Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial.

BACKGROUND: We have shown previously that lumpectomy with radiation therapy was more effective than lumpectomy alone for the treatment of ductal carcinoma in situ (DCIS). We did a double-blind randomised controlled trial to find out whether lumpectomy, radiation therapy, and tamoxifen was of more benefit than lumpectomy and radiation therapy alone for DCIS. METHODS: 1804 women with DCIS, including those whose resected sample margins were involved with tumour, were randomly assigned lumpectomy, radiation therapy (50 Gy), and placebo (n=902), or lumpectomy, radiation therapy, and tamoxifen (20 mg daily for 5 years, n=902). Median follow-up was 74 months (range 57-93). We compared annual event rates and cumulative probability of invasive or non-invasive ipsilateral and contralateral tumours over 5 years. FINDINGS: Women in the tamoxifen group had fewer breast-cancer events at 5 years than did those on placebo (8.2 vs 13.4%, p=0.0009). The cumulative incidence of all invasive breast-cancer events in the tamoxifen group was 4.1% at 5 years: 2.1% in the ipsilateral breast, 1.8% in the contralateral breast, and 0.2% at regional or distant sites. The risk of ipsilateral-breast cancer was lower in the tamoxifen group even when sample margins contained tumour and when DCIS was associated with comedonecrosis. INTERPRETATION: The combination of lumpectomy, radiation therapy, and tamoxifen was effective in the prevention of invasive cancer.

A complementary role for thallium-201 scintigraphy with mammography in the diagnosis of breast cancer.

Physical examination and mammography are currently the only proven and reliable methods of early detection of breast cancer. Although both procedures are highly sensitive, their limited specificity often requires surgical biopsy in order to differentiate between malignant and benign lesions. The purpose of this prospective study is to investigate the diagnostic specificity of thallium imaging for breast cancer and to determine its efficacy as a complement to mammography. Two groups were studied: Group A: Patients found to have breast abnormalities and scheduled for biopsy or surgery and Group B: Patients who were suspected to have a recurrence of cancer after mastectomies or lumpectomies. In Group A, thallium scans of 32 breasts in 30 patients were performed prior to biopsy or surgery, yielding pathological diagnoses of 31 breasts in 29 patients. Results for Group A included seven true-positive thallium scans, twenty-two true-negative scans, two false-negative scans, and one false-positive scan. In Group B, seven patients were scanned to evaluate subcutaneous nodules for breast cancer following mastectomy or lumpectomy. Results for Group B included five true-positive scans, one true-negative scan, one false-negative scan and no false-positive scans. Thallium breast scanning was shown to have high specificity for cancer (specificity 96% and sensitivity 80%), suggesting that this technique should be evaluated in additional patient studies to determine its role in clinical situations.

New surgical method to prevent pelvic radiation enteropathy.

Pelvic radiation doses exceeding 4,000-4,500 cGy are known to be associated with acute and chronic radiation enteropathy. This same radiation dose is, at the same time, only moderately effective in the elimination of microscopic malignancy, let alone gross clinical disease. Numerous medical and surgical attempts to minimize this complication have been uniformly unsuccessful. With the availability of a new synthetic, absorbable, polyglycolic acid mesh, an intestinal sling surgical procedure has been devised to exclude the small bowel from the pelvis and subsequent radiation fields. Twenty-five patients have been treated by this new technique with only one complication presenting as a fungal infection. Small-bowel barium contrast studies in 16 patients referred for postoperative radiation demonstrated 13 satisfactory exclusions of the small bowel from the translateral pelvic irradiation field. In 16 evaluable patients, three had unsatisfactory exclusion two of which were due to technical error. This has permitted high-dose (5,500-6,500 cGy) radiotherapy to the critical treatment volume without posttreatment complication. Mean follow-up time is 14.8 months. Several patients have been reexplored demonstrating complete absorption of the mesh without fibrinous adhesions or other foreign body reaction. It is concluded that this new technique of small bowel exclusion will permit the routine delivery of much higher doses of radiation in patients requiring improved local-regional control of their pelvic cancers and without morbidity from radiation-associated small bowel injury.

Efficacy of polyglycolic acid mesh sling in keeping the small bowel in the upper abdomen after abdominal surgery: a 12-month study in baboons.

The purpose of this study was to determine if a "sling" made of polyglycolic acid (PGA) would be a reliable method of preventing small bowel descent into the pelvis following abdominal surgery. Baboons were used, as they respond to infection and ambulate similarly to humans. Animals had the small bowel mobilized to the upper abdomen and had the PGA "sling" sewn into place. Documentation of small bowel position was evaluated by upper gastrointestinal series over the 12-month study. Small bowel descent into the pelvis was prevented by utilization of the PGA "sling." Animals were sacrificed and autopsied, and sections of small bowel were taken. There was no evidence of mesh, obstruction, sepsis, fistulae, or herniation in animals at autopsy. Small bowel sections were considered normal histologically. Utilization of PGA sling appears to be a safe and reliable method of preventing small bowel descent into the pelvis after abdominal surgery.

New surgical approach to minimize radiation-associated small bowel injury in patients with pelvic malignancies requiring surgery and high-dose irradiation. A preliminary report.

Complications associated with small bowel intolerance to radiation therapy at doses higher than 4500 to 5000 cGy have been the limiting factor in delivering pelvic radiation either as an adjuvant to surgery or alone in the treatment of pelvic malignancies. Despite numerous surgical, medical, and radiation therapy technical measures to minimize small bowel injury, none have been uniformly successful in eliminating this problem. With the availability of a new synthetic absorbable mesh, a pelvic sling can be placed at the time of exploration or definitive surgery aimed at suspending the small bowel out of the pelvis. Preliminary work in animal models has shown the mesh sling to be well-tolerated and successful. Barium-contrast simulation studies of seven patients with pelvic malignancies requiring resectional surgery and postoperative radiation therapy in whom the mesh sling was placed at the time of surgery demonstrate total exclusion of the small bowel from the pelvic radiation treatment field. All patients have been followed for at least 4 months since mesh placement, and to date no complications have occurred. It is possible that this technique of bowel exclusion will permit the delivery of larger doses of radiation therapy in patients with pelvic malignancies aiming at more effective local and regional control of cancer without increased complications from radiation-associated small bowel injury.

Small bowel exclusion from the pelvis by a polyglycolic acid mesh sling.

Radiation enteritis is seen in patients receiving radiation therapy for various pelvic malignancies. Attempts to prevent this have included various surgical as well as nutritional approaches with little success. The use of a polyglycolic acid mesh sling sewn above the pelvic inlet has prevented small bowel descent into the true pelvis in rats and in humans. The technique has been successful in both with no attendant morbidity during an 11-month follow up. Several patients have received additional doses of radiation therapy that would not have been given if the small bowel were not removed from the area to be irradiated.