Trimodality treatment—chemotherapy, surgery, and radiation therapy—has been shown to significantly extend five- and 10-year survival for women with inflammatory breast cancer (IBC), yet many patients are not receiving all three, especially women from low-income backgrounds and those receiving public health care coverage, as well as women in certain regions of the country. That is the conclusion of a review of data on 10,197 patients treated between 1998 and 2010.
In a study now available online ahead of print in the Journal of Clinical Oncology (doi: 10.1200/JCO.2014.55.1978), researchers from the University of Texas MD Anderson Cancer Center analyzed data in the National Cancer Data Base (NCDB) and found that while overall use of trimodality treatment for IBC increased over the years studied—annual rates fluctuated between 58.4 and 73.4 percent—the highest five- and 10-year survival rates were found among patients who received trimodality treatment (55.4% and 37.3%, respectively), compared with those who received a combination of surgery plus chemotherapy, surgery plus radiotherapy, or surgery alone.
“We found statistically significant differences in treatment and associated outcomes based on patients' demographic status. We need to better identify and understand barriers to care,” said Natasha M. Rueth, MD, who led the team while at MD Anderson in the Department of Surgical Oncology, but is now a surgical oncologist at the Virginia Piper Cancer Institute, Abbott Northwestern Hospital, in Minneapolis.
A number of factors may be behind underutilization of trimodality treatment in such patients, she said in an interview, emphasizing the need for criteria and the importance of developing biomarkers for IBC to help oncologists better recognize and differentiate such cancer patients at the earliest possibility.
“We need to identify these patients, especially women with aggressive IBC, and ensure they are receiving all of the treatment options available. We know that trimodality treatment is best for optimizing survival, yet many women are not being given that opportunity—for whatever reasons. Having biomarkers for IBC and implementing criteria would surely help, but right now we have neither.”
The study included only women who had access to medical care who were clinically well enough to undergo aggressive treatment; excluded were those with advanced disease; those who had disease progression while on chemotherapy, rendering them nonsurgical candidates; and those in such a medically frail condition that full multimodality treatment was precluded.
The study showed that trimodality treatment rates fluctuated and that women were significantly less likely to receive therapy if they were older, diagnosed earlier in the study period, lived in regions of the country outside of the Midwest, had lower incomes or received public insurance, and had more comorbidities.
But even after adjusting for potential confounding variables, trimodality therapy remained a significant independent predictor of survival, the results showed.
“The bottom line is that there are several factors that appear to play an important role in whether or not patients with IBC received full therapy,” Ruehl said. “Most of the patients were initially treated at academic hospitals, but then returned home for follow-up care, where awareness of the need for ongoing treatment may not be as well understood. For elderly patients, transportation appears to be a big problem, so we need to expand social support programs to help.”
Special Problems Facing MDs
One especially troubling finding, according to the study, was that almost one third of the women did not have pathologic lymph node status reported, despite the knowledge that IBC is associated with axillary lymph node involvement in 55 to 85 percent of cases, and is a predictor of patient survival.
A critical issue, she said, is that existing recommendations for the care of patients with IBC are largely based on observational studies or are extrapolated from studies of patients with noninflammatory, locally advanced breast cancer, resulting in consensus-based rather than evidence-based treatment recommendations. Clinicians are further challenged by the fact that IBC is a clinical diagnosis representing a broad spectrum of disease presentations, she added.
Ruehl said it was not surprising that treatment varied by year and geographic location because treatment patterns may fluctuate with current expert opinion, community awareness, or geographic trends. The researchers were, however, disappointed, she said, to find that 5.3 percent of women were treated with substandard segmental mastectomy rather than total mastectomy—a surgical option that is associated with poor cosmetic outcomes and unacceptably high positive margin and local recurrence rates.
Little has changed since the study ended in 2010, she noted. “There are still no criteria or diagnostic tests to differentiate IBC from other breast cancers, which is why having both biomarkers and separate criteria is so important.”
Lack of Awareness a Big Barrier
Asked for her opinion for this article, Beth Overmoyer, MD, Director of the Inflammatory Breast Cancer Program at the Susan F. Smith Center for Women's Cancers at Dana-Farber Cancer Institute, said that lack of awareness of inflammatory breast cancer is a big barrier.
“Trimodality is the optimal treatment for women with IBC, and is supported by the medical literature, but this study lends support for the need to increase awareness of this fact among patients and providers alike,” she said.
The reported similarity in outcomes between radiation treatment and surgery in the absence of chemotherapy was surprising, she said. “It is likely that this was due to the small number of patients in the study, but this is not supported by other research. My only concern is that the findings lend some support to the idea that these women do not require chemotherapy, which is an incorrect assumption.”
Overmoyer explained that diagnosing IBC can be difficult, and the criteria for breast cancer diagnosis have changed over the study period, which could limit the validity of diagnosis of some women included, but this further underscores the need for biological criteria for diagnosis.
With regard to regional variations, she said the incidence of IBC is greater in the Midwest and the Northeast, so it is not surprising that there is better understanding of the condition among oncologists and diagnosticians in those regions, and therefore a higher rate of trimodality treatment.
“This indicates that greater awareness and experience among clinicians leads to better diagnosis and treatment, but if this is being missed in other regions, then more women are not receiving appropriate care.”
Using biomarkers might help, but there too there are problems, she said. “There are data that different expression markers can work to identify inflammatory breast cancer, but right now they are not used on a routine basis—perhaps because of their cost, or the time involved in testing. The IBC community needs to focus on this, and the International IBC Consortium should be taking the lead.”
Overmoyer also said she was not surprised that the researchers found that many women are not undergoing post-surgical radiation treatment: “Treatment is very aggressive and takes approximately one year, but many of these patients are already exhausted following chemotherapy and surgery, and the prospect of ongoing radiotherapy is difficult for them despite the evidence supporting its use.
“All of these treatments are necessary for women with IBC, and we need to be the cheerleaders driving this point home. It is really a matter of bringing the issue forward and motivating clinicians and patients to comply with the data on improved outcomes with trimodality treatment.”