Noninvasive (in situ) breast cancer:

Noninvasive (in situ) breast cancer: DCIS (ductal carcinoma in situ) or LCIS (lobular carcinoma in situ) are lesions with malignant cells that have not penetrated the basement membrane of the mammary ducts or lobules, respectively.

A. DCIS

DCIS, or intraductal carcinoma, is treated as a malignancy because DCIS has the potential to develop into invasive cancer.

• It is usually detected by mammography as clustered pleomorphic calcifications.

• Physical examination is normal in the majority of patients.

• It may advance in a segmental manner, with gaps between disease areas.

• It can be multifocal (two or more lesions >5 mm apart within the same index quadrant) or multicentric (in different quadrants).

a.Histology

1.There are five architectural subtypes: papillary, micropapillary, solid, cribriform, and comedo. Specimens are also grouped as comedo versus noncomedo.

2.The high-grade subtype is often associated with microinvasion, a higher proliferation rate, aneuploidy, gene amplification, and a higher local recurrence rate.

3.ER and PR expression levels should be obtained if hormone therapy is being considered.

b.Treatment

1.Surgical excision alone (via partial mastectomy) with margins greater than 10 mm is associated with a local recurrence rate of 14% at 12 years (Am J Surg 2006;192:420). The addition of adjuvant radiation reduces the local recurrence rate to 2.5%. Approximately half of the recurrences present as invasive ductal carcinomas. Surgical options depend on the extent of disease, grade, margin status, multicentricity of disease, and patient age.

• Partial mastectomy: For unicentric lesions. Needle localization is required to identify the area to be excised in most cases. Bracket needle localization (two or more wires to map out the extent of disease to be resected) for more extensive lesions is occasionally used.

• Mastectomy: Total (simple) mastectomy with or without immediate reconstruction is recommended for patients with multicentric lesions, extensive involvement of the breast (disease extent relative to breast size), or persistently positive margins with partial mastectomy.

2.Assessment of axillary lymph nodes: Axillary dissection is not performed for pure DCIS.

• Sentinel lymph node biopsy (SNLB, see later discussion) may be considered when there is a reasonable probability of finding invasive cancer on final pathologic examination (e.g., >4 cm, palpable, or high grade).

• Some surgeons perform SLNB in all patients with DCIS undergoing mastectomy because SLNB cannot be performed postmastectomy if an occult invasive cancer is found. This is an area of ongoing controversy and research.

• A positive sentinel node indicates invasive breast cancer and changes the stage of the disease; a completion axillary dissection is then indicated.

c.Adjuvant therapy

• For pure DCIS, there is no added benefit from systemic chemotherapy because the disease is confined to the ducts of the breast. However, in those patients with ER-positive DCIS, adjuvant tamoxifen can reduce the risk of breast cancer recurrence by 37% over 5 years and the risk of developing a new contralateral breast cancer (NSABP B-24 trial). However, there is no survival benefit. Aromatase inhibitors (e.g., anastrazole, exemestane, letrozole), which block the peripheral conversion of androgens into estrogens by inhibiting the enzyme aromatase but does not affect estrogen produced by the ovaries, are sometimes used as an alternative in postmenopausal patients.

• Adjuvant radiation should be given to patients with DCIS treated with partial mastectomy to decrease the local recurrence rate (NSABP B-17 trial). This is especially true for younger women with close margins or large tumors. However, there is no survival benefit. For older patients with smaller, widely excised DCIS of low or intermediate grade, the benefit of radiation therapy is so small that adjuvant radiation is not recommended.

d.The Van Nuys Prognostic Index (Table 27-3) is a numerical algorithm (based on lesion size, margin, tumor grade, presence of necrosis, and age) used to stratify patients with DCIS into three groups to determine which patient is at greatest risk of recurrence and would therefore benefit the most from a more aggressive treatment approach. The low-scoring group may be treated with partial mastectomy alone. The intermediate-scoring group has been shown to benefit from adjuvant radiation therapy, and the high-scoring group should undergo mastectomy because the risk of recurrence with partial mastectomy with or without radiation is high.

B. LCIS

• It may be multifocal and/or bilateral.
• The cancer that develops may be invasive ductal or lobular and may occur in either breast.
• LCIS has loss of E-cadherin (involved in cell–cell adhesion), which can be stained for on pathology slides to clarify cases that are borderline DCIS versus LCIS.
• Pleomorphic LCIS is a particularly aggressive subtype of LCIS that is treated more like DCIS; it tends to have less favorable biological markers.
• Treatment options are (1) lifelong close surveillance, (2) bilateral total mastectomies with immediate reconstruction for selected women with a strong family history after appropriate counseling, or (3) prophylaxis with tamoxifen.