Changes in Hormone-Pathway Genes Associate with Breast Cancer Risk
Single-nucleotide polymorphisms (SNPs) in genes for estrogen and progesterone receptors may be a factor that determines whether women are protected from breast cancer or are at risk for getting it, collaborative research teams from NCI's Center for Cancer Research (CCR), Memorial Sloan-Kettering Cancer Center, and Celera Diagnostics report in the December 15 Cancer Research.
Scientists collected DNA samples from 1,006 breast cancer patients, comparing them with DNA samples from 613 control subjects. They then examined SNPs in two estrogen receptor genes (ESR1 and ESR2) and looked at SNPs in a progesterone receptor gene (PGR). They found two SNPs in ESR1 that are linked to increased breast cancer risk - one in women over age 50 (though only rarely in African Americans) and the other exclusively in Ashkenazi women over the age of 50; three SNPs in ESR1 that conferred protective effects against breast cancer; a group of ESR2 SNPs that increased risk for breast cancer in Ashkenazi women; and neither protective nor risk-associated links to SNPs in PGR. Noting that only half of the familial breast cancer cases have been linked to specific genes, the results suggest that "Individual differences in hormonal regulation may result from haplotypes that confer an increased risk or protection from risk of breast cancer in a subset of the population."
Post-Op Chemo, Age, and Menopause Status
The National Surgical Adjuvant Breast and Bowel Project (NSABP), an NCI-sponsored clinical trial cooperative group, enrolled women with axillary lymph node-negative, estrogen receptor-negative breast cancer between 1981 and 1988. In 2003, NSABP reported that the addition of cyclophosphamide to methotrexate and 5-fluorouracil (CMF) improved outcomes after surgery and that doxorubicin with cyclophosphamide (AC) was equally as effective as the CMF regimen. In the December 15 Journal of the National Cancer Institute, researchers present new data that clarify the implications of these findings for women according to their age and menopause status.
The recent data show that women aged 49 or younger experienced a 65 percent reduction in treatment failure when given post-surgical CMF or AC chemotherapy, while women aged 50 to 59 experienced a 54 percent reduction in treatment failure with the chemotherapy. Women aged 60 or over, however, experienced an even lesser benefit; overall the younger the woman was upon entering the study, the greater the difference in recurrence rate with the treatment, compared with women who had surgery alone. Premenopausal women experienced a greater recurrence-free survival benefit than post-menopausal women (28 percent versus 48 percent) with the post-operative chemotherapy.
They conclude that outcomes in CMF- or AC-treated women with estrogen receptor-negative tumors and negative axillary lymph nodes were similar in all age groups. The decreased benefit from chemotherapy with increasing age resulted from a better outcome associated with advancing age in women who underwent surgery alone rather than a poorer outcome resulting from the use of chemotherapy.
Lung Screening Study Shows What Happens after Positive CT Scan
Research has shown that low-dose spiral computed tomography (CT) is more sensitive than chest X-ray at detecting abnormal lung tissue. CT is so sensitive that it poses a risk for false positives in lung cancer screening. Furthermore, there are no standard recommendations for follow-up after positive CT. Researchers from NCI's Division of Cancer Prevention surveyed the outcomes after a group of 1,660 current or former heavy smokers who had quit within the last 10 years were randomized to receive the procedure and were referred to their personal health care providers for next steps. These individuals were participants in the Lung Screening Study, a pilot for the National Lung Screening Trial. The results of the follow-up of the positive results appear in the January 1 Cancer.
Of the 522 patients with a positive CT scan at baseline or 1 year after baseline, researchers found that the most common follow-up procedure was a second CT scan without biopsy (55 percent) followed by follow-up biopsy or comparison of current CT results with those from a prior X-ray or CT (12 percent). Four percent of patients underwent only a clinical examination and 3 percent received no follow-up. Of those who were not diagnosed with lung carcinoma, 45 percent were diagnosed with another condition as part of the follow-up. "These data may be useful in estimating the potential burden and cost of CT screening," the authors noted.
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