CHICAGO—Although several studies of breast-conserving treatment have been conducted in women with multicentric or multifocal breast cancer, mastectomy is still the standard of care for this patient population, Monica Morrow, MD, said the 8th Annual Lynn Sage Breast Cancer Symposium. Dr. Morrow is chairman of Surgical Oncology and G. Willing Pepper Chair in Cancer Research at Fox Chase Cancer Center.
The rationale for mastectomy in patients with multicentric cancer arises from pathology studies of surgical specimens that show additional disease beyond the gross appearance of breast cancer seen on mammography, Dr. Morrow said. She noted that in one study, 23 of 51 specimens from women with multifocal or multicentric breast cancer showed evidence of residual invasive or intraductal malignancy in three or four quadrants, in addition to gross lesions.
Nevertheless, she said, breast-conserving surgery has been performed on patients with multicentric cancer for cases that meet four principal selection criteria: (1) the presence of fewer than two lesions that are clinically and mammographically evident and that can be completely removed surgically, (2) the absence of disease in surgical margins, (3) the lack of any sign of extensive intraductal components, and (4) the likelihood of an acceptable cosmetic result.
Studies of breast-conserving surgery for women with multicentric cancer have had intrinsic flaws, Dr. Morrow said: In many studies, surgical margins have not been inked, the quality of diagnostic mammography has been poor, and the sample sizes have been extremely small.
Risk of Local Recurrence
The most serious limitation to the use of breast-conserving surgery in these patients is the risk of local recurrence, she said. In two studies that compared local recurrence rates following breast-conserving surgery for women with unicentric and multicentric disease, the percentage of local treatment failure was significantly higher in those with multicentric breast cancer. In women with unicentric cancer, the local recurrence rate was 11% in both studies; in multicentric cancer, it was 40% in one study and 25% in the other. In the study with the 25% recurrence rate for multifocal disease, the rate was 16% in women with two or fewer tumors and 35% in those with more than three tumor foci.
In two additional studies, breast-conserving therapy had a 3.0% to 3.7% rate of local recurrence in multicentric breast cancer even when multiple lumpectomies were performed.
A Major Risk Factor
Multicentricity is, in fact, a well-known risk factor for local disease recurrence, Dr. Morrow emphasized. A multivariate logistic regression analysis of 491 patients with multicentric cancer and 1,098 controls treated between 1981 and 1990 found that multicentricity was one of three significant risk factors for local treatment failure. In this analysis, the odds ratios for local recurrence were 1.8 for multicentricity, 1.4 for age younger than 40, and 1.9 for a positive surgical margin.
The presence of multifocal disease has been associated with a poor prognosis for women with stage I or II breast cancer, she said. In a study of 605 stage I/II patients, 80 had a local recurrence. A major predictor of poor prognosis was skin recurrence (hazard ratio 3.38), and the only factor that predicted skin recurrence was multifocality (hazard ratio 4.08).
"It would be nice to see trials of breast-conserving therapy in a well-defined population of patients with multicentric breast cancer," Dr. Morrow said. However, she emphasized, "mastectomy remains the standard therapy for multicentric breast cancer detected clinically or by mammography."