Therapy for Intraductal Carcinoma of the Breast
Therapy for Intraductal Carcinoma of the Breast
Abstract & commentary
Synopsis: Tamoxifen added to lumpectomy and radiation therapy improves outcome after treatment of intraductal carcinoma in situ of the breast.
Source: Fisher B, et al. Lancet 1999;353:1993-2000.
The national surgical adjuvant breast and Bowel Project B-24 was a double-blind, randomized, controlled trial, comparing lumpectomy, radiation therapy, and tamoxifen with lumpectomy and radiation therapy alone for ductal carcinoma in situ of the breast. A total of 1804 women with ductal carcinoma in situ participated in the study, including those whose resected sample margins were involved with a tumor. Each group involved 899 patients. The tamoxifen-treated group had an 8.2% incidence of breast cancer events at five years compared with 13.4% in the placebo group, including events in both the ipsilateral and contralateral breasts. The relative risk indicated a 37% reduction in breastcancer events in the tamoxifen-treated group. In ipsilat-eral breasts, tamoxifen treatment produced a 44% reduc-tion in invasive disease. In contralateral breasts, therewas a 52% reduction in breast tumors in the tamoxifen-treated group. Fisher and colleagues conclude that the combination of lumpectomy, radiation therapy, and tamoxifen is more effective than lumpectomy and radia- tion therapy alone, with the added benefit of a decrease in the rate of invasive cancer in the ipsilateral breast.
Comment by Leon Speroff, MD
Until the mid-1980s, ductal carcinoma in situ of the breast was treated by mastectomy and axillary dissection. Before the availability of mammography, less than 3% of newly diagnosed breast cancers were ductal carcinoma in situ. With the improvement in and greater availability of diagnostic equipment, 20-30% of mammographically- detected cancers are now ductal carcinoma in situ. The National Surgical Adjuvant Breast and Bowel Project reported in 1993, and again in 1998, that lumpectomyand radiation therapy were effective treatments, and thatmastectomy was not warranted in women who had ductal carcinoma in situ. This report demonstrates that the addition of tamoxifen (10 mg bid for 5 years) improves theoutcome with all breast cancer events, including invasive and non-invasive tumors in the ipsilateral breast, in thecontralateral breast, and at metastatic sites. After five
years, lumpectomy alone is associated with a 25% incidence of breast cancer-related events. Adding radiotherapy reduced the percentage to 13%. Adding radiotherapy and tamoxifen reduces the percentage to 8%. A study is currently underway to determine the effectiveness of tamoxifen in treating ductal carcinoma in situ after lumpectomy without radiation therapy.
Because mammography has made the diagnosis of ductal carcinoma in situ of the breast relatively common, the proper management of this carcinoma in situ is a major issue. Although ductal carcinoma in situ is viewed as a precursor to invasive disease, this does not always occur. Because of the small but real chance of invasive disease, women with ductal carcinoma in situ have often been treated with mastectomy. There has not been a trial comparing the results with mastectomy to lumpectomy and radiotherapy. Cancer clinicians accept that there is a low, although not zero, rate of occurrence after mastec- tomy. The possibility exists that a combination of lumpectomy, radiation therapy, and tamoxifen may bring the risk of recurrence to a rate that is comparable to mastectomy. Adding tamoxifen treatment to lumpectomy and radiation therapy makes the decision to avoid mastectomy relatively easier.
These results are relevant to the use of tamoxifen for the prevention of breast cancer. In my view, the administration of tamoxifen to healthy women is not a clear-cut necessity. Added to the real incidence of side effects, including endometrial cancer, venous thrombosis, and possibly cataracts, there is also the concern that tamoxifen treatment is not preventing, but delaying the onset of breast cancer. For this reason, the decision to take tamoxifen as preventive treatment is not an easy one for healthy women. The data offers convincing evidence that women with ductal carcinoma in situ of the breast, or atypical hyperplasia in a breast biopsy, are good can-didates for tamoxifen treatment.
The following statements are true of tamoxifen and breast cancer except:
a. Tamoxifen alone is adequate adjuvant therapy after lumpectomy for ductal carcinoma in situ.
b. The duration of tamoxifen adjuvant therapy is five years.
c. The combination of lumpectomy, radiation therapy, and tamoxifen for ductal carcinoma in situ may be as effective as mastectomy.
d. Twenty to 30% of breast cancers detected by mammography screening are ductal carcinoma in situ.
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