Women with different types of noncancerous breast lesions have differing risks of developing subsequent breast cancer, according to a study in the July 21 New England Journal of Medicine.
The research team, led by Dr. Lynn Hartman of the Mayo Clinic School of Medicine, looked at medical records of 9,087 women diagnosed with benign breast disease, and then noted the incidence of breast cancer for a median of 15 years after the initial diagnosis.
Among the study population, 707 women developed breast cancer, which revealed a relative risk of 1.56 for any type of positive biopsy; 67 percent had nonproliferative lesions, which showed a relative risk of 1.27 for subsequent breast cancer; 30 percent had proliferative changes but no abnormalities in the ducts or lobes, which carried a relative risk of 1.88; and 4 percent had atypical hyperplasia, which represented a relative risk of 4.24. Among the general population over 15 years, 5 in 100 women developed breast cancer; among women with nonproliferative disease, the cases of breast cancer increased to 6 in 100.
Such risk ratios are important, say the study authors, because greater use of mammography to screen women for breast disease is increasing the number of biopsies performed and the discovery of more benign disease. An accompanying editorial notes that the study results "help stratify women with a benign lesion into high-risk and low-risk groups for breast cancer." The editorial also stressed the need for effective communication by physicians when explaining risk factors to their patients.
The long-term risk of testicular cancer patients developing a second cancer in the opposite (contralateral) testicle is very low, according to a study in the July 20 Journal of the National Cancer Institute (JNCI).
Based on data from 29,515 U.S. men with testicular cancer - as reported in NCI's Surveillance, Epidemiology, and End Results database from 1973 through 2001 - 287 patients developed subsequent (metachronous) cancer in the contralateral testicle. Led by Dr. Sophie D. Fossa of the Norwegian Radium Hospital in Oslo, the investigators concluded that there is a 15-year cumulative risk of 1.9 percent for developing disease in the other testicle, with a 10-year overall survival rate of 93 percent after diagnosis of metachronous contralateral cancer.
"The need to perform a routine biopsy of the contralateral testis in patients with newly diagnosed unilateral testicular cancer is a matter of ongoing discussion," the researchers observe. They also note that the study results demonstrate "the low cumulative risk of metachronous contralateral testicular cancer and favorable overall survival of patients diagnosed with metachronous contralateral testicular cancer is in accordance with the current U.S. approach of not performing a biopsy on the contralateral testis."
However, the researchers caution, "A biopsy may be justified for high-risk patients, especially those with a history of testicular maldescent, infertility, testicular atrophy, or a family history of testicular cancer."
The very mechanism by which anti-angiogenesis agents work to attack tumors - disrupting the vasculature and blood supply that provides the nutrients for the tumors' existence and growth - may fuel resistance to the agents in cells that survive their initial onslaught.
The findings, from an NCI-funded study published in the July 1 Cancer Research, indicate that by cutting off the blood supply, the drugs actually induce a super-state of oxygen and glucose deprivation that spurs the production of a prosurvival protein, GRP78. For tumor cells that aren't destroyed early in treatment, says study lead author Dr. Amy Lee, of the USC Keck School of Medicine, the proteins provide protection against subsequent treatments.
"Most researchers in the past concentrated on genetic mutations" as the root of tumor cell drug resistance, Dr. Lee says. "But in this study we're talking about…the tumor cells protecting themselves in the microenvironment." A study, published in 2003 and led by Dr. Lee, looked at how GRP78 blocks cell death and found increased GRP78 production in cancer cells that had become resistant to the chemotherapy drug etoposide.
For the recent study, the researchers tested two investigational agents in a mouse model of breast cancer: combrestatin A4P, which targets tumor vasculature; and contortrostatin, an anti-angiogenesis agent. In tumor cells that survived the initial treatment, increases in GRP78 levels were seen. They also found that GRP78 was overproduced in human cell lines from etoposide-resistant breast cancer. However, the tumor microenvironment must be critical to GRP78's production, the authors concluded, because in tissue culture, treating the human breast cancer cells used to create the xenograft mouse model failed to increase GRP78 levels.
Elderly Americans are consistently underrepresented in cancer clinical trials, making it difficult to know whether study results are relevant for the broader population. But there is another source of data on the use of cancer chemotherapy in the elderly: Medicare reimbursement records. To test whether these data are reliable for retrospective studies, researchers compared the records from two gold-standard clinical trials, in which the mean age of participants was 71, with those kept by Medicare for the same patients. The study results are published in the July 20 JNCI.
The research team used data from two Cancer and Leukemia Group B (CALGB) clinical trials, one for breast cancer patients and another for lung cancer patients. They linked these data with contemporaneous Medicare reimbursement records and looked for J9XXX codes, which track specific intravenous agents. After analyzing records from 175 patients, the team found that 89 percent of chemotherapy treatments recorded in the CALGB records were also tracked in Medicare records and that the specific chemotherapy regimens tracked were equal between the two data sets.
"Broadly, these results support the validity of the growing body of published observational research that uses Medicare chemotherapy claims from within the National Cancer Institute's SEER-Medicare data to describe chemotherapy use and outcomes among elderly Medicare beneficiaries," the authors concluded.