Objective:

Over 170,000 women are diagnosed with breast cancer yearly in the United States, incurring enormous individual and societal costs. The objective of this systematic review is to assess the quantity and quality of published evidence regarding specific current issues of diagnosis and management of women with breast disease.

Search Strategy:

Literature published from January 1, 1994 to September 15, 1999 was searched using Medline and Current Contents^® databases. These searches were supplemented by manually reviewing bibliographies of all accepted studies and review articles.

Selection Criteria:

Accepted studies included observational studies, randomized controlled trials (RCTs), non-randomized controlled trials (nRCTs), and uncontrolled case series (UCSs). All accepted publications were required to address the prospectively identified areas of interest and have a total sample size of at least 10 patients. Only English language studies were accepted.

Data Collection and Analysis:

Pertinent data were extracted from accepted studies by one researcher, and reviewed by a second. Studies were evaluated for quality and level of evidence. The data were summarized and synthesized qualitatively. A panel of multidisciplinary clinical experts provided recommendations throughout the project.

Main Results:

The database includes 51 studies (30,178 patients) regarding breast symptoms and risk factors, 20 studies (3,501 patients) pertinent to lobular carcinoma in situ (LCIS) or atypical hyperplasia (AH), and 39 studies (5,900 patients) regarding sentinel node biopsy.

Incomplete reporting of outcomes in patients with different risk factors precludes assessment of the relationship between risk factors, breast symptoms, and cancer incidence.

When managed by observation alone, LCIS was associated with a 4.2-9.3 percent incidence of cancer within 5 years and 7.7-26.3 percent incidence in studies that followed patients for at least 5 years. AH was associated with a 3.7-19.3 percent incidence of cancer within 5 years, and 13.6-33.6 percent incidence in longer-term studies. Selective estrogen receptor modulator (SERM) therapy with Tamoxifen markedly decreased the incidence of breast cancer following a diagnosis of LCIS or AH. After excisional biopsy was done, approximately half of the atypical ductal hyperplasias (ADHs) diagnosed by stereotactic core needle biopsy (SCBX) were changed, usually to a more worrisome diagnosis.

Regardless of tumor location, size, or history of breast surgery, sentinel node biopsy had a false negative rate of 1.9 to 3.3 percent. Sentinel nodes were positive for metastatic disease in approximately one third of cases.

Conclusions:

The best available evidence suggests that breast symptoms are evaluated initially by clinical breast exam and imaging study, with supplemental studies when the diagnosis is unclear. There is no evidence to support modifying the work-up of breast symptoms or mammographic abnormalities based on risk factors other than age. Strong evidence supports the necessity of performing excisional biopsy following SCBX diagnosis of ADH, as excisional biopsy often leads to a change in diagnosis. Preliminary evidence strongly suggests that Tamoxifen therapy markedly decreases the incidence of cancer following a diagnosis of LCIS or AH, but it is associated with increased risk of endometrial cancer, thromboembolic disease, and other complications. While studies to date strongly suggest that sentinel node biopsy is successful in most breast cancer patients, long-term cancer outcomes and survival data are required before sentinel node biopsy could be considered the standard of care.