Combination Hormone Replacement Therapy Linked to Lower-Risk Breast Cancers

Reuters Health Information 2007. © 2007 Reuters Ltd.
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NEW YORK (Reuters Health) May 09 - The types of breast tumors that occur after combination hormone replacement therapy in the peri- and post-menopausal period tend to have a better prognosis than those that occur after estrogen-only replacement therapy, Swedish researchers report.

A team at Malmo University Hospital conducted a prospective cohort study involving 12,583 peri- or post-menopausal women whose medical records were linked to national cancer registries. Of the cohort, 513 had a history of breast cancer prior to enrollment.

During a mean of 4.5 years of follow-up, 332 cases of incident breast cancer were diagnosed, lead investigator Dr. Signe Borgquist and colleagues report in the May 15th issue of the International Journal of Cancer.

Tumor samples from 283 breast cancers were analyzed for histological type, grade and mitotic index, estrogen and progesterone receptor status, expression of the oncogene cyclin D1, tumor suppressor gene p27 expression and the Ki67 index as a measure of proliferative potential.

Among the 2369 current users of hormone replacement therapy, 1347 used combined therapy and 984 used estrogen-only therapy; 38 women reported using progestin-only therapy. The incidence of breast cancer was higher in combination hormone replacement users than non-users, but estrogen replacement was not associated with significantly increased risk of breast cancer.

The risk profile of breast cancers developing after combination hormone replacement therapy was more favorable than tumors that occurred in women who received estrogen replacement therapy alone.

Specifically, combination therapy was associated with more lobular tumors, more grade 1 tumors and more tumors with a low mitotic index than tumors recurring after estrogen-only hormone replacement therapy. Combination therapy was also associated with a low Ki67 index, low expression of cyclin D1 and high expression of gene p67.

Dr. Borgquist and colleagues conclude, "These findings correspond well with the image of combination hormone replacement therapy as related to tumors with a favorable prognosis."

"To date," they add, "no other study has reported on the association between combination hormone replacement therapy and cell cycle regulators."

Int J Cancer 2007;120:2202-2207.

Mortality Greater for Hip Fracture Than Breast Cancer in Elderly Women

Laurie Barclay, MD

Medscape Medical News 2007. © 2007 Medscape

May 18, 2007 — Older women are at greater risk for death after hip fracture than after breast cancer, according to a presentation at the American Geriatrics Society (AGS) annual meeting held in Seattle, Washington. The investigators suggest that increased awareness of mortality associated with hip fracture is needed to improve preventive measures.

"This study should raise the general level of awareness of the impact of hip fracture on the lives of elderly women," coauthor Jane A. Cauley, DrPH, a professor of epidemiology at the University of Pittsburgh in Pennsylvania, told Medscape. "There is already a greater general level of awareness of the public health impact of breast cancer, but, in fact, our study showed that the mortality of breast cancer in this population was less than that of hip fracture. The public health impact on mortality was much greater for hip fracture than for breast cancer, even after adjustment."

To test the hypothesis that hip fracture would be associated with worse survival than breast cancer, the investigators compared survival after an incident hip fracture and a diagnosis of invasive breast cancer in a longitudinal cohort of 9704 women enrolled in the Study of Osteoporotic Fractures (SOF). Participants were all aged 65 years or older at enrollment. Mean duration of follow-up was 12.4 ± 2.9 years, and follow-up of the cohort is over 95% complete.

Time from diagnosis to death or last follow-up was calculated by subtracting the time at diagnosis from the total follow-up time, and survival after hip fracture or diagnosis of breast cancer were compared using univariate and multivariate survival analysis. Covariate data available in SOF included demographics, general health, functional status, and cognitive mental status.

During follow-up, there were 457 incident cases of invasive breast cancer confirmed by pathology report, and 803 incident cases of hip fracture confirmed from radiographic reports. Compared with women diagnosed with invasive breast cancer, those with hip fracture were older, with higher levels of education, lower body mass index (BMI), decreased mental status, and less weight change.

After hip fracture, total mortality was 48.1% (n = 386) compared with 25.1% (n = 94) after diagnosis of breast cancer (P < .0001), and survival estimates were significantly different (log rank, 134.63; P < .0001). Mortality rates per 1000 person-years were 40.5 for hip fracture, 15.4 for breast cancer, and 27.9 for the remaining cohort. Adjustment for BMI, age, education, mental status, weight change since age 25 years, functional status, self-rated health, and amount of time spent on feet did not abolish this survival difference (likelihood ratio, 226.16; P < .0001; hazard ratio, 0.376 (95% confidence interval, 0.295 - 0.480).

The authors concluded that older women are at a greater risk for death after hip fracture than after breast cancer diagnosis, and that increased awareness of mortality associated with hip fracture is needed to promote preventive measures.

"The implications of this study are that we should aim more studies at the correct treatment of the patient with a hip fracture," S. K. Bulstra, MD, a professor of orthopaedic surgery at the University Medical Center Groiningen in the Netherlands, told Medscape. Dr. Bulstra was not involved with this study but was asked by Medscape to provide independent commentary.

"Of course it is important to know whether these patients also had more comorbidity than the breast cancer patients," Dr. Bulstra said. "The reduced weight of the hip fracture group suggests a higher frequency of osteoporosis. It is also important to know if patients came from a home situation or a nursing home and how the mental status was assessed, because indeed there is a connection between survival and mental status."

Dr. Bulstra's own research and experience suggest an increased mortality rate for 10 years or more after hip fracture, although the survival rate stabilizes after 2 years. Many patients are no longer able to live at home after hip fracture, which is related to their walking ability both before and after the fracture. Congestive heart failure, renal failure, liver disease, lymphoma, and weight loss each increased the 1-year mortality risk by approximately 2-fold.

"Future studies should compare the effect of hip fracture and of breast cancer on quality of life in this population, in terms of functional disability, pain, mobility, and other outcomes," Dr. Cauley concluded.

Medical Student Training in Aging Research, which is sponsored by the American Federation for Aging Research and the National Institute on Aging, helped support this study. Dr. Cauley and Dr. Bulstra report no relevant financial relationships.

AGS 2007 Annual Scientific Meeting: Abstract P28. May 2-6, 2007.