Multicentric and Multifocal Cancer
Multicentric and Multifocal Cancer
Abstract & Commentary
Synopsis: Breast ultrasound was performed on 40 patients with known breast cancer or highly suspicious findings for cancer in an attempt to identify other sites of unsuspected malignancy and to determine optimal definitive management.
Source: Berg WA, Gilbreath PL. Multicentric and multifocal cancer: Whole-breast US in preoperative evaluation. Radiology 2000;21:59-66.
The management of breast cancer diagnosed by clinical examination, mammography, or both varies not only with geographic regional preferences, but with the extent of disease. Size and extent of disease as well as multiple malignant lesions influences both the choice of conservation therapy (lumpectomy and radiotherapy plus adjuvant chemo/hormonal treatment) or mastectomy (plus adjuvant chemo/hormonal treatment), as well as prognosis. While microscopic dissections of mastectomy specimens have shown frequent involvement of malignant sites in addition to the known cancer—especially within close proximity to the index lesion—the clinical significance of this observation is unclear. For most stage I lesions (lesions that constitute a majority of breast cancers seen at dedicated breast evaluation centers) overall recurrence rates do not differ significantly for conservation therapy and mastectomy, providing a clinical basis for alternative approaches. Thus, the issue remains: what is the significance of a known multifocal or multicentric incidence of malignancy that approximates 50%?
On the other hand, local recurrence rates range from 11% to 40% within five years—the lesser percentage attributed to unifocal disease. One explanation for the higher percentage is that when multifocal lesions are sufficiently large, radiotherapy may not be as effective for cure. MRI has shown additional tumor foci in patients with known breast cancer that were not identified clinically or mammographically. This report studied the feasibility of using whole breast ultrasound as a method for detecting second or third lesions in the breast.
Berg and Gilbreath identified 45 of 48 invasive tumor foci (94%) and seven of 16 (44%) foci of intraductal carcinoma. Nine of 64 lesions (14%) were seen only at ultrasound (US). Two of 11 foci (18%) were missed by both mammography and US. In this group of 40 patients, 13 (32%) incidentally detected solid masses were biopsied and found to represent malignancy. These findings prompted wider resections in three (15%) patients than might otherwise have been performed. Berg and Gilbreath suggest that whole breast US complements mammography in preoperative evaluation of patients with a high likelihood (not simply risk) of breast cancer and identifies clinically and mammographically occult lesions that affect surgical management. In addition, US confirms focal areas of clinical or mammographic concern, raising the confidence level of predicting malignancy.
Comment by R. James Brenner, MD, JD
The study is of interest for two reasons. First, the ability to detect additional cancer sites that would predict who fails conservation therapy and who does not would provide a more rational basis for surgical treatment decisions. While advocates of MRI have proposed that additional lesions are best evaluated by this modality where sensitivity has been generally considered to be higher than mammography, the lack of specificity of MRI for cancer combined with the difficulty of localizing lesions seen only on MRI presents formidable treatment issues. If US can perform the same task, both tissue sampling and localization issues are easily resolved. There are real limitations to this report, however. The number of patients studied was small, a disproportionate number of large lesions (mean size, 18 mm; 55% palpable) were evaluated, a high number of infiltrating lobular carcinomas were included in the study group (more than twice the relative incidence), and the lesions identified by US only were also large (mean size, 27 mm), likely representing a patient with more advanced disease even for the index lesion.
The study begs an even more important question; namely, what is the feasibility of whole breast US for breast cancer screening, especially given cancers found only on ultrasound? Berg and Gilbreath report that 13 incidentally detected solid masses among these 40 patients were malignant, a ratio that would invite a true consideration of screening ultrasonography. But these patients were of the highest risk (they had breast cancer) rather than simply at elevated risk, the latter criteria being the basis for suggesting screening studies such as US in addition to mammography. When US has been applied in a screening fashion to patients without known breast cancer (and, thus, a lower likelihood that incidentally discovered solid masses will be malignant), biopsy yields for cancer of otherwise benign appearing lesions are less than 4%, with insufficient follow-up to determine actual sensitivity. In other words, in a cohort of patients with known cancer, false-positive biopsy rates for masses detected only by sonography may be acceptable. However, when patients who do not have breast cancer—and are not at increased risk for additional cancers not seen by mammography or clinical examination—are screened by whole breast ultrasound, the likelihood of identifying malignancy from biopsying a large population of otherwise benign appearing solid masses is much lower, and perhaps too low to justify the application of this approach.
This study suggests that in a group of patients with a sufficiently high risk of additional cancers, a more aggressive approach toward biopsy of additional solid masses may be valid. Their continued work with contralateral whole breast US in a similar cohort of patients will advance the feasibility of this approach one step further.
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