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Official reprint from UpToDate www.uptodate.com.sci­hub.cc ©2015 UpToDate

AuthorsMichael S Sabel, MDLori J Pierce, MD

Section EditorsAnees B Chagpar, MD, MSc, MA,MPH, MBA, FACS, FRCS(C)Daniel F Hayes, MD

Deputy EditorWenliang Chen, MD, PhD

Breast conserving therapy

All topics are updated as new evidence becomes available and our peer review process is complete.Literature review current through: Nov 2015. | This topic last updated: Jul 27, 2015.

INTRODUCTION — Breast conserving therapy (BCT) refers to breast conserving surgery (BCS), followed bymoderate­dose radiation therapy (RT) to eradicate any microscopic residual disease. The goals of BCT are toprovide the survival equivalent of mastectomy, a cosmetically acceptable breast, and a low rate of recurrence inthe treated breast.

While modern techniques are less morbid than radical mastectomy, a mastectomy still requires the loss of thebreast. For this reason, the question arose as to whether the breast could be preserved without compromisingsurvival. Six modern, prospective, randomized clinical trials directly comparing BCT with mastectomy [1­9] and anoverview of all completed trials [10] have shown equivalent survival between the two treatment approaches. Thesuccess of BCT is contingent upon moderate­dose RT in eliminating subclinical foci of disease in the ipsilateralbreast. (See "Adjuvant radiation therapy for women with newly diagnosed, non­metastatic breast cancer".)

The major issues related to breast conservation techniques for surgical treatment of breast cancer will be reviewedhere. The diagnosis and management of breast cancer is discussed elsewhere. (See "Overview of the treatment ofnewly diagnosed, non­metastatic breast cancer".)

PATIENT SELECTION FOR BCT — The selection of appropriate patients is crucial to the success of breastconserving therapy (BCT). Although BCT provides an acceptable alternative to mastectomy for the treatment ofinvasive breast cancer, it is not applicable to all patients. Mastectomy is mandatory for tumor control for somesubgroups of patients with breast cancer, and it may provide more satisfactory outcomes in others. (See"Mastectomy: Indications, types, and concurrent axillary lymph node management".)

The American College of Surgeons, the American College of Radiology, the College of American Pathologists, andthe Society of Surgical Oncology have developed consensus standards of care for BCT [11]. Similarrecommendations have been made by the Canadian Steering Committee on Clinical Practice Guidelines for theCare and Treatment of Breast Cancer [12]. The following issues are emphasized in the appropriate selection ofpatients for BCT:

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A complete history and physical examination prior to treatment.

Tissue biopsy with core needle sampling to provide conclusive proof of malignancy. Needle biopsy ispreferred over surgical biopsy to reduce unnecessary surgery and avoid scars that may complicate theplacement of the subsequent lumpectomy incision. (See "Breast biopsy".)

Accurate histologic assessment of the primary tumor, including histologic subtype, hormone receptor status,and HER2 status. (See "Pathology of breast cancer" and "Prognostic and predictive factors in early, non­metastatic breast cancer", section on 'Tissue markers' and "HER2 and predicting response to therapy inbreast cancer", section on 'Testing for HER2 expression' and "Hormone receptors in breast cancer: Clinicalutility and guideline recommendations to improve test accuracy", section on 'Assays for ER and PR' and"Prognostic and predictive factors in metastatic breast cancer", section on 'Tests done on breast tissue'.)

Once the diagnosis of cancer is made, multidisciplinary coordination among breast and reconstructivesurgeons, radiation and medical oncologists, and radiologists and pathologists facilitates treatment planning

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Selection criteria for BCT — The individual patient's needs and expectations should be accurately assessed.This requires that the patient and physician discuss the benefits and risks of mastectomy compared to breastconserving therapy (BCT) in regards to long­term survival, the possibility and consequence of local recurrence witheither treatment, and the impact on cosmetic outcome and psychosocial adjustment. There are many issues toconsider regarding this decision:

and streamlines patient care [13]. In some cases, neoadjuvant chemotherapy is warranted to decrease thetumor size and improve the success rate of breast conservation. (See "Diagnostic evaluation of women withsuspected breast cancer" and "Neoadjuvant therapy for breast cancer: Rationale, pretreatment evaluation,and therapeutic options".)

Preoperative breast imaging, to define the extent of disease and identify multifocal or multicentric cancer thatcould preclude breast conservation or potential difficulty in achieving clear surgical margins. Imaging typicallyincludes a combination of bilateral mammographic evaluation, with appropriate magnification views, andultrasound, if appropriate. The tumor size should be included in the mammographic report, as well asdocumentation of associated microcalcifications, and the extent of the calcifications within and outside themass. (See "Clinical features, diagnosis, and staging of newly diagnosed breast cancer", section on'Assessing the extent of disease'.)

Some surgeons may incorporate breast magnetic resonance imaging (MRI) in the work­up of patientsconsidering BCT, however the use of routine MRI in this setting is not indicated. The indications for breastMRI for the preoperative assessment of disease in newly diagnosed breast cancer are listed here anddiscussed in detail elsewhere. (See "Diagnostic evaluation of women with suspected breast cancer", sectionon 'Breast MRI'.)

For a clinical presentation of disease that is larger than what is appreciated by mammography(particularly in the setting of dense breasts which lower the sensitivity of mammography)

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For invasive cancers that are contiguous to the chest wall and not completely included onmammographic projections,

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For patients with axillary nodal metastases and a clinically and mammographically occult primary tumor•

For women with Paget’s disease of the breast who have a negative physical examination andmammogram

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In women with locally advanced breast cancer who are being considered for neoadjuvant systemictherapy to assess tumor response to therapy

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For women with very high risk for contralateral disease because of an inherited predisposing condition,or prior chest wall irradiation

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Women should be informed of the risks and benefits of preoperative breast MRI. The limits of the accuracyof MRI should be discussed with patients, so that they understand the need for biopsy of MRI detectedlesions before definitive surgery. Breast MRI should be performed with a dedicated breast coil by expertbreast imaging radiologists in institutions that have the capability to perform MRI guided needle biopsy and/orwire localization of the findings.

Surgical decisions should not be based on MRI findings alone. MRI findings alone should not be used tochange surgical planning and conversion from breast conservation to mastectomy. All suspicious findings onMRI require pathologic confirmation.

Age is not a contraindication to BCT; physiologic age and the presence of comorbid conditions should be theprimary determinants of local therapy in older women.

Retraction of the skin, nipple, or breast parenchyma is not necessarily a sign of locally advanced breast

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In addition, MRI was performed more often in patients with dense breast tissue (65 versus 33 percent). However,breast density was not associated with positive margins for BCS or conversion to a mastectomy, and preoperativeMRI did not decrease the risk of positive margins.

Special considerations

Connective tissue disease — Some patients with a history of connective tissue disease tolerate irradiationpoorly, and so the use of RT as a component of BCT must be weighed against the possible complications [19­24].However, despite numerous case reports describing radiation­induced toxicities, none of the three publishedretrospective matched­control studies have shown a statistically significant increase in acute toxicities in thispatient population as a whole [20,22,23]. Only one was able to show a statistically significant increase in the riskof late complications in patients with connective tissue disease, and this effect disappeared in subset analysis bydisease in all patients but those with scleroderma [22].

In contrast, the largest of the three studies noted that patients with scleroderma and systemic lupuserythematosus (SLE), but not rheumatoid arthritis, were at a significantly increased risk of late toxicities. As aresult, many radiation oncologists consider scleroderma and active SLE to be relative contraindications to BCT[11,24]. (See "Overview of the clinical manifestations of systemic sclerosis (scleroderma) in adults".)

cancer and does not contraindicate BCT. However, if a portion of skin or the nipple areolar complex will needto be resected to achieve negative margins, the cosmetic implications of this should be factored into thedecision to proceed with BCT.

Histologic subtypes other than invasive ductal carcinoma (eg, invasive lobular cancer) are not associatedwith an increased risk of breast cancer recurrence [14,15]; these women are candidates for BCT if the tumordistribution is not diffuse and it can be excised with negative margins [16]. (See "Pathology of breastcancer".)

The presence of an extensive intraductal component (EIC) is an indicator that disease extent may be greaterthan clinically suspected but is not a contraindication to BCT by itself. Patients with negative margins arestill acceptable candidates for BCT. (See 'Extensive intraductal component (EIC)' below.)

Lymph node positivity is a marker of worse prognosis, but positive lymph nodes are not a contraindication forBCT, as BCT and mastectomy have equivalent outcomes independent of nodal metastases. (See "Adjuvantradiation therapy for women with newly diagnosed, non­metastatic breast cancer", section on 'Patientstreated with mastectomy'.)

Tumor location should not influence the choice of treatment. Tumors in a superficial subareolar location mayrequire resection of the nipple­areolar complex to achieve negative margins; oncologic outcomes will not beaffected, but the cosmetic result may be. Although oncoplastic techniques improve cosmesis [17], thepatient and her clinician need to assess whether such a resection is preferable to mastectomy.

A family history of breast cancer is not a contraindication to BCT (see 'Inherited susceptibility' below);however, women with a strong family history suggestive of a genetic predisposition should be informed abouttheir increased risk of a second primary cancer. (See "Overview of hereditary breast and ovarian cancersyndromes".)

A high risk of systemic relapse is not a contraindication for BCT but instead indicates the need for adjuvantsystemic therapy.

Breast conservation surgery (BCS) is not contraindicated for women with dense breast tissue. In aprospective study of 1052 patients undergoing attempted BCS, patients with dense breast tissue weresignificantly more likely to be treated with an initial mastectomy compared with women with less densebreast tissue (74 versus 52 percent, odds ratio [OR] 1.94, 95% CI 1.44­2.62, p <0.0001) [18]. This mayreflect surgeon or patient bias rather than an inability to fulfill criteria for BCS.

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Tumor size — Tumor size relative to breast size is an important consideration in selecting patients for BCT. Alarge tumor in a small breast is a relative contraindication, since an adequate resection would result in significantcosmetic alteration. However, tumor size in itself is not an absolute contraindication to BCT. Breast size is alsonot in itself a contraindication to BCT. Women with large or pendulous breasts can undergo breast irradiationsuccessfully as long as reproducibility of patient setup can be ensured, and it is technically possible to obtainadequate dose homogeneity.

Role of neoadjuvant treatment — Neoadjuvant treatment with chemotherapy or hormonal therapy can reducetumor size significantly and allow for breast conservation with acceptable rates of local recurrence (table 1) [25].

Clip placement in the tumor bed under ultrasound guidance should be accomplished before or soon afterneoadjuvant treatment begins if possible. The metallic clip ensures that the surgeon can accurately localize thetumor bed in case there is a complete response to chemotherapy.

The presence of multicentric disease, extensive micro­calcifications, extensive skin changes, a clinical diagnosisof inflammatory breast cancer, and dermal lymphatic involvement are considered contraindications for thisapproach.

Contraindications — There are few absolute contraindications to BCT. They include:

PREOPERATIVE PREPARATION

Antibiotics — A preoperative antibiotic, such as cefazolin, should be administered after arriving in the operatingroom and before the incision is made [27­29]. The efficacy of antibiotic prophylaxis decreases if administered morethan one hour before surgery (table 2) [30­32]. A meta­analysis of the randomized controlled trials of preoperativeantibiotics versus placebo in patients undergoing breast surgery found that the use of preoperative antibiotics wasassociated with a significant reduction in infection (relative risk = 0.60; CI = 0.45 to 0.81) [33]. (See "Antimicrobialprophylaxis for prevention of surgical site infection in adults".)

Deep venous thrombosis prophylaxis — For patients undergoing general anesthesia, primary prophylaxis forprevention of deep venous thrombosis, such as sequential compression devices, should be employed (table 3).(See "Prevention of venous thromboembolic disease in surgical patients".)

SURGICAL TECHNIQUE — The type and location of the incision is important for several reasons. It isimperative to remember that any patient who undergoes lumpectomy may ultimately require a mastectomy, andincisions should be planned with possible mastectomy incisions in mind. The incision should be placed close tothe tumor to avoid extensive tunneling. In the upper part of the breast, incisions should be curvilinear or transverseand follow the natural skin creases (Langer's lines). In the lower part of the breast, the choice of a curvilinear orradial incision is dependent upon the contour of the breast, the distance from the skin to the tumor, and the amountof breast tissue to be resected. At the completion of the procedure, the incision should be closed with asubcuticular suture to avoid cross­hatching of the skin.

In deeper lesions, it is not necessary to remove skin, and preservation of the subcutaneous fat and avoidance of

Multicentric disease with two or more primary tumors in separate quadrants of the breast such that theycannot be encompassed in a single excision.

Diffuse malignant microcalcifications on mammography.

A history of prior therapeutic RT that included a portion of the affected breast, which when combined with theproposed treatment, would result in an excessively high total radiation dose to the chest wall.

Pregnancy is an absolute contraindication to the use of breast irradiation; however, it may be possible toperform breast­conserving surgery in the third trimester, deferring breast irradiation until after delivery. (See"Gestational breast cancer: Epidemiology and diagnosis".)

Persistently positive resection margins after multiple attempts at reexcision [26].

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thin skin flaps are important in maintaining a normal post­treatment breast contour. If the tumor is superficial, itmay be necessary to remove the overlying skin. Skin removal with a curvilinear incision in the inferior breastdistorts the breast contour and should be avoided. It is also not necessary to remove needle tracks from core­needle biopsies or fine­needle aspirations.

Meticulous hemostasis is important, because a large hematoma distorts the appearance of the breast and makesre­excision and follow­up evaluation more difficult. The presence of a postbiopsy hematoma is not acontraindication to breast conserving therapy (BCT). Reapproximation of the breast tissue without tissueadvancement is best avoided, since it can result in distortion of the breast contour, which may not be apparentwith the patient supine on the operating table [11]. Cosmetic outcomes can be improved with oncoplastictechniques. (See "Oncoplastic techniques in breast conserving surgery".)

Long­term complications of both BCT and mastectomy are presented elsewhere. (See "Overview of breastreconstruction" and "Patterns of relapse and long­term complications of therapy in breast cancer survivors",section on 'Long­term adverse effects of primary therapy'.)

Evaluation of the axilla — Evaluation of the axilla provides information for treatment decisions in patients withinvasive breast cancer. Sentinel node biopsy is the standard initial approach for patients with a clinically negativeaxillary examination. The management of the regional lymph nodes in breast cancer, sentinel node biopsy, andaxillary dissection, are discussed elsewhere. (See "Management of the regional lymph nodes in breast cancer" and"Diagnosis, staging and the role of sentinel lymph node biopsy in the nodal evaluation of breast cancer" and"Technique of axillary lymph node dissection".)

Margins of resection — Microscopic resection margins are the major selection factor for breast conservingtherapy (BCT), because of their marked influence on local recurrence. Women with negative excision marginshave low rates of local recurrence following BCT [1,34­46], while positive resection margins (ie, carcinoma at theinked margin) are associated with a higher risk of local recurrence [36,38­41,43­45,47].

The appropriate macroscopic margin of normal breast tissue to resect around the tumor for women undergoingBCT should be 0.5 to 1.0 cm of grossly normal breast tissue, which will usually result in histologically negativemargins (ie, no tumor at ink) in the majority of patients [48]. Larger resections may be necessary for invasivecarcinomas with an extensive intraductal component (EIC) [49­51] or for infiltrating lobular carcinomas [1,52­54].Preoperative wire localization, specimen orientation, specimen radiography, intraoperative margin assessment, andpost­excision whole cavity shaving are all helpful for obtaining negative excision margins, as discussed below.

Wire localization For resection of nonpalpable lesions, preoperative wire localization by the radiologistallows accurate identification of the area requiring resection [55]. Multiple bracketing wires may be helpful fordelineation of the boundaries of the resection, but do not ensure clear histologic margins of resection. As anexample, in one study of wire bracketing for preoperative localization of 75 cancers, clear histologic marginsof resection were obtained in 33 patients (44 percent).

Specimen orientation The specimen can be removed as a single piece of tissue. Gross inspection of thespecimen in the operating room, with or without frozen section analysis, permits identification of positive orclose margins and immediate reexcision, if appropriate [56]. This will decrease the need to return to theoperating room for re­excision. Sutures, clips, and/or multicolored inks are used to orient the specimen by theoperating surgeon. Inking kits are available with six colors for labeling all of the surgical margins (superior,inferior, medial, lateral, superficial, and deep). Clear uniformity between surgeon and pathologist in terms ofwhat suture or color corresponds to each margin is required. This facilitates reporting of the status ofindividual margins and if re­excision is required, the surgeon can limit the re­excision to the involved margin[57].

Specimen radiography Specimen radiography should be performed during the surgical procedure toconfirm excision of the targeted lesion when the lesion was not palpable. Additional oriented margins can beresected prior to closure when the radiograph suggests inadequate resection, which may eliminate the need

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Indications for wider excision of margins — The indication for a wider excision following breast conservingsurgery is a histologically positive tumor margin identified on the surgical specimen. A histologically positivemargin is defined as the presence of ink at the surface of the invasive or noninvasive cancer; a positive marginimplies a potentially incomplete resection. Patients with a positive tumor margin have an at least twofold increasein ipsilateral local breast cancer recurrence [48]. The risk of a local recurrence with a positive margin was notreduced by the use of radiation boost to tumor bed, adjuvant endocrine therapy, or chemotherapy.

Thus, research has been focused on the optimal amount of normal tissue that should surround the tumor tominimize the risk of a local recurrence [43,48,78,79]. Based upon a meta­analysis that included 33 studies and28,162 patients with 1506 ipsilateral recurrences, a multidisciplinary consensus panel supports the use of no inkon the tumor as an adequate negative margin of resection for invasive breast cancers [48].

There was no evidence that a wider margin of normal tissue than no ink on the tumor decreased the rate of localrecurrence in the clinical setting of multimodality treatment. This includes many subgroups previously thought torequire more aggressive treatment, including younger patients (<40 years of age), those with aggressive biologicsubtypes or invasive lobular carcinoma, and extensive intraductal carcinoma without residual microcalcifications[80­85].

While recognizing that routine practice to obtain wider margins than ink on tumor is not indicated, some expertshave advocated for flexibility in the application of the above guidelines in light of the generally weak (retrospective)evidence supporting the recommendations [86]. We suggest an individualized approach to patients with close (<1mm) margins with regard to re­excision [87].

Cosmetic outcome — Many surgical factors will play a role in the ultimate cosmetic appearance of the breast.These include the size and placement of the incision, management of the lumpectomy cavity, and the extent ofaxillary dissection if necessary. The surgeon has control over several of these issues, and careful attention todetail will improve the aesthetic results [88,89].

In addition to local recurrence, a major goal of BCT is the preservation of a cosmetically acceptable breast. Withmodern treatment techniques, an acceptable cosmetic outcome can be achieved in almost all patients without

for a delayed re­excision. In a retrospective study of 123 patients undergoing BCS, specimen radiographyidentified 19 patients with a margin ≤2 mm who underwent additional intraoperative excision [58]. In 63percent of cases (12/19) histological assessment confirmed that the margins of the first surgical specimenwere positive and intraoperative re­excision eliminated the need for a second operation. In another study of264 patients undergoing BCS, specimen radiography identified 54 patients with close margins (6 with DCISand 48 with invasive cancer), who underwent additional intraoperative excision [56]. Of these, 25 percent ofpatients with DCIS and 63 percent of patients with invasive cancer were rendered margin negative withintraoperative reexcision.

Intraoperative margin assessment Several approaches can be used for intraoperative marginassessment, including frozen section [56,59­61], cytologic touch prep analysis [62­67], shaved marginanalysis [68], intraoperative ultrasound [69], as well as intraoperative margin assessment devices such asMarginProbe [70]. There is no prevailing standard of care for intraoperative margin assessment and practicesvary widely [71]. The use of these techniques may assist in obtaining negative margins, but does notguarantee the absence of microscopic tumor on permanent sections. Patients should be advised thatadditional surgery to obtain clean margins may be necessary.

Post­excision whole cavity shaving An alternative approach is post­excision whole cavity shaving,where an additional margin of normal­appearing tissue is excised from each margin of the cavity (superior,inferior, lateral, medical, anterior, posterior) after lumpectomy has been completed. This has been shown toreduce re­excision rates [57,72­76], including in a randomized trial where the rate of positive marginsdecreased from 34 to 19 percent, and the re­operation rate decreased from 21 to 10 percent [77]. Furtherstudies are needed to determine whether this translates into lower recurrence rates or improved survival.

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compromise of local tumor control. In a series of women treated with a whole breast dose of 45 to 46 Gy (dailydose ≤2 Gy), a boost dose of 18 Gy, and precise field matching techniques, excellent or excellent/good cosmeticresults were noted at three years in 73 and 96 percent of women, respectively [90]. Although treatment­relatedchanges in the breast stabilize at approximately three years, other factors that affect the untreated breast, such aschange in size because of weight gain or the normal ptosis seen with aging, continue to affect breast symmetry.

To help assess the cosmetic outcome after BCT, a scoring system to standardize the grading of cosmeticoutcome has been recommended by a joint committee of the ACS, the ACR, the College of AmericanPathologists, and the Society of Surgical Oncology (SSO) [91], and used at the Joint Center for Radiation Therapy(JCRT) [92]. The following scores are assigned:

The amount of resected breast tissue is the major determinant of appearance following BCT [49,92­94], asillustrated by the following:

POSTOPERATIVE COMPLICATIONS — Complications after breast conserving surgery include seromaformation, infection, and arm morbidity.

Seroma — Seroma formation occurs in virtually all patients after breast and axillary surgery, and should beconsidered a transient side effect rather than a major long­lasting complication of these procedures [96]. Althoughall patients will have some serous fluid collect at the surgical site, seromas are not clinically significant in mostcases. A clinically significant seroma can be defined as a postoperative fluid collection that requires one or moreaspirations or subsequent drain placement [97].

The rates of clinically significant seromas of the breast or axilla vary with the surgical procedure performed. In aretrospective review of 324 patients who underwent 561 breast or axillary surgeries, 8.4 percent developed aseroma that required intervention [97]. Seroma rates were significantly lower after breast conserving surgery thanafter mastectomy (6 versus 14 to 16 percent). The presence of a seroma significantly increased the risk of aconcurrent or subsequent surgical site infection (8.5 versus 4 percent in the absence of a seroma). In addition toinfection, prolonged seroma formation may also be associated with delayed wound healing [98­100].

Breast cellulitis and abscess — Breast cellulitis is an emerging problem in women undergoing breast conservingtherapy (BCT) and represents a shift from the ipsilateral arm cellulitis observed in the past following mastectomyand axillary lymph node dissection (ALND) [101­103]. (See "Breast cellulitis and other skin disorders of thebreast".)

BCT may also be associated with the relatively late occurrence of a postoperative breast abscess (median 5

Excellent: The treated and untreated breast are almost identicalGood: Minimal differences between the treated and untreated breastsFair: Obvious differences between the treated and untreated breastsPoor: Major aesthetic sequelae in the treated breast

In a trial from the National Cancer Institute of Milan that compared quadrantectomy to gross tumor excision(lumpectomy), both combined with RT, cosmetic evaluations were performed 18 to 24 months post­treatmentin 148 patients [49]. Women undergoing quadrantectomy had significantly greater discrepancies in the inferiorprofile of the breasts, greater distance from the midline to the nipple, and were more likely to have more thana 3 cm difference in height between the nipples (21 versus 7 percent) than those treated with lumpectomy.

Similar data were noted by the JCRT in a series that correlated cosmetic outcome to the volume of breasttissue resected (estimated by multiplying the dimensions of the resected breast specimens) [92]. For womenwith <35 cm resected tissue, excellent and excellent or good scores were reported by 85 and 96 percent,respectively. In contrast, when the volume of resected tissue was >85 cm , excellent, and excellent or goodscores were reported by 51 and 94 percent of women, respectively. In a later series, cosmetic resultsdeclined over the first three years and then stabilized; they were still judged by clinicians to be excellent in77 percent, and good, fair, or poor in 9, 9, and 5 percent, respectively [95].

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months, range 1.5 to 8.0 months). In one report, the only factor that correlated with abscess formation was size ofthe lumpectomy specimen; necrosis of marginally viable fat in the lumpectomy cavity may contribute to thisproblem [104].

Arm morbidity — Arm morbidity is common after breast cancer treatment and can include arm swelling, armpain, arm numbness, arm stiffness, shoulder stiffness, shoulder pain, or nerve injury [105]. Arm problems are lesscommon after BCT as compared to mastectomy; they are also less frequent with sentinel lymph node (SLN)biopsy than after axillary lymph node dissection (ALND) [106].

After breast cancer treatment, patients should be informed about methods to improve shoulder function and reducethe risk of lymphedema [107,108]. Prevention and treatment of arm edema are discussed separately. (See"Clinical features and diagnosis of peripheral lymphedema" and "Prevention and treatment of lymphedema".)

Elderly — Risk of postoperative complications increases with increasing age as well as associated comorbidillnesses. In a retrospective review of 3672 patients age 65 years and older with invasive or noninvasive breastcancer managed with either BCT or mastectomy, patients >85 years old were significantly more likely to developcomplications compared with the overall complication rate (25.1 versus 19.4 percent, odds ratio [OR] 1.85 95% CI1.37­2.50, p = 0.001) [109]. In addition, women age 65 to 69 years had a significantly lower complication rate of15.3 percent. The most common complications included wound infection and bleeding for all ages 65 and older,including women >85 years.

On univariate analysis, other factors that increased the risk of postoperative complications included:

LOCAL RECURRENCE — The local recurrence (LR) rate following breast conserving surgery increases withyoung age, node positivity, estrogen receptor negativity, and absence of radiation therapy [110]. In comparing theresults of breast conserving therapy (BCT) with mastectomy and assessing the probability and impact of localrecurrence, it is important to identify factors that may increase the risk of local recurrence. While notcontraindications to BCT, these factors may influence the choice of treatment.

Mastectomy does not guarantee freedom from local recurrence. In randomized studies using variable surgical andRT techniques, long­term recurrence rates in the treated breast following BCT (with radiation) range from 5 to 22percent, compared to 4 to 14 percent with mastectomy [2­6,8,9]. The time course of local recurrence differs withBCT versus mastectomy. Although most postmastectomy local failures occur in the first three postoperativeyears, they tend to occur later in women treated by BCT [92,111­113]. In one report, as an example, the actuarialincidence of local recurrence was 7, 14, and 20 percent at 5, 10, and 20 years following BCT [112]. This, in part,may reflect the inclusion of new primaries rather than only true recurrences in the definition of in­breast tumorrecurrence.

Interpretation of data on local recurrence following BCT is hampered by methodologic problems. Many reportsdiffer with regard to patient selection, surgical and radiation techniques, and the use of adjuvant systemic therapy.Furthermore, the competing risks of distant recurrence and second primary cancers also complicate the estimationof true local recurrence risk [114,115]. Nevertheless, despite these issues, several predictive factors for localrecurrence following BCT have been identified. These include tumor factors, treatment factors, and patient­relatedfactors.

Young age — Young age, defined as ≤40 years, by itself, is not a contraindication to BCT and is a prognostic,rather than predictive, factor [80,110,113,115­121]. Data from two randomized trials with long­term follow­up did

Polypharmacy versus none (OR 1.84, 1.46­2.32)Axillary lymph node dissection versus no axillary procedure (OR 1.76, 1.36­2.27)Mastectomy versus BCT (OR 1.72, 1.42­2.09)Comorbid illness one versus none (OR 1.32, 1.01­1.72) Neoadjuvant therapy (OR 1.43, 1.03­1.98)Smoking at time of diagnosis (OR 1.41, 1.07­1.86)

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not identify an advantage for either BCT or mastectomy in younger women compared with older women [1,3]. Aretrospective review of 3512 women age ≤40 years with T1 breast cancer found that women treated with BCT (n =1951) had a similar 10­year overall survival (OS) rate compared with women undergoing a mastectomy (95.0versus 92.1 percent) [122]. Women undergoing BCT also had a similar 10­year breast cancer specific survival(BCSS) rate (96.9 versus 94.9 percent). In addition, there was no significant difference in OS or BCSS based uponlocal management for node positive or node negative women.

In those series that identified an increase in local recurrence rates for young women, adverse pathologic featuresand attempts to perform a less extensive breast resection may explain those findings [110,118,119]. In multipleseries, younger women had a higher frequency of adverse pathologic features, such as larger tumor size,lymphatic vessel invasion, poorly differentiated histologic grade, absence of estrogen receptors (ER), and thepresence of an EIC [113,116,117]. However, even when adjusted for these findings, younger age has still beenassociated with shorter survival and an increased likelihood of local recurrence after BCT. However, young agehas also been associated with an increase in local failure following mastectomy in most [121,123,124], but not allstudies [120].

Extensive intraductal component (EIC) — The term EIC applies to an invasive ductal carcinoma in whichintraductal cancer is present in greater than 25 percent of the tumor and/or in sections of grossly normal adjacentbreast tissue, or microinvasive breast cancer. Although EIC had previously been considered a contraindication toBCT, it is only a risk factor for local recurrence when the margins of resection are not evaluated [125]. Comparedwith EIC­negative cancers, those with EIC and positive margins have a higher rate of true local recurrence, but notnew ipsilateral primaries, contralateral breast tumors, or an increased likelihood of distant relapse. These datareflect the higher incidence of multifocality and residual cancer following excision of tumors with an EIC [50,126].As an example, in one study of 214 women who underwent mastectomy with detailed histologic evaluation of thespecimen, EIC­positive tumors were more likely to have prominent residual intraductal carcinoma at least 2 mmbeyond the edge of the primary tumor (30 versus 2 percent in EIC­negative cancers) [126].

In contrast, women with EIC and negative resection margins do not have an increased risk of ipsilateral recurrencefollowing BCT [34­38]. Therefore, routine assessment of the margins of resection is an important component of thehistologic evaluation in women undergoing BCT, particularly those with an EIC. A larger breast resection in suchwomen might result in a smaller residual tumor burden and a reduced risk of ipsilateral recurrence following RT.

Recognition of EIC­positive cancers has been greatly facilitated by mammographic magnification views [127]. Theintraductal component in these lesions is frequently suggested by the presence of suspicious microcalcifications.(See "Breast ductal carcinoma in situ: Epidemiology, clinical manifestations, and diagnosis".)

Associated lobular carcinoma in situ — The association between lobular carcinoma in situ (LCIS) within theresection specimen and local recurrence is controversial. At least two studies suggest that the presence of LCISwithin the specimen is associated with higher rates of local recurrence (table 4) [128,129]. In the larger of the two,1274 women with stage I or II breast cancer undergoing BCT, the 10­year cumulative rate of ipsilateral breasttumor recurrence was significantly higher in women with associated LCIS (29 versus 6 percent, p = 0.03) [128]. Aprotective effect of systemic adjuvant hormonal therapy was suggested, since among women receiving adjuvanttamoxifen, the local recurrence rates with and without LCIS were 8 and 6 percent, respectively. (See "Atypia andlobular carcinoma in situ: High risk lesions of the breast" and "Pathology of breast cancer".)

On the other hand, several other studies support the view that the presence of LCIS within the specimen is not arisk factor for local recurrence (table 4) [130­133]. In at least one of the reports, there were no differences in localrecurrence rate in women who either received or did not receive adjuvant therapy [130]. (See "Tumor nodemetastasis (TNM) staging classification for breast cancer".)

LCIS should not be considered a contraindication to BCT.

Inherited susceptibility — An inherited susceptibility to breast and other cancers has been linked to germ­linemutations in BRCA1 and BRCA2 in some women. Young women with a strong family history of either breast or

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ovarian cancer have a significant probability of and should be offered genetic counseling about these mutations(table 5). (See "Overview of hereditary breast and ovarian cancer syndromes" and "Genetic counseling and testingfor hereditary breast and ovarian cancer".)

Following treatment of a primary breast cancer, women with an inherited susceptibility for breast cancer are atincreased risk (approximately five­fold) of developing a contralateral breast cancer [134­139]. Some, but not all,studies show that women with an inherited susceptibility for breast cancer treated with BCT are also at higher riskof local failure when compared to women with sporadic breast cancer treated with BCT [137­142]. In addition,women with breast cancer and a BRCA1/2 mutation have a higher rate of local failure when treated with BCT ascompared with mastectomy [142]. In a multi­institutional analysis of 655 women with BRCA1/2 mutations, localfailure was more likely in those treated with BCT (302 women) compared to mastectomy (353 women); thecumulative estimated risk at 15 years was 23.5 and 5.5 percent, respectively [142]. Chemotherapy has aprotective effect and reduced the risk of local failure at 15 years to 11 percent in the patients treated with BCT.There were no differences seen in regional or systemic recurrences between the BCT and mastectomy groups,and no difference in overall survival.

Prophylactic oophorectomy also has a protective effect in mutation carriers. This may reduce the risk ofdeveloping subsequent breast cancer in patients treated with breast conservation. A multi­institutional seriescompared the outcomes of 160 BRCA1/2 mutation carriers with stage I or II breast cancer treated with BCT with445 control women with sporadic breast cancer undergoing BCT [139]. At 15 years, there was no significantdifference in the rate of in­breast tumor recurrence (24 versus 17 percent for controls, p = 0.19). However,BRCA1/2 mutation status was a significant risk factor for in­breast tumor recurrence in multivariate analysis whencarriers who had undergone prophylactic oophorectomy were removed from the analysis (hazard ratio 2.0). Theseresults indirectly suggest a protective effect of oophorectomy in carriers treated with breast conservation althoughmore study is needed. (See "Risk­reducing bilateral salpingo­oophorectomy in women at high risk of epithelialovarian and fallopian tubal cancer" and "Management of patients with hereditary and/or familial breast and ovariancancer".)

The decision whether to pursue BCT in known BRCA1/2 carriers should be made following extensive discussionwith an experienced surgeon.

UNDERUTILIZATION OF BCT — Breast conserving therapy (BCT) continues to be underutilized in the UnitedStates despite consistent evidence that BCT and mastectomy are therapeutically equivalent and therecommendation of a 1991 National Institutes of Health Consensus Conference that BCT is the preferabletreatment for early stage breast cancer [143]. More than one­fourth of American women with stages I and II breastcarcinoma are still undergoing mastectomy, with considerable geographic and age variation [54,89,143­151].

Potential explanations for these observations include:

The first explanation, medical contraindications, is not a major cause of underuse of BCT [152­154]. In one reportthat included 432 women with stage I or II invasive breast cancer or ductal carcinoma in situ (DCIS) who wereprospectively evaluated by a multidisciplinary team, only 97 (22 percent) had contraindications to BCT [152].Contraindications to BCT can be readily identified with a careful history, physical examination and detailedmammography, including magnification views of the primary site. Using these parameters, in a series of 263consecutive women, patients eligible for BCT could be selected with 97 percent accuracy [154]. (See 'Patientselection for BCT' above.)

The second explanation, clinician­related inappropriate medical and demographic selection factors, has beenthought to be a major cause of high mastectomy rates in the United States [155,156]. A joint study of the

Contraindications to BCTThe use of inappropriate selection criteria by cliniciansIncreasing use of breast magnetic resonance imaging (MRI)Patient preference

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American College of Surgeons (ACS) and the American College of Radiology (ACR) evaluated factors predictinguse of mastectomy as local therapy in 17,931 women with stage I or II breast cancer [155]. Women with largertumor size, a clinically positive axilla, EIC in association with the invasive cancer, and higher histologic gradewere more likely to undergo mastectomy than those with more favorable features. Other patient­related factors (eg,older age, insurance status, and geographic location) also predicted a higher mastectomy rate. Older women aremore likely to have mastectomy recommended by their clinicians, and the majority undergo the procedure that isrecommended by their clinician [156].

Magnetic resonance imaging identifies additional ipsilateral disease in 16 percent of women with a new diagnosisof breast cancer and may influence surgical planning, leading to an increase in the mastectomy rate. (See"Diagnostic evaluation of women with suspected breast cancer", section on 'Breast MRI' and "Breast ductalcarcinoma in situ: Epidemiology, clinical manifestations, and diagnosis", section on 'Role of magnetic resonanceimaging'.)

There are data to suggest that patient rather than surgeon preference for mastectomy is more of a factor thanpreviously appreciated. Several studies have shown that more patient involvement in breast surgery decisionmaking actually leads to a greater probability of mastectomy [157,158]. Even well informed patients may choosemastectomy over BCT because concerns about the side effects of radiation therapy and the hope of avoiding acancer recurrence with the need for another cancer operation.

Studies show that only 50 to 70 percent of women with early breast cancer actively participate in the surgicaldecision [157,159]. The use of decision aids (paper, visual, audiotape, or computerized audiovisual) can enhancepatient knowledge of treatment options [160].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and“Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5 to 6 gradereading level, and they answer the four or five key questions a patient might have about a given condition. Thesearticles are best for patients who want a general overview and who prefer short, easy­to­read materials. Beyondthe Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are writtenat the 10 to 12 grade reading level and are best for patients who want in­depth information and are comfortablewith some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e­mail thesetopics to your patients. (You can also locate patient education articles on a variety of subjects by searching on“patient info” and the keyword(s) of interest.)

SUMMARY AND RECOMMENDATIONS

th th

th th

Basics topics (see "Patient information: Choosing treatment for early­stage breast cancer (The Basics)")

Beyond the Basics topics (see "Patient information: Breast cancer guide to diagnosis and treatment (Beyondthe Basics)" and "Patient information: Surgical procedures for breast cancer — Mastectomy and breastconserving therapy (Beyond the Basics)")

Breast conserving therapy (BCT) allows women with invasive breast cancer to preserve their breast withoutsacrificing oncologic outcome. Successful BCT requires complete surgical removal of the tumor (withnegative surgical margins) followed by moderate­dose RT to eradicate any residual disease. (See'Introduction' above.)

Contraindications to BCT include multicentric disease, diffuse malignant microcalcifications onmammography, prior radiation therapy to the affected breast, and persistently positive resection margins aftermultiple attempts at re­excision. (See 'Patient selection for BCT' above.)

Pregnancy is an absolute contraindication to the use of breast irradiation. It may be possible to performbreast­conserving surgery for pregnant women if surgery can be performed in the third trimester and breast

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irradiation is deferred until after delivery. (See 'Patient selection for BCT' above.)

For patients with a positive margin of resection, defined as ink on the tumor, we perform a wider excision.While obtaining wider margins than ink on tumor is not indicated for routine patients with a negative margin ofresection, we use an individualized approach to patients with close (<1 mm) margins with regard to re­excision. (See 'Indications for wider excision of margins' above.)

Certain connective tissue disorders are a relative contraindication to BCT as these disorders may lead todelayed toxicity from radiation. (See 'Patient selection for BCT' above.)

Large tumor size has been considered a relative contraindication to BCT. However, neoadjuvantchemotherapy or hormonal therapy can decrease tumor size significantly and allow BCT for large tumors withacceptable local recurrence rates. (See 'Patient selection for BCT' above.)

Acceptable cosmetic outcome can be achieved in almost all patients undergoing BCT without compromise oflocal tumor control. (See 'Surgical technique' above.)

Complications after breast conserving surgery include seroma formation, infection, and arm morbidity. (See'Postoperative Complications' above.)

Clear margins of resection and postoperative radiation therapy are important for reducing local recurrencerates after BCT. (See 'Local recurrence' above.)

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130. Abner AL, Connolly JL, Recht A, et al. The relation between the presence and extent of lobular carcinoma insitu and the risk of local recurrence for patients with infiltrating carcinoma of the breast treated withconservative surgery and radiation therapy. Cancer 2000; 88:1072.

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134. Chabner E, Nixon A, Gelman R, et al. Family history and treatment outcome in young women after breast­conserving surgery and radiation therapy for early­stage breast cancer. J Clin Oncol 1998; 16:2045.

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137. Pierce LJ, Strawderman M, Narod SA, et al. Effect of radiotherapy after breast­conserving treatment inwomen with breast cancer and germline BRCA1/2 mutations. J Clin Oncol 2000; 18:3360.

138. Haffty BG, Harrold E, Khan AJ, et al. Outcome of conservatively managed early­onset breast cancer byBRCA1/2 status. Lancet 2002; 359:1471.

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140. Smith TE, Lee D, Turner BC, et al. True recurrence vs. new primary ipsilateral breast tumor relapse: ananalysis of clinical and pathologic differences and their implications in natural history, prognoses, andtherapeutic management. Int J Radiat Oncol Biol Phys 2000; 48:1281.

141. Robson M, Levin D, Federici M, et al. Breast conservation therapy for invasive breast cancer in Ashkenaziwomen with BRCA gene founder mutations. J Natl Cancer Inst 1999; 91:2112.

142. Pierce LJ, Phillips KA, Griffith KA, et al. Local therapy in BRCA1 and BRCA2 mutation carriers withoperable breast cancer: comparison of breast conservation and mastectomy. Breast Cancer Res Treat 2010;121:389.

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144. Guadagnoli E, Weeks JC, Shapiro CL, et al. Use of breast­conserving surgery for treatment of stage I andstage II breast cancer. J Clin Oncol 1998; 16:101.

145. Nattinger AB, Gottlieb MS, Veum J, et al. Geographic variation in the use of breast­conserving treatment forbreast cancer. N Engl J Med 1992; 326:1102.

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Med 1992; 326:1097.147. Riley GF, Potosky AL, Klabunde CN, et al. Stage at diagnosis and treatment patterns among older women

with breast cancer: an HMO and fee­for­service comparison. JAMA 1999; 281:720.148. Temple WJ, Russell ML, Parsons LL, et al. Conservation surgery for breast cancer as the preferred choice:

a prospective analysis. J Clin Oncol 2006; 24:3367.149. Gregorio DI, Kulldorff M, Barry L, et al. Geographical differences in primary therapy for early­stage breast

cancer. Ann Surg Oncol 2001; 8:844.150. Hiotis K, Ye W, Sposto R, Skinner KA. Predictors of breast conservation therapy: size is not all that

matters. Cancer 2005; 103:892.151. Chagpar AB, Studts JL, Scoggins CR, et al. Factors associated with surgical options for breast carcinoma.

Cancer 2006; 106:1462.152. Morrow M, Bucci C, Rademaker A. Medical contraindications are not a major factor in the underutilization of

breast conserving therapy. J Am Coll Surg 1998; 186:269.153. Foster RS Jr, Farwell ME, Costanza MC. Breast­conserving surgery for breast cancer: patterns of care in a

geographic region and estimation of potential applicability. Ann Surg Oncol 1995; 2:275.154. Morrow M, Schmidt R, Hassett C. Patient selection for breast conservation therapy with magnification

mammography. Surgery 1995; 118:621.155. Morrow M, White J, Moughan J, et al. Factors predicting the use of breast­conserving therapy in stage I and

II breast carcinoma. J Clin Oncol 2001; 19:2254.156. Cyran EM, Crane LA, Palmer L. Physician sex and other factors associated with type of breast cancer

surgery in older women. Arch Surg 2001; 136:185.157. Katz SJ, Lantz PM, Janz NK, et al. Patient involvement in surgery treatment decisions for breast cancer. J

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GRAPHICS

Locoregional recurrence rate for breast­conserving surgery afterNACT

Study nLRR

(percent)

Medianfollow­up(mo)

Year ofpublication

Asoglu, et al 28 14 60 2005

Chen, et al 340 5 60 2004

Clark, et al 34 6.6 30 1998

Hunt, et al 93 9.7 55 1998

Mauriac, et al 272 22.5 124 1999

McIntoch, etal

173 2 62 2003

NSABP B18 1531 10.7 114 2001

Shen, et al 33 6 60 2004

BCS: breast­conserving surgery; LRR: locoregional recurrence rate; NSABP: National Surgical AdjuvantBreast and Bowel Project.* Data available for 166.

Data from:1. Asoglu, O, Muslumanoglu, M, Igci, A, et al. Breast conserving surgery after primary chemotherapy

in locally advanced breast cancer. Acta Chir Belg 2005; 105:62.2. Chen, AM, Meric­Bernstam, F, Hunt, KK, et al. Breast conservation after neoadjuvant

chemotherapy: the MD Anderson cancer center experience. J Clin Oncol 2004; 22:2303.3. Clark, J, Rosenman, J, Cance, W, et al. Extending the indications for breast­conserving treatment

to patients with locally advanced breast cancer. Int J Radiat Oncol Biol Phys 1998; 42:345.4. Hunt, KK, Singletary, SE, Smith, TL. Conservation surgery and radiation: the M.D. Anderson

experience. In: The Breast, 2nd ed, Bland, KI, Copeland, EM III (Eds), Saunders, Philadelphia1998. p.1179.

5. Mauriac, L, MacGrogan, G, Avril, A, et al. Neoadjuvant chemotherapy for operable breastcarcinoma larger than 3 cm: a unicentre randomized trial with a 124­month median follow­up.Institut Bergonie Bordeaux Groupe Sein (IBBGS). Ann Oncol 1999; 10:47.

6. McIntosh, SA, Ogston, KN, Payne, S, et al. Local recurrence in patients with large and locallyadvanced breast cancer treated with primary chemotherapy. Am J Surg 2003; 185:525.

7. Wolmark, N, Wang, J, Mamounas, E, et al. Preoperative chemotherapy in patients with operablebreast cancer: Nine­year results from National Surgical Adjuvant Breast and Bowel Project B­18. JNatl Cancer Inst Monogr 2001; 30:96.

8. Shen, J, Valero, V, Buchholz, TA, et al. Effective local control and longterm survival in patientswith T4 locally advanced breast cancer treated with breast conservation therapy. Ann Surg Oncol2004; 11:854.

Data from: Alm El­Din, M, Taghian, A. Breast conserving therapy for patients with locally advancedbreast cancer. Semin Radiat Oncol 2009; 19:229.

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[2]

[3]

[4]

[5]

[6]*

[7]

[8]

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Timing of prophylactic antibiotic administration and subsequentrates of SSIs

Time ofadministration*

Percent withSSI

Odds ratio 95 percent CI

Early 3.8 4.3 1.8­10.4

Preoperative 0.6 1 ­

Perioperative 1.4 2.1 0.6­7.4

Postoperative 3.3 5.8 2.4­13.8

SSI: surgical site infection.* "Early" denotes 2 to 24 hours before incision, "preoperative" 0 to 2 hours before incision,"perioperative" within 3 hours after incision, and "postoperative" more than 3 hours after incision.¶ Odds ratio determined by logistic­regression analysis.

Adapted from: Classen DC, Evans RS, Pestotnik SL, et al, N Engl J Med 1992; 326:281.

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Hospital Quality Alliance/Centers for Medicare & Medicaid Services(CMS) Surgical Care Improvement quality measures forperioperative VTE prevention*

Surgery type Recommended prophylaxis options

Intracranial neurosurgery Any of the following:

• Intermittent pneumatic compression devices (IPC) with orwithout graduated compression stockings (GCS)

• Low­dose unfractionated heparin (LDUH)

• Low molecular weight heparin (LMWH)

• LDUH or LMWH combined with IPC or GCS

General surgery Any of the following:

• Low­dose unfractionated heparin (LDUH)

• Low molecular weight heparin (LMWH)

• Factor Xa Inhibitor (fondaparinux)

• LDUH or LMWH or Factor Xa Inhibitor combined with intermittentpneumatic compression devices (IPC) or graduatedcompression stockings (GCS)

General surgery withcontraindications topharmacological prophylaxis

Any of the following:

• Graduated compression stockings (GCS)

• Intermittent pneumatic compression devices (IPC)

Gynecologic surgery Any of the following:

• Low­dose unfractionated heparin (LDUH)

• Low molecular weight heparin (LMWH)

• Factor Xa Inhibitor (fondaparinux)

• Intermittent pneumatic compression devices (IPC)

• LDUH or LMWH or Factor Xa Inhibitor combined with IPC orgraduated compression stockings (GCS)

Urologic surgery Any of the following:

• Low­dose unfractionated heparin (LDUH)

• Low molecular weight heparin (LMWH)

• Factor Xa Inhibitor (fondaparinux)

• Intermittent pneumatic compression devices (IPC)

• Graduated compression stockings (GCS)

• LDUH or LMWH or Factor Xa Inhibitor combined with IPC or GCS

Elective total hip replacement Any of the following started within 24 hours of surgery:

• Low molecular weight heparin (LMWH)

• Factor Xa Inhibitor (fondaparinux)

• Warfarin

Δ

◊

◊

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Excluded populations:

• Patients less than 18 years of age

• Patients who have a length of stay >120 days

• Burn patients

• Patients with procedures performed entirely by laparoscope

• Patients enrolled in clinical trials

• Patients who are on warfarin prior to admission

• Patients whose ICD­9­CM principal procedure occurred prior to the date of admission

• Patients whose total surgery time is less than or equal to 60 minutes

• Patients who stayed less than or equal to three calendar days postoperatively

• Patients with contraindications to both mechanical and pharmacological prophylaxis

* Taken from: Specifications Manual for National Hospital Inpatient Quality Measures. Available at:www.qualitynet.org.Δ Patients who receive neuraxial anesthesia or have a documented contraindication to pharmacologicalprophylaxis may pass the performance measure if either appropriate pharmacological or mechanicalprophylaxis is ordered.◊ Current guidelines recommend postoperative low molecular weight heparin for intracranialneurosurgery.

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LCIS as a risk factor for local recurrence in women treated withbreast conserving therapy for early breast cancer

Study,year

Number of patientsw/LCIS within the

specimen

Number ofcontrolpatients

MedianF/u,mos

Risk of localfailure,percent

+LCIS ­LCIS

Sasson,AR;2001

65 1209 76 5 3

(5 yr, NSS)

29 6

(10 yr, p = .003)

Jolly, S;2006

56 551 104 14 7

(10 yr, p = 0.04)

Moran,M; 1998

51 1045 127 23 16

(NSS)

Abner,AL;2000

137 1062 161 13 12

(NSS)

Ben­David,M; 2006

64 121* 45 1.7 1.6

(NSS)

NSS: not statistically significant.* Matched for histology, stage, age, and date of diagnosis.

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Relationship between family history of breast and ovarian cancerand likelihood of BRCA1 mutation

Chance of BRCA1 mutation,

percent

Single affected patient In individual

Breast cancer, <age 30 12

Breast cancer, ages 30­39 6

Breast cancer, ages 40­49 3

Ovarian cancer, <age 50 7

Sisters In family

2 breast cancers, <age 40 37

2 breast cancers, ages 40­49 20

Breast cancer <age 50, ovarian cancer <age50

46

2 ovarian cancers, <age 50 61

Families

≥3 breast cancers, all before age 50 40

≥2 breast cancers, ≥1 ovarian cancer 82

≥2 breast cancers, ≥2 ovarian cancers 92

Adapted from Greene, MH, Mayo Clin Proc 1997; 72:54.

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Disclosures: Michael S Sabel, MD Consultant/Advisory Boards: IceCure Medical [Cryoablation (IceSense III)]. Lori J Pierce, MDNothing to disclose. Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C) Nothing to disclose. Daniel F Hayes, MDGrant/Research/Clinical Trial Support: Janssen R&D, LLC [Breast cancer (Abiraterone)]; Janssen R&D, LLC [Breast cancer(CellSearch)]; Puma Biotechnology, Inc. [Breast cancer (Neratinib)]; Pfizer [Breast cancer (Palbociclib)]; Astra Zeneca [Breast cancer(Circulating tumor cells)]. Speaker's Bureau: Lilly Oncology (Breast cancer). Consultant/Advisory Boards: Pfizer [Breast cancer(Palbociclib)]. Other Financial Interest: Janssen R&D, LLC [Breast cancer (CellSearch)]. Wenliang Chen, MD, PhD Nothing to disclose.Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through amulti­level review process, and through requirements for references to be provided to support the content. Appropriately referencedcontent is required of all authors and must conform to UpToDate standards of evidence.Conflict of interest policy

Disclosures