© 2007 WebMD, Inc. All rights reserved.                                                     ACS Surgery: Principles and Pr...
© 2007 WebMD, Inc. All rights reserved.                                               ACS Surgery: Principles and Practice...
© 2007 WebMD, Inc. All rights reserved.                                                            ACS Surgery: Principles...
© 2007 WebMD, Inc. All rights reserved.                                                     ACS Surgery: Principles and Pr...
© 2007 WebMD, Inc. All rights reserved.                                                            ACS Surgery: Principles...
© 2007 WebMD, Inc. All rights reserved.                                                         ACS Surgery: Principles an...
© 2007 WebMD, Inc. All rights reserved.                                                      ACS Surgery: Principles and P...
© 2007 WebMD, Inc. All rights reserved.                                                       ACS Surgery: Principles and ...
© 2007 WebMD, Inc. All rights reserved.                                                                          ACS Surge...
© 2007 WebMD, Inc. All rights reserved.                                                                                ACS...
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Acs0309 Benign Breast Disease

  1. 1. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 9 Benign Breast Disease — 1 9 BENIGN BREAST DISEASE Doreen M. Agnese, M.D., F.A.C.S., Stephen P. Povoski, M.D., F.A.C.S., and Wiley W Souba, M.D., Sc.D., F.A.C.S. . One in two women will PHYSICAL EXAMINATION consult a health care A thorough physical examination is an essential second step in provider for a breast-relat- the evaluation of any patient with a breast complaint. The breasts ed complaint during her should be inspected for any asymmetry, skin or nipple changes, lifetime.1 Accordingly, all nipple retraction, erythema, or peau d’orange (orange-peel appear- clinicians should have a ance). Skin dimpling can be accentuated by having the patient sit fundamental understand- with her hands pushing against her hips to contract the pectoral ing of the evaluation and muscles. Each breast should then be carefully palpated from the management of breast dis- clavicle to below the inframammary fold and from the sternum to orders. Although most breast complaints do not result in a diag- the posterior axillary line, with careful attention to the subareolar nosis of cancer, women who present with symptoms suggestive area. Palpation is done with the patient both supine and sitting. If of a breast disorder experience substantial anxiety and a sense of examination identifies an abnormal area, the location, size, consis- urgency about their symptoms. Therefore, any woman present- tency, contour, tenderness, and mobility of the abnormality ing with a breast complaint should receive a comprehensive eval- should be described; a diagram of the lesion may also be made for uation. The fundamental task facing a physician who is evaluat- future reference. Benign masses tend to have smooth, regular bor- ing a patient with a breast complaint is to determine whether the ders and are freely mobile. Although certain physical findings abnormality is benign or malignant. In this chapter, we focus on (e.g., skin changes, irregular borders, firmness, irregular margins, the evaluation and management of benign breast conditions. and immobility) are associated with a greater likelihood of cancer, Breast cancer is discussed in greater detail elsewhere [see 3:1 their absence does not exclude the diagnosis of cancer. Breast Cancer]. The axillary, supraclavicular, and infraclavicular areas should then be palpated bilaterally for suspicious adenopathy. If enlarged nodes Clinical Evaluation are discovered, their size, mobility, and number should be record- ed. Any matting of nodes or fixation of nodes to the chest walls HISTORY should also be recorded. Tenderness of enlarged nodes may sug- gest a reactive process and should therefore be recorded as well. The first step in the eval- uation of any breast com- plaint is a complete history. Investigative Studies The duration of the breast complaint, any observed IMAGING changes, and all associated symptoms should be recorded. Changes in the size or tenderness Mammography of any palpable abnormalities since their initial discovery are par- The first imaging study employed to evaluate breast abnormal- ticularly important, and special attention should be paid to how ities is bilateral mammography. Diagnostic mammography is a these changes may relate to the menstrual cycle. Previous breast more comprehensive examination than screening mammography, complaints, breast biopsies, and breast operations should also be consisting of multiple specialized images (e.g., magnification views documented, and pathology reports from any such interventions or spot compression views). Digital mammography is now being should be obtained. All imaging studies or medical evaluations used with increasing frequency in this setting. It has a number of that have already been performed should be reviewed. advantages over film-screen mammography, including lower radi- Next, the clinician should identify any risk factors for breast ation doses and easier image storage. Overall, digital mammogra- cancer that may be present. A reproductive history should be phy is not significantly better at detecting malignancies, but there obtained that notes age at menarche, age at menopause, parity, are certain subgroups that may derive particular benefit from this and age at first full-term pregnancy. A thorough personal and fam- modality, including younger women with denser breast tissue.2 ily history of other malignancies, with particular attention to breast, ovarian, or endometrial cancer, should be obtained. Both Ultrasonography maternal and paternal family histories play important roles in Ultrasonography is employed mainly to distinguish cystic from determining risk. The patient’s use of oral contraceptives, fertility solid lesions.When the patient has a palpable lesion, direct needle hormones, or postmenopausal hormone replacement therapy aspiration, which is both diagnostic and therapeutic, can also be should be noted as well. used for this purpose.When the patient has a nonpalpable lesion, Finally, as with any surgical patient, an overview of the gen- ultrasonography can determine whether the lesion is cystic and eral medical history should be obtained that includes current thus may eliminate the need for additional workup or treatment. medications, allergies, tobacco and alcohol use, previous surgi- Ultrasonography is not useful for screening: it fails to detect calci- cal procedures, medical problems, and a brief social history. fications, misses a large number of malignancies, and identifies a
  2. 2. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 9 Benign Breast Disease — 2 Patient presents with breast complaint The most common presenting problems are Assessment and • Palpable mass • Normal physical examination with abnormal mammogram • Vague thickening or nodularity • Nipple discharge • Breast pain Management of • Breast infection or inflammation Breast Complaints Evaluate likelihood that lesion reflects cancer and be aware of patient risk factors for cancer [see Table 2]. Palpable mass Abnormal mammogram after Vague thickening or nodularity normal breast examination Factors increasing suspicion of Factors increasing suspicion of malignancy: Factors increasing suspicion of malignancy: • Skin dimpling malignancy: • Skin changes • Palpable axillary nodes • Previous normal mammogram • Asymmetry between right and left • Mass with irregular borders • Localized soft tissue mass breast • Increasing age • Stellate-appearing lesion • No generic hormonal changes Determine whether mass is cystic • Clustered microcalcifications (e.g., pregnancy, beginning or or solid. ceasing contraception) • Palpable axillary nodes Order mammogram if patient is > 35 yr or > 30 yr with a family history of breast cancer. Mass is cystic Mass is solid Mammogram Mammogram is suspicious is not suspicious If fluid is bloody Obtain tissue or mass remains diagnosis Perform biopsy Thickening is Thickening is after aspiration, by means of (open or Follow up with suspicious not suspicious obtain tissue fine-needle stereotactic or mammograms diagnosis. If aspiration, ultrasound-guided every 6 mo for not, follow up core-needle). 2 yr. Perform open Reexamine core-needle, as for asimple biopsy (FNA patient after 2 or open cyst. is not menstrual surgical biopsy. appropriate). cycles. If area resolves, provide routine follow-up. If lesion persists or worsens, perform open biopsy. Malignancy is present No malignancy is present Treat as appropriate Continue routine screening, as [see 3:1 Breast Cancer]. appropriate for patient's age.
  3. 3. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 9 Benign Breast Disease — 3 Work up patient: • History, with particular attention to risk factors for breast cancer • Physical examination • Imaging studies (e.g., mammography) Initiate evaluation of specific breast problem. Nipple discharge Breast pain Breast infection or inflammation Factors increasing Factors increasing suspicion of Factors increasing suspicion of suspicion of malignancy: malignancy: malignancy: • Bloody discharge • Abnormal skin changes • No elevation of white blood cell • Unilateral discharge • Noncyclic pain count • Palpable mass (see Order mammogram if pain is • No response to antibiotics facing page) noncyclic and patient is > 35 yr or • Symptoms not associated with • Abnormal mammogram > 30 yr with a family history of breast lactation (see facing page) cancer. High-risk patients without symptons Mammogram Mammogram is normal, and Perform risk assessment (e.g., is abnormal, physical examination yields using Gail or Claus model). or palpable normal results Consider genetic testing mass is for risk gene mutations. detected Offer comfort, reassure, and perform Discuss risk with patient. follow-up examination in 2 mo. Select treatment option: Work up as If pain resolves or there is still no 1. Close surveillance indicated for palpable abnormality, reassure further palpable mass and follow up routinely. If there is a 2. Prophylactic mastectomy or abnormal palpable abnormality, obtain tissue 3. Chemoprevention with mammogram. diagnosis. tamoxifen or participation in chemoprevention trial Discharge is Discharge is not suspicious suspicious (physiologic Patient is Patient is not lactating Order discharge lactating mammogram. or galactorrhea) Incise and drain any Perform biopsy Give oral abscesses, and give of any lesions If discharge is antibiotics antibiotics to cover skin found. physiologic, reassure to cover gram- organisms (including If a single duct is patient; no further positive cocci, anaerobes). the source of the treatment is needed. use warm If there is no response to pathologic If galactorrhea soaks, and short course of antibiotics, discharge, is present, initiate attempt to rule out inflammatory excise duct. If appropriate workup keep breast carcinoma; perform source of (serum prolactin emptied. biopsy, including skin. discharge can levels, thyroid If abscess If infection is chronic, only be localized function tests, and forms, incise excise subareolar to a quadrant, MRI if necessary). and drain. duct complex. excise ducts in that quadrant.
  4. 4. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 9 Benign Breast Disease — 4 great deal of normal breast texture as potential nodules. It is use- the aspirate is not bloody, the fluid should not be sent for cytolog- ful, however, for directing fine-needle aspiration (FNA) biopsy or ic analysis, because it is unlikely to yield a diagnosis of cancer. If core-needle biopsy (CNB) of the lesions that it does visualize. the aspirate is bloody, it should be sent for cytologic examination, and tissue sampling should be considered (with biopsy or excision Magnetic Resonance Imaging of any residual solid component). Complex cysts with indistinct The main approved use of magnetic resonance imaging in the walls or intracystic solid components are more likely to be associ- workup of breast disease is for identification of leaks in silicone ated with carcinoma; therefore, imaging-guided aspiration, biopsy, breast implants, because it is capable of detecting the ruptured sil- or both should be performed. icone membrane within the silicone gel. MRI also plays a role in distinguishing benign from malignant lesions, though its sensitivi- Solid Masses ty and specificity in this setting are still being assessed. MRI after If a discrete mass in the breast is believed to be solid, either on injection of gadolinium contrast enhances many malignant lesions the basis of ultrasonographic findings or because attempts at in relation to normal breast parenchyma. This technique also aspiration yield no fluid, a tissue diagnosis is necessary to rule enhances some benign lesions (e.g., fibroadenomas), but gadolin- out malignancy. Physical examination alone is insufficient: it cor- ium does appear to enhance malignant lesions more rapidly and rectly identifies masses as malignant in only 60% to 85% of often to a greater extent. cases.4 Furthermore, experienced examiners often disagree on whether biopsy is needed for a particular lesion: in one study, Other Modalities four surgeons unanimously agreed on the necessity of biopsy for Nuclear medicine studies, such as sestamibi scintimammogra- only 11 (73%) of 15 palpable masses that were later shown by phy and positron emission tomography or mammography (PET biopsy to be malignant. Tissue diagnosis may be accomplished or PEM), remain primarily investigational tools. At present, there by means of FNA biopsy, CNB, or open surgical biopsy [see 3:5 is no proven role for thermography or xerography in the evaluation Breast Procedures]. of breast problems. Fibroadenoma Fibroadenomas are benign tumors that BIOPSY show evidence of both connective tissue and epithelial prolifera- Breast biopsies should be performed percutaneously whenever tion. They are most commonly diagnosed in women in their 20s possible.3 For a palpable lesion, either FNA biopsy or CNB is or 30s. Their characteristic clinical presentation is that of a well- appropriate. For a nonpalpable lesion, an imaging-guided tech- circumscribed, smooth, rubbery, mobile mass. Mammography is nique is advisable. Either stereotactic or ultrasound-guided percu- generally not required for a young woman with the classic clinical taneous core biopsy is less invasive and more expedient than open presentation but should be obtained when the diagnosis is being biopsy. With any imaging-guided approach, however, it is impor- considered in an older woman. Ultrasonography may be quite use- tant to confirm that the interpretation of the imaging abnormality ful in this setting. On sonograms, these lesions generally appear as agrees with the pathologic analysis of the specimen. Follow-up oval or rounded hypoechoic masses with regular margins. should be based both on the pathologic findings and on the If the findings from ultrasonography and clinical examination appearance of the breast abnormality on diagnostic imaging. are consistent with a fibroadenoma, then the lesion can safely be followed clinically with serial sonograms, breast self-examination (BSE), or both. If the lesion enlarges, biopsy may be required. If Management of Specific there is any question, a core biopsy may be performed. If the pres- Breast Problems ence of a fibroadenoma is confirmed, clinical follow-up is appro- priate, provided that the lesion does not enlarge. If the fibroadeno- PALPABLE MASS ma enlarges, excision is required to rule out phyllodes tumor (see The workup and man- below). Of course, nonenlarging fibroadenomas may also be agement of a discrete breast excised, either percutaneously (with vacuum-assisted core biopsy mass are governed by the [VACB] devices) or via an open surgical approach. In addition, age of the patient, the phys- cryoablation of fibroadenomas has yielded favorable outcomes at ical characteristics of the some centers.5,6 palpable lesion, and the patient’s medical history.The likelihood of malignancy is greater when the patient is 40 years of age or older, Phyllodes tumor The phyllodes tumor is a rare fibroepithe- when the mass has irregular borders, or when skin dimpling or lial breast lesion that clinically mimics a fibroadenoma. Most phyl- enlarged axillary nodes are present [see 3:1 Breast Cancer]. A pre- lodes tumors present as palpable, solitary, well-defined, mobile, biopsy mammogram is indicated for women older than 35 years and painless breast masses. With the widespread availability of and for those younger than 35 years who have a strong family his- screening mammography, an increasing number of these tumors tory of premenopausal breast cancer. are being discovered mammographically. Large phyllodes tumors may be associated with visible venous dilation in the skin overlying Cystic Masses the tumor. Axillary nodal metastasis rarely occurs (< 5% of cases). Cysts are a common cause of dominant breast lumps, particu- Tumors are classified histologically as low, intermediate, or high larly in premenopausal women. They can often be differentiated grade on the basis of five criteria: stromal cellularity, stromal atyp- from solid lesions by means of ultrasonography. Sonographically, ia, the microscopic appearance of the tumor margin (infiltrating, simple cysts tend to be oval or lobulated and anechoic, with well- effacing, or bulging), mitoses per 10 high-power fields, and the defined borders. For asymptomatic simple cysts, no further inter- macroscopic size of the tumor. Structural7 and cytogenetic8 stud- vention is required. For symptomatic cysts, FNA is appropriate. If ies of constituent cells have demonstrated similarities between the mass does not disappear completely after aspiration, then fibroadenomas and phyllodes tumors, and there is evidence that biopsy of any residual solid component should be performed. If certain fibroadenomas develop into phyllodes tumors. FNA is
  5. 5. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 9 Benign Breast Disease — 5 Table 1 American College of Radiology Breast ing mammogram is the most common initial presentation for Imaging Reporting and Data System (BIRADS) women with breast cancer. In the Breast Imaging Reporting And Data System (BIRADS), developed by the American College of Radiology, six different assessments (numbered 0 through 5) are Category Assessment Description/Recommendation used in the interpretation of a screening mammogram [see Table 1].11 Women with either a negative or a benign assessment (category 1 or Additional imaging evaluation 0 Additional imaging recommended 2) should undergo routine screening mammography in 1 to 2 years. required Women with a possibly benign assessment (category 3) should Nothing to comment on; routine undergo a repeat study in 6 months, at which time the mammo- I Negative finding screening recommended graphic abnormality is assessed for stability. Negative mammogram, but In general, whenever the radiologist states that a lesion identi- interpreter may wish to describe 2 Benign finding a finding; routine screening fied on mammography is suspicious, a tissue diagnosis should be recommended obtained, preferably by means of mammographically guided stereotactic CNB [see 3:5 Breast Procedures]. Very high probabillity of benignity; 3 Probably benign finding short-interval follow-up suggest- ed to establish stability VAGUE THICKENING OR NODULARITY Probability of malignancy; biopsy 4 Suspicious abnormality Normal breast texture is should be considered often heterogeneous, par- Abnormality highly sugges- High probability of cancer; appro- 5 tive of malignancy priate action should be taken ticularly in premenopausal women. Consequently, vague thickenings or ten- usually nondiagnostic, primarily because of the difficulty of der or nontender areas of obtaining adequate numbers of stromal cells for cytogenic analy- nodularity are frequently sis. On core biopsy, it may be impossible to distinguish a phyllodes detected by the patient or the clinician. It is important to distin- tumor from a fibroadenoma. Although most phyllodes tumors guish this vague breast thickening or nodularity from a discrete or have minimal metastatic potential, they have a proclivity for local dominant breast mass. A dominant breast mass is defined as a dis- recurrence and should be excised with at least a 1 cm margin. crete lump that is distinctly different from the surrounding breast Local recurrence has been correlated with excision margins but tissue. Overall, approximately 10% of dominant breast masses are not with tumor grade or size.9 The most common site of metasta- malignant. sis from malignant phyllodes tumors is the lungs (via the In clinical practice, the first step in evaluating a nodular area is hematogenous route). to compare it with the corresponding area of the opposite breast. The diagnosis of phyllodes tumor should be considered in all Symmetrical tender nodularity—for example, in the upper outer patients with a history of a firm, rounded, well-circumscribed, solid quadrant of both breasts—is rarely pathologic. These areas often (i.e., noncystic) lesion in the breast. Because phyllodes tumors represent fibrocystic changes that may resolve with time and thus mimic fibroadenomas, they are often subjected to percutaneous should be followed clinically. Asymmetrical areas of vague thick- biopsied or enucleated with a close margin. If percutaneous biop- ening in premenopausal women should be reexamined after one sy has been performed, wide-margin excision should follow. If the or two menstrual cycles. If the asymmetrical thickening persists, original percutaneous biopsy was consistent with fibroadenoma the possibility of malignancy is increased, and biopsy should be and the lesion increases in size on follow-up examination or ultra- performed. Women 35 years of age or older who have not had a sonography, excision should be performed. If, after excisional biop- mammogram in the past 6 months should undergo mammogra- sy, examination of the permanent section shows that an adequate phy to rule out synchronous lesions. The accuracy of a negative margin was not obtained, the patient should undergo reexcision to FNA biopsy in the presence of a vague thickening (as opposed to obtain wider margins and avoid a 15% to 20% recurrence rate. If a discrete mass) is questionable; therefore, open biopsy is general- a simple excision cannot be accomplished without gross cosmetic ly required for adequate sampling. deformity or if the tumor burden is too large, a simple mastectomy NIPPLE DISCHARGE should be performed. In certain circumstances, radiation therapy may have a role to play in the management of patients with phyl- Nipple discharge is a lodes tumor. Chemotherapy, which is reserved for patients with common breast complaint, metastatic disease, is based on guidelines for the treatment of sar- occurring in approximately comas, rather than breast adenocarcinomas. 20% to 25% of women.12 It may be classified as physio- ABNORMAL SCREENING logic discharge, pathologic MAMMOGRAM discharge, or galactorrhea. The increased use of Although the actual inci- screening mammography dence of malignancy in women with nipple discharge is low, this has led to a dramatic rise in complaint produces significant anxiety among women because of the number of nonpalpable the fear that it may be a harbinger of breast cancer. Galactorrhea breast lesions that call for tis- can be a complex diagnostic challenge for the clinician; a thorough sue acquisition. Generally, history, a focused physical examination, and appropriately chosen 5% to 10% of all screening investigative studies are required for diagnosis. mammograms are abnormal, and 10% of women with abnormal Nipple discharge should be evaluated with respect to its dura- mammograms have breast cancer.10 Currently, an abnormal screen- tion, character (i.e., bloody, nonbloody, or milky), location (i.e.,
  6. 6. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 9 Benign Breast Disease — 6 unilateral or bilateral), and precipitating factors (i.e., whether it and biopsy of the mammary ducts possible.13 Flexible fiberoptic is spontaneous or expressed). Because endocrine disorders (e.g., ductoscopy [see 3:5 Breast Procedures] may permit direct identifica- hypothyroidism and hyperprolactinemia) can produce galactor- tion and treatment of pathologic conditions affecting the ducts. At rhea, symptoms indicative of these conditions (e.g., lethargy, present, this technology is available only at a few centers, and as constipation, cold intolerance, and dry skin) should be looked with all new technologies, there is a learning curve associated with for.The patient should also be questioned about symptoms of an its use. Further experience with ductoscopy is required to deter- intracranial mass, such as headache, visual field disturbances, mine its precise role in the evaluation and management of nipple and amenorrhea. discharge. Numerous medications are associated with galactorrhea, includ- After a thorough history, a focused physical examination, and ing various antidepressants (e.g., fluoxetine, buspirone, alprazolam, appropriate diagnostic studies, pathologic nipple discharge that and chlorpromazine). Other classes of drugs associated with nip- persists should be treated surgically. Operative therapy can ple discharge include antihypertensives, H2-receptor antagonists, resolve the discharge and provide a diagnosis. Excision of a duct and antidopaminergic medications (e.g., metoclopramide). or ducts can usually be performed with the patient under local A focused physical examination is the next step in the evalua- anesthesia supplemented with intravenous sedation (so-called tion of nipple discharge; obviously, a detailed breast examination monitored anesthesia care [MAC]).The traditional surgical man- is essential. If nipple discharge is not immediately apparent, the agement of pathologic nipple discharge is a central, or major, duct clinician should attempt to elicit the discharge by gently squeezing excision, which effectively removes all of the central lactiferous the nipple.The clinician should then attempt to determine whether ducts and sinuses, thereby preventing further discharge [see 3:5 the discharge is limited to a single duct or involves multiple ducts. Breast Procedures]. Single-duct excision, or microdochectomy, can Attention should also be paid to any physical findings suggestive be performed when the offending duct is clearly identified. The of endocrine imbalance, such as thyromegaly (hypothyroidism) or advantage of this latter procedure is that it conserves breast tissue visual field deficits (prolactinoma). and causes only minimal deformity; the nipple-areola complex Nipple discharge is physiologic during pregnancy, developing as remains intact, so that the patient retains the ability to breast- early as the second trimester and sometimes continuing for as long feed. The main disadvantage of single-duct excision is that the as 2 years post partum. Therefore, evaluation of nipple discharge discharge may be more likely to recur than it would be after cen- in women of childbearing years should include a pregnancy test. tral duct excision. Elevated thyroid-stimulating hormone (TSH) levels associated BREAST PAIN with hypothyroidism can increase prolactin secretion and produce galactorrhea. Accordingly, women with nipple discharge should Breast pain, or mastal- undergo thyroid function testing.When the level of suspicion for a gia, is one of the most com- prolactinoma is sufficiently high, the serum prolactin level should mon symptoms for which be checked. If the serum prolactin level is elevated, MRI of the women seek medical atten- head (i.e., of the sella turcica) is indicated to determine whether a tion. At present, the causes prolactin-secreting pituitary tumor is present. of breast pain are poorly Mammography is the first imaging study performed to evaluate understood. Although pain nipple discharge. It may reveal nonpalpable masses or microcalci- is not usually a presenting symptom for breast cancer, it still war- fications that necessitate biopsy. Because most pathologic causes rants a comprehensive evaluation.The elements of the history that of nipple discharge are located close to the nipple, magnification are important in the evaluation of breast pain are the location, views of the retroareolar region may help identify the underlying character, severity, and timing of the pain. Breast pain occurring condition. The absence of any mammographic abnormalities, in a predictable pattern just before the menstrual cycle is called however, should not lead to a false sense of security; further eval- cyclical mastalgia and is probably hormonally mediated. Notably, uation is still required. however, several studies have shown no differences in circulating The role of exfoliative cytology in the management of nonlacta- estrogen levels between women with mastalgia and pain-free con- tional galactorrhea is unclear. Although cytology can be diagnos- trol subjects. It has been postulated that in women with breast tic of cancer, its utility is limited by its low sensitivity, and at pre- pain, progesterone levels may be decreased or prolactin release sent, it generally is not recommended.The high false-negative rate may be increased in response to thyrotropin-releasing hormone.14 mandates further evaluation when the cytologic findings are neg- Although histologic findings consistent with cysts, apocrine meta- ative or nondiagnostic. Discharge that is bloody, unilateral, and plasia, and ductal hyperplasia have been noted in the breasts of spontaneous is more likely to yield a diagnosis of cancer, though women with mastalgia, there is no convincing evidence that any of the incidence is still quite low. these pathologic changes actually cause breast pain. Ductography, or galactography, consists of mammography per- Mammography and physical examination usually yield normal formed after the offending lactiferous duct has been cannulated results in patients with breast pain. The likelihood of malignancy and filled with a contrast agent. It can be performed only when is increased when a patient with mastalgia is postmenopausal and active discharge is present and when the secreting duct can be not taking estrogens or when the pain is associated with skin identified and accessed. Not infrequently, ductography is techni- changes or palpable abnormalities; however, these situations are cally impossible, or else the images are uninterpretable as a conse- uncommon. quence of incomplete ductal filling or contrast extravasation. For most women with breast pain, treatment consists of reliev- Solitary papillomas, the most common cause of abnormal nipple ing symptoms and reassuring the patient that the workup has not discharge, typically appear as a ductal cutoff or filling defect on identified an underlying breast carcinoma. Nonsteroidal anti-in- ductography. Unfortunately, a normal ductogram does not flammatory drugs and supportive bras are helpful. Several lifestyle exclude a pathologic condition, and as with a normal mammo- interventions have been proposed as effective breast pain treat- gram, further evaluation is still required. ments. Dietary recommendations, such as avoidance of methyl- Advances in endoscopic technology have made visualization xanthines (found in coffee, tea, and sodas), are not evidence
  7. 7. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 9 Benign Breast Disease — 7 based.15 However, oral ingestion of evening primrose oil has been areolar duct complex and intravenous antibiotic coverage, infec- reported to produce significant or complete pain relief in about tions recur in some patients; excising the nipple and the areola can 50% of women with cyclic mastalgia.16 treat these.21 For the rare patients who have severe pain that does not MAINTENANCE OF HEALTH: BREAST CANCER SCREENING respond to conservative measures, administration of hormones or drugs may be appropriate. Danazol has been successful In the absence of a specific breast complaint, patients at risk for against breast pain and should be considered the first-line agent, breast cancer may be identified through screening. The three main though its androgenic effects may be troubling to many methods of breast cancer screening are BSE, clinical breast exami- women.17 Bromocriptine (a prolactin antagonist) and tamoxifen nation (CBE), and screening mammography.22 American Cancer have also been used to treat mastalgia.18 Pharmacotherapy for Society screening guidelines for women aged 40 years and older mastalgia is contraindicated in patients who are trying to specify that mammography and CBE should be included as part of become pregnant. an annual health examination.23 In addition, health care providers should tell women about the benefits and limitations of BSE, stress- BREAST INFECTION OR ing the importance of promptly reporting any new breast symptoms. INFLAMMATION Breast infections can be Breast Self-Examination divided into two general In BSE, the patient herself inspects and palpates the complete categories: (1) lactational breast and the axilla. Given that women themselves detect many infections and (2) chronic breast tumors, one might reasonably assume that BSE instruction subareolar infections asso- would improve breast cancer detection.There is, however, no con- ciated with duct ectasia. clusive evidence that BSE is of significant value in this regard. Both cellulitis and abscesses Many self-detected tumors are in fact found incidentally, not dur- may occur in lactating women, either during weaning or when ing BSE. In addition, the best technique for BSE and the optimal engorgement occurs. In the absence of an abscess, breast infec- frequency have not been established.The American Cancer Society tions are treated by (1) giving oral antibiotics that cover gram-pos- recommends monthly self-examination as part of a breast cancer itive cocci, (2) applying warm packs to the breast, and (3) keeping screening process that includes mammography and CBE.23 the breast emptied.Weaning is not necessary, because the infant is not adversely affected by nursing from an infected breast.19 A Clinical Breast Examination diagnosis of mastitis in a nonlactating woman must be viewed In CBE, a qualified health care professional carries out a com- with suspicion, and the possibility of inflammatory breast cancer plete examination of the breast and the axilla. As with BSE, there must be excluded. Inflammatory breast cancer is a clinicopatho- is little conclusive evidence indicating that annual or semiannu- logic variant of breast cancer that is clinically characterized by the al CBE increases breast cancer detection rates.24 Nevertheless, rapid onset of erythema, edema, and increased temperature in the we believe that it is prudent for the clinician to include CBE as breast, with or without a palpable mass.The diagnosis is made by part of the physical examination performed on every female means of a skin biopsy; the pathologic hallmark is tumor cell inva- patient. sion of the dermal lymphatics. Once a breast abscess forms, however, surgical drainage is Screening Mammography necessary. Because of the network of fibrous septa within the There has been considerable debate regarding the value of breast, breast abscesses in lactating women rarely form fluctuant screening mammography.The studies done to date suffer from flaws masses. The clinical picture of breast erythema, tenderness, in the conduct of the trials and in the methods used to analyze the fever, and leukocytosis establishes the diagnosis. Ultrasound- data. This state of affairs has led not only to uncertainty among guided percutaneous drainage in conjunction with administra- practitioners but also to confusion among patients. Nevertheless, tion of appropriate antibiotics may be attempted. If this measure screening mammography is recommended by several profession- is unsuccessful, open drainage will be required. For optimal al societies, including both the American Cancer Society and the abscess drainage, general anesthesia is usually necessary because National Cancer Institute (NCI). The NCI continues to evaluate of the tenderness of the affected area and the amount of manip- data from ongoing studies and to promote and fund research ulation necessary to break up the loculated abscess cavity. As aimed at developing more effective screening tools and strategies. with any abscess, a culture should be performed and the cavity In a statement from January 31, 2002, the NCI made the follow- should be packed open. ing recommendations25: Nonlactational infections of the breast often present as chronic relapsing infections of the subareolar ducts associated with 1. Women 40 years of age and older should be screened every 1 periductal mastitis or duct ectasia.These infections usually involve to 2 years with mammography. multiple organisms, including skin anaerobes.20 Retraction or 2. Women who are at higher than average risk of breast cancer inversion of the nipple, subareolar masses, recurrent periareolar should seek expert medical advice about whether they should abscesses, or a chronic fistula to the periareolar skin may result, as begin screening before 40 years of age and about the frequen- may palpable masses and mammographic changes that mimic cy of screening. carcinoma. In the acute phase of infection, treatment entails inci- A woman should continue to undergo screening mammogra- sion, drainage, and administration of antibiotics that cover skin phy as long as she is in reasonably good health and would be a organisms, including anaerobes. In cases of repeated infection, the candidate for treatment if cancer were detected. Thus, although entire subareolar duct complex should be excised after the acute no specific age has been established as a definitive cutoff point infection has completely resolved, with antibiotic coverage provid- beyond which screening yields no benefit,26 patients with comor- ed during the perioperative period. Whether drain placement is bidities whose life expectancy is shorter than 5 years would not be necessary remains debatable. Even after wide excision of the sub- expected to benefit from routine mammography.
  8. 8. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 9 Benign Breast Disease — 8 High-Risk Patients Most of the carcinomas that develop after a biopsy showing LCIS Despite significant pro- are of ductal histology.43 The increased risk of subsequent carcino- gress in management, at ma is equally distributed between the breast undergoing biopsy least one third of women and the contralateral breast and is thought to be between 20% and with breast cancer will ulti- 25% in patients with LCIS and no other risk factors; it may be mately die of their disease. additive with other risk factors (see above). This harsh reality has led to Genetic testing and the use of mathematical models have signif- efforts aimed at providing icantly improved our ability to define breast cancer risk. The Gail primary prevention to high- model,44 which relies on data from the Breast Cancer Detection risk women.Various factors that place women at increased risk for Demonstration Project, and the Claus model,45 which relies on breast carcinoma have been identified [see Table 2].27 These risk data from the Cancer and Steroid Hormone Project, are two of the factors include increasing age; mutations in breast cancer risk tools that have been used to make this determination. At present, genes (including BRCA1 and BRCA2, PTEN, and p53) and other there are three treatment options for women at high risk for breast factors related to a family history of breast cancer28; hormonal and cancer: (1) close surveillance, (2) prophylactic mastectomy, and reproductive factors, including early menarche, late menopause, (3) chemoprevention with tamoxifen, raloxifene, or other agents in nulliparity, the absence of lactation,29 and the use of exogenous the setting of a clinical trial. Currently, no evidence-based conclu- hormones27,30-35; environmental factors, including diet and the sions can be made as to which of these management strategies is lifestyle characteristic of developed Western nations36-38; certain superior. Research involving high-risk women includes few ran- pathologic findings within breast tissue, including previous breast domized, controlled trials, and many reports are based on uncon- cancer and various premalignant lesions (e.g., ductal or lobular trolled studies of selected populations with varying degrees of hyperplasia with atypia and lobular carcinoma in situ [LCIS]39-41); breast cancer risk. Although most women at high risk choose the and certain nonbreast malignancies, including ovarian and option of close surveillance, the growing body of data on chemo- endometrial carcinomas. Previous exposure to radiation, especial- prevention and prophylactic mastectomy may increase selection of ly in the area of the chest wall, should also be considered. the other two options. Recognition of risk factors facilitates appropriate screening and For women with LCIS or a family history of breast carcinoma, clinical management of individual patients. It must be recognized, surveillance should include twice-yearly physical examinations. however, that many women in whom breast cancer develops have Mammography should be performed annually after the diagnosis none of the known risk factors for breast carcinoma. The absence of LCIS or atypical hyperplasia. For women with a family history of these risk factors should not prevent full evaluation or biopsy of of breast cancer, mammography should be performed annually, a suspicious breast lesion. beginning at least 5 years before the earliest age at which cancer Approximately 10% of all breast cancers are hereditary.42 was diagnosed in a relative and in any case no later than the age of Hereditary breast cancer is characterized by early age at onset, 35 years.46 For women who carry BRCA1 or BRCA2 mutations bilaterality, autosomal dominant transmission through either the and other women from families with an autosomal dominant pat- maternal or the paternal line, and familial association with tumors tern of breast cancer transmission, annual mammographic screen- of other organs, particularly the ovary and the prostate gland. ing should begin at least 10 years before the earliest age at which Therefore, an accurate and complete family history is essential for the cancer was diagnosed in a relative and no later than 25 years quantifying a woman’s genetic predisposition to breast cancer. Questions about breast cancer in family members should go back several generations and should extend to third-degree relatives, with age at diagnosis recorded if available. Similarly, any family Table 2 Risk Factors for Breast Cancer history of ovarian or other cancers (particularly those that devel- oped when the relative was young) should be recorded, along with Increasing age age at diagnosis. Any personal history of cancer should be record- White race ed, with particular attention paid to breast, ovarian, and endome- Age at menarche ≤ 11 years trial cancers. Admittedly, it is not always possible to obtain com- Age at menopause ≥ 55 years plete and precise family history data, whether because of time con- Nulliparity straints or because of family issues such as premature deaths, small Age at first pregnancy ≥ 30 years Absence of history of lactation family size, and distant or broken families. ? Prolonged use of oral contraceptives before first pregnancy It is difficult for practicing surgeons to stay current with the Use of postmenopausal estrogen or progesterone replacement, explosive growth of knowledge related to the genetics of breast especially if prolonged cancer.Two genes—BRCA1 and BRCA2—account for the major- Use of other hormones, fertility regimens, or diethylstilbestrol ity of hereditary breast cancers and are associated with increased Mutations in breast cancer risk genes, including BRCA1 and BRCA2, risks of other cancers, most notably ovarian cancer; mutations in PTEN, and p53 other genes (e.g., p53 and PTEN) may also confer an increased Family history of breast cancer: multiple affected relatives, early onset, bilaterality risk of breast cancer. Specific founder mutations in BRCA1 and Family history of ovarian cancer: multiple affected relatives, early BRCA2 occur within certain ethnic groups (e.g., Ashkenazi onset Jews).42 Tests that detect mutations in these genes are commercial- Pathologic findings that indicate increased risk (e.g., atypical hyper- ly available. Whether to pursue genetic testing and how to inter- plasia, lobular carcinoma in situ, proliferative fibrocystic disease) pret the results are complex issues. Accordingly, clinicians should Previous breast cancer consult a professional genetics counselor if the option is available. Previous breast problems It is now generally accepted that LCIS is a predictor of Previous breast operations increased risk of subsequent invasive breast carcinoma rather than Previous exposure to radiation a marker of the site at which the subsequent carcinoma will arise.
  9. 9. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 9 Benign Breast Disease — 9 of age.46 Several studies have demonstrated that MRI is an excel- risk women. Long-term follow-up data are now available from the lent screening tool in women at high risk for the subsequent devel- Royal Marsden randomized, double-blinded tamoxifen breast opment of breast cancer.47-50 This finding has led to the incorpo- cancer prevention trial54 and the International Breast Cancer ration of annual MRI into the current screening recommenda- Intervention Study (IBIS-1),55 both of which report a statistically tions for any woman with a BRCA mutation, any untested first- significant reduction in the incidence of ER-positive breast cancer degree relative of a BRCA carrier, and anyone whose lifetime risk that persists for at least 10 years. exceeds 20% to 25%.51 In addition, MRI should be performed Concerns about the side effects of tamoxifen have generated annually in all persons who have undergone irradiation of the interest in the use of selective estrogen receptor modulators chest between the ages of 10 and 30 years and all those with Li- (SERMs) as chemopreventive agents. One such SERM, ralox- Fraumeni syndrome (p53 mutation carriers) or Cowden syn- ifene, has been approved by the FDA for the treatment of post- drome (PTEN mutation carriers). menopausal osteoporosis and is known also to exert beneficial Chemoprevention may be defined as the use of nutrients or effects on lipid profiles.The Study of Tamoxifen And Raloxifene pharmacologic agents to augment physiologic mechanisms that (STAR) trial, a randomized, double-blind trial whose purpose protect against the development of malignancy. Chemopreventive was to compare the effectiveness of raloxifene with that of strategies are designed either to block the initiation of the carcino- tamoxifen in postmenopausal women at increased risk for breast genic process or to prevent (or reverse) the progression of the pre- cancer, demonstrated that raloxifene was as effective as tamox- malignant cell to an invasive cancer.52 Chemoprevention began ifen in reducing the risk of invasive breast cancer and possessed with the development of the antiestrogen tamoxifen. The efficacy a superior side effect profile.56 It is noteworthy, however, that of tamoxifen in ER-positive breast cancer patients was recognized raloxifene was not found to prevent noninvasive breast cancers early on, but its chemopreventive potential was not established in this trial. until some time later. There are several newer agents that may also possess some The first study to be published on breast cancer chemopreven- capacity for breast cancer chemoprevention. Aromatase tion was the NSABP P-1 trial, in which women at increased risk inhibitors, which are used to treat ER-positive breast cancers, for breast cancer were randomly assigned to receive either tamox- reduce the risk of contralateral cancers and may have a role to play ifen, 20 mg/day, or placebo.53 Increased risk was determined on in chemoprevention. In addition, gonadotropin-releasing hor- the basis of (1) age greater than 60 years, (2) a 5-year predicted mone agonists, monoterpenes, isoflavones, retinoids, rexinoids, incidence of breast cancer of at least 1.66% (determined accord- vitamin D derivatives, and inhibitors of tyrosine kinase are all ing to Gail’s criteria), or (3) a personal history of LCIS. After a undergoing evaluation in clinical or preclinical studies with a view median follow-up period of 55 months, the overall risk of breast to assessing their potential chemopreventive activity.Whether any cancer was reduced by 49% in the tamoxifen group, and the risk of these compounds will play a clinically useful role in preventing of noninvasive breast cancer was reduced by 50%. The reduction breast cancer remains to be seen. in breast cancer risk was limited to ER-positive breast cancers. Long-term results of prophylactic mastectomy in high-risk Several adverse side effects were noted in the tamoxifen group, the women indicate that breast cancer risk was reduced by at least most worrisome of which were a threefold increase in the inci- 90% in women at high or very high risk who underwent this pro- dence of endometrial cancer, a higher incidence of deep vein cedure, compared with women who did not.57,58 There is, howev- thrombosis and pulmonary embolism, and a higher incidence of er, no clear consensus on the indications for risk-reduction stroke. The Food and Drug Administration (FDA) found the surgery; the benefits of prophylactic mastectomy must be weighed results of the NSABP P-1 trial to be compelling enough to war- against the irreversibility and the psychosocial consequences of rant approval of tamoxifen as a chemopreventive agent in high- the procedure. References 1. Seltzer MH: Breast complaints, biopsies, and can- tumors of the breast. 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Newcomb PA, Storer BE, Longnecker MP, et al: ease: pathology of atypical lobular hyperplasia and results of tamoxifen prophylaxis for breast can- Lactation and a reduced risk of premenopausal lobular carcinoma in situ. Breast Cancer Res cer—96-month follow-up of the randomized IBIS- breast cancer. N Engl J Med 330:81, 1994 5:258, 2003 I trial. J Natl Cancer Inst 99:258, 2007 30. Marchant DJ: Estrogen-replacement therapy after 44. Gail MG, Brinton LA, Byar DP, et al: Projecting 56. Vogel VG, Constantino JP, Wickerham DL, et al: breast cancer: risk versus benefits. Cancer individualized probabilities of developing breast Effects of tamoxifen vs raloxifene on the risk of 71(suppl):2169, 1993 cancer for white females who are being examined developing invasive breast cancer and other disease 31. Squitieri R, Tartter PI, Ahmed S, et al: Carcinoma annually. J Natl Cancer Inst 81:1879, 1989 outcomes: the NSABP Study of Tamoxifen and of the breast in postmenopausal hormone user and 45. Claus EB, Risch N, Thompson WD: Autosomal Raloxifene (STAR) P-2 trial. JAMA 295:2727, nonuser control groups. J Am Coll Surg 178:167, dominant inheritance of early-onset breast cancer: 2006 1994 implications for risk prediction. Cancer 73:643, 57. Hartmann LC, Schaid DJ, Woods JE, et al: 32. Steinberg KK, Thacker SB, Smith SJ, et al: A 1994 Efficacy of bilateral prophylactic mastectomy in meta-analysis of the effect of estrogen replacement 46. Dershaw DD: Mammographic screening of the women with a family history of breast cancer. N therapy. JAMA 265:1985, 1991 high-risk woman. Am J Surg 180:288, 2000 Engl J Med 340:77, 1999 33. Wingo PA, Lee NC, Ory H, et al: Age specific dif- 47. Kriege M, Brekelmans CT, Boetes C, et al: 58. Rebbeck TR, Friebel T, Lynch HT, et al: Bilateral ferences in the relationship between oral contra- Efficacy of MRI and mammography for breast- ceptive use and breast cancer. Obstet Gynecol prophylactic mastectomy reduces breast cancer cancer screening in women with a familial or risk in BRCA1 and BRCA2 mutation carriers: the 78:161, 1991 genetic predisposition. N Engl J Med 351:427, PROSE Study Group. J Clin Oncol 22:1055, 2004 34. Colditz GA, Stampfer MJ,Willett WC: Prospective 2004 study of estrogen replacement therapy and risk of 48. Warner E, Plewes DB, Hill KA, et al: Surveillance breast cancer in post-menopausal women. JAMA of BRCA1 and BRCA2 mutation carriers with 264:2648, 1990 magnetic resonance imaging, ultrasound, mam- Acknowledgment 35. Dupont WD, Page DL: Menopausal estrogen- mography, and clinical breast examination. JAMA replacement therapy and breast cancer. Arch 292:1317, 2004 The authors gratefully acknowledge the contributions Intern Med 151:67, 1991 49. Kuhl CK, Schrading S, Leutner CC, et al: of D. Scott Lind, M.D., F.A.C.S., and Barbara L. 36. Hunter DJ, Manson JE, Colditz GA, et al: A Mammography, breast ultrasound, and magnetic Smith, M.D., Ph.D., F.A.C.S., coauthors of the previ- prospective study of the intake of vitamins C, E, resonance imaging for surveillance of women at ous iteration of this chapter, to the development and and A and the risk of breast cancer. N Engl J Med high familial risk for breast cancer. J Clin Oncol writing of the current iteration.