COMMON OSTEOPOROSIS DRUGS ARE ASSOCIATED WITH A DECREASE IN RISK OF BREAST CANCER

COMMON OSTEOPOROSIS DRUGS ARE ASSOCIATED WITH A DECREASE IN RISK OF BREAST CANCER
SEATTLE – 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 today 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.
COMMON OSTEOPOROSIS DRUGS ARE ASSOCIATED WITH A DECREASE IN RISK OF BREAST CANCER
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).
COMMON OSTEOPOROSIS DRUGS ARE ASSOCIATED WITH A DECREASE IN RISK OF BREAST CANCER
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.
COMMON OSTEOPOROSIS DRUGS ARE ASSOCIATED WITH A DECREASE IN RISK OF BREAST CANCER
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.
COMMON OSTEOPOROSIS DRUGS ARE ASSOCIATED WITH A DECREASE IN RISK OF BREAST CANCER
The National Cancer Institute funded the study, which was conducted in collaboration with researchers at the University of Wisconsin Carbone Comprehensive Cancer Center.

Vaccine Extends Glioblastoma Patients' Survival in Phase II Trial

Vaccine Extends Glioblastoma Patients' Survival in Phase II Trial
A vaccine that turns the immune system against brain tumor cells bearing a genetic mutation that drives the most aggressive form of glioblastoma multiforme improved survival of patients in a phase II clinical trial, researchers at Duke University and The University of Texas MD Anderson Cancer Center reported today in the Journal of Clinical Oncology.

Eighteen newly diagnosed patients who were vaccinated after undergoing standard treatment - surgery followed by radiation and chemotherapy - had median overall survival of 26 months compared with 15 months for 17 patients in a control group who received standard treatment. Median survival for newly diagnosed patients with glioblastoma multiforme is 14.6 months.

Vaccinated patients also experienced a longer period before their disease progressed, 14.2 months, compared with 6.3 months for the control group. Side effects were limited mainly to irritation at the injection site.
Vaccine Extends Glioblastoma Patients' Survival in Phase II Trial

Vaccine Extends Glioblastoma Patients' Survival in Phase II Trial
This promising targeted therapy blocks a key molecular signal that drives the malignant features of these tumors," said Amy Heimberger, M.D., associate professor in MD Anderson's Department of Neurosurgery and co-lead author of the paper. "If a patient's tumor expresses the target of this vaccine, she usually has only a 5 percent chance to live for two years."

All patients in the trial had the target variation, called epidermal growth factor receptor variant III (EGFRvIII), which occurs in about a third of glioblastomas and also is found in breast, lung and head and neck cancers. The flawed gene produces a protein that aids tumor development, migration and resistance to chemotherapy and radiation. It is not found in normal tissue.

Out of 11 tumor recurrences analyzed from vaccinated patients, the EGFRvIII cells were completely gone in nine, indicating that the vaccine had done its job eliminating the most aggressive cells, said co-lead author John Sampson, M.D., Ph.D., professor of Neurosurgery at Duke.

Other findings hint at the vaccine's likely effectiveness against EGFRvIII. Of six patients who had an immune response to the vaccine as indicated by blood tests, overall survival was 47.7 months compared with 22.8 months for those lacking a response. Median survival had not been reached after 50 months among three patients who had a T cell response to the vaccine.

However, the limited size of the sample calls for cautious interpretation of these results, Heimberger said. The next step for the vaccine, known as CDX-110, is a large phase III clinical trial, Heimberger said, which is in the planning stage.
Vaccine Extends Glioblastoma Patients' Survival in Phase II Trial
The EGFRvIII variant was co-discovered by Bert Vogelstein, M.D., and Albert Wong, M.D., at Johns Hopkins University and Darrell Bigner, M.D., Ph.D., director of the brain tumor center at Duke and corresponding author of the JCO paper.

Glioblastomas have other molecular drivers, so tumors come back, which the authors say points to a need to develop vaccines that address more than one target.

Heimberger sees the addition of vaccines to glioblastoma treatment as one more way to convert the deadly tumors more of a chronic disease. Developments in recent years, including approval of the chemotherapy drug temozolomide, have extended expected survival from around seven months to 14.

Funding for the work came from the National Institutes of Health, the American Brain Tumor Association, Accelerate Brain Cancer Cure, the Brain Tumor Society, the Commonwealth Cancer Foundation, the Adam Singer Foundation, the Dr. Marnie Rose Foundation and Golfers Against Cancer.

Co-authors are Kenneth Aldape, M.D., of MD Anderson’s Department of Pathology; Raymond Sawaya, M.D., and Mark Gilbert, M.D., of MD Anderson’s Department of Neurosurgery, and Weiming Shi of the Office of Performance Improvement at MD Anderson; and Gary Archer, Ph.D., Allan Friedman, M.D., Henry Friedman, M.D., James Herndon II, Ph.D., Robert Schmittling, Roger McLendon, M.D., Duane Mitchell, M.D., Ph.D., David Reardon, M.D., and James Vredenburgh, M.D. from Duke.

Bigner, Heimberger and Sampson, along with Duke University and MD Anderson report potential conflicts of interest from consulting agreements, stock options and potential further licensing fees. The institutions have plans in place to manage them.

The Medical Research: What Breast Cancer Patients Need to Know

Introduction:

When discussing the surgical treatment of your breast cancer with you, your surgeon will discuss whether or not your breast cancer is invasive. Breast cancers can be confined within the lining of the endothelial cells along the breast duct (in-situ cancers); or it can start to spread beyond the breast duct (invasive cancers). This is important because the blood vessels and lymph vessels that potentially spread the cancer beyond the breast run along this area (See Figure 1). If the cancer has spread beyond the lining of the breast duct, and is picked up by the blood vessels or lymph vessels, then it can potentially spread elsewhere in the body, or “metastasize.” Lymph vessels are small channels that drain all the tissues of the body. Lymph vessels drain excess fluid back into your circulation. As lymph fluid drains back into your circulation, it goes through lymph nodes. Lymph nodes are collections of lymph tissue that have a high concentration of white blood cells, the cells in your body that fight infection and cancer. The lymph vessels of the breast drain into the lymph nodes in your axilla (underneath your arm), and sometimes into the lymph nodes along your sternum, (or breastbone), and above your clavicle (collarbone) (See Figure 2).
What Breast Cancer Patients Need to Know
What Breast Cancer Patients Need to Know
Axillary Lymph Node Dissection:

Traditionally, if your breast cancer is invasive, an axillary lymph node dissection is recommended by your surgeon in order to see if the cancer has spread to the lymph nodes underneath the arm. During an axillary lymph node dissection, the surgeon makes an incision underneath your arm, and removes the bulk of the lymph node tissue that drains from the breast. The lymph node tissue is then sent to the laboratory, and a pathologist looks at the lymph nodes under a microscope and determines if any of them contain cancer. On average, approximately 10 to 15 lymph nodes are removed with this operation. An axillary lymph node dissection usually requires an overnight stay in the hospital. Since the remaining tissues underneath the arm tend to “leak” some lymph fluid when the lymph nodes are removed, a drain is left in place for the first 2-3 weeks after the operation until the area heals. The drain is a flexible plastic tube that exits the skin, and is connected to a plastic collection bulb. When the drainage diminishes to a certain amount, the drain is removed in the clinic. After you go home you are given physical therapy exercises to maintain strength and flexibility in your shoulder while this area heals. Approximately 5-10% of the patients who undergo an axillary lymph node dissection experience chronic problems related to the dissection such as arm swelling (lymphedema), or pain or discomfort in the area of the dissection. Almost all women will have some residual numbness under the inside of the arm.

Sentinel Lymph Node Biopsy:

A sentinel lymph node biopsy is a new technique. This was developed as a test to determine if breast cancer has spread to the lymph ducts or lymph nodes in the axilla without having to do a traditional axillary lymph node dissection. Experience has shown us that the lymph ducts of the breast usually drain to one lymph node first, before draining through the rest of the lymph nodes underneath the arm. That first lymph node is called the sentinel lymph node. That is the lymph node that helps sound the warning that the cancer has spread. Lymph node mapping helps identify that lymph node, and a sentinel lymph node biopsy removes only that lymph node. The sentinel lymph node is identified in one of two ways, either by a weak radioactive dye (technetium-labeled sulfur colloid) that can be measured by a hand held probe, or by a blue dye (isosulfan blue) that stains the lymph tissue a bright blue so it can be seen. Most breast cancer surgeons use a combination of both dyes. This procedure is new. The “best” way to administer the dye, which dye to use, and the benefits and risks of the procedure in various situations is still being studied. A traditional axillary lymph node dissection is the “tried and true” method, and is still considered the “gold standard”.

Advantages:

The advantages to the sentinel lymph node procedure are many. There is no need to stay overnight in the hospital. There is no need for a drain, or physical therapy exercises. Your recuperation from the procedure is faster. You are typically doing your regular activities within a few days, and the incision is well healed within a few weeks. A sentinel lymph node biopsy can lead to a more accurate assessment of whether the cancer has spread to the lymph nodes. In a traditional axillary dissection, the pathologist receives at least 10 lymph nodes or more; there is no way of telling which one is the sentinel lymph node. So the pathologist makes one cut in each lymph node and looks for cancer. When the pathologist receives only one, or a few, lymph nodes from a sentinel lymph node procedure, he or she can make many cuts through that lymph node to look for cancer. A negative sentinel lymph node(s) indicates a >95% chance that the remaining lymph nodes in the axilla are also cancer free. Therefore, there is no need to undergo a full axillary lymph node dissection, or to risk the long term complications and side effects from an axillary dissection.


What to Expect:

If you decide to undergo the procedure, the morning of your operation, you will go see a nuclear medicine specialist who is a physician specifically trained in injecting the radioactive dye used for the procedure. The injections are done into the area of the breast where the tumor is, and/or around the nipple areolar complex of the breast. You will then return to the nuclear medicine department a few hours later, and pictures will be taken which show the pathways the dye takes as it leaves the breast. (See Figure 3) This will help guide your surgeon in identifying the sentinel lymph node. Then you will proceed to the operating room. At the beginning of the operation, your surgeon will inject the blue dye. The surgeon then makes an incision underneath your arm in the area of the axillary lymph tissue. A hand-held sterile probe measures areas that have the radioactive dye. (See Figure 4) The lymph nodes that have taken up the radioactive dye, or are stained with the blue dye, are removed. Usually one to three nodes are removed. These nodes are sent to the pathologist, who then looks at them under a microscope to see if the sentinel node contains cancer. Your incision is closed, and there is no need for a drain. There is no need for physical therapy exercises. Unless you are having another operation done which requires that you stay overnight, you can go home from the hospital that day. The sentinel lymph node biopsy can be done in combination with a lumpectomy, or a mastectomy. The procedure is successful in >90% of those patients whom we think are good candidates for the procedure. If the procedure is unsuccessful in identifying the sentinel node, a full axillary dissection is done.
What Breast Cancer Patients Need to Know
What Breast Cancer Patients Need to Know
Who Shouldn’t Undergo the Procedure:

Unfortunately, the sentinel lymph node biopsy procedure can’t be performed on everyone with an invasive breast cancer. People who have had radiation therapy or surgery in their breast or axilla should not undergo the technique, as changes in the breast and axilla from the radiation therapy or surgery may make the results inaccurate. People who have enlarged lymph nodes underneath their arm, or people who we know already have breast cancer metastatic to their axillary lymph nodes should undergo a traditional axillary lymph node dissection. People who already have had a mastectomy can’t undergo the procedure because there is no accurate way to inject the dye to identify the lymph node. People with large tumors (greater then 5cm) have a higher incidence of lymph node spread of their cancer, and may be better served by a traditional lymph node dissection. They should discuss this with their surgeon. People, in whom it will be difficult to accurately inject the dye, would likely be better served by a full axillary lymph node dissection. This includes those people in whom we are unable to find the primary breast tumor (an “occult” malignancy), and people in whom the tumor is dispersed through more then one area of the breast (a multifocal tumor).

If the Sentinel Lymph Node is Positive:

If the pathology results show that the breast cancer has spread to the sentinel lymph node, then typically you will need to return to the operating room to undergo a complete axillary lymph node dissection. This is done to remove the remaining lymph nodes, which may contain cancer. Since the majority of patients with breast cancer involving lymph nodes receive chemotherapy, the new question for breast cancer specialists has been whether or not it matters if there is cancer in any of the other lymph nodes within the axilla. The answer is that we don’t know yet. There is currently a large national clinical trial called Z0011, which is evaluating exactly that question. In this trial some patients are chosen (randomized) to receive a full axillary lymph node dissection if their sentinel lymph node is positive. Some patients are chosen to not undergo any further lymph node dissection, and they are carefully watched. All of these patients will receive chemotherapy. The two groups of patients will be compared to see if there is a benefit to doing the full axillary dissection if the sentinel lymph node is positive. Or, alternatively, they will be compared to see if there is a detriment to not doing a full axillary dissection if the sentinel lymph node is positive. This is still experimental, and should only be done under controlled circumstances after being enrolled in this trial by a participating breast cancer surgeon. Doing a full axillary lymph node dissection if the sentinel lymph node is positive is still considered “the standard of care” with which all patients should be treated. To do otherwise, risks under treating your breast cancer.


Who Should Do the Procedure:

One of the factors that influences the results obtained with the procedure, is the qualification of the breast surgeon doing the procedure. Initial studies have shown that most surgeons need to do 20-30 sentinel lymph node biopsy procedures before obtaining accurate results using the technique. Surgeons can perform these cases during an accredited residency or fellowship at an institution that does a large number of these cases a year. Alternatively, surgeons attend a conference to learn the technique, then acquire these 20-30 cases as part of a training protocol. During the training period, the surgeon will perform the sentinel lymph node biopsy, and then complete a full axillary lymph node dissection at the same operation. After obtaining the pathology results, the surgeon can then determine if the sentinel lymph node was correctly identified. In addition, the surgeon can determine that the cancer was found in the sentinel node, and not in the lymph nodes that would otherwise have been left behind (false negative rate). After a surgeon has done 20-30 cases in which the sentinel lymph node is identified in >90% of the cases, and the false negative rate is less then 5%, then the surgeon “goes off protocol”, and does sentinel lymph node biopsies without a full axillary dissection. Until the surgeon has completed a large number of cases, and determined her/his accuracy for doing the technique, any cases done “off protocol” may inaccurately determine if there has been spread of cancer to the axillary lymph nodes. It is therefore important, to ask your surgeon if they have done a large number of cases during an accredited residency or fellowship, or if they have completed their learning protocol for the technique. No matter how the training for doing the procedure was acquired, there is some evidence to show that the surgeons who continue to perform this procedure on a regular basis, will have more accurate results from the technique

Summary:

Invasive breast cancer can spread through the lymph ducts and blood vessels to other areas of the body. The sentinel lymph node is the first lymph node that the lymph ducts drain into. Whether or not the cancer has spread to the sentinel lymph node indicates whether the cancer has started to spread beyond the breast. A new technique called sentinel lymph node biopsy identifies this lymph node, and allows only this lymph node to be removed. Removing only the sentinel lymph node can allow breast cancer patients to avoid many of the complications and side effects associated with a traditional axillary lymph node dissection. Patients with invasive breast cancer should discuss sentinel lymph node biopsy with their surgeon.

The Medical Letter on Drugs and Therapeutics

The Medical Letter on Drugs and Therapeutics
The Medical Letter on Drugs and Therapeutics (commonly referred to as The Medical Letter) is a scientific journal providing evaluations of drugs. It has a print and electronic circulation of well over 450,000 subscribers in 125 countries worldwide.

It is published biweekly (26 issues/year) in several languages: English (US and Canadian editions), French (Canadian and European editions), Italian, Japanese, and Spanish.

The Medical Letter is published by The Medical Letter, Inc., which also publishes the monthly Treatment Guidelines from The Medical Letter.

Articles for The Medical Letter are drafted by either an editor or external consultant using both published and available unpublished studies that are reviewed for methodological rigor with special attention to the results of clinical trials. A preliminary draft is circulated to every member of the advisory board and 10-20 other investigators with relevant clinical or experimental experience with the article's topic. Drafts are also provided to the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC), all first authors of articles cited in the text, and to the pharmaceutical companies that manufacture the drug, or similar compounds. The evaluation of each drug includes a discussion of its efficacy, side effects, and a comparison with older, more established agents. The final version of the paper includes comments from the reviewers and is checked and edited for accuracy and readability.
Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

Cool Girls and The Medical Letter on Drugs and Therapeutics

 
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