Treatment of ductal carcinoma in situ: an uncertain harm-benefit balance

Ductal carcinoma in situ develops in the milk ducts without invading the surrounding connective tissue. Progression to invasive carcinoma is slow and infrequent and is thus difficult to predict. Screening mammography has increased the number of women diagnosed with early-stage ductal carcinoma in situ. What is the best management strategy for patients whose breast biopsy suggests ductal carcinoma in situ? Is watchful waiting a reasonable option? To answer these questions, we conducted a review of the literature using the standard Prescrire methodology. Surgical resection is usually proposed to women with ductal carcinoma in situ but has not been compared with watchful waiting. Resection does not appear to have a major impact on mortality: trials of screening mammography showed no major reduction in breast cancer mortality, but screening does increase the number of diagnoses of ductal carcinoma in situ and, thus, the number of women who undergo surgery. When ductal carcinoma in situ is diagnosed by biopsy, histological examination of the surgically resected tumour reveals invasive breast cancer in about 13% to 24% of cases. Surgical removal of the tumour is usually proposed to women with ductal carcinoma in situ. Excision may be either localised (lumpectomy) or extensive (mastectomy). We found no randomised trials comparing the two approaches. Lumpectomy is usually proposed when the tumour is small (less than 20 mm) and appears to be amenable to complete excision with acceptable cosmetic results. A follow-up study of nearly 2000 women showed a recurrence rate of about 27% between 8 and 10 years after lumpectomy without further treatment. Mastectomy is usually proposed when the tumour appears to be extensive on mammography, or when complete resection with acceptable cosmetic results does not appear feasible, or when the patient chooses this option. Following mastectomy, the risk of carcinoma is similar to that of the general female population. Mastectomy and lumpectomy can both result in persistent pain, which is severe in about 13% of women. Systematic reviews of data for more than 10 000 women have shown that the following factors are statistically associated with an increased risk of recurrence after lumpectomy: age less than 50 years at diagnosis, tumours larger than 25 mm, high-grade tumours, and comedo-type necrosis. Healthy surgical margins of at least 2 mm are associated with a lower risk of recurrence. The impact of radiation therapy after lumpectomy for ductal carcinoma in situ has been evaluated in four randomised trials including a total of 3925 women. Radiation therapy reduced the risk of recurrence but did not prevent death from breast cancer. Irradiation carries a risk of skin burns and long-term cardiovascular and pulmonary toxicity. It also increases the risk of persistent post-surgical pain. In two randomised placebo-controlled trials of lumpectomy with or without radiation therapy for ductal carcinoma in situ, tamoxifen (an antiestrogen) did not affect either overall or breast cancer mortality, but it reduced the risk of recurrence by about one-quarter. Adverse effects of tamoxifen include venous thrombosis and pulmonary embolism, and endometrial cancer. In practice, women diagnosed with ductal carcinoma in situ have a number of options, none of which seems to have a clearly superior harm-benefit balance. Surgical excision reduces the risk of progression but can lead to persistent pain. Following radical mastectomy, the risk of breast cancer is similar to that of the general population. Lumpectomy is associated with a higher risk of recurrence and thus requires closer monitoring. Radiation therapy reduces the risk of recurrence in high-risk situations but has noteworthy adverse effects. Simple clinical monitoring is a valid option for asymptomatic patients: it carries a risk of progression to invasive cancer but avoids exposing many women to the adverse effects of surgery and radiation therapy.