No Surrender Breast Cancer Foundation by Survivor ~ for Survivor Message Forum

Searching for answers

bottkota — Fri, 12 Mar 2010 21:24:09 GMT

As chemo continues to drone on and I continue to get sick and tired of being sick and tired am starting to consider giving myself a "break" from all of this and pursue a PARP trial. I know that with TN bc that chemo is my only "option" but really doesn't it seem praciticle to get a break and not wait for your body to become "toxic" or the drugs to stop working because the cancer has become resistant to the drugs. The abraxane, gemzar and avastin have been working and I will have another CT scan on the 25th, do you ever not see lymph nodes on a scan or because there is still cancer in them they light up? How fast does TN grow after stopping chemo for a short period of time? Is it wise to stop chemo with TNBC???? I am just so tired of all of this and just want a break, I want some normalcy, I want my hair back, even if it's a GI Jane sort of look. I want to enjoy the summer with my kids but this chemo keeps knocking me down. Do I seek a different oncologist, or do I just sit back and see what the next scan shows? Tired of it all. sorry for the rant, just needed to get it off my chest. Seems that every time I talk to my husband about this I just cry. Is wishing for a break like giving up on my life? Thanks again for letting me vent! I feel a little bit better!

Cathi

Forum: ~Club Mets~

Latest from FDA re: oral bisphosphonate meds and subtrochanteric femur fractures

muffy — Fri, 12 Mar 2010 00:44:53 GMT

FDA Drug Safety Communication: Ongoing safety review of oral bisphosphonates and atypical subtrochanteric femur fractures

Safety Announcement

Additional Information for Patients

Additional Information for Healthcare Professionals

Safety Announcement

Patients and healthcare professionals may have questions about oral bisphosphonate medications and atypical subtrochanteric femur fractures fractures in the bone just below the hip joint. Oral bisphosphonates are commonly prescribed to prevent or treat osteoporosis in postmenopausal women. Common brand names of medications in this class include Fosamax, Actonel, Boniva, and Reclast.

Recent news reports have raised the question about whether there is an increased risk of this type of fracture in patients with osteoporosis using these medications. At this point, the data that FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures. FDA is working closely with outside experts, including members of the recently convened American Society of Bone and Mineral Research Subtrochanteric Femoral Fracture Task Force, to gather additional information that may provide more insight into this issue.

Based on published case reports of atypical subtrochanteric femur fractures occurring in women with osteoporosis using bisphosphonates, FDA, in June 2008, requested information from all bisphosphonate drug manufacturers regarding this potential safety signal. All available case reports and clinical trial data were requested. FDA's review of these data did not show an increase in this risk in women using these medications.

In addition, FDA reviewed a December 2008 article in the Journal of Bone and Mineral Research by Abrahamsen et al¹, that analyzed data from two large observational studies in patients with osteoporosis. The authors concluded that atypical subtrochanteric femur fractures had many similar features in common with classical osteoporotic hip fractures, including patient age, gender, and trauma mechanism. The data showed that patients taking bisphosphonates and those not taking bisphosphonates had similar numbers of atypical subtrochanteric femur fractures relative to classical osteoporotic hip fractures.

This communication is in keeping with FDA's commitment to inform the public about its ongoing safety review of drugs. The agency will continue to review new information as it becomes available and will update the public once the agency's review is complete.

Healthcare professionals should continue to follow the recommendations in the drug label when prescribing oral bisphosphonates. Patients should not stop taking their medication unless told to do so by their healthcare professional. Patients should talk to their healthcare professional about any concerns they have with these medications.

Additional Information for Patients

If you currently take an oral bisphosphonate you should:

Not stop taking your medication unless told to do so by your healthcare professional.
Talk to your healthcare professional if you develop new hip or thigh pain or have any concerns with your medications.
Report any side effects with your bisphosphonate medication to FDA's MedWatch program using the information at the bottom of the page in the "Contact Us" box.

Additional Information for Healthcare Professionals

FDA recommends that healthcare professionals should:

Be aware of the possible risk of atypical subtrochanteric femur fractures in patients taking oral bisphosphonates.
Continue to follow the recommendations in the drug label when prescribing oral bisphosphonates.
Discuss with patients the known benefits and potential risks with using oral bisphosphonates.
Report any adverse events with the use of oral bisphosphonates to FDA's MedWatch program using the information at the bottom of the page in the "Contact Us" box.

References:

1. Abrahamsen B., Eiken P., Eastell R. Subtrochanteric and Diaphyseal Femur Fractures in Patients Treated With Alendronate: A Register-Based National Cohort Study. J Bone Miner Res. 2009 Jun;24(6):1095-102.

----------------------------------------

Oral Bisphosphonates: Ongoing Safety Review of Atypical Subtrochanteric Femur Fractures

Audience: Orthopedic healthcare professionals, patients

FDA notified healthcare professionals and patients that at this point, the data that FDA has reviewed have not shown a clear connection between bisphosphonate use and a risk of atypical subtrochanteric femur fractures. FDA is working with outside experts, including members of the recently convened American Society of Bone and Mineral Research Subtrochanteric Femoral Fracture Task Force, to gather more information and evaluate the issue further.

FDA recommends that healthcare professionals follow the recommendations in the drug label when prescribing oral bisphosphonates.

Patients should continue taking oral bisphosphonates unless told by their healthcare professional to stop. Patients should talk to their healthcare professional if they develop new hip or thigh pain or have any concerns with their medications.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm204127.htm

Forum: Breaking Breast Cancer News

Scientific Proof Backs Before Forty!

nosurrender — Thur, 11 Mar 2010 16:54:47 GMT

Breast Cancer Screening: MRI Sensitive, No Added Value With Mammography, Study Suggests

ScienceDaily (Mar. 8, 2010) Do we need a revision of current recommendations for breast cancer screening? According to a recent prospective multicenter cohort study published in the Journal of Clinical Oncology, this appears advisable at least for young women carrying an increased risk of breast cancer. The results of the EVA trial confirm once more that magnetic resonance imaging (MRI) is substantially more accurate for early diagnosis of breast cancer than digital mammography or breast ultrasound: MRI is three times more sensitive for breast cancer than digital mammography.

For the EVA trial, almost 700 women were enrolled. Aim of the trial was to refine existing guidelines for surveillance of women at high and moderately increased risk of breast cancer. Findings suggest that in these women, MRI is essential for early diagnosis -- and that a mammogram or an ultrasound examination does not increase the "cancer yield" compared to what is achieved by MRI alone. Researchers conclude that annual MRI is not only necessary, but in fact sufficient for screening young women at elevated risk of breast cancer. In women undergoing screening MRI, mammograms will have no benefit and should be discontinued. Moreover, MRI screening is important not only for women at high risk, but also for those at moderately increased risk.

Between 2002 and 2007, the EVA trial recruited 687 women who carried a moderately increased risk of breast cancer (lifetime risk of 20% and over). Women underwent 1679 screening rounds consisting of annual MRI, annual digital mammography and half-annual screening ultrasound examinations. During this time span, 27 women received a new diagnosis of invasive cancer or DCIS (Ductal Carcinoma In Situ).

Of all imaging methods under investigation (digital mammography, ultrasound and MRI), MRI offered by far the highest sensitivity: MRI identified 93% of breast cancers. 37% of cancers were picked up by ultrasound. The lowest sensitivity was achieved by digital mammography, which identified only one-third of breast cancers (33%). These results confirm once more that MRI is essential for surveillance not only of women at high risk, but also for women at moderately increased risk of breast cancer. Moreover, the results contradict current guidelines according to which mammography is considered indispensable for breast cancer screening. One aim of the EVA trial was to question this concept and to ask whether it is still appropriate to require that MRI should only be used in addition to mammography. The results speak for themselves: If an MRI is available, then the added value of mammography is literally negligible. Researchers conclude that MRI is necessary as well as sufficient for screening young women at elevated risk of breast cancer. Since mammography appears to be unnecessary in women undergoing MRI, its use is no longer justifiable, and current guidelines should be revised to reflect this.

Current guidelines questionable

Current guidelines for women at high familial risk of breast cancer recommend annual MRI (with or without ultrasound) and annual MRI starting at age 25-30. "These guidelines were set up based on little or no scientific evidence, and mainly reflect expert opinion," summarizes Prof. Christiane Kuhl, radiologist at the University of Bonn and principal investigator of the EVA trial. "In the light of the results of the EVA trial, such recommendations should be revisited." This seems even more important because digital mammography uses x-rays (ionizing radiation) to detect breast cancer. "The radiation dose associated with regular mammographic screening is clearly acceptable and safe," underscores Kuhl. "However, regular mammographic screening usually starts at age 40-50." The situation is different if systematic annual mammographic screening is started at age 25-30. "Not only because these women will undergo more mammograms and therefore will experience a cumulative lifetime radiation dose that will be substantially higher, but also because the breast tissue of young women is more vulnerable to the mutagenic effects of radiation." This appears to be especially true for BRCA mutation carriers. "Accordingly, we impose more radiation on less radiation-tolerant breast tissue -- for a very limited, if any, diagnostic benefit." Therefore, Kuhl advocates a revision of existing guidelines: "It is no longer justifiable to insist on annual mammographic screening women in their thirties if they have access to screening MRI."

MRI is a mature technology

In the past, MRI was used strictly in addition to mammography only. The allegedly high rate of "false positive" diagnoses and the allegedly insufficient sensitivity for DCIS were the main reason to discourage its use as a stand-alone method for breast cancer screening. "In this multicenter trial, with basic quality assurance implemented not only for mammography, but also for MRI, we were able to prove that false positive diagnoses are avoidable if MRI studies are interpreted with adequate radiologist expertise." In the EVA cohort, the Positive Predictive Value achieved with MRI was already even higher than that of mammography or breast ultrasound. "Moreover, we found that MRI offered the highest sensitivity especially for DCIS," adds Dr. Kuhl. "It is simply wrong to state that we need a mammogram to detect intraductal cancer."

Kuhl et al. Prospective Multicenter Cohort Study to Refine Management Recommendations for Women at Elevated Familial Risk of Breast Cancer: The EVA Trial. Journal of Clinical Oncology, 2010; DOI: 10.1200/JCO.2009.23.0839

Forum: The Before Forty Initiative & The Sister Corps

No Recon? No Problem!

nosurrender — Mon, 08 Mar 2010 16:14:11 GMT

Ms. Theron's helpful fashion advice for those who have chosen not to reconstruct...

Forum: Your Surgery & Breast Reconstruction

Highlights . . . More

edge — Mon, 08 Mar 2010 16:10:59 GMT

Hope Happens Here

Fact Checks

Evidence Reviews

What You Need To Know

Forum: The Cutting Edge

Advanced Breast Cancer Site

Indigoblue — Mon, 08 Mar 2010 02:26:31 GMT

Inspire.com, Advanced Breast Cancer...
http://www.inspe.com/groups/advanced-breast-cancer.html

This site seems, in my opinion, a great place for Mets...

Thank you Edge, and Analemma. This appears to be an informative site for anyone experiencing Advanced Breast Cancer or Mets. I never heard of it, until now, and found it to be an extremely uplifting site. Like all Breast Cancer sites, you must be selective about what you read...I think this site is pretty fantastic!

Love,
Indi

Forum: ~Club Mets~

Zippidy Doo Da!

nosurrender — Fri, 05 Mar 2010 22:54:47 GMT

Like our new look?
You can thank our Constantine! THE COMPUTER WHIZ!!!!!!!!!

More to come!

Forum: Site Information

Treatment to prevent Invasive Cancers

nosurrender — Fri, 05 Mar 2010 16:51:33 GMT

Trial Launched to Test New Treatment for Pre-Invasive Breast Cancer

ScienceDaily (Mar. 2, 2010) Can a drug that has been used to treat malaria for years possibly be used to treat breast cancer before it becomes invasive? That's what researchers at George Mason University's Center for Applied Proteomics and Molecular Medicine (CAPMM) and Inova Breast Care Institute (IBCI) are trying to prove.

In January, the IBCI and CAPMM launched the PINC Trial, short for Preventing Invasive Breast Neoplasia with Chloroquine. This three-year clinical trial will test the effectiveness of the anti-malarial drug chloroquine in treating 90 women with ductal carcinoma in situ (DCIS), a type of breast cancer in which the cancer cells start in the milk ducts but have not yet become invasive and spread in the breast. Once the cancer cells start to spread in the breast and throughout the body, the condition is considered invasive and can often be fatal.

With an estimated 254,650 patients diagnosed in 2009 alone, breast cancer is the most common form of cancer in women according to statistics by the American Cancer Society. Approximately one quarter of those patients will have DCIS. Many more women are being diagnosed with DCIS, non-invasive breast cancer, with the routine use of screening mammography.

According to Kirsten Edmiston, MD, the trial's principal investigator and medical director of cancer services at Inova Health System, the trial is designed to prevent breast cancer cells from becoming deadly by killing pre-invasive cancer cells using a novel therapy with chloroquine, which has been used to treat malaria in the past.

"We have identified a particular cellular process called autophagy that is very involved in the survival of DCIS. In pre-clinical work, our team found that if we block autophagy in DCIS cells with chloroquine, that it kills the cells so that they're not able to become invasive," says Edmiston. "What this trial is proposing is to treat DCIS patients with chloroquine, an autophagy blocker before they receive standard of care surgery to treat their DCIS disease. We believe that the treatment will kill the DCIS cells before they become invasive and shrink the size of the DCIS. We may be able to prevent someone from needing a mastectomy and offer them breast conserving surgery."

Once patients have consented and enrolled, the size of their breast tumor will be measured through a non-invasive imaging technique called magnetic resonance imaging (MRI). Tissue samples will be taken from patients by Inova's doctors and transported to CAPMM for analysis. The PINC trial will combine chloroquine with Tamoxifen depending on the patient's tumor profile. After treatment, the MRI will be repeated to see if the tumor has shrunk and the patient will then proceed with surgery and follow up therapy.

What made the researchers think to use a malaria drug to treat breast cancer? According to Ginny Espina, a CAPMM research assistant professor, it works by starving the cancerous cells.

"Pre-cancerous cells have adapted to survive inside the milk duct without a blood supply and with very few nutrients. They overcome starvation through a process called autophagy. It's a way for a cell to make its own food and store it in a 'cookie jar.' In the breast ducts, the DCIS cells use these 'cookies' to survive and potentially spread. Simply put, chloroquine goes into the cell's 'cookie jars' and prevents the cells from using that food so that they eventually die from starvation," says Espina.

Of note, researchers are also using chloroquine in patients with unique types of brain tumors.

The treatment of DCIS is controversial because most DCIS lesions remain dormant and do not become invasive. Physicians do not want to over treat DCIS and cause unnecessary side effects if the DCIS does not become aggressive. However, chloroquine is a relatively safe treatment that does not have the severe side effects of typical chemotherapy.

"I think the most exciting thing is that we are able to offer women a new clinical trial using a well tolerated therapy in a new way to help prevent the development of invasive breast cancer and hopefully, ultimately, it will keep them from needing any additional treatment or surgery," says Edmiston. "We look forward to a future where all breast cancer can be prevented or destroyed."

The clinical study is being funded by George Mason University and Inova Health System. This study is based on scientific findings made under a Department of Defense funded breast cancer grant to George Mason University (Lance Liotta MD, PhD) in partnership with Inova.

Forum: DCIS/LCIS and "pre" Cancers

TNBC TARGETTED BREAKTHROUGH

nosurrender — Fri, 05 Mar 2010 16:40:11 GMT

New Subtype of Breast Cancer Responds to Targeted Drug

ScienceDaily (Mar. 2, 2010) A newly identified cancer biomarker could define a new subtype of breast cancer as well as offer a potential way to treat it, say researchers at Washington University School of Medicine in St. Louis.

Their findings will be published in the March 1 online early edition issue of the Proceedings of the National Academy of Sciences.

The research could further refine what recent breast cancer research has concluded: that breast cancer is not one disease, but many. So far, research has firmly established that at least five subtypes of breast cancer exist, each having distinct biological features, clinical outcomes and responses to traditional therapies.

The biomarker identified by the Washington University researchers is found frequently in breast cancers and especially in those that have poorer outcomes. It stems from overactivation of a gene called LRP6 (low-density lipoprotein receptor-related protein 6), which stimulates an important cell-growth signaling pathway. LRP6 can be inhibited by a protein discovered in the same laboratory, which could become an effective drug against the breast cancer type, the researchers say.

"We found increased expression of the LRP6 gene in about a quarter of breast cancer specimens we examined, and we think LRP6 overexpression could be a marker for a new class of breast cancer," says Guojun Bu, Ph.D., professor of pediatrics and of cell biology and physiology. "In addition, we found that this biomarker is often associated with breast cancers that are either harder to treat or more likely to recur. We already have an agent that seems to be effective against LRP6-overexpressing tumors, which could someday become a therapy for tumors that right now have few treatment options."

The research was conducted primarily by Chia-Chen Liu, a graduate student in the Bu lab, who is a fellow in the Cancer Biology Pathway Program at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.

The researchers' analysis of human breast cancer tissue samples found significant increases in LRP6 levels in 20 percent to 36 percent of the tumors. LRP6 was increased more frequently in ER (estrogen receptor)-negative or HER2 (human epidermal growth factor receptor 2)-negative samples. LRP6 was also increased more frequently in so-called triple-negative breast tumor samples, which test negative for ER, HER2 and PR (progesterone receptor).

In general, patients who have triple-negative breast cancers have an increased risk of disease recurrence after initial treatment and a poorer prognosis. Furthermore, although ER-positive and HER2-positive tumors can be targeted with specific therapies, ER-negative and HER2-negative tumors cannot. So it appears that LRP6 overexpression is often associated with tumors that are currently difficult to treat, says Bu.

Research in the lab had earlier discovered a protein that binds to and inhibits LRP6. This study showed that the protein, called Mesd (mesoderm development), was able to slow the growth of breast cancer cells in the laboratory and to inhibit mammary tumor growth in laboratory mice.

Importantly, mice treated with Mesd did not experience any of the known side effects, such as bone lesions, skin disorders or intestinal malfunctions, associated with inhibition of this growth pathway.

"Our work introduces Mesd as a promising antitumor agent that might be further developed for breast cancer therapy," Bu says. "It would be analogous to such successful breast cancer therapies as Herceptin (trastuzumab), which specifically targets HER2-positive breast cancer."

The researchers also found that a small segment of Mesd has the same effect as the larger molecule. This segment, or peptide, is more stable than the whole protein molecule and can be easily synthesized.

The researchers have patented the protein and the peptide through the university's Office of Technology Management. Recently, Raptor Pharmaceutical Corp. licensed Mesd from the university to develop it for clinical use.

Funding from the National Institutes of Health and the Siteman Cancer Center supported this research.

Forum: Triple Negative Breast Cancer

Bilateral should be considered for some...

nosurrender — Fri, 05 Mar 2010 16:36:52 GMT

Contralateral Prophylactic Mastectomy Associated With Survival in Select Breast Cancer Patients

ScienceDaily (Mar. 3, 2010) Contralateral prophylactic mastectomy (CPM), a preventive procedure to remove the unaffected breast in patients with disease in one breast, may only offer a survival benefit to breast cancer patients age 50 and younger, who have early-stage disease and are estrogen receptor (ER) negative, according to researchers at The University of Texas M. D. Anderson Cancer Center.

Published online February 25 in the Journal of the National Cancer Institute, it's the first population-based study to find an association between the procedure and survival in any group of breast cancer patients. The findings should offer evidence to both the women making this often agonizing decision and the physicians responsible for their care.

According to Isabelle Bedrosian, M.D., assistant professor in M. D. Anderson's Department of Surgical Oncology, a growing number of breast cancer patients are opting for the procedure; recent statistics have shown that the rate of CPM in women with stage I-III breast cancer increased by 150 percent from 1998 to 2003 in the United States.

"In our clinic, we've seen a dramatic increase in the number of women requesting CPM, and across the breast cancer community, studies have shown that the utilization of the procedure is skyrocketing," said Bedrosian, the study's co-corresponding author. "Until now, we've counseled these patients on a very important, personal decision in a vacuum. With our study, our goal was to understand the implications of the surgery and who may benefit."

For the retrospective, population-based study, the researchers used the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry, the premier population-based cancer registry now representing 26 percent of the country's population, to identify 107,106 breast cancer patients who underwent a mastectomy for treatment, as well as a subset of 8,902 women who had CPM. All of the women were treated for stages I -- III breast cancer between 1998 and 2003. Patients were stratified for ER status, stage of disease and age. Breast cancer-specific survival served as the study's primary endpoint.

Rigorous analysis was paramount in the design of the study, said George J. Chang, M.D., assistant professor in M. D. Anderson's Department of Surgical Oncology.

"It was important to take a critical eye and look at all the different ways the data could be misinterpreted to ensure that biases were not impacting our findings," said Chang, the study's co-corresponding author. "Using multi-variable analysis as well as risk stratification, we did our analysis in many different ways -- through SEER, comparing the survival of these patients to that of the general population, as well as examining non-cancer related versus cancer-specific survival. All alternative analyses resulted in the same conclusion; we found one group for whom this surgery offers a true survival benefit."

The researchers found a clear survival benefit for a select group of women that represents less than 10 percent of the breast cancer population. Those younger than age 50 with stage I or II cancer with ER negative disease had a survival benefit of 4.8 percent at five years. However, both Bedrosian and Chang expect that future research will show increased survival benefit with longer follow-up in the population, as a patient's likelihood of getting a second breast cancer increases with time.

While the findings should serve as a guideline for breast cancer patients and their physicians to have an informed, medically-based discussion about CPM, they do not determine that CPM is medically inappropriate for all others with the disease, said the researchers.

"Our research found that breast cancer patients over the age of 60 can be reassured that they will not benefit from CPM," said Bedrosian. "However, there are other populations -- such as women between the age of 50 and 60 -- where the findings about the procedure remain less clear. In addition, for young women with early stage, estrogen receptive positive breast cancer who receive Tamoxifen for only five years, we really do not know whether they would derive a life-long protective effective from a second breast cancer event. Therefore, for some additional breast cancer patients, CPM may very well be a medically-appropriate option."

In addition, the researchers note, the study captured neither family history nor BRCA status; it also did not include DCIS, or stage 0 breast cancer patients.

In addition to Bedrosian and Chang, Chung Yuan Hu in the Department of Surgical Oncology, also authored the all-M. D. Anderson study.

Forum: Your Surgery & Breast Reconstruction

Even MORE proof on benefit of Bone Building Drugs!

nosurrender — Fri, 05 Mar 2010 16:34:28 GMT

Common Osteoporosis Drugs Are Associated With a Decrease in Risk of Breast Cancer, Study Finds

ScienceDaily (Mar. 3, 2010) Women who take some types of bone-building drugs used to prevent and treat osteoporosis may be at lower risk of breast cancer, according to a study by U.S. researchers published in the British Journal of Cancer.

The study found that women who used bisphosphonate drugs, such as Fosamax, Boniva and Zomita, for more than two years had a nearly 40 percent reduction in risk as compared to those who did not, according to lead author Polly Newcomb, Ph.D., M.P.H., head of the Cancer Prevention Program at Fred Hutchinson Cancer Research Center.

"This large study provides new evidence that the use of bisphosphonates is associated with a potentially important reduction in breast cancer risk," Newcomb said.

The protective effect was observed only among women who were not obese. "Obese women may have elevated estrogen levels, so underlying hormones may influence the ability of bisphosphonates to reduce breast cancer risk," Newcomb said.

The way in which these drugs may prevent breast cancer is not known, but several research observations may be relevant. "These drugs may affect cell function and be important in cell growth and death -- specifically the death of tumors or even premalignant disease," Newcomb said. Researchers have found that some kinds of bisphosphonates directly cause tumor apoptosis (cellular suicide), inhibit angiogenesis (prevent tumors from establishing a blood supply) and prevent tumor-cell adhesion (the ability of cancer cells to bind to one another).

The study involved nearly 6,000 Wisconsin women, aged 20 to 69. Half had been diagnosed with invasive breast cancer and, for comparison purposes, half had not. The women were interviewed about their bone health -- their history of fractures, whether they'd been diagnosed with osteoporosis and their history of bisphosphonate use.

Breast cancer risk factors such as first-degree family history of the disease, age at first birth, postmenopausal hormone use and body mass index were accounted for in the analysis. "Because we were able to account for important cofounders, these findings may reflect real benefits due to the anti-tumor mechanisms of these medications," the authors wrote.

The National Cancer Institute funded the study, which was conducted in collaboration with researchers at the University of Wisconsin Carbone Comprehensive Cancer Center.

NOTE: IT IS TIME TO ASK YOUR DOC ABOUT GETTING A BONE BUILDING DRUG FOR PROPHYLACTIC THERAPY!!!

Forum: Your New Life as a Survivor

ACUPUNCTURE HELPS EASE AI PAIN

nosurrender — Fri, 05 Mar 2010 16:31:45 GMT

Acupuncture May Relieve Joint Pain Caused by Some Breast Cancer Treatments

ScienceDaily (Mar. 5, 2010) A new study, led by researchers at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center, demonstrates that acupuncture may be an effective therapy for joint pain and stiffness in breast cancer patients who are being treated with commonly used hormonal therapies.

Results were published in the Journal of Clinical Oncology.

Joint pain and stiffness are common side effects of aromatase inhibitor therapy, in which the synthesis of estrogen is blocked. The therapy, which is a common and effective treatment for early-stage, hormone-receptor-positive breast cancer in post-menopausal women, has been shown in previous research to cause some joint pain and stiffness in half of women being treated.

"Since aromatase inhibitors have become an increasingly popular treatment option for some breast cancer patients, we aimed to find a non-drug option to manage the joint issues they often create, thereby improving quality of life and reducing the likelihood that patients would discontinue this potentially life-saving treatment," said Dawn Hershman, M.D, M.S., senior author of the paper, and co-director of the breast cancer program at the Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian Hospital/Columbia University Medical Center, and an assistant professor of medicine (hematology/oncology) and epidemiology at Columbia University Medical Center.

To explore the effects of acupuncture on aromatase inhibitor-associated joint pain, the research team randomly assigned 43 women to receive either true acupuncture or sham acupuncture twice a week for six weeks. Sham acupuncture, which was used to control for a potential placebo effect, involved superficial needle insertion at body points not recognized as true acupuncture points. All participants were receiving an aromatase inhibitor for early breast cancer, and all had reported musculoskeletal pain.

Among the women treated with true acupuncture, findings demonstrated that they experienced significant improvement in joint pain and stiffness over the course of the study. Pain severity declined, and overall physical well-being improved. Additionally, 20 percent of the patients who had reported taking pain relief medications reported that they no longer needed to take these medications following acupuncture treatment. No such improvements were reported by the women who were treated with the sham acupuncture.

"This study suggests that acupuncture may help women manage the joint pain and stiffness that can accompany aromatase inhibitor treatment," said Katherine D. Crew, M.D., M.S., first author of the paper, and the Florence Irving Assistant Professor of Medicine (hematology/oncology) and Epidemiology at Columbia University Medical Center and a hematological oncologist at NewYork-Presbyterian Hospital/Columbia University Medical Center. "To our knowledge, this is the first randomized, placebo-controlled trial establishing that acupuncture may be an effective method to relieve joint problems caused by these medications. However, results still need to be confirmed in larger, multicenter studies."

Forum: Endocrine/Hormonal Therapy

Pomegranate Reduces ER+ cancer growth

nosurrender — Fri, 05 Mar 2010 16:29:20 GMT

Natural Compounds in Pomegranates May Prevent Growth of Hormone-Dependent Breast Cancer

ScienceDaily (Jan. 6, 2010) Eating fruit, such as pomegranates, that contain anti-aromatase phytochemicals reduces the incidence of hormone-dependent breast cancer, according to results of a study published in the January issue of Cancer Prevention Research, a journal of the American Association for Cancer Research.

Pomegranate is enriched in a series of compounds known as ellagitannins that, as shown in this study, appear to be responsible for the anti-proliferative effect of the pomegranate.

"Phytochemicals suppress estrogen production that prevents the proliferation of breast cancer cells and the growth of estrogen-responsive tumors," said principal investigator Shiuan Chen, Ph.D., director of the Division of Tumor Cell Biology and co-leader of the Breast Cancer Research Program at City of Hope in Duarte, Calif.

Previous research has shown that pomegranate juice -- punica granatum L -- is high in antioxidant activity, which is generally attributed to the fruit's high polyphenol content. Ellagic acid found in pomegranates inhibits aromatase, an enzyme that converts androgen to estrogen. Aromatase plays a key role in breast carcinogenesis; therefore, the growth of breast cancer is inhibited.

Chen, along with Lynn Adams, Ph.D., a research fellow at Beckman Research Institute of City of Hope, and colleagues, evaluated whether phytochemicals in pomegranates can suppress aromatase and ultimately inhibit cancer growth.

After screening and examining a panel of 10 ellagitannin-derived compounds in pomegranates, the investigators found that those compounds have the potential to prevent estrogen-responsive breast cancers. Urolithin B, which is a metabolite produced from ellagic acid and related compounds, significantly inhibited cell growth.

"We were surprised by our findings," said Chen. "We previously found other fruits, such as grapes, to be capable of the inhibition of aromatase. But, phytochemicals in pomegranates and in grapes are different."

According to Gary Stoner, Ph.D., professor in the Department of Internal Medicine at Ohio State University, additional studies will be needed to confirm the chemopreventive action of Urolithin B against hormone-dependent breast cancer.

"This is an in vitro study in which relatively high levels of ellagitannin compounds were required to demonstrate an anti-proliferative effect on cultured breast cancer cells," said Stoner, who is not associated with this study. "It's not clear that these levels could be achieved in animals or in humans because the ellagitannins are not well absorbed into blood when provided in the diet."

Stoner believes these results are promising enough to suggest that more experiments with pomegranate in animals and humans are warranted.

Powel Brown, M.D., Ph.D., medical oncologist and chairman of the Clinical Cancer Prevention Department at the University of Texas M. D. Anderson Cancer Center, agreed with Stoner's sentiments and said these results are intriguing. He recommended that future studies focus on testing pomegranate juice for its effect on estrogen levels, menopausal symptoms, breast density or even as a cancer preventive agent.

"More research on the individual components and the combination of chemicals is needed to understand the potential risks and benefits of using pomegranate juice or isolated compounds for a health benefit or for cancer prevention," Brown said. "This study does suggest that studies of the ellagitannins from pomegranates should be continued."

Until then, Stoner said people "might consider consuming more pomegranates to protect against cancer development in the breast and perhaps in other tissues and organs."

PERSONAL NOTE: I was eating pomegranate seeds almost daily for a couple of years before my ER+ cancer showed up....

Forum: Invasive Cancers: Ductal and Lobular

FEVER FEW TO THE RESCUE...

nosurrender — Fri, 05 Mar 2010 16:25:04 GMT

Flower Power May Reduce Resistance to Breast Cancer Drug Tamoxifen

ScienceDaily (Feb. 27, 2010) Combining tamoxifen, the world's most prescribed breast cancer agent, with a compound found in the flowering plant feverfew may prevent initial or future resistance to the drug, say researchers at Georgetown Lombardi Comprehensive Cancer Center.

The finding, reported online Feb. 12 in The FASEB Journal, provides new insight into the biological roots of that resistance, and also tests a novel way to get around it.

"A solution to tamoxifen resistance is sorely needed, and if a strategy like this can work, it would make a difference in our clinical care of breast cancer," says the study's lead investigator, Robert Clarke, PhD, DSc, a professor of oncology and physiology & biophysics at Lombardi, a part of Georgetown University Medical Center (GUMC). Clarke is also the interim director of GUMC's Biomedical Graduate Research Organization.

Clarke added that the purified research chemical they tested, parthenolide, a derivative of feverfew, is being tested by other scientists as treatment for a variety of cancers, as well as other health conditions. Feverfew has long been a staple of natural medicine, and is particularly known for its effects on headaches and arthritis. Latin for "fever reducer," feverfew is a common garden bush with small daisy-like flowers.

"The chemical clearly has potential, and we ought to be able to figure out fairly quickly if it can help solve tamoxifen's resistance problem," Clarke says.

Tamoxifen is a treatment of choice for breast cancer that is estrogen receptor positive (ER+), meaning that the hormone estrogen drives cancer growth. Most newly diagnosed breast cancers -- about 70 percent -- fall into that category. But about half of these cancers do not initially respond to tamoxifen, which is designed to block the hormone from binding to the cell's protein receptor, and many patients that do respond are at risk for developing resistance and cancer relapse.

In this study, Clarke and a team of researchers set out to study if, as previous research had suggested, tamoxifen resistance is regulated by the protein complex NF-B (nuclear factor kappa B), which is often found to be over-expressed in ER+ breast cancer. NF-B is known to help cells survive when damaged. The researchers had earlier discovered that NF-B is over-expressed in cells that are resistant to tamoxifen, and they had found that resistance to another tamoxifen-like drug, fulvestrant, was controlled by a protein (Bcl2) that is, itself, regulated by NF-B.

"Our scientific quest was to see if blocking NF-?B affects tamoxifen resistance, and if it does, why?" says Clarke.

They conducted a variety of tests using parthenolide, which has been shown to act on NF-B. They found that in resistant breast cancer cells, the chemical blocked the activity of NF-B, making the cells sensitive once again to tamoxifen. They then silenced NF-B in tamoxifen resistant cells, and found that this had the same effect as using parthenolide.

They further found that increased activation of NF-B can alter sensitivity of tamoxifen by modulating the protein CASP8, which is involved in programmed cell death. That then affects Bcl2, which also helps push a damaged cell to die.

"When you give tamoxifen to a breast cancer cell, that is essentially a pro-death signal, because you are blocking the cell's access to estrogen, and the cell recognizes this is a mortal blow," Clarke says. "Such a damaged cell uses CASP8 and Bcl2 to trigger the cell machinery needed for dying.

"But the cell has ways to counteract the pro-death signal, and one important one is to activate NF-B, which can control expression of genes necessary for survival," he says. "Now the cell thinks it should be living, not dying."

Because NF-B controls CASP8 and Bcl2, it can turn those proteins essentially off, Clarke says. "The pro-survival signals override the pro-death signals."

Still, as much as this study advances the understanding of tamoxifen resistance, there is much that is not understood, he adds. "We don't know when NF-B becomes over-expressed in the transformation of tamoxifen-sensitive to a tamoxifen-resistant breast cancer cells, and we don't know of other adaptations the cell may have made," he says. "It is probably fair to say this is a hideously complex process."

To that end, Clarke cannot predict how many women who try a combination of tamoxifen and parthenolide will benefit. He says the science is much too early to make any recommendations and strongly warns women against adding feverfew supplements to their cancer treatment.

Still, he is hopeful. "Every breast tumor slightly different, but we know many do use NF-B because excess amounts of the protein are found in these cancers," he says. "That suggests they may be sensitive to targeted approaches that shut down this pro-survival signal."

Forum: Endocrine/Hormonal Therapy

New Triple Negative genetic treatment study

SoCalLisa — Fri, 05 Mar 2010 16:25:03 GMT

OVERVIEW

Background: Drug companies have developed an

array of drugs to attack cancer and other

conditions influenced by genetics, but its

difficult to tell which patients will respond

to which drugs.

Whats happening: A new study will sequence

the genomes of cancer tissue from 14 breast

cancer patients whose tumors have progressed

despite multiple treatments.

The future: Proponents of genomic medicine

think it will become increasingly possible to

use sequencing to steer individual patients to

the drugs most likely to work.

A Carlsbad biotechnology company is helping

launch an unusual cancer study that may

eventually lead to doctors tailoring

treatments to patients genes.

Life Technologies says the study involving

sequencing the genomes of 14 patients with a

tough-to-treat form of breast cancer is a

step toward a future of genomic medicine, a

decade after the sequencing of the first human

genome.

Its evidence of how quickly work in this area

is progressing, with the $2.6 billion that

went into the Human Genome Project reduced to

$6,000 per genome on Life Technologies latest

sequencing instrument.

This is a pretty amazing example of how far

these tools of genomics are moving into direct

patient applications, said Jeffrey Trent,

president of the Phoenix-based Translational

Genomics Research Institute, which is working

with Life Technologies on the project.

The company will announce the study today to

coincide with the opening of a two-day

conference on genomic medicine in La Jolla, at

which experts will discuss the latest

breakthroughs and the outlook for more

advances in the field.

Already, biotechnology research has created

numerous drugs that target genetic problems

that lead to cancer and other conditions. In

the case of breast cancer, at least a dozen

such drugs are on the market, said Dr. Daniel

D. Von Hoff, physician-in-chief at the

translational genomics institute.

A big problem, however, is that its difficult

to predict which drugs will work for a

particular patient. Thats where sequencing is

supposed to help.

For those mutations for which we do have

drugs, we can help the physician make more

informed decisions than theyre making today,

said Linh Hoang, director of personalized

medicine at Life Technologies.

The study could also help scientists identify

promising areas to explore for future drugs.

Its impossible to know ahead of time whether

the 14 patients have genetic patterns that

current drugs address, but researchers will

also look for similarities in the DNA of the

14.

It may lead to more targets that

pharmaceutical companies will want to design

drugs around, Hoang said.

The study will involve patients with whats

known as triple-negative breast cancer whose

tumors have progressed despite multiple

therapies. That type of cancer makes up about

a fifth of breast cancer cases and doesnt

respond to common drugs, such as Herceptin.

Patients will be enrolled by U.S. Oncology, a

Houston-area company that specializes in

cancer-treatment services, and Von Hoff said

the plan is to take the first 14 people who

meet the study criteria.

A spokeswoman for U.S. Oncology said the

company plans to enroll patients from about a

half-dozen of its sites with the highest

incidences of triple-negative cases. Sites in

Colorado, Oregon, Texas and Virginia have

already been identified.

Tissue samples will be obtained through

noninvasive surgery, Von Hoff said. Then the

patients will go home to await sequencing

results that should be produced within a few

weeks.

The idea is to then direct them to appropriate

treatment, but Von Hoff declined to predict in

how many cases that will be possible.

We dont know, Von Hoff said. We do know

there are more and more drugs out there for

patients who have mutations.

There have been other studies that sequenced

disease tumors, most notably an ongoing

government effort known as the Cancer Genome

Atlas that aims to produce comprehensive

genetic maps of at least 20 types of cancer.

What separates the new study is its attempt

use the data to drive treatment strategies,

not merely to collect information.

Its a different question, the genomics

institutes Trent said. This is a study about

how were going to start to use this in a

precision medicine approach.

A big effort will go into bioinformatic

analysis, which Von Hoff said will involve a

trillion pieces of data per patient. Hoang

said one project in lung cancer found 30,000

mutations.

In coming years, scientists expect the cost of

sequencing to decline and the sophistication

of the tools to improve to the point that

sequencing becomes more viable as a diagnostic

device.

Hoang said Life Technologies expects the cost

of the reagent chemicals that it sells, which

enable genome sequencing, to drop from $6,000

to $3,000 by the end of the year.

This is really laying the foundation for a

future that may take five or 10 years to

materialize, Hoang said. But it is truly

groundbreaking.

Thomas Kupper: (619) 293-1037;

thom.kupper@uniontrib.com

Forum: Breaking Breast Cancer News