MRI Detects Breast Tumors in High-Risk Women

Adding magnetic resonance imaging (MRI) scans to annual mammography screenings dramatically increases breast cancer detection in women at high risk for the disease, researchers from the Institute of Cancer Research in the United Kingdom reported on May 16 in an early online release from The Lancet.

Contrast-enhanced MRI scans were nearly twice as effective - finding 77 percent of tumors - as x-ray mammograms - which found only 40 percent - in women aged 35 to 49 with a strong family history of breast cancer. When researchers gave both tests concurrently, they found 94 percent of the tumors.

Less than 1 percent of women carry mutations in either the BRCA1 or BRCA2 genes, which confer a 60 to 85 percent lifetime risk of developing breast cancer. Cancer tends to appear at younger-than-usual ages, and sometimes displays features associated with poor prognosis. Annual screening beginning at a young age is the choice for many women having one of the gene mutations or a first-degree relative with the disease. However, mammograms do not identify about half of the breast tumors in younger women, whose denser breast tissue inhibits x-ray penetration.

The researchers, led by lead author Dr. Martin O. Leach, recruited 649 healthy women aged 35 to 49. Eighty-two (13 percent) had a known BRCA1 mutation, and 38 (6 percent) had a BRCA2 mutation. The rest had family histories of breast cancer. Each woman received between two and seven annual screenings with both imaging methods conducted on the same day. The researchers diagnosed 35 cancers: 19 appeared on MRI alone, 6 appeared on mammography alone, and 8 appeared on both. The other two tumors were discovered between annual screenings via other means.

Study Links Obesity to Aggressive Prostate Cancer

Obesity may not only increase the risk of prostate cancer, it may also amplify the risk of aggressive prostate cancer, researchers reported last week at the American Urological Association (AUA) annual meeting in San Antonio, Texas.

The study, led by Dr. Stephen J. Freedland of Johns Hopkins University, included 787 men undergoing biopsy after an elevated prostate-specific antigen (PSA) test result or an abnormal physical exam between 1998 and 2002. The researchers looked at the association between body mass index (BMI) and prostate cancer, as well as between BMI and the Gleason score, an assessment of the likelihood of the cancer spreading based on the biopsied cells' histopathology.

A high BMI was associated with an increased risk of a prostate cancer diagnosis. Among those diagnosed, high BMI also was associated with a higher Gleason score. The findings echo those of a study conducted by some of the same investigators, published last year in the Journal of Clinical Oncology. In that study, obese prostate cancer patients who underwent radical prostatectomy were more likely to have aggressive tumors and recurrence of the cancer compared with normal-weight or overweight men.

The researchers noted that a potential association between obesity and prostate cancer is significant because there are some hurdles in diagnosing prostate cancer in obese men. According to Dr. Martha K. Terris, a urologist at the Veterans Affairs Medical Center in Augusta, Ga., and a senior author of the study presented at the AUA meeting, performing digital rectal exams is difficult in obese men. In addition, excess fat can produce estrogen-like compounds that lower the levels of PSA in the blood circulation which could, in turn, affect PSA test results.

One component of a recent NCI Program Project grant - The Biology of the Prostate Cancer Prevention Trial (PCPT) - intended primarily to identify molecular markers of prostate cancer risk, will involve nested case-control studies using patient data and biospecimens collected during the PCPT to examine the relationship between diet and diet-related factors, including obesity and prostate cancer prevalence and grade.

Broken Bones, Osteoporosis Protect Against Ovarian Cancer

A protein related to broken bones, osteoporosis, and Caesarian sections can help protect women against ovarian cancer, according to research published in the May issue of Cancer Epidemiology, Biomarkers & Prevention.

Each of these events releases into the bloodstream a protein called human mucin 1 (MUC1). The immune system attacks the protein with antibodies that later may protect against cancer, say scientists from Brigham and Women's Hospital in Boston.

Other events that generate MUC1 and reduce ovarian cancer risk include mastitis during breast feeding, use of intrauterine devices for birth control, and tubal ligation. All of these events produce high levels of anti-MUC1 antibodies.

In a study of 691 women, the researchers found that the risk of ovarian cancer decreases with each MUC1-generating event. Women experiencing two events had a 30-percent decrease in ovarian cancer risk; those experiencing five or more events experienced a 70-percent risk reduction.

Lead researcher Dr. Daniel Cramer noted in the article that some of these events previously had been known to reduce risk of ovarian cancer, but that the MUC1 theory unifies and explains the phenomenon. He speculated that the work could lead to vaccines against ovarian and other tumors that overproduce MUC1.

Colonoscopy May be Superior to Sigmoidoscopy in Many Women

Using only flexible sigmoidoscopy to screen women 50 years of age or older who are at average risk of colorectal cancer would miss nearly two-thirds of advanced polyps, according to a new study. The findings, the authors concluded, could indicate that colonoscopy should be the standard for colorectal cancer screening in this patient population.

Although the tests commonly used to screen average-risk women, flexible sigmoidoscopy and fecal occult blood tests (FOBT), "are less expensive, faster, and require no sedation," said study lead author Dr. Phillip Schoenfeld, of the University of Michigan Medical School, "65 percent of women with advanced precancerous polyps in our study would have lesions missed if these were the only screening tests performed because precancerous polyps are found deeper in the colon in women."

The study, dubbed CONCeRN and partially funded by NCI, was published in the May 19 New England Journal of Medicine. It included 1,463 asymptomatic women, aged 50 to 79, at average risk for colorectal cancer, who had a negative FOBT but had been referred for further screening at one of four military medical centers.

Participants underwent colonoscopy, during which the location of all identified polyps was carefully mapped. The colonoscopy findings were then compared against those from men in a nearly identical study published 5 years ago, the VA Cooperative Study 380.

Men in that study were nearly twice as likely to have advanced precancerous polyps as women in CONCeRN: 8.6 vs. 4.9 percent. However, based on the colonoscopy findings and the extent to which a flexible sigmoidoscope is capable of scanning the colon, the researchers determined that, had only flexible sigmoidoscopy been performed in those women, advanced precancerous lesions would have been identified in only 1.7 percent of them.

Blood Stem Cells Linked to ALL

On the road from blood stem cell to mature blood cell, at least three wrong turns dead-end in malignancy, according to new research published in the May 22 online advance edition of Nature Medicine.

Blood stem cells continuously generate the whole panoply of red and white blood cell types from their home in the bone marrow. Because they self-renew, blood stem cells survive longer than mature cells, and thus are more prone to accumulate the multiple mutations needed to spark leukemia. For this reason, cancer researchers have long thought that when leukemia appears, blood stem cells, rather than mature white cells, are the culprits.

Researchers in Sweden have verified this theory by identifying the blood stem cell origins of three subtypes of acute lymphoblastic leukemia (ALL). The subtype called TEL-AML1 (named after the genes that go haywire) grows from a type of blood stem cell called a committed progenitor B cell - about halfway down the road to maturity. Leukemias dubbed P210 BCR-ABL1 originate much earlier, at the beginning of the blood stem cell growth process in hematopoietic stem cells, whereas P190 BCR-ABL1 leukemias originate from progenitor B cells.

The authors suggest that each subtype leads to a distinct clinical disease, which should "eventually lead to a better understanding of the transformation process and the development of improved diagnostic and therapeutic strategies."