Tag Archives: breast cancer

Study: Moderate red wine drinking may help cut women’s breast cancer risk

Posted on by
Reply

LOS ANGELES – Drinking red wine in moderation may reduce one of the risk factors for breast cancer, providing a natural weapon to combat a major cause of death among U.S. women, new research from Cedars-Sinai Medical Center shows.

The study, published online in the Journal of Women’s Health, challenges the widely-held belief that all types of alcohol consumption heighten the risk of developing breast cancer. Doctors long have determined that alcohol increases the body’s estrogen levels, fostering the growth of cancer cells.

But the Cedars-Sinai study found that chemicals in the skins and seeds of red grapes slightly lowered estrogen levels while elevating testosterone among premenopausal women who drank eight ounces of red wine nightly for about a month.

White wine lacked the same effect.

Researchers called their findings encouraging, saying women who occasionally drink alcohol might want to reassess their choices.

“If you were to have a glass of wine with dinner, you may want to consider a glass of red,” said Chrisandra Shufelt, MD, assistant director of the Women’s Heart Center at the Cedars-Sinai Heart Institute and one of the study’s co-authors. “Switching may shift your risk.”

Shufelt noted that breast cancer is the leading type of women’s cancer in the U.S., accounting for more than 230,000 new cases last year, or 30 percent of all female cancer diagnoses. An estimated 39,000 women died from the disease in 2011, according to the American Cancer Society.

In the Cedars-Sinai study, 36 women were randomized to drink either Cabernet Sauvignon or Chardonnay daily for almost a month, then switched to the other type of wine. Blood was collected twice each month to measure hormone levels.

Researchers sought to determine whether red wine mimics the effects of aromatase inhibitors, which play a key role in managing estrogen levels. Aromatase inhibitors are currently used to treat breast cancer.

Investigators said the change in hormone patterns suggested that red wine may stem the growth of cancer cells, as has been shown in test tube studies.

Co-author Glenn D. Braunstein, MD, said the results do not mean that white wine increases the risk of breast cancer but that grapes used in those varieties may lack the same protective elements found in reds.

“There are chemicals in red grape skin and red grape seeds that are not found in white grapes that may decrease breast cancer risk,” said Braunstein, vice president for Clinical Innovation and the James R. Klinenberg, MD, Chair in Medicine.

###

The study will be published in the April print edition of the Journal of Women’s Health, but Braunstein noted that large-scale studies still are needed to evaluate the safety and effectiveness of red wine to see if it specifically alters breast cancer risk. He cautioned that recent epidemiological data indicated that even moderate amounts of alcohol intake may generally increase the risk of breast cancer in women. Until larger studies are done, he said, he would not recommend that a non-drinker begin to drink red wine.

The research team also included C. Noel Bairey Merz, MD, director of the Women’s Heart Center, director of the Preventive and Rehabilitative Cardiac Center and the Women’s Guild Chair in Women’s Health, as well as researchers from the University of Southern California Keck School of Medicine and Hartford Hospital in Connecticut.

Source: Eurekalert

Risk for developing new cancer in other breast increased for survivors with BRCA mutation

Posted on by
Reply

SAN ANTONIO — Breast cancer survivors who carry the BRCA1 or BRCA2 genetic mutation are at high risk for developing contralateral breast cancer — a new primary tumor in the other breast — and certain women within this group of carriers are at an even greater risk based on age at diagnosis and first tumor status, according to data presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

“Our studies show that certain subgroups of women [with this mutation] who have already had cancers are also at risk for developing a second new cancer in their other breast, much more so than survivors who do not carry the mutation,” said Alexandra J. van den Broek, M.Sc., a doctoral candidate at the Netherlands Cancer Institute. “Our study is, as far as we know, the first study showing that within certain carriers of BRCA mutations, subgroups with an increased or decreased risk for contralateral breast cancer (CBC) can be made.”

Researchers surveyed 5,061 women diagnosed with unilateral, invasive breast cancer at 10 hospitals in the Netherlands. Two hundred eleven women (4.2 percent) were carriers of the BRCA1 or BRCA2 mutation. Overall, at a median of 8.4 years of follow-up, 8.6 percent of participants developed CBC.

Van den Broek and colleagues found that the overall 10-year risk for developing CBC in noncarriers was 6.0 percent, while risk for carriers was 17.9 percent.

For carriers diagnosed with their first breast cancer when aged younger than 40 years, the 10-year risk for CBC jumped to 26.0 percent. For carriers between the ages of 40 and 50 years at first diagnosis, the risk was 11.6 percent. In addition, mutation carriers with a triple-negative first tumor had a 10-year cumulative CBC risk of 18.9 percent compared with 11.2 percent among carriers with a non-triple-negative first tumor.

Although these numbers can be overwhelming to carriers who have already survived breast cancer, van den Broek said it is crucial to know who is most at risk and by how much.

“Guidelines for prophylactic measures and screening in the follow-up of patients with breast cancer carrying the BRCA1 or BRCA2 mutation are important to provide patients with the best information and counseling,” she said. “If these results are confirmed, [it will be] possible to personalize the guidelines for these specific subgroups.”

The next step will be to confirm the results in larger studies and to look at other factors that define subgroups of patients with an increased or decreased risk for CBC.

Source Eurekalert December 8 2011

Many women do not undergo breast reconstruction after mastectomy

Posted on by
Reply

SAN ANTONIO — Despite the benefits, only a small minority of women, regardless of age, are opting for immediate reconstructive breast surgery after undergoing mastectomy for treatment of breast cancer, according to data presented at the 2011 CTRC-AACR San Antonio Breast Cancer Symposium, held Dec. 6-10, 2011.

Research has shown that immediate breast reconstruction after mastectomy improves psychological well-being and quality of life and provides women with improved body image and self-esteem compared with delaying the procedure.

However, data from this study, presented by Dawn Hershman, M.D., associate professor of medicine and epidemiology at Columbia University Medical Center in New York, indicate that only about one third of women undergo the procedure.

Hershman and colleagues identified 106,988 women with breast cancer who underwent mastectomy between 2000 and 2010. They identified these women using insurance codes and then examined data on the frequency of reconstruction by a number of factors including age, race, number of procedures performed in the hospital and type of insurance.

Of the women examined, 22.6 percent underwent immediate reconstruction. Although overall rates of reconstruction have increased since 2000, the greatest increases were seen among women with commercial insurance — from 25.3 percent to 54.6 percent — and among women aged younger than 50 years — from 29 percent to 60 percent. Among women aged 50 years or younger who also had commercial insurance, 67.5 percent underwent immediate breast reconstruction. Overall, women with commercial insurance had more than a threefold higher likelihood of undergoing immediate reconstruction compared with women without health insurance.

“We were surprised to see that although the use of immediate postmastectomy reconstruction has increased, the rates still remain low, with 41.8 percent of women aged younger than 50 years and less than 20 percent of women aged older than 50 years receiving reconstruction during this time frame,” Hershman said.

Researchers found that patients were more likely to undergo immediate reconstruction if their surgeon did more mastectomies or they were in a hospital where more mastectomies were performed.

“This is something that could be modified by training and patient education,” Hershman said.

Other factors associated with a decreased likelihood for undergoing mastectomy were increasing age, black race, rural hospital location, nonteaching hospital or having other medical illnesses.

Women who underwent immediate breast reconstruction postmastectomy did have a longer hospital stay, but in-hospital complication rates were similar between women who had reconstruction and those who did not.

“Our study shows that there are factors that can be modified to increase the likelihood that women undergo postmastectomy reconstruction,” Hershman said. “Public policy should ensure that access to reconstructive surgery is available to all women regardless of insurance status.”

In the future, Hershman and colleagues plan to explore other factors that may be associated with immediate reconstruction to better target interventions to appropriate institutions.

Source Eurekalert December 8 2011

Researchers find genetic rearrangements driving 5 to 7 percent of breast cancers

Posted on by
Reply

ANN ARBOR, Mich. — Researchers at the University of Michigan Comprehensive Cancer Center have discovered two cancer-spurring gene rearrangements that may trigger 5 to 7 percent of all breast cancers.

These types of genetic recombinations have previously been linked to blood cancers and rare soft-tissue tumors, but are beginning to be discovered in common solid tumors, including a large subset of prostate cancers and some lung cancers.

Looking at the genetic sequencing of 89 breast cancer cell lines and tumors, researchers found two distinct types of genetic rearrangements that appear to be driving this subset of breast cancers. The recurrent patterns were seen in the MAST kinase and Notch family genes. The findings were published online in Nature Medicine ahead of print publication.

“What’s exciting is that these gene fusions and rearrangements can give us targets for potential therapies,” says Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology, Howard Hughes Medical Institute Investigator, and S.P. Hicks Professor of Pathology at the U-M Medical School. “This is a great example of why treating cancer is so challenging. There are so many different ways genes get recombined and so many molecular subtypes, that there’s not one solution that will work for all of them.”

“The research provides additional evidence that these types of genetic rearrangements seem to be a significant cause of solid tumors,” he adds.

The discoveries illuminate a promising path for future research, Chinnaiyan says. Gene sequencing offers opportunities to develop treatments for individuals whose tumors carry specific genetic combinations – a process commonly known as “personalized medicine.”

The study demonstrated that the genetic rearrangements had profound effects on breast cancer cells in the lab, both in tissue culture and in mouse models.

“We cloned each of these rearrangements and introduced them into normal breast cell lines, where they appeared to have cancer-causing effects,” Chinnaiyan says.

Previous U-M research showed that half of prostate cancers have a genomic rearrangement that causes the fusion of two genes called TMPRSS2 and ERG. This gene fusion, believed to be the triggering event for these prostate cancers, was initially discovered in 2005 by U-M researchers led by Chinnaiyan.

###

Additional authors: Dan R. Robinson, Shanker Kalyana-Sundaram, Yi-Mi Wu, Sunita Shankar, Xuhong Cao, Bushra Ateeq, Irfan A. Asangani, Matthew Iyer, Christopher A. Maher, Catherine S. Grasso, Robert J. Lonigro, Michael Quist, Javed Siddiqui, Rohit Mehra, Xiaojun Jing, Thomas J. Giordano, Michael S. Sabel, Celina G. Kleer, Nallasivam Palanisamy, Chandan Kumar-Sinha, all of U-M. Kalyana-Sundaram also of Bharathidasan University, Tiruchirappalli, India

Rachael Natrajan, Maryou B. Lambros, Jorge S. Reis-Filho, of the Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.

Disclosures: The researchers report no conflicts of interest. U-M has filed for patent protection for these developments.

Funding: The specific aims of this project were supported by the Department of Defense Breast Cancer Research Program. The project was also supported in part by an American Association for Cancer Research Stand Up to Cancer (SU2C) breast cancer award, the National Functional Genomics Center supported by the Department of Defense, and the National Institutes of Health. Chinnaiyan is supported by the National Cancer Institute Early Detection Research Network, the Doris Duke Charitable Foundation and the Burroughs Welcome Foundation; he is also an American Cancer Society research professor and Taubman Scholar.

Source: Eurekalert

Depression and pain increase fatigue in breast cancer survivors

Posted on by
Reply

In Spain, 5-year survival following breast cancer diagnosis is more than 83%. Around 66% suffer fatigue following treatment. A Spanish research establishes the factors associated with tiredness in cancer survivors to improve their quality of life and rehabilitation.

“Cancer-related fatigue is the symptom that most limits quality of life and is most common in patients that survive cancerous processes,” explained Manuel Arroyo, researcher from the University of Granada and lead author of a study that links psychological disorders and physical pain episodes with fatigue after treating a breast tumour.

More than 66% of breast cancer survivors suffer tiredness following recovery, caused directly by the disease, physical deterioration or the treatment received. Therefore, understanding the factors related with fatigue and how they can be alleviated optimises survivors’ recovery.

Fifty-nine female patients treated for breast cancer were followed-up one year after having clinically overcome the disease. The researchers assessed their psychological and physical condition as well as different aspects linked to the typical medical symptoms following a cancerous process (tiredness, pain, limited movement, depression, etc.).

A statistical procedure (resampling) allowed inferences to be made similar to those that would be obtained from larger samples. “This method means that the data were more reliable and eliminated the problem of having a reduced sample size,” explained Arroyo. “It is difficult to find volunteers because patients are not often very willing to participate in research after having been through such harsh treatment.”

The results show that the patients most affected by tiredness following treatment also suffer episodes of depression and body image deterioration, neck and shoulder pain, and limited arm movement, possibly due to the surgical intervention.

Effects of survival

Following breast cancer treatment, patients present with physical and psychological symptoms that influence their health.

Previous studies have already observed self-esteem- and body image-related disorders following the cancerous process. But for the first time, a team of researchers has associated sensory hypersensitivity, limited movement and certain psychological conditions with fatigue observed following cancer treatment.

“These findings should motivate patient support programmes which improve their psychological condition and offer resources that can reduce pain,” pointed out Arroyo, who further stressed that “if fatigue is not treated, patients can suffer it for years, having a serious physical, emotional, social and economic impact.”

###

References: Cantarero Villanueva, Antarero Villanueva, C- Fernández Lao, C. Fernández de las Peñas, L. Díaz Rodríguez, E. Sánchez Cantalejo, M. Arroyo Morales. “Associations among musculoskeletal impairments, depression, body image and fatigue in breast cancer survivors within the first year after treatment”. European Journal of Cancer Care 20 (2011): 632-636, 11th Septembre 2011.

Study: Gene therapy causes breast cancer stem cells to self-destruct

Posted on by
Reply

Targeted agent avoids healthy cells, blocks proteins that prevent cell death in tumors

HOUSTON — Gene therapy delivered directly to a particularly stubborn type of breast cancer cell causes the cells to self-destruct, lowers chance of recurrence and helps increase the effectiveness of some types of chemotherapy, researchers at The University of Texas MD Anderson Cancer Center reported in the Sept. 13 edition of Cancer Cell.

In cellular and mouse studies, scientists found the gene mutation BikDD significantly reduced treatment-resistant breast-cancer initiating cells (BCICs), also known as breast cancer stem cells, by blocking the activity of three proteins in the Bcl-2 family. This genetic approach increased the benefits of lapatinib, one of the most common chemotherapy drugs for breast cancer.

“There are no effective methods to target BCICs, and they’re urgently needed, especially for relapsed breast cancer patients,” said senior author Mien-Chie Hung, Ph.D., vice president for basic research, professor and chair of MD Anderson’s Department of Molecular and Cellular Oncology. “This research suggests a potential therapeutic approach to breast cancer stem cells that will minimize recurrence and drug resistance.”

Special delivery system targets cells

Gene therapy was deposited directly into breast cancer cells with an innovative delivery system called VISA, short for versatile expression vector, which was developed at MD Anderson. It includes a targeting agent, also called a promoter, two components that boost gene expression in the target tissue and a payload — a Bik mutant gene called BikDD known to kill cancer cells. It’s all packaged in a fatty ball called a liposome and delivered intravenously.

This system has been successfully applied in pancreatic, lung, liver and ovarian cancer preclinical models. MD Anderson clinical researchers are preparing a phase I clinical trial for pancreatic cancer.

Stem cells frequently stymie treatment

Breast cancer stem cells, often resistant to chemotherapy and radiotherapy, are a major obstacle for breast cancer treatment, Hung said. If any of these cells remain after treatment, a new tumor often forms. Although lapatinib, known commercially as Tykerb®, can stabilize the level of these cells, no drugs are available to reduce them.

The Bcl-2 family of proteins – especially the subtypes Bcl-2, Bcl-xL and Mcl-1 — is essential for breast cancer tumor growth and treatment resistance. If too many of these three proteins are present, they can cause poor prognosis and resistance to chemotherapy drugs including lapatinib, as well as paclitaxel, doxorubicin and cisplatin.

This study shows that Bcl-2 proteins help breast cancer stem cells survive, causing resistance to treatment and likelihood of recurrence. However, using VISA to deliver BikDD can block the three key Bcl-2 proteins, eliminating the stem cells.

VISA-claudin4-BikDD cuts tumor burden

The researchers engineered a VISA that contained claudin4, a protein over-expressed in breast cancer, as a targeting agent to preferentially express BikDD in breast cancer cells. This process silenced the three Bcl-2 proteins and caused the cancer cells to self-destruct. Since the VISA focused the BikDD on cancer cells, normal cells were not affected.

Treating mice with the VISA-claudin4-BikDD therapy reduced tumor volume by 75 percent compared to control mice.

They also compared VISA-claudin4-BikDD therapy to BikDD packaged with a non-specific strong promoter from cytomegalovirus. Both versions reduced tumor burden and extended survival of mice, but tumor volume in mice treated with VISA-claudin4-BikDD was half that of the CMV-BikDD-treated mice. In a safety study using an unusually high dose, 60 percent of mice treated with CMV-BikDD survived after three days; all mice treated with VISA-Claudin4-BikDD survived for the duration of the 14-day safety profile study.

In cell line experiments, the CMV-BikDD also invaded and destroyed normal cells, while the VISA-Claudin4-BikDD did not.

Agent energizes lapatinib, other drugs

BikDD made HER2-positive breast cancer cells more sensitive to lapatinib when all three Bcl-2 proteins were inhibited but not when they were inhibited separately. HER2-positive breast cancer is a particularly aggressive type that makes too much human epidermal growth factor 2; it accounts for about 20 percent of breast cancers. BikDD also sensitized EGFR+ (epidermal growth factor positive) breast cancer cells to lapatinib and several other breast cancer cells lines to paclitaxel.

Moving discovery forward

Hung said this approach is promising for breast cancer treatment, especially recurrent disease.

“VISA-claudin4-BikDD gene therapy may provide an effective strategy to inhibit breast tumor growth,” he said. “It demonstrates virtually no toxicity in normal cells and produces a profound killing effect in multiple breast cancer cell lines and synergy with other agents.”

Hung said the next step is to move VISA-claudin4-BikDD into a Phase I clinical trial to test its effect on patients with breast cancer.

###

 

This work was supported by grants from the National Cancer Institute, including MD Anderson’s Specialized Program in Research Excellence grant, the MD Anderson/China Medical University Hospital Sister Institution Fund, the Breast Cancer Research Foundation, National Breast Cancer Foundation, Inc., Patel Memorial Breast Cancer Research Fund, MD Anderson’s Center for Biological Pathways and NCI Cancer Center Support Grant, and the Taiwan Department of Health Cancer Center Research of Excellence Grant.

In addition to Hung, MD Anderson researchers include first author Jing-Yu Lang, Ph.D., first author, Jennifer Hsu, Ph.D., Chun-Ju Chang, Ph.D., Qingfei Wang, Ph.D., Xiaoming Xie, Ph.D., Yi Bao, Ph.D., Hirohito Yamaguchi, Ph.D. and Dihua Yu, M.D., Ph.D., Department of Molecular and Cellular Oncology; Funda Meric-Bernstam, M.D., Department of Surgical Oncology; Wendy Woodward, M.D., Ph.D., Department of Radiation Oncology; and Gabriel Hortobagyi, M.D., Department of Breast Medical Oncology.

Hung and Hsu hold joint appointments at China Medical University and Asia University, Taichung, Taiwan. Xie holds an appointment at Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China.

Study: Chemotherapy is as effective before breast cancer surgery as after

Posted on by
Reply

Approach may help some women avoid mastectomy

San Francisco, CA – Whether chemotherapy is given before or after breast-conserving therapy (BCT) does not have an impact on long-term local-regional outcomes, suggesting treatment success is due more to biologic factors than chemotherapy timing, according to a study by researchers at The University of Texas MD Anderson Cancer Center.

Presented today at the 2011 Breast Cancer Symposium, the study also found that neoadjuvant chemotherapy (given before surgery), often shrinks breast cancer tumors, making them more likely to be treatable with BCT, or a lumpectomy to remove a portion of the breast followed by radiation.

“Even women who present with clinical Stage 2 or 3 breast cancer may have good results with BCT after chemotherapy and not need a mastectomy,” said Elizabeth Ann Mittendorf, M.D., assistant professor in the Department of Surgical Oncology and lead author of the study. “The molecular characteristics of the tumor and other factors have an impact on treatment success, but not the order in which chemotherapy and surgery are given.”

The retrospective study of almost 3,000 women treated for breast cancer at MD Anderson from 1987 to 2005 also confirmed several prior studies showing BCT offers high rates of cancer control for certain patients.

Approaches have similar outcomes

Of the patients surveyed, 78 percent had surgery before chemotherapy and 22 percent received chemotherapy first. Overall, women with more cancers that had more adverse prognostic factors tended to be treated with chemotherapy first.

Five and 10-year local-regional recurrence-free survival rates were excellent for both groups: 97 percent and 94 percent respectively for those who had surgery before chemotherapy, 93 percent and 90 percent for patients who received chemotherapy first.

Mittendorf said that if adverse features, such as stage and grade of the cancer, age of the patient and tumor hormone expression, were factored in, survival rates were essentially the same for both groups of women.

Neoadjuvant chemotherapy resulted in complete pathologic response in 20 percent of patients and lowered cancer stage in almost half of patients who had Stage 2 or 3 cancer before chemotherapy, increasing the likelihood that BCT may be effective for many women after chemotherapy.

Carrying results forward

“This study shows that women appropriately selected for BCT, even some women with Stage 3 breast cancer, can have excellent rates of local-regional control,” Mittendorf said. “The most important thing is putting all the factors together to determine who can most benefit from this approach.”

The group plans to extend the study into MD Anderson patients treated after 2005.

“Since 2005, treatment techniques have improved, including the ability to add targeted therapies to chemotherapy,” she said. “In the future we will look at the effects of newer agents, and we anticipate the results will be even more favorable for women who received these treatments before surgery.”

###

Other MD Anderson team members included Thomas Buchholz, M.D., Department of Radiation Oncology; Susan Tucker, Ph.D., Department of Bioinformatics and Computational Biology; Funda Meric-Bernstam, M.D., Henry Kuerer, M.D., Ph.D., Isabelle Bedrosian, M.D., Gildy Babiera M.D., Merrick Ross, M.D. and Kelly Hunt, M.D., Min Yi, M.D., Ph.D., Department of Surgical Oncology; Ana Gonzalez-Angulo, M.D. and Gabriel Hortobagyi M.D., Department of Breast Medical Oncology.

Key function of mutation in BRCA1 gene discovered

Posted on by
Reply

Richmond, Va. (September 1, 2011) –It is widely known that mutations in the breast cancer susceptibility 1 (BRCA1) gene significantly increase the chance of developing breast and ovarian cancers, but the mechanisms at play are not fully understood. Now, researchers at Virginia Commonwealth University Massey Cancer Center have shown that certain BRCA1 mutations result in excessive, uncontrolled DNA repair, which challenges the prior assumption that mutations in BRCA1 only contribute to breast cancer through a reduction in function.

Recently published in the journal Aging, the study led by Kristoffer Valerie, Ph.D., discovered that certain BRCA1 mutations affecting the BRCA1 C-terminal (BRCT) binding site resulted in excessive DNA repair, or hyper-recombination, which may contribute to the development of breast and ovarian cancers. The BRCT domain is a protein binding site typically found on DNA repair proteins like BRCA1 that are responsible for maintaining genomic stability and facilitating DNA repair. This study has implications for the treatment, diagnosis and development of therapies for patients with breast and ovarian cancer.

“Our findings suggest that caution should be exercised when targeting BRCA1 for breast and ovarian cancer therapies,” says Valerie, co-leader of the Radiation Biology and Oncology program and a professor in the Department of Radiation Oncology at VCU Massey Cancer Center. “We need to better understand the biological mechanisms that lead to the development of breast and ovarian cancer before we attempt to attack it through targeted therapies aimed at causing DNA damage.”

When DNA damage occurs, various forms of BASC (BRCA1-associated genome surveillance complex) bind to the BRCT domain on BRCA1. BASC is a protein complex that in part binds to the BRCT domain and serves as a “docking site” for other proteins and enzymes to come in, effectively repair the DNA damage and leave when repair is completed. However, certain BRCT mutants unable to bind to BASC disrupt the delicate DNA repair process. Previously, it was assumed this meant that BRCA1 was unable to assist with the repair process and, thus, recombination did not occur.

Valerie and his colleagues showed through experiments with cultured breast cancer cells and tissue samples from breast cancer patients that BRCT mutants increased ubiquination of BASC, which, in turn, increased recombination several-fold over normal levels. Ubiquitin is a small protein in all living organisms that “marks” other proteins for degradation or, as more recently discovered, the participation in specific cellular processes such as recombination. The researchers proposed that the hyper-recombination resulting from increased ubiquination of the BASC might result in improperly repaired DNA and increased genomic instability, which could lead to the development and aggressive progression of breast and ovarian cancers.

“Our results point to ubiquitination as a potential therapeutic target,” says Valerie. “By disrupting ubiquitination we may be able to prevent hyper-recombination and stop the growth of cancer cells with these BRCT mutations. This might sensitize the cancer cells to radiation therapy while having little effect on cells with normal BRCA1 function.”

The researchers hope to continue studying the role of BRCA1 in DNA double-strand break repair in order to determine whether the mutations they examined are important for the onset of cancer and whether targeted therapies can be developed.

###

The full manuscript of this study is available online at: http://www.impactaging.com/papers/v3/n5/abs/100325a.html.

Valerie collaborated on this study with Seth M. Dever, Ph.D., Sarah E. Golding, Ph.D., Elizabeth Rosenberg, M.S., Bret R. Adams, Michael O. Idowu, M.D., M.P.H., John M. Quillin, Ph.D., C.G.C., Nicholas Valerie, and Lawrence F. Povirk, Ph.D., from Virginia Commonwealth University, and Bo Xu, M.D., Ph.D., from The Methodist Hospital in Houston, Texas.

Funding for this study was provided by the National Institutes of Health.

PET scans confirm effectiveness of estrogen-blocking drugs in breast cancer patients

Posted on by
Reply

SEATTLE – For the first time, researchers at Seattle Cancer Care Alliance have demonstrated the feasibility of using serial positron emission tomography (PET) scans, using a special estrogen-containing isotope, to confirm the relative effectiveness of estrogen-blocking and estrogen-depleting therapy in patients with metastatic breast cancer. The results of the research are published online in Clinical Cancer Research.

The PET scans, taken before, during and after hormonal therapy, confirmed the superior effectiveness of estrogen-receptor-blocking drugs such as tamoxifen and fulvestrant over estrogen-depleting therapies such as aromatase inhibitors in blocking the estrogen receptor in cancer cells. The study also confirmed that tamoxifen is superior to fulvestrant in blocking estrogen.

While the results were expected they had never before been proven, according to corresponding author Hannah Linden, M.D., a breast oncologist at SCCA and an associate professor of Medicine at the University of Washington School of Medicine.

Linden and colleagues measured regional estrogen-receptor blocking and binding by using PET scans with 18F-flouroestradiol (FES), a trace amount of estrogen in isotope form, prior to and during treatment with aromatase inhibitors, tamoxifen and fulvestrant in a series of 30 patients whose breast cancer had spread to the bones. Tumor FES uptake declined more markedly in patients who took estrogen-receptor blockers compared to those who took estrogen-depleting aromatase inhibitors (an average decline of 54 percent versus 15 percent, respectively). Among the two estrogen-blocking drugs studied, the rate of complete tumor blockade was highest following use of tamoxifen versus fulvestrant.

“What we’re suggesting in the paper — that we couldn’t fully test for before — is if estrogen is incompletely blocked you’re not getting a good outcome for the patient,” Linden said.

“Our findings support the ability of FES PET to visualize the in vivo activity of endocrine therapy,” the authors concluded. “This technology could be used early in drug development to measure effectiveness at the intended therapeutic targets, and to help refine selection and dosing for agents to move forward in drug development.”

Additionally, pharmacodynamic imaging could provide clinicians with a promising tool for therapeutic selection and for predicting and evaluating response to estrogen-receptor-targeted therapy, Linden said.

###

The isotope was manufactured by the chemistry group at the UW as part of the UW Nuclear medicine program project grant. Key collaborators in the study include David Mankoff, M.D., Jeanne Link, M.D., and Kenneth Krohn, M.D., at the SCCA, and UW, and Brenda Kurland, a statistician at Fred Hutchinson Cancer Research Center. .

Grants to Linden, Mankoff and Krohn from The National Institutes of Health and the Mary Kay Ash Foundation funded the study.

Breast Feeding & Breast Cancer in African-American women

Posted on by
Reply

Investigators from the Boston University’s Slone Epidemiology Center have reported findings that may shed light on why African American women have a disproportionately higher risk of developing more aggressive and difficult-to-treat breast cancers, specifically estrogen and progesterone receptor negative (ER-/PR-) cancers.

The study, which appears online in Cancer Epidemiology, Biomarkers & Prevention, found that high parity (giving birth to two or more children) was associated with an increased risk of ER-/PR- cancer, but only among women who had not breastfed.

The findings were based on the ongoing Black Women’s Health Study, which has followed 59,000 African American women by biennial questionnaire since 1995.

In 14 years of follow-up, 318 women developed breast cancers negative for estrogen and progesterone receptors (ER-/PR-), while 457 developed breast cancers with estrogen and progesterone receptors (ER+/PR+). Giving birth to two or more children was associated with a 50 percent increase in the incidence of ER-/PR- breast cancer, but the association was not present among women who had breastfed.

According to the researchers, the results for ER+/PR+ breast cancer, which is more common among white women, were strikingly different. High parity was associated with a decreased risk, and breast feeding had no influence on that association.

“The higher incidence of ER-/PR- breast cancer in African American women may be explained in part by their higher parity and lower prevalence of breastfeeding relative to white women,” explained lead author Julie Palmer, ScD, MPH, a senior epidemiologist at the Slone Epidemiology Center and a professor of epidemiology at Boston University School of Public Health.

“Our results, taken together with recent results from studies of triple negative and basal-like breast cancer, suggest that breastfeeding can reduce risk of developing the aggressive, difficult-to-treat breast cancers that disproportionately affect African American women,” she said.

###

This study was supported by a grant from the National Cancer Institute of the National Institutes of Health.