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IN THIS ISSUE
Quality of Care Indicators for Colorectal Cancer SurgeryMeasures of quality of care are increasingly being developed for a variety of diseases, including cancer. These indicators can be used by regulatory agencies and accrediting organizations, as well as by individual hospitals and providers. McGory et al. (p. 1623) describe the development of quality indicators for colorectal cancer surgery. An initial set of 142 candidate indicators was identified through literature reviews and interviews with leaders in the field. An expert panel then evaluated these indicators through a formal rating process and identified 92 as valid. The indicators address all domains of surgical care—preoperative, intraoperative, and postoperative—for patients undergoing colorectal cancer surgery.
Breast Cancer Risk and Age-Related Lobular Involution
As women age, the breast's milk-producing glands, called lobules, undergo involution or regression. Milanese et al. (p. 1600) investigated whether lobular involution in women with benign breast disease (who have elevated risks of breast cancer) was associated with subsequent breast cancer risk. The authors examined lobular involution in benign breast biopsies from 8,736 women who were followed for breast cancer for a median of 17 years. They found that the risk of breast cancer was reduced as the degree of involution increased. Moreover, the greater the extent of lobular involution, the lower the breast cancer risk for all subsets of women analyzed, including those with atypia. The authors conclude that, in this large cohort of women with benign breast disease, lobular involution was associated with a reduced risk of breast cancer and that abnormal involution may be important in breast cancer biology.
In an editorial, Henson et al. (p. 1589) write that the association between lobular involution and the risk of breast cancer marks a new paradigm for breast cancer research and prevention. The next step should be to explore the natural history of involution and the process of normal breast aging. They conclude that involution may eventually become a useful surrogate endpoint for research in breast cancer prevention and that it may be useful for risk prediction.
Dietary Folate Intake, MTHFR, and Breast Cancer Risk
There is conflicting evidence from observational studies on the association between dietary folate intake and the risk of breast cancer. To investigate this relationship, Lewis et al. (p. 1607) conducted meta-analyses of this association and of the association between a common polymorphism (C677T) in the methylenetetrahydrofolate reductase (MTHFR) gene and breast cancer risk. The authors found no association between folate intake and breast cancer risk in a meta-analysis that included 13 case–control studies and nine cohort studies. They also observed no difference in breast cancer risk between MTHFR 677 TT homozygotes and CC homozygotes in a meta-analysis of 17 studies of MTHFR C677T genotype and breast cancer risk. They did, however, find evidence of publication and other biases. The authors conclude that low dietary folate intake is not associated with the risk of breast cancer.
In an editorial, Huang (p. 1590) discusses study design issues that must be considered before it can be concluded that folate does not protect against breast cancer. She notes that dietary data collected through questionnaires are more useful for exploring patterns of intake than for quantifying intake. She concludes that randomized controlled trials remain the study design of choice for making conclusions about the effects of a nutrient on cancer risk.
Specific Targeting of Tumor Vasculature with Endorepellin
Endorepellin is a protein fragment that is generated by the cleavage of its parent molecule, perlecan, which is a component of the scaffolding that supports developing blood vessels. Endorepellin was previously shown to be a potent inhibitor of angiogenesis using in vitro assays. Bix et al. (p. 1634) injected endorepellin into the peritoneum of tumor-bearing mice and found that it became localized in the perivascular zones of the tumors, where it persisted for several days. The administered endorepellin inhibited the formation of tumor blood vessels, leading to decreased metabolism that was accompanied by hypoxia and reduced cell division. The endorepellin was internalized by tumor-derived endothelial cells via a specific receptor, 
2
1 integrin, with both proteins then co-localizing to punctate deposits adjoining the vasculature. These results suggest that agents targeting the tumor vasculature should be explored as therapeutics to combat cancer.
BMI, Chemotherapy, and Colon Cancer Outcomes
Associations between obesity and cancer risk have been reported. To determine whether body mass index (BMI) is associated with the outcome of colon cancer patients treated with adjuvant chemotherapy, Dignam et al. (p. 1647) analyzed data from more than 4,200 colon cancer patients who participated in National Surgical Adjuvant Breast and Bowel Project randomized trials. After a median of 11.2 years of follow-up, the authors found direct associations between BMI at diagnosis and cancer recurrence and mortality. The authors conclude that having a BMI greater than 35.0 kg/m2 at diagnosis is associated with an increased risk for recurrence and death from colon cancer. Future studies are needed to identify the mechanisms and determine whether weight reduction would improve the outcomes.
Ovarian Cancer Survival and Chemotherapy Regimens
Numerous randomized trials have been used to compare chemotherapy regimens for women with ovarian cancer. Kyrgiou et al. (p. 1655) used multiple-treatments meta-analysis to combine information from indirect and direct comparisons of all chemotherapy regimens used in randomized ovarian cancer treatment trials in the last 40 years. Using data from 60 trials of more than 15,000 women and 120 regimens, the authors found that platinum and taxane combinations with intraperitoneal administration prolonged survival the most, with a greater than 55% reduction in risk of mortality compared with nonintraperitoneal monotherapy using neither platinum nor taxane. The authors conclude that a doubling or more of time to death is possible with platinum and taxane combinations, particularly if given through intraperitoneal administration.
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