Posts Tagged ‘breast’

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

Enzyme controlling metastasis of breast cancer identified

“The take-home message of the study is that we have found a way to target breast cancer metastasis through a pathway regulated by an enzyme,” said lead author Xuefeng Wu, PhD, a postdoctoral researcher at UC San Diego.

The enzyme, called UBC13, was found to be present in breast cancer cells at two to three times the levels of normal healthy cells. Although the enzyme’s role in regulating normal cell growth and healthy immune system function is well-documented, the study is among the first to show a link to the spread of breast cancer.

Specifically, Wu and colleagues with the UC San Diego Moores Cancer Center found that the enzyme regulates cancer cells’ ability to transmit signals that stimulate cell growth and survival by regulating the activity of a protein called p38 which when “knocked down” prevents metastasis. Of clinical note, the researchers said a compound that inhibits the activation of p38 is already being tested for treatment of rheumatoid arthritis.

In their experiments, scientists took human breast cancer cell lines and used a lentivirus to silence the expression of both the UBC13 and p38 proteins. These altered cancer cells were then injected into the mammary tissues of mice. Although the primary tumors grew in these mice, their cancers did not spread.

“Primary tumors are not normally lethal,” Wu said. “The real danger is cancer cells that have successfully left the primary site, escaped through the blood vessels and invaded new organs. It may be only a few cells that escape, but they are aggressive. Our study shows we may be able to block these cells and save lives.”

Researchers have also defined a metastasis gene signature that can be used to evaluate clinical responses to cancer therapies that target the metastasis pathway.

source : http://www.sciencedaily.com/releases/2014/09/140902205145.htm