Background:In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90%. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes. Methods: We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models. Results: We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of followup (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculations

Background An optimal staging system to estimate the risk of recurrence following the complete resection of localized, primary gastrointestinal stromal tumor (GIST) has not been established. Recently, it has been shown that adjuvant imatinib mesylate prolongs recurrence-free survival (RFS) following the resection of localized, primary GIST. We sought to develop a nomogram to predict RFS after surgery in the absence of adjuvant therapy to help guide patient selection for adjuvant imatinib therapy. Methods A nomogram to predict RFS based on tumor size (in cm), location (stomach, small intestine, colon/rectum, or other), and mitotic index (<5 or ≥5 mitoses per 50 high power fields) was developed from 127 patients treated at Memorial Sloan-Kettering Cancer Center. The nomogram was tested in cohorts of patients from the Spanish national registry (GEIS; n=212) and the Mayo Clinic (Mayo; n=148). The nomogram was evaluated by calculating concordance probabilities as well as testing calibration of predicted RFS with observed RFS. Concordance probabilities were also compared with those of 3 commonly employed staging systems. Findings The nomogram had a concordance probability of 0.78 (±0.02) in the MSKCC dataset and 0.76 (±0.03) and 0.80 (±0.02) in the validation cohorts. The nomogram predictions were well calibrated. Remodeling the nomogram to include tyrosine kinase mutation status did not improve its discriminatory ability. Concordance probabilities of the nomogram were superior to those of the 2 NIH staging systems (0.76 (±0.03) versus 0.70 (±0.04) (p=0.04) and 0.66 (±0.04) (p=0.01) in the GEIS validation cohort; 0.80 (±0.02) versus 0.74 (±0.02) (p=0.04) and 0.78 (±0.02) (p=0.05) in the Mayo cohort) and equivalent to the AFIP-Miettinen staging system (0.76 (±0.03) versus 0.73 (±0.004) (p=0.28) in the GEIS cohort; 0.80 (±0.02) versus 0.76 (±0.003) (p=0.09) in the Mayo cohort). Nomogram predictions of RFS appeared better calibrated than predictions made using the AFIP-Miettinen system. Interpretation The nomogram accurately predicts RFS following the resection of localized, primary GIST and may be useful to select patients for adjuvant imatinib therapy.

Pancreatoduodenectomy for adenocarcinoma in the head of pancreas can provide long-term survival in a subset of patients, particularly in the absence of lymph node metastasis. One of 8 patients can achieve 10-year survival with a potential for cure.

Gastrointestinal metastasis occurred more often in patients with invasive lobular carcinoma. Surgical intervention did not significantly extend overall survival but may be considered in a select group of patients.

Although PMP is an indolent disease, aggressive surgical debulking followed by intraperitoneal radioisotopes and/or chemotherapy should be considered because of the diffuse peritoneal involvement.