Pagets Disease of the Nipple

This is an uncommon form of breast cancer that is clinically characterized by an eczematoid reaction of the nipple and symptoms of itching, erythema and nipple discharge. In 45% of patients there is an associated underlying breast mass which is an infiltrating ductal carcinoma or ductal carcinoma in situ. It is often treated with mastectomy but may be treated by central breast lumpectomy if the cancer is well localized. Prognosis is similar to infiltrating ductal carcinoma and is determined similarly by the stage of the disease.

Table 1.1. TNM system of breast cancer staging

Primary Tumor

Tis

Ductal carcinoma in situ, Paget's disease of the breast with no tumor

T1

Tumor equal or less than 2 cm

T2

Tumor greater than 2 cm but no greater than 5 cm

T3

Tumor more than 5 cm

T4

Tumor of any size with direct extension to chest wall or skin (includes peau d'orange, skin ulceration, inflammatory carcinoma

Lymph Node Involvement

NO

No regional lymph node metastases

N1

Metastases to movable ipsilateral axillary nodes

N2

Metastases to fixed ipsilateral axillary nodes

N3

Metastases to internal mammary lymph nodes

Distant Metastases

MO

No distant metastases

Distant metastases

Distant metastases

Table 1.2. Stage grouping of breast cancer

Stage

T

N

M

I

T1

NO

MO

IIA

TO

N1

MO

T1

N1

MO

T2

NO

MO

IIB

T2

N1

MO

T3

NO

MO

IIIA

TO

N2

MO

T1

N2

MO

T2

N2

MO

T3

N1

MO

T3

N2

MO

IIIB

T4

Any N

MO

Any T

N3

MO

IV

Any T

Any N

M1

dthe tumor with a sufficient rim of normal breast tissue. It is unproven how large the margin of normal tissue should be in order to achieve optimal local control. A partial mastectomy is typically combined with whole breast irradiation (RT). The combination of PM and RT is termed breast conserving therapy. It is usually indicated in any woman who has a malignancy measuring less than or equal to 4 cm. and in which the cosmetic result will be considered satisfactory. Contraindications include: first or second trimester of pregnancy, two or more gross tumors in separate quadrants of the breast (multicentric disease), diffuse, indeterminate, or malignant-appearing microcalcifications, and a history of prior therapeutic irradiation to the breast. A history of collagen vascular (connective tissue) disease has also been relative contraindication based on a number of anecdotal reports of severe fibrotic reactions to irradiation in patients with lupus and scleroderma.

Patients positive for BRCA1 or BRCA2 gene mutations may have a higher local recurrence rate. Retrospective data is being gathered to determine whether patients with strong family histories in fact have higher recurrence rates with breast sparing surgery. Positive margins on a lumpectomy specimen indicate that the tumor was incompletely excised. Except for very frail or patients of advanced age, pathologically positive margins are not acceptable. Re-resection is required and this may result in the need for a mastectomy.

Since 1970, there have been six prospective randomized trials using modern radiation techniques in which conservative surgery and radiation therapy have been compared with mastectomy. These trials differ somewhat in patients selection, the methods of surgery and radiation therapy, and the length of follow-up. Nevertheless, all of these trials show equivalent survival between the two treatment options and are summarized in Table 1.3. A recent overview of these randomized trials, as well as a number of other unpublished results, showed equivalence in mortality.5 It should be remembered that patients have a choice of mastectomy versus breast conserving surgery and should be offered such a choice. There is frequently no single "right" choice for a woman with breast cancer and it is helpful to arrange for visits with the radiation oncologist, the medical oncologist and to encourage her to not rush making a decision.

Total Mastectomy

This refers to removal of the breast. Total mastectomy may be performed as the only operative procedure in which case regional lymph nodes are not removed. An older term for total mastectomy without removal of regional lymph nodes is simple mastectomy. The indication for this procedure includes DCIS that cannot be encompassed by a partial mastectomy. DCIS may not be encompassed effectively by a partial mastectomy because it is very extensive or because it is present simultaneously in diverse locations of the breast. Other indications include patient preference for management of DCIS even though eligible for breast conserving therapy. Mastectomy is also indicated for local recurrence in a breast previously treated for cancer with partial mastectomy and breast irradiation. When patients with invasive cancer are treated with total mastectomy, an axillary dissection is usually included. However, frail patients or those of advanced age are frequently considered for lessor surgical procedures that may include total mastectomy without a regional node resection.

Total Mastectomy and Axillary Lymphadenectomy (TM and AD)

This involves removal of the breast and removal of the regional axillary lymph nodes. TM and AD replaces the older term "modified radical mastectomy". In order to explain to a patient the meaning of modified radical mastectomy, the meaning of radical mastectomy must be explained. Since radical mastectomy is rarely performed and is an alarming procedure to patients, avoiding this reference is desired. The indications for TM and AD are multifocal cancer, large tumor to breast ratio, positive margins following partial mastectomy, and patient preference.

Radical Mastectomy

Removal of the breast, the skin of the breast, axillary lymph nodes, and the pectoralis major muscle. This procedure was introduced by Halsted6 in the late 1800s. It is rarely used now. Even tumors that are locally invading the muscle are usually treated with limited excision of the pectoralis muscle, thus obtaining negative margins but not removing the muscle in its entirety. Clinical trials have demonstrated no observable survival difference between total mastectomy and axillary resection versus radical mastectomy.

Axillary Dissection or Axillary Lymphadenectomy

This procedure usually means removal of level I and II axillary lymph nodes (lateral and posterior to the pectoralis minor muscle). More thorough node resection includes level III lymph nodes and interpectoral lymph nodes. The rationale for surgically removing axillary nodes are:

1. staging and prognosis,

2. regional control, and

3. possible improved survival.

Regional node resection usually is performed when the primary breast tumor is an invasive cancer. The extent of resection of axillary nodes and the value of axillary lymphadenectomy is controversial. Clinical trial data indicate that the status of the regional nodes is an independent prognostic indicator. The status of the nodes is an integral element of the TNM staging system. It is also clear that surgical resection of the axillary nodes results in excellent (nearly 100%) long term regional control. It carries significant morbidity including edema, sensory (and uncommonly motor) neurological complication, and increased susceptibility to serious infection of the upper extremity. Associated psychological distress is noted in a high percentage of women and this side effect is frequently underestimated. Since about 60-70% of patients do not have regional metastases, there is significant motivation to find alternatives to axillary lymphadenectomy. With the introduction of sentinel node biopsy for breast cancer (discussed below), it has become clear that the role of axillary dissection is in transition. Axillary dissection can probably be eliminated for patients with localized DCIS, DCIS with small areas of microinvasion, and for pure tubular carcinoma less than 1 cm in size because the risk of nodal involvement is extremely low.

The NSABP-06 clinical trial randomized patients to prophylactic regional lym-phadenectomy at the time of surgical treatment of the primary breast cancer or to delayed regional lymphadenectomy only if regional lymph nodes subsequently became clinically involved with tumor. This did not show a statistically meaningful difference din survival between the two groups. Three other prospective randomized European studies however did show a survival advantage to performing prophylactic axillary node dissection. Although in the United States it is generally assumed that axillary lymphadenectomy has no bearing on survival, it is possible that there regional lym-phadenectomy results in improved survival by as much as a 5-10%.

Sentinel Node Biopsy

This is a new technique that maps the drainage pattern of a tumor to the first set of lymph nodes most likely to contain metastatic disease. As applied to breast cancer it appears that a limited removal of the set of lymph nodes (usually 1-3 nodes) allows determination of whether regional metastases have occurred. Validation of the accuracy of this method of identifying the nodes most likely to contain metastases has been performed in a multi-center study for breast cancer.7 This study showed that injection of a radioactive tracer (technetium sulfur colloid) into normal breast tissue immediately surrounding the tumor resulted in labeling those nodes most likely to contain cancer. Intraoperatively a hand held gamma detector was used to identify the radiolabeled sentinel nodes. Interestingly, a small percentage of patients had drainage to pathologically positive lymph nodes which were located outside the axillary area. If those patients had only a conventional axillary lymph node resection, nodes containing cancer would have been left behind. Although it appears that the status of sentinel nodes predicts whether regional metastases have occurred, there is no data as to whether this will result in long term survival or long term regional control as good as conventional regional lymphadenectomy. This technique is now being evaluated in prospective randomized trials and is considered experimental until such data is available.

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