A link between relatively short-term use of estrogen and progestin has been associated with decreased risk for colorectal cancer in postmenopausal women by investigators with the Women's Health Initiative (WHI). Observational studies have long shown an association, but they involved postmenopausal women taking estrogen alone or compared women taking estrogen alone with those on combination therapy. In the 1990s, WHI enrolled more than 16,000 healthy, postmenopausal women and randomly assigned them to receive estrogen plus progestin or a placebo. The trial was stopped in 2002 because the general health risks associated with combination hormone therapy outweighed the benefits. Yet investigators again observed an association between the combination therapy and a decreased risk for colorectal cancer.
In the latest study, published in the March 4 New England Journal of Medicine, WHI investigators have further compared the incidence, stages, and types of colorectal cancers between the hormone group and the placebo group. Fewer invasive colorectal cancer cases were diagnosed for the hormone group, 43 compared with 72. Even after data were adjusted for history of colorectal cancer and number of first-degree relatives with colorectal cancer, the number of cases observed in the hormone group was lower than that for the placebo group. However, investigators also noted that the cancers diagnosed for women in the hormone group were more advanced and showed more lymph node involvement than those diagnosed in the placebo group. The reason for this is unclear, but the study's findings support a wider implementation of bowel screening among postmenopausal women taking hormone therapy, the study author's wrote.
The National Institutes of Health (NIH) last week announced that it was halting the estrogen-alone study of the WHI after reviewing the data and concluding that, on its own, estrogen doesn't appear to increase or decrease the risk of heart disease - a primary end point of the study.
Participants in the estrogen-alone study had an increased risk of stroke. All 11,000 participants were postmenopausal women who had had a hysterectomy. "The NIH has determined that the [estrogen-alone study] results would not likely change if the estrogen trial continued to its planned completion in 2005," said WHI Director Dr. Barbara Alving in an NIH press release. "Furthermore, enough data have been obtained to assess the overall risks and benefits of the use of estrogen in this trial."
The review also showed that estrogen did not increase participants' risk of breast cancer during the study period, in contrast to findings from a separate WHI study of estrogen-progestin combination therapy that was stopped two years ago. In that study, which involved postmenopausal women who had not had a hysterectomy, participants on hormone replacement therapy were at increased risk for breast cancer, coronary heart disease, stroke, and blood clots but at decreased risk for colorectal cancer (see related story) and hip fractures. A detailed analysis of the estrogen-alone study data is under way, with complete results expected to be published in two months.
Women who have finished breast cancer treatment and are transitioning to survivorship often feel emotionally and mentally stable but still experience a broad range of physical symptoms, according to a study published in the March 3 Journal of the National Cancer Institute.
The study, which involved 558 women who had just finished primary breast cancer treatment, found that regardless of what treatment patients received - mastectomy or lumpectomy, with or without chemotherapy - they reported good emotional functioning during this early recovery period. However, many patients reported physical problems such as muscle stiffness, aches and pains, and difficulty concentrating, especially those who underwent mastectomy or chemotherapy. Sexual functioning was worse for women who had had chemotherapy, no matter the type of surgery.
"Having a better understanding of how patients navigate this transitional period is increasingly important [given the current longer adjuvant treatment period and short-term toxicity]," the researchers wrote. "It is clear that more attention must be paid to the symptoms that women report at the end of treatment because they are associated with poorer physical and emotional well-being."
Though a large fraction of human cancers commonly contain an abnormal number of chromosomes, scientists have not been able to identify a genetic basis for this phenomenon, called aneuploidy. A study published by Harith Rajagopalan and colleagues in the March 4 issue of Nature is the first to show that a specific mutation, in the hCDC4 gene, can cause aneuploidy in human colorectal cancer cells. hCDC4, also known as Fbw7 and Archipelago, is believed to play a role in cell cycle regulation and had been previously proposed to play a role in genetic instability. The investigators showed that hCDC4 was mutated in over 10 percent of the colorectal cancer tumors studied. They also discovered mutations in precancerous adenomas, which suggests that these mutations can occur prior to a cancer cell's conversion to malignancy.
"Aneuploidy…has been recognized as a hallmark of human cancer for nearly a century; however, the mechanisms responsible for this abnormality have remained elusive," the researchers note. "Our results suggest that mutational inactivation of hCDC4 is likely to be a chief cause of chromosomal instability in cancers and that this mutation can occur at an early stage."