[The presence of medications in the water cycle]. / Geneesmiddelen in de watercyclus.

Medications and radiographic contrast dyes are sometimes detected in surface waters, ground water and drinking water; these have proven detrimental effects on organisms living in such waters The concentration of medications found in drinking water is at least a thousand times below their minimum therapeutic dosages. In humans, the long-term effects of daily exposure to low dosages of medications and 'mixture toxicity' is not known; based on the concentrations and substance toxicity, it is presumed that the risk is nil.. Physicians can play their part in controlling the problem of medications becoming part of the water cycle by taking this into account when prescribing medications. Users can make a difference by handling their medications with care and by returning all unused portions to the pharmacy. The pharmaceutical industry can also do its part by taking degradability, options for removal and the environmental effects of medications into account during their stages of development.

Optimal age to start preventive measures in women with BRCA1/2 mutations or high familial breast cancer risk.

Women from high-risk families consider preventive measures for breast cancer including screening. Guidelines on screening differ considerably regarding starting age. We investigated whether age at diagnosis in affected relatives is predictive for age at diagnosis. We analyzed the age of breast cancer detection of 1,304 first- and second-degree relatives of 314 BRCA1, 164 BRCA2 and 244 high-risk participants of the Dutch MRI-SCreening study. The within- and between-family variance in the relative's age at diagnosis was analyzed with a random effect linear regression model. We compared the starting age of screening based on risk-group (25 years for BRCA1, 30 years for BRCA2 and 35 years for familial risk), on family history, and on the model, which combines both. The findings were validated in 63 families from the UK-MARIBS study. Mean age at diagnosis in the relatives varied between families; 95% range of mean family ages was 35-55 in BRCA1-, 41-57 in BRCA2- and 44-60 in high-risk families. In all, 14% of the variance in age at diagnosis, in BRCA1 even 23%, was explained by family history, 7% by risk group. Determining start of screening based on the model and on risk-group gave similar results in terms of cancers missed and years of screening. The approach based on familial history only, missed more cancers and required more screening years in both the Dutch and the United Kingdom data sets. Age at breast cancer diagnosis is partly dependent on family history which may assist planning starting age for preventive measures.

BRCA1-associated breast cancers present differently from BRCA2-associated and familial cases: long-term follow-up of the Dutch MRISC Screening Study.

PURPOSE: The Dutch MRI Screening Study on early detection of hereditary breast cancer started in 1999. We evaluated the long-term results including separate analyses of BRCA1 and BRCA2 mutation carriers and first results on survival. PATIENTS AND METHODS: Women with higher than 15% cumulative lifetime risk (CLTR) of breast cancer were screened with biannual clinical breast examination and annual mammography and magnetic resonance imaging (MRI). Participants were divided into subgroups: carriers of a gene mutation (50% to 85% CLTR) and two familial groups with high (30% to 50% CLTR) or moderate risk (15% to 30% CLTR). RESULTS: Our update contains 2,157 eligible women including 599 mutation carriers (median follow-up of 4.9 years from entry) with 97 primary breast cancers detected (median follow-up of 5.0 years from diagnosis). MRI sensitivity was superior to that of mammography for invasive cancer (77.4% v 35.5%; P<.00005), but not for ductal carcinoma in situ. Results in the BRCA1 group were worse compared to the BRCA2, the high-, and the moderate-risk groups, respectively, for mammography sensitivity (25.0% v 61.5%, 45.5%, 46.7%), tumor size at diagnosis≤1 cm (21.4% v 61.5%, 40.9%, 63.6%), proportion of DCIS (6.5% v 18.8%, 14.8%, 31.3%) and interval cancers (32.3% v 6.3%, 3.7%, 6.3%), and age at diagnosis younger than 30 years (9.7% v 0%). Cumulative distant metastasis-free and overall survival at 6 years in all 42 BRCA1/2 mutation carriers with invasive breast cancer were 83.9% (95% CI, 64.1% to 93.3%) and 92.7% (95% CI, 79.0% to 97.6%), respectively, and 100% in the familial groups (n=43). CONCLUSION: Screening results were somewhat worse in BRCA1 mutation carriers, but 6-year survival was high in all risk groups.

Prophylactic mastectomy in BRCA1 and BRCA2 mutation carriers: very low risk for subsequent breast cancer.

AIM: To examine the outcome of prophylactic mastectomy in a hospital-based series of BRCA1/2 gene mutation carriers with and without a history of breast cancer. PATIENTS AND METHODS: A center-based consecutive series of 254 BRCA1/2 gene mutation carriers that had prophylactic mastectomy after a normal surveillance round including breast-magnetic resonance imaging were identified. One hundred forty-seven asymptomatic carriers underwent bilateral mastectomy and 107 symptomatic women had contralateral mastectomy after a mean cancer free interval of 3.6 years. All removed breasts were histopathologically examined. RESULTS: In one asymptomatic BRCA2 carrier (0.7%) an occult small invasive breast cancer was diagnosed, while in 6 asymptomatic carriers (4.0% BRCA1 and 4.3% BRCA2) and in 5 symptomatic carriers (2.5% BRCA1 and 10.7% BRCA2) DCIS was detected at prophylactic mastectomy. No breast cancer occurred in the asymptomatic group after a postprophylactic follow-up period of 778 women-years. In the symptomatic carriers 1 invasive breast cancer was detected after 580 follow-up years. From age-, cohort-, and gene-specific reference data we calculated that 15 invasive first cancers in the asymptomatic carriers were prevented during follow-up. CONCLUSION: One invasive breast cancer in 147 bilateral prophylactic mastectomies (0.7%) was detected, this makes a sentinel node procedure redundant and preoperative imaging vital. The prophylactic procedure is highly effective in preventing invasive breast cancer in BRCA1/2 mutation carriers. Since the remaining risk is less than 0.2%/woman-year, continued surveillance of the asymptomatic carriers is not warranted.