NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
March 4, 2008 • Volume 5 / Number 5 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

Cancer Risk Persists After Ending Hormone Therapy

The increased risk of breast cancer associated with combination hormone therapy (estrogen plus progestin) may not go away once the hormones are stopped. More than two years after discontinuing hormones, women who had used the treatment for 5 years still had a higher risk of breast cancer than women who never used the hormones, according to an update from the Women's Health Initiative (WHI).

The results, in the March 5 Journal of the American Medical Association, confirm the main finding of the WHI's estrogen-plus-progestin trial - that the health risks of this treatment for menopausal symptoms such as hot flashes outweigh the benefits. The trial was halted in 2002 largely because women using hormones had an increased risk of breast cancer and experienced no clear health benefits. (A WHI trial of estrogen-alone therapy did not show increased cancer risks.)

To update the findings, Dr. Gerardo Heiss of the University of North Carolina, Chapel Hill, and his colleagues tracked 95 percent of the original 16,608 trial participants for an additional 2.4 years. In the post-treatment period, women who had stopped taking hormones were 27 percent more likely to develop breast cancer than women who did not take hormones. However, this finding was not statistically significant (79 women in the post-treatment group developed breast cancer compared with 60 in the placebo group).

The risk of any type of cancer was 24 percent higher in women who had stopped taking hormones, and this was statistically significant (281 women in the post-treatment group developed cancer compared with 218 in the placebo group). The reasons for the additional cancers are not yet clear, but the researchers stress the importance of carefully monitoring women for any long-term effects of hormone use in the years ahead.

"When we started the WHI, the prevailing belief was that menopausal hormones were good for women and that we could prevent many major age-related diseases with them," said Dr. Marcia Stefanick of Stanford University, who chaired the WHI steering committee during the trial.

"But we learned during the trial that the risks of combined estrogen-and-progestin therapy, which included increases in breast cancer, heart attacks, stroke, and serious blood clots, clearly outweighed the benefits of fewer fractures and colorectal cancers," Dr. Stefanick continued. "And we now know that the risk of cancer, and in particular, breast cancer, continues years after stopping the hormones, whereas, none of the benefits persist."

The good news is that the cardiovascular risks for the most part disappear after stopping the combined hormone therapy. Still, many experts recommend that women avoid combined hormone therapy or minimize their exposure. Another WHI follow-up study recently showed that combined hormone therapy leads to abnormal mammograms and compromises the ability of mammograms and breast biopsies to detect cancers.

Together, the two reports highlight complementary downsides of this therapy. "Not only does the breast cancer risk not disappear once hormone therapy is stopped, but the sensitivity of mammograms to detect cancer is not as good and women may continue to have abnormal mammograms for at least a year," said Dr. Leslie Ford of NCI's Division of Cancer Prevention and the institute's WHI liaison.

Hormone Therapy Interferes with Breast Cancer Detection

Two tools used to detect breast cancer - mammograms and breast biopsies - are less effective in women who use combined hormone therapy (estrogen plus progestin) than in women who do not. And the diminished ability to find cancers may persist for at least a year after women have discontinued therapy, according to a follow-up study of participants in the Women's Health Initiative (WHI).

It has been known that breast cancer is often detected at a later stage in women who use hormones to treat menopausal symptoms than in other women. This study also shows that women who use combined hormone therapy have more mammograms with abnormalities and more breast biopsies than women who do not use hormones.

Dr. Rowan Chlebowski of Harbor-UCLA Medical Center and his colleagues followed nearly 16,000 women in the WHI estrogen-plus-progestin trial for an extra year after the study ended. During this year, women who had used hormones during the study continued to have more mammogram abnormalities than women who had not. This suggests that discontinuing hormone therapy for a short interval before mammography may not affect either mammogram findings or breast cancer diagnoses, the researchers note in the February 25 Archives of Internal Medicine.

Women considering even short-term combined hormone therapy should factor the adverse effects on breast cancer detection into their risk-benefit analyses, the researchers conclude. During the original WHI estrogen-plus-progestin trial, women used either hormones or placebo for 5.6 years. The study was cut short in 2002 after the increased health risks associated with combined hormone therapy became evident.

A second WHI follow-up study, released this week, reports that the increased risk of breast cancer in women using combined hormone therapy persists for up to 3 years after treatment ends.

Study Confirms Clot, Mortality Risks with Anemia Drugs

A meta-analysis of clinical trials testing anti-anemia drugs in cancer patients has confirmed findings from earlier studies demonstrating increased risk of blood clots and death.

The findings, published in the February 27 Journal of the American Medical Association, come less than a month before the Food and Drug Administration's (FDA) Oncologic Drugs Advisory Committee (ODAC) will meet for the third time in 4 years to discuss the safety of the drugs, known as erythropoiesis-stimulating agents (ESAs).

Overall, the analysis found a 57 percent increased risk of venous thromboembolism (VTE) and a 10 percent increased mortality risk in patients treated with ESAs. The review included 51 phase III trials with survival information and 38 trials with data on VTEs.

"Our findings, in conjunction with basic science studies, raise the concern that the drug may be stimulating cancer and shortening cancer patients' survival," said the study's lead author, Dr. Charles L. Bennett from Northwestern University Feinberg School of Medicine.

The review - which involved trials with patients with anemia caused by cancer, as well as chemotherapy- or radiotherapy-related anemia - included data from eight recent phase III trials in patients with a variety of cancer types. With one exception, the recent trials were all designed to achieve hemoglobin levels in the 13 to 15 g/dl range, what have been referred to as "beyond anemia correction" studies.

The FDA, which issued two public health advisories on ESA use in 2007, is engaged in an ongoing safety review of the drugs.

Sentinel Node Dissection Safe in Early Vulvar Cancer Treatment

An international group of researchers led by the University Medical Center Groningen in the Netherlands has shown that sentinel lymph node dissection (SLND) to detect microscopic metastases in women with early-stage cancer of the vulva is safe compared with the standard treatment of inguinofemoral lymphadenectomy, which involves removing extensive lymph nodes in the groin and upper leg and can have long-lasting side effects.

The investigators enrolled 403 women into their study, all of whom underwent resection of their primary tumor and SLND. Of these, 127 had metastatic cells in the examined nodes, and underwent full inguinofemoral lymphadenectomy. The other 276 women did not have evidence of metastases on SLND, and did not undergo additional surgery.

All women returned for follow-up visits at least every 2 months for the first 2 years after surgery. Only four women were lost to follow-up; for the rest, the investigators compared short- and long-term complications and incidences of groin recurrences of the cancer between those who did and did not undergo inguinofemoral lymphadenectomy.

Women who only underwent SLND had significantly fewer short- and long-term complications - including difficulty with wound healing, lymphedema, and persistent infections - than women who underwent inguinofemoral lymphadenectomy. The overall rate of groin recurrence in women who only underwent SLND was 3 percent, which the authors deemed comparable to a calculated historical rate of 2 percent.

"The low groin recurrence rate...and excellent disease-specific survival rate of 97 percent at 3 years in sentinel node-negative patients suggest that the sentinel node procedure is a safe alternative to inguinofemoral lymphadenectomy for selected vulvar cancer patients," concluded the authors. However, they stress, extensive clinical experience with SLND for both the surgeon and the multidisciplinary team supporting the procedure is essential for replicating these positive results.

Smoking Threatens Pregnant Women in Developing Countries

A survey of nearly 8,000 pregnant women from 9 developing nations in Latin America, Asia, and Africa indicates that "rising tobacco use in the developing world threatens to impede or reverse hard-won global health gains." The multicenter, cross-sectional survey examined pregnant women's tobacco use, secondhand smoke (SHS) exposure, and attitudes toward women's tobacco use. Results were published online February 28 in the American Journal of Public Health.

The authors conclude that cigarette smoking during pregnancy is a current or emerging problem in the five Latin American countries surveyed. In Uruguay, 78.3 percent of pregnant women surveyed had ever tried cigarettes and two-thirds of those went on to become regular smokers, a third of whom continued to smoke while pregnant. Argentina - and to a lesser extent Ecuador, Brazil, and Guatemala­ - had similar patterns. If women's smoking were to become more culturally acceptable, say the authors, these other sites could expect much higher levels of smoking by pregnant women.

Pakistan had the most homes where smoking was allowed: 92 percent of those surveyed. Consequently, half of Pakistani pregnant women and half of their young children are frequently or always exposed to SHS. The use of other tobacco products, like smokeless tobacco and snuff, was highest in Orissa, India (34 percent).

The study was conducted by an international team of investigators, including researchers from two NIH institutes - NCI and the National Institute of Child Health and Human Development (NICHD). The researchers conducted the study at nine sites in the Global Network for Women's and Children's Health Research, operated by NICHD, with funding from the Bill and Melinda Gates Foundation. The Department of Health and Human Services' Office on Women's Health also provided study support.

The findings "highlight the urgent need to implement evidence-based interventions to prevent and control tobacco use among pregnant women" in these countries, writes lead author Dr. Michele Bloch of NCI's Tobacco Control Research Branch and colleagues.