Clinical Abstracts From Overseas

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United Kingdom

How Do Vegetables Fight Prostate Cancer?

It has long been suspected that eating plenty of fruits and vegetables had a protective effect against cancer, but it was not understood why this relationship existed. Recently, British researchers reported a seemingly important mechanism in this process.

It is known that cruciferous vegetables contain isothiocyanate, which has been suspected to play a role. Broccoli has high concentrations of sulforaphane, a potent inducer of phase 2 enzyme gene transcription, which can also cause cell-cycle arrest and apoptosis. Investigators hypothesized that this could translate into anticarcinogenic activity.

The study group comprised 21 men (age range, 57—70 yr) who had high-grade prostatic intraepithelial neoplasia, which has a high risk of developing into adenocarcinoma. Over the course of 12 months, 13 were given 400 g of steamed broccoli each week, and eight were given given 400 g of steamed peas per week, in addition to their normal diet. Prostate samples were obtained by biopsy at baseline, at six, and after 12 months. To monitor whether participants ate their veggies, all subjects were asked to complete weekly sheets, documenting on which days they ate their assigned food and in what quantity.

The researchers found that a comparison of biopsies obtained at baseline and after the dietary intervention revealed more changes in gene expression occurred in individuals on a broccoli-rich diet than in those on a pea-rich diet. Although they reported changes in androgen signaling in both groups of men, men eating the broccoli-rich diet had additional changes to mRNA processing, and TGFβ1, EGF and insulin signaling. For instance, they could not detect differences in gene expression between participants receiving the pea-rich diet who were positive for glutathione S-transferase mu 1 (GSTM1) and those who tested negative for activity of this gene. However, for those receiving the broccoli-rich diet, gene expression was significantly different for those with GSTM1-positive and -negative genotypes. This gene expression is associated with transforming growth factor beta 1 (TGFβ1) and epidermal growth factor (EGF) signalling pathways.

They did not report on the number of participants whose high-grade neoplasia had evolved to adenocarcinoma in each group, but the study group size would not likely result in valid measures of statistical significance.

The investigators concluded that a broccoli-rich diet activated certain cancer-fighting genes, and deactivated others that help cancers develop, which may explain the association between high broccoli intake and low prostate cancer incidence.

Traka M, Gasper AV, Melchini A, et al: Broccoli consumption interacts with GSTM1 to perturb oncogenic signalling pathways in the prostate.

2008;3(7): e2568.

PLoS ONE

Canada

More Implications of BRCA2: Note for Women Only

An interesting oncological twist was reemphasized recently by Canadian researchers, who found that the mutated BRCA2 gene, the expression of which portends higher breast cancer risk, also may point to significantly worse prostate cancer outcomes in men.

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Investigators from the University of Toronto studied 301 men with prostate cancer and compared the survival of those with a BRCA2 mutation with those who had a BRCA1 mutation. Men with the BRCA2 mutation lived roughly half as long as those with the BRCA1 mutation (median survival, 4.0 vs. 8.0 yr, respectively; < .01). Previously, the existence of the BRCA2 mutation had been linked to a multifold higher likelihood for developing prostate cancer compared with men without the mutation. Now, it seems that its presence has implications for prostate cancer survival as well.

Narod SA, Neuhausen S, Vichodez G, et al: Rapid progression of prostate cancer in men with a BRCA2 mutation.

2008;99:371-374.

Br J Cancer

Multiple Centers in Europe

Endometrial Cancer Risk and Endogenous Sex Hormone Levels in Postmenopausal Women

It is well known that exogenous sex hormone intake can affect the risk of several cancers in women; however, relatively little is known about the risk associated with high endogenous sex hormone levels. Investigators from multiple centers in Europe utilized the European Prospective Investigation into Cancer and Nutrition (EPIC) study to address this question.

In the EPIC trial, 500,000 women across Europe completed extensive questionnaires in the 1990s and provided blood samples. Patients’ menopausal status was assessed at the time they gave blood. For this study, 247 patients with endometrial cancer were matched to 481 random healthy women based on multiple factors.

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Fifty-five women with endometrial cancer had not reached menopause at the time of the blood sampling, and 192 had. The median time between recruitment into the study and cancer incidence was approximately three years. One of the principal differences among case patients and matched controls was a higher body mass index in the former group (27.4 vs. 26.0 kg/m2, respectively, = .0001).

The researchers also found that significantly higher endogenous free testosterone, circulating estrone, free estradiol, and total estradiol levels were related to increased endometrial cancer risk in postmenopausal women. In comparison, none of the sex hormone concentrations seemed to be related to endometrial cancer risk in premenopausal women. In postmenopausal women, the level of sex-hormone binding globulin was observed to be inversely proportional to risk for this cancer.

Although they believe that the number of premenopausal women with endometrial cancer may have been too small to draw conclusions based on these data, the researchers believe that relatively high blood concentrations of estrogens and free testosterone, in particular, were related to increased risk for endometrial cancer.

Allen NE, Key TJ, Dossus L, et al: Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC).

2008;15:485-497.

Endocr Relat Cancer

Sweden

Family History of Breast Cancer: When Is the Risk Greatest?

A woman’s sister had breast cancer at age 45. Even though your patient is now 60 years old, does this mean she is no longer at significantly higher risk? A study from Stockholm, Sweden, delved into the question of how risk is spread over time in cases of patients with a family history of breast cancer.

Using a population database from Sweden, scientists studied 24,000 sisters of women who developed breast cancer between 1958 and 2001 and compared their risk with nearly 1.7 million sisters of women without breast cancer.

They found that women with a sibling family history of breast cancer were at higher risk than the general population at all adult ages. However, the risk for breast cancer was greatest in unaffected women between the ages of 20 and 39 years (incidence rate ratio, 6.6), and this risk was reduced to nearly twice the risk after age 50.

However, the researchers found that the age at which the sister developed breast cancer did not materially affect the sibling’s risk as she aged; that is, the risk was the same whether the unaffected sibling approached or passed the age at which her sister developed breast cancer.

Therefore, women with a sibling who had breast cancer are at higher risk for developing the disease their entire adult life, but the risk does diminish somewhat as they age.

Rebora P, Czene K, Reilly M: Timing of familial breast cancer in sisters.

2008;100:721-727.

J Natl Cancer Inst

Italy, Germany, Australia, UK

Radiofrequency Ablation Is an Alternative in Lung Cancer

For large tumors, percutaneous radiofrequency ablation has proven to be an effective option in patients with hepatic cancer who were not candidates for other alternative treatments. An international research team of clinicians decided to test this modality in patients with lung tumors for whom other active interventions were not recommended.

In this single-arm study, 106 patients were identified with lung tumors that were no larger than 3.5 cm (mean, 1.7 cm). These patients had 183 lung tumors; 33 patients had non—small cell lung cancer, and 53 patients had lung metastases from primary colorectal tumors. Patients were recruited for this study only if they were deemed ineligible for surgical excision, conventional radiotherapy, or chemotherapy. Radiofrequency ablation was performed using computed tomography guidance. Patients’ progress was followed for a maximum of two years.

The researchers noted that the ablation catheter was correctly placed in all but 1 patient (small tumor size was deemed to be the reason for failure). The procedure was associated with no effects that significantly reduced pulmonary function, although pneumothorax was common (26%) and pleural effusion did occur (4%).

In 85 patients evaluable after one year, 75 (88%) registered a complete response in the targeted tumor. In patients with non—small cell lung cancer, overall 1-year and 2-year survival was 70% and 48%, respectively. Cancerspecific survival was 92% after one year and 73% after two years in these patients. In those with colorectal metastases, survival at one and two years was 89% and 66%, respectively.

Based on the safety and efficacy of this treatment, the investigators believe that controlled trials should be performed against other nonsurgical treatment options in patients with lung cancer.

Lencioni R, Crocetti L, Cioni R, et al: Response to radiofrequency ablation of pulmonary tumors: A prospective, intention-to-treat, multicentre clinical trial (the RAPTURE study).

2008;9:621-628.

Lancet Oncol

Canada

Less Obesity Through Gastric Bypass Equals Less Cancer?

It has been well documented that high rates of obesity are associated with a number of health issues, including relatively high frequencies of diabetes, heart disease, and cancer. For patients who are morbidly obese, bariatric surgery offers an effective option for losing weight. Investigators from McGill University, Montreal, Canada, sought to determine whether patients who lose weight rapidly through the use gastric bypass surgery also decrease their risk of cancer over relatively short periods.

The researchers evaluated 1,035 patients who underwent bariatric surgery (81% underwent gastric bypass, 19% other procedures involving banding to restrict stomach capacity) between 1986 and 2002. They compared five-year outcomes with 5,746 matched individuals who were also obese but did not undergo the procedure.

Patients undergoing bariatric surgery lost an average two-thirds of their baseline body weight. Over the five-year follow-up, 21 patients (2%) undergoing bariatric surgery developed cancer compared with 487 (8%) of those in the matched control group. The researchers revealed that breast cancer and colorectal cancer incidence were most affected (Figure).

Although this study confirms that cancer risk can be lowered with weight loss, and over fairly short periods, it does not indicate how bariatric surgery results in lowered cancer incidence. The authors of this trial recommend that future investigations should focus on the mechanisms of this effect.

Christou N: Bariatric surgery improves/prevents cancer in morbidly obese patients. Presented at the 25th annual meeting of the American Society for Metabolic and Bariatric Surgery, Washington, DC, June 15—20, 2008.