CLEVELAND, June 26 — The nationwide drop in breast cancer rates linked to the decline of hormone replacement therapy tracks both income and locale, with more significant reductions observed in affluent, urban areas, a new study shows.

• Explain to interested patients that a number of recent studies have suggested a link between the declining use of hormone therapy and a decline in breast cancer incidence. This report supports that hypothesis.
• Explain to interested patients that current guidelines recommend hormone therapy only for relief of menopause symptoms such as hot flushes and night sweats. Evidence from randomized trials does not support the use of hormone therapy for prevention of heart disease.

From 2001 to 2004 the overall incidence of invasive breast cancer fell by 13.8% in urban areas, versus a 7.5% decline in rural areas, according to Amelia K. Hausauer, PhD, of the Northern California Cancer Center in Fremont, and colleagues.

Likewise, invasive breast cancer rates fell by 13% in neighborhoods in high-income counties, compared to a 9.6% decline in poor counties, although the intracounty changes from baseline were significant in each case (P<0.001), the group reported in the open access journal BMC Medicine.

“Breast cancer incidence trends for rural counties, which peaked in 1999 and then declined steadily, differed from those in observed in urban counties, where rates fell most dramatically after 2002,” they remarked.

This distinctly different pattern of decline is “consistent with the changing pattern of [hormone therapy] prevalence and cessation or noninitiation,” the authors concluded.

The use of hormone replacement increased steadily until 1999, when it peaked at 92 million prescriptions. It remained steady until the watershed moment of July 9, 2002.

On that day, the National Health Lung and Blood Institute announced that it had pulled the plug on a study investigating health claims for hormone replacement (estrogen-progestin) in 14,749 healthy women, when it discovered that the five-year incidence of breast cancer was significantly higher among women assigned to hormone therapy compared with those taking placebo.

Following that announcement, there was a significant decline in the use of hormone therapy, and in the past year a number of studies have reported a subsequent decline in breast cancer incidence.

Dr. Hausauer and colleagues analyzed data from 29 population-based cancer registries that participate in the North American Association of Central Cancer Registries.

According to the registry, there were 475,523 cases of invasive breast cancer and 111,885 cases of in situ breast cancer diagnosed between from 1997 through 2004.

The researchers limited their analysis to cases reported in non-Hispanic white women age 50 to 74, and stratified the findings by counties of residence at the time of diagnosis. The counties were further stratified by rural/urban status and by income.

Among the findings:

• Breast cancer was most likely be diagnosed in urban areas, with 85.7% of invasive breast cancers and 88% of in situ breast cancer diagnosed in cities versus suburban or rural communities.
• From 2001 to 2004 the breast cancer rate declined by 13.8% in urban areas (P<0.001 for change), 10.7% in the suburbs (P<0.001), and 7.5% in rural areas (P=0.02).

Although hormone therapy seems a likely explanation for the declines seen in this analysis, the authors cautioned that some of the change — especially the slow but steady decline observed in rural communities — could be explained by “saturation of or decreases in mammographic screening.”

The authors said their report was limited by the lack of individual socioeconomic information, and a lack of adjustment for possible delays in reporting. Moreover, the authors could not stratify the results by gene-expression subtype or by hormone receptor status.

Dr. Hausauer declared that she had no competing interests. The registries used in the study were supported by individual states with additional funding from the CDC, and, in some cases, the National Cancer Institute’s SEER Program.

Primary source: BMC Medicine

Source reference:

Hausauer AK, et al “Recent trends in breast cancer incidence in US white women by county-level urban/rural and poverty status” BMC Med 2009.

LITTLE FALLS, N.J., June 30 — The metabolic syndrome appears to be related to an increased risk for breast cancer in postmenopausal women, a longitudinal study showed.

• Explain to interested patients that this observational study could not establish a causal relationship between the metabolic syndrome and its components and increased breast cancer risk.

Although there was no relationship with baseline presence of metabolic syndrome, identification of the condition three to five years before a breast cancer diagnosis was associated with an elevated risk of total and invasive cancer, according to Geoffrey Kabat, PhD, of Albert Einstein College of Medicine in New York, and colleagues.

In time-dependent analyses, higher blood glucose levels, triglycerides, and diastolic blood pressure were individually linked to greater cancer risk, the researchers reported in the July issue of Cancer Epidemiology, Biomarkers & Prevention.

“The metabolic syndrome could influence the risk of breast cancer through changes in a number of interrelated hormonal pathways, including those involving insulin, estrogen, cytokines, and growth factors,” the researchers said.

The metabolic syndrome is defined as at least three of the following: abdominal obesity, high blood glucose, impaired glucose tolerance, dyslipidemia, and hypertension.

The condition has been associated with type 2 diabetes and coronary heart disease.

Previous studies that have looked at the contribution of the individual components to breast cancer risk have yielded mixed results, and no studies have explored the relationship with metabolic syndrome as a whole, according to the researchers.

So Dr. Kabat and colleagues used data on 4,888 postmenopausal women from the Women’s Health Initiative to explore the issue. All were free from diabetes at baseline.

Through a median follow-up of eight years, there were 165 incident cases of breast cancer — 131 invasive and 34 in situ.

Baseline presence of the metabolic syndrome was not associated with an increased risk for cancer.

Diastolic blood pressure was the only component at baseline to have a significant association with total breast cancer (HR 1.55, 95% CI 1.02 to 2.36).

However, in an analysis using repeated measurements over time, identification of the metabolic syndrome three to five years before a breast cancer diagnosis was associated with elevated risks of total (HR 1.84, 95% CI 1.12 to 3.01) and invasive (HR 1.77, 95% CI 1.01 to 3.12) breast cancer.

Among individual components, there were significant associations between elevated blood glucose and total breast cancer (P=0.04), triglycerides and total and invasive breast cancer (P=0.03 for both), and average diastolic blood pressure and total (P=0.002) and invasive (P=0.001) breast cancer.

The researchers said hyperinsulinemia may be the major mechanism underlying the relationships.

“Insulin has mitogenic activity in addition to metabolic effects and can promote cell proliferation in normal mammary epithelial cells and breast cancer cell lines,” they said.

“Insulin may also contribute to tumor promotion by up-regulating the secretion of ovarian hormones,” they continued.

“In theory,” they said, “high glucose levels could additionally increase the risk of postmenopausal breast cancer by conferring a selective growth advantage on malignant cells, as high rates of glucose uptake and glycolysis are a common feature of malignant growth.”

The researchers said some of the associations observed could have been due to chance given the number of comparisons performed and the limited number of breast cancer cases.

Thus, they said, “it would be premature to draw definitive conclusions about whether the associations with individual components or with the composite metabolic syndrome are more informative in our data [than in other studies] or how convincing a biological rationale exists for the observed associations with individual components.”

The authors also noted that the study was limited by the absence of data on circulating estrogen levels.

The authors did not disclose any potential conflicts of interest.

Primary source: Cancer Epidemiology, Biomarkers & Prevention

Source reference:

Kabat G, et al “A longitudinal study of the metabolic syndrome and risk of postmenopausal breast cancer” Cancer Epidemiol Biomarkers Prev 2009; 18: 2046-53.

A new technique for transplanting the ovaries of women who have lost their fertility as a result of cancer treatment was outlined to the 25th annual conference of the European Society of Human Reproduction and Embryology. Dr. Pascal Piver, manager of the IVF Centre at Limoges University Hospital, Limoges, France, described a new, two-step method of ovarian transplant that has produced excellent results in women whose ovaries have been frozen because of cancer treatment. He said that his team’s technique worked to restore ovarian function quickly and already one patient from his clinic had had a baby and another had become pregnant.

“On June 22, a baby girl was born to a mother who had been menopausal for two years as a result of treatment for sickle cell anaemia. After transplanting her own ovarian tissue she started ovulating in four months and became pregnant naturally six months after transplantation. Both mother and baby are doing well”, he said.

Dr. Piver and colleagues set out to tackle one of the biggest problems of ovarian transplantation: the low response to stimulation caused by insufficient vascularisation of the transplanted tissue.

“In order for a woman to become pregnant, the ovaries need to be responsive to the action of hormones that cause them to release eggs each month,” he explained. “If the blood supply to the ovaries is insufficient, this will not happen, even though the transplant may look as though it has been successful.”

To overcome this problem they carried out a two-stage procedure, first grafting small pieces of the frozen ovarian tissue in the ovarian and peritoneal areas three days before the real transplant. The first graft encourages the growth of blood vessels and paves the way for the ovary to become fully functioning in a shorter time scale than would be possible if all the tissue were to be transplanted at the same time.

The researchers have so far utilised this technique with two patients who had been treated for cancer and had their ovaries frozen. In addition to the first patient, treated for sickle cell anaemia, the second patient had been treated for periarteritis nodosa, an inflammation of medium-sized arteries, which become swollen and damaged from attack by rogue immune cells.

“She suffered menopause for eight and a half years before transplantation,” said Dr. Piver. “But after transplanting half of the frozen ovary, she recovered spontaneous ovulation in four months. Her right fallopian tube had been destroyed by the ovarian retrieval, and the function of the ovary and hence the chances of pregnancy are limited in time. Hence we decided to collect the highest number of eggs we could, and carry out an IVF procedure on this patient.

“Six months after the operation, we transferred two blastocysts. A total of 22 oocytes were retrieved and produced 16 embryos, which in turn produced seven blastocysts. Unfortunately the first time round this patient developed an ectopic pregnancy, but she is now pregnant again.”

The technique was developed by Dr. Piver and his team, he told the conference. “This is the first time that a pregnancy has been obtained after a ten year gap between ovarian cryopreservation and grafting. We believe that it represents a considerable advance on the methods of ovarian transplantation used until now, not least because we are able to obtain large numbers of oocytes. We hope that it will enable more young patients who have been cured of cancer to regain their reproductive health and become pregnant with their own children,” he said.

Source:
Mary Rice

European Society for Human Reproduction and Embryology