Locoregional Breast Cancer Recurrence

Breast cancer recurrence can occur after both mastectomy and BCT (partial mastectomy and radiation

therapy), with the median time to recurrence after mastectomy of 2 to 3 years versus 3 to 4 years after

BCT.437–439 When breast cancer reappears on the chest wall, it is defined as a local recurrence. However,

breast cancer that involves the lymph nodes such as the ipsilateral axillary, supraclavicular,

infraclavicular, or internal mammary nodes is referred to as a regional recurrence. Among patients who

undergo mastectomy for an operable breast cancer, 5% to 10% of patients will have a local or regional

recurrence within 10 years whereas patients who undergo BCT have a risk of 10% to 15%, and in

patients who forego radiation therapy after a partial mastectomy, the risk of recurrence is as high as

35%.440 Although BCT is associated with an increased risk of locoregional recurrence, there are no

differences in overall survival as supported by a single institutional National Institutes of Health

randomized study (n = 237)278 and two European randomized trails (EORTC trial 10801 and DBCG

trial 82-TM). The latter involved approximately 1,800 patients with stage I and II breast cancer who

were randomized to undergo a modified radical mastectomy or BCT. Patients who developed a local

recurrence in these trials were then analyzed for survival and time to subsequent local recurrence after

salvage treatment. There were no differences between the two groups in regard to survival and time to

subsequent local recurrence after treatment of an early locoregional recurrence.437

The primary risk factors for postmastectomy recurrence include the size of the primary cancer and the

number of positive axillary lymph nodes, where ≥4 involved nodes have been consistently shown to

increase axillary recurrence rate to more than 20%.441 In women with four or more positive lymph

nodes, tumor size larger than 5 cm, or those with positive surgical margins, postmastectomy radiation

therapy is often recommended as it can reduce the rate of chest wall recurrence by 65% to

75%.70,334–336 The most common presenting sign of a postmastectomy recurrence is a clinical mass or

multiple small nodules on the chest wall or overlying skin in or near the mastectomy scar/skin flaps.

Other signs of a recurrence can include inflammatory changes without an associated mass and painless

masses found in the axilla or the supraclavicular fossa. Workup for a recurrence should also be

undertaken for patients who present with lymphedema or a brachial plexopathy. When a recurrence is

suspected, a core biopsy should be obtained to confirm the diagnosis and to evaluate hormone and

HER2 receptor status. In addition, a metastatic workup should be performed. The 5-year survival rate

for patients based on site of recurrence is 52% for chest wall alone, 50% for axilla alone, 28% for

supraclavicular nodes alone, 28% for chest wall plus axilla, and 7% when both the supraclavicular nodes

and chest wall/axilla are involved.442 The subsequent treatment plan for patients with recurrent breast

cancer is complex and requires a multidisciplinary team.

After BCT, the primary risk factors for recurrence are the use of radiation therapy and pathologic

margin status. When an ipsilateral breast cancer is identified, it is important to determine whether this

is indeed a true recurrence versus a second primary cancer; a true recurrence is often found within the

primary tumor site or the boost volume of the treated breast. Unlike postmastectomy recurrences,

which are commonly detected on physical examination, post-BCT recurrences are often identified by

surveillance mammography. However, it is important to note that any physical examination changes

that occur more than 1 year after completion of radiation therapy warrant further workup, even in the

presence of a normal mammogram. In this setting, consideration should be made for MRI and biopsy.

For any recurrent disease, biopsy is obtained to confirm diagnosis and tumor receptor status, followed

by a complete metastatic staging workup. In the absence of metastatic disease, the standard approach to

a local recurrence after BCT is a mastectomy, with most patients surviving at least 10 years.443 In the

setting of more advanced recurrent disease, such as that associated with skin involvement or

inflammatory changes of the skin, systemic therapy may need to be considered prior to mastectomy.

The decision to proceed with axillary restaging should be considered by a multidisciplinary team.

Furthermore, the management of regional recurrence after BCT is complex and should be planned with

a multidisciplinary approach.

Paget Disease of the Breast

Although the presentation of breast cancer is commonly associated with a mass or a mammographic

abnormality, it must be considered in the setting of chronic nipple ulceration. PDB was first noted by Sir

James Paget in 1874 when he described 15 women with chronic nipple ulcerations who then developed

cancer of the involved breast within 2 years.444 The hallmark of Paget disease is a scaly, raw, vesicular,

or ulcerated lesion that begins on the nipple and then spreads to the areola (Fig. 74-27). This is often

nilateral process and can be associated with bloody nipple discharge. Symptoms that can occur prior to

the development of clinically apparent disease include pain, burning, and pruritus. PDB is a rare disease

accounting for only 1% to 3% of new cases of breast cancer in females in the United States.

Figure 74-27. Paget disease of the nipple. Depigmentation and desquamation of the nipple and areola are evident.

The diagnostic workup of PDB is to first establish the diagnosis and then to identify the underlying

breast cancer that is present in 85% to 88% of cases, despite often not being associated with a breast

mass or a mammographic abnormality.445 Full-thickness wedge or punch biopsy of the nipple should be

performed. PBD is characterized histologically by the presence of large cells with prominent nucleoli

and a pale cytoplasm (Paget cells) occurring singly or in small groups within the epidermis of the

nipple. Other characteristics of Paget cells include the presence of low-molecular-weight cytokeratins

such as CK7. Approximately 50% of PDB cases express hormone receptors and between 70% and 90% of

cases overexpress HER2.

For patients with PDB, a physical examination including bilateral breast examination and

mammography should be performed to help identify the underlying breast cancer. Approximately onehalf of patients with PDB will have an associated mammographic abnormality. Interestingly, these

abnormalities can occur distant from the nipple areolar complex. If no palpable masses are found and

mammography is normal, there is a greater likelihood of DCIS than an invasive cancer.446 If

mammography and breast imaging fail to locate disease, then a MRI can be obtained, recognizing that

although it is highly sensitive it is not highly specific. As such, MRI-detected lesions should be biopsied

to confirm the diagnosis of a breast cancer.

The treatment of PDB is either a mastectomy or breast-conserving therapy, which includes a partial

mastectomy and whole breast radiation therapy. Breast-conserving surgery includes resection of the

nipple–areola complex and the underlying cancer with negative margins obtained (central lumpectomy).

Given that the nipple–areola complex is removed, some women may consider this cosmetically

unacceptable. Evaluation and treatment of the axilla is dependent on the underlying cancer identified.

Adjuvant systemic therapy is also determined by the involved breast cancer.

Breast Sarcomas

Breast sarcomas are rare, accounting for less than 1% of all breast malignancies, characterized by its

derivation from the connective tissue within the breast.447 It is a heterogeneous disease comprising

multiple histologic subtypes including fibrosarcoma (24%), angiosarcoma (24%), undifferentiated

pleomorphic sarcoma (24%), myxofibrosarcoma (12%), leiomyosarcoma (8%), hemangiopericytoma

(4%), and osteosarcoma (4%).448 Primary breast sarcomas can result from genetic conditions such as

with the TP53 mutation (Li–Fraumeni syndrome which is characterized by breast sarcoma, leukemia,

and adrenal cortical carcinoma), familial adenomatous polyposis and its variants, and with

neurofibromatosis type 1.448 Although the causative factor for primary disease is often not known, risk

factors for secondary breast sarcomas include ionizing radiation,449 conditions causing chronic

lymphedema (Stewart–Treves syndrome),450 chemicals such as arsenic compounds and vinyl chloride,

and with immunosuppression such as with HIV.448

A breast sarcoma often presents as a firm, large, unilateral, and painless mass. Mammographic

findings are commonly nonspecific with no associated calcifications or spiculations, presenting as

noncalcified oval masses with indistinct margins or can even be associated with a normal

mammogram.451 Core biopsy is recommended to confirm the diagnosis. Given that the biology and

prognosis differs significantly from invasive breast cancers, breast sarcomas are staged using the

2090

American Joint Committee on Cancer (AJCC)/International Union Against Cancer system for sarcomas

arising from other sites.452 As most breast sarcomas do not spread through the lymphatic system, even

in the presence of large tumors, the lymph nodes are negative for disease. The primary site for

metastases is the lung and as such chest CT should be obtained for all newly diagnosed patients.453

Phyllodes Tumor

Phyllodes tumors are uncommon (<0.5% of all breast malignancies) fibroepithelial breast tumors first

described by Johannes Muller in 1838 as cystosarcoma phyllodes.454 Given that these tumors often do not

have cystic components and are not true sarcomas, they are now referred to simply as phyllodes tumors

(Fig. 74-28). The malignant potential of phyllodes tumors differs widely, with some behaving like

fibroadenomas and others that can degenerate histologically into sarcomatous lesions and metastasize

distantly. As such, they are histologically classified as benign (50%), borderline (25%), or malignant

(25%) based upon the degree of stromal cellularity and atypia, mitotic rate, and the presence or absence

of stromal overgrowth and infiltrative margins. Risk factors for phyllodes tumors are not known, aside

from their association with Li–Fraumeni syndrome.455

Patients with phyllodes tumors present with a smooth, multinodular, well-demarcated, firm mass that

is both mobile and painless. The average tumor size is 4 to 7 cm. Although palpable axillary

lymphadenopathy can be found in up to 20% of patients, lymph node involvement is rare.456 Imaging is

notable for a smooth multilobulated mass that resembles a fibroadenoma. Core needle biopsy is

recommended for diagnosis. However, it has a false-negative rate of 25% to 30%.457,458 As such, in the

presence of a rapidly enlarging mass, excisional biopsy should be performed.

Figure 74-28. Breast asymmetry resulting from a benign phyllodes tumor. Skin changes are caused by pressure necrosis.

The treatment of all phyllodes tumors is wide excision to achieve negative histologic margins, with a

goal of 1 cm. Even large tumors can be treated with breast-conserving surgery without compromising

cancer-specific survival. Lymph node involvement is also very rare; in the SEER database, only 8 of 498

women had involved nodes.459 As such, most surgeons do not routinely perform SLNB for phyllodes

tumors. The use of adjuvant radiation therapy and chemotherapy is controversial; however, in the

setting of a large borderline or malignant phyllodes tumor, these treatments should be considered. If

systemic therapy for malignant phyllodes tumor is undertaken, it is based on guidelines for treating

sarcomas. Similar to breast sarcomas, malignant phyllodes tumors can metastasize to the lungs and as

such patients should undergo chest x-ray every 6 months for 2 years and then annually. Unfortunately,

once metastasis develops, the mean overall survival is 30 months.460

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