© 2007 WebMD, Inc. All rights reserved.                                                     ACS Surgery: Principles and Pr...
© 2007 WebMD, Inc. All rights reserved.                                                                ACS Surgery: Princi...
© 2007 WebMD, Inc. All rights reserved.                                                                   ACS Surgery: Pri...
© 2007 WebMD, Inc. All rights reserved.                                                       ACS Surgery: Principles and ...
© 2007 WebMD, Inc. All rights reserved.                                                                                   ...
© 2007 WebMD, Inc. All rights reserved.                                                       ACS Surgery: Principles and ...
© 2007 WebMD, Inc. All rights reserved.                                                        ACS Surgery: Principles and...
© 2007 WebMD, Inc. All rights reserved.                                                       ACS Surgery: Principles and ...
© 2007 WebMD, Inc. All rights reserved.                                                     ACS Surgery: Principles and Pr...
© 2007 WebMD, Inc. All rights reserved.                                                       ACS Surgery: Principles and ...
© 2007 WebMD, Inc. All rights reserved.                                                                                   ...
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Acs0301 Breast Cancer

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Acs0301 Breast Cancer

  1. 1. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 1 Breast Cancer — 1 1 BREAST CANCER 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. . Breast cancer is the most common cancer among women and the should be described. Certain physical findings, such as skin second leading cause of cancer-related death overall. One in eight changes, irregular borders, firmness, irregular margins, and immo- women will be diagnosed with breast cancer in the course of her bility, are associated with a greater likelihood of cancer, though lifetime.1 Generally, patients with breast cancer present in one of their absence does not exclude the diagnosis.The lymph nodes in three ways: with a palpable breast mass, with a change in the skin the supraclavicular, infraclavicular, and axillary basins should be of the breast or the nipple, or with an abnormal mammogram. As thoroughly examined, and any enlargement should be noted.The is the case for patients with benign breast complaints [see 3:9 size, mobility, and number of enlarged nodes should be recorded, Benign Breast Disease], the evaluation begins with a thorough his- as should matting of nodes or fixation of nodes to the chest wall. tory and a careful physical examination. Investigative Studies Clinical Evaluation IMAGING HISTORY A complete medical history should be obtained, including cur- Mammography rent medications, allergies, tobacco and alcohol use, previous sur- Diagnostic mammography is the first imaging study employed gical procedures, medical problems, and a brief social history. to evaluate breast abnormalities. It differs from screening mam- Special attention should be paid to the duration of the symptoms mography in that it is performed when a breast abnormality is and the changes that took place over time. It is important to deter- already present; it is a more comprehensive examination and con- mine whether there have been any previous breast problems; if sists of multiple specialized images (e.g., magnification views or breast biopsies were performed earlier, the pathologic findings of spot compression views). Diagnostic mammography includes a these biopsies should be obtained. mammogram of the contralateral breast to rule out synchronous, A thorough search for risk factors for breast cancer [see 3:9 nonpalpable lesions whenever a woman older than 35 years pre- Benign Breast Disease] should be undertaken, though the absence sents with a palpable breast mass or other specific symptoms. of these risk factors does not exclude the presence of breast can- Approximately 4% to 5% of breast cancers occur in women cer. An accurate and complete family history is essential for quan- younger than 40 years, and about 25% occur in women younger tifying a woman’s genetic predisposition to breast cancer. than 50 years. Approximately 5% to 10% of breast cancers are hereditary.2 Mammography fails to detect 10% to 15% of all palpable Questions about breast cancer in family members should go back malignant lesions, and its sensitivity is particularly decreased in several generations and should extend to third-degree relatives, women with lobular carcinoma or radiographically dense breast with age at diagnosis recorded if available. Similarly, any family tissue. Such patients may benefit from digital mammography, history of ovarian or other cancers (particularly those that devel- which is not more effective than traditional mammography in the oped when the relative was young) should be recorded, along with general population but which seems to be more effective in the age at diagnosis. Any personal history of cancer should be record- subset of patients with dense breast tissue.3 Because of the limita- ed, with particular attention paid to breast, ovarian, and endome- tions of diagnostic mammography, a negative mammogram trial cancers. Previous exposure to radiation, especially in the area should not influence the decision to perform a biopsy of a clinical- of the chest wall, should be noted. Admittedly, it is not always pos- ly palpable lesion.The purpose of mammography in this setting is sible to obtain complete and precise family history data, whether to look for synchronous lesions or nonpalpable calcifications sur- because of time constraints or because of family issues (e.g., pre- rounding the palpable abnormality, not to determine whether mature deaths, small family size, or distant or broken families). biopsy of the palpable abnormality is indicated. PHYSICAL EXAMINATION Ultrasonography The physical examination begins with inspection of the breasts The main value of ultrasonography lies in its ability to distin- for asymmetry, skin or nipple changes, nipple retraction, erythe- guish cystic from solid lesions. It is also very useful for directing ma, or peau d’orange (orange-peel appearance). Skin dimpling, fine-needle aspiration (FNA) or core-needle biopsy (CNB): it per- which can be indicative of an underlying mass lesion, can be ac- mits real-time manipulation of the needle and direct confirmation centuated by having the patient sit with her hands pushing against of the position of the needle within the lesion. It has also been used her hips to contract the pectoral muscles. Each breast should then to guide the performance of investigational tumor-ablating tech- be carefully palpated from the clavicle to below the inframamma- niques [see 3:5 Breast Procedures]. ry fold and from the sternum to the posterior axillary line, with careful attention to the subareolar area. This is done with the Magnetic Resonance Imaging patient both supine and sitting. If an abnormal area is identified, Magnetic resonance imaging after injection of gadolinium con- its location, size, consistency, contour, tenderness, and mobility trast enhances many malignant lesions in relation to normal breast
  2. 2. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 1 Breast Cancer — 2 Assessment and Management of Breast Cancer Patient has ductal carcinoma in situ (DCIS) Patient has early-stage invasive breast cancer (stage I or II) Treatment depends on extent of disease. Treatment choices are • Lumpectomy, SLNB, and radiation • Total mastectomy and SLNB Choice depends on patient preference and on presence or absence of any contraindications to limited surgery with radiation. Patient undergoes mastectomy Look for positive nodes. SLNB is negative SLNB is positive If primary tumor is < 1 cm, follow up. Perform complete lymph node dissection. If primary tumor is ≥ 1 cm, administer adjuvant chemotherapy and/or hormone therapy if tumor is estrogen receptor (ER) positive. Then, if tumor is > 5 cm, irradiate chest wall and Nodes are unfavorable, there are Nodes are favorable, and there are follow up; if tumor is ≥ 1 cm but ≤ 5 > 4 positive nodes, or there is < 4 positive nodes cm, follow up. extracapsular extension Administer adjuvant chemotherapy Administer adjuvant chemotherapy and/or hormone therapy if patient (hormone therapy if patient is is ER positive. Consider chest wall postmenopausal). irradiation. Mastectomy patients Limited surgery patients Mastectomy patients Irradiate chest wall and Irradiate breast and axilla If tumor is > 5 cm, irradiate chest axilla and follow up. and follow up. wall and follow up; if tumor is ≤ 5 cm, follow up. DCIS is not extensive DCIS is extensive Treatment choices are Perform simple mastectomy ± reconstruction. • Simple mastectomy ± reconstruction Consider SLN biopsy. • Wide excision Patient undergoes simple Patient undergoes wide excision mastectomy ± reconstruction Assess margin status. Consider SLN biopsy. Margins are positive Margins are negative Treatment choices are Irradiate breast and follow up, • Reexcision to negative margins and radiation therapy or follow up only. • Simple mastectomy ± reconstruction
  3. 3. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 1 Breast Cancer — 3 Patient has breast cancer Management depends on clinical stage. Patient has locally advanced breast cancer Patient has distant metastases (stage III or inflammatory carcinoma) (stage IV) Perform needle or incisional biopsy to obtain Determine whether patient is eligible tissue diagnosis and hormone receptor data. for therapy on protocol. Administer “neoadjuvant” chemotherapy. Consider radiation therapy to relieve Restage to identify distant metastases. pain from bone marrow metastases or avert pathologic fracture at metastatic site. Consider “toilet mastectomy” if patient has locally advanced and ulcerated Metastases are identified No metastases are primary tumor that hinders Patient undergoes lumpectomy on restaging identified on restaging administration of chemotherapy. If clean margins are not obtained, perform mastectomy (see left). Initiate appropriate Determine whether If clean margins are obtained, look management. tumor is operable. for positive nodes. Tumor is inoperable Tumor is operable SLNB is negative Administer a different Perform modified radical chemotherapy or hormone mastectomy. Lumpectomy with therapy regimen. axillary dissection is an option Administer radiation therapy. If primary for some patients. Consider tumor < 1 cm, follow up. If primary Restage to assess operability. radiation to chest wall and tumor ≥ 1 cm, administer adjuvant axilla. (Most patients require chemotherapy and/or hormone both surgery and radiation therapy if tumor is ER positive and in addition to chemotherapy.) follow up. Follow up. (Note: chemotherapy may precede radiation therapy.) Patient is ineligible for Patient is eligible for Limited surgery patients therapy on protocol therapy on protocol Irradiate breast and follow up. Initiate palliative Initiate therapy on chemotherapy protocol. or hormone therapy.
  4. 4. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 1 Breast Cancer — 4 parenchyma. Although some benign lesions (e.g., fibroadenomas) the abdomen, or the head; and (3) laboratory studies, including a are also enhanced by gadolinium, the contrast agent appears to complete blood count (CBC) and liver function tests. enhance malignant lesions more rapidly and often to a greater The extent of preoperative staging should be guided by the size extent. and other characteristics of the primary tumor and by the patient’s The sensitivity and specificity of MRI in distinguishing benign history and physical examination. The majority of patients with from malignant lesions are still being assessed.The main approved breast cancer present with early-stage disease and a low probabil- use of MRI in breast disease is for identification of leaks in silicone ity of metastatic disease; therefore, extensive testing adds cost breast implants, because MRI can detect the ruptured silicone without offering much benefit. For patients with stage I or II dis- membrane within the silicone gel. MRI is also useful in identify- ease, mammography and routine preoperative blood work should ing occult primary tumors in women who have palpable axillary be performed before definitive surgical therapy is initiated; further nodes but no palpable or mammographically identified primary imaging studies should be reserved for patients who have abnor- breast lesion. MRI appears to be effective for assessing the extent mal test results or clinical symptoms that suggest metastatic dis- of vaguely defined tumors, identifying unsuspected multifocal dis- ease (e.g., bone pain). For patients with higher-stage disease at ease, and helping identify patients who are not eligible for breast- presentation, the use of additional staging studies should be guid- conserving surgery. In addition, it appears that MRI can distin- ed by the patient’s clinical situation. guish between a locally recurrent tumor and surgical scarring or radiation-induced change after lumpectomy and radiation, Changes in American Joint Committee on Cancer Breast though the technology may not provide reliable readings until 18 Cancer Staging System months or more after surgery or the completion of radiation ther- A number of evidence-based changes to the sixth edition of the apy. MRI can also detect contralateral breast cancer that was missed American Joint Committee on Cancer (AJCC) TNM staging sys- by clinical breast examination and mammography at the time of tem for breast cancer were adopted for use in tumor registries in breast cancer diagnosis in approximately 3% of cases.4 To date, January 2003 [see Tables 1 and 2].6 These changes reflected grow- however, MRI has not been incorporated into the standard algo- ing use of sentinel lymph node biopsy (SLNB) and of immuno- rithms for the evaluation of breast cancer patients; most authori- histochemical and molecular technologies to detect nodal metas- ties recommend that it be employed selectively. tases. They also included quantitative criteria for distinguishing micrometastases from isolated tumor cells and specific identifiers Other Modalities for recording the use of SLNB, immunohistochemical staining, Nuclear medicine studies, such as sestamibi scintimammogra- and molecular biologic techniques. In addition, the classification phy and positron emission tomography (PET), remain primarily of lymph node status was modified to include the number of investigational tools. At present, there is no proven role for ther- affected axillary lymph nodes, and changes were made to the clas- mography or xerography in the evaluation of breast problems. sification of level III axillary lymph nodes and lymph nodes out- side the axilla. These modifications of the AJCC staging system BIOPSY should bring standardization to the collection of important clini- Whenever possible, biopsies should be performed percuta- copathologic information. neously.5 If the lesion is palpable, either FNA biopsy or CNB is NONINVASIVE CANCER suitable [see 3:5 Breast Procedures]. FNA biopsy is less invasive, but its performance requires the specialized expertise of a cytopathol- ogist. CNB has the advantage of allowing histologic evaluation, Ductal Carcinoma in Situ which permits invasive cancers to be distinguished from in situ Before mammographic cancers and facilitates receptor analysis. If the lesion is not palpa- screening was widely prac- ble, biopsy can be performed under the guidance of diagnostic ticed, ductal carcinoma in imaging. Stereotactic and ultrasound-guided percutaneous core situ (DCIS) was generally biopsy techniques are minimally invasive and more expedient identified either as a palpable than open biopsy. With any of the imaging-guided approaches, lesion (usually with comedo however, it is important to verify that the visual interpretation of histology) or as an incidental the imaging abnormality is in concordance with the pathologic finding on a biopsy performed for another lesion. With the analysis of the specimen. increasing use of mammography, DCIS is accounting for a grow- ing proportion of breast cancer cases. According to the Surveillance Epidemiology and End Results (SEER) database, Management 15.9% of newly diagnosed breast cancers between 1997 and 2000 were DCIS.7 STAGING It was recognized early on that DCIS had a very favorable prog- In patients with newly nosis compared with other forms of breast cancer: long-term sur- diagnosed breast cancer, it is vival approached 100% after treatment with mastectomy. Axillary important to determine the lymph nodes were positive in only 1% to 2% of patients, most of overall extent of disease whom had large or palpable lesions or comedo histology. The before embarking on defini- prognosis for DCIS continues to be very favorable in relation to tive therapy. This process, referred to as clinical staging, includes that for invasive breast cancers. In theory, there is no potential for (1) physical examination to identify any areas of palpable disease metastatic disease with a purely in situ lesion. In practice, howev- in the breasts or the axillary and supraclavicular nodes, along with er, axillary node metastases continue to be found in 1% to 2% of a detailed clinical history to identify symptoms that may suggest patients thought to have pure DCIS, presumably arising from a metastatic disease; (2) imaging studies, including mammography, small area of invasion that was missed on pathologic evaluation. chest x-ray, and sometimes bone scans or CT scans of the chest, DCIS is believed to be a true anatomic precursor of invasive
  5. 5. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 1 Breast Cancer — 5 breast cancer. There are at least two lines of evidence that sup- 25% to 50% of patients at the site of the initial biopsy; all these port this conclusion. First, when DCIS is treated with biopsy tumors appear within 10 years and are of ductal histology. alone (usually because it was missed on the initial biopsy and not Second, when DCIS recurs locally after breast conservation, found until subsequent review), invasive carcinoma develops in invasive ductal carcinoma appears in about 50% of patients.The Table 1 American Joint Committee on Cancer TNM Clinical Classification of Breast Cancer TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ; intraductal carcinoma, lobular carcinoma in situ, or Paget disease of nipple with no associated tumor* T1 Tumor ≤ 2.0 cm in greatest dimension T1mic: microinvasion ≤ 0.1 cm in greatest dimension T1a: tumor > 0.1 cm but ≤ 0.5 cm in greatest dimension T1b: tumor > 0.5 cm but ≤ 1.0 cm in greatest dimension Primary tumor (T) T1c: tumor > 1.0 cm but ≤ 2.0 cm in greatest dimension T2 Tumor > 2.0 cm but ≤ 5.0 cm in greatest dimension T3 Tumor > 5.0 cm in greatest dimension T4 Tumor of any size with direct extension to (a) chest wall† or (b) skin T4a: extension to chest wall T4b: edema (including peau d'orange) or ulceration of the skin of the breast or satellite skin nodules confined to the same breast T4c: both of the above (T4a and T4b) T4d: inflammatory carcinoma‡ NX Regional lymph nodes cannot be assessed (e.g., previously removed) N0 No regional lymph node metastasis Regional lymph nodes (N) N1 Metastasis to movable ipsilateral axillary lymph node(s) N2 Metastasis to ipsilateral axillary lymph node(s) fixed to each other or to other structures N3 Metastasis to ipsilateral internal mammary lymph node(s) pNX Regional lymph nodes cannot be assessed (not removed or previously removed) pN0 No regional lymph node metastasis, no additional examination for isolated tumor cells pN0(i–): No regional lymph node metastasis histologically, negative IHC pN0(i+): No regional lymph node metastasis histologically, positive IHC, no IHC cluster > 0.2 mm pN0(mol–): No regional lymph node metastasis histologically, negative molecular findings (RT-PCR) pN0(mol+): No regional lymph node metastasis histologically, positive molecular findings (RT-PCR) pN1 Metastasis to 1–3 axillary lymph node(s) and/or in internal mammary nodes with microscopic disease detected by SLN dissection but not clinically apparent pN1mi: micrometastasis (> 0.2 mm, none > 2 mm) pN1a: metastasis in 1–3 lymph nodes pN1b: metastasis in internal mammary nodes with microscopic disease detected by SLN dissection but not clinically apparent Pathologic classification of lymph nodes (pN) pN1c: metastasis in 1–3 lymph nodes and in internal mammary nodes with microscopic disease detected by SLN dissection but not clinically apparent pN2 Metastasis in 4–9 axillary lymph nodes, or in clinically apparent internal mammary lymph nodes in the absence of axillary lymph node metastasis pN2a: metastasis in 4–9 axillary lymph nodes (at least 1 tumor deposit > 2.0 mm) pN2b: metastasis in clinically apparent internal mammary lymph nodes in the absence of axillary lymph node metastasis pN3 Metastasis in 10 or more axillary lymph nodes or in infraclavicular lymph nodes, or in clinically apparent ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes with clinically negative microscopic metastasis in internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes pN3a: metastasis in 10 or more axillary lymph nodes (at least 1 tumor deposit > 2.0 mm) or in infraclavicular lymph nodes pN3b: metastasis in clinically apparent ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by SLN dissection but not clinically apparent pN3c: metastasis in ipsilateral supraclavicular lymph nodes MX Presence of distant metastasis cannot be assessed Distant metastasis (M) M0 No distant metastasis M1 Distant metastasis present (includes metastasis to ipsilateral supraclavicular lymph nodes) * Paget disease associated with a tumor is classified according to the size of the tumor. †The chest wall includes ribs, the intercostal muscles, and the serratus anterior, but not the pectoral muscle. ‡Inflammatory carcinoma is a clinicopathologic entity characterized by diffuse brawny induration of the skin of the breast with an erysipeloid edge, usually without an underlying palpable mass. Radiologically, there may be a detectable mass and characteristic thickening of the skin over the breast. This clinical presentation is attributable to tumor embolization of dermal lymphatics with engorgement of superficial capillaries. SLN—sentinel lymph node IHC—immunohistochemistry RT-PCR—reverse transcriptase polymerase chain reaction
  6. 6. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 1 Breast Cancer — 6 Table 2 American Joint Committee on local, possibly invasive, recurrence after breast conservation against Cancer Staging System for Breast Cancer her feelings about the cosmetic and psychological effects of mastec- tomy. Mastectomy remains a reasonable treatment even for pa- tients with very small DCIS lesions if the primary concern is to max- Stage T N M imize local control of the cancer. Breast reconstruction after mas- tectomy for DCIS is an option that is open to most such patients. Stage 0 Tis N0 M0 SLNB [see 3:6 Lymphatic Mapping and Sentinel Lymph Node Stage I T1 N0 M0 Biopsy] usually is not required for the management of DCIS but should be considered in certain high-risk DCIS patients.12 It is gen- T0 N1 M0 erally offered to patients with palpable DCIS because of the high Stage IIA T1 N1 M0 T2 N0 M0 risk of invasive carcinoma associated with this condition. It is also offered to patients scheduled to undergo mastectomy for DCIS, T2 N1 M0 the rationale being that if invasive carcinoma is detected at the time Stage IIB T3 N0 M0 of mastectomy, SLNB would be impossible and a full axillary node T0 N2 M0 dissection would be required. Some surgeons offer SLNB to T1 N2 M0 patients with high-grade DCIS, particularly if comedonecrosis is Stage IIIA T2 N2 M0 present, but this measure is optional if breast conservation is T3 N1, N2 M0 planned. There are certain patients with DCIS for whom mastectomy Stage IIIB T4 N0, N1, N2 M0 remains the preferred treatment, such as those who have lesions Stage IIIC Any T N3 M0 larger than 5 cm in diameter or extensive microcalcifications on mammography. Some surgeons would also include in this catego- Stage IV Any T Any N M1 ry those who have comedo lesions larger than 2.5 cm and those who present with palpable DCIS. In these patients, the local recur- rence rate after breast conservation, even in conjunction with radi- true relationship between DCIS and invasive ductal carcinoma ation therapy, remains high. As many as half of these recurrences awaits a better understanding of the molecular biology of breast will contain invasive cancer with metastatic potential. cancer development. INVASIVE CANCER The consequence of the view that DCIS is a precursor of inva- sive cancer is that treatment is required once the diagnosis is Invasive breast cancer is made. Treatment options for DCIS include mastectomy and the most common malig- breast conservation, consisting of partial mastectomy followed by nancy affecting women. radiation; however, it should be remembered that although the risk Most breast malignancies of local recurrence is greater after breast conservation for DCIS arise from the terminal than after mastectomy, the likelihood of metastatic disease is very duct–lobular unit. The small.Wide excision to microscopically clean margins followed by majority are of ductal histol- radiation therapy has become an accepted alternative to mastecto- ogy, and a small proportion my. The National Surgical Adjuvant Breast and Bowel Project (10% to 15%) are of lobular histology.The histologic type makes (NSABP) B-17 study,8 which examined the role of radiation in the no difference to treatment, which is based on clinical staging and treatment of DCIS, found that the addition of radiation therapy to various patient factors. Lobular carcinomas can be challenging wide excision reduced the recurrence rate at 43 months after oper- both diagnostically and therapeutically. In particular, they may ation by approximately half, from 16.4% with wide excision alone be difficult to identify because they are often mammographical- to 7.0% with wide excision and radiation.The report also suggest- ly occult and tend to have an insidious growth pattern, infiltrat- ed that the addition of radiation therapy might reduce the inci- ing into the surrounding breast parenchyma. Special subtypes of dence of invasive recurrences. Partial-breast irradiation is now ductal carcinoma have also been described. One such subtype is being studied as an alternative to whole-breast irradiation.To date, tubular carcinoma, which represents about 3% to 5% of all inva- the results have been generally favorable, though the follow-up sive carcinomas. Pure tubular carcinomas are associated with a periods have been short.9,10 Smaller areas of DCIS, particularly significantly better prognosis, and distant metastasis is highly those that are of low to intermediate nuclear grade and are excised unlikely. Mucinous, or colloid, carcinoma is also associated with with wide margins, are increasingly being treated without radia- an excellent prognosis when diagnosed in its pure form. tion.11 Omission of radiation therapy is a complex decision that Medullary carcinoma, a subtype common in women with a should be based on the patient’s histology, the presence or absence hereditary predisposition to breast cancer, is associated with a of other risk factors, the presence or absence of contraindications more favorable prognosis as well. to radiation therapy, and the degree to which the patient is willing Evaluation of newly diagnosed breast cancers should also to accept a higher local recurrence rate. This option is probably include determination of estrogen receptor (ER) and progesterone best pursued in the context of a clinical trial. If clean margins can- receptor (PR) status and assessment of HER-2/neu amplification. not be obtained or if the cosmetic result is expected to be poor TREATMENT OPTIONS after excision to clean margins, mastectomy should be performed. Most patients in whom DCIS is identified mammographically Mastectomy versus Limited Surgery can choose between mastectomy and wide excision with or without radiation, either of which yields excellent long-term survival. Given Several randomized prospective studies have documented that the lack of any significant difference in survival between the two segmental resection (lumpectomy), axillary dissection, and post- options, the patient must weigh her feelings about the risk of a operative irradiation of an intact breast result in overall survival
  7. 7. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 1 Breast Cancer — 7 rates equal to those of modified radical mastectomy.13-16 Although surgery.17 Other patients have medical or psychiatric disorders most women with stage I and II breast cancers—indeed, most that would make it extremely difficult for them to comply with the women with breast cancer—are candidates for breast conserva- daily treatment schedule. Still others have specific medical con- tion therapy [see Table 3], some still require or desire mastectomy. traindications to radiation therapy, including pregnancy, collagen When a patient is eligible for limited surgery, the decision between vascular disease, or previous irradiation of the chest wall (as in a mastectomy and breast conservation with radiation therapy is woman with a local recurrence of a breast carcinoma that was made on the basis of patient and physician preference, access or treated with radiation therapy). Although there are some clinical lack of access to radiation therapy, and the presence or absence of data supporting the use of repeat local excision without further contraindications to breast conservation. irradiation to treat local recurrence after radiation therapy, most Patients undergoing lumpectomy and radiation therapy are at authorities favor mastectomy.19 Prospective, randomized trials risk for local recurrence in the treated breast, as well as for the have been initiated to determine the safety of partial-breast irradi- development of a new primary tumor in the remaining breast tis- ation, and the 66-month follow-up data currently available sug- sue. Local recurrences can generally be managed with mastecto- gest that partial-breast irradiation does not differ significantly my; overall survival is equivalent to that of women who underwent from whole-breast radiation with respect to local recurrence risk mastectomy at the time of initial diagnosis. There may, however, and yields better cosmetic results.18 be a significant cost to the patient in terms of anxiety about recur- When resection of the primary tumor to clean margins would rence, as well as the morbidity and potential mortality associated render the appearance of the remaining breast tissue cosmetically with undergoing a second surgical procedure. unacceptable, mastectomy may be preferable. This is likely to be On the other hand, patients who choose mastectomy as their the case, for example, in patients with large primary tumors rela- initial surgical treatment face the psychological consequences of tive to their breast size: resection of the primary tumor would losing a breast. Although they are at lower risk for local recurrence remove a substantial portion of the breast tissue. Another exam- than patients who choose lumpectomy, axillary node dissection, ple is patients with multiple primary tumors, who would have not and radiation, their overall survival does not seem to be signifi- only an increased risk of local recurrence but also poor cosmetic cantly improved. Each physician and each patient must weigh the results after multiple wide excisions. Patients with superficial cen- inconvenience and potential complications of radiation therapy tral lesions, including Paget disease, are eligible for wide excision and the risk of local recurrence against the value of breast preser- (including the nipple and the areola) followed by radiation thera- vation, keeping in mind that the choice between procedures py, provided that clean margins are obtained. The survival and appears to have no significant effect on survival. local recurrence rates in these patients are equivalent to those in other groups of patients undergoing lumpectomy and radiation.20-22 Contraindications to breast conservation Patients for In many cases, the cosmetic results of this procedure are prefer- whom mastectomy is still clearly the treatment of choice fall into able to those of immediate reconstruction, and there is always the four broad categories: (1) those in whom radiation therapy is con- option to reconstruct the nipple and areola later. traindicated, (2) those in whom lumpectomy would have an unac- Patients who are at high risk for local recurrence often choose ceptable cosmetic result, (3) those for whom local recurrence is a mastectomy as primary therapy. Features of primary tumors that concern, and (4) those high-risk patients in whom surgical pro- are associated with higher local recurrence rates after limited phylaxis is appropriate. surgery and irradiation include gross residual disease after lump- Radiation therapy may be contraindicated for any of several ectomy, multiple primary tumors within the breast, an extensive reasons. Some patients choose not to undergo radiation therapy, intraductal component, large tumor size, lymphatic vessel inva- either because it is inconvenient or because they are concerned sion, and lobular histologic findings.23 about potential complications (including the induction of second In practice, obtaining tumor-free margins is probably the most malignancies). Some patients simply do not have access to radia- critical factor in decreasing the risk of local recurrence.The diffi- tion therapy, either because they live in a rural area or because culty of obtaining microscopically clean margins in tumors with they have physical conditions that make daily trips for therapy an extensive intraductal component and in lobular carcinomas onerous. Time and travel issues related to weeks-long courses of may account for the higher local recurrence rates sometimes seen conventional radiotherapy have led to studies investigating partial- with these tumors. Histologic analysis of mastectomy specimens breast or limited-field irradiation after breast-conserving from patients with tumors with an extensive intraductal compo- nent has shown a high rate of multifocality within ipsilateral breast tissue; this residual disease is thought to be the nidus for local recurrence.24 The long-term benefits of choosing mastectomy to reduce local Table 3 Determinants of Patient Eligibility for recurrences are not clear. Whereas the appearance of distant Lumpectomy and Radiation Therapy metastases typically heralds incurable and ultimately fatal disease, Primary tumor ≤ 5 cm (may be larger in selected cases) local recurrence after breast conservation appears to have little, if Tumor of lobular or ductal histology any, impact on overall survival. Prospective, randomized trials Any location of primary within breast if lumpectomy to clean margins have had difficulty showing a statistically significant reduction in (including central lesions) will yield acceptable cosmetic results survival in women who have had a local recurrence after limited Clinically suspicious but mobile axillary nodes surgery and radiation therapy. It has been suggested that addition- Tumor either positive or negative for estrogen and progesterone al follow-up may eventually confirm reduced survival in some receptors patients with local recurrences. Still, most of the evidence suggests Any patient age that local recurrences are not the source of subsequent distant Absence of contraindication to radiation therapy (e.g., previous radi- ation therapy to breast or severe collagen vascular disease, such metastases. It is worthwhile to keep in mind, however, that even if as scleroderma) mastectomy to prevent local recurrence does not actually improve survival, it may nevertheless provide significant benefit by reduc-
  8. 8. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 1 Breast Cancer — 8 ing patient anxiety, the amount of follow-up testing required, and ma of the arm, it is appropriate only when there is sufficient risk the need for subsequent treatment. of axillary relapse to justify the increased complication rate. As a rule, supraclavicular node fields are irradiated only in patients with Options for axillary staging The histologic status of the multiple positive axillary nodes, who are at increased risk for supr- axillary nodes is the single most important predictor of outcome aclavicular disease. The role of prophylactic irradiation of the for breast cancer. Traditionally, axillary dissection has been a rou- internal mammary nodes remains controversial. tine part of the management of breast cancer. It has been used to Postmastectomy radiation therapy involves irradiation of the guide subsequent adjuvant therapy and provide local control, and chest wall after removal of the breast; it is mainly reserved for it may have contributed a small overall benefit in terms of sur- patients with T3 or T4 primary tumors or multiple positive lymph vival.25 Unfortunately, axillary dissection can be associated with nodes. Such therapy is recommended particularly when there are sensory morbidities and lymphedema. multiple positive axillary lymph nodes: significant axillary disease SLNB is a minimally invasive, less morbid, and quite accurate predicts higher rates of chest wall recurrence after mastectomy. method of detecting or ruling out occult lymph node metastasis Two series have suggested that postmastectomy radiation therapy [see 3:6 Lymphatic Mapping and Sentinel Lymph Node Biopsy]. It is significantly improves survival in premenopausal women with any based on the principle that the sentinel lymph node (SLN) is the positive axillary nodes.27,28 first node to which the tumor spreads; thus, if the SLN is tumor Irradiation of the breast or the chest wall is generally well toler- free, the patient can be spared the morbidity of an axillary dissec- ated: most women experience only minor side effects, such as tion. SLN biopsy identifies an increased number of patients with transient skin erythema, mild skin desquamation, and mild micrometastases, with some identified by immunohistochemical fatigue. Because a small amount of lung volume is included in the staining alone. Treatment of patients who have only micrometas- irradiated fields, there is usually a clinically insignificant but mea- tases to axillary nodes remains a topic of debate. Unfortunately, surable reduction in pulmonary function. In addition, because the the clinical trial of SLNB that the American College of Surgeons heart receives some radiation when the left breast or the left chest Oncology Group initiated in an attempt to address this question wall is treated, there may be a slightly increased risk of future (ACOSOG Z11) closed because of lack of accrual. myocardial infarction. There is also a 1% to 2% chance that the radiation will induce a second malignancy (sarcoma, leukemia, or Breast reconstruction after mastectomy Advances in a second breast carcinoma). These radiation-induced malignan- reconstructive techniques have made breast reconstruction cies appear after a long lag time, generally 7 to 15 years or longer. increasingly popular [see 3:5 Breast Procedures]. Reconstruction may be done either at the time of the mastectomy (immediate recon- Systemic Drug and Hormone Therapy struction) or later (delayed reconstruction). In the past, recon- Despite the success of surgical treatment and radiation therapy struction was generally delayed for 1 to 2 years after mastectomy; in achieving local control of breast cancer, distant metastases still now, it is most often performed immediately after mastectomy. In develop in many patients.Various drugs and hormones have there- general, however, immediate reconstruction is not ideal for pa- fore been used to treat both measurable and occult metastatic dis- tients likely to require postoperative adjuvant therapy. Although it ease. Now that many clinical trials have demonstrated a survival can still be done in these circumstances, the cosmetic outcome benefit, more and more women are receiving adjuvant cytotoxic may be inferior because irradiation can produce capsular contrac- chemotherapy. It became clear in early trials that multiple-agent ture in patients undergoing prosthetic reconstruction. (or combination) chemotherapy was superior to single-agent Prosthetic reconstruction involves the use of an implant to chemotherapy.29,30 It also became clear that chemotherapy and restore the breast contour. It is technically the simplest type of re- hormone therapy were limited in their ability to control large tu- construction but can still result in complications such as contrac- mor masses, though on occasion, patients with large tumor mass- ture, infection, and rupture, which may necessitate further surgery. es showed dramatic partial responses or even complete responses Autologous reconstruction involves the transfer of the patient’s to therapy. own tissue to reconstruct the breast. Tissue from various sites With the goal of eradicating breast cancer metastases while they (e.g., the rectus abdominis and the latissimus dorsi) has been used are still microscopic, systemic therapy is now administered in a so- for breast reconstruction. Skin-sparing mastectomy with immedi- called adjuvant setting—that is, when there is no evidence of dis- ate reconstruction consists of resection of the nipple-areola com- tant metastases but there is sufficient suspicion that metastasis plex, any existing biopsy scar, and the breast parenchyma, followed may have occurred. Until the late 1980s, adjuvant chemotherapy by immediate reconstruction. The generous skin envelope that was given primarily to women who had axillary node metastases remains optimizes the cosmetic result after breast reconstruction. but no other evidence of disease. In node-positive premenopausal The procedure is oncologically safe and does not lead to an women, adjuvant chemotherapy appeared to be significantly more increase in the incidence of local recurrence.26 beneficial than adjuvant hormone therapy. In node-positive post- menopausal women, on the other hand, hormone therapy Radiation Therapy appeared to be as beneficial as chemotherapy and less toxic. Current radiation therapy regimens consist of the delivery of This approach to adjuvant systemic therapy changed in 1988, approximately 50 Gy to the whole breast at a dosage of approxi- when the National Cancer Institute (NCI) issued a clinical alert mately 2 Gy/day, along with, in most cases, the delivery of an addi- stating that there was sufficient evidence of benefit to allow rec- tional 10 to 15 Gy to the tumor bed, again at a dosage of 2 Gy/day. ommendation of adjuvant chemotherapy or hormone therapy Axillary node fields are not irradiated unless there is evidence that for even node-negative breast cancer patients.31 By that time, a the patient is at high risk for axillary relapse—namely, multiple number of studies had shown that adjuvant chemotherapy could (generally more than four) positive lymph nodes, extranodal improve survival in node-negative breast cancer patients.32-34 A extension of tumor, or bulky axillary disease (i.e., palpable nodes consensus conference of experts in the field suggested that such several centimeters in diameter). Because the combination of sur- therapy be reserved for node-negative women with primary gical therapy and radiation therapy increases the risk of lymphede- tumors larger than 1 cm in diameter.35 In 1992, a meta-analysis
  9. 9. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 1 Breast Cancer — 9 that reviewed the treatment of 75,000 women in 133 random- which of the various strategies for their use is the best. Further ized clinical trials of adjuvant therapy for breast cancer conclud- study is needed to determine the optimal sequence of therapy. ed that in node-negative premenopausal women, overall long- Now that it has been established that hormonal agents are high- term survival was 20% to 30% higher for those who received ly effective in treating hormone receptor–positive tumors, the next chemotherapy than for those who did not.36 This benefit also challenge is how best to determine which early node-negative, appeared to extend to postmenopausal women between 50 and hormone receptor–positive tumors might behave aggressively and 60 years of age. thus might usefully be treated with adjuvant chemotherapy. The A number of prospective, randomized clinical trials have now traditional predictive tools have led physicians to treat a substan- shown that the use of trastuzumab with adjuvant chemotherapy tial number of women in order to benefit very few. However, mol- leads to a marked improvement in disease-free and overall survival ecular diagnostic tests now exist that may facilitate decision mak- in patients with HER-2/neu–positive tumors.37,38 One study has ing for patients with these tumors. The most widely used of these found trastuzumab therapy to be associated with a 33% reduction tests is Oncotype DX (Genomic Health, Inc., Redwood City, in the risk of death.37 Trastuzumab has also been associated with California), a 21-gene assay that addresses the biology of the tumor a 0.5% to 4.1% 3-year cumulative risk of class III/IV congestive and generates a recurrence score. Patients with low recurrence heart failure or cardiac death. In view of this risk, along with the scores tend to do well with hormonal therapy alone, whereas those known cardiotoxicity associated with anthracycline use, cardiac with high recurrence scores tend to benefit from the addition of function should be monitored during trastuzumab therapy. adjuvant chemotherapy.45,46 A 1998 overview of the use of adjuvant tamoxifen in random- ized trials demonstrated that women with ER-positive tumors Locally Advanced Cancer who were given tamoxifen for 5 years had a 47% reduction in Patients with locally tumor recurrence and a 26% reduction in mortality, compared advanced breast cancer with similar patients who were given placebo.39 In this analysis, the include those with primary effects of tamoxifen on recurrence and survival were independent tumors larger than 5 cm of age and menopausal status. Tamoxifen did not appear to im- (particularly those with pal- prove survival, however, in women with ER-negative tumors.These pable axillary lymph nodes), results, together with data on the efficacy of tamoxifen for chemo- those with fixed or matted prevention, have led to increased use of tamoxifen for premeno- axillary nodes, and those pausal women and for women with small tumors. with inflammatory breast carcinoma.These patients are at high risk Although tamoxifen is an excellent therapeutic agent and re- for systemic disease, as well as for local failure after standard local mains the standard therapy for hormone receptor–positive therapy. Current practice is to administer multimodality therapy, breast cancers in premenopausal women, aromatase inhibitors with chemotherapy as the first treatment modality. This so-called have proved to be superior for treating such cancers in post- neoadjuvant chemotherapy often has the effect of downstaging menopausal women. These agents are pure antiestrogens: they local disease, in some cases making inoperable tumors amenable to function by preventing the peripheral conversion of fat and other surgical resection. Patients are treated with FNA, core-needle, or substrates to estrogen. The first published study to demonstrate open incisional biopsy to obtain a tissue diagnosis, hormone recep- the superiority of an aromatase inhibitor to tamoxifen was the tor data, and HER-2/neu status; they then undergo careful restag- Arimidex (i.e., anastrozole), Tamoxifen, Alone or in ing after systemic therapy to identify any distant metastases. If the Combination (ATAC) trial.40 This study showed that anastro- tumor responds to chemotherapy, the patient may then undergo zole, 1 mg daily, was superior to tamoxifen, 20 mg daily, and that radiation therapy, surgery, or both. Most patients require all three there was no added benefit to the combination of the two drugs. modalities for optimum local and systemic control. These two medications have different side-effect profiles: tamox- The optimal treatment of patients with stage IIIa breast cancer ifen is associated with an increased risk of thromboembolic remains controversial. Some practitioners favor neoadjuvant events and endometrial cancer, whereas anastrozole is associat- chemotherapy, whereas others favor surgery followed by ed with bone loss and joint aches. After a median follow-up peri- chemotherapy and radiation therapy. The choice of surgical pro- od of 68 months, anastrozole therapy was associated with signif- cedure for women with locally advanced breast cancer is also con- icant prolongation of disease-free survival (575 events with anas- troversial. Whereas many surgeons favor mastectomy for all trozole versus 651 with tamoxifen) and time to recurrence (402 tumors larger than 5 cm, others offer wide excision with axillary recurrences versus 498), as well as significant reduction of dis- dissection to patients in whom excision to clean margins will leave tant metastases (324 distant metastases versus 375) and con- a cosmetically acceptable breast. tralateral breast cancers (35 contralateral cancers versus 59); however, it yielded no significant improvement in overall sur- Stage IV Cancer vival.41 Anastrozole seems to be particularly effective for treat- Patients with distant ment of ER-positive, PR-negative tumors, which are more resis- metastases, whether at their tant to tamoxifen therapy. Other aromatase inhibitors have also initial presentation or after been evaluated against tamoxifen. One such agent, letrozole, has previous treatment for an been shown to be superior to tamoxifen as initial therapy and to earlier-stage breast cancer, be beneficial when taken for an additional 5 years after comple- are rarely cured. Before treat- tion of a 5-year course of tamoxifen.42,43 Another such agent, ment begins, a tissue diagno- exemestane, has been studied in a crossover fashion: 2 to 3 years sis consistent with breast of tamoxifen followed by 2 to 3 years of exemestane has been cancer must be obtained shown to be superior to 5 years of tamoxifen alone.44 Although from the primary lesion (at the initial presentation of the disease) it seems clear that in general, aromatase inhibitors are superior or from a metastasis (if there is any doubt about the metastatic to tamoxifen, the data are currently insufficient to determine nature of the lesion or the source of the metastatic disease). Any tis-
  10. 10. © 2007 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 3 BREAST, SKIN, AND SOFT TISSUE 1 Breast Cancer — 10 sue samples obtained should be sent for ER and PR assays and large majority of male breast cancers are ER positive, and deci- determination of HER-2/neu status. sions regarding adjuvant systemic treatment should be made on The usual first-line treatment for metastatic breast cancer is the same basis as for breast cancer in women. cytotoxic chemotherapy or hormone therapy. Radiation therapy FOLLOW-UP AFTER TREATMENT may be used to relieve pain from bone metastases or to avert a pathologic fracture at a site of metastatic disease. There is also Patients who have been treated for breast cancer remain at risk occasionally a role for so-called toilet mastectomy for patients who for both the recurrence of the original tumor and the development have metastatic disease and a locally advanced and ulcerated pri- of a new primary breast cancer. The rate of recurrence of breast mary tumor if the condition of the primary tumor prevents the cancer is nearly linear over the first 10 years after treatment. administration of needed chemotherapy. In fact, the current liter- Recurrence becomes less likely after the first decade, but it contin- ature suggests that even in the presence of metastatic disease, sur- ues at a significant rate through the second decade and beyond. In gical removal of the primary tumor improves survival.47,48 patients who have undergone limited surgery and radiation thera- Treatment for stage IV breast cancer should be on protocol py, radiation-induced breast and chest wall malignancies begin to whenever possible. For patients who are ineligible for therapy on appear 7 or more years after treatment and continue to appear for protocol, palliative chemotherapy or hormone therapy may be the at least 20 years after treatment. best treatment option. Unfortunately, there is little in the way of evidence-based guid- ance to help the clinician determine the optimal posttreatment BREAST CANCER IN PREGNANCY surveillance strategy for breast cancer patients. As a result, practice Breast cancer is the second most common malignancy associat- patterns vary considerably with respect to the use of follow-up ed with pregnancy (after cervical cancer), occurring during 1 of tests in this population. Exhaustive posttreatment testing does not every 3,000 pregnancies.49 The diagnosis of breast cancer in preg- seem warranted in early-stage breast cancer patients. There is no nancy is often delayed because of the physiologic changes that evidence to support the use of routine bone scans, computed pregnancy induces in the breast.To minimize diagnostic delays, all tomography, PET brain imaging, or serum tumor markers in breast masses detected in pregnant women should be thoroughly asymptomatic patients after treatment for early-stage disease.The evaluated. If mammography is truly indicated, it may be safely per- use of such intensive surveillance is based on the presumption that formed on a pregnant patient, provided that the fetus is appropri- detecting disease recurrence at its earliest stage would offer the ately shielded. Ultrasonography may also be quite helpful in eval- best chance of cure, improved survival, or, at least, improved qual- uating breast masses in pregnant women. ity of life. Given that the majority of recurrences are detected by Once the diagnosis is made, therapy depends on the stage of the patients themselves, educating patients about the symptoms of pregnancy. Termination of pregnancy usually is not necessary for recurrent disease is likely to be a more effective strategy. treatment of the cancer. Because exposure to radiation is con- Follow-up of early-stage breast cancer patients should include a traindicated at all stages of pregnancy, mastectomy is generally ne- thorough history and physical examination and mammography. cessary for all patients except those whose cancers are diagnosed For patients treated with breast conservation, annual mammogra- at a late stage, for whom radiation therapy can reasonably be de- phy is appropriate, beginning after any acute radiation reaction has layed until after delivery. For this reason, mastectomy is the pre- resolved (generally 6 to 9 months after completion of radiation ferred surgical therapy in most instances. Breast conservation may therapy). For patients treated with mastectomy, mammography be performed if the cancer is diagnosed in the third trimester. As should be continued on an annual basis for the contralateral far as axillary staging is concerned, there have been no reported breast. Physical examination and review of symptoms are general- consequences to either the mother or the fetus from injections of ly performed at 3- to 6-month intervals for the first 5 years after technetium-99m–labeled sulfur colloid, and it is generally consid- completion of therapy, though these intervals have not yet been ered fairly safe to use radioisotopes in the performance of SLNB. tested in a prospective fashion. The safety of isosulfan blue dye in pregnancy is less clear, and vital Although there has been little debate about the value of early blue dyes usually are best avoided.With respect to chemotherapy, detection of a local recurrence within the treated breast or of a new administration of cytotoxic agents should be avoided in the first primary tumor in either breast, there has been a great deal of trimester but is considered to be much less risky—and therefore debate about the value of early detection of metastatic disease. acceptable—in the second and third trimesters. Two prospective, randomized trials addressed this issue. In one, a group of breast cancer patients was intensively followed with blood BREAST CANCER IN MEN tests every 3 months and with chest x-rays, bone scans, and liver Fewer than 1% of all breast carcinomas occur in men. Pre- ultrasonography annually.51 There was no difference in survival or disposing risk factors include conditions associated with increased quality of life between this group and the control group, and estrogen levels (e.g., cirrhosis and Klinefelter syndrome) and radi- metastatic disease was diagnosed, on average, less than 1 month ation therapy.50 In addition, an increased incidence of male breast earlier in the intensively followed group than in the control group. cancer has been reported in families in which the BRCA2 muta- In the second study, a group of breast cancer patients received tion has been identified. As with breast cancer in women, the most chest x-rays and bone scans every 6 months for 5 years.52 common tumor type is infiltrating ductal cancer. Because breast Pulmonary and bone metastases were detected significantly earli- cancer tends to be detected at a later stage in men than in women, er in this group than in the control group, but there was no there is a misconception that male breast cancer has a worse prog- improvement in survival. This study demonstrated that early nosis. Stage for stage, however, the prognosis for men with breast detection of metastatic disease could be achieved with short-inter- cancer is similar to that for women with breast cancer. To prevent val screening, but given current therapeutic options, early detec- late detection, men with a breast mass must be evaluated with the tion had no beneficial effect on survival. Both studies concluded same degree of suspicion as women with a breast mass. that at present, there is no role for routine imaging studies in the Surgical treatment includes mastectomy. In the absence of clin- follow-up of breast cancer patients and that imaging studies ically palpable nodes, SLNB is appropriate for staging the axilla. A should be ordered only as prompted by clinical findings.
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Ductal carcinoma in situ: trends in geo- nent residual disease in the remainder of the tial adjuvant therapy for postmenopausal women graphic, temporal, and demographic patterns of breast. J Clin Oncol 8:113, 1990 with endocrine-responsive early breast cancer: care and survival. Breast J 12:20, 2006 update of study BIG 1-98. J Clin Oncol 25:486, 25. Morrow M: A survival benefit from axillary dissec- 2007 8. Fisher B, Costantino J, Redmond C, et al: tion: was Halsted correct? Ann Surg Oncol 6:17, Lumpectomy compared with lumpectomy and 1999 43. Goss PE, Ingle JN, Martino S, et al: A randomized radiation therapy for the treatment of intraductal trial of letrozole in postmenopausal women after 26. Simmons RM, Adamovich TL: Skin-sparing mas- breast cancer. N Engl J Med 328:1581, 1993 five years of tamoxifen therapy for early-stage tectomy. Surg Clin North Am 83:885, 2003 breast cancer. N Engl J Med 349:1793, 2003 9. Benitez PR, Streeter O, Vicini F, et al: Preliminary 27. 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Fisher B, Costantino J, Redmond C, et al: A ran- improves survival of patients with metastatic breast 14. Fisher B, Bauer M, Margolese R, et al: Five-year domized trial evaluating tamoxifen in the treat- cancer at diagnosis. J Clin Oncol 24:2743, 2006 results of a randomized clinical trial comparing ment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N 49. Allen HH, Nisker JA: Cancer in pregnancy thera- total mastectomy and segmental mastectomy with peutic guidelines. Cancer and Therapy: Therapeu- or without radiation in the treatment of breast can- Engl J Med 320:479, 1989 tic Guidelines. Allen HH, Nisker JA, Eds. Futura cer. N Engl J Med 312:665, 1985 33. Fisher B, Redmond C, Dimitrov NV, et al: A ran- Publishing, Mount Kisco, New York, 1986 15. Fisher B, Redmond C, Poisson R, et al: Eight year domized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of 50. Buzdar AU: Breast cancer in men. Oncology results of a randomized clinical trial comparing (Huntingt) 17:1361, 2003 total mastectomy and lumpectomy with or without patients with node-negative breast cancer who irradiation in the treatment of breast cancer. N have estrogen-receptor-negative tumors. N Engl J 51. GIVIO Investigators: Impact of follow-up testing Engl J Med 320:822, 1989 Med 320:473, 1989 on survival and health-related quality of life in 34. Mansour EG, Gray R, Shatila NH, et al: Efficacy breast cancer patients. JAMA 271:1587, 1994 16. Fisher B, Anderson S, Bryant J, et al: Twenty-year follow-up of a randomized trial comparing total of adjuvant chemotherapy in high-risk node-nega- 52. Del Turco MR, Palli D, Cariddi A, et al: National mastectomy, lumpectomy, and lumpectomy plus tive breast cancer. N Engl J Med 320:485, 1989 Research Council Project on Breast Cancer irradiation for the treatment of invasive breast can- 35. NIH Consensus Conference: Treatment of early- Follow-up. Intensive diagnostic follow-up after cer. N Engl J Med 347:1233, 2002 stage breast cancer. JAMA 265:391, 1991 treatment of primary breast cancer: a randomized 17. Wallner P, Arthur D, Bartelink H, et al: Workshop trial. JAMA 271:1593, 1994 36. Early Breast Cancer Trialists’ Collaborative on partial breast irradiation: state of the art and the Group: Systemic treatment of early breast cancer science. Bethesda, MD, December 8–10, 2002. J by hormonal, cytotoxic, or immune therapy: 133 Natl Cancer Inst 96:175, 2004 randomised trials involving 31,000 recurrences Acknowledgment 18. Polgar C, Fodor J, Major T, et al: Breast-conserv- and 24,000 deaths among 75,000 women. Lancet ing treatment with partial or whole breast irradia- 339:71, 1992 The authors gratefully acknowledge the contributions tion for low-risk invasive breast carcinoma—5-year 37. Romond EH, Perez EA, Bryant J, et al: of D. Scott Lind, M.D., F.A.C.S., and Barbara L. results of a randomized trial. Int J Radiat Oncol Trastuzumab plus adjuvant chemotherapy for Smith, M.D., Ph.D., F.A.C.S., coauthors of the previ- Biol Phys, May 24, 2007 [Epub ahead of print] operable HER2-positive breast cancer. N Engl J ous iteration of this chapter, to the development and 19. Newman LA, Washington TA: New trends in Med 353:1673, 2005 writing of the current iteration.

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