Surgical Biopsy Is Overused for Evaluating Suspicious Breast Imaging Findings
A comprehensive study of health care data from Florida shows that physicians are using surgical biopsy to investigate suspicious breast lesions much more often than is warranted, researchers reported in a study published online February 8 in the American Journal of Surgery. Medical guidelines recommend that in most cases doctors use a needle biopsy rather than more invasive open surgical biopsy to investigate suspicious lesions found during breast imaging exams such as mammography.
Dr. Stephen Grobmyer and his colleagues at the University of Florida examined records from the Florida Agency for Health Care Administration outpatient surgery and procedure database. Although the percentage of patients in Florida who had minimally invasive breast biopsy (MIBB), also known as percutaneous needle biopsy, increased over the 5-year study period (2003 to 2008), the rate of open surgical biopsy in 2008 was still around 30 percent. That rate was substantially higher than the 5 to 10 percent that a 2009 consensus panel suggested as an appropriate rate of open biopsy, the study authors noted. The use of MIBB was higher at academic medical centers than at nonacademic centers.
MIBB causes less scarring and fewer complications, such as infection and bruising, and is less expensive than open surgical biopsy. Most biopsied breast lesions turn out to be benign. And because MIBB is highly accurate, the authors noted, in most cases having a needle biopsy can prevent the need for a patient to have an open surgical biopsy procedure.
“These findings suggest the need for further efforts to educate practitioners and patients about the numerous advantages of MIBB for the evaluation of suspicious image-detected breast lesions,” the authors wrote. “Achieving a reduction in the rate of open surgical biopsy should remain a priority.”
Combined data from five randomized clinical trials indicate that patients with early-stage Hodgkin lymphoma should receive radiation therapy in addition to chemotherapy. The combination of the two therapies is currently the standard treatment for Hodgkin lymphoma.
However, some researchers have suggested that forgoing radiation therapy may not lower survival for patients with early-stage disease. Radiation therapy can cause late side effects in survivors, who tend to be young at the time of treatment. These side effects include second cancers, most commonly breast cancer in young women who receive radiation therapy to the chest.
Researchers from the Cochrane Collaboration performed a meta-analysis using data from 1,245 patients enrolled in the five trials. Each trial compared outcomes among patients treated with six cycles of chemotherapy alone with those among patients treated with six cycles of chemotherapy plus radiation therapy. Patients had stage I or stage II disease and either a favorable or unfavorable prognosis. Median follow-up for the trials ranged between 2 and 11.4 years.
Patients who received the combination of radiation therapy and chemotherapy lived longer than patients who received chemotherapy alone. The authors estimated that one life would be saved for every 11 to 55 patients treated with combination therapy instead of chemotherapy alone. Patients who received combination therapy also had a lower risk of relapse. For every six patients treated with combination therapy instead of chemotherapy alone, the authors estimated, one relapse would be prevented.
Patients receiving either treatment experienced similar side effects during the trials. However, “long-term adverse effects such as secondary malignancies…can occur later than the reported observation times of the discussed trials,” explained the authors. This long lag time makes it impossible to determine from the available data if deaths due to late side effects differ between the two groups.
Two ongoing clinical trials are testing whether positron emission tomography (PET) scans can be used to determine if some patients with early-stage Hodgkin lymphoma can safely skip radiation therapy. (Descriptions of those trials can be found here and here .)
Treatment with trastuzumab (Herceptin) for 1 year following standard chemotherapy improved disease-free survival in women with HER2-positive early breast cancer. The finding comes from the third analysis of the Herceptin Adjuvant (HERA) trial , a large multicenter study that compared outcomes in patients randomly assigned to receive standard chemotherapy followed by trastuzumab with those in patients randomly assigned to receive chemotherapy alone (the observation group). The 4-year follow-up results were reported February 25 in Lancet Oncology.
Dr. Luca Gianni of the San Raffaele Institute in Milan, Italy, and his colleagues randomly assigned 1,703 women to receive 1 year of adjuvant therapy with trastuzumab and 1,698 women to the observation group. (A third group, not included in this analysis, received 2 years of trastuzumab.) After a median follow-up of 4 years, more than 78 percent of women in the trastuzumab group were free of recurrence or other disease-free survival event, compared with about 72 percent in the observation group. This 24 percent reduction in risk of an event was highly statistically significant .
Trastuzumab is a monoclonal antibody that targets tumor cells that overproduce a protein called HER2 and interferes with their growth. HER2-positive cancers, which make up about 20 percent of all breast cancers, are more aggressive and women with this form of breast cancer have a higher risk of disease recurrence and death. Trastuzumab extends survival of women with HER2-overexpressing metastatic breast cancer, and the HERA trial is one of several trials that were initiated to determine whether this treatment would benefit patients with early-stage disease as well.
Unlike results from an earlier analysis of the HERA trial, the 4-year follow-up results do not show a statistically significant difference in overall survival between the two groups. “These results are probably heavily influenced by the 52 percent of patients who crossed over from the observation group to the trastuzumab group,” noted Dr. Heikki Joensuu of Helsinki University Central Hospital in an accompanying editorial . Patients in the observation group who were disease free and did not have heart problems (a possible side effect of trastuzumab) were given the option of crossing over to receive trastuzumab because initial results of the HERA trial had shown a clear benefit in terms of reducing recurrence risk with 1 year of trastuzumab.
The latest analysis “provides further assurance” that giving trastuzumab after standard chemotherapy is effective for treatment of early HER2-positive breast cancer and that such treatment “continues to show a generally favorable safety profile with a low rate of congestive heart failure,” Dr. Joensuu wrote. Questions still remain about whether it’s best to give trastuzumab with chemotherapy or after chemotherapy ( the risk for heart complications increases when trastuzumab is combined with some chemotherapy drugs), and how long to treat with trastuzumab, he noted.
Also in the Journals: Denosumab Also Effective for Multiple Myeloma and Solid Tumors
Results from another randomized phase III trial of denosumab for cancer were published online February 22 in the Journal of Clinical Oncology (JCO). FDA approval of denosumab for the reduction of skeletal-related events (SREs) was based in part on this study as well. The nearly 1,800-patient trial had a design similar to that of the prostate cancer trial and included patients with multiple myeloma and a variety of advanced solid tumors (but specifically excluded patients with prostate and breast cancer). Patients who received denosumab had a reduced risk of SREs compared with patients who received zoledronic acid, although the reduction did not reach statistical significance. In an accompanying commentary in JCO, Dr. Howard West of the Swedish Cancer Institute in Seattle also addressed the economic implications of denosumab treatment, as well as a potential biomarker-driven approach to its use in patients with metastatic cancer.
The biological agent denosumab (Xgeva) is more effective than zoledronic acid at decreasing the risk of bone fractures and other skeletal-related events (SRE) in men with castration-resistant metastatic prostate cancer, according to results from a 1,904-patient phase III randomized clinical trial. The findings, in part, led to the FDA's 2010 approval of denosumab to reduce the risk of SREs in patients with solid tumors. (Denosumab is also approved to treat osteoporosis in postmenopausal women at increased risk of bone fractures and SREs and is sold under the trade name Prolia for that indication). Results from the trial, which was funded by denosumab’s manufacturer, Amgen, were reported online February 25 in The Lancet.
Participants in the trial had never received treatment with bisphosphonates, a class of drugs that includes zoledronic acid, the current standard of care to prevent SREs in men with advanced prostate cancer. SREs were defined as the first incidence of a bone fracture, spinal cord compression, or the use of radiation or surgery to alleviate bone pain. Men who received denosumab had an 18 percent increase in median time before a first SRE compared with men who received zoledronic acid (20.7 months versus 17.1 months), the trial’s lead investigator Dr. Karim Fizazi and colleagues reported. Denosumab treatment was not associated with improvements in either progression-free or overall survival .
The rate and type of side effects were similar in both treatment groups. Break down and death of bone in the jaw (osteonecrosis) was more common in the denosumab group, but the increased risk was not statistically significant.
Zoledronic acid must be delivered intravenously and can have serious side effects, including acute allergic reactions and damage to kidney function, the researchers explained. “These limitations do not apply to denosumab,” they wrote.
The trial results are “yet another milestone in the treatment of men with metastatic, castrate-resistant prostate cancer,” wrote Dr. Jeanny B. Aragon-Ching of George Washington University in a related commentary . But the results, she continued, raise “several issues” about the clinical use and impact of denosumab in cancer treatment. Because denosumab is more expensive than zoledronic acid, for example, Dr. Aragon-Ching posed the question of whether the modest delay in time to first SRE compared with zoledronic acid is “clinically significant enough to justify the choice of denosumab over zoledronic acid…especially in the absence of survival or progression benefit.”
A study of the incidence of genital human papillomavirus (HPV) infections in men has found that half of the participants were infected with at least one type of the virus, including types that can cause genital warts and cancer. The incidence of infection was both high and relatively constant across age groups (from 18 to 70 years of age), Dr. Anna Giuliano of the H. Lee Moffitt Cancer Center and Research Institute and her colleagues reported in a study published online February 28 in The Lancet.
Approximately 40 HPV types can be transmitted sexually. Some of these HPV types cause genital warts, and others (so-called high-risk or oncogenic types) can cause cancer. In men, HPV-related cancers include cancers of the penis , oral cavity , oropharynx (a subset of the head and neck that includes the tonsils), and anal canal .
Two vaccines that prevent persistent infections with the two high-risk types of HPV responsible for 70 percent of cervical cancers have been approved by the FDA for use in young women for the prevention of cervical cancer and some vulvar and vaginal cancers. One of these vaccines, Gardasil , also protects against infection with the two HPV types that cause 90 percent of genital warts and has been approved for use in young men and women for prevention of genital warts. And last December, Gardasil was approved for use in young men and women for the prevention of anal cancer. The new findings about the natural history of HPV infections in men provide much-needed information for developing realistic cost-effectiveness models about the use of HPV vaccinations in males internationally, the researchers said.
The cohort study enrolled 1,159 men from Brazil, Mexico, and the United States to investigate the prevalence and clearance of HPV in men. The acquisition of new infections was strongly associated with sexual behavior, as was the likelihood of clearing an infection. The median duration of infection with any HPV type was about 7 months, and for HPV 16, an oncogenic type, it was about 12 months. By the end of the 3-year study period, the majority of men had cleared their HPV infection.
In women, the risk of HPV infection is known to decline with increasing age. But this study found that in men, by contrast, the risk of infection appears to be stable throughout their lives. “If indeed men remain at high risk of acquiring new HPV infections throughout their lives, then vaccination of older men might be warranted,” the researchers said.
Because of strict criteria used for enrollment, the estimates of HPV incidence cannot be generalized to all men in the three countries, the researchers noted. They also cautioned against drawing conclusions about infection rates in other populations based on these results, although they noted that all studies to date have found high acquisition rates of HPV infection in men.
For more see: Human Papillomaviruses and Cancer
Also in the Journals: 2006 Lung Cancer Study Retracted
The authors of a study published in the New England Journal of Medicine—and reported in the August 15, 2006, issue of the NCI Cancer Bulletin—have retracted their research article. Dr. Anil Potti and his colleagues requested a retraction of their article on a genomic model to refine the prognosis of early-stage non-small cell lung cancer because they “tried and failed to reproduce results supporting the validation of the lung metagene model” using data from studies conducted by the American College of Surgeons Oncology Group and the Cancer and Leukemia Group B cooperative groups. A note about the retraction has been added to the NCI Cancer Bulletin article on this study.