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Soy supplementation adversely effects expression of breast cancer-related genes

The impact of soy consumption on breast cancer prevention and treatment is not clear although many women believe soy supplementation is beneficial based primarily on results from epidemiological studies. Moshe Shike, M.D., from the Department of Medicine at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College in New York, NY, and colleagues conducted a randomized placebo-controlled study of the effects of soy supplementation on gene expression and markers of breast cancer risk among women diagnosed with invasive breast cancer. The study, run between 2003 and 2007 at Memorial Sloan-Kettering, enrolled a total of 140 patients who were randomized to either soy supplementation (soy protein) or placebo (milk protein), which lasted from the initial surgical consultation to the day before surgery (range=7-30 days). Tumor tissues from the diagnostic biopsy (pre-treatment) and at the time of resection (post-treatment) were then analyzed. They observed changes in several genes that promote cell cycle progression and cell proliferation among women in the soy group.

The authors conclude, “These data raise concern that soy may exert a stimulating effect on breast cancer in a subset of women.”

In an accompanying editorial, V. Craig Jordan, O.B.E., D.Sc., Ph.D., FMedSci, from the Department of Oncology at the Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC, discusses how timing of soy supplementation is critical and reviews the evidence in the literature on phytoestrogens, which are contained in soy, and their known action in breast cancer. He writes, the study by Shike et al. “…illustrates the dangers of phytoestrogen consumption too soon, around menopause, but the biology of estrogen in estrogen-deprived conditions suggests that phytoestrogen could have benefit a decade after menopause.” He cautions that appropriate doses of soy and timing of consumption are critical considerations.

source : http://www.sciencedaily.com/releases/2014/09/140904183725.htm

Breast conserving therapy shows survival benefit compared to mastectomy in early-stage patients with hormone receptor positive disease

The study findings defy the conventional belief that the two treatment interventions offer equal survival, and show the need to revisit some standards of breast cancer practice in the modern era.

The research was presented at the 2014 Breast Cancer Symposium by Catherine Parker, MD, formerly a fellow at MD Anderson, now at the University of Alabama Birmingham.

In the 1980s, both US-based and international randomized clinical studies found that BCT and mastectomy offered women with early stage breast cancer equal survival benefit. However, those findings come from a period in time when very little was understood about breast cancer biology, explains Isabelle Bedrosian, M.D., associate professor, surgical oncology at MD Anderson.

“Forty years ago, very little was known about breast cancer disease biology — such as subtypes, differences in radio-sensitivities, radio-resistances, local recurrence and in metastatic potential,” explains Bedrosian, the study’s senior author. “Since then, there’s been a whole body of biology that’s been learned — none of which has been incorporated into patient survival outcomes for women undergoing BCT or a mastectomy.

“We thought it was important to visit the issue of BCT versus mastectomy by tumor biology,” Bedrosian continues.

The researchers hypothesized that they would find that patients’ surgical choice would matter and impact survival with tumor biology considered.

For the retrospective, population-based study, the researchers used the National Cancer Database (NCDB), a nation-wide outcomes registry of the American College of Surgeons, the American Cancer Society and the Commission on Cancer that captures approximately 70 percent of newly-diagnosed cases of cancer in the country. They identified 16,646 women in 2004-2005 with Stage I disease that underwent mastectomy, breast conserving surgery followed by six weeks of radiation (BCT), or breast conserving surgery without radiation (BCS). Bedrosian notes that it was important that the study focused solely on women with Stage I disease in order to keep the study group homogenous and because in this cohort few would be ineligible for BCT.

Since estrogen receptor (ER) and progesterone receptor (PR) data were available and HER2 status was not, the researchers categorized the tumors as ER or PR positive (HR positive), or both ER and PR negative (HR negative). Patients were rigorously matched using propensity-score for a broad range of variables, including age, receiving hormone therapy and/or chemotherapy, as well as type of center where patients were treated and comorbidities.

Of the 16,646 women: 1,845 (11 percent) received BCS; 11,214 (67 percent) received BCT and 3,857 (22 percent) underwent a mastectomy. Women that had BCT had superior survival to those that had a mastectomy or BCS — the five-year overall survival was 96 percent, 90 percent and 87 percent, respectively. After adjusting for other risk factors, the researchers again found an overall survival benefit for BCT compared to BCS and mastectomy. In a matched cohort of 1,706 patients in each arm, the researchers still found an overall survival benefit with BCT over mastectomy in the HR positive subset but not in the HR negative subset.

While provocative, Bedrosian cautions that the findings are not practice changing, as the study is retrospective. Still, the research complements other recent studies that showed BCT was associated with a survival benefit compared to mastectomy. Also, she points to the delivery of radiation therapy as the possible driver of the overall survival benefit.

“We’ve historically considered surgery and radiation therapy as tools to improve local control,” says Bedrosian. Yet recent studies suggest that there are survival-related benefits to radiation in excess of local control benefits. Therefore, radiation may be doing something beyond just helping with local control. Also, we know hormone receptive positive tumors are much more sensitive to radiation, which could explain why we found the survival benefit in this group of patients.”

As follow up, Bedrosian and her team hope to mine the randomized controlled trial findings from the 1980s, matching those cohorts to current NCDB patients to see if a similar survival benefit could be observed.

“While retrospective, I think our findings should give the breast cancer community pause. In the future, we may need to reconsider the paradigm that BCT and mastectomy are equivalent,” she says. “When factoring in what we know about tumor biology, that paradigm may no longer hold true.”

source : http://www.sciencedaily.com/releases/2014/09/140904103336.htm

Disparities persist in early-stage breast cancer treatment

The study, to be presented at the 2014 Breast Cancer Symposium, finds that those barriers that still exist are socio-economic, rather than medically-influenced. Meeghan Lautner, M.D., formerly a fellow at MD Anderson, now at The University of Texas San Antonio, will present the findings.

BCT for early stage breast cancer includes breast conserving surgery, followed by six weeks of radiation. It has been the accepted standard of care for early stage breast cancer since 1990 when randomized, prospective clinical trials confirmed its efficacy — leading to the National Institute of Health issuing a consensus statement. Yet, a number of patients still opt for a mastectomy. In hopes of ultimately democratizing care, it was important to look at surgical choices made by women and their association with disparities, explains Isabelle Bedrosian, M.D., associate professor, Surgical Oncology at MD Anderson.

“What’s particularly novel and most meaningful about our study is that we looked at how the landscape has changed over time,” says Bedrosian, the study’s senior author. “We hope this will help us understand where we are and are not making progress, as well as identify the barriers we need to overcome to create equity in the delivery of care for our patients.”

For the retrospective, population-based study, the MD Anderson team used the National Cancer Database, a nation-wide outcomes registry of the American College of Surgeons, the American Cancer Society and the Commission on Cancer that captures approximately 70 percent of newly-diagnosed cases of cancer in the country. They identified 727,927 women with early-stage breast cancer, all of whom were diagnosed between 1998 and 2011 and had undergone either BCT or a mastectomy.

Overall, the researchers found that BCT rates increased from 54 percent in 1998 to 59 percent in 2006, and stabilized since then. Adjusting for demographic and clinical characteristics, BCT use was more common in women: age 52-61 compared to younger or older patients; with a higher education level and median income; with private insurance, compared to those uninsured; and who were treated at an academic medical center versus a community medical center.

Geographically, BCT rates were higher in the Northeast than in the South, and in those women who lived within 17 miles of a treatment facility compared to those who lived further away.

An important question to then ask, says Bedrosian, was to compare barriers for women receiving BCT in 1998 to 2011 — and understand how have those barriers changed. The researchers found that, overall, usage of BCT has dramatically increased across all demographic and clinical characteristics, however, significant disparities related to insurance, income and distance to a treatment facility still exist.

Bedrosian is gratified to see that in the areas where physicians and the medical field can make a direct impact — such as geographic distribution and practice type — disparities have equalized over time. However, she notes that factors outside the influence of the medical field, such as insurance type, income and education, still remain. Of great interest is the insurance disparity, says Bedrosian.

“Now with healthcare exchanges providing new insurance coverage options, will we rectify the disparity and overall increase BCT use? We will have wait to see,” she says.

Bedrosian hopes that health policy makers will take note of the findings and barriers related to women receiving BCT and make appropriate changes to democratize care.

source : http://www.sciencedaily.com/releases/2014/09/140904103338.htm