To establish a baseline breast mammogram and reevaluate patients at yearly intervals to diagnose a potentially curable breast cancer before it has been diagnosed clinically. 4. To search for occult breast cancer in a patient with metastatic disease in axillary nodes or elsewhere from an unknown primary origin. 5. To screen for unsuspected cancer before cosmetic operations or biopsy of a mass. 6. To monitor breast cancer patients who were treated with a breast-conserving surgery and radiation.


Gynecology_Novak

Gynecology_Novak. Screening programs to evaluate asymptomatic, healthy women combine physical examination with mammographic screening to identify breast abnormalities. During the past 30 years, there was an increase in the use of mammography, mammographic screening, and public awareness of breast health care. The cancer detection rate for screening mammography is 5 per 1,000 screening examinations (24). The cancer detection rate is 11-fold higher, at 55 per 1,000 examinations, when breast imaging is performed for a specific finding (i.e., diagnostic imaging) (24). Of seven randomized mammographic screening trials performed, five demonstrated a reduction in overall mortality from breast cancer screening programs (25–32). A study from the Rhode Island Cancer Registry indicates that the institution of population-based breast cancer screening programs can result in the reduction in the median tumor size at initial detection from 2.0 to 1.5 cm, which is associated with a 25% reduction in mortality (33). A


Gynecology_Novak

Gynecology_Novak. breast cancer screening programs can result in the reduction in the median tumor size at initial detection from 2.0 to 1.5 cm, which is associated with a 25% reduction in mortality (33). A study from the Norwegian breast-cancer screening program was associated with a reduction in the rate of death from breast cancer, but the screening itself accounted for only about a third of total reduction (30). Detecting breast cancer before it spreads to the axillary nodes greatly increases the chance of survival; about 85% of women with such cancer will survive at least 5 years (31,34). Because breast cancer presents first as local disease, screening mammography for breast cancer in asymptomatic women can detect small tumors and offer a better prognosis. These tumors had less opportunity to metastasize regionally or systemically; thus women have more options for treatment with reduced toxicity.


Gynecology_Novak

Gynecology_Novak. The American Cancer Society published an extensive review of the benefits, limitations, and potential harms of screening mammography (35). It addresses the role of physical examination, discusses screening in older and high-risk women, and reviews the role of newer technologies. A summary of the guidelines recommends that women of average risk for breast cancer begin mammographic screening at age 40. The rationale for beginning mammographic screening at age 40 is a 24% reduction in mortality in screened populations (28). For women in their 20s and 30s, a clinical breast examination is suggested at least every 3 years, and preferably annually, as part of a well-woman examination. For women older than age 40 years, annual clinical breast examination and mammography are recommended. For older women, recommendations for mammographic screening may be individualized based on the presence of any comorbidities. Chronologic age alone should not be considered a contraindication to mammographic


Gynecology_Novak

Gynecology_Novak. women, recommendations for mammographic screening may be individualized based on the presence of any comorbidities. Chronologic age alone should not be considered a contraindication to mammographic screening as long as a woman is in reasonable health and would be a candidate for breast cancer surgery (35).


Gynecology_Novak

Gynecology_Novak. The American Geriatrics Society recommends annual or at least biennial mammography for women up to age 75 years, and after that age, every 2 to 3 years if the woman has a life expectancy of more than 4 years (36). The reasons for liberalization of the screening interval recommendations for older women include improved biology profile, slower growth rate, and lower risk for recurrence (37–41). The natural history of the disease in older women must be balanced against life expectancy as a function of overall health (42). For high-risk women, consideration can be given to earlier initiation of screening (5 to 10 years earlier than the age of the index case) and shorter intervals between screening, and the use of additional imaging modalities such as breast ultrasonography and magnetic resonance imaging (MRI) with dedicated breast coils. No screening test is perfect, and false-negative imaging studies or benign clinical examinations may lead the patient to an erroneous sense of well-being


Gynecology_Novak

Gynecology_Novak. imaging (MRI) with dedicated breast coils. No screening test is perfect, and false-negative imaging studies or benign clinical examinations may lead the patient to an erroneous sense of well-being only to be confronted later with a subsequent cancer. Likewise, a false-positive result can lead to significant anxiety and unnecessary biopsy.


Gynecology_Novak

Gynecology_Novak. A mammographic abnormality includes a mass (solid versus cystic), microcalcifications (benign, indeterminate, suspicious), asymmetric density, architectural distortion, and appearance of a new density. There are eight morphologic categories of mammographic abnormalities (43,44): 1. 2. Number of calcifications 3. Description of calcifications 4. 5. Shape of mass 6. Density of mass 7. 8.


Gynecology_Novak

Gynecology_Novak. Mammographic abnormalities should be visible on two views, usually craniocaudal (CC) and mediolateral oblique (MLO). The lesion should triangulate to the same location on those two views. Calcifications can be macrocalcifications, which are coarse and usually represent benign degenerative breast conditions. Calcifications associated with breast cancer are clustered pleomorphic microcalcifications; typically five to eight or more calcifications are aggregated in one part of the breast (45). These calcifications may be associated with a mammographic mass density. A mass density may appear without evidence of calcifications. It can represent a cyst, benign tumor, or a malignancy. A malignant density usually has irregular or ill-defined borders and may lead to architectural distortion, which may be subtle and difficult to detect in a dense breast. Other mammographic findings suggesting breast cancer are architectural distortion, asymmetric density, skin thickening or retraction, or nipple


Gynecology_Novak

Gynecology_Novak. be subtle and difficult to detect in a dense breast. Other mammographic findings suggesting breast cancer are architectural distortion, asymmetric density, skin thickening or retraction, or nipple retraction. Examples of mammographic abnormalities can be found in several electronic sources (46).


Gynecology_Novak

Gynecology_Novak. The American College of Radiology recommended the Breast Imaging Reporting and Data System (BI-RADS) as a standardized scheme for describing mammographic lesions (47). In the BI-RADS system, there are six categories for mammographic findings (other than incomplete) (43,44). 0. Incomplete, needs further imaging 1. 2. 3. Probably benign, short-interval follow-up recommended 4. 5. Highly suggestive of malignancy and appropriate action should be undertaken 6. Known malignancy (a category that is often used for follow-up of a lesion that is undergoing neoadjuvant treatment) The patient should be referred for tissue diagnosis if the report identifies a lesion as a category 4 or 5 (47). A category 0 indicates incomplete evaluation, and further diagnostic studies are required. Category 3 connotes a finding that is most likely benign; a short-interval follow-up is recommended, and breast examination by an expert should be considered. Correlation of Findings


Gynecology_Novak

Gynecology_Novak. Correlation of Findings Biopsy must be performed on patients with a dominant or suspicious mass despite absence of mammographic findings (48). Mammography should be performed before biopsy so other suspicious areas can be noted and the contralateral breast can be checked (Fig. 21.2). Mammography is never a substitute for biopsy because it may not reveal clinical cancer, especially when it occurs in the dense breast tissue of young women with fibrocystic changes. The sensitivity of mammography is 75%, with a specificity of 92.3% depending on the patient’s age; breast density; use of hormone therapy; and the size, location, and mammographic appearance of the tumor (49). Mammography is less sensitive in young women with dense breast tissue than in older women, who tend to have fatty breasts, in which mammography can detect at least 90% of malignancies (50). Small tumors, particularly those without calcifications, are more difficult to detect, especially in women with dense breasts.


Gynecology_Novak

Gynecology_Novak. Ultrasonography Breast ultrasonography is used for focused scanning of a questionable finding or for evaluation of a mammographic finding (51). Reliable, portable, computer-enhanced ultrasonography with high-frequency transducers and improved imaging is available to evaluate and treat problems of the breast (52). It is a sensitive, minimally invasive technique that is used frequently to evaluate some breast symptoms, especially in younger women with dense breast tissue, but is dependent on the availability of a skilled ultrasonographer (53). Some lesions can be detected only with ultrasonography (54). It is the preferred modality to distinguish a solid from a cystic mass (51). Breast ultrasonography is not recommended for routine screening, but is being studied as a means to screen women with dense breast tissue (54). Ultrasonography has a higher false-positive rate than mammography (51,53–55).


Gynecology_Novak

Gynecology_Novak. Figure 21.2 Bilateral mammography shows the extent of breast carcinoma, illustrating the importance of bilateral mammography in the workup of a clinically apparent mass. (From Kruper L, Giuliano AE. Breast disease. In: Berek JS, Hacker NF, eds. Berek & Hacker’s Gynecologic Oncology, 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010:617, with permission.) Following are indications for breast ultrasonography: Characterization: Palpable abnormality Ambiguous mammographic findings Silicone leak Mass in woman younger than 30 years, lactating, or pregnant


Gynecology_Novak

Gynecology_Novak. Characterization: Palpable abnormality Ambiguous mammographic findings Silicone leak Mass in woman younger than 30 years, lactating, or pregnant Ultrasonography is useful in distinguishing benign from malignant lesions identified by mammography (56). Ultrasonography may be especially useful if the patient feels a mass, but the physician cannot detect an abnormality and the mammogram does not disclose one. It may identify cancers in the dense breast tissue of premenopausal women, but it is usually used to distinguish a benign cyst from a solid tumor. Ultrasonography cannot reliably detect microcalcifications, and it is not as useful as mammography in assessing women with fatty breasts.


Gynecology_Novak

Gynecology_Novak. Handheld or real-time ultrasonography is 95% to 100% accurate in differentiating solid masses from cysts (57). This finding is of limited clinical value because a dominant mass should be evaluated by biopsy, and a cystic mass can be studied by needle aspiration, which is far less expensive than ultrasonography. If a lesion proves to be a simple cyst, no further evaluation is necessary. Rarely ultrasonography may identify a small cancer within a cyst, an intracystic carcinoma. These complex cysts warrant surgical biopsy.


Gynecology_Novak

Gynecology_Novak. Magnetic Resonance Magnetic resonance imaging may be of value in assessing breast lesions of an indeterminate Imaging nature detected by clinical and mammographic examination or occurring in patients who have implants (58). Both MRI and positron emission tomography (PET) are used to identify occult lesions, and MRI is increasing in popularity as a means of imaging the breast (58–60). It tends to be highly sensitive but not specific, leading to biopsies of benign lesions. Image enhancement with gadolinium discriminates between benign and malignant lesions with varying degrees of accuracy.


Gynecology_Novak

Gynecology_Novak. Several roles are proposed for breast MRI. The lack of radiation exposure makes MRI theoretically an ideal method for screening of healthy women, but widespread use is not cost-effective. Focal asymmetry is usually benign but can represent a malignancy. MRI may help identify those patients with focal asymmetric areas who should undergo biopsy. A scar can easily be distinguished from recurrent tumor based on the evaluation and diminution of the scar over time. Some scars do not resolve rapidly and are confused with cancer or, more commonly, with recurrent cancer after breast-conserving surgery and whole breast irradiation. Ideally, such cases are evaluated with MRI, sometimes obviating the need for biopsy. MRI is extremely useful in identifying silicone released by ruptured breast implants in patients with augmented breasts (Fig. 21.3). In patients with implants, MRI with gadolinium may be performed to detect breast cancer even if silicone release is not suspected. There may be a role


Gynecology_Novak

Gynecology_Novak. in patients with augmented breasts (Fig. 21.3). In patients with implants, MRI with gadolinium may be performed to detect breast cancer even if silicone release is not suspected. There may be a role for MRI in evaluation of specific conditions. It is used for the following indications:


Gynecology_Novak

Gynecology_Novak. Stage tumor to rule out multicentric disease. Differentiate postoperative scar from recurrence after breast-conserving surgery. Figure 21.3 Mammography shows implant and extracapsular free silicone (arrow). Find a lesion seen in only one view of mammogram. Evaluate positive axillary nodes in the presence of negative mammogram and clinical breast examination results. Rule out silicone implant rupture. Assess focal asymmetry. Detect additional ipsilateral and contralateral cancers. Evaluate the effect of neoadjuvant chemotherapy.


Gynecology_Novak

Gynecology_Novak. Assess focal asymmetry. Detect additional ipsilateral and contralateral cancers. Evaluate the effect of neoadjuvant chemotherapy. The American Cancer Society recommends annual MRI screening for women who are high risk (greater than 20% lifetime risk) and consideration given to women with moderate risk (15% to 20% lifetime risk) (61). A study from the Netherlands in high-risk women reported 71% sensitivity for MRI compared with 17.9% for clinical breast examination and 40% for mammography (62). The International Cooperative Magnetic Resonance Mammography Study will help identify the advantages and limitations of MRI. At present, MRI should be considered only after conventional imaging is performed; it should not be used as a screening tool or a substitute for mammography or biopsy. Centers that perform MRI should have the ability to perform MRI-guided biopsies of lesions detected with MRI only and that are not visible with mammogram or ultrasound.


Gynecology_Novak

Gynecology_Novak. PET scanning is a diagnostic modality that assesses the metabolic activity of tumors. Radioactive ﬂuorodeoxyglucose (FDG) is an analogue of glucose that is metabolized by tissues of high metabolic activity. Although not specifically approved for the initial diagnosis of breast cancer or for staging the axilla, it can be useful in patients with advanced disease (59,63). This technique is used to identify occult breast lesions with positive axillary lymph nodes (59). Breast Tissue Evaluation: Histology and Cytology


Gynecology_Novak

Gynecology_Novak. The safest course is tissue or cytologic biopsy evaluation of all dominant masses found on physical examination and, in the absence of a mass, evaluation of suspicious lesions shown by breast imaging. Over 1 million women have breast biopsies each year in the United States. Between 70% and 80% of these biopsies yield a benign lesion (64). The diagnosis of a benign breast lesion versus breast cancer is often difficult to determine based on clinical examination and requires evaluation of tissue by fine needle aspiration cytology (FNAC), core needle biopsy (CNB), or excisional biopsy (EB). Both FNAC and CNB are reasonable techniques for the evaluation of a palpable or image-identified lesion. CNB evolved as the diagnostic procedure of choice. More than half of all breast biopsies use a core-needle technique. The sensitivity of CNBs performed using either stereotactic or ultrasound guidance is 97% to 99% (65). CNB is used increasingly to diagnose breast cancer and to determine tumor


Gynecology_Novak

Gynecology_Novak. core-needle technique. The sensitivity of CNBs performed using either stereotactic or ultrasound guidance is 97% to 99% (65). CNB is used increasingly to diagnose breast cancer and to determine tumor histology, grade, and marker expression; select neoadjuvant therapy; and predict sentinel lymph node status (66). CNB and fine needle aspiration (FNA) are less invasive and achieve better cosmesis than excisional or even incisional biopsy. The main limitations of FNA are high rate of insufficient sampling and inability to distinguish invasive from noninvasive cancers. CNB is a well-accepted alternative to surgical biopsy and can avoid surgical biopsies in most patients (67). Investigators of the Fifth Radiologic Diagnostic Oncology Group demonstrated that image-guided biopsy of breast lesions provides high diagnostic accuracy. The sensitivity, specificity, and accuracy of CNB were 0.91, 1.00, and 0.98, respectively (68).


Gynecology_Novak

Gynecology_Novak. About 30% of lesions suspected to be cancer prove on biopsy to be benign, and about 15% of lesions believed to be benign prove to be malignant (23). Dominant masses or suspicious nonpalpable breast lesions require histopathological examination. Histologic or cytologic diagnosis should be obtained before the decision is made to monitor a breast mass (69). An exception may be a premenopausal woman with a nonsuspicious mass presumed to be fibrocystic disease. An apparently fibrocystic lesion that does not completely resolve within several menstrual cycles should be sampled for biopsy. Any mass in a post-menopausal woman who is not taking estrogen therapy should be presumed to be malignant. Some clinicians will monitor a mass when results of the clinical diagnosis, breast imaging studies, and cytologic studies are all in agreement, such as with fibroadenoma. Many clinicians will not leave a dominant mass in the breast even when FNAC or CNB results are negative, unless the FNA or CNB shows


Gynecology_Novak

Gynecology_Novak. cytologic studies are all in agreement, such as with fibroadenoma. Many clinicians will not leave a dominant mass in the breast even when FNAC or CNB results are negative, unless the FNA or CNB shows fibroadenoma. Such cases require periodic follow-up. Some surgeons excise lesions when the sampling technique shows only fibrocystic disease. Figures 21.4 and 21.5 present algorithms for management of breast masses in premenopausal and postmenopausal patients. Simultaneous evaluation of a breast mass using clinical breast examination, radiography, and needle biopsy can lower the risk of missing cancer to only 1%, effectively reducing the rate of diagnostic failure and increasing the quality of patient care (70).


Gynecology_Novak

Gynecology_Novak. If the presence of breast cancer is strongly suggested by physical examination, the diagnosis can be confirmed by FNAC or CNB, and the patient may be counseled regarding treatment. Treatment should not be determined based on results of physical examination and mammography alone, in the absence of biopsy results. The most reasonable approach to the diagnosis and treatment of breast cancer is outpatient biopsy (either FNAC, CNB, or EB), followed by definitive surgery at a later date if needed. This two-step approach allows patients to adjust to the diagnosis of cancer, carefully consider alternative forms of therapy, and seek a second opinion. Studies show no adverse effect from the 1to 2-week delay associated with the two-step procedure (71). Because cancer is found in the minority of patients who require biopsy for diagnosis of a breast mass, definitive treatment should not be undertaken without an unequivocal histologic diagnosis of cancer.


Gynecology_Novak

Gynecology_Novak. Fine-Needle Aspiration With FNAC, cells from a breast tumor are aspirated with a small (usually 22-gauge) needle and examined by a pathologist. Precise guidelines for this technique are available (72). It can be performed easily, with no morbidity, and is much less expensive than excisional or open biopsy. It requires the availability of a pathologist skilled in the cytologic diagnosis of breast cancer to interpret the results, and it is subject to sampling problems, particularly when lesions are deep. Cytologic diagnoses must be correlated with clinical and imaging findings to achieve triple-test concordance and to decrease the false-negative rate (73). The triple-test concordance (i.e., concordance between fine-needle aspiration, physical examination, and mammography) is the foundation of breast evaluation. The triple-test results are more powerful than each modality alone (74). The incidence of false-positive diagnoses was 0% to 0.3%, and the rate of false-negative diagnoses was


Gynecology_Novak

Gynecology_Novak. of breast evaluation. The triple-test results are more powerful than each modality alone (74). The incidence of false-positive diagnoses was 0% to 0.3%, and the rate of false-negative diagnoses was 1.4% to 2.3% in several recent studies (74,75).


Gynecology_Novak

Gynecology_Novak. Core Needle Biopsy A core of tissue can be obtained from palpable lesions using a large cutting needle (76). Image-guided large-core needle biopsy is a reliable diagnostic alternative to surgical excision of suspicious nonpalpable breast lesions (77). As in the case of any needle biopsy, the main drawback is false-negative findings caused by improper positioning of the needle. False-negative findings may be reduced if core biopsy is performed with ultrasonographic guidance. The interpretation of results from CNB is classified by categories B1 to B5 (78): B1: Normal tissue B2: Benign lesions: fibroadenomas, fibrocystic change, sclerosing adenosis, duct ectasia, fat necrosis, abscess B3: Uncertain malignant potential: atypical epithelial hyperplasia, lobular neoplasia, phyllodes tumor, papillary lesions, radial scar, complex sclerosing lesions B4: Suspicious B5: Malignant


Gynecology_Novak

Gynecology_Novak. B3: Uncertain malignant potential: atypical epithelial hyperplasia, lobular neoplasia, phyllodes tumor, papillary lesions, radial scar, complex sclerosing lesions B4: Suspicious B5: Malignant Open Excisional Biopsy Open biopsy with local anesthesia as a separate procedure before deciding on definitive treatment is the most reliable means of diagnosis. Its utility is reserved for when the results of needle biopsy are nondiagnostic or equivocal. Figure 21.4 Algorithm for management of breast masses in premenopausal women. (Revised and updated from Kruper L, Giuliano AE. Breast disease. In: Berek JS, Hacker NF, eds. Berek & Hacker’s Gynecologic Oncology, 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010:628, with permission.)


Gynecology_Novak

Gynecology_Novak. Figure 21.5 Algorithm for management of breast masses in postmenopausal women. (Revised and updated from Kruper L, Giuliano AE. Breast disease. In: Berek JS, Hacker NF, eds. Berek & Hacker’s Gynecologic Oncology, 5th ed. Philadelphia: Lippincott Williams & Wilkins, 2010:629, with permission.)


Gynecology_Novak

Gynecology_Novak. Histologic Analysis Histologic evaluation with hematoxylin and eosin (H&E) staining confirms benign or malignant disease. Images of benign and malignant breast lesions can be viewed through the Internet Pathology Laboratory for Medical Education (79). Assessment of prognostic factors, tumor grade; estrogen, progesterone, her-2/neu receptor status; and proliferative indices is performed on paraffin-fixed tissue by immunohistochemistry (78). Her-2/neu assessment in breast cancer by immunohistochemistry (IHC) is appropriate for patients with tumors that score 3+. Fluorescence in situ hybridization (FISH) is recommended for 2+ IHC to more accurately assess her-2/neu amplification and provide better prognostic information (80).


Gynecology_Novak

Gynecology_Novak. Ductal Lavage Cytology Ductal lavage using a microcatheter is a modality that was investigated in high-risk women (81). Patients undergo gentle nipple suction to elicit nipple ﬂuid. A duct that yields ﬂuid is cannulated with a microcatheter, and 10 to 20 mL of saline are introduced in 2-to 4-mL increments. The cytologic assessment of a sample obtained by ductal lavage is more sensitive than that of nipple aspiration. Ductal lavage performed to identify abnormal cells is not an effective tool in detecting breast cancer and is rarely performed (81).


Gynecology_Novak

Gynecology_Novak. Benign breast disorders account for most breast problems. These conditions are frequently considered in the context of excluding breast cancer and often are unrecognized for their own associated morbidity (82). To provide appropriate management, it is important to consider benign breast disorders from four aspects: (i) clinical picture, (ii) medical significance, (iii) treatment intervention, and (iv) pathologic etiology (83). A framework for understanding benign breast problems is called Aberrations of Normal Development and Involution (ANDI) (2,82,83). It includes symptoms, histology, endocrine state, and pathogenesis in a progression from a normal to a disease state. Most benign breast conditions arise from normal changes in breast development, hormone cycling, and reproductive evolution (82). Three life cycles reﬂect different reproductive phases in a woman’s life and are associated with unique breast manifestations. 1.


Gynecology_Novak

Gynecology_Novak. Three life cycles reﬂect different reproductive phases in a woman’s life and are associated with unique breast manifestations. 1. During the early reproductive period (15–25 years), lobule and stromal formation occurs. The ANDI conditions associated with this period are fibroadenoma (mass) and juvenile hypertrophy (excessive breast development). In this first stage, the progression from ANDI to a disease state results in the formation of giant fibroadenomas and multiple fibroadenomas. 2. During the mature reproductive period (25 to 40 years), cyclic hormonal changes affect glandular tissue and stroma. In this second period, the ANDI is an exaggeration of these cyclic effects, such as cyclic mastalgia and generalized nodularity. 3.


Gynecology_Novak

Gynecology_Novak. 3. The third phase is involution of lobules and ducts or turnover of epithelia, which occurs during ages 35 to 55 years. The ANDI associated with lobular involution are macrocysts (lumps) and sclerosing lesions (mammographic abnormalities). Those associated with ductal involution are duct dilation (nipple discharge) and periductal fibrosis (nipple retraction), and those with epithelial turnover are mild hyperplasia (pathologic description). Disease conditions with increased epithelial turnover are epithelial hyperplasias with atypia. Breasts are under endocrine control and show a wide range of appearances during reproductive life. ANDI classification allows the clinician to understand the pathogenesis of these conditions and to understand that these disorders are aberrations of a normal process that does not usually require any specific treatment (82).


Gynecology_Novak

Gynecology_Novak. Fibrocystic Change Fibrocystic change, the most common lesion of the breast, is an imprecise term that covers a spectrum of clinical signs, symptoms, and histologic changes (76). The term refers to a histologic picture of fibrosis, cyst formation, and epithelial hyperplasia (83). Cysts arise from the breast lobules and are an aberration of normal breast involution (82). Macroscopic cysts occur in approximately 7% of women, and microscopic, nonpalpable cysts occur in about 40% of women (84). It is common in women 35 to 55 years of age, but rare in postmenopausal women not taking hormone therapy. The presence of estrogen seems necessary for the clinical symptoms to occur. This finding is supported by the observation that it is present bilaterally, increased in the perimenopausal age group, and responsive to endocrine therapy (85). In essence, a diagnosis of fibrocystic change can lead to significant patient anxiety but is of little clinical significance as long as malignancy is excluded


Gynecology_Novak

Gynecology_Novak. responsive to endocrine therapy (85). In essence, a diagnosis of fibrocystic change can lead to significant patient anxiety but is of little clinical significance as long as malignancy is excluded (86). These lesions are associated with benign changes in the breast epithelium.


Gynecology_Novak

Gynecology_Novak. Cyst Fluid Analysis Investigators examined the electrolyte and protein content of cyst ﬂuid, but this is of little significance in the clinical management of fibrocystic disease. The potassium-to-sodium ratio is a marker that may be used to distinguish cyst subtypes (87). Cysts are either lined by apocrine epithelium with a high potassium-to-sodium ratio and a higher hormone or steroid concentration (type I); or by ﬂattened lobule epithelium with a low potassium-to-sodium ratio and a higher concentration of albumin, carcinoembryonic antigen, CA125, and steroid hormone–binding globulin (type II) (87). Apocrine cysts produce and secrete large amounts of prostate-specific antigen (PSA) (88). The role of this serine protease in proliferative breast disease is not fully understood.


Gynecology_Novak

Gynecology_Novak. Fibrocystic changes may produce an asymptomatic mass that is smooth, mobile, and potentially compressible. Fibrocystic change is more often accompanied by pain or tenderness and sometimes nipple discharge. In many cases, discomfort coincides with the premenstrual phase of the cycle, when the cysts tend to enlarge. Fluctuations in size and rapid appearance or disappearance of a breast mass are common. Multiple or bilateral masses appear frequently, and many patients have a history of a transient mass in the breast or cyclic breast pain. Cyclic breast pain is the most commonly associated symptom of fibrocystic changes.


Gynecology_Novak

Gynecology_Novak. Differential Diagnosis Pain, ﬂuctuation in size, multiplicity of lesions, and bilaterality are the features most helpful to differentiate fibrocystic disease from carcinoma. If a dominant mass is present, the diagnosis of cancer should be suspected until it is disproved by complete aspiration of a cyst, or histopathologic analysis if a mass is present after aspiration, or by breast imaging. Microscopic findings associated with fibrocystic disease include cysts (gross and microscopic), papillomatosis, adenosis, fibrosis, and ductal epithelial hyperplasia (89). Diagnostic Tests Patients with cystic disease may have a discrete fibrocystic mass that is frequently indistinguishable from carcinoma, based on clinical findings. Mammography may be helpful, but there are no mammographic signs diagnostic of fibrocystic change. Ultrasonography is useful in differentiating a cystic from a solid mass. Characteristic findings on ultrasonography that confirm a simple cyst include the following:


Gynecology_Novak

Gynecology_Novak. Mass with thin walls Absence of internal echoes If these imaging criteria are not met, a tissue diagnosis of the mass usually requires a FNA, FNAC, or EB. The finding of a simple cyst by ultrasonography rules out carcinoma. Any lesion that is suspicious by mammography or ultrasonography should be biopsied.


Gynecology_Novak

Gynecology_Novak. When the diagnosis of fibrocystic change is established by ultrasonography or is practically certain because the history is classic, aspiration of a discrete mass, suggestive of a cyst, is indicated if the patient is symptomatic, the cyst obscures visualization of breast tissue on mammography and prevents adequate imaging, or if the ultrasonographic criteria are not met. In one study of a screened population, 1% of individuals developed a new cyst that resolved in more than 50% of cases (90). Aspiration may be performed with ultrasonographic guidance, but image guidance is usually not necessary if the cyst is palpable (91). FNA of a cyst is a minimally invasive procedure performed with a 21-or 22-gauge needle without local anesthesia and is not associated with significant risks or complications. There is minimal pain and little risk for infection or bleeding. Benign cyst ﬂuid is straw colored to dark green to brownish and does not need to be submitted for cytologic evaluation (6).


Gynecology_Novak

Gynecology_Novak. There is minimal pain and little risk for infection or bleeding. Benign cyst ﬂuid is straw colored to dark green to brownish and does not need to be submitted for cytologic evaluation (6). Injection of air into the cyst cavity is reported to reduce the likelihood of cyst recurrence but generally is not performed. The patient should be reexamined at a short interval thereafter for cyst recurrence. Cysts will reoccur in 30% of patients, cause anxiety, and require repeated evaluations (84). Tissue biopsy should be performed in the presence of the following findings:


Gynecology_Novak

Gynecology_Novak. No cyst ﬂuid is obtained. The ﬂuid is bloody. The ﬂuid is thick. The cyst is complex. There is an intracystic mass. A mass persists after aspiration. A persistent mass is noted at any time during follow-up. If a needle biopsy is performed and results are negative for malignancy, a suspicious mass that does not resolve over several months should be excised. Surgery should be conservative, because the primary objective is to exclude cancer. Simple mastectomy or extensive removal of breast tissue is not indicated for fibrocystic disease. Most patients do not require treatment for fibrocystic changes, just reassurance that fibrocystic change is a transient phenomenon of aging that is associated with hormonal effects on the breast glandular tissue that eventually subsides.


Gynecology_Novak

Gynecology_Novak. Fibrocystic change is not associated with an increased risk of breast cancer unless there is histologic evidence of epithelial proliferative changes, with or without atypia (92–97). The common coincidence of fibrocystic disease and malignancy in the same breast reﬂects the fact that both processes are common events. Approximately 80% of biopsies show fibrocystic changes. In an evaluation of the relationship between fibrocystic change and breast cancer in 10,366 women who underwent biopsy between 1950 and 1968 and were followed for a median of 17 years, approximately 70% of the biopsies showed nonproliferative breast disease, whereas 30% showed proliferative breast disease (95). Cytologic atypia were present in 3.6% of cases. Women with nonproliferative disease had no increased risk of breast cancer, whereas women with proliferative breast disease and no atypical hyperplasia had a twofold higher risk of breast cancer. Patients whose biopsy results showed atypical ductal or lobular


Gynecology_Novak

Gynecology_Novak. breast cancer, whereas women with proliferative breast disease and no atypical hyperplasia had a twofold higher risk of breast cancer. Patients whose biopsy results showed atypical ductal or lobular hyperplasia had an approximately fivefold higher risk than women with nonproliferative disease to develop invasive breast cancer in either breast. Patients with carcinoma in situ have an eight-to tenfold risk of developing breast cancer. This risk is bilateral for lobular lesions and ipsilateral for ductal lesions. A family history of breast cancer added little risk for women with nonproliferative disease, but family history plus atypia increased breast cancer risk 11-fold. The presence of cysts alone did not increase the risk of breast cancer, but cysts combined with a family history of breast cancer increased the risk about threefold (76,92–97). Women with these risk factors (family history of breast cancer and proliferative breast disease) should be followed carefully with physical


Gynecology_Novak

Gynecology_Novak. cancer increased the risk about threefold (76,92–97). Women with these risk factors (family history of breast cancer and proliferative breast disease) should be followed carefully with physical examination and mammography. For such women, age-specific probability of developing invasive breast carcinoma in the next 10 years is 1 in 2,000 (age 20), 1 in 256 (age 30), 1 in 67 (age 40), 1 in 39 (age 50), and 1 in 29 (age 60) (93). The relative risk for developing breast cancer depends on the type of proliferative lesion diagnosed.


Gynecology_Novak

Management of Fibrocystic Change

Gynecology_Novak. Management of Fibrocystic Change


Gynecology_Novak

Gynecology_Novak. Fibrocystic change is a normal evolutionary change in breast development and involution and does not require a specific treatment other than a good clinical breast examination and age-appropriate mammographic screening or imaging studies directed to signs and symptoms. A number of nutritional and dietary supplements were investigated to relieve symptoms. The role of caffeine consumption in the aggravation of fibrocystic change is controversial (98– 101). Results of some studies suggest that eliminating caffeine from the diet is associated with improvement of symptoms (100,101). Many patients are aware of these studies and report relief of symptoms after discontinuing intake of coffee, tea, and chocolate. Similarly, many women find vitamin E (150 to 600 IU daily) or B6 (200 to 800 mg per day) helpful (102,103). Observations about these effects are difficult to confirm and are anecdotal (104–106). A recent review of nutritional interventions for fibrocystic breast conditions that


Gynecology_Novak

Gynecology_Novak. per day) helpful (102,103). Observations about these effects are difficult to confirm and are anecdotal (104–106). A recent review of nutritional interventions for fibrocystic breast conditions that evaluated evening primrose oil, vitamin E, or pyridoxine suggested that there are insufficient data to draw clear conclusions about their effectiveness (107). Exacerbations of pain, tenderness, and cyst formation may occur at any time until menopause, when symptoms usually subside unless patients are taking estrogen. A patient with fibrocystic changes should be advised to examine her own breasts each month just after menstruation and to inform her physician if a mass appears.


Gynecology_Novak

Gynecology_Novak. Mastalgia Mastalgia is a recognized organic condition that is studied less thoroughly than other breast problems (108,109). Inﬂammatory cytokines were implicated in the etiology of breast pain. A study evaluating expression of interleukin-6 and tumor necrosis factor-α in painful and non-painful breast tissue showed lower levels of these cytokines in painful breast tissue during the luteal phase; however, these levels did not reach statistical significance (110). Elevated estrogen, low progesterone, or an imbalance in the ratio of estrogen and progesterone were suggested as a possible cause for the symptoms (111). Natural History of Mastalgia


Gynecology_Novak

Gynecology_Novak. Natural History of Mastalgia Approximately 70% to 80% of women experience severe breast pain at some time in their lives (112,113). Mastalgia accounts for 30% to 47% of breast clinical evaluations (111,114). In 15% of the patients, the mastalgia is so severe that it alters lifestyle and requires repeated investigations and treatment (112). Mastalgia interferes with sexual (48%), physical (37%), social (12%), and work or school activities (8%) (115).


Gynecology_Novak

Gynecology_Novak. Types of Mastalgia Breast pain is a distressing constellation of symptoms that is classified as cyclic, noncyclic, or extramammary (116). Cyclic mastalgia is related to exaggerated premenstrual symptoms beginning in the luteal phase of the menstrual cycle, associated with breast engorgement, pain, ache, heaviness, and tenderness that is bilateral and can last for more than 7 days in 11% of women (116–118). Cyclical mastalgia is more prevalent in women in their third and fourth decades of life and accounts for two-thirds of all breast pain symptoms (119). Noncyclic mastalgia is independent of menstrual cycles and is described as achy, burning soreness. It may be intermittent or constant, is usually unilateral, occurs in the fourth and fifth decades, and is more difficult to treat than cyclic mastalgia (116). Extramammary pain is perceived to be located in the breast but is related to an extramammary site. Chest wall muscular pain, costal cartilage symptoms, herpes zoster,


Gynecology_Novak

Gynecology_Novak. than cyclic mastalgia (116). Extramammary pain is perceived to be located in the breast but is related to an extramammary site. Chest wall muscular pain, costal cartilage symptoms, herpes zoster, radiculopathies, and rib fractures are among some of the more common causes of extramammary pain. Costochondritis (Tietze syndrome) is a manifestation of chest wall pain that is frequently interpreted as breast pain.


Gynecology_Novak

Gynecology_Novak. Management of Mastalgia Breast pain is an unlikely symptom of malignancy, and when malignancy is excluded by a clinical breast examination and age-appropriate breast imaging for focal breast pain, the most important treatment is reassurance. Treatments include medications, such as anesthetics, diuretics, bromocriptine, and tamoxifen; vitamins and supplements, such as evening primrose oil; mechanical support with a well-fitting bra; local excision; and decreased fat intake and reduction in methylxanthines from caffeine, tea, and chocolate (108,116). Discontinuation of hormone therapy may be effective in some women. Maintenance of a pain score diary is important to understand the relationship of pain to factors such as the menstrual cycle, activities of daily living, and stress. External support may be effective for breast pain associated with generalized fibrocystic changes and is best treated by avoiding trauma and by wearing (night and day) a brassiere that gives good support and


Gynecology_Novak

Gynecology_Novak. support may be effective for breast pain associated with generalized fibrocystic changes and is best treated by avoiding trauma and by wearing (night and day) a brassiere that gives good support and protection (120). One study evaluated resolution of symptoms in 200 women randomized either to a regimen of danazol (200 mg per day) or to mechanical support with a sports brassiere worn for regular activities for 12 weeks. The group using mechanical support had 85% relief of symptoms compared with 58% improvement in the danazol group. Symptoms recurred after discontinuance of treatment with danazol (113). The danazol group experienced drug-related side effects in 42%, which led to discontinuance of the medication in 15%. The breast has minimal structural support and is at significant risk for motion-related displacement resulting in mastalgia. The use of external support to minimize breast motion appears to be effective in reducing breast pain. The application of heat packs or cold packs


Gynecology_Novak

Gynecology_Novak. motion-related displacement resulting in mastalgia. The use of external support to minimize breast motion appears to be effective in reducing breast pain. The application of heat packs or cold packs and light breast massage may reduce symptoms in some individuals (116).


Gynecology_Novak

Gynecology_Novak. Hormone-modulating drugs, including danazol, bromocriptine, tamoxifen, and Depo-Provera, are recognized drug treatments for mastalgia, although tamoxifen is not approved for this use in the United States (116,121–124). These drugs are associated with significant side effects that limit their general use (116). Withdrawal of birth control pills or hormone therapy may be all that is required to alleviate symptoms (116).


Gynecology_Novak

Gynecology_Novak. Danazol is a synthetic androgen that suppresses release of pituitary gonadotropin, prevents luteinizing hormone surge, and inhibits ovarian steroid formation. It is the only medication approved by the U.S. Food and Drug Administration for mastalgia (116). The androgenic effects—acne, edema, change in voice, weight gain, headaches, depression, and hirsutism— often are intolerable, and many patients stop taking danazol even when symptoms are improved (122). It can be initiated at doses of 100 to 200 mg twice daily orally for patients with severe pain and then tapered to a lower dose of 100 mg per day (122). A survey of surgeons in Great Britain revealed that 75% prescribed danazol as first-line therapy (108). A study conducted to evaluate the response to administration of danazol revealed a 79% amelioration of symptoms (125). This approach reduced the premenstrual mastalgia and resulted in virtually no side effects.


Gynecology_Novak

Gynecology_Novak. The use of oral progesterone agents reduces cyclical breast pain (111). Further studies may be warranted to see whether medroxyprogesterone acetate suppresses cyclic mastalgia in reproductive-age women. Breast pain is increased in some individuals who have elevated prolactin (PRL) levels induced by thyrotropin-releasing hormone (TRH) (116). Bromocriptine is a dopamine antagonist that inhibits the release of PRL. Bromocriptine (2.5 mg twice daily) given for 3 to 6 months is effective in reducing mastalgia in women who have TRH-induced elevation of PRL (123). Patients who have normal TRH levels, are resistant to bromocriptine, or do not tolerate the side effects of nausea, vomiting, and headache respond favorably to progesterone and systemic nonsteroidal anti-inﬂammatory drugs (NSAIDs).


Gynecology_Novak

Gynecology_Novak. Prolactin induces active transport of iodine in breast tissue (126,127). Iodine deficiency in rats causes hyperplasia and atypia (128). Iodine replacement is associated with improvement in subjective pain (129). A randomized, double-blind study with supraphysiologic levels of iodine in women with documented cyclic mastalgia demonstrated dose-dependent reduction in physician-assessed and self-reported pain at 3 and 6 months of treatment (130).


Gynecology_Novak

Gynecology_Novak. Goserelin is a potent synthetic analogue of luteinizing hormone-releasing hormone (LHRH) that causes reversible reduction in serum estrogen level and decrease in breast pain (131). Side effects of goserelin include vaginal dryness, hot ﬂushes, decreased libido, oily skin and hair, and decreased breast size. A recent clinical trial randomized 147 women into goserelin versus placebo groups. The study had a 49% drop-out rate. The mean breast pain score decreased by 67% in the goserelin arm and 35% in the placebo arm. The authors concluded that goserelin is an effective treatment for mastalgia with significant side effects and should be kept as second-line therapy. Hormonal blockade of the estrogen receptor is another approach to minimizing the effects of circulating estrogen on breast pain. Treatment with the selective estrogen receptor modulator tamoxifen demonstrated reduction in breast pain at 10 and 20 mg per day, with equivalent effects compared with danazol and bromocriptine in


Gynecology_Novak

Gynecology_Novak. Treatment with the selective estrogen receptor modulator tamoxifen demonstrated reduction in breast pain at 10 and 20 mg per day, with equivalent effects compared with danazol and bromocriptine in most studies (124,132–134). Topical nonsteroidal therapy is another option for women with mastalgia (135). Gel forms of NSAIDs often are used for relief of pain. Patients were stratified by cyclic versus noncyclic pain and then randomized to treatment with NSAIDs versus placebo. There was a significant reduction in cyclic and noncyclic pain in all groups, but the magnitude of change was greater in the treatment arms and similar for cyclic and noncyclic pain. Use of NSAIDs appears to be a less toxic treatment and may be considered as an option for both cyclic and noncyclic breast pain.


Gynecology_Novak

Gynecology_Novak. Nonhormonal therapies such as dietary restrictions, vitamins and supplements, and restriction of methylxantines were investigated as possible treatments for mastalgia because they are less likely to be associated with adverse drug-related side effects (116). Because mastalgia is one of the symptoms associated with fibrocystic disease, the treatments described for fibrocystic disease are relevant to mastalgia. A low-fat diet was effective in one randomized trial (136). Ninety percent of patients taking in 15% dietary fat experienced resolution of pain symptoms after 6 months compared with only 22% of those on a diet containing 36% fat (p = .0023). Evening primrose oil containing essential fatty acids (γ -linolenic acid [GLA]) was studied because of its affect on prostaglandin synthesis (137). It was used as first-line therapy, reserving danazol and bromocriptine for treatment of more severe symptoms (112). In a small prospective mastalgia trial, women were given eight capsules of


Gynecology_Novak

Gynecology_Novak. (137). It was used as first-line therapy, reserving danazol and bromocriptine for treatment of more severe symptoms (112). In a small prospective mastalgia trial, women were given eight capsules of evening primrose oil daily for 4 months (320 mg GLA) (138). Those who responded had a lower level of essential fatty acids at the time of initiation when compared with poor responders, suggesting that evening primrose oil increases essential fatty acids and that this increase may be associated with the improvement in symptoms in the responders. Two other trials failed to demonstrate efficacy of evening primrose oil capsules over placebo (139,140). In a Dutch trial, 124 women with cyclic or noncyclic pain lasting on average 7 or more days (minimum 5 days) were randomized to receive the following regimens: (i) fish oil and control oil, (ii) evening primrose oil and control oil, (iii) fish and evening primrose oil, or (iv) both control oils for 6 months (139). There was a statistically


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Gynecology_Novak. regimens: (i) fish oil and control oil, (ii) evening primrose oil and control oil, (iii) fish and evening primrose oil, or (iv) both control oils for 6 months (139). There was a statistically significant reduction in the number of days per month with pain but not in the pain score in the entire study population. There was a greater reduction in cyclic than noncyclic pain symptoms, and this finding was true for both the test oils and for the control oils. The authors concluded that neither fish oil nor evening primrose oil had a better effect than the less expensive wheat germ and corn oils. A second large double-blind randomized prospective trial was conducted in 555 women with cyclic mastalgia of moderate to severe degree present for at least 7 days of a menstrual cycle (140). The four groups were (i) GLA and placebo antioxidants, (ii) placebo fatty acids and antioxidants, (iii) GLA and placebo antioxidants, and (iv) placebo fatty acids and placebo antioxidants. The treatments were


Gynecology_Novak

Gynecology_Novak. groups were (i) GLA and placebo antioxidants, (ii) placebo fatty acids and antioxidants, (iii) GLA and placebo antioxidants, and (iv) placebo fatty acids and placebo antioxidants. The treatments were given in a blinded fashion for 4 months. All groups had a similar 35% reduction in symptoms. This treatment was followed by open treatment with GLA in all groups and blinded treatment with antioxidants. There was continued improvement of symptoms in all groups with a reduction in mastalgia by 50% over the next 12 months. This is the largest and best-controlled study to date evaluating GLA for relief of mastalgia, and GLA was not found to be superior to placebo. The results of this study were not consistent with those from previous smaller studies. The authors cannot exclude a significant psychologic impact that may confound the effect of GLA. GLA use was found to be safe, without any significant side effects, and was prescribed as therapy for mastalgia because of its lack of side effects.


Gynecology_Novak

Gynecology_Novak. impact that may confound the effect of GLA. GLA use was found to be safe, without any significant side effects, and was prescribed as therapy for mastalgia because of its lack of side effects. The randomized trials, however, bring into serious question the efficacy of these options.


Gynecology_Novak

Gynecology_Novak. Fibroadenoma Fibroadenomas are the most common benign tumors of the breast. In one series, they accounted for 50% of all breast biopsies (141). They usually occur in young women (age 20 to 35 years) and may occur in teenagers (142). In women younger than 25 years, fibroadenomas are more common than cysts. They rarely occur after menopause, although occasionally they are found, often calcified, in postmenopausal women. For this reason, it is postulated that fibroadenomas are responsive to estrogen stimulation. A study reports the de novo occurrence of fibroadenoma in 51 women older than age 35 years who had no evidence of a palpable or mammographic visualized lesion in well-documented prior visits (143). Fibroadenomas may appear as single masses or as multiple lesions.


Gynecology_Novak

Gynecology_Novak. Clinically, a young woman usually notices a mass while showering or dressing. Most masses are 2 to 3 cm in diameter when detected, but they can become extremely large (i.e., the giant fibroadenoma). On physical examination, they are firm, smooth, and rubbery. They do not elicit an inﬂammatory reaction, are freely mobile, and cause no dimpling of the skin or nipple retraction. They are often bilobed, and a groove can be palpated on examination. On mammographic and ultrasonographic imaging, the typical features are of a well-defined, smooth, solid mass with clearly defined margins and dimensions that are longer than wide and craniocaudad dimensions that are less than the length.


Gynecology_Novak

Gynecology_Novak. Fibroadenoma is not associated with an increased risk for breast cancer (144). The natural history of fibroadenoma can be regression, growth, or no change in size. Most fibroadenomas are static or cease growth at approximately 2 to 3 cm, about 15% of tumors regress spontaneously, and only 5% to 10% progress (145). Because transformation of a fibroadenoma into cancer is rare and regression is frequent, current management recommendations are conservative unless there is evidence of growth (141). A suspected fibroadenoma should be confirmed by FNAC or CNB and observed for increase in size or excised based on patient preference. Rarely will the fibroadenoma increase to more than 2 to 3 cm in size. Large or growing fibroadenomas must be excised. Complete excision of a fibroadenoma with local anesthesia can be performed to treat the lesion and confirm the absence of malignancy. Less invasive local treatment of a fibroadenoma is advocated by some and can be performed with either


Gynecology_Novak

Gynecology_Novak. with local anesthesia can be performed to treat the lesion and confirm the absence of malignancy. Less invasive local treatment of a fibroadenoma is advocated by some and can be performed with either ultrasonographically guided percutaneous vacuum-assisted biopsy devices or percutaneous cryoablation (146,147). A young woman with a clinical fibroadenoma can undergo needle cytology and observation of the mass (148). Acceptance of observation varies, and many women choose to have the fibroadenoma excised (149).


Gynecology_Novak

Gynecology_Novak. On gross examination of an excised mass, the fibroadenoma appears encapsulated and sharply delineated from the surrounding breast parenchyma. Microscopically, there is proliferation of both the epithelial and stromal component. In longstanding lesions and in postmenopausal patients, calcifications may be observed within the stroma.


Gynecology_Novak

Gynecology_Novak. Multiple Fibroadenomas Multiple fibroadenomas occur in some women and were reported to occur more frequently in premenopausal women undergoing immunosuppression for transplant (150–152). Excision of all lesions through separate incisions could leave significant scarring and deformity. Excision of these mobile lesions through a single periareolar incision was suggested, but this approach can lead to significant ductal disruption (153). Another approach is through an incision in the inframammary crease. Alternatively, these lesions can be treated with observation based on triple-test concordance of results of a classic clinical examination with histologic corroboration with FNAC and ultrasonographic diagnostic criteria consistent with a fibroadenoma (151).


Gynecology_Novak

Gynecology_Novak. Phyllodes Tumor Phyllodes tumors are rare fibroepithelial tumors that display a spectrum of clinical and pathologic behaviors that are benign, borderline, and malignant (154,155). The distribution of phyllodes tumors demonstrates that most tumors are benign (70%) compared with malignant (23%) and borderline lesions (7%) (156). This distribution is similar to a larger, older study that reported an incidence of 64% benign, 21% malignant, and 14% borderline phyllodes tumors (157). The incidence in some studies should be viewed with caution because of variation in histologic interpretation (156). Phyllodes tumors may occur at any age but tend to be more common in women who are in their late 30s, 40s, and 50s (156,158–162). These lesions are rarely bilateral and usually appear as isolated masses that are difficult to distinguish clinically from a fibroadenoma. Patients often relate a long history of a previously stable nodule that suddenly increases in size. Reported sizes range from 1.0


Gynecology_Novak

Gynecology_Novak. that are difficult to distinguish clinically from a fibroadenoma. Patients often relate a long history of a previously stable nodule that suddenly increases in size. Reported sizes range from 1.0 to 50 cm (154,163,164). Size is not a dependable diagnostic criterion, although phyllodes tumors tend to be larger than fibroadenomas, probably because of their rapid growth. There are no good clinical criteria by which to distinguish a phyllodes tumor from a fibroadenoma. Whereas observation of a fibroadenoma is acceptable, excision of a phyllodes tumor is necessary for local control and for determination of benign or malignant features. To avoid unnecessary excision of benign fibroadenomas that are indistinguishable from phyllodes tumors on clinical examination, imaging criteria were sought to aid in identifying patients who require EB for complete histopathologic evaluation and local control. Mammography may show a halo around a phyllodes tumor mass but cannot reliably distinguish a


Gynecology_Novak

Gynecology_Novak. to aid in identifying patients who require EB for complete histopathologic evaluation and local control. Mammography may show a halo around a phyllodes tumor mass but cannot reliably distinguish a fibroadenoma from a phyllodes tumor (165–167). Ultrasonography evaluation has limitations even when color and pulse Doppler ultrasonography are used in conjunction with it (163).


Gynecology_Novak

Gynecology_Novak. Microscopic evaluation of a lesion is important to determine the diagnosis. The histologic distinction between fibroadenoma, benign, borderline, and malignant phyllodes tumor can be very difficult on minimal tissue sampling with FNAC or CNB (168,169). It may be easier to distinguish benign phyllodes from malignant phyllodes tumors than benign phyllodes tumors from fibroadenomas (170). Histologic features that stratify lesions include number of mitoses per high power field, stromal cellularity, pushing or infiltrating tumor margin, cellular atypia, tumor necrosis, and stromal overgrowth (171). If a lesion cannot be clearly characterized as a fibroadenoma, excision may be necessary.


Gynecology_Novak

Gynecology_Novak. If a lesion cannot be clearly characterized as a fibroadenoma, excision may be necessary. Factors that are considered in recommending excision include older age, new mass in a well-screened individual, rapid growth, size greater than 2.5 to 3 cm, suspicious FNAC or CB, and mammographic or ultrasonographic features that demonstrate lobulation and intramural cysts. If observation is elected, repeat clinical examination and imaging in a short interval is essential to evaluate change in size.


Gynecology_Novak

Gynecology_Novak. Treatment of biopsy-proven phyllodes tumor is wide local excision, attempting to obtain a 1-to 2-cm margin (156–161). Massive tumors, or large tumors in relatively small breasts, may require mastectomy; otherwise, mastectomy should be avoided, and axillary lymph node dissection is not indicated. Often, however, a patient will undergo excisional biopsy of a mass believed to be fibroadenoma, and final histologic examination reveals a phyllodes tumor. Reexcision with normal breast margins is recommended for borderline and malignant phyllodes tumors (159). An expectant approach is an option for unanticipated diagnosis of benign phyllodes tumors (157). The prognosis of benign and malignant phyllodes tumors is variable (154,155,157,162,172).


Gynecology_Novak

Gynecology_Novak. The prognosis of benign and malignant phyllodes tumors is variable (154,155,157,162,172). Tumors judged to be benign phyllodes tumors can recur locally in up to 10% of patients (159–161). Recurrence is associated with margin involvement, whereas mortality correlates with size and grade (173). In a series reviewing only high-grade malignant phyllodes tumors, size and excision margins were associated with local recurrence and metastatic spread, and mastectomy may be required to achieve complete surgical excision (174). Malignant phyllodes tumors tend to recur locally and occasionally may metastasize to the lung, although brain, pelvic, and bone metastases also may occur (160–162). The stromal component of the tumor is malignant and metastasizes, behaving like a sarcoma. Axillary involvement is extremely unusual. Often, the appearance of metastasis is the first sign that a phyllodes tumor is malignant.


Gynecology_Novak

Gynecology_Novak. Chemotherapy for metastatic phyllodes tumors should be based on regimens for sarcoma, not adenocarcinoma (159). Radiation therapy generally is not used in the treatment of phyllodes tumors. In the presence of a bulky tumor, positive margins, recurrence, or malignant histology, radiation therapy may be of some benefit (175).


Gynecology_Novak

Gynecology_Novak. Nipple Discharge Nipple discharge is a presenting breast symptom in 4.5% of patients seeking evaluation of a breast symptom, with 48% spontaneous and 52% provoked (176). Nipple discharge that does not occur spontaneously has no pathologic significance. Provoked or self-induced nipple discharge should be managed by reassurance and instruction to discontinue manipulation. Spontaneous nipple discharge is more likely to be associated with an underlying pathologic problem than provoked discharge. Although it is a distressing finding, spontaneous nipple discharge is infrequently found to be associated with carcinoma, ranging from 4% to 10% (176–178). Nipple discharge can be caused by neoplastic or nonneoplastic processes (179). Nonneoplastic processes include galactorrhea, physiologic changes resulting from mechanical manipulation, parous condition, periductal mastitis, subareolar abscess, fibrocystic change, and mammary duct ectasia. Neoplastic causes of nipple discharge in nonlactating


Gynecology_Novak

Gynecology_Novak. resulting from mechanical manipulation, parous condition, periductal mastitis, subareolar abscess, fibrocystic change, and mammary duct ectasia. Neoplastic causes of nipple discharge in nonlactating women are solitary intraductal papilloma, carcinoma, papillomatosis, squamous metaplasia, and adenosis (176,179,180). Extramammary causes are related to hormones and drugs (179). Following are the important characteristics of the discharge and other factors to be evaluated by history and physical examination (180): 1.


Gynecology_Novak

Gynecology_Novak. Nature of discharge (serous, bloody, or milky) 2. Association with a mass 3. 4. 5. Discharge that is spontaneous (persistent or intermittent) or expressed by pressure at a single site or on entire breast 6. Relation to menses 7. 8.


Gynecology_Novak

Gynecology_Novak. Unilateral, spontaneous, bloody, or serosanguinous discharge from a single duct is usually caused by an intraductal papilloma or, rarely, by an intraductal cancer. In either case, a mass may not be palpable. The involved duct may be identified by pressure at different sites around the nipple and at the margin of the areola. Bloody discharge is more suggestive of cancer but usually is caused by a benign papilloma in the duct. In premenopausal women, spontaneous multiple-duct discharge, unilateral or bilateral, is most marked just before menstruation. It often is caused by fibrocystic change. Discharge may be green or brownish. Papillomatosis and ductal ectasia are usually seen on biopsy. If a mass is present, it should be removed. Milky discharge from multiple ducts in nonlactating women presumably reﬂects increased secretion of pituitary prolactin; serum prolactin and thyroid-stimulating hormone levels should be evaluated to detect a pituitary tumor or hypothyroidism. Hypothyroidism


Gynecology_Novak

Gynecology_Novak. presumably reﬂects increased secretion of pituitary prolactin; serum prolactin and thyroid-stimulating hormone levels should be evaluated to detect a pituitary tumor or hypothyroidism. Hypothyroidism may cause galactorrhea. Alternatively, phenothiazines may cause milky discharge that disappears when the medication is discontinued. Oral contraceptive agents may cause clear, serous, or milky discharge from multiple ducts or, less often, from a single duct. The discharge is more evident just before menstruation and disappears when the medication is stopped.


Gynecology_Novak

Gynecology_Novak. Chronic unilateral nipple discharge, especially if it is bloody, is an indication for resection of the involved ducts. Mammography and ultrasonography are performed to rule out an associated mass. On occasion, ductography may be performed to identify a filling defect before excision of the duct system, but usually this technique is of little value (178). Ductography is not a substitute for excision because it misses multiple lesions and cannot visualize the periphery (181). Fiberoptic ductoscopy is a technology used to evaluate patients with nipple discharge (182). In 259 patients with nipple discharge, fiberoptic ductoscopy successfully detected intraductal


Gynecology_Novak

Gynecology_Novak. Fiberoptic ductoscopy is a technology used to evaluate patients with nipple discharge (182). In 259 patients with nipple discharge, fiberoptic ductoscopy successfully detected intraductal Erosive Adenomatosis of the Nipple papillary lesions in 92 patients (36%). Office-based, minimally invasive breast ductoscopy with intraductal biopsy is available in some centers (183,184). It was performed for diagnosis in 83 patients with nipple discharge (183). A diagnosis of severe or malignant atypia was established in 21% of patients.


Gynecology_Novak

Gynecology_Novak. Cytologic examination of nipple discharge or cyst ﬂuid rarely is performed. Cytologic examination usually is of no value but may identify malignant cells (178). Negative findings do not rule out cancer, which is more likely in women older than 50 years of age. In any case, the involved duct—and a mass, if present—should be excised (177,178,180,185). Complete histopathologic evaluation of the involved ductal system is the preferred method of diagnosis, and cytologic assessment should not be relied on for diagnosis.


Gynecology_Novak

Gynecology_Novak. The usual approach for nipple discharge is surgical excision through a periareolar incision adjacent to the trigger point, the pressure point that elicits nipple discharge (179). A microdochetomy of a single duct or a central duct excision of the major subareolar ducts can be performed under local or general anesthesia. The putative duct can be cannulated, methylene blue can be injected, or a lacrimal probe can be inserted into the duct for localization. A resection of breast tissue for 3 to 5 cm, or until no bloody ﬂuid can be identified in the ductal system, is performed. The patient must be warned of possible skin and nipple loss as a result of compromised vascularity, change in nipple sensation, deformity, inability to breastfeed, and recurrence if only a single duct if removed.


Gynecology_Novak

Gynecology_Novak. When there is a history of unilateral nipple discharge, localization is not possible, and no mass is palpable, the patient should be reexamined every week for 1 month. When unilateral discharge persists, even without definite localization or tumor, surgical exploration should be considered. The alternative is careful follow-up at intervals of 1 to 3 months. Mammography should be performed. Purulent discharge may originate in a subareolar abscess and requires excision of the related lactiferous sinus (186).


Gynecology_Novak

Gynecology_Novak. Erosive adenomatosis is a rare benign condition of the nipple that mimics Paget’s disease (187). Patients seek treatment for pruritus, burning, and pain. On clinical examination, the nipple can appear ulcerated, crusting, scaling, indurated, and erythematous. The nipple can be enlarged and more prominent during menstrual cycles (188). The differential diagnosis includes squamous cell carcinoma, psoriasis, contact dermatitis, seborrheic keratosis, adenocarcinoma metastatic to the skin, and unusual primary tumors of the nipple (187). Biopsy should be performed to diagnose the lesion. Local excision is curative (187). 10 days. If the lesion progresses to a localized mass with local and systemic signs of infection, an abscess is present. It should be drained, and breastfeeding should be discontinued.


Gynecology_Novak

Gynecology_Novak. Nonlactational Abscess Rarely, infections or abscesses may develop in young or middle-aged women who are not lactating (193). The approach to nonlactational abscess is conservative (194,195). A suspected abscess should be evaluated with preliminary ultrasonography to detect the presence of an inﬂammatory mass, frank pus, solitary cavity, or a multiloculated abscess (196). Aspiration of pus, if present, and antibiotic therapy is instituted with reaspiration, if necessary (196). When the ﬂuid collection is greater than 3 mL, percutaneous drain placement is an option (194). A single aspiration is sufficient in about one-half of patients (194). Recurrent abscess formation is low (10%) (194). Bacteriologic analysis of 190 abscesses in nonlactating and lactating women showed a preponderance of gram-positive cocci. S. aureus was the most common organism isolated (51.3%). Of these, 8.6% were methicillin-resistant S. aureus. Other common organisms included mixed anaerobes (13.7%) and anaerobic


Gynecology_Novak

Gynecology_Novak. cocci. S. aureus was the most common organism isolated (51.3%). Of these, 8.6% were methicillin-resistant S. aureus. Other common organisms included mixed anaerobes (13.7%) and anaerobic cocci (6.3%) (196). If these infections recur after multiple aspirations, incision and drainage followed by excision of the involved lactiferous duct or ducts at the base of the nipple may be necessary during a quiescent interval. In virtually all cases, mammillary sinus (lactiferous duct fistula) can be confirmed as the cause of reinfection or persistent infection (197). Inﬂammatory carcinoma is a consideration when erythema of the breast is present. Patients should not undergo prolonged treatment for an apparent infection unless biopsy eliminated the possibility of inﬂammatory carcinoma.


Gynecology_Novak

Gynecology_Novak. Disorders of Breast Augmentation Estimates indicate that nearly 4 million women in the United States have undergone augmentation mammoplasty. Breast implants are usually placed under the pectoralis muscle or, less desirably, in the subcutaneous tissue of the breast. Most implants are made of an outer silicone shell filled with a silicone gel or saline.


Gynecology_Novak

Gynecology_Novak. The complications of breast implantation are significant. Rates of contracture vary in the literature from less than 10% to over 60%. Capsular contraction or scarring around the implant, leading to firmness and distortion of the breast, can be painful and sometimes requires removal of the implant and capsule. Implant rupture may occur in as many as 5% to 10% of women, and bleeding of gel through the capsule is even more common (201). In 2006, the U.S. Food and Drug Administration approved silicone gel filled implants for use in women 22 years or older for cosmetic purposes and for reconstruction after breast surgery or in women with traumatic or congenital breast defects (202). The agency recommends MRI scanning 3 years after the first implant surgery and then every 2 years for the detection of implant rupture.


Gynecology_Novak

Gynecology_Novak. The agency advised symptomatic women with ruptured implants to discuss the need for surgical removal with their physicians. When there is no evidence of associated symptoms or rupture, implant removal is generally not indicated because the risks of removal are probably greater than the risk of retention. If screening ultrasonography shows no rupture, the probability of rupture is 2.2% (203). If ultrasonography shows rupture, true rupture is present in 37.8%. In this setting, a large number of women would have normal implants removed. When MRI is used in addition to ultrasonography, the probability of rupture increases to 86%.


Gynecology_Novak

Gynecology_Novak. The suggested association between silicone gel and autoimmune disease is poorly documented (204,205). Among the multiple meta-analyses conducted thus far, none have identified a significant association between breast implants and connective-tissue disease (206). Subsequent studies demonstrated no clinical data proving an increased incidence of connective tissue disorders in patients with silicone gel breast implants (207–209). The data continue to reaffirm previous observations that there is no evidence of an association between breast implants and connective tissue diseases (210). In a study of Danish women undergoing reduction mammoplasty compared with silicone implant augmentation, there was no increased incidence of antinuclear antibodies or other autoantibodies between the groups (211). The augmentation group experienced capsular contraction and more pain than the group undergoing reduction mammoplasty. Any association between implants and an increased incidence of breast cancer


Gynecology_Novak

Gynecology_Novak. The augmentation group experienced capsular contraction and more pain than the group undergoing reduction mammoplasty. Any association between implants and an increased incidence of breast cancer is unlikely (212). Breast cancer may develop in any patient with a silicone gel prosthesis.


Gynecology_Novak

Gynecology_Novak. 1. Pearlman, MD, Giffin JL. Benign breast disease. Obstet Gynecol 2010;116:747–747. 2. Harris J, Morrow M, Lippman M, et al. Diseases of the breast. Philadelphia: Lippincott Williams & Wilkins, 2009. 3. Miltenburg DM, Speights VO Jr. Benign breast disease. Obstet Gynecol Clin North Am 2008;35:285–300. 4. Gail Risk Assessment. Breast cancer risk assessment tool. Available online at: http://www.cancer.gov/bcrisktool 5. O’Brien MM, Donaldson SS, Balise RR, et al. Second malignant neoplasms in survivors pediatric Hodgkin’s lymphoma treated with low-dose radiation and chemotherapy. J Clin Oncol 2010;28:1232– 1239. 6. Rodden AM. Common breast concerns. Prim Care 2009;36:103– 113. 7. Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States, 2008: a review of current American Cancer Society guidelines and cancer screening issues. CA Cancer J Clin. 2008;58:161–179. 8.


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Gynecology_Novak. 8. Kosters JP, Gotzsche PC. Regular self-examination or clinical examination for early detection of breast cancer. Cochrane Database Syst Rev 2003;2:CD003373. 9. Austoker J. Breast self examination. BMJ 2003;326:1–2. 10. Weiss NS. Breast cancer mortality in relation to clinical breast examination and breast self-examination. Breast J 2003;9:86–89. 11. Nelson HD, Tyne K, Naik A, et al. Screening for breast cancer: systematic evidence review update for the US Preventative Services Task Force. Rockville (MD) Agency Healthcare Res Qual (US); 2009;1005142-EF-1. 12. Newcomer L, Newcomb P, Trentham-Dieatz A, et al. Detection method and breast carcinoma histology. Cancer 2002;95:470–477. 13. van Dooren S, Rijnsburger AJ. Psychological distress and breast self-examination frequency in women at increased risk for hereditary or familial breast cancer. Community Genet 2003;6:235–241. 14. Breast self-examination tutorial. Available online at: http://www.


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Gynecology_Novak. 14. Breast self-examination tutorial. Available online at: http://www. komen.org/bse http://ww5.komen.org/BreastCancer/BreastSelf Awareness.html?ecid=vanityurl:28 15. Committee on Technologies for the Early Detection of Breast Cancer. Mammography and beyond: developing technologies for the early detection of breast cancer. Washington, DC: National Academy Press, 2005. 16. Lewin J, Hendrick RE, D’Orsi CJ, et al. Comparison of full-field digital mammography with screen-film mammography for cancer detection: results of 4,945 paired examinations. Radiology 2001;218:873–880. 17. Nees AV. Digital mammography: are there advantages in screening for breast cancer? Acad Radiol 2008;15:401–407. 18. Pisano E, Gatsonis C, Hendrick E, et al. Diagnostic performance of digital versus film mammography for breast cancer screening. N Engl J Med 2005;353:1773–1783. 19. Paquelet JR, Hendrick RE. Lesion size inaccuracies in digital mammography. AJR Am J Roentgenol 2010;194:115–118. 20.


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Gynecology_Novak. 19. Paquelet JR, Hendrick RE. Lesion size inaccuracies in digital mammography. AJR Am J Roentgenol 2010;194:115–118. 20. Buist DS, Porter PL, et al. Factors contributing to mammography failure in women age 40–49 years. J Natl Cancer Inst 2004;96:1432– 1440. 21. Palka I, Kelemen G, Ormandi K, et al. Tumor characteristics in screen-detected and symptomatic breast cancers. Pathol Oncol Res 2008;14:161–167. 22. Hendrick RE, Pisano ED, Averbukh A, et al. Comparison of acquisition parameters and breast dose in digital mammography and screen-film mammography in the American College of Radiology Imaging Network digital mammographic imaging screening trial. AJR Am J Roentgenol 2010;194:362–369. 23. Bassett L, Liu TH, Giuliano AE, et al. The prevalence of carcinoma in palpable vs. impalpable, mammographically detected lesions. Am J Roentgenol 1991;157:21–24. 24. Tice JA, Kerlikowse K. Screening and prevention of breast cancer in primary care. Prim Care 2009;36:533–558. 25.


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Gynecology_Novak. 24. Tice JA, Kerlikowse K. Screening and prevention of breast cancer in primary care. Prim Care 2009;36:533–558. 25. Nystrom L, Anderson T, Bjurstam N, et al. Long-term effects of mammography screening: updated overview of the Swedish randomised trials. Lancet 2002;359:909–919. 26. Miller A, To T, Baines CJ, et al. National breast screening study-1: breast cancer mortality after 11 to 16 years of follow-up: a randomized screening trial of mammography in women age 40–49 years. Ann Intern Med 2002;137:305–312. 27. Miller A, To T, Baines CJ, et al. Canadian national breast screening study-2: 13-year results of a randomized trial in women aged 50–59 years. J Natl Cancer Inst 2000;92:1490–1499. 28. Duffy S, Tabar L, Smith R. The mammographic screening trials: commentary on the recent work of Olsen Gotzsche. CA Cancer J Clin 2002;52:68–71. 29.


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Gynecology_Novak. 28. Duffy S, Tabar L, Smith R. The mammographic screening trials: commentary on the recent work of Olsen Gotzsche. CA Cancer J Clin 2002;52:68–71. 29. Alexander F, Anderson T, Brown HK, et al. 14 years of follow-up from the Edinburgh randomised trial of breast-cancer screening. Lancet 1999;353:1903–1908. 30. Kalager M, Zelen M, Langmark F, et al. Effect of screening mammography on breast-cancer specific mortality in Norway. N Engl J Med 2010;363:1203–1210. 31. Tabar L, Vitak B, Chen, HH, et al. Two-county trial twenty years later: updated mortality results and new insights from long-term follow-up. Radiol Clin North Am 2000;38:625–651. 32. UKDG, UK Trials of Early Detection of Breast Cancer Group. 16-year mortality from breast cancer in the UK trial of early detection of breast cancer. Lancet 1999;353:1909–1914. 33.


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Gynecology_Novak. 36. American Geriatrics Society Clinical Practice Committee. AGS position statement: breast cancer screening in older women. JAm Geriatr Soc 2000;48:842–844. 37. Mandelblatt JS, Schechter CB, Yabroff KR, et al. Toward optimal screening strategies for older women. Costs, benefits and harms of breast cancer screening by age, biology and health status. J Gen Intern Med 2005;20:487–496. 38. Schonberg MA, Silliman RA, Marcantonio ER. Weighing the benefits and burdens of mammography screening among women age 80 years or older. J Clin Oncol 2009;27:1774–1780. 39. Badgwell BD, Giordano SH, Duan ZZ, et al. Mammography before diagnosis among women age 80 years and older with breast cancer. J Clin Oncol 2008;26:2482–2488. 40. U.S. Preventative Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009;151:716–726. 41.


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Gynecology_Novak. 40. U.S. Preventative Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2009;151:716–726. 41. Smith RA, Cokkinides V, Brooks D, et al. Cancer screening in the United States, 2010: a review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin 2010;60:99–119. 42. Albert RH, Clark MM. Cancer screening in the older patient. Am Fam Phys 2008;78:1369–1374. 43. American College of Radiology. Breast imaging reporting and data system (BI-RADS). 4rd ed. Reston, VA: American College of Radiology, 2003. 44. Elmore J, Armstrong K, Lehman C, et al. Screening for breast cancer. JAMA 2005;293:1245–1256. 45. Weigel S, Decker T, Korsching E, et al. Calcifications in digital mammographic screening; improvement of early detection of invasive breast cancer? Radiology 2010;255:738–745. 46.


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Gynecology_Novak. 45. Weigel S, Decker T, Korsching E, et al. Calcifications in digital mammographic screening; improvement of early detection of invasive breast cancer? Radiology 2010;255:738–745. 46. Lanzieri CF, Molter JP, Legan GJ. University Hospitals of Cleveland. Available online at: uhrad.com//mamarc.htm 47. Lazarus E, Mainiero MB, Schepps B, et al. BI-RADS lexicon for UD and mammography interobserver variability and PPV. Radiology 2006;239:385–391. 48. Parikh JR. ACR appropriateness criteria on palpable breast masses. J Am Coll Radiol 2007;285–288. 49. Carney P, Miglioretti D, Yankaskas BC, et al. Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography. Ann Intern Med 2003;138:168–175. 50. Stone J, Warren RM, Pinney E, et al. Determinants of percentage and area measures of mammographic density. Am J Epidemiol 2009;170:1571–1578. 51.


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Gynecology_Novak. 50. Stone J, Warren RM, Pinney E, et al. Determinants of percentage and area measures of mammographic density. Am J Epidemiol 2009;170:1571–1578. 51. Madjar H. Role of breast ultrasound for the detection and differentiation of breast lesions. Breast Care 2010;5:109–114. 52. Dillion MF, Hill AD, Quinn CM, et al. The accuracy of ultrasound, stereotactic and clinical core biopsies in the diagnosis of breast cancer with an analysis of false negative cases. Ann Surg 2005;242:701– 707. 53. Kelly KM, Dean J, Columada WS, et al. Breast cancer detection using automated whole breast ultrasound and mammography in radiologically dense breasts. Eur Radiol 2010;20:734–742. 54. Nothacker M, Duda V, Hahn M, et al. Early detection of breast cancer: benefits and risk of supplemental breast ultrasound in asymptomatic women with mammographically dense breast tissue. A systematic review. BMC Cancer 2009;9:335–344. 55.


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Gynecology_Novak. 55. Irwig L, Houssami N, van Vliet C. New technologies in screening for breast cancer: a systematic review of their accuracy. Br J Cancer 2004;90:2118–2122. 56. Hong AS, Rosen E, Soo MS, et al. BI-RADS for sonography: positive and negative predictive values of sonographic features. AJR Am J Roentgenol 2005;184:1260–1265. 57. Chang YW, Kwon KH, Goo DE, et al. Sonographic differentiation of benign and malignant cystic lesions of the breast. J Ultrasound Med 2007;26:47–53. 58. Weinstein S, Rosen M. Breast MR imaging: current indications and advanced imaging techniques. Radiol Clin North Am 2010;48:1013– 1042. 59. Veronesi U, De Cicco C, Galimberti VE, et al. A comparative study on the value of FDG-PET and sentinel node biopsy to identify occult axillary metastases. Ann Oncol 2007;18:473–478. 60. Buchanan Cl, Morris EA, Dorn PL, et al. Utility of breast magnetic resonance imaging in patients with occult primary breast cancer. Ann Surg Oncol 2005;12:1045–1053. 61.


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Gynecology_Novak. 60. Buchanan Cl, Morris EA, Dorn PL, et al. Utility of breast magnetic resonance imaging in patients with occult primary breast cancer. Ann Surg Oncol 2005;12:1045–1053. 61. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening and MRI as an adjunct to mammography. CA Cancer J Clin 2007;57:75–89. 62. Kriege M, Brekelmans C, Coetes C, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 2004;351:427– 437. 63. Tafra L. Positron emission tomography (PET) and mammography (PEM) for breast cancer: importance to surgeons. Ann Surg Oncol 2007;14:3–13. 64. Berner A, Davidson B, Sigstad E, et al. Fine-needle aspiration cytology vs. core biopsy in the diagnosis of breast lesions. Diagn Cytopathol 2003;29:344–348. 65.


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Gynecology_Novak. 64. Berner A, Davidson B, Sigstad E, et al. Fine-needle aspiration cytology vs. core biopsy in the diagnosis of breast lesions. Diagn Cytopathol 2003;29:344–348. 65. Bruening W, Schoelles K, Treadwell J, et al. Comparative effectiveness of core-needle and open surgical biopsy for the diagnosis of breast lesions. Agency for Healthcare Research and Quality. Dec. 2009. Report NO. 10-EHC007-EF. 66. Ough M, Velasco J, Hieken T. A comparative analysis of core needle biopsy and final excision for breast cancer: histology and marker expression. Am J Surg 2010;201:685–687. 67. Usami S, Moriya T. Pathological aspects of core needle biopsy for non-palpable breast lesions. Breast Cancer 2005;12:272–278. 68. Fajardo LL, Pisano ED. Radiologist investigators of the radiologic diagnostic oncology group V: stereotactic and sonographic large-core biopsy of nonpalpable breast lesions. Acad Radiol 2004;11:293–308. 69.


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Gynecology_Novak. 69. Bevers T, Anderson B, Borgen P, et al. Breast cancer screening and diagnosis. NCCN Practice Guidelines in Oncology 2004;1:1–74. 70. Kerlikowske K, Smith-Bindman, Ljung BM, et al. Evaluation of abnormal mammography results and palpable breast abnormalities. Ann Intern Med 2003;139:274–284. 71. Brazda A, Estroff J. Delays in time to treatment and survival impact in breast cancer. Ann Surg Oncol 2010;17:291–296. 72. Abati A, Simsir A. Breast fine needle aspiration biopsy: prevailing recommendations and contemporary practices. Clin Lab Med 2005;25:631–654. 73. Morris AM, Flowers CR. Comparing the cost effectiveness of the triple test score to traditional methods for evaluating palpable breast masses. Med Care 2003;41:962–971. 74. Ahmed I, Nazir R, Chaudhary MY, et al. Triple assessment of breast lump. J Coll Physician Surg 2007;17:535–538. 75.