NEW YORK (Reuters Health) Jun 16 - Breast-conserving therapy may provide better five-year locoregional control for women with triple-negative breast cancer than modified radical mastectomy without adjuvant radiation, according to a retrospective study from Canada.
National Comprehensive Cancer Network guidelines recommend adjuvant radiotherapy after modified radical mastectomy based only on tumor size and lymph node status, without regard to biologic subtype.
But the new results challenge the "paradigm in breast cancer that breast-conserving surgery followed by radiation therapy is equivalent to mastectomy alone" in all patients, said Dr. Jean-Philippe Pignol of Sunnybrook Health Sciences Centre in Toronto and colleagues in an editorial.
Instead, mastectomy for aggressive disease like triple-negative breast cancer may be the wrong approach, they wrote.
As reported online June 13 in the Journal of Clinical Oncology, Dr. Bassam Abdulkarim and colleagues at McGill University in Montreal reviewed all cases of triple-negative breast cancer at their institution from 1998-2008 (n=768), i.e., all women whose tumors didn't express receptors for estrogen, progesterone, or human epidermal growth factor receptor-2 (HER2).
As initial treatment, 42% of patients received breast-conserving therapy, 37% had modified radical mastectomy alone, and 21% had modified radical mastectomy plus adjuvant radiotherapy. Eighty-five percent received chemotherapy. The median follow-up in the study was 7.2 years.
Five-year, locoregional recurrence-free survival was 94%, 85%, and 87% for breast-conserving therapy, modified radical mastectomy and modified radical mastectomy plus radiotherapy, respectively (P<.001).
When investigators analyzed only the type of initial treatment, the rate of locoregional recurrence was significantly higher in the modified radical mastectomy group (HR, 2.61, P<.001) and the modified radical mastectomy plus radiotherapy group (HR, 2.38, P<.001) compared to patients receiving breast conserving therapy.
When they analyzed multiple variables, including tumor size, grade, lymph node status, lymph vascular invasion and adjuvant chemotherapy, modified radical mastectomy without radiotherapy was an independent predictor of local recurrence (HR 3.44, P<.001) however, there was no difference between those who also underwent radiotherapy and those who received breast conserving therapy.
The investigators also looked separately at 468 women with T1-2N0 disease. In this group, five-year locoregional recurrence-free survival was 96% after breast-conserving therapy and 90% after modified radical mastectomy without radiation (P=.022). On multivariate analysis, modified radical mastectomy without radiotherapy was the only independent factor associated with higher local recurrence (HR, 2.53, P=.027).
"Taken together, our findings emphasize that the current guidelines should take into account the intrinsic risk associated with this biologic subtype," the investigators, the authors say.
In their editorial, Dr. Pignol and colleagues say that clinically, the data should be used to inform triple-negative breast cancer patients of their likely outcomes. Also, they suggest, "adjuvant radiotherapy after mastectomy should at least be discussed" with such women.
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PROSTATE CANCER KILLS 50% IN UK BU ONLY 15% IN USA-PSA TESTING MAY BE THE ANSWER
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New data from the United Kingdom show that prostate cancer kills half of the men diagnosed with this disease, and challenge the notion that prostate cancer patients "are more likely to die with, rather than of, their disease," according to the researchers.
The situation is much different in the United States, where recent estimates suggest that only about 15% of men diagnosed with prostate cancer die from this disease.
The main reason for this huge difference is the high uptake of testing for prostate-specific antigen (PSA) in asymptomatic men in the United States, and the low uptake in the United Kingdom, say experts on both sides of the Atlantic.
Both situations are described as extreme by those on the other side. British researchers say that routine PSA testing in the United States is picking up disease that might be clinically insignificant, leading to overdiagnosis and overtreatment of prostate cancer. American researchers argue that PSA testing is picking up prostate cancer at an earlier stage of disease, when it is still treatable and curable, which results in the much lower mortality rates.
"If you are screening too aggressively, there is no question that you will overtreat, but the other end of the spectrum is that you have a cancer that is very curable but you still end up having half of the patients dying of the disease because they are presenting at late stages" said Brantley Thrasher, MD, FACS, professor of urology at the University of Kansas in Kansas City, who acts as a spokesperson for the American Urological Association.
"I would rather have the potential — and I emphasize the potential — for overtreating than swing the other way and lose all of these patients to a disease that is curable," Dr. Thrasher explained in an interview with Medscape Medical News.
New British Analysis
The new British data come from an analysis of 50,066 men diagnosed with prostate cancer between 1997 and 2006 from the Thames Cancer Registry, which covers a population of 12 million in South East England. Subjects were followed to the end of 2007.
During that period of time, there was little uptake of PSA testing in asymptomatic men in the United Kingdom.
The situation is different in the United States, where there is a high uptake of PSA testing, and has been for some time, lead researcher Simon Chowdhury, MD, consultant oncologist at Guy's and St Thomas' NHS Foundation Trust in London, United Kingdom, told Medscape Medical News.
Dr. Chowdhury presented the findings at the 2011 Meeting of United Kingdom Association of Cancer Registries and National Cancer Intelligence Network (NCIN), held in London.
The analysis found that prostate cancer was the cause of death in 49.7% of the men who had been diagnosed with the disease. The other causes of death were cardiovascular disease (17.8%), other cancers (11.8%), pneumonia (7.5%), and other causes (13.25%).
Prostate cancer remained an important cause of death even when the data were analyzed according to age, cancer stage, and first treatment, the researchers note.
Prostate cancer was the cause of death in 74.3% of men who had stage IV cancer at diagnosis, in 46.4% of all men 75 years and older, and in 31.6% of all men who underwent radical prostatectomy.
"Prostate cancer was the underlying cause of death in a substantial proportion of men," the researchers conclude, "and remained an important cause of death in all subgroups, including those treated with curative intent and older men."
"Our data show that a high proportion of men with prostate cancer die from the cancer," commented study author Henrik Møller, BA, BSc, MSc, DM, FFPH, professor of epidemiology at King's College London, and director of the Thames Cancer Registry. Dr. Møller, who is also head of analysis and research at the NCIN, added: "Our findings challenge the commonly-held view that most men with prostate cancer will die with the disease, rather than from it."
Setting of Low PSA Testing
The British researchers point out that their findings pertain to settings where there is a low uptake of PSA testing in asymptomatic men. In such a setting, "our findings challenge the notion that prostate cancer is a negligible problem in any subgroup, as defined by age, stage, or treatment," they note.
Dr. Chowdhury explained in an interview with Medscape Medical News that PSA testing was introduced in the United Kingdom in the early 1990s, but it is not routinely performed in asymptomatic men.
The situation is different in the United States, where there is a high uptake of PSA testing, with reports that more than 50% of men older than 65 years of age are tested, and many of the men tested are asymptomatic. This PSA testing in asymptomatic men might result in overdiagnosis and overtreatment of prostate cancer, Dr. Chowdhury said, because "some of the prostate cancers that are picked up are small and some may be clinically insignificant."
Dr. Chowdhury noted that the ratio of prostate cancer deaths to prostate cancer diagnoses is very different in the 2 regions — about 1 to 6.0 in the United States (based on estimates from the 2010 SEER database, showing a diagnosis in 215,000 men and 30,000 deaths) and about 1 to 3.7 in the United Kingdom (based on 2008 Cancer Research UK data, which show that there were 37,000 diagnoses and 10,100 deaths from prostate cancer).
There is a difference in the stage of prostate cancer at diagnosis — some American reports suggest that about 80% of the disease is localized, whereas in the United Kingdom, although most disease is also localized, there is a higher proportion of cancers diagnosed at an advanced stage, Dr. Chowdhury explained. Widespread PSA testing picks up prostate cancer at an earlier stage, which might be less aggressive and less clinically significant, he said.
"Not a Trivial Disease"
This is an extremely important study, which highlights the fact that prostate cancer is not a trivial disease for a large number of men in the United Kingdom who suffer from it," said Malcolm Mason, MD, head of oncology and palliative medicine at Cardiff University School of Medicine, United Kingdom. Dr. Mason is also chair of the UK National Cancer Research Institute's Prostate Cancer Clinical Studies Group, and was commenting in a statement issued by Cancer Research UK.Particularly for men with advanced prostate cancer, their disease poses a significant threat to their health and their life, and the old notion that 'most men die with it, not of it' is simply not true."
Since that study was carried out, there have been a number of important advances in treatment, Dr. Mason noted. "It is possible that not all of the men in this study who died of prostate cancer would die of it today with modern treatment," he said. In addition, many more men are diagnosed at a much earlier stage; for these men, the outlook is excellent, even without treatment, he added.
Need for Earlier Diagnosis and Treatment
Dr. Thrasher agreed with the conclusion that prostate cancer is not a trivial disease. "This study highlights the fact that prostate cancer can be a deadly disease," he said. "It speaks volumes about what happens when the cancer is advanced and out of the confines of the organ — it will kill you."
These data add weight to the argument for screening for prostate cancer, he said. They reinforce the need for earlier diagnosis and earlier treatment of the disease, and although the PSA test has its problems, it does result in both.
"There is no question that this is happening in the United States; we are finding and treating prostate cancer earlier," he said.
Dr. Thrasher cited 2010 estimates, from the Cancer Journal for Clinicians,that there were 217,000 new cases of prostate cancer diagnosed in the United States and 32,500 cancer deaths, which gives a mortality rate from the disease of 15%. In the United Kingdom, the rate is 50%.
There is a similar situation in Japan, he noted, where there is no routine PSA screening. Dr. Thrasher explained that he recently had the opportunity to talk to Japanese urologists during a joint meeting of the American and Japanese urological associations in Hawaii, and they were saying that by the time they see prostate cancer, it has often advanced to a stage where it is inoperable and not suitable for radiation.
Dr. Thrasher acknowledged that routine PSA testing can lead to the overdiagnosis and overtreatment of prostate cancer that might not be clinically significant. "We are starting to see some pullback as a result of this," he said, and although it is slow to gain ground in the United States, there is more use now of active surveillance as a treatment option, he told Medscape Medical News."We are starting to do this, especially in older men with low-grade, low-volume disease," he said. "However, right now, that is not mainline, and it is not a standard of care," he emphasized: "It is one option."
The very real benefit from PSA testing — finding prostate cancer at an earlier stage of disease, when it is still curable, which saves lives — has to be weighed against the potential for overdiagnosis and overtreatment, and the potential for anxiety from routine testing, he concluded. These latest data from the United Kingdom show that when there is no PSA testing, "you are losing about half your patients to the disease, and so it lends credibility toward leaning the other way," he said.
2011 Meeting of United Kingdom Association of Cancer Registries and National Cancer Intelligence Network (NCIN): Abstract 86. Presented June 16, 2011.
The situation is much different in the United States, where recent estimates suggest that only about 15% of men diagnosed with prostate cancer die from this disease.
The main reason for this huge difference is the high uptake of testing for prostate-specific antigen (PSA) in asymptomatic men in the United States, and the low uptake in the United Kingdom, say experts on both sides of the Atlantic.
Both situations are described as extreme by those on the other side. British researchers say that routine PSA testing in the United States is picking up disease that might be clinically insignificant, leading to overdiagnosis and overtreatment of prostate cancer. American researchers argue that PSA testing is picking up prostate cancer at an earlier stage of disease, when it is still treatable and curable, which results in the much lower mortality rates.
"If you are screening too aggressively, there is no question that you will overtreat, but the other end of the spectrum is that you have a cancer that is very curable but you still end up having half of the patients dying of the disease because they are presenting at late stages" said Brantley Thrasher, MD, FACS, professor of urology at the University of Kansas in Kansas City, who acts as a spokesperson for the American Urological Association.
"I would rather have the potential — and I emphasize the potential — for overtreating than swing the other way and lose all of these patients to a disease that is curable," Dr. Thrasher explained in an interview with Medscape Medical News.
New British Analysis
The new British data come from an analysis of 50,066 men diagnosed with prostate cancer between 1997 and 2006 from the Thames Cancer Registry, which covers a population of 12 million in South East England. Subjects were followed to the end of 2007.
During that period of time, there was little uptake of PSA testing in asymptomatic men in the United Kingdom.
The situation is different in the United States, where there is a high uptake of PSA testing, and has been for some time, lead researcher Simon Chowdhury, MD, consultant oncologist at Guy's and St Thomas' NHS Foundation Trust in London, United Kingdom, told Medscape Medical News.
Dr. Chowdhury presented the findings at the 2011 Meeting of United Kingdom Association of Cancer Registries and National Cancer Intelligence Network (NCIN), held in London.
The analysis found that prostate cancer was the cause of death in 49.7% of the men who had been diagnosed with the disease. The other causes of death were cardiovascular disease (17.8%), other cancers (11.8%), pneumonia (7.5%), and other causes (13.25%).
Prostate cancer remained an important cause of death even when the data were analyzed according to age, cancer stage, and first treatment, the researchers note.
Prostate cancer was the cause of death in 74.3% of men who had stage IV cancer at diagnosis, in 46.4% of all men 75 years and older, and in 31.6% of all men who underwent radical prostatectomy.
"Prostate cancer was the underlying cause of death in a substantial proportion of men," the researchers conclude, "and remained an important cause of death in all subgroups, including those treated with curative intent and older men."
"Our data show that a high proportion of men with prostate cancer die from the cancer," commented study author Henrik Møller, BA, BSc, MSc, DM, FFPH, professor of epidemiology at King's College London, and director of the Thames Cancer Registry. Dr. Møller, who is also head of analysis and research at the NCIN, added: "Our findings challenge the commonly-held view that most men with prostate cancer will die with the disease, rather than from it."
Setting of Low PSA Testing
The British researchers point out that their findings pertain to settings where there is a low uptake of PSA testing in asymptomatic men. In such a setting, "our findings challenge the notion that prostate cancer is a negligible problem in any subgroup, as defined by age, stage, or treatment," they note.
Dr. Chowdhury explained in an interview with Medscape Medical News that PSA testing was introduced in the United Kingdom in the early 1990s, but it is not routinely performed in asymptomatic men.
The situation is different in the United States, where there is a high uptake of PSA testing, with reports that more than 50% of men older than 65 years of age are tested, and many of the men tested are asymptomatic. This PSA testing in asymptomatic men might result in overdiagnosis and overtreatment of prostate cancer, Dr. Chowdhury said, because "some of the prostate cancers that are picked up are small and some may be clinically insignificant."
Dr. Chowdhury noted that the ratio of prostate cancer deaths to prostate cancer diagnoses is very different in the 2 regions — about 1 to 6.0 in the United States (based on estimates from the 2010 SEER database, showing a diagnosis in 215,000 men and 30,000 deaths) and about 1 to 3.7 in the United Kingdom (based on 2008 Cancer Research UK data, which show that there were 37,000 diagnoses and 10,100 deaths from prostate cancer).
There is a difference in the stage of prostate cancer at diagnosis — some American reports suggest that about 80% of the disease is localized, whereas in the United Kingdom, although most disease is also localized, there is a higher proportion of cancers diagnosed at an advanced stage, Dr. Chowdhury explained. Widespread PSA testing picks up prostate cancer at an earlier stage, which might be less aggressive and less clinically significant, he said.
"Not a Trivial Disease"
This is an extremely important study, which highlights the fact that prostate cancer is not a trivial disease for a large number of men in the United Kingdom who suffer from it," said Malcolm Mason, MD, head of oncology and palliative medicine at Cardiff University School of Medicine, United Kingdom. Dr. Mason is also chair of the UK National Cancer Research Institute's Prostate Cancer Clinical Studies Group, and was commenting in a statement issued by Cancer Research UK.Particularly for men with advanced prostate cancer, their disease poses a significant threat to their health and their life, and the old notion that 'most men die with it, not of it' is simply not true."
Since that study was carried out, there have been a number of important advances in treatment, Dr. Mason noted. "It is possible that not all of the men in this study who died of prostate cancer would die of it today with modern treatment," he said. In addition, many more men are diagnosed at a much earlier stage; for these men, the outlook is excellent, even without treatment, he added.
Need for Earlier Diagnosis and Treatment
Dr. Thrasher agreed with the conclusion that prostate cancer is not a trivial disease. "This study highlights the fact that prostate cancer can be a deadly disease," he said. "It speaks volumes about what happens when the cancer is advanced and out of the confines of the organ — it will kill you."
These data add weight to the argument for screening for prostate cancer, he said. They reinforce the need for earlier diagnosis and earlier treatment of the disease, and although the PSA test has its problems, it does result in both.
"There is no question that this is happening in the United States; we are finding and treating prostate cancer earlier," he said.
Dr. Thrasher cited 2010 estimates, from the Cancer Journal for Clinicians,that there were 217,000 new cases of prostate cancer diagnosed in the United States and 32,500 cancer deaths, which gives a mortality rate from the disease of 15%. In the United Kingdom, the rate is 50%.
There is a similar situation in Japan, he noted, where there is no routine PSA screening. Dr. Thrasher explained that he recently had the opportunity to talk to Japanese urologists during a joint meeting of the American and Japanese urological associations in Hawaii, and they were saying that by the time they see prostate cancer, it has often advanced to a stage where it is inoperable and not suitable for radiation.
Dr. Thrasher acknowledged that routine PSA testing can lead to the overdiagnosis and overtreatment of prostate cancer that might not be clinically significant. "We are starting to see some pullback as a result of this," he said, and although it is slow to gain ground in the United States, there is more use now of active surveillance as a treatment option, he told Medscape Medical News."We are starting to do this, especially in older men with low-grade, low-volume disease," he said. "However, right now, that is not mainline, and it is not a standard of care," he emphasized: "It is one option."
The very real benefit from PSA testing — finding prostate cancer at an earlier stage of disease, when it is still curable, which saves lives — has to be weighed against the potential for overdiagnosis and overtreatment, and the potential for anxiety from routine testing, he concluded. These latest data from the United Kingdom show that when there is no PSA testing, "you are losing about half your patients to the disease, and so it lends credibility toward leaning the other way," he said.
2011 Meeting of United Kingdom Association of Cancer Registries and National Cancer Intelligence Network (NCIN): Abstract 86. Presented June 16, 2011.
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