Elisa Rush Port, MD
Breast Service, Department of Surgery
Memorial Sloan-Kettering Cancer Center
New York, New York
Controversy over the benefits of annual mammography in the reduction of breast cancer-related mortality has recently received much attention. Seven randomized trials investigating the benefit of mammography compared to observation alone have been performed. While flaws can be identified with each individual study, the majority of them, individually and collectively, indicate that mammography reduces breast cancer-related mortality.
Various imaging modalities, such as MRI and ultrasound, can be used in addition to mammography; these tests, however, must be used selectively and judiciously, as there are advantages and disadvantages to each intervention. The goal of using adjunctive imaging modalities is early detection of the estimated 10%-15% of cancers missed by mammography. The effectiveness of mammography is most limited in young patients and those with dense breast tissue, which makes mammographic detection of cancer more difficult. Thus, young, premenopausal patients with a known increased breast cancer risk comprise one important group for whom the addition of screening ultrasound and/or MRI should be considered. While both ultrasound and MRI can detect cancers that are missed by mammography, the absolute number of additional cancers detected by each modality alone is low; ultrasound detects otherwise occult cancer in = 1% and MRI does so in approximately 4% of a highly selected group of patients. Both tests, however, are also associated with substantial false-positive rates.
Although breast carcinoma is the most common cancer affecting American women, with nearly 212,000 new cases diagnosed in 2003, all women are not at equal risk for its development. Various factors are known to increase a woman's risk, while some of a woman's risk remains unable to be predicted. For example, age is important; 75% or more of new cases occur in women >- 50 years. Identification of populations at increased risk for breast cancer is important to select appropriate strategies for breast cancer screening.
The degree of increased risk associated with a family history of breast cancer ranges from a somewhat higher risk than the general population to the very high risk associated with BRCA1 or 2 mutations. In order to estimate the risk, the family histories of both parents must be ascertained since these gene mutations can be passed to progeny by either parent. There is a higher incidence of BRCA mutations within the Ashkenazi Jewish population, with approximately one in 40 Ashkenazi Jews (2%) harboring either a BRCA1 or 2 mutation; BRCA mutations are seen in only one in 400 women (0.2%) in the general population. There is also an increased incidence of breast cancer in males associated with the presence of the BRCA2 mutation.
Family history of ovarian cancer should also be determined, as this is part of the familial breast and ovarian cancer syndrome, as is seen with BRCA1 or 2 mutations. Other cancers that have been shown to be associated with hereditary breast and ovarian cancer syndromes that may place a patient at higher risk for developing breast cancer include prostate cancer, colon cancer, and possibly pancreatic cancer. If family members were diagnosed at early ages or if bilateral breast cancers occurred in any relatives, the patient's estimated risk would be substantially higher.
Other risk factors for breast cancer include atypical hyperplasia (either lobular or ductal) or LCIS on a previous breast biopsy. The increased risk associated with atypical hyperplasia alone is approximately two to three times that of the average woman, or a lifetime risk of 20%-25%. The presence of LCIS confers a slightly higher lifetime risk of approximately 25%-30%. Usually, LCIS and/or atypia is identified incidentally when a biopsy is performed for another reason, such as the presence of new calcifications seen on mammogram. The LCIS or atypia is a marker of increased future risk, rather than necessarily the specific precursor lesion of cancer. The future risk of breast cancer applies to both breasts equally, not merely the breast in which the LCIS or atypia was found.
In addition to family history and the presence of atypical hyperplasia or LCIS, there are other risk factors that play some role in determining an individual woman's risk for breast cancer, such as age at menarche, age at menopause, age at first birth, and parity. Statistical models can be used to estimate the risk of breast cancer for the individual patient. This risk estimate can help to guide patient/physician discussions regarding breast cancer screening and other prevention strategies.
The decision to perform additional imaging tests depends on the risks and benefits for each patient in view of their individual risks, as determined by age, menopausal status, BRCA1 or 2 mutations, family history, breast density as determined by mammography, and findings on physical examination. The potential benefit of detecting an otherwise occult cancer must be weighed against the potential risk of a false-positive finding, which would necessitate an unnecessary biopsy and its associated anxiety for the patient. Proper patient selection is, therefore, of utmost importance. Future investigations will need to further define the subgroups of high-risk patients who will benefit most from these and other interventions.
