Novel treatments and improvements in screening are responsible for the improvements in mortality rates from breast cancer from 2000 to 2012, a new study concludes.
The study was published online January 9 in JAMA.
It reports that 37% of the overall reduction in breast cancer mortality in 2012 was due to screening and that the rest was due to treatment, although these percentages vary with different molecular subtypes of breast cancer.
Of the 63% mortality reduction associated with treatment, 31% was attributable to chemotherapy, 27% to hormone therapy, and 4% to treatment with trastuzumab (multiple brands).
“These numbers represent very positive news for breast cancer patients,” commented lead author Sylvia K. Plevritis, PhD, Departments of Radiology and Biomedical Data Science, James H. Clark Center, Stanford, California.
“Advances in screening and treatment are saving patients’ lives, and this paper quantifies just how much of a difference these advances are making,” she said in a statement.
Senior author Jeanne Mandelblatt, MD, MPH, professor of oncology and medicine at Georgetown University School of Medicine, Washington, DC, added: “Newer drugs, particularly ones that are molecularly targeted, are associated with a greater reduction in breast cancer mortality than screening.
“However, screening is still having a significant effect in reducing breast cancer deaths,” she added.
Approached for comment, Deborah J. Rhodes, MD, professor of medicine at the Mayo Clinic, Rochester, Minnesota, said that the study is “valuable,” particularly inasmuch as the models agreed with each other with respect to general trends.
As such, she believes that the data in the study are important, “not only to assess how far we’ve come but also to look at opportunities in the future.”
However, Dr Rhodes thinks that the article “has the potential to be easily misinterpreted.
“One of the things that I’m struck by in this paper [is], frankly, how little of the gains were attributed to advances in imaging,” she said.
A previous study by the same authors found a higher contribution from screening in earlier years. In a study published in 2005, Dr Plevritis and colleagues reported that from 1970 to 2000, breast cancer screening contributed a median of 46% to the overall reduction in breast cancer mortality; developments in adjuvant treatment contributed the rest.
Since 2000, mammography has evolved from film to digital technology, and treatments such as aromatase inhibitors and trastuzumab have been added to the arsenal of adjuvant therapy, so Dr Plevritis and colleagues decided to conduct another study.
“There have been many investments in screening and treatment,” Dr Plevritis explained, adding: “We want to know what impact those investments have had in reducing mortality.
“It also helps us think about the future and how to make sure technologies and drugs that are making the biggest difference are disseminated most widely,” she said.
Study Details
For the current study, six independent research teams from across the United States added data covering the years 2000 to 2012 to the original dataset.
Each center developed a CISNET model that incorporated updated breast cancer incidence estimates, estrogen receptor (ER)/HER2 survival trends, screening use, and treatment patterns, as well as US mortality trends.
The team calculated that for women aged 30 to 79 years, screening and treatment were associated with a reduction in overall breast cancer mortality in 2000 of 37%, against an estimated baseline mortality rate of 64 deaths per 100,000 women.
Of this reduction, 44% was attributable to screening and 56% to treatment.
In 2012, the overall reduction in breast cancer mortality with screening and treatment was 49%, against an estimated baseline mortality rate of 63 deaths per 100,000 women. Of this reduction, 37% was attributable to screening, and 63% to treatment.
Variation by Breast Cancer Subtype
The relative contribution of screening and treatment to reductions in breast cancer mortality varied by the molecular subtype of the disease.
For women with ER+/HER2- breast cancer, screening contributed 36% of the mortality reduction, vs 64% for treatment.
For women with ER+/HER2+ disease, the figures were 31% and 69%, respectively; for ER-/HER2+ disease, they were 40% and 60%, respectively; and for ER-/HER2- disease, they were 48% and 52%, respectively.
Speaking to Medscape Medical News, Dr Plevritis said that to build on these findings, there is a “need to work towards not only predicting the risk of an individual woman developing breast cancer but also trying to predict the subtype.
“So if we know that some women are at risk for a specific subtype of cancer, we may have a very personalized approach in terms of more or less screening,” she said.
“The community has been thinking that this is necessary, and I think this study adds another dimension to that issue by showing the differences by molecular subtype.”
Dr Plevritis explained that although there is “a lot of activity” to determine the risk for a given subtype, particularly for women carrying a BRCA mutation, “for the vast majority of the population, we still are trying to determine what is the likely subtype of cancer they may develop if they develop breast cancer.”
She emphasized that breast cancer “is, of course, not just one disease; it’s a complex set of diseases, and they are really different from each other.
“They respond differently to different treatments, and it seems that we really do need to think about different screening strategies for women, depending on whether or not they are at risk for one subtype vs another.”
Dr Plevritis added: “In terms of policy, I think that that’s an important direction, that we really need to collect more data in order to understand that patient-specific risk by subtype.”
In an interview with Medscape Medical News, Dr Rhodes commented on the fact that screening in recent years appears to be making a smaller contribution to the overall reduction in breast cancer mortality than it had in the past. But it would be misleading to conclude that screening is having less of an impact on breast cancer mortality because of the inherent limitations of screening itself but rather that this reflects a continuing reliance on outdated technologies with poor yields, particularly for women with dense breasts, she said.
Dr Rhodes pointed out that as far back as 2010, she said in a TED Talk that, compared with film-based techniques, digital mammography “was a giant leap for imaging companies but a very tiny step for womenkind.”
The current article supports that view, because the findings suggest that only 4% of the incremental gain in breast cancer mortality reduction can be attributed to digital mammography.
Dr Rhodes said that, in her opinion, x-ray technology “is not the future” for detecting breast cancer, because “we know full well that dense breast tissue and cancers look the same on x-ray,” regardless of whether film, digital, or three-dimensional techniques are used.
She continued: “We’re stuck, in terms of contributing further reductions in breast cancer mortality, if we’re wedded to the idea that x-rays are the way we’re going to detect breast cancer.
“Half of women in here United States have dense breast tissue, so we’re effectively using a tool which we know does not work well in half of the women being screened. To me, that’s troubling.”
Dr Rhodes noted that mammography is inexpensive and widely accessible, and it is effective in detecting cancer in nondense breast. As such, it “meets many of the requirements that we tend to favor when we’re selecting a screening tool.
“But for women with dense breast tissue, it’s a poor tool.”
A number of functional techniques are available, such as MRI, positron-emission tomographic scanning, and molecular breast imaging. Studies have indicated that these modalities can detect between three and four times as many cancers as mammography in women with dense breasts.
Dr Rhodes said that her concern is that people will read the current study and think, ” ‘Okay, well, screening is not really contributing that much to the advances in breast cancer mortality.’ “
She added: “But that is not really, in my opinion, a fair assessment, because we are stuck in a screening paradigm that has barely changed in the last 20 years.
“If anything, we’re doing less screening by guidelines than we were doing 20 years ago, whereas treatment advances get almost immediately adopted.”
Dr Rhodes pointed out that “if you look at almost any other field in medicine, there has not been this degree of stagnation, but there has for imaging, and I don’t think anyone can argue with the fact that our approach to imaging has been stagnant.
“Yes, there have been these incremental advances for digital tomosynthesis, but the overall general approach has not changed, and therefore, why would we expect to see great reductions in breast cancer mortality from imaging, when we’re continuing to do the same things?”
She said that several important studies are underway to assess the potential for a shortened, or fast, MRI protocol to improve detection rates over those available with tomosynthesis in women with dense breast tissue. This approach should also lead to cost reductions compared with use of standard MRI.
Dr Rhodes added: “Another really important point that this paper doesn’t take into account is, the earlier you detect a cancer, the less morbidity is associated with your treatment.
“You might be eligible for a less invasive surgery, you might not need chemotherapy…so earlier detection is important, not just for mortality but also for morbidity,” she said.
This work was supported by a grant from the National Cancer Institute of the National Institutes of Health and in part by a grant from the American Cancer Society. The Collection of Breast Cancer Surveillance Consortium (BCSC) data used in the study was supported by grants from the National Cancer Institute. The collection of cancer and vital status data from the BCSC was supported in part by several state public health departments and cancer registries throughout the United States. Dr Plevritis has consulted for GRAIL. Several coauthors also have disclosed relevant financial relationships, which are listed in the original article. Dr Rhodes has disclosed no relevant financial relationships.
JAMA. Published online January 9, 2018. Abstract
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