Stages 0 and I Breast Cancer

STAGE 0 BREAST CANCER

Stage 0 breast cancer includes noninvasive breast cancer--lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS)-- as well as Paget’s disease of the nipple when there is no associated invasive disease.

Lobular carcinoma in situ

LCIS is nonpalpable, produces no consistent mammographic changes, and is often an incidental finding after breast biopsy performed for another reason.

The biologic behavior of LCIS continues to be an issue of debate. Most clinicians agree that it is a marker for increased risk for all types of breast cancer (both noninvasive and invasive).

Epidemiology and etiology

The incidence of LCIS has doubled over the past 25 years and is now 2.8 per 100,000 women. In the past, the peak incidence of LCIS was in women in their 40s. Over the past 3 decades, the peak incidence has increased to the 50s. The incidence of LCIS decreases in women who are in their 60s–80s. It has been suggested that the increase in the age of peak incidence of LCIS is related to the use of hormone replacement therapy (HRT). It is also possible that the use of HRT prevents the usual regression of LCIS normally seen at the time of menopause.

Signs and symptoms

LCIS is nonpalpable and has no consistent features on breast imaging. Most often, LCIS is found in association with a completely separate mammographic abnormality or palpable mass.

Risk of invasive cancer

Approximately 20%–25% of women with LCIS will develop invasive cancer within 15 years after the diagnosis of LCIS. More often, the invasive cancer is ductal in origin, and both breasts are at risk. At this point, there are no reliable molecular markers to determine which patients with LCIS will progress to invasive cancer.

Just as the incidence of LCIS has increased, there has also been an associated increase in the incidence of cases of infiltrating lobular carcinoma in postmenopausal women. The increase in invasive lobular carcinoma peaks in women in their 70s.

Pathology

LCIS appears to arise from the terminal duct-lobular apparatus, and the disease tends to be multifocal, multicentric, and bilateral. Subsequently, other types of LCIS have also been described and include pleomorphic LCIS. This entity tends to be associated with infiltrating lobular carcinoma, and the cytologic features are similar to those of intermediate- or high-grade DCIS. Pleomorphic LCIS may be more aggressive, with a higher likelihood of progression to invasion than classic LCIS.

Treatment options

The management of LCIS is continuing to evolve since the disease appears to be heterogeneous. Presently, treatment options include close follow-up, participation in a chemoprevention trial, tamoxifen, or bilateral prophylactic total mastectomy with or without reconstruction. At present, the decision for a given treatment will depend upon the patient’s individual risk profile for DCIS or invasive breast cancer after careful counseling. In the future, treatment decisions may be based upon an analysis of a series of molecular markers, which can separate those patients with a low risk for invasion from those who are at high risk for disease progression.

DUCTAL CARCINOMA IN SITU

DCIS is being encountered more frequently with the expanded use of screening mammography. In some institutions, DCIS accounts for 25%–50% of all breast cancers.

Epidemiology

DCIS, like invasive ductal carcinoma, occurs more frequently in women, although it accounts for approximately 5% of all male breast cancers. The average age at diagnosis of DCIS is 54–56 years, which is approximately a decade later than the age at presentation for LCIS.

Signs and symptoms

The clinical signs and symptoms of DCIS include a mass, breast pain, or bloody nipple discharge. On mammography, the disease most often appears as microcalcifications. Because these microcalcifications are nonpalpable and are not always associated with a mass, DCIS is often discovered with mammography alone. Approximately 5% of patients who present with pathologic nipple discharge will have underlying breast cancer, and many of them will have DCIS alone.

Risk of invasive cancer

The risk of developing an invasive carcinoma following a biopsy-proven diagnosis of DCIS is between 25% and 50%. Virtually all invasive cancers that follow DCIS are ductal and ipsilateral and generally present in the same quadrant within 10 years of the diagnosis of DCIS. For these reasons, DCIS is considered a more ominous lesion than LCIS (which is considered a marker for risk) and appears to be a more direct precursor of invasive cancer.

Pathology

A variety of histologic patterns are seen with DCIS, including solid, cribriform, and papillary. Some researchers have divided DCIS into two subgroups: comedo and noncomedo types. As compared with the noncomedo subtypes, the comedo variant has a higher proliferative rate, overexpression of HER2/neu, and a higher incidence of local recurrence and microinvasion. DCIS is less likely to be bilateral and has approximately a 30% incidence of multicentricity.

Treatment of noninvasive breast carcinoma

DUCTAL CARCINOMA IN SITU

Breast-conserving surgery

Breast-conservation surgery, followed by radiation therapy to the intact breast, is now considered the standard treatment of DCIS. Since the incidence of positive lymph nodes after axillary lymph node dissection for DCIS is ~1%–2%, axillary dissection is not indicated in most instances.

The most important factor in determining local control within the breast is margin status. A surgical margin of 1 mm has been associated with a 43% chance of having residual disease at the time of reexcision. When a surgical margin of 10 mm can be obtained, there is an extremely low rate of recurrence (4%). A 10-mm surgical margin may not be practical, however, when trying to provide a good cosmetic outcome. When breast-conserving therapy is used alone (without irradiation), a margin of at least 10 mm is required, and the tumor should be small (< 1 cm) and a noncomedo type. Although a wide margin is always desirable, narrower margins are acceptable for DCIS when radiation therapy is used after lumpectomy.

Sentinel node biopsy

The sentinel lymph node is the first node in the draining lymphatic basin that receives primary lymph flow. The technique of sampling the first draining lymph node was initially described in the management of patients with melanoma to determine who would benefit from regional lymph node dissection and was performed using a vital blue dye. This same technique has been used in patients with breast cancer, and sentinel lymph node biopsy represents a minimally invasive way to determine whether the axilla is involved with disease. If the sentinel lymph node is negative, the patient may be spared lymph node dissection. The precise methods for identifying the sentinel lymph node (filtered vs unfiltered Tc-99m sulfur colloid and/or blue dye) and assessing the node (hematoxylin and eosin staining vs immunohistochemistry [IHC] vs polymerase chain reaction [PCR]) are being studied.

When blue dye is used, it can be injected into the breast parenchyma at the primary tumor or subareolar site. The radioactive tracer can be injected subdermally or intraparenchymally at the site of the primary tumor or in the subareolar location. The site and technique of injection will be based upon individual patient factors, including the type and location of the previous breast biopsy.

When lymphatic mapping and sentinel lymph node biopsy are performed, a blue vital dye and/or a radioactive tracer (generally technetium-labeled sulfur colloid) can be used. When a radiotracer is used, lymphoscintigraphy can also be performed to aid in locating the sentinel node. When a sentinel node biopsy is performed using blue dye, the axillary surgery should be performed carefully to avoid disrupting the blue-stained afferent lymphatic channels. When a radioisotope is used, a hand-held gamma counter is used to locate the sentinel node.

Axillary lymph node dissection is not routinely recommended for patients with DCIS. Recently, however, investigators have used sentinel lymph node biopsy to determine whether individuals with DCIS may harbor occult nodal metastases. Current studies have identified metastatic disease to the axillary nodes in up to 12% of patients who have undergone sentinel lymph node biopsy. Despite this relatively high percentage of positive sentinel nodes, recurrence in the nodal basins is rare (about 2%). Based on this and recent work, there is no indication for routine sentinel lymph node biopsy in patients with DCIS.

Factors associated with an increased risk of axillary metastasis with a diagnosis of DCIS are extensive DCIS requiring mastectomy, suspicion of microinvasion, DCIS associated with a palpable mass, and evidence of lymphovascular permeation or invasion seen on review of the slides. These factors likely are associated with a preoperatively nondiagnosed invasive component. However, for patients diagnosed with DCIS who are scheduled for mastectomy, sentinel lymph node sampling, prior to mastectomy, is a reasonable practice. In the event that an occult invasive cancer within the mastectomy is found, a negative sentinel node would be reassuring and perhaps would make it possible to avoid follow-up axillary dissection.