Early Stage Testicular Cancer - Surveillance Is Best Follow-Up Strategy

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Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology
Article Date: 17 May 2013 - 0:00 PDT Current ratings for:
Early Stage Testicular Cancer - Surveillance Is Best Follow-Up Strategy

A long-term study of men with stage I seminoma, a common form of testicular cancer, suggests that surveillance for cancer recurrence, rather than additional chemotherapy or radiation therapy, is sufficient for the vast majority of patients who have undergone successful surgery for their cancer.

In a new long-term study conducted in Denmark, researchers analyzed a national clinical database and found that 99.6% of patients who only underwent surveillance (following a successful surgery) were alive after 10 years of being diagnosed with testicular cancer.

Surveillance means carrying out routine CT scans, physical exams, chest X-ray exams, and blood tests for a period of five years after surgery.

In some countries, such as Denmark (where the study took place), the preferred follow-up strategy is surveillance alone. In the U.S. half of patients undergo either radiotherapy or chemotherapy as follow-up treatment, while the other half only receive surveillance.

There has been a recent increase in the number of patients undergoing surveillance alone in the U.S., a trend that will likely continue following this new finding.

Treatment options such as chemotherapy or radiotherapy can cause very harmful side effects, including a higher risk of secondary cancers (such as leukemia). Therefore, other follow-up strategies that don't incur such drastic risks, such as surveillance alone, are preferred.

Mette Sakso Mortensen, MD, a PhD student at the Department of oncology at the Copenhagen University Hospital in Copenhagen, Denmark, said:

"To our knowledge, this study is the largest to address this issue in patients with stage I seminoma, and with the longest follow-up. Now we have solid proof that surveillance is safe and appropriate for most patients with this particular cancer.

We also characterized key prognostic factors for relapse, which can help us identify high-risk patients who may need adjuvant therapy instead of surveillance. However, in general, seminoma stage I patients can safely be followed on a surveillance program."

A total of 1,822 men with stage I seminoma, who underwent successful surgery were followed on a five year surveillance program. The researchers were able to follow the patients for an average of 15.4 years.

19.5 percent of the patients experienced a relapse, of whom 216 received radiotherapy while 136 received chemotherapy and only 3 underwent surgery.

The 10-year-cancer-specific survival rate was 99.6 percent, which translates into four men dying out of every 1,000 who underwent surveillance alone.

The risk of relapse increased among patients whose tumor size was bigger than 1.5 inches and spread to lymphatic vessels or blood, as well as those whose levels of a blood marker called human chorionic gonadotropin were high.

Even though testicular cancer is quite rare among the general population, it is the most common solid tumor among young men. Approximately 4,000 people will be diagnosed with stage I seminoma this year in the U.S.

ASCO President-Elect Clifford A. Hudis, MD, said:

"This important study is one of several recent reminders that sometimes "less is more? in patient care. Opting for surveillance spares patients, most of whom are young men, from the harmful side effects of chemotherapy and radiation without diminishing their chances for a long and healthy life."

Scientists at UC Davis found that frequent CT scanning for testicular cancer surveillance was associated with secondary malignancies.

Written by Joseph Nordqvist
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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Micrometastases Affect Breast Cancer Prognosis

Among women with early breast cancer, those with very small areas of cancer (micrometastases) in the axillary lymph nodes tend to have a higher risk of recurrence than those whose lymph nodes are completely free of cancer. These results were published in the Journal of Clinical Oncology.

Evaluation of the axillary (under the arm) lymph nodes for the presence of cancer is an important part of breast cancer staging. To assess the axillary lymph nodes, a surgeon will perform either an axillary lymph node dissection, in which many lymph nodes are surgically removed and evaluated, or a less extensive procedure known as a sentinel lymph node biopsy.

For some women, evaluation of the lymph nodes will reveal very small areas of cancer. Areas of cancer that measure between 0.2 mm and 2.0 mm are referred to as “micrometastases.” Even smaller areas of cancer are referred to as “isolated tumor cells.” The clinical significance of lymph node micrometastases and isolated tumor cells has been uncertain but was evaluated in a study conducted in Sweden.

The study collected information about the treatment and outcomes of 3,369 breast cancer patients. A total of 2,383 were node-negative, 107 had isolated tumor cells in the axillary lymph nodes, 123 had micrometastases, and 756 had macrometastases (larger areas of cancer in the lymph nodes).

Five-year survival without cancer recurrence was 87.1% among women with no lymph node metastases, 88.9% among women with isolated tumor cells, 79.6% among women with micrometastases, and 80.1% among women with macrometastases. Compared with node-negative women, overall survival was not significantly worse among women with micrometastases or isolated tumor cells, but was worse among women with macrometastases.

These results suggest that women with lymph node micrometastases have a higher risk of breast cancer recurrence than women with cancer-free lymph nodes. Isolated tumor cells in the lymph nodes did not appear to affect outcomes in this population.

Reference:?

Andersson Y, Frisell J, Sylvan M, de Boniface J, Bergkvist L. Breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes. Journal of Clinical Oncology [early online publication]. May 10, 2010.

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Male BRCA2 Carriers Have Increased Lifetime Risk of Breast Cancer

Men who carry the BRCA2 genetic mutation have a 7.1% chance of developing breast cancer by age 70 and an 8.6% chance of developing the disease by age 80, according to the results of a study published early online in the Journal of Medical Genetics.[1]

Inherited mutations in two genes—BRCA1 and BRCA2—have been found to greatly increase the lifetime risk of developing breast cancer (as well as ovarian cancer in women). Alterations in these genes can be passed down through either the mother’s or the father’s side of the family. Research is ongoing to determine the level of risk presented by these genetic mutations; however, very few studies have focused on male BRCA carriers.

In only the fourth study to do so, researchers from the UK assessed the lifetime risk of breast cancer among men with the BRCA2 mutation. Previous studies have suggested that the BRCA2 mutation places men at higher risk of breast cancer than the BRCA1 mutation.

Using a database that included all male first-degree relatives of BRCA2 carriers over the age of 20, the researchers identified 321 families with proven mutations and 905 male first-degree relatives of proven BRCA2 carriers. Performing a retrospective and prospective analysis of the data, the researchers ascertained that the risk of male BRCA2 carriers developing breast cancer by age 70 was 7.1% and by age 80 was 8.6%.

The researchers concluded that this risk was sufficient to warrant increased awareness about breast cancer among men in BRCA2 families.

Reference:

[1] Evans DG, Susnerwala I, Dawson J, et al. Risk of breast cancer in male BRCA2 carriers. Journal of Medical Genetics [early online publication]. June 28, 2010.

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Study Suggests Cutaneous Squamous Cell Carcinoma Carries Risk Of Metastasis And Death

Main Category: Cancer / Oncology
Also Included In: Dermatology
Article Date: 17 May 2013 - 2:00 PDT Current ratings for:
Study Suggests Cutaneous Squamous Cell Carcinoma Carries Risk Of Metastasis And Death

JAMA Dermatology Study Highlights

A study by Chrysalyne D. Schmults, M.D., M.S.C.E., of Brigham and Women's Hospital, Boston, and colleagues suggests cutaneous squamous cell carcinoma (CSCC) carries a low but significant risk of metastasis and death.

The ten-year retrospective cohort study was conducted at an academic medical center in Boston, and included 985 patients with 1,832 tumors. Main measures of the study were subhazard ratios for local recurrence, nodal metastasis, disease-specific death, and all-cause death adjusted for presence of known prognostic risk factors. The median follow-up was 50 months.

Local recurrence occurred in 45 patients (4.6 percent) during the study period; 36 (3.7 percent) developed nodal metastases; and 21 (2.1 percent) died of CSCC. Independent predictors for nodal metastasis and disease-specific death were tumor diameter of at least 2 centimeters, poor differentiation, invasion beyond fat, and ear or temple location. Perineural invasion, cancer spreading to the space surround a nerve, was also associated with disease-specific death, as was anogenital location. Overall death was associated with poor differentiation and invasion beyond fat, the study finds.

"Tumor diameter of at least 2 centimeters, invasion beyond fat, poor cellular differentiation, perineural invasion, and ear, temple, or anogenital location were risk factors for poor outcomes. These 5 risk factors may be among the most significant drivers of CSCC outcomes, but further studies are needed to replicate our findings" the authors conclude.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. JAMA Dermatol. Published May 15, 2013. 2013;149(5):541-547. Please use one of the following formats to cite this article in your essay, paper or report:

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Updated Guidelines Address Hormonal Therapy for Breast Cancer

Among postmenopausal women with hormone receptor-positive breast cancer, use of an aromatase inhibitor at some point in the course of adjuvant (post-surgery) treatment results in a lower risk of cancer recurrence than use of tamoxifen only. Based on these results, updated guidelines from the American Society of Clinical Oncology recommend consideration of aromatase inhibitor therapy for this group of patients.[1]??

Each year roughly 200,000 U.S. women are diagnosed with breast cancer. Many of these breast cancers will be hormone receptor-positive, meaning that they are stimulated to grow by the circulating female hormones estrogen and/or progesterone.

Treatment of hormone receptor-positive breast cancer often involves hormonal therapies that suppress or block the action of estrogen. These therapies include tamoxifen as well as agents known as aromatase inhibitors. Tamoxifen acts by blocking estrogen receptors, whereas aromatase inhibitors suppress the production of estrogen in postmenopausal women. Aromatase inhibitors include ArimidexR (anastrozole), FemaraR (letrozole), and AromasinR (exemestane).

Several large trials comparing aromatase inhibitors to tamoxifen have established the efficacy of aromatase inhibitors for the treatment of hormone receptor-positive breast cancers among postmenopausal women. Whether aromatase inhibitors are used as initial hormonal therapy or sequentially with tamoxifen, use of an aromatase inhibitor at some point during the course of adjuvant treatment has been shown to reduce the risk of breast cancer recurrence compared with tamoxifen alone.

Based on these results, the American Society of Clinical Oncology recently updated its hormonal therapy guidelines.? As recommended in the latest guideline, the panel recommends that “postmenopausal women with hormone receptor-positive breast cancer consider incorporating [aromatase inhibitor] therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine therapy treatment remain unresolved.”

Potential side effects of aromatase inhibitors that will need to be considered by the patient and her physician include bone loss and joint pain. Aromatase inhibitors also appear to be more likely than tamoxifen to cause increases in blood pressure and cholesterol levels.

Reference:

[1] Burstein HJ, Prestrud AA, Seidenfeld J et al. American Society of Clinical Oncology Clinical Practice Guidelines: Update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. Journal of Clinical Oncology [early online publication]. July 12, 2010.

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Bankruptcy An Increased Risk Following Cancer Diagnosis

Main Category: Cancer / Oncology
Also Included In: Public Health;??Health Insurance / Medical Insurance
Article Date: 17 May 2013 - 0:00 PDT Current ratings for:
Bankruptcy An Increased Risk Following Cancer Diagnosis

People diagnosed with cancer are more than two-and-a-half times more likely to declare bankruptcy than those without cancer, according to a new study from Fred Hutchinson Cancer Research Center. Researchers also found that younger cancer patients had two- to five-fold higher bankruptcy rates compared to older patients, and that overall bankruptcy filings increased as time passed following diagnosis.

The study, led by corresponding author Scott Ramsey, M.D., Ph.D., an internist and health economist at Fred Hutch, was published online as a Web First in the journal Health Affairs. The article will also appear in the journal's June edition.

Ramsey and colleagues, including a chief judge for a U.S. Bankruptcy Court, undertook the research because the relationship between receiving a cancer diagnosis and bankruptcy is less well understood than the much-studied link between high medical expenses and likelihood of bankruptcy filing.

"This study found strong evidence of a link between cancer diagnosis and increased risk of bankruptcy," the authors wrote. "Although the risk of bankruptcy for cancer patients is relatively low in absolute terms, bankruptcy represents an extreme manifestation of what is probably a larger picture of economic hardship for cancer patients. Our study thus raises important questions about the factors underlying the relationship between cancer and financial hardship."

For this study, researchers analyzed data from a population-wide registry of individuals over age 21 who lived in western Washington and who were diagnosed with cancer between Jan. 1, 1995 and Dec. 31, 2009. They were compared to a randomly sampled age-, sex-, and ZIP code-matched population of people without cancer. Cancer cases were identified using the Cancer Surveillance System of Western Washington, a population-based cancer registry based at Fred Hutch that is part of the National Cancer Institute's Surveillance Epidemiology and End Results Program (SEER).

The cancer and control cohorts were both linked with the records of the U.S. Bankruptcy Court for the Western District of Washington. The court serves 19 counties in western Washington, including all 13 counties represented in the Cancer Surveillance System of Western Washington. Researchers included Chapter 7 or Chapter 13 bankruptcy filings only.

"This is the strongest evidence we have between a disease and risk for severe financial distress," Ramsey said. "I've not seen other studies that linked databases of this quality."

Ramsey directs the Hutchinson Institute for Cancer Outcomes Research (HICOR), which is dedicated to health economics and cancer outcomes research. Its mission is to improve the efficiency and effectiveness of cancer prevention, early detection and treatment to reduce the economic and human burdens of cancer. HICOR is believed to be the first of its kind among comprehensive cancer centers nationwide.

Among the study's key findings: Between 1995 and 2009 there were 197,840 people in western Washington who were diagnosed with cancer and met the inclusion criteria for the study. Of those, 4,408 (2.2 percent) filed for bankruptcy protection after diagnosis. Of the matched controls who were not diagnosed with cancer, 2,291 (1.1 percent) filed for bankruptcy. Compared to cancer patients who did not file for bankruptcy, those who did were more likely to be younger, female and nonwhite. The youngest age groups had up to 10 times the bankruptcy rate as compared to the older age groups. The authors noted that because cancer is generally a sudden and unexpected event, the risk of bankruptcy is influenced by factors such as debt load before diagnosis, assets, presence and terms of health and disability insurance, number of dependent children, and incomes of others in the household at the time of the cancer diagnosis. "The youngest groups in the study were diagnosed at a time when their debt-to-income ratios are typically highest - often unavoidably, because they are paying off student loans, purchasing a home, or starting a business," the authors wrote. "All working-age people who develop cancer face loss of income and, in many cases, loss of employer-sponsored insurance, both of which can be devastating for households in which the patient is the primary wage earner." In contrast, people age 65 or older generally have Medicare insurance and Social Security benefits. These older people are likely to have more assets and possibly more income than working-age people. "However, it is likely that having stable insurance (specifically, coverage not tied to employment) plays a major role in mitigating the risk of bankruptcy for those over age sixty-five," the authors wrote. The proportion of cancer patients who filed for bankruptcy within one year of diagnosis was 0.52 percent, compared to 0.16 percent within one year for the control group. For bankruptcy filings within five years of diagnosis, the proportion of cancer patients was about 1.7 percent, compared to 0.7 percent for the control group. The incidence rates for bankruptcy at one year after diagnosis, per 1,000 person-years, for the cancers with the highest overall incidence rates were as follows: thyroid, 9.3; lung, 9.1; uterine, 6.8; leukemia/lymphoma, 6.2; colorectal, 5.9; melanoma, 5.7; breast, 5.7; and prostate. 3.7. The incidence rate for all cancers combined was 6.1. The high bankruptcy incidence rate for those with thyroid cancer may be because thyroid cancer affects younger women more often than other cancers do according to the researchers. "Compared to men, younger women are more likely to live in single-income households and to have lower wages and lower rates of employment, and therefore less access to high-quality health insurance - leaving them more financially vulnerable," the authors wrote.Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. The National Center on Minority Health and Health Disparities at the National Institutes of Health funded the research. Co-authors included Karen Overstreet, chief judge of the U.S Bankruptcy Court, Western District of Washington; and researchers from the University of Washington; University of Utah School of Medicine; and University of Bristol (U.K.).
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Lapatinib Approved for Initial Treatment of Metastatic Breast Cancer

The U.S. Food and Drug Administration (FDA) has expanded its approval of lapatinib (TykerbR) to include initial treatment of metastatic, postmenopausal breast cancer that is both HER2-positive and hormone receptor-positive. In this setting, lapatinib is approved for use in combination with the aromatase inhibitor drug letrozole (FemaraR).

Twenty to thirty percent of breast cancers overexpress (make too much of) a protein known as HER2. Overexpression of this protein leads to increased growth of cancer cells. Fortunately, the development of treatments that specifically target HER2-positive cells has improved outcomes among women with HER2-positive breast cancer. Drugs that target HER2 include trastuzumab (HerceptinR) and lapatinib.

Lapatinib was initially approved in 2007 for use in combination with the chemotherapy drug capecitabine (XelodaR) for the treatment of HER2-positive advanced or metastatic breast cancer that has progressed following prior therapy with an anthracycline, a taxane, and trastuzumab.

The expansion of lapatinib’s approval to include the initial treatment of metastatic breast cancer was based on a study in 219 postmenopausal women with HER2-positive, hormone receptor-positive, metastatic breast cancer. Women were treated with either letrozole alone or letrozole plus lapatinib. Both drugs are given orally.

Progression-free survival was 5.2 months longer among women treated with letrozole and lapatinib than among women treated with letrozole alone.

The most common side effects of lapatinib include diarrhea, rash, nausea, and fatigue.

Reference: FDA News Release. FDA expands use of approved breast cancer drug. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm199374.htm. Accessed February 1, 2010.

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Data Addressing Patient And Physician Barriers To Clinical Trials To Be Presented By Experts

Main Category: Cancer / Oncology
Also Included In: Clinical Trials / Drug Trials
Article Date: 17 May 2013 - 1:00 PDT Current ratings for:
Data Addressing Patient And Physician Barriers To Clinical Trials To Be Presented By Experts

Researchers from University Hospitals Case Medical Center's (UHCMC) Seidman Cancer Center in Cleveland, OH, will present findings from two studies evaluating new technologies designed to address common barriers to patient enrollment in clinical trials. Results from a large-scale, randomized trial demonstrated that the use of tailored, web-based videos delivering educational information to patients before an oncologist visit can significantly improve knowledge and reduce attitudinal barriers that impact enrollment in clinical trials. A second, preliminary study showed that a new automated technology created by UHCMC researchers helped oncologists identify clinical trials for individual patients in a busy outpatient oncology clinic.

"Although clinical trials are the key to developing new, better cancer treatments, less than 10 percent of cancer patients participate in them," says Neal J. Meropol, MD, study author, Chief of the Division of Hematology and Oncology at UHCMC and Case Western Reserve University School of Medicine and member-elect of the ASCO Board of Directors. "We know there are multiple barriers to clinical trials for both patients and oncologists, and the new technologies being evaluated at University Hospitals Case Medical Center Seidman Cancer Center are designed to break down those obstacles by providing individualized education for patients and new technology to help oncologists efficiently identify appropriate trials for their patients."

Common barriers to patient enrollment in clinical trials include fear of side effects, receiving placebo instead of treatment, financial concerns and the misperception that clinical trials should only be considered as a "last resort" option. For oncologists, a common obstacle is the time needed to help identify appropriate clinical trials - thousands of which are currently in progress across the country - for their patients. At the UHCMC Seidman Cancer Center, there are currently more than 300 ongoing clinical trials focused on cancer.

About the Studies

Oral Abstract Session: Health Services Research
Randomized Trial of a Web-based Intervention to Address Barriers to Clinical Trials
Abstract #6500: June 3, 8:00 - 8:15 a.m.

Dr. Meropol will present findings from a trial examining the use of PRE-ACT - Preparatory Education About Clinical Trials - a tailored, interactive, web-based intervention to address patient barriers and improve preparation for consideration of clinical trials as a treatment option. The prospective, randomized, multicenter, Phase 3 clinical trial evaluated 1,255 patients and utilized baseline assessments to determine their top clinical trial barriers. Patients in the PRE-ACT group were presented with a video library of 30-90 second clips that addressed their individual barriers, as indicated by their assessment results. Patients in the control group received online, text-based information that wasn't tailored to their individual barriers. A follow-up survey was conducted to reassess patient knowledge and attitudes.

Results showed that PRE-ACT significantly improved patient understanding and attitudes towards clinical trials when viewed before a visit to an oncologist. The control group also had improved knowledge, reduced attitudinal barriers and improved preparation, but the PRE-ACT group was more satisfied with the amount and format of information presented to them and felt more prepared to consider enrollment in clinical trials when compared to patients who received written information.

Funding for this study was provided by a National Cancer Institute (NCI) grant (R01CA127655) to Case Western Reserve University School of Medicine.

General Poster Session: Health Services Research
Trial Prospector: An Automated Clinical Trials Eligibility Matching Program
Abstract #111482: June 3, 1:15 - 5:00 p.m.

Co-authors Andrew Parchman, MD, Hematology and Oncology Fellow at UHCMC, and Dr. Meropol will present findings examining the use of Trial Prospector - an automated, HIPAA-compliant program pioneered by UHCMC that matches patients to clinical trials based on information extracted from their electronic medical records. Its user-friendly interface allows for physician perusal of relevant clinical trials and eligibility checklists at the point of care without requiring manual data entry. For this study, pilot testing was performed in a GI oncology subspecialty clinic. Eleven oncologists completed surveys after each patient visit to assess the usability and impact of Trial Prospector.

Results showed that the Trial Prospector matching algorithm was 100 percent accurate and saved time identifying potential clinical trials. Physicians generally found it to be easy to use, and 90.9 percent said they would recommend its use for clinical trial eligibility screening. Based on these preliminary findings, Dr. Parchman and team intend to expand data elements to increase the precision of trial matching and expand to other disease specialties and practice locations.

Funding for this study was provided by the Clinical and Translational Science Collaborative of Cleveland, UL1TR000439 from the National Center for Advancing Translational Sciences (NCATS) component of the National Institutes of Health and NIH roadmap for Medical Research to Case Western Reserve University School of Medicine.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. ASCO Annual Meeting: May 31-June 4, 2013 | McCormick Place | Chicago, Illinois
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Midlife Weight Gain Increases Postmenopausal Breast Cancer Risk

Women who gain weight in midlife may have an increased risk of developing postmenopausal breast cancer, according to research findings presented at the 2010 Annual Meeting of the American Association for Cancer Research.

Research into lifestyle factors that influence breast cancer risk or prognosis allows us to make more informed decisions about how to manage our own health. Body weight is a factor that appears to influence not only the risk of developing several types of cancer but also cancer survival.

To further understand how weight gain in midlife affects risk of postmenopausal breast cancer, researchers studied the effects of weight gain during two periods: 1) from age 20 to age 50 and 2) after age 50. The study consisted of approximately 72,000 women, age 55 to 74 at the beginning of the study. Results were presented for participants who had never used menopausal hormone therapy, as this group showed the strongest association between midlife weight gain and postmenopausal breast cancer risk.

Between age 20 and the start of the study, 57% of study participants had an increase in body mass index (BMI) of 5 kg/m2 or more. For a woman with a height of 5’4”, this equates to a weight gain of approximately 30 pounds.

Regardless of weight at age 20, weight gain during midlife increased the risk of postmenopausal breast cancer. Women with a BMI increase of 5 kg/m2 between age 20 and study entry (at age 55-74) were almost twice as likely to develop postmenopausal breast cancer as women who maintained a stable BMI. Weight gain during either of the two age periods (20-50 and 50+) increased risk.

The researchers concluded that maintaining weight throughout adulthood may help women decrease their risk of postmenopausal breast cancer.

Reference: Sue LY, Genkinger JM, Schairer C, et al. Body mass index gain throughout adulthood may increase risk of postmenopausal breast cancer. Paper presented at: Annual Meeting of the American Association for Cancer Research; April 20, 2010; Washington, D.C. Abstract 4823.

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The Many Benefits Of Robot-Assisted Kidney Cancer Surgery Do Not Include Cost

Main Category: Urology / Nephrology
Also Included In: Cancer / Oncology;??Medical Devices / Diagnostics
Article Date: 09 May 2013 - 1:00 PDT Current ratings for:
The Many Benefits Of Robot-Assisted Kidney Cancer Surgery Do Not Include Cost

Robot-assisted surgery to remove kidney cancers has seen a rapid increase in use, and has both replaced and proven safer than laparoscopic procedures for the same purpose, according to a study by the Vattikuti Urology Institute at Henry Ford Hospital in Detroit.

However, the study also shows that robotic partial nephrectomy (RPN) - while resulting in fewer complications than both open (OPN) and laparoscopic (LPN) removal of cancerous kidney tissue - also involves more "excessive" hospital charges.

"Excessive hospital charges were significantly higher with robotic partial nephrectomy," says Khurshid R. Ghani, M.D., of Vattikuti Urology Institute and lead author of the study. "While we can report no cost-savings with the procedure - quite the opposite - the benefits are obvious."

"It is a safe operation that has rapidly replaced LPN as the most common minimally invasive approach for partial nephrectomy. It has shown superior results compared to open surgery, and was better than laparoscopy in every respect but cost," he adds

The findings were presented at the annual meeting of the American Urological Association in San Diego.

Dr. Ghani says data was mined from the Nationwide Inpatient Sample (NIS), which includes inpatient discharge information from 1,044 U.S. hospitals.

Between October 2008 - when the NIS first included an identifier for robot-assisted procedures - and December 2010, the researchers found a total of 38,064 patients who underwent OPN, LPN or RPN to treat kidney cancers that had not metastasized.

Of the total, nearly 70 percent had open surgery, nearly 24 percent had robot-assisted surgery and a little more than 9 percent were treated laparoscopically.

Researchers also noted that while all three forms of kidney surgery had increased in 2010, robot-assisted partial nephrectomy soared by more than 45 percent, far overshadowing the other two types.

Complications were tracked during and after each procedure. The Henry Ford team found: Patients undergoing RPN were least likely to receive a blood transfusion, while those who had open surgery were most likely to need one. The same was true for developing complications after surgery or requiring a prolonged hospital stay. Only those undergoing RPN were less likely to develop complications during surgery.Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our urology / nephrology section for the latest news on this subject. Funding source: Henry Ford Hospital
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Worse Outcomes for Breast Cancer Patients with Other Illnesses

Older breast cancer patients who have additional medical conditions have worse survival than patients without other illnesses.? These findings were recently published in the Journal of the National Cancer Institute.?

According to results from previous studies, illness in addition to breast cancer may shorten survival and increase death rates among older women with breast cancer. Studies to date have assessed the association between other illness as a whole and breast cancer death but have not evaluated specific illnesses independently.??

To better understand how medical conditions in addition to breast cancer may affect survival among older women, researches selected 13 medical conditions to evaluate; these included stroke, chronic obstructive pulmonary disease, chronic renal failure, congestive heart failure, dementia, diabetes, liver disease, heart attack, paralysis, peripheral vascular disease, previous cancer, rheumatoid arthritis, and ulcers. A total of 64,034 breast cancer patients were included in the study. Patients were 66 years old and older and had been diagnosed with breast cancer between 1992 and 2000.??

42% of patients had a history of one or more of the selected illness. ?Patients with selected illnesses experienced shorter overall survival times and increased overall deaths from breast cancer and other conditions compared with patients without another illness.?When patients between 66 and 74 years of age were further analyzed according to age and type of illness other than breast cancer, overall survival was worse or similar among patients with Stage I breast cancer and another illness compared with patients with Stage II breast cancer and no other illness.??

It appears that certain illnesses in addition to breast cancer may decrease overall survival and increase death among older women with breast cancer. These findings may help doctors more accurately predict survival among breast cancer patients. As well, they underscore the importance of balancing treatment for breast cancer with treatment for other conditions.?

Reference: Patnaik JL, Byers T, DiGuiseppi C, et al. The influence of comorbidities on overall survival among older women diagnosed with breast cancer. Journal of the National Cancer Institute [online publication]. June 30, 2011.?

Posted July 21, 2011

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Screening Mammography Performs Poorly in Young Women

Screening mammography in women under age 40 results in high rates of callbacks, low rates of cancer detection, and high rates of false-positive results, according to the results of a study published early online in the Journal of the National Cancer Institute.[1]?

Screening mammography refers to mammograms that are conducted in the absence of breast symptoms. The goal of screening mammography is to detect breast cancer at an early stage when it is most easily treated.

The performance of screening mammography is known to vary by age. Younger women are less likely than older women to have breast cancer, and more likely to experience some of downsides of screening such as false-positive test results. This has made it challenging to identify the optimal age at which screening should begin. The U.S. Preventive Services Task Force recommends that routine screening of average-risk women begin at age 50. The American Cancer Society recommends that screening begin at age 40.

Although a great deal of attention has focused on the performance of screening mammography among women over the age of 40, there has been little information available about how mammography performs in very young women—those under the age of 40. To address this question, researchers from the University of North Carolina pooled data from six mammography registries in the United States. Their data included 117,738 women who underwent their first mammogram between the ages of 18 and 39. The researchers then followed the women for a year to determine the accuracy of the tests, evaluate the recall rate, and measure the cancer detection rates. The study included women who had screening mammograms as well as those who underwent diagnostic mammograms (due to a symptom such as a lump).

The researchers found that mammography performance improved in the presence of a breast lump – for diagnostic mammograms, the rate of detection was 14.3 cancers per 1,000 women tested, whereas for screening mammograms, the rate of detection was 1.6 cancers per 1,000 women. The researchers found that the screening mammograms had poor accuracy and high rates of recall for further testing.

The authors concluded that “in a theoretical population of 10,000 women aged 35-39 years, 1,266 women who are screened will receive further workup, with 16 cancers detected and 1,250 women receiving a false-positive result.” They found no cancers in women under the age of 25 and a poor performance of screening mammography in women ages 35-39.

It should be noted that the researchers did not have complete family history information or information about BRCA1 or BRCA2 mutation status, and were therefore not able to fully assess mammography performance in the subset of young women at high risk of breast cancer.

Women who have questions about when to begin breast cancer screening are advised to talk with their doctor.

Reference:

[1] Yankaskas BC, Haneuse S, Kapp JM, et al. Performance of first mammography examination in women younger than 40 years. Journal of the National Cancer Institute. Published early online: May 3, 2010.

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Improvement In Quality Of End-Of-Life Care Offered By The Liverpool Care Pathway

Main Category: Cancer / Oncology
Also Included In: Palliative Care / Hospice Care
Article Date: 13 May 2013 - 1:00 PDT Current ratings for:
Improvement In Quality Of End-Of-Life Care Offered By The Liverpool Care Pathway

Death in hospital remains very common for cancer patients in developed countries. Although hospital surveys show that death was highly expected, patients dying in hospital have a high probability of unrelieved and poorly treated physical suffering, and emotional, spiritual and social distress. Quality improvement programmes in the United States and United Kingdom suggest that aspects of the 'excellent practice' of palliative care can be transferred to other settings. The Liverpool Care Pathway (LCP) for the dying patient is one pathway that seeks to achieve this. It offers a structured programme aimed at providing improvements in the quality of care for all relevant dimensions at the end of life.

This study aims to assess the effectiveness of the LCP on the quality of end-of-life care provided to adult cancer patients during their last week of life in hospital. It implements an uncontrolled before-after intervention cluster trial performed within four hospital wards participating in the pilot. A total of 2 months after the patient's death, bereaved family members were interviewed. The results provide the first robust data collected from family members, in any reasonably sized sample, of a potential clinically significant improvement in some aspects of quality of care - in particular respect, kindness and dignity, family emotional support, self-efficacy of the family and coordination of care.

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Herceptin plus Epirubicin and Cyclophosphamide Tolerable and Effective for HER2-positive Metastatic Breast Cancer

For women with metastatic, HER2-positive breast cancer, the combination of HerceptinR (trastuzumab) with epirubicin and cyclophosphamide appears to offer a promising treatment option with a relatively low rate of heart complications. These results were published in the Journal of Clinical Oncology.

Twenty to 25 percent of breast cancers overexpress (make too much of) a protein known as HER2. Overexpression of this protein leads to increased growth of cancer cells and a worse breast cancer prognosis. Fortunately, the development of drugs such as Herceptin that specifically target HER2-positive cells has improved prognosis for women with HER2-positive breast cancer.

Herceptin may be used in addition to chemotherapy. Anthracycline-based chemotherapy regimens are effective against breast cancer but can increase the risk of heart problems when combined with Herceptin.

Epirubicin is an anthracycline that may produce fewer heart problems than some other commonly used anthracyclines. To evaluate the combination of Herceptin with epirubicin and cyclophosphamide, researchers in Europe conducted a Phase I/II clinical trial known as HERCULES. The study enrolled 120 women with HER2-positive, metastatic breast cancer and adequate heart function. These women were treated with Herceptin, one of two doses of epirubicin (60 mg/m2 or 90 mg/m2), and cyclophosphamide. Herceptin was then given alone until cancer progression.

Outcomes in the women with HER2-positive breast cancer were compared with outcomes among 60 women with metastatic, HER2-negative breast cancer. The women with HER2-negative breast cancer were treated with the higher dose of epirubicin and cyclophosphamide alone (without Herceptin).

Among women treated with Herceptin plus chemotherapy, dose-limiting heart problems occurred in 5% of women given the higher dose of epirubicin and 1.7% of women given the lower dose of epirubicin. These heart problems were described as “manageable,” and no heart-related deaths occurred. None of the women with HER2-negative cancer (who were treated with chemotherapy without Herceptin) developed dose-limiting heart problems.Tumor response rates were 57% among women treated with Herceptin and the lower dose of epirubicin and 60% among women treated with Herceptin and the higher dose of epirubicin.

The researchers conclude that the combination of Herceptin, epirubicin, and cyclophosphamide is a promising approach for the treatment of HER2-positive metastatic breast cancer and warrants additional research.

Reference: Untch M, Muscholl M, Tjulandin S et al. First-Line Trastuzumab Plus Epirubicin and Cyclophosphamide Therapy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Cardiac Safety and Efficacy Data From the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) Trial. Journal of Clinical Oncology. 2010; 28:1473-1480.

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Non-surgical treatments for multiple tumors approximation One Step

Main category: Cancer / Oncology
Also included in: Neurology / neuroscience
Article Date: 19 may 2013-0:00 PDT current ratings for:
Non-surgical treatments for multiple tumors approximation One Step

A study conducted by researchers at the University of Plymouth peninsula schools of medicine and dentistry has revealed for the first time how the loss of a particular tumor suppressing protein leads to the abnormal growth tumours of the brain and the nervous system.

The study is published in the brain: A Journal of Neurology.

Tumour suppressors exist in cells to prevent abnormal cell division in our body. The loss of a known tumor suppressor Merlin leads to tumors in many types of cells in our nervous system. There are two copies of a tumor suppressor, one on each chromosome that we inherit from our parents. The loss of Merlin may be caused by the random loss of two copies in a single cell, causing sporadic tumours, or by inheriting an abnormal copy and lose the second copy throughout our lives as seen in hereditary disease neurofibromatosis type 2 (NF2).

With sporadic loss or hereditary NF2, these tumors lack the Merlin protein develop in the Schwann cells that form the sheaths that surround and electrically isolate the neurons. These tumors are called schwannomas, but tumors can also arise in cells that form the membrane around the brain and spinal cord and the cells that line the ventricles of the brain.

Although the schwannomas are benign and slow growing, they are common and come in numbers. The number of tumors caused by this genetic defect can overwhelm a patient, often leading to the death, invalidity and possibly hearing loss. Patients can suffer 20 to 30 tumors at any time, and the condition usually manifests in adolescence and adulthood.

No effective treatment for these tumors there, other than the repeated invasive surgery or radiation to a single tumor at a time and that is unlikely to eradicate the entire tumor.

The study of the brain studied how the loss of a protein called Sox10 functions in these tumors. Sox10 is known to play a major role in the development of Schwann cells, but this is the first time, it has been shown to be involved in the growth of tumor cells Schwannoma. By understanding the mechanism, the research team has paved the way for new therapies to develop which will provide a viable alternative to surgery or radiotherapy.

The study, conducted by researchers at the University of Plymouth peninsula schools of medicine and dentistry with colleagues from the State University of New York and the University Erlangen-Nurnberg, was led by Professor David Parkinson.

He said: "we have for the first time shown that human Schwannoma cells reduced expression of Sox10 and messenger RNA protein. '' By identifying this correlation and understand the mechanism of this process, we hope that drug-based therapies can in time be created and introduced to reduce or deny the need for surgery or radiation therapy. ?

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Oncotype DX® Influences Breast Cancer Treatment Decisions

Among women with early breast cancer, use of the Oncotype DXR test changed oncologist treatment recommendations in approximately 32% of cases. Use of the test also increased oncologist confidence in the treatment recommendation and decreased patient anxiety. These results were published in the Journal of Clinical Oncology.

The Oncotype DX test measures the expression of 21 genes in a sample of tumor tissue and generates a Recurrence Score. The Recurrence Score predicts the magnitude of chemotherapy benefit and the likelihood of breast cancer recurrence for women with early-stage, estrogen receptor-positive breast cancer.

To explore how use of the Oncotype DX test influences oncologist and patient treatment decisions and satisfaction, researchers collected information from 89 patients treated by 17 medical oncologists. Information about adjuvant treatment plan was collected before and after obtaining the Oncotype DX Recurrence Score.

Based on the Recurrence Score, the oncologist’s treatment recommendation changed for 31.5% of patients. The most common change was from chemotherapy plus hormonal therapy to hormonal therapy alone.Recurrence Score results increased oncologist confidence in the treatment plan in 76% of the cases.
27% of patients changed their treatment decision based on the Recurrence Score.Patient anxiety was lower after receipt of the Recurrence Score results.These results provide additional evidence that Recurrence Score results can influence treatment recommendations and treatment decisions for women with early breast cancer, and can help relieve patient anxiety.

Reference: Lo SS, Mumby PB, Norton J et al. Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. Journal of Clinical Oncology [early online publication]. January 11, 2009.

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Study reveals widespread support for rationing of certain Types of cancer care

Main Category: Cancer / Oncology
Article Date: 18 May 2013-0:00 PDT Current ratings for:
Study Finds Broad Support For Rationing Of Some Types Of Cancer Care

The majority of cancer doctors, patients, and members of the general public support cutting health care costs by refusing to pay for drugs that don't improve survival or quality of life, according to results of a new study that will be presented by researchers from the Perelman School of Medicine at the University of Pennsylvania during the annual meeting of the American Society of Clinical Oncology in Chicago in early June (Abstract #6518).

The Penn Medicine team surveyed 326 adult cancer patients receiving treatment at Penn's Abramson Cancer Center, a random sample of 891 adults in the general public, and 250 oncologists across the United States during 2012 to probe their opinions about tactics for controlling costs associated with cancer care.

"We found that the majority of respondents considered Medicare spending a big or moderate problem, and many suggested that Medicare could spend less without causing harm," said the study's lead author, John Gogineni, MD, MSHP, an instructor in the division of Hematology-Oncology in Penn's Abramson Cancer Center. "We know that cancer patients and their doctors face decisions every day that stand to raise health care costs without conferring much benefit to patients, and our survey has identified some common themes in how these groups of stakeholders might propose to lower costs of care while still protecting patients."

More than 90 percent of all three groups surveyed attributed rising costs to drug companies charging too much, and more than 80 percent of each group cited insurance company profits as a driver of rising costs. Many also thought hospitals and doctors conducted unnecessary tests and provided unnecessary treatments (69 percent of patients, 81 percent of the general public, and 70 percent of doctors).

The research team, which includes senior author Ezekiel J. Emanuel, MD, PhD, chairman of the department of Medical Ethics and Health Policy, presented a variety of potential cost-lowering options to each group and asked whether they supported the idea. Cancer patients, members of the general public, and oncologists tended to be about as likely to say patients who can afford to pay more for care should be asked to pay more (56, 58, and 52 percent, respectively). And large numbers signed not paying for more expensive drugs when cheaper alternatives are equally as effective (78 percent of patients, 86 percent of the general public, and 90 percent of physicians). The majority also supported refusing to cover drugs that do not improve survival or quality of life, though physicians were more apt to refuse payment under those circumstances (79 percent compared to 52 percent of patients and 57 percent of the general public).

Even drugs that confer only incremental gains in survival, however, were found to be worth covering in the eyes of all groups surveyed: Just 12 percent of physicians were willing to refuse payment for a drug that extends life by four months, compared to 20 percent of patients and 28 percent of the general public.

Greater differences of opinion were observed around coverage for drugs offering benefits other than survival gains. When queried about a drug that doesn't extend life but reduces pain, for instance, only 5 percent of patients and 10 percent of the general public voiced support for refusing to cover the medication, compared to 32 percent of physicians. On coverage for a drug that doesn't extend life but adds convenience, 27 and 32 percent of patients and the general public, respectively, said those costs should not be covered, compared to 59 percent of physicians.

"These results suggest that patients and the lay public prioritize quality of life, while oncologists appear focused on controlling disease and increasing length of life," Gogineni says. "Patients have a much broader set of concerns, from the cost of their doctor's visits to the side effects of treatment and the emotional toll of their illness."

Sixty four percent of physicians said they supported the idea of an independent expert panel that would decide which therapies to cover, but that plan was met with resistance from patients (33 percent approved) and the general public (46 percent approved). The authors suggest this may be because physicians are more familiar with such models, which are already used for decision-making around scarce medical resources such as ICU beds and organs for transplantation. And, Gogineni notes, "distancing the locus of responsibility for access to high cost, low benefit cancer treatment may create less strain on the physician-patient relationship."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. ASCO Annual Meeting: May 31-June 4, 2013 | McCormick Place | Chicago, Illinois
Gogineni will present the team's findings at ASCO on Sunday, June 2, 2013 in the Health Services Research poster session from 8 a.m. to noon in McCormick Place S405.
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Weighing the Risks and Benefits of Tamoxifen and Raloxifene for Breast Cancer Prevention

Researchers have developed a tool that can help guide decisions about which drug—tamoxifen or raloxifene (EvistaR)—is the best choice for breast cancer prevention in high-risk postmenopausal women. These results were published in the Journal of Clinical Oncology.???

Drugs that block the effects of estrogen have been shown to reduce the risk of breast cancer in women at high risk of the disease. Two drugs that have been approved for breast cancer risk reduction in certain groups of women are tamoxifen and raloxifene. Tamoxifen is approved for breast cancer risk reduction in women who are at high risk of the disease (including high-risk premenopausal women). Raloxifene—originally approved for the prevention and treatment of osteoporosis—is approved for breast cancer risk reduction in postmenopausal women with osteoporosis or postmenopausal women at high risk of breast cancer.??

To help postmenopausal women and their healthcare providers evaluate the likely effect of each drug, researchers developed a benefit-risk index. In addition to considering the extent to which each drug reduced breast cancer risk, the researchers also assessed other health outcomes, such as bone fractures, blood clots, stroke, and endometrial (uterine) cancer.???

The researchers found that the risks and benefits of tamoxifen and raloxifene vary by a woman’s age, race/ethnicity, risk of breast cancer, and whether the woman has had a hysterectomy.????

The researchers write “By combining this information with information on clinical features and personal preferences, the health care provider and patient can make an informed decision.” The researchers provide tables to help specific subgroups of women evaluate the likely benefit (or harm) of each drug.?

Women who have a high risk of breast cancer as a result of their family or personal medical history may wish to talk with their doctor about ways to reduce their cancer risk.?

Reference: Freedman AN, Yu B, Gail MG et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. Journal of Clinical Oncology. Early online publication May 2, 2011.?

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Genetic Differences May Influence the Severity of Joint Pain Among Breast Cancer Patients Taking Aromatase Inhibitors

Aromatase inhibitor-associated arthralgia (AIAA)? is a major side effect in breast cancer survivors, producing joint pain so severe that as many as ten percent of women discontinue their therapy prematurely while undergoing treatment with these lifesaving drugs. New research presented by investigators from the University of Pennsylvania’s Abramson Cancer Center at the 2010 meeting of the American Society of Clinical Oncology reveals a possible genetic basis for why these side effects occur and shows promise for treating these symptoms without interfering with the drugs’ efficacy. Additional research will also be presented shedding light on the physical and psychological factors that influence women’s decisions to stop taking the drugs.

Jun Mao, MD, MSCE, an assistant professor of Family Medicine and Community Health who heads the Abramson Cancer Center’s integrative oncology program, led a team that studied individual genetic variations that could potentially influence both the onset and the severity of AIAA.[1] His team studied 390 postmenopausal women with Stage 0 to III breast cancer receiving adjuvant therapy with aromatase inhibitors who reported joint pain related to their drug therapy.? They found that among this group, women carrying at least one copy of a “7-repeat” genetic variant in the aromatase enzyme (CYP19A1, the target of aromatase inhibitors) had a lower chance of developing AAIA than those with at least one “8-repeat” allele of the same gene. Having at least one copy of a specific IL-6 haplotype was also correlated with increased pain severity, while the presence of a different variant of that gene was associated with decreased pain.? Both these findings support previous research that indicates an important role for host estrogen metabolism and inflammation in causing AIAA.

“Due to genetic differences, women respond differently to aromatase inhibitors with regard to estrogen levels and inflammatory processes, and as a result, some women are more likely to have this pain or have more severe pain,” says Angela DeMichele, MD, MSCE, an associate professor of Hematology/Oncology and Epidemiology and Biostatistics, and a co-author on all three of the studies. “There are millions of women receiving AIs, as many as 50 percent of them experience some level of arthralgia, and up to 10 percent discontinue their treatment prematurely, so this is a significant issue.”

The investigators say that as more breast cancer patients become breast cancer survivors, clinicians must become more knowledgeable about the quality of life issues impacting women after they end active treatment for their cancers. The new findings are key to identifying which women may be at risk of problems like arthralgia—and then, Mao says, to developing more targeted interventions at both the physical and psychological levels.

The multidisciplinary team is also looking at issues related to clinician-patient communication, exercise, and co-factors such as arthritis or fibromyalgia that can increase pain and disability in order to keep more women on their treatment regimen. Mao, who is also a licensed physician acupuncturist, has begun a clinical trial examining the effectiveness of acupuncture for aromatase inhibitor associated arthralgia as part of conventional breast cancer survivorship care. These efforts are part of the Abramson Cancer Center’s comprehensive Wellness After Breast Cancer program.

“We believe that proactively informing women about the possibility that their breast cancer treatment may cause arthralgia and then intervening early is probably important to keeping them on these potentially life-saving cancer treatments,” Mao says. “When they are not prepared, or become frustrated because they didn’t know this could happen to them, they are far more likely to make the decision to stop treatment. Some studies have suggested that women with the most severe symptoms are those with the most complete blockage of aromatase. We want to do everything we can to assure that the women most likely to benefit from therapy don’t end it too soon because they are experiencing pain related to their treatment.”

In a related study, University of Pennsylvania researchers surveyed 300 breast cancer survivors to assess the impact of AIAA on upper and lower extremity functioning.[2] They found that women with AIAA had greater impairment of both upper and lower extremities than those who did not experience these symptoms. As many as 29 percent of participants reported that the pain limited their ability to perform their normal activities.

In a third study, Carrie Stricker, PhD, RN, clinical assistant professor of Nursing and an oncology nurse practitioner, led the team of researchers in surveying 490 postmenopausal, non-metastatic breast cancer patients to assess the factors that influenced their stopping AI therapy prematurely.[3]? This is one of only a few studies to analyze the rates at which women discontinue AI therapy and the variables that predict their decision to do so, and the only designed to evaluate patient-reported reasons for ending AI treatment. The study found that 7 percent of the patients studied had discontinued their AI treatment early, at a mean of 15.7 months from the beginning of treatment. The most significant predictors for stopping therapy were a previous history of taking tamoxifen, which can also cause arthralgia and other symptoms; having other inflammatory conditions such as arthritis; communication about difficulties with taking AIs, and being married. Patients who stopped AI treatment early cited side effects as the main reason, with arthralgia being the most common complaint. Effects on bone, hot flashes, and cognitive effects were also named as reasons for cessation of therapy.

“These data suggest that we can develop a profile of the women who are most likely to make the decision to terminate their AI therapy prematurely, and if we can do that, we can design better supportive interventions for these women and incorporate them into our clinical practice,” DeMichele says. “This information, derived directly from the patients themselves, reinforces our understanding that assessing and managing the side effects of cancer therapy, including joint pain, is critical to the overall success we can achieve in managing the disease itself.”

References:

[1] Mao J, Su I, Feng R et al. Genetic variation in CYP19A1 and interleukin-6 and aromatase inhibitor-associated arthralgia in breast cancer survivors. Presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract 526.

[2] Stricker CT, Palmer SC, DeMichele A, Mao J. Understanding premature discontinuation of aromatase inhibitor (AI) therapy in postmenopausal breast cancer survivors. Presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract 6073.

[3] Friedman CF, Bruner D, Xie S et al. Functional disability and aromatase inhibitor-associated arthralgia in breast cancer survivors. Presented at the 2010 annual meeting of the American Society of Clinical Oncology. June 4-8, 2010. Chicago, IL. Abstract 9156.

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Depressive symptoms are linked to premature death among Cancer Survivors

Main category: Cancer / Oncology
Also included in: Depression;??Colorectal cancer;??Lymphoma / leukemia / myeloma
Article Date: 20 may 2013-0:00 PDT current ratings for:
Depressive symptoms are linked to premature death among Cancer Survivors

Surviving cancer depressed are twice as likely to die prematurely than those who do not suffer from depression, regardless of the site of the cancer. This is according to a new study, Floortje Mols and his colleagues, from the University of Tilburg in the Netherlands. Their work is published online in the Journal from Springer to Cancer survival.

The prevalence of cancer is on the rise, as are the number of people who are cured of their cancer or live with it as a chronic disease. This is partly due to the aging of the population and more effective treatments. Thus, many of these survivors face persistent problems due to cancer and its treatments, such as a high prevalence of depression.

Mols and the team considered whether symptoms of depression observed between one and ten years after the diagnosis of cancer were related to an increased risk of premature death of two or three years later. Their work focused on endometrial cancer survivors, colorectal, lymphoma or multiple myeloma, where little work by watching this possible link was made so far.

They analyzed data collected from several major surveys on the population in 2008 and 2009. A total of 3,080 cancer survivors completed questionnaires to identify the symptoms of depression.

The authors found that depression increased the risk of death: high levels of depressive symptoms clinically were more common in those who died than those who survived. Overall, after controlling for treatment, cancer type, comorbidity, and metastasis, cancer one-to-ten years suffering from depression survivors were two times more likely to have died at the beginning.

The researchers conclude: "attention to the recognition and treatment of depressive symptoms in this group of patients is the key. The next step is to study possible mechanisms that could explain the association between depressive symptoms and the death from cancer. We also need to better understand if the treatment of depressive symptoms in cancer patients have effects extend the life. ?

Article adapted by Medical News Today press release original. Click on "references" tab above for the source.
Visit our cancer / Oncology section for the latest news on this subject. Mols, f. et al. (2013), depressive symptoms are a risk factor for all-cause mortality: results of a prospective study on the population among 3,080 cancer survivors from the register of profiles, Journal of Cancer survival. DOI 10.1007/s11764-013-0286-6
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WHI Trial Suggests Possible Reduction in Breast Cancer Risk with Estrogen Alone

Postmenopausal women who take hormone therapy consisting of estrogen alone may have a somewhat reduced risk of breast cancer. These findings—from longer-term follow-up of the Women’s Health Initiative trial of estrogen alone—were published in the Journal of the American Medical Association. It should be noted that this report addressed only estrogen alone; it did not include combined estrogen plus progestin, which has previously been linked with an increased risk of breast cancer.

Menopause—when menstrual cycles end and ovarian hormone production drops dramatically—produces symptoms such as hot flashes and night sweats in up to 80% of women. When these symptoms are severe, they can have a profound effect on a woman’s quality of life and ability to function.

For many years, hormone therapy with estrogen (with or without progestin) has provided an effective way for women to manage menopausal symptoms. Studies over the last several years, however, have raised some concerns about the health effects of hormone therapy. In the Women’s Health Initiative (WHI) clinical trial of estrogen plus progestin, hormone use decreased the risks of fracture and colorectal cancer, but increased the risks of heart disease, breast cancer, stroke, and blood clots.[1] More recent reports suggest that combined hormone therapy may also increase lung cancer mortality.[2]

Initial reports from the WHI study of estrogen alone found that estrogen alone did not appear to increase the risk of breast or lung cancer, but did increase risk of stroke.[3] Because estrogen alone increases the risk of endometrial (uterine) cancer, it is generally only used in women who have had a hysterectomy.

Treatment with hormone therapy was stopped in both of the WHI hormone trials after these early reports, but study participants continue to be followed in order to document longer-term health effects. The current report addressed a range of health outcomes among women who had participated in the study of estrogen alone.[4] Information was available for 7,645 of the original 10,739 women.

Overall, risk of breast cancer was 0.27% among women who had been assigned to the estrogen group compared with 0.35% among women who had been assigned to the placebo group. The increased risk of stroke that was observed during estrogen treatment was no longer apparent after treatment stopped.Younger women (those in their 50s) tended to have more favorable health outcomes with estrogen than older women. Among younger women, for example, estrogen alone was linked with a decreased risk of heart attack; no such decrease was observed among older women.

The researchers note that their results “emphasize the need to counsel women about hormone therapy differently depending on their age and hysterectomy status.”

The finding that estrogen alone may decrease the risk of breast cancer was questioned in an accompanying editorial, which noted that this finding is “inconsistent with a longstanding, corroborated body of evidence…”[5]

Women who are considering using hormone therapy to manage menopausal symptoms are advised to discuss the risks and benefits with their physician.

References:

[1] Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002; 288:321-33

[2] Chlebowski RT, Schwartz AG, Wakelee H et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women’s Health Initiative trial): a post-hoc analysis of a randomised controlled trial. Lancet. 2009;374:1243-1251.

[3] Anderson GL, Limacher M, Assaf AR et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA. 2004; 291:1701-1712.

[4] LaCroix AZ, Chlebowski RT, Manson JE et al. Health outcomes after stopping conjugated equine estrogens among postmenopausal women with prior hysterectomy: a randomized controlled trial. JAMA. 2011;305:1305-1314.

[5] Jungheim ES, Colditz GA. Short-term use of unopposed estrogen: a balance of inferred risks and benefits. JAMA. 2011;305:1354-1355.

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Gene-Silencing Activity Discovery Could Lead To Treatment For Viral Infections, Cancers And Other Diseases

Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: Cancer / Oncology;??Genetics
Article Date: 13 May 2013 - 0:00 PDT Current ratings for:
Gene-Silencing Activity Discovery Could Lead To Treatment For Viral Infections, Cancers And Other Diseases

A team led by scientists at The Scripps Research Institute (TSRI) has found how to boost or inhibit a gene-silencing mechanism that normally serves as a major controller of cells' activities. The discovery could lead to a powerful new class of drugs against viral infections, cancers and other diseases.

"Learning to control natural gene silencing processes will allow an entirely new approach to treating human disease," said Ian J. MacRae, assistant professor in TSRI's Department of Integrative Structural and Computational Biology and principal investigator for the study, which appears as the cover story in the May 9, 2013 issue of the journal Molecular Cell.

A Scientific Mystery and Technical Conundrum

The gene-silencer in question is Argonaute 2, a molecular machine in cells that can grab and destroy the RNA transcripts of specific genes, preventing them from being translated into proteins. Argonaute 2 and other Argonaute proteins regulate the influence of about a third of the genes found in humans and other mammals - and thus are among the most important modulators of our cells' day-to-day activities. Argonautes' gene-silencing functions also help cells cope with rogue genetic activity from invading viruses or cancer-promoting DNA mutations.

Yet Argonautes' workings are complex and not yet entirely understood. For example, before it starts a search-and-destroy mission against a specific type of target RNA, an Argonaute 2 protein takes on board a target-recognition device: a short length of "guide RNA," also known as a microRNA (miRNA). The miRNA's sequence is mostly complementary to the target RNA's - a sort of chemical mirror-image - so that it can stick tightly to it.

But how do an Argonaute protein and its miRNA guide, having formed their partnership, manage to part company? It has been a scientific mystery and technical conundrum for researchers, who have found it hard to separate Argonaute proteins from miRNAs in the lab dish.

"That problem led us to look for a way to get Argonautes to unload these miRNAs," said Nabanita De, a postdoctoral fellow in MacRae's laboratory who was first author of the new study.

Matches and Mismatches

In an initial set of experiments, the team demonstrated that when an miRNA hooks up with an Argonaute 2, the pair do remain locked together and functioning for an exceptionally long time: days to weeks, whereas solo miRNA normally is degraded within minutes.

Yet prior studies by other laboratories have hinted at the existence of mechanisms that can hasten the separation of miRNAs from Argonautes. Some viruses, for example, produce decoy target RNAs that virtually nullify the activity of the corresponding miRNAs, seemingly by destabilizing the miRNA-Argonaute pairing. A key feature of these decoy target RNAs is that they make an almost perfect complementary match to the miRNAs - especially at one end of the miRNAs, known as the three-prime or 3' end. In this respect, they match the miRNAs much better than the natural gene transcripts that the miRNAs evolved to target.

De confirmed that decoy RNAs designed to match miRNAs this way can greatly hasten the miRNAs' "unloading" from Argonautes, thus effectively dialing down these miRNAs' normal gene-silencing activities. By contrast, mismatches at the 3' end delayed unloading, enhancing the gene-silencing activity.

Why do these matches and mismatches have such effects on the miRNA-Argonaute pairing? The mechanisms aren't obvious. But De noted that mismatches at the opposite end of miRNAs - the 5' end - have the opposite effect. "Targets with 5'-end mismatches are actually better at unloading miRNAs from Argonaute," she said.

"The next thing we're trying to figure out is how all that works," said MacRae. "We have some guesses but no clear answer."

In a study reported last year, MacRae's laboratory used X-ray crystallography to determine the first high-resolution atomic structure of an Argonaute 2-miRNA complex. Now the team is working on a structural study of the complex as it grabs a target RNA. "When we can see the structural details of that interaction, then I think we'll have a much better handle on this loading and unloading process," said MacRae.

Many Potential Applications

Scientists already have begun developing gene-silencing drugs that work like miRNAs; they are taken up by Argonaute proteins as guide RNAs and lead to the silencing of targeted gene transcripts. Pharmaceutical companies also are developing drugs that bind directly to miRNAs to inhibit their activity. The findings here suggest a new and, in principle, more powerful class of miRNA inhibitors/enhancers, aimed at destabilizing or stabilizing the miRNA-Argonaute complex.

"I can think of many applications for these," said MacRae. "One of the most obvious would be against hepatitis C virus, which requires a certain miRNA in liver cells for efficient replication; an RNA-based drug that speeds up the unloading of this virus-enhancing miRNA would be a powerful approach for shutting down the virus."

A better understanding of the miRNA loading and unloading process also should lead to better miRNA-type drugs, he added.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our infectious diseases / bacteria / viruses section for the latest news on this subject. Other contributors to the study, "Highly Complementary Target RNAs Promote Release of Guide RNAs from Human Argonaute 2," were Lisa Young, Nicole-Claudia Meisner and David V. Morrissey of the Novartis Institutes for Biomedical Research, and Pick-Wei Lau of the MacRae laboratory at TSRI.
The study was funded by the National Institutes for Health (grant R01 GM086701).
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Olaparib Active Against Advanced Ovarian Cancer and Breast Cancer with BRCA Mutations

Previously treated advanced breast and ovarian cancer patients with BRCA1 or BRCA2 gene mutation may benefit from treatment with the oral investigational drug olaparib. These findings were recently published in the journal The Lancet.[1],[2]

Although most ovarian cancer patients initially respond to platinum-based chemotherapy, most will eventually experience a return (relapse) of their cancer. Treatment of metastatic breast cancer often includes chemotherapy, but options can become limited when the cancer stops responding to conventional chemotherapy regimens. Outcomes remain poor after treatment of relapsed disease, and researchers continue to explore new approaches to treatment.

Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target,” targeted therapies may slow cancer cell growth or increase cancer cell death.

Olaparib is an oral investigational drug called a PARP inhibitor. The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Drugs that inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy.

Cancers that result from BRCA1 or BRCA2 gene mutations may be particularly responsive to PARP inhibitors. The BRCA genes provide another source of DNA repair. BRCA gene mutations result in a loss of this DNA repair capability and may make cells particularly vulnerable to the loss of other DNA repair mechanisms such as those provided by PARP.

The current Phase II studies evaluated low and high doses of olaparib in previously treated breast cancer and ovarian cancer patients with BRCA1 or BRCA2 gene mutations. Patients in both studies were treated with either 100 mg or 400 mg of oral olaparib twice a day. The studies was designed to determine overall response rate in 57 ovarian cancer patients and 54 breast cancer patients in order to validate the concept of targeting treatment for the BRCA1 or BRCA2 gene mutation, regardless of disease.

Overall response rate in the ovarian cancer study was 33% in the high-dose group and 13% in the low-dose group. Patients in the low-dose group were reported to have prognostic factors somewhat worse than the patients in the high-dose group in this study.Overall response rate in the breast cancer study was 41% in the high-dose group and 22% in the low-dose group.Side effects were tolerable in both groups.

The researchers concluded that olaparib was active in previously treated ovarian and breast cancer patients and that BRCA1 or BRCA2 mutations may play a role as a predictor for responsiveness to olaparib. Further studies are warranted to confirm these data and determine the role of BRCA mutation as a predictive biomarker that may help individualize treatment strategies for optimal results.

References:

[1] Audeh MW, Carmichael J, Penson RT, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. The Lancet [early online publication]. July 6, 2010.

[2] Tutt A, Robson M, Garber JE, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. The Lancet [early online publication]. July 6, 2010.

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