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Treatment with lumpectomy and radiotherapy was associated with a significant reduction in breast cancer mortality in patients with ductal carcinoma in situ (DCIS), compared with a lumpectomy alone or a mastectomy alone, investigators reported in JAMA Oncology.
Among women who received adjuvant radiation, there was an associated 23% reduced risk of dying of breast cancer. This extrapolated to a cumulative mortality of 2.33% for those treated with lumpectomy alone and 1.74% for women treated with lumpectomy and radiotherapy at 15 years (adjusted hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; P less than .001).
“Although the clinical benefit is small, it is intriguing that radiotherapy has this effect, which appears to be attributable to systemic activity rather than local control,” wrote Vasily Giannakeas, MPH, of the Women’s College Research Institute, Toronto, and colleagues.
Emerging evidence suggests that adding radiotherapy to breast conserving surgery can reduce the risk of breast cancer mortality among women with DCIS and lower the risk of local recurrence. Because of the low rate of mortality associated with DCIS, the authors noted that it has been difficult to investigate deaths related to DCIS. The association of adjuvant radiotherapy with breast cancer survival in this population has also not yet been clearly established.
To determine the extent to which radiotherapy is associated with reduced risk of breast cancer mortality in patients treated for DCIS and identify patient subgroups who might derive the most benefit from radiotherapy, the authors conducted a historical cohort study using the Surveillance, Epidemiology, and End Results database. A total of 140,366 women diagnosed with first primary DCIS between 1998 and 2014 were identified, and three separate comparisons were made using 1:1 matching: lumpectomy with radiation versus lumpectomy alone, lumpectomy alone versus mastectomy, and lumpectomy with radiation therapy versus mastectomy.
A total of 35,070 women (25.0%) were treated with lumpectomy alone, 65,301 (46.5%) were treated with lumpectomy and radiotherapy, and 39,995 (28.5%) were treated with mastectomy.
The overall cumulative mortality for the entire cohort from breast cancer at 15 years was 2.03%. The actuarial 15-year mortality rate for the mastectomy group (2.26%) was similar to those who had lumpectomy without radiotherapy (2.33%).
The adjusted HR for death for mastectomy versus lumpectomy alone (based on 20,832 propensity-matched pairs) was 0.91 (95% CI, 0.78-1.05). The adjusted hazard ratios for death were 0.77 (95% CI, 0.67-0.88) for lumpectomy and radiotherapy versus lumpectomy alone (29,465 propensity-matched pairs), 0.91 (95% CI, 0.78-1.05) for mastectomy alone versus lumpectomy alone (20,832 propensity-matched pairs), and 0.75 (95% CI, 0.65-0.87) for lumpectomy and radiotherapy versus mastectomy (29,865 propensity-matched pairs).
When looking at subgroups and the effect of radiotherapy on mortality, the authors found the following: The HR was 0.59 (95% CI, 0.43-0.80) for patients aged younger than 50 years and 0.86 (95% CI, 0.73- 1.01) for those aged 50 years and older; it was 0.67 (95% CI, 0.51-0.87) for patients with ER-positive cancers, 0.50 (95% CI, 0.32-0.78) for ER-negative cancers, and 0.93 (95% CI, 0.77-1.13) for those with unknown ER status.
“How exactly radiotherapy affects survival is an important question that should be explored in future studies,” the authors concluded.
There was no outside funding source reported. Mr. Giannakeas is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award.
SOURCE: Giannakeas V et al. JAMA Network Open. 2018 Aug 10. doi:10.1001/jamanetworkopen.2018.1100.
In an accompanying editorial, Mira Goldberg, MD, and Timothy J. Whelan, BM, BCh, of the department of oncology at McMaster University, Hamilton, Ont., noted that the primary goal of using adjuvant radiotherapy in patients with ductal carcinoma in situ (DCIS) is to reduce the risk of local recurrence of DCIS or of invasive breast cancer.
Despite widespread screening with mammography, along with improvements in technology so as to detect even smaller lesions, “there is increased concern about the overdiagnosis of DCIS,” they wrote. Results from recent studies generally suggest that patients with good prognostic factors and who have a low risk of local recurrence at 10 years (10%) are unlikely to gain any major benefit from being treated with radiotherapy.
They also pointed out that there is growing interest in the use of molecular markers as a means to help detect patients who are at a lower risk of recurrence and thus who may not benefit from radiotherapy.
“The results of the study by Giannakeas and colleagues are reassuring,” the editorialists wrote, as it demonstrated that the risk of breast cancer mortality in patients with DCIS is very low, and the potential absolute benefit of radiotherapy is also quite small. (The number of patients that need to be treated to prevent a breast cancer death was 370.) These data continue to support a strategy for low-risk DCIS of omitting radiotherapy after lumpectomy. This is especially pertinent when “one considers the negative effects of treatment: the cost and inconvenience of 5-6 weeks of daily treatments, acute adverse effects such as breast pain and fatigue, and potential long-term toxic effects of cardiac disease and second cancers.”
The editorialists also highlighted the authors’ speculation that there could be additional systemic effects of radiotherapy, possibly resulting from an elicited immune response or radiation scatter to distant tissues. While this hypothesis is theoretically possible, their results could also be explained by confounding factors, such as a higher use of endocrine therapy in patients who received adjuvant radiotherapy.
Dr. Whelan has received research support from Genomic Health. This editorial accompanied the article by Giannakeas et al. (JAMA Network Open. 2018;1[4]e181102). No other disclosures were reported.
In an accompanying editorial, Mira Goldberg, MD, and Timothy J. Whelan, BM, BCh, of the department of oncology at McMaster University, Hamilton, Ont., noted that the primary goal of using adjuvant radiotherapy in patients with ductal carcinoma in situ (DCIS) is to reduce the risk of local recurrence of DCIS or of invasive breast cancer.
Despite widespread screening with mammography, along with improvements in technology so as to detect even smaller lesions, “there is increased concern about the overdiagnosis of DCIS,” they wrote. Results from recent studies generally suggest that patients with good prognostic factors and who have a low risk of local recurrence at 10 years (10%) are unlikely to gain any major benefit from being treated with radiotherapy.
They also pointed out that there is growing interest in the use of molecular markers as a means to help detect patients who are at a lower risk of recurrence and thus who may not benefit from radiotherapy.
“The results of the study by Giannakeas and colleagues are reassuring,” the editorialists wrote, as it demonstrated that the risk of breast cancer mortality in patients with DCIS is very low, and the potential absolute benefit of radiotherapy is also quite small. (The number of patients that need to be treated to prevent a breast cancer death was 370.) These data continue to support a strategy for low-risk DCIS of omitting radiotherapy after lumpectomy. This is especially pertinent when “one considers the negative effects of treatment: the cost and inconvenience of 5-6 weeks of daily treatments, acute adverse effects such as breast pain and fatigue, and potential long-term toxic effects of cardiac disease and second cancers.”
The editorialists also highlighted the authors’ speculation that there could be additional systemic effects of radiotherapy, possibly resulting from an elicited immune response or radiation scatter to distant tissues. While this hypothesis is theoretically possible, their results could also be explained by confounding factors, such as a higher use of endocrine therapy in patients who received adjuvant radiotherapy.
Dr. Whelan has received research support from Genomic Health. This editorial accompanied the article by Giannakeas et al. (JAMA Network Open. 2018;1[4]e181102). No other disclosures were reported.
In an accompanying editorial, Mira Goldberg, MD, and Timothy J. Whelan, BM, BCh, of the department of oncology at McMaster University, Hamilton, Ont., noted that the primary goal of using adjuvant radiotherapy in patients with ductal carcinoma in situ (DCIS) is to reduce the risk of local recurrence of DCIS or of invasive breast cancer.
Despite widespread screening with mammography, along with improvements in technology so as to detect even smaller lesions, “there is increased concern about the overdiagnosis of DCIS,” they wrote. Results from recent studies generally suggest that patients with good prognostic factors and who have a low risk of local recurrence at 10 years (10%) are unlikely to gain any major benefit from being treated with radiotherapy.
They also pointed out that there is growing interest in the use of molecular markers as a means to help detect patients who are at a lower risk of recurrence and thus who may not benefit from radiotherapy.
“The results of the study by Giannakeas and colleagues are reassuring,” the editorialists wrote, as it demonstrated that the risk of breast cancer mortality in patients with DCIS is very low, and the potential absolute benefit of radiotherapy is also quite small. (The number of patients that need to be treated to prevent a breast cancer death was 370.) These data continue to support a strategy for low-risk DCIS of omitting radiotherapy after lumpectomy. This is especially pertinent when “one considers the negative effects of treatment: the cost and inconvenience of 5-6 weeks of daily treatments, acute adverse effects such as breast pain and fatigue, and potential long-term toxic effects of cardiac disease and second cancers.”
The editorialists also highlighted the authors’ speculation that there could be additional systemic effects of radiotherapy, possibly resulting from an elicited immune response or radiation scatter to distant tissues. While this hypothesis is theoretically possible, their results could also be explained by confounding factors, such as a higher use of endocrine therapy in patients who received adjuvant radiotherapy.
Dr. Whelan has received research support from Genomic Health. This editorial accompanied the article by Giannakeas et al. (JAMA Network Open. 2018;1[4]e181102). No other disclosures were reported.
Treatment with lumpectomy and radiotherapy was associated with a significant reduction in breast cancer mortality in patients with ductal carcinoma in situ (DCIS), compared with a lumpectomy alone or a mastectomy alone, investigators reported in JAMA Oncology.
Among women who received adjuvant radiation, there was an associated 23% reduced risk of dying of breast cancer. This extrapolated to a cumulative mortality of 2.33% for those treated with lumpectomy alone and 1.74% for women treated with lumpectomy and radiotherapy at 15 years (adjusted hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; P less than .001).
“Although the clinical benefit is small, it is intriguing that radiotherapy has this effect, which appears to be attributable to systemic activity rather than local control,” wrote Vasily Giannakeas, MPH, of the Women’s College Research Institute, Toronto, and colleagues.
Emerging evidence suggests that adding radiotherapy to breast conserving surgery can reduce the risk of breast cancer mortality among women with DCIS and lower the risk of local recurrence. Because of the low rate of mortality associated with DCIS, the authors noted that it has been difficult to investigate deaths related to DCIS. The association of adjuvant radiotherapy with breast cancer survival in this population has also not yet been clearly established.
To determine the extent to which radiotherapy is associated with reduced risk of breast cancer mortality in patients treated for DCIS and identify patient subgroups who might derive the most benefit from radiotherapy, the authors conducted a historical cohort study using the Surveillance, Epidemiology, and End Results database. A total of 140,366 women diagnosed with first primary DCIS between 1998 and 2014 were identified, and three separate comparisons were made using 1:1 matching: lumpectomy with radiation versus lumpectomy alone, lumpectomy alone versus mastectomy, and lumpectomy with radiation therapy versus mastectomy.
A total of 35,070 women (25.0%) were treated with lumpectomy alone, 65,301 (46.5%) were treated with lumpectomy and radiotherapy, and 39,995 (28.5%) were treated with mastectomy.
The overall cumulative mortality for the entire cohort from breast cancer at 15 years was 2.03%. The actuarial 15-year mortality rate for the mastectomy group (2.26%) was similar to those who had lumpectomy without radiotherapy (2.33%).
The adjusted HR for death for mastectomy versus lumpectomy alone (based on 20,832 propensity-matched pairs) was 0.91 (95% CI, 0.78-1.05). The adjusted hazard ratios for death were 0.77 (95% CI, 0.67-0.88) for lumpectomy and radiotherapy versus lumpectomy alone (29,465 propensity-matched pairs), 0.91 (95% CI, 0.78-1.05) for mastectomy alone versus lumpectomy alone (20,832 propensity-matched pairs), and 0.75 (95% CI, 0.65-0.87) for lumpectomy and radiotherapy versus mastectomy (29,865 propensity-matched pairs).
When looking at subgroups and the effect of radiotherapy on mortality, the authors found the following: The HR was 0.59 (95% CI, 0.43-0.80) for patients aged younger than 50 years and 0.86 (95% CI, 0.73- 1.01) for those aged 50 years and older; it was 0.67 (95% CI, 0.51-0.87) for patients with ER-positive cancers, 0.50 (95% CI, 0.32-0.78) for ER-negative cancers, and 0.93 (95% CI, 0.77-1.13) for those with unknown ER status.
“How exactly radiotherapy affects survival is an important question that should be explored in future studies,” the authors concluded.
There was no outside funding source reported. Mr. Giannakeas is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award.
SOURCE: Giannakeas V et al. JAMA Network Open. 2018 Aug 10. doi:10.1001/jamanetworkopen.2018.1100.
Treatment with lumpectomy and radiotherapy was associated with a significant reduction in breast cancer mortality in patients with ductal carcinoma in situ (DCIS), compared with a lumpectomy alone or a mastectomy alone, investigators reported in JAMA Oncology.
Among women who received adjuvant radiation, there was an associated 23% reduced risk of dying of breast cancer. This extrapolated to a cumulative mortality of 2.33% for those treated with lumpectomy alone and 1.74% for women treated with lumpectomy and radiotherapy at 15 years (adjusted hazard ratio, 0.77; 95% confidence interval, 0.67-0.88; P less than .001).
“Although the clinical benefit is small, it is intriguing that radiotherapy has this effect, which appears to be attributable to systemic activity rather than local control,” wrote Vasily Giannakeas, MPH, of the Women’s College Research Institute, Toronto, and colleagues.
Emerging evidence suggests that adding radiotherapy to breast conserving surgery can reduce the risk of breast cancer mortality among women with DCIS and lower the risk of local recurrence. Because of the low rate of mortality associated with DCIS, the authors noted that it has been difficult to investigate deaths related to DCIS. The association of adjuvant radiotherapy with breast cancer survival in this population has also not yet been clearly established.
To determine the extent to which radiotherapy is associated with reduced risk of breast cancer mortality in patients treated for DCIS and identify patient subgroups who might derive the most benefit from radiotherapy, the authors conducted a historical cohort study using the Surveillance, Epidemiology, and End Results database. A total of 140,366 women diagnosed with first primary DCIS between 1998 and 2014 were identified, and three separate comparisons were made using 1:1 matching: lumpectomy with radiation versus lumpectomy alone, lumpectomy alone versus mastectomy, and lumpectomy with radiation therapy versus mastectomy.
A total of 35,070 women (25.0%) were treated with lumpectomy alone, 65,301 (46.5%) were treated with lumpectomy and radiotherapy, and 39,995 (28.5%) were treated with mastectomy.
The overall cumulative mortality for the entire cohort from breast cancer at 15 years was 2.03%. The actuarial 15-year mortality rate for the mastectomy group (2.26%) was similar to those who had lumpectomy without radiotherapy (2.33%).
The adjusted HR for death for mastectomy versus lumpectomy alone (based on 20,832 propensity-matched pairs) was 0.91 (95% CI, 0.78-1.05). The adjusted hazard ratios for death were 0.77 (95% CI, 0.67-0.88) for lumpectomy and radiotherapy versus lumpectomy alone (29,465 propensity-matched pairs), 0.91 (95% CI, 0.78-1.05) for mastectomy alone versus lumpectomy alone (20,832 propensity-matched pairs), and 0.75 (95% CI, 0.65-0.87) for lumpectomy and radiotherapy versus mastectomy (29,865 propensity-matched pairs).
When looking at subgroups and the effect of radiotherapy on mortality, the authors found the following: The HR was 0.59 (95% CI, 0.43-0.80) for patients aged younger than 50 years and 0.86 (95% CI, 0.73- 1.01) for those aged 50 years and older; it was 0.67 (95% CI, 0.51-0.87) for patients with ER-positive cancers, 0.50 (95% CI, 0.32-0.78) for ER-negative cancers, and 0.93 (95% CI, 0.77-1.13) for those with unknown ER status.
“How exactly radiotherapy affects survival is an important question that should be explored in future studies,” the authors concluded.
There was no outside funding source reported. Mr. Giannakeas is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award.
SOURCE: Giannakeas V et al. JAMA Network Open. 2018 Aug 10. doi:10.1001/jamanetworkopen.2018.1100.
FROM JAMA ONCOLOGY
Key clinical point: Lumpectomy and adjuvant radiotherapy together was superior to lumpectomy or mastectomy alone.
Major finding: The 15-year breast cancer mortality rate was 2.33% for lumpectomy alone, 1.74% for lumpectomy and radiation, and 2.26% for mastectomy.
Study details: A historical cohort study using Surveillance, Epidemiology, and End Results data that included 140,366 women diagnosed with first primary ductal carcinoma in situ.
Disclosures: There was no outside funding source reported. Mr. Giannakeas is supported by the Canadian Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award. No other disclosures were reported.
Source: Giannakeas V et al. JAMA Network Open. 2018 Aug 10. doi: 10.1001/jamanetworkopen.2018.1100.