Is growing MRI use leading to more invasive breast cancer surgery?

Heavy use of magnetic resonance imaging (MRI) may be leading to unnecessary breast removal in older women with breast cancer, according to a study by Yale School of Medicine researchers in the current issue of Breast Cancer Research and Treatment.

“These data are concerning because the long-term benefits associated with bilateral mastectomy for older women with breast cancer are unclear,” said the study’s lead author Cary Gross. M.D., associate professor of internal medicine at Yale School of Medicine and director of the Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center at Yale Cancer Center.

“Patient concern about recurrence and survival must be balanced with the increased risk for complications associated with more aggressive cancer surgery, particularly when there is no proven benefit of the more aggressive option,” Gross added.

The research team tracked the use of breast MRI and surgical care of 72,461 female Medicare beneficiaries age 67-94 who were diagnosed with breast cancer during 2000 to 2009.

The team found a considerable increase in the use of preoperative breast MRI over the study period from 1% in 2000-2001 to 25% in 2008-2009. The researchers also found that women who received an MRI were more likely to subsequently undergo more aggressive surgical treatment. In women who received mastectomy, 12.5% of those who had MRI received bilateral mastectomy, while only 4.1% of those who did not have MRI had bilateral mastectomy.

The study also revealed that women undergoing MRI were more likely to have a contralateral prophylactic mastectomy (surgery to remove both breasts when cancer was only found in one breast). Among women who underwent mastectomy, 6.9% of women who had an MRI underwent contralateral prophylactic mastectomy, compared to 1.8% in women who did not have an MRI.

“There has been no randomized controlled clinical trial demonstrating improved outcomes for women who undergo preoperative breast MRI at any age,” said Brigid Killelea, M.D., assistant professor of surgery at Yale School of Medicine, and first author on the study. “Breast conserving therapy, when feasible, remains the preferred approach for women with early stage breast cancer.”

Killelea et al., (2013). Trends and clinical implications of preoperative breast MRI in Medicare beneficiaries with breast cancer. Breast Cancer Res. Treat., EPub Ahead of Print, doi:10.1007/s10549-013-2656-1 [Abstract]

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Effect of obesity on patients with advanced non-small cell lung cancer

Obesity increases health risks for many things. Researchers wanted to know the impact of obesity on outcomes of patients with advanced non-small cell lung cancer. In the September issue of the International Association for the Study of Lung Cancer’s journal, the Journal of Thoracic Oncology (JTO), researchers conclude that obese patients had superior outcomes early on in the study, but then experienced increased hazards.

During the period from 1993 to 2004, the Eastern Cooperative Oncology Group enrolled 2684 patients to three phase III trials of first-line systemic chemotherapy for advanced NSCLC. At a median follow-up of 64.9 months, 2585 of the patients were declared eligible and included in this research. The patients had their body mass index (BMI) calculated. Consistent with the general population, 4.6 percent of patients were underweight, 44.1 percent were normal weight, 34.3 percent of patients were classified as overweight, and 16.9 percent were obese.

The median overall survival estimated among underweight patients was 7.0 months, among normal weight patients was 8.6 months, among overweight patients was 9.3 months and among obese patients was 11.0 months.

In multivariable models, obese patients had significantly different overall survival when compared with normal-weight and overweight patients; however, their risk of death from any cause increased dramatically once they had been on study longer than 16 months.

Researchers says, “this indicates that the protective effect of obesity in lung cancer patients is for a limited time, after which the ultimate impact of obesity on survival from all causes supersedes.”

Dahlberg et al., (2013). Body Mass Index and Its Association with Clinical Outcomes for Advanced Non-Small-Cell Lung Cancer Patients Enrolled on Eastern Cooperative Oncology Group Clinical Trials. J.Thoracic Oncol., EPub Ahead of Print [Abstract]

 

Emerging cancer drugs may drive bone tumors

Cancer drugs should kill tumors, not encourage their spread. But new evidence suggests that an otherwise promising class of drugs may actually increase the risk of tumors spreading to bone, according to researchers at Washington University School of Medicine in St. Louis.

The drugs, IAP antagonists, block survival signals that many cancer cells rely on to stay alive. Working in mice, the investigators found that targeting the same protein that makes tumors vulnerable to death also overactivates cells called osteoclasts, which are responsible for tearing down bone. The research appears in the February issue of Cancer Discovery.

“These investigational drugs are getting broad attention right now because they seem to be very effective against primary tumors,” says senior author Deborah V. Novack, MD, PhD, associate professor of medicine. “There is also excitement because until now, these drugs have not appeared to have major side effects.”

In light of the study, Novack urges oncologists to think about protecting bone in patients taking IAP antagonists, including patients with cancers that don’t typically spread to bone. Numerous IAP antagonists are in early clinical trials against breast, lung, pancreatic, ovarian, prostate, liver, skin and blood cancers.

“For many of these cancers, doctors are not watching bone,” Novack says. “Osteoporosis is not the biggest concern when treating cancer, but if they’re not doing bone scans, they may miss a cancer spreading to bone.”

To maintain healthy bone, osteoclasts work in tandem with cells that build new bone. But IAP antagonists overactivate osteoclasts, destroying bone that is not replaced. In mice, the researchers showed that the drug led to osteoporosis, creating an environment that encouraged tumor growth in degrading bone, even while simultaneously killing breast cancer cells elsewhere.

After showing that the problem with IAP antagonists is specific to bone, Novack and her colleagues tested long-established drugs called bisphosphonates that inhibit osteoclasts and are used to treat osteoporosis.

“We found that bisphosphonate treatment protected bone from the negative effects of these drugs,” Novack says. “While bisphosphonates are common for breast cancer patients, they’re not, for example, commonly given to lung cancer patients. But since IAP antagonists are now in lung cancer trials, we’re saying doctors may want to consider bisphosphonate treatment for lung cancer or other cancer patients receiving these drugs. Or at least closely monitor the bone status.”

IAP antagonists are now only available to patients enrolled in phase 1 or 2 clinical trials. While these kinds of trials examine the short-term safety and effectiveness of new drugs, the researchers say they may not catch bone metastasis.

“These trials do not necessarily look for long-term effects of the drugs,” says Chang Yang, MD, PhD, staff scientist and the paper’s first author. “If the cancer is going to metastasize to bone, it may take six months to two years to see that outcome. This may not be seen during the clinical trial.”

Numerous drug companies are developing IAP antagonists intended for many kinds of cancer, but only Genentech agreed to provide Novack and her colleagues with its drug, called BV6, to evaluate in the study. Because the investigators could not obtain other proprietary IAP antagonists, they also made two other similar drug compounds and found them to have the same detrimental effects on the bone.

And to further ensure that over-stimulated osteoclasts are the only culprit in the bone metastasis associated with these new drugs, they performed studies in mice that lack the ability to dial up the production of osteoclasts. Even when given IAP antagonists, these mice were protected from osteoporosis and osteoclast activation.

Together, Novack says the studies have demonstrated that these results are unlikely to be a quirk of a particular compound.

“The osteoporosis and spread of tumors we see in bone are unintended side effects of IAP antagonists, but they’re not off-target effects,” she says. “They’re based on the mechanism of action for the entire class of drugs.”

Yang et al., (2013). Anticancer IAP inhibition increases bone metastasis via unexpected osteoclast activation. Cancer Discovery3: 125-127 [Abstract]