taxanes and anthracyclines. Other options, especially for patients with bone-predominant ER+

metastatic disease who have failed two trials of endocrine therapy, include capecitabine, which is

derived from the antimetabolite fluorouracil. Capecitabine also may be indicated for metastatic disease

to the brain as it appears to cross the blood–brain barrier.268–270 Other agents include eribulin,

gemcitabine, ixabepilone, etoposide, and platinum agents.

Although combination chemotherapy conveys a higher risk of toxicity, its use is indicated when tumor

burden is large or when patients have significant symptomatic disease. This includes anthracyclinecontaining regimens, non–anthracycline taxane-based regimens, and combination regimens

incorporating platinum salts. It is important to note that no prospective study has shown that

combination chemotherapy improves overall survival compared with single agent sequential

chemotherapy.

For women with metastatic breast cancer, data exist that extending chemotherapy duration is

associated with improved progression-free and overall survival. However, prolonged chemotherapy can

be associated with more serious toxicities such as neutropenia and neuropathy.271,272 As such, an

individualized approach should be undertaken weighing tumor response against side effects. During

treatment of metastatic disease, the patient needs to be monitored for treatment failure, which includes

clinical deterioration during treatment, evidence of new metastatic disease, and increasing size of

previously documented metastatic lesions.

The recommendations for adjuvant therapy are summarized in Table 74-13.

Surgical Therapy

Partial Mastectomy

BCT consists of breast-conserving surgery (partial mastectomy) followed by radiation therapy (Fig. 74-

22). The use of BCT is supported by six prospective randomized clinical trials demonstrating that partial

mastectomy plus radiation therapy offers equivalent survival to mastectomy with a low rate of local

recurrence (Table 74-14).273–281 The local recurrence rate with BCT is 5% to 22% versus 4% to 14%

with mastectomy. Of note, most recurrences after mastectomy occur within the first 3 years, but

recurrences after BCT tend to occur later.282–284 Factors that increase local recurrence rate following

partial mastectomy include young age, lymph node involvement, ER− disease, and absence of radiation

therapy.285 The American College of Surgeons, the American College of Radiology, the College of

American Pathologists, and the Society of Surgical Oncology have developed consensus standards of

care for BCT.286 Most patients can be offered BCT except for those with (1) multicentric disease, (2)

diffuse suspicious microcalcifications on mammography, (3) a history of radiation therapy that includes

a portion of the affected breast such that when combined with the current proposed treatment would

result in an excessively high total radiation dose to the chest wall, (4) pregnancy (although if in the

third trimester, partial mastectomy can be performed with planned breast irradiation deferred

postpartum), (5) IBC, and (6) persistently positive margins after multiple attempts at breast-conserving

surgery (Table 74-15).

Figure 74-22. Cosmetic outcome after breast-conserving therapy with radiation. A: Excellent cosmetic outcome. The treated breast

(left) is identical to the untreated breast. B: Fair cosmetic outcome. Significant shrinkage and loss of ptosis is evident in the treated

right breast.

RESULT S

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Table 74-14 Survival in Prospective Randomized Trials Comparing BreastConserving Therapy with Mastectomy

8, 9 The operative approach for a partial mastectomy is very similar to an excisional biopsy and is

sometimes referred to as a wide excision, lumpectomy, or segmental mastectomy. The considerations

for placement of the incision are similar to those for excisional biopsy; however, it is best to keep the

incision within the boundaries of a potential mastectomy incision, and the incision should be made

directly over the lesion rather than at the wire insertion site to minimize tunneling. As negative margins

are associated with lower rates of recurrence, many techniques have been developed to ensure negative

margins at the time of the initial surgery. One common technique is to remove the breast cancer with

surrounding normal tissue and then obtain additional shave margins. Each shave margin is labeled and

oriented in relationship to the primary cancer.293–298 In a randomized controlled trial, it was found that

cavity shaving at the time of partial mastectomy halved the rates of positive margins (34% vs. 19%, P

= 0.01) and reexcision (21% vs. 10%, P = 0.02).299 Approaches to evaluate intraoperative margin

status include frozen section, cytologic touch prep analysis, and intraoperative ultrasound. However, no

method has proven superior and there is no established standard of care. In patients undergoing breastconserving surgery, it is important to discuss the potential need for reexcision. A histologically positive

margin is defined as a margin that has tumor present at the inked margin. Patients with a positive

margin have at least a twofold increase in ipsilateral local breast cancer recurrence. As such,

controversy has centered on the optimal amount of normal tissue that should be excised around the

cancer to minimize local recurrence risk. A recent multidisciplinary consensus panel supports the use of

“tumor at ink” as the criteria for positive margin/reexcision based on a meta-analysis that included 33

studies with 28,162 patients and 1,506 ipsilateral recurrences.300 Like most other institutions, we have

adopted this new definition of a positive margin for invasive breast cancers to guide decisions about

reexcision. However, given the concern for gaps between lesions or skip lesions in DCIS, we continue to

define a negative margin for this pathology as ≥2 mm, understanding that this practice may evolve

pending more study results.

INDICATIONS/CONTRAINDICATIONS

Table 74-15 Contraindications to Breast-Conserving Therapy in Invasive

Carcinoma

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Axillary Lymph Node Dissection

Until recently, ALND was performed in all patients with newly diagnosed breast cancer to facilitate

staging, medical decision- making, and to minimize locoregional recurrence. More recently, SLNB has

replaced ALND for axillary staging, and the therapeutic impact of ALND may be limited to specific

subsets of patients with breast cancer. In the American College of Surgeons Oncology Group Z0011

trial, eligible patients had T1-T2 invasive breast cancers, no palpable adenopathy, and 1 to 2 SLNs

containing metastases identified by frozen section, touch preparation, or H&E staining. Patients were

randomized to undergo ALND or no further axillary treatment. Systemic therapy was at the discretion of

the treating physician. Patients ineligible for the trial included those with matted lymph nodes, ≥3

positive nodes, gross extranodal disease, and those treated with neoadjuvant therapy.301 After 6 years of

follow-up, SLNB alone was not inferior to ALND in patients with limited sentinel lymph node

involvement treated with BCT. Of note, these findings have been compared with those of the NSABP

B04 trial that was conducted over a decade ago, which randomized women with clinically negative

nodes to treatment with radical mastectomy, total mastectomy plus axillary radiation, or total

mastectomy with delayed ALND if nodal recurrences were observed. No statistically significant survival

differences were observed between any of the groups initially or at any of the analyses up to 25 years

of follow-up.244 These studies suggest that for contemporary women, ALND may not provide a survival

benefit in patients who are clinically node-negative. Currently, ALND is limited to patients with positive

sentinel lymph nodes who do not meet Z0011 criteria, those with a contraindication to SLNB such as

those with clinically palpable pathologic lymph nodes and patients with IBC.

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Figure 74-23. A: Anatomical landmarks of the axilla. The boundaries of the axillary lymph node dissection are the axillary vein

superiorly, the latissimus dorsi and thoracodorsal bundle laterally, and the serratus anterior muscle and long thoracic nerve

medially. B: Lymphatic drainage of the breast. During an axillary lymph node dissection, level 1 and 2 lymph nodes are removed.

The boundaries of an ALND are the axillary vein superiorly, the serratus anterior muscle and long

thoracic nerve medially, and the latissimus dorsi muscle and thoracodorsal nerve laterally.

Contemporary axillary dissection in breast cancer involves removal of the level 1 and 2 lymph nodes

(Fig. 74-23).302 Level 3 nodes are palpated and only in the presence of gross disease is dissection

performed, as removal of these nodes greatly increases the risk of lymphedema and is rarely (<1%)

involved in the absence of level 1 and 2 diseases.303,304 Typically, a yield of ≥10 axillary lymph nodes

is achieved with ALND.

The procedure is performed under a general anesthetic that does not include a muscle relaxant as

identification of the long thoracic and thoracodorsal nerves is critical to the dissection. Preoperative

antibiotics and deep venous thrombosis prophylaxis with sequential compression devices are employed.

The patient is placed in the supine position with the ipsilateral arm abducted ≤90 degrees. Use of a

stockinette allows for mobilization of the arm during dissection. If the ALND is performed through a

mastectomy incision (modified radical mastectomy), no additional incisions are required. Also, for

partial mastectomies performed in the upper outer quadrant, the partial mastectomy incision can be

extended to the axilla. For palpable nodes that are close to, or have eroded the skin, it is important to

take the overlying skin during the dissection.

For an ALND performed during a partial mastectomy or as a separate procedure, a curvilinear skin

incision is made 1 to 2 cm below the hair-bearing area of the axilla, following Langer’s lines from the

border of the pectoralis major muscle to the latissimus dorsi muscle. Although flaps can be developed

superiorly, inferiorly, laterally, and medially, most surgeons find that this is not necessary. Once the

skin incision is made, the lateral edge of the pectoralis major muscle (PM) is palpated and the PM fascia

is then opened with electrocautery. The lateral edge of the PM is then retracted medially to expose the

pectoralis minor muscle (PMi), with care to avoid injury to the medial pectoral nerve, which innervates

both the PM and the PMi. The tissue at the border of the PMi is then incised with care to avoid injury to

the axillary vein or brachial plexus superiorly. If the arm is in a stockinette, it should be flexed medially

and anteriorly to relax the PMi. The PM and PMi are then retracted and using blunt dissection, the

axillary vein at the medial extent of the dissection can be identified. Further blunt dissection can be

performed just below the medial aspect of the axillary vein and just lateral to the chest wall to identify

the long thoracic nerve. The long thoracic nerve can also be palpated along the chest wall and once it is

identified, the nerve is dissected free of surrounding tissue inferiorly to the insertion. To avoid injury,

the fascial layer on the serratus anterior muscle that holds the nerve in place should not be opened.

Attention is now turned to identification of the thoracodorsal nerve. Dissection is initiated midaxilla just

inferior to the axillary vein. Anterior to the bundle is often the thoracoepigastric vein, which is a large

superficial venous tributary arising from the axillary vein. Although the thoracoepigastric vein may

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need to be transected to allow for completion of the dissection, it is important to first identify the

thoracodorsal nerve. The axillary fat pad/contents can then be dissected away from the thoracodorsal

bundle using blunt dissection from superiorly to inferiorly with a long fine tonsil clamp. Once the long

thoracic and thoracodorsal nerves are identified and dissected free of surrounding tissue, the axillary

contents can be mobilized and removed. Of note, there are usually three to five intercostobrachial

nerves that supply sensation to the medial–posterior aspect of the arm and run medial to lateral in the

field of dissection. An attempt should be made to spare these nerves but only if they do not directly

interfere with the dissection. The axillary contents are retracted inferiorly, and using electrocautery or

sharp dissection, it is freed from the teres major posteriorly. The axillary contents are then sent en bloc

to the pathologist. A single 15 or 19 French round Blake drain can be placed above or below the bra

line. However, some surgeons do not place drains for ALNDs, as in the absence of an associated

mastectomy, the drainage is often scant. If a drain is placed, it is removed when drainage is less than 30

mL per 24 hours. No antibiotic prophylaxis is necessary.

The approach to ALND described above is a medial to lateral approach with the long thoracic nerve,

axillary vein, and thoracodorsal nerve identified in sequence. Alternatively, one can approach the

dissection through a lateral to medial approach. With this method, once the clavipectoral fascia is

incised to enter the true axilla, the anterior surface of the latissimus dorsi is identified at the lateral

extent of the axillary dissection. The clavipectoral fascia is then incised along the superior and medial

aspects of the axilla. Dissection is then performed to first identify the thoracodorsal nerve, then the

axillary vein superiorly, and then the long thoracic nerve medially. Once all the nerves and vascular

structures are identified, the axillary contents are mobilized and removed.

Complications from ALND include motor and/or sensory nerve injury. Injury to the long thoracic

nerve may result in winged scapula, whereas injury to the thoracodorsal nerve leads to weakness of

internal rotation and extension, characterized by the functional inability to hold a book under the arm.

Other risks include seroma formation, infection, and lymphedema.305–307 The risk of lymphedema is

lifelong and is as high as 30%.

Simple Mastectomy

A mastectomy is performed for patients with breast cancer who are not candidates for BCT or for

patients who prefer a mastectomy. For women at high risk for the development of breast cancer, it can

be performed as a prophylactic procedure. The goal of mastectomy is complete removal of the breast

tissue while preserving muscle function and viable skin flaps for primary closure. Preoperatively, the

patient is examined in the holding area, where the breast is marked and the correct site of surgery is

confirmed. An intravenous antibiotic that covers skin flora, such as cefazolin, given before skin incision

has been shown to significantly decrease the risk of infection in patients undergoing mastectomy (RR

0.60; 95% CI, 0.450 to 0.81).308 The patient is then placed in the supine position with the arms

abducted up to 90 degrees with padding placed beneath the arms and wrist to avoid brachial nerve and

radial nerve injury. The skin is then cleansed with a preparation of chlorhexidine gluconate/isopropyl

alcohol or Betadine solution and the patient is draped in a sterile fashion. The most common skin

incision used is an elliptical incision in the horizontal (Stewart Incision) or diagonal plane (Orr Incision),

although historically a vertical plane incision for high lying or infraclavicular lesions has also been used

(Fig. 74-24). The medial border of this incision is 2 cm from the sternal edge and the lateral border is at

the midaxillary line. The elliptical incision should include the skin directly over the tumor, especially if

the tumor is superficial. Once the incision is made, a superior skin flap is developed in the relatively

avascular plane between the skin and the breast parenchyma to the level of the clavicle. The fascia of

the pectoralis major muscle is then incised from the sternum to the edge of the lateral edge of the

muscle with care to preserve the internal mammary perforators. The inferior flap is then developed to

the level of the rectus muscle (just at or below the level of the inframammary fold). The underlying

fascia is then incised from the sternum to the mid axillary line. The medial flap is then developed

similarly, connecting the superior and inferior flaps, with attention to the internal mammary perforators

in this area. As these vessels tend to retract, ligation of any bleeding vessel is performed. Unlike the

other skin flaps, the lateral dissection tends to be less well defined. The flap is taken down to the level

of the latissimus muscle. Care should be taken to avoid the axillary contents and sensory nerves. The

breast is then removed en bloc with the fascia of the pectoralis muscle by retracting the breast

downward and dissecting the plane between the muscle fibers and the fascia. The wound is then

irrigated with warm sterile saline, and the flaps and chest wall are then systematically inspected to

ensure hemostasis. A drain is then placed to prevent seroma formation. Skin closure can be performed in

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different ways, such as with a 3-0 running polydioxanone suture with a 4-0 subcuticular stitch or with

interrupted 3-0 Vicryl sutures with a 4-0 subcuticular stitch. Postmastectomy, the patient is admitted to

the hospital overnight to ensure adequate pain control and to monitor for acute bleeding. When drain

output is less than 30 mL for 2 consecutive days, the drain is removed (typically between postoperative

days 7 and 14). No antibiotic coverage is necessary while drains are in place. In less than 1% of cases,

hematomas can occur and if small can be observed. For large or enlarging hematomas (encompassing

greater than one-fourth of the chest wall), surgical exploration is required to evacuate the hematoma

and stop any sources of bleeding. Other complications associated with mastectomy include skin flap

necrosis, pneumothorax, cellulitis, neurapraxia, and lymphedema.

Figure 74-24. Incision placement for modified radical mastectomy. The incision should include the nipple–areola complex, biopsy

scar, and excess skin of the breast.

10 If immediate reconstruction is planned, a skin-sparing incision is made, which often consists of

making a smaller horizontal ellipse around the nipple–areola complex, a circular incision just

encompassing the nipple–areola complex, or a lollipop incision (Fig. 74-25). In some circumstances, the

patient may be a candidate for a nipple-sparing mastectomy if her breasts are small to moderate in size,

often no larger than a C cup, with minimal ptosis, and the breast cancer is an acceptable distance (often

at least 2 cm) from the nipple. Tumor size, histology, or lymph node status is no longer considered

exclusion criteria for nipple-sparing mastectomy, and current exclusion criteria include clinical

involvement of the nipple areolar complex, PDB, bloody nipple discharge, multicentric disease,309

and/or inflammatory carcinoma.310 Nipple-sparing mastectomies are often performed through an

inframammary fold incision or a radial lateral incision. More recently, a lateral vertical incision has

been described. This incision is associated with a significant reduction in hypertrophic scar formation

versus the radial lateral incision.311 Intraoperatively, a biopsy of the retroareolar margin is performed

and must be histologically negative for malignancy. BRCA mutation carriers are also candidates for

nipple-sparing mastectomies. In a study of 26 patients with BRCA mutations undergoing prophylactic

mastectomies, DCIS was identified in one patient compared with two cases of DCIS in the matched

control group. There were no locoregional recurrences in the patients with BRCA mutations at 37

months of follow-up.312 These findings support that nipple-sparing options are reasonable for patients

with BRCA mutations.

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Figure 74-25. Skin-sparing mastectomy. A: The only skin removed was the nipple–areola complex. B: Cosmetic outcome after

bilateral skin-sparing mastectomy and transverse rectus abdominis myocutaneous (TRAM) flap reconstruction.

Although the goal of a mastectomy is to completely remove the breast cancer and normal breast

tissue, local recurrence remains a risk. The risk of local recurrence is 6% at 5 years in patients with no

lymph node involvement and 16% at 5 years in patients with one to three lymph nodes involved. With

the addition of radiation therapy, the risk of local recurrence decreases to 2%. When four or more

lymph nodes are involved, the risk of recurrence is 26% at 5 years, decreasing to 6% with the addition

of radiation therapy.313

In women with a personal history of breast cancer, the absolute risk of contralateral breast cancer is

estimated to be 0.5% to 1.0% per year or 5% to 10% during the 10 years following diagnosis.314 As

such, most women will not develop a contralateral breast cancer. As no randomized clinical trials have

been performed, it is not known whether contralateral prophylactic mastectomy (CPM) is associated

with a survival benefit in women with a personal history of breast cancer. However, a survival benefit

for CPM has been shown for patients with a deleterious BRCA1 or BRCA2 mutation.315–318 The decision

to perform a CPM must be individualized with each individual patient. Of note, a twofold increased risk

of major complications exists with CPM when compared with unilateral mastectomy.319,320

Breast Reconstruction

All patients undergoing mastectomy should be offered consultation with a plastic surgeon for

consideration of breast reconstruction, recognizing that some women may choose to forego this

procedure and prefer the use of a breast prosthesis. The two main types of breast reconstruction include

implant-based and autologous tissue breast reconstruction. Implants include silicone or saline implants.

Autologous tissue techniques used for breast reconstruction often include either the transverse rectus

abdominis myocutaneous (TRAM) flap or the deep inferior epigastric perforator (DIEP) flap.

Breast reconstruction can be performed immediately after a mastectomy procedure (immediate

reconstruction) or at a later time (delayed reconstruction). For implant-based breast reconstruction, the

most common technique involves a two-stage method with placement of a tissue expander under the

pectoralis major muscle at the time of the mastectomy (Fig. 74-26). The tissue expander can then be

filled incrementally with saline with the first fill typically occurring 1 to 3 weeks postoperatively with

additional fills every 1 to 2 weeks until the desired expansion is achieved. The tissue expander is then

left in place for several months to allow for maximal skin remodeling. During the second stage, the

tissue expander is removed and is replaced with a silicone or saline implant. This two-stage

reconstruction method is particularly beneficial for women who will need adjuvant radiation therapy as

radiation can result in flap necrosis, fibrosis, and shrinkage, resulting in poor cosmetic outcomes after

immediate implant and/or tissue flap reconstruction. Instead, the tissue expander allows for skin

preservation and the ability to then proceed with either an implant or autologous reconstruction at a

later date. The complications associated with tissue expander placement include infection requiring

removal. This occurs at a rate of 1.2% but may be higher in women being treated with chemotherapy

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