Stages 0 and I Breast Cancer
Stages 0 and I Breast Cancer
This chapter focuses on the diagnosis and management of early-stage breast cancer, ie, stages 0 and I disease. This is an important area, since more noninvasive and small breast cancers are being diagnosed due to increasing use of screening mammography. Treatment of these malignancies will continue to evolve as the results of clinical trials lead to further refinements in therapy.
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 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 seen on a 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 of 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 shifted to individuals in their 50s. The incidence of LCIS decreases in women who are in their 60s to 80s. The age at which the peak incidence of LCIS occurs may be related to the use of hormone replacement therapy. It is also possible that use of hormone replacement therapy 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 separate mammographic abnormality or palpable mass.
Risk of invasive cancer
Approximately 20% to 25% of women 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.
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. One of these, pleomorphic LCIS, tends to be associated with infiltrating lobular carcinoma, and its cytologic features are similar to those of intermediate- or high-grade DCIS. Pleomorphic LCIS may be more aggressive and more likely to progress to invasion than classic LCIS.
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, use of tamoxifen, or bilateral prophylactic total mastectomy with or without reconstruction. At present, the decision regarding a given treatment will depend upon the patient’s individual risk profile for DCIS or invasive breast cancer, determined after careful counseling. In the future, treatment decisions may be based upon an analysis of a series of molecular markers, which can separate 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 2012, an estimated 63,300 new cases of in situ breast cancer were estimated to occur among women, with approximately 85% being DCIS. In some institutions, DCIS accounts for 25% to 50% of all breast cancers.
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 to 56 years, which is approximately a decade later than the age at presentation for LCIS.
Parikh et al compared the clinicopathologic features and long-term outcomes from women with DCIS vs DCIS with microinvasion (DCISM) treated with breast conservation, to assess the impact of microinvasion. They concluded that natural history of DCISM closely resembles that of DCIS. The incidence of axillary metastasis in DCISM appears to be small (less than 3%) and does not appear to correlate with outcomes. Furthermore, the incidence of locoregional and distant failures in DCISM is low. Thus, microinvasion should not be the sole criterion for more aggressive treatment.
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.
Kuhl et al investigated the sensitivity of mammography vs magnetic resonance imaging (MRI) in detecting DCIS and compared the biological profiles of abnormalities detected by each method. Over a 5-year study period, 198 women had a pathologic diagnosis of pure DCIS without associated invasive breast cancer or microinvasion. In all, 167 of these women underwent both imaging tests preoperatively; 93 (56%) of these cases were diagnosed by mammography, and 153 (92%) were diagnosed by MRI (P < .001). The sensitivity of mammography decreased with nuclear grade; it was highest in patients with low-grade DCIS and lowest in cases of high-grade DCIS. The sensitivity of MRI was superior to that of mammography across all DCIS subtypes. In addition, sensitivity increased with nuclear grade of DCIS; it was lowest in low-grade cases (80%) and highest in high-grade cases (98%), independent of the presence or absence of necrosis.
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 they generally present in the same quadrant within 10 years of the DCIS diagnosis. 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.
A variety of histologic patterns are seen with DCIS (eg, solid, cribriform, 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 human epidermal growth factor receptor 2 (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.