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The study team, led by researchers at the Moores Cancer Center at the University of California, San Diego, along with six other sites, including the University of California, Davis, reported its results online December 15, 2008, in the Journal of Clinical Oncology.

The results come on the heels of a report last year on the findings of the original study, the Women’s Healthy Eating and Living Trial (WHEL), which compared the effects of the two diets on cancer recurrence in more than 3,000 early-stage breast cancer survivors. That study showed no overall difference in recurrence among the two diet groups.

“Women with early stage breast cancer who have hot flashes have better survival and lower recurrence rates than women who don’t have hot flashes,” said Ellen B. Gold, Ph.D., professor and chair of the UC Davis Department of Public Health Sciences and first author of the study. “Our results suggest that a major change in diet may help overcome the difference in prognosis between women with and without hot flashes.”

“Our interest in looking at this subgroup came because hot flashes are associated with lower circulating estrogen levels, while the absence of hot flashes is associated with higher estrogen levels. Reducing the effect of estrogen is a major treatment strategy in breast cancer,” said the WHEL study principal investigator John P. Pierce, Ph.D., Sam M. Walton Professor for Cancer Prevention and director of Cancer Prevention and Control at the UC San Diego School of Medicine and the Moores UCSD Cancer Center. “It appears that a dietary pattern high in fruits, vegetables and fiber, which has been shown to reduce circulating estrogen levels, may only be important among women with circulating estrogen levels above a certain threshold.”

About 30 percent of the original group of 3,088 breast cancer survivors did not report hot flashes at study entry. The women had been randomly assigned to one of the two diets between 1995 and 2000 and were followed until 2006. About one-half (447) of the “no hot flashes” group were randomized to the special, “intervention” high-vegetable fruit diet while the other half (453) was given the generally recommended diet of five servings of fruits and vegetables a day. The team found that those on the intervention diet had a significantly lower rate of a second breast cancer event (16.1 percent) compared to those eating the government-recommended five-a-day dietary pattern (23.6 percent).

The dietary effect was even larger (a 47 percent lower risk) in women who had been through menopause.

According to Pierce, another possible mechanism has been proposed recently for why this diet may have affected only 30 percent of the WHEL study population. Women with estrogen receptor-positive cancers usually receive hormone therapy (tamoxifen or aromatase inhibitors) aimed at combating the effect of circulating estrogen. However, more than 30 percent of these women appear to have a gene-drug interaction that prevents them from getting an effective dose of this therapy.

“This hypothesis says that if the endocrine therapy is working, no further reduction in estrogen levels would be needed,” said Pierce. “If your genes are preventing you from getting a therapeutic dose, then following this rigorous dietary pattern may reduce estrogen levels enough to reduce risk.” Because this is speculation, he said, the research team will be using biological samples collected throughout the study to further investigate the mechanisms behind the study diet’s protective effects.

Women who don’t benefit from a drug used to prevent breast cancer recurrence may have low levels of a protein linked to improved survival, U.K. researchers found.

They also found that high levels of another protein could stop the drug tamoxifen from working as it should, according to a study online today in the journal Nature. Researchers said from 25 percent to 35 percent of women with breast cancer eventually develop resistance to the medicine.

Breast cancer is the most frequently diagnosed cancer in U.S. women, excluding cancer of the skin, according to the American Cancer Society. Determining why some women develop resistance to tamoxifen and others don’t may help scientists develop better treatments for the disease, the researchers said.

“For the first time, we’ve started to identify what the key and critical factors are that can cause drug resistance,” said study author Jason Carroll, a researcher at Cancer Research UK Cambridge Research Institute, in a Nov. 11 conference call with reporters.

Carroll said developing tests that doctors can use on a regular basis to determine if women have low levels of the protein, called PAX2, or high levels of a competing protein, known as AIB-1, are still at least five years away.

“This is a really interesting study. It certainly helps to supplement what we already know,” said Eric Winer, an oncologist and director of the breast oncology center at Dana-Farber Cancer Institute in Boston in a Nov. 11 telephone interview. “It is already being looked at in the clinic as a potential strategy to overcome resistance to hormonal therapy.”

Estrogen Receptors

About two out of three breast cancers grow because they are sensitive to the hormone estrogen, according to the American Cancer Society. Tamoxifen, a generic drug, temporarily blocks estrogen receptors on breast cancer cells and stops the estrogen from binding to them. Most women receive tamoxifen for five years after they are diagnosed with breast cancer to stop the disease from returning. Over time, some women can develop resistance to the treatment, which may allow their cancer return.

Tamoxifen works by turning off a breast cancer gene, ErbB2, through the protein PAX2, the researchers said. Resistance to tamoxifen occurs when ErbB2 remains turned on because of low levels of PAX2. In women with high levels of PAX2, drug resistance can still occur if the body has higher levels of the other protein, AIB-1, they said. High levels of AIB-1 can cause PAX2 to not function properly, allowing cancer cells to divide and spread.

Learning the Mechanics

“We knew that women developed resistance to tamoxifen but previously our understanding of why this occurred could be compared with trying to fix a broken car without knowing how the engine worked,” Carroll said in a statement issued by Cancer Research UK. “Now we understand how all the engine parts operate and we can try to think about ways to make repairs.”

Winer said that this may be only one of the ways women become resistant to tamoxifen.

Tamoxifen is the generic name for AstraZeneca Plc’s Nolvadex, no longer made in the U.S., which was developed 30 years ago. About 28,000 U.S. women receive tamoxifen as a first- line therapy, according to Cancer Research UK.

The researchers looked at 109 breast cancer tumors, all of which had been treated with tamoxifen. They found that 68 were PAX2-positive and 41 were PAX2-negative. Patients whose tumors were PAX2-positive had a “significantly improved” chance of survival without their cancer returning than those whose tumors were PAX2-negative.

The patients whose tumors tested PAX2-positive and also positive for AIB-1 had a worse outcome than those whose tumors were AIB-1 negative, the study found. The tumors that were PAX2- positive and AIB-1 negative had the best outcomes, they said.

Carroll said on the conference call that larger studies are needed to duplicate these findings. Once that occurs, researchers and drug companies can begin developing treatments that target these proteins, he said.

Survival rates for breast cancer have been improving for more than 20 years. More than 80 percent of women diagnosed with the cancer survive at least five years, compared with only 50 percent of women 30 years ago.

Measuring quality of life in breast cancer patients is of importance in assessing treatment outcomes. This study examined the impact of breast cancer diagnosis and its treatment on quality of life of women with breast cancer.

Methods: This was a prospective study of quality of life in breast cancer patients.

Quality of life was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its breast cancer supplementary measure (QLQ-BR23) at three points in time: baseline (pre-diagnosis), three months after initial treatment and one year after completion of treatment (in all 18 months follow-up). At baseline the questionnaires were administered to all suspected identified patients while both patients and the interviewer were blind to the final diagnosis.

Socio-demographic and clinical data included: age, education, marital status, disease stage and initial treatment. Repeated measure analysis was performed to compare quality of life differences over the time.

Results: In all, 167 patients diagnosed with breast cancer.

The mean age of breast cancer patients was 47.2 (SD = 13.5) years and the vast majority (82.6%) underwent mastectomy. At eighteen months follow-up data for 99 patients were available for analysis.

The results showed there were significant differences in patients’ functioning and global quality of life at three points in time (P<0.001). Although there were deteriorations in patients’ scores for body image and sexual functioning, there were significant improvements for breast symptoms, systematic therapy side effects and patients’ future perspective (P<0.05).

Conclusions: The findings suggest that overall breast cancer patients perceived benefit from their cancer treatment in long-term.

However, patients reported problems with global quality of life, pain, arm symptoms and body image even after 18 months following their treatments. In addition, most of the functional scores did not improve.