User login
‘Strong evidence’ links obesity to cancers
There is strong evidence linking adiposity to esophageal adenocarcinoma, multiple myeloma, and cancer of the colon, rectum, biliary tract, pancreas, endometrium, kidney, and postmenopausal breast, according to the authors of an umbrella review published in the Feb. 28 edition of the BMJ.
“Several meta-analyses support the link between obesity and cancer, but substantial heterogeneity exists between studies,” wrote Maria Kyrgiou, MD, of Imperial College London and her coauthors. “The reported associations may be causal, but they may also be flawed, as inherent study biases such as residual confounding and selective reporting of positive results may exaggerate the effect of obesity on cancer.”
In this umbrella review, researchers analyzed 49 papers that included a total of 204 meta-analyses, which in turn summarized 2,179 individual study estimates from 507 unique cohort or case-control studies.
When researchers applied a threshold for significance of P less than .000001, the summary random effects were significant in 35 meta-analyses; 31 of these found increased risk with adiposity of esophageal adenocarcinoma, multiple myeloma, and cancers of the colon, rectum, liver, biliary tract system (cancers of gallbladder, extrahepatic bile duct, and ampulla of Vater), pancreas, postmenopausal breast, endometrium, and kidney.
“The effect of obesity on the incidence and mortality of cancer is well recognized and was evident in our umbrella review, with approximately 77% of the included meta-analyses reporting a nominally statistically significant summary random effects estimate,” the authors reported.
Overall, the summary estimates were similar between men and women for esophageal adenocarcinoma, esophageal squamous cell carcinoma, multiple myeloma, leukemia, and gastric, lung, kidney, and thyroid cancers.
However, men had a 30% higher risk of colon cancer per 5-kg/m2 increase of body mass index, compared with a 9% increase in risk in women for the same rise in BMI. Men also showed an increased risk of melanoma with increasing BMI, whereas women did not.
Women who had never used hormone therapy showed an 11% increase in the risk of postmenopausal breast cancer with each 5 kg of weight gained. Similarly, each 0.1 increase in waist-to-hip ratio in these women was associated with a 21% increase in the risk of endometrial cancer.
The analysis also revealed an inverse relationship in four meta-analyses for esophageal squamous cell carcinoma and lung cancer.
The authors said their findings agree with those of the World Cancer Research Fund, which currently states there is a convincing causal relationship with obesity for esophageal adenocarcinoma and cancers of the pancreas, colorectum, postmenopausal breast, endometrium, kidney, and liver.
While this umbrella analysis did not find strong evidence for an association with liver cancer, the authors said the evidence was “highly suggestive” but suffered from small study effects, excess significance bias, and substantial heterogeneity between studies.
“To draw firmer conclusions, we need prospective studies and large consortiums with better assessment of the changing nature of body fatness and with comprehensive standardized reporting of analyses,” they wrote. “As obesity becomes one of the greatest public health problems worldwide, evidence of the strength of the associations between obesity and cancer may allow finer selection of people at high risk, who could be selected for personalized primary and secondary prevention strategies.”
The study was supported by the Genesis Research Trust, Sigrid Jusélius Fellowship, the World Cancer Research Fund International Regular Grant Programme, Ovarian Cancer Action, the Imperial Experimental Cancer Medicine Centre, the Cancer Research UK Imperial Centre, Imperial Healthcare NHS Trust NIHR BRC. No relevant conflicts of interest were declared.
There is strong evidence linking adiposity to esophageal adenocarcinoma, multiple myeloma, and cancer of the colon, rectum, biliary tract, pancreas, endometrium, kidney, and postmenopausal breast, according to the authors of an umbrella review published in the Feb. 28 edition of the BMJ.
“Several meta-analyses support the link between obesity and cancer, but substantial heterogeneity exists between studies,” wrote Maria Kyrgiou, MD, of Imperial College London and her coauthors. “The reported associations may be causal, but they may also be flawed, as inherent study biases such as residual confounding and selective reporting of positive results may exaggerate the effect of obesity on cancer.”
In this umbrella review, researchers analyzed 49 papers that included a total of 204 meta-analyses, which in turn summarized 2,179 individual study estimates from 507 unique cohort or case-control studies.
When researchers applied a threshold for significance of P less than .000001, the summary random effects were significant in 35 meta-analyses; 31 of these found increased risk with adiposity of esophageal adenocarcinoma, multiple myeloma, and cancers of the colon, rectum, liver, biliary tract system (cancers of gallbladder, extrahepatic bile duct, and ampulla of Vater), pancreas, postmenopausal breast, endometrium, and kidney.
“The effect of obesity on the incidence and mortality of cancer is well recognized and was evident in our umbrella review, with approximately 77% of the included meta-analyses reporting a nominally statistically significant summary random effects estimate,” the authors reported.
Overall, the summary estimates were similar between men and women for esophageal adenocarcinoma, esophageal squamous cell carcinoma, multiple myeloma, leukemia, and gastric, lung, kidney, and thyroid cancers.
However, men had a 30% higher risk of colon cancer per 5-kg/m2 increase of body mass index, compared with a 9% increase in risk in women for the same rise in BMI. Men also showed an increased risk of melanoma with increasing BMI, whereas women did not.
Women who had never used hormone therapy showed an 11% increase in the risk of postmenopausal breast cancer with each 5 kg of weight gained. Similarly, each 0.1 increase in waist-to-hip ratio in these women was associated with a 21% increase in the risk of endometrial cancer.
The analysis also revealed an inverse relationship in four meta-analyses for esophageal squamous cell carcinoma and lung cancer.
The authors said their findings agree with those of the World Cancer Research Fund, which currently states there is a convincing causal relationship with obesity for esophageal adenocarcinoma and cancers of the pancreas, colorectum, postmenopausal breast, endometrium, kidney, and liver.
While this umbrella analysis did not find strong evidence for an association with liver cancer, the authors said the evidence was “highly suggestive” but suffered from small study effects, excess significance bias, and substantial heterogeneity between studies.
“To draw firmer conclusions, we need prospective studies and large consortiums with better assessment of the changing nature of body fatness and with comprehensive standardized reporting of analyses,” they wrote. “As obesity becomes one of the greatest public health problems worldwide, evidence of the strength of the associations between obesity and cancer may allow finer selection of people at high risk, who could be selected for personalized primary and secondary prevention strategies.”
The study was supported by the Genesis Research Trust, Sigrid Jusélius Fellowship, the World Cancer Research Fund International Regular Grant Programme, Ovarian Cancer Action, the Imperial Experimental Cancer Medicine Centre, the Cancer Research UK Imperial Centre, Imperial Healthcare NHS Trust NIHR BRC. No relevant conflicts of interest were declared.
There is strong evidence linking adiposity to esophageal adenocarcinoma, multiple myeloma, and cancer of the colon, rectum, biliary tract, pancreas, endometrium, kidney, and postmenopausal breast, according to the authors of an umbrella review published in the Feb. 28 edition of the BMJ.
“Several meta-analyses support the link between obesity and cancer, but substantial heterogeneity exists between studies,” wrote Maria Kyrgiou, MD, of Imperial College London and her coauthors. “The reported associations may be causal, but they may also be flawed, as inherent study biases such as residual confounding and selective reporting of positive results may exaggerate the effect of obesity on cancer.”
In this umbrella review, researchers analyzed 49 papers that included a total of 204 meta-analyses, which in turn summarized 2,179 individual study estimates from 507 unique cohort or case-control studies.
When researchers applied a threshold for significance of P less than .000001, the summary random effects were significant in 35 meta-analyses; 31 of these found increased risk with adiposity of esophageal adenocarcinoma, multiple myeloma, and cancers of the colon, rectum, liver, biliary tract system (cancers of gallbladder, extrahepatic bile duct, and ampulla of Vater), pancreas, postmenopausal breast, endometrium, and kidney.
“The effect of obesity on the incidence and mortality of cancer is well recognized and was evident in our umbrella review, with approximately 77% of the included meta-analyses reporting a nominally statistically significant summary random effects estimate,” the authors reported.
Overall, the summary estimates were similar between men and women for esophageal adenocarcinoma, esophageal squamous cell carcinoma, multiple myeloma, leukemia, and gastric, lung, kidney, and thyroid cancers.
However, men had a 30% higher risk of colon cancer per 5-kg/m2 increase of body mass index, compared with a 9% increase in risk in women for the same rise in BMI. Men also showed an increased risk of melanoma with increasing BMI, whereas women did not.
Women who had never used hormone therapy showed an 11% increase in the risk of postmenopausal breast cancer with each 5 kg of weight gained. Similarly, each 0.1 increase in waist-to-hip ratio in these women was associated with a 21% increase in the risk of endometrial cancer.
The analysis also revealed an inverse relationship in four meta-analyses for esophageal squamous cell carcinoma and lung cancer.
The authors said their findings agree with those of the World Cancer Research Fund, which currently states there is a convincing causal relationship with obesity for esophageal adenocarcinoma and cancers of the pancreas, colorectum, postmenopausal breast, endometrium, kidney, and liver.
While this umbrella analysis did not find strong evidence for an association with liver cancer, the authors said the evidence was “highly suggestive” but suffered from small study effects, excess significance bias, and substantial heterogeneity between studies.
“To draw firmer conclusions, we need prospective studies and large consortiums with better assessment of the changing nature of body fatness and with comprehensive standardized reporting of analyses,” they wrote. “As obesity becomes one of the greatest public health problems worldwide, evidence of the strength of the associations between obesity and cancer may allow finer selection of people at high risk, who could be selected for personalized primary and secondary prevention strategies.”
The study was supported by the Genesis Research Trust, Sigrid Jusélius Fellowship, the World Cancer Research Fund International Regular Grant Programme, Ovarian Cancer Action, the Imperial Experimental Cancer Medicine Centre, the Cancer Research UK Imperial Centre, Imperial Healthcare NHS Trust NIHR BRC. No relevant conflicts of interest were declared.
FROM BMJ
Key clinical point: An umbrella analysis of systematic reviews has found strong evidence linking adiposity to a range of cancers including esophageal adenocarcinoma, and cancer of the colon, kidney, and pancreas.
Major finding: Adiposity is significantly associated with cancers of the esophagus, colon, rectum, biliary tract, pancreas, endometrium, kidney, postmenopausal breast, and to multiple myeloma.
Data source: An umbrella review of 204 meta-analyses.
Disclosures: The study was supported by the Genesis Research Trust, Sigrid Jusélius Fellowship, the World Cancer Research Fund International Regular Grant Programme, Ovarian Cancer Action, the Imperial Experimental Cancer Medicine Centre, the Cancer Research UK Imperial Centre, Imperial Healthcare NHS Trust NIHR BRC. No relevant conflicts of interest were declared.
More than one-third of tumors found on breast cancer screening represent overdiagnosis
The purpose of screening mammography is to detect tumors when they are small and nonpalpable in order to prevent more advanced breast tumors in women. Overdiagnosis, which leads to unnecessary treatment, refers to screen-detected tumors that will not lead to symptoms. Overdiagnosis cannot be measured directly and, therefore, understanding this concept is problematic for both women and clinicians.
Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns
Observations from other types of cancer screening put overdiagnosis in perspective
To help us grasp the overall issue of overdiagnosis, we can consider screening mammography alongside cervical cancer screening and colon cancer screening. For instance, screening with cervical cytology has reduced the incidence of and mortality from invasive cervical cancer.1 Likewise, colonoscopy repeatedly has been found to reduce colon cancer mortality.2,3 Decades of media messaging have emphasized the benefits of screening mammograms.4 However, and in contrast with cervical cytology and colonoscopy, screening mammography has not reduced the incidence of breast cancer presenting with metastatic (advanced) disease.5 Likewise, as the Danish authors of a recent study published in Annals of Internal Medicine point out, screening mammography has not achieved the promised reduction in breast cancer mortality.
New data from Denmark highlight overdiagnosis concerns
Jørgensen and colleagues conducted a cohort study to estimate the incidence of screen-detected tumors that would not become clinically relevant (overdiagnosis) among women aged 35 to 84 years between 1980 and 2010 in Denmark.6 This country offers a particularly well-suited backdrop for a study of overdiagnosis because biennial screening mammography was introduced by region beginning in the early 1990s. By 2007, one-fifth of the country’s female population aged 50 to 69 years were invited to participate. In the following years, screening became universal for Danish women in this age group.
For the study, researchers identified the size of all invasive breast cancer tumors diagnosed over the study period and then compared the incidence rates of advanced tumors (more than 20-mm in size at detection) with nonadvanced tumors in screened and unscreened Danish regions. The investigators took into account regional differences not related to screening by assessing the trends in diagnosis of advanced and nonadvanced tumors in screened and unscreened regions among women older and younger than those screened. This gave them a better estimate of the incidence of overdiagnosis.6
Jørgensen and colleagues found that breast cancer screening resulted in an increase in the incidence of nonadvanced tumors, but that it did not reduce the incidence of advanced tumors. They estimated that 39% of the invasive tumors found among women aged 50 to 69 were overdiagnosed.6
These Danish study results, that more than one-third of screen-detected tumors represent overdiagnosis, are similar to those found for studies conducted in the United States and other countries.7,8 The lengthy follow-up after initiation of screening and the assessment of trends in unscreened women represent strengths of the study by Jørgensen and colleagues, and speak to concerns voiced by those skeptical of reported overdiagnosis incidence rates.9
Although breast cancer mortality is declining, the lion’s share of this decline has resulted from improvements in systemic therapy rather than from screening mammography. Widespread screening mammography has resulted in a scenario in which women are more likely to have a breast cancer that was overdiagnosed than in having earlier detection of a tumor destined to grow larger.5 In the future, by targeting higher-risk women, screening may result in a better benefit:risk ratio. However, and as pointed out by Otis Brawley, MD, Chief Medical and Scientific Officer of the American Cancer Society, we must acknowledge that overdiagnosis is common, the benefits of screening have been overstated, and some patients considered as “cured” from breast cancer have in fact been harmed by unneeded treatment.10
Related article:
No surprises from the USPSTF with new guidance on screening mammography
My breast cancer screening approach
As Brawley indicates, we should not abandon screening.10 I continue to recommend screening based on US Preventive Services Taskforce guidance, beginning biennial screens at age 50.11 I also recognize that some women prefer earlier and more frequent screens, while others may prefer less frequent or even no screening.
- Nieminen P, Kallio M, Hakama M. The effect of mass screening on incidence and mortality of squamous and adenocarcinoma of cervix uteri. Obstet Gynecol. 1995;85(6):1017-1021.
- Baxter NN, Goldwasser MA, Paszat LF, Saskin R, Urbach DR, Rabeneck L. Association of colonoscopy and death from colorectal cancer. Ann Intern Med. 2009;150(1):1-8.
- Singh H, Nugent Z, Demers AA, Kliewer EV, Mahmud SM, Bernstein CN. The reduction in colorectal cancer mortality after colonoscopy varies by site of the cancer. Gastroenterology. 2010;139(4):1128-1137.
- Orenstein P. Our feel-good war on breast cancer. New York Times website. http://www.nytimes.com/2013/04/28/magazine/our-feel-good-war-on-breast-cancer.html?pagewanted=all& _r=0. Published April 25, 2013. Accessed February 21, 2017.
- Welch HG, Gorski DH, Albertsen PC. Trends in metastatic breast and prostate cancer. N Engl J Med. 2016;374(8):596.
- Jørgensen KJ, Gøtzsche PC, Kalager M, Zahl PH. Breast cancer screening in Denmark: a cohort study of tumor size and overdiagnosis. Ann Intern Med. 2017 Jan 10. doi:10.7326/M16-0270.
- Welch HG, Prorok PC, O'Malley AJ, Kramer BS. Breast-cancer tumor size, overdiagnosis, and mammography screening effectiveness. N Engl J Med. 2016;375(15):1438-1447.
- Autier P, Boniol M, Middleton R, et al. Advanced breast cancer incidence following population-based mammographic screening. Ann Oncol. 2011;22(8):1726-1735.
- Kopans DB. Breast-cancer tumor size and screening effectiveness. N Engl J Med. 2017;376(1):93-94.
- Brawley OW. Accepting the existence of breast cancer overdiagnosis [published online ahead of print January 10, 2017]. Ann Intern Med. doi:10.7326/M16-2850.
- Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151(10):727-737.
Dr. Kaunitz is University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. He is Medical Director and Director of Menopause and Gynecologic Ultrasound Services at UF Women’s Health Specialists–Emerson. He also serves on the OBG Management Board of Editors.
The authors report no financial relationships relevant to this quiz.
Dr. Kaunitz is University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. He is Medical Director and Director of Menopause and Gynecologic Ultrasound Services at UF Women’s Health Specialists–Emerson. He also serves on the OBG Management Board of Editors.
The authors report no financial relationships relevant to this quiz.
Dr. Kaunitz is University of Florida Research Foundation Professor and Associate Chairman, Department of Obstetrics and Gynecology, University of Florida College of Medicine–Jacksonville. He is Medical Director and Director of Menopause and Gynecologic Ultrasound Services at UF Women’s Health Specialists–Emerson. He also serves on the OBG Management Board of Editors.
The authors report no financial relationships relevant to this quiz.
The purpose of screening mammography is to detect tumors when they are small and nonpalpable in order to prevent more advanced breast tumors in women. Overdiagnosis, which leads to unnecessary treatment, refers to screen-detected tumors that will not lead to symptoms. Overdiagnosis cannot be measured directly and, therefore, understanding this concept is problematic for both women and clinicians.
Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns
Observations from other types of cancer screening put overdiagnosis in perspective
To help us grasp the overall issue of overdiagnosis, we can consider screening mammography alongside cervical cancer screening and colon cancer screening. For instance, screening with cervical cytology has reduced the incidence of and mortality from invasive cervical cancer.1 Likewise, colonoscopy repeatedly has been found to reduce colon cancer mortality.2,3 Decades of media messaging have emphasized the benefits of screening mammograms.4 However, and in contrast with cervical cytology and colonoscopy, screening mammography has not reduced the incidence of breast cancer presenting with metastatic (advanced) disease.5 Likewise, as the Danish authors of a recent study published in Annals of Internal Medicine point out, screening mammography has not achieved the promised reduction in breast cancer mortality.
New data from Denmark highlight overdiagnosis concerns
Jørgensen and colleagues conducted a cohort study to estimate the incidence of screen-detected tumors that would not become clinically relevant (overdiagnosis) among women aged 35 to 84 years between 1980 and 2010 in Denmark.6 This country offers a particularly well-suited backdrop for a study of overdiagnosis because biennial screening mammography was introduced by region beginning in the early 1990s. By 2007, one-fifth of the country’s female population aged 50 to 69 years were invited to participate. In the following years, screening became universal for Danish women in this age group.
For the study, researchers identified the size of all invasive breast cancer tumors diagnosed over the study period and then compared the incidence rates of advanced tumors (more than 20-mm in size at detection) with nonadvanced tumors in screened and unscreened Danish regions. The investigators took into account regional differences not related to screening by assessing the trends in diagnosis of advanced and nonadvanced tumors in screened and unscreened regions among women older and younger than those screened. This gave them a better estimate of the incidence of overdiagnosis.6
Jørgensen and colleagues found that breast cancer screening resulted in an increase in the incidence of nonadvanced tumors, but that it did not reduce the incidence of advanced tumors. They estimated that 39% of the invasive tumors found among women aged 50 to 69 were overdiagnosed.6
These Danish study results, that more than one-third of screen-detected tumors represent overdiagnosis, are similar to those found for studies conducted in the United States and other countries.7,8 The lengthy follow-up after initiation of screening and the assessment of trends in unscreened women represent strengths of the study by Jørgensen and colleagues, and speak to concerns voiced by those skeptical of reported overdiagnosis incidence rates.9
Although breast cancer mortality is declining, the lion’s share of this decline has resulted from improvements in systemic therapy rather than from screening mammography. Widespread screening mammography has resulted in a scenario in which women are more likely to have a breast cancer that was overdiagnosed than in having earlier detection of a tumor destined to grow larger.5 In the future, by targeting higher-risk women, screening may result in a better benefit:risk ratio. However, and as pointed out by Otis Brawley, MD, Chief Medical and Scientific Officer of the American Cancer Society, we must acknowledge that overdiagnosis is common, the benefits of screening have been overstated, and some patients considered as “cured” from breast cancer have in fact been harmed by unneeded treatment.10
Related article:
No surprises from the USPSTF with new guidance on screening mammography
My breast cancer screening approach
As Brawley indicates, we should not abandon screening.10 I continue to recommend screening based on US Preventive Services Taskforce guidance, beginning biennial screens at age 50.11 I also recognize that some women prefer earlier and more frequent screens, while others may prefer less frequent or even no screening.
The purpose of screening mammography is to detect tumors when they are small and nonpalpable in order to prevent more advanced breast tumors in women. Overdiagnosis, which leads to unnecessary treatment, refers to screen-detected tumors that will not lead to symptoms. Overdiagnosis cannot be measured directly and, therefore, understanding this concept is problematic for both women and clinicians.
Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns
Observations from other types of cancer screening put overdiagnosis in perspective
To help us grasp the overall issue of overdiagnosis, we can consider screening mammography alongside cervical cancer screening and colon cancer screening. For instance, screening with cervical cytology has reduced the incidence of and mortality from invasive cervical cancer.1 Likewise, colonoscopy repeatedly has been found to reduce colon cancer mortality.2,3 Decades of media messaging have emphasized the benefits of screening mammograms.4 However, and in contrast with cervical cytology and colonoscopy, screening mammography has not reduced the incidence of breast cancer presenting with metastatic (advanced) disease.5 Likewise, as the Danish authors of a recent study published in Annals of Internal Medicine point out, screening mammography has not achieved the promised reduction in breast cancer mortality.
New data from Denmark highlight overdiagnosis concerns
Jørgensen and colleagues conducted a cohort study to estimate the incidence of screen-detected tumors that would not become clinically relevant (overdiagnosis) among women aged 35 to 84 years between 1980 and 2010 in Denmark.6 This country offers a particularly well-suited backdrop for a study of overdiagnosis because biennial screening mammography was introduced by region beginning in the early 1990s. By 2007, one-fifth of the country’s female population aged 50 to 69 years were invited to participate. In the following years, screening became universal for Danish women in this age group.
For the study, researchers identified the size of all invasive breast cancer tumors diagnosed over the study period and then compared the incidence rates of advanced tumors (more than 20-mm in size at detection) with nonadvanced tumors in screened and unscreened Danish regions. The investigators took into account regional differences not related to screening by assessing the trends in diagnosis of advanced and nonadvanced tumors in screened and unscreened regions among women older and younger than those screened. This gave them a better estimate of the incidence of overdiagnosis.6
Jørgensen and colleagues found that breast cancer screening resulted in an increase in the incidence of nonadvanced tumors, but that it did not reduce the incidence of advanced tumors. They estimated that 39% of the invasive tumors found among women aged 50 to 69 were overdiagnosed.6
These Danish study results, that more than one-third of screen-detected tumors represent overdiagnosis, are similar to those found for studies conducted in the United States and other countries.7,8 The lengthy follow-up after initiation of screening and the assessment of trends in unscreened women represent strengths of the study by Jørgensen and colleagues, and speak to concerns voiced by those skeptical of reported overdiagnosis incidence rates.9
Although breast cancer mortality is declining, the lion’s share of this decline has resulted from improvements in systemic therapy rather than from screening mammography. Widespread screening mammography has resulted in a scenario in which women are more likely to have a breast cancer that was overdiagnosed than in having earlier detection of a tumor destined to grow larger.5 In the future, by targeting higher-risk women, screening may result in a better benefit:risk ratio. However, and as pointed out by Otis Brawley, MD, Chief Medical and Scientific Officer of the American Cancer Society, we must acknowledge that overdiagnosis is common, the benefits of screening have been overstated, and some patients considered as “cured” from breast cancer have in fact been harmed by unneeded treatment.10
Related article:
No surprises from the USPSTF with new guidance on screening mammography
My breast cancer screening approach
As Brawley indicates, we should not abandon screening.10 I continue to recommend screening based on US Preventive Services Taskforce guidance, beginning biennial screens at age 50.11 I also recognize that some women prefer earlier and more frequent screens, while others may prefer less frequent or even no screening.
- Nieminen P, Kallio M, Hakama M. The effect of mass screening on incidence and mortality of squamous and adenocarcinoma of cervix uteri. Obstet Gynecol. 1995;85(6):1017-1021.
- Baxter NN, Goldwasser MA, Paszat LF, Saskin R, Urbach DR, Rabeneck L. Association of colonoscopy and death from colorectal cancer. Ann Intern Med. 2009;150(1):1-8.
- Singh H, Nugent Z, Demers AA, Kliewer EV, Mahmud SM, Bernstein CN. The reduction in colorectal cancer mortality after colonoscopy varies by site of the cancer. Gastroenterology. 2010;139(4):1128-1137.
- Orenstein P. Our feel-good war on breast cancer. New York Times website. http://www.nytimes.com/2013/04/28/magazine/our-feel-good-war-on-breast-cancer.html?pagewanted=all& _r=0. Published April 25, 2013. Accessed February 21, 2017.
- Welch HG, Gorski DH, Albertsen PC. Trends in metastatic breast and prostate cancer. N Engl J Med. 2016;374(8):596.
- Jørgensen KJ, Gøtzsche PC, Kalager M, Zahl PH. Breast cancer screening in Denmark: a cohort study of tumor size and overdiagnosis. Ann Intern Med. 2017 Jan 10. doi:10.7326/M16-0270.
- Welch HG, Prorok PC, O'Malley AJ, Kramer BS. Breast-cancer tumor size, overdiagnosis, and mammography screening effectiveness. N Engl J Med. 2016;375(15):1438-1447.
- Autier P, Boniol M, Middleton R, et al. Advanced breast cancer incidence following population-based mammographic screening. Ann Oncol. 2011;22(8):1726-1735.
- Kopans DB. Breast-cancer tumor size and screening effectiveness. N Engl J Med. 2017;376(1):93-94.
- Brawley OW. Accepting the existence of breast cancer overdiagnosis [published online ahead of print January 10, 2017]. Ann Intern Med. doi:10.7326/M16-2850.
- Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151(10):727-737.
- Nieminen P, Kallio M, Hakama M. The effect of mass screening on incidence and mortality of squamous and adenocarcinoma of cervix uteri. Obstet Gynecol. 1995;85(6):1017-1021.
- Baxter NN, Goldwasser MA, Paszat LF, Saskin R, Urbach DR, Rabeneck L. Association of colonoscopy and death from colorectal cancer. Ann Intern Med. 2009;150(1):1-8.
- Singh H, Nugent Z, Demers AA, Kliewer EV, Mahmud SM, Bernstein CN. The reduction in colorectal cancer mortality after colonoscopy varies by site of the cancer. Gastroenterology. 2010;139(4):1128-1137.
- Orenstein P. Our feel-good war on breast cancer. New York Times website. http://www.nytimes.com/2013/04/28/magazine/our-feel-good-war-on-breast-cancer.html?pagewanted=all& _r=0. Published April 25, 2013. Accessed February 21, 2017.
- Welch HG, Gorski DH, Albertsen PC. Trends in metastatic breast and prostate cancer. N Engl J Med. 2016;374(8):596.
- Jørgensen KJ, Gøtzsche PC, Kalager M, Zahl PH. Breast cancer screening in Denmark: a cohort study of tumor size and overdiagnosis. Ann Intern Med. 2017 Jan 10. doi:10.7326/M16-0270.
- Welch HG, Prorok PC, O'Malley AJ, Kramer BS. Breast-cancer tumor size, overdiagnosis, and mammography screening effectiveness. N Engl J Med. 2016;375(15):1438-1447.
- Autier P, Boniol M, Middleton R, et al. Advanced breast cancer incidence following population-based mammographic screening. Ann Oncol. 2011;22(8):1726-1735.
- Kopans DB. Breast-cancer tumor size and screening effectiveness. N Engl J Med. 2017;376(1):93-94.
- Brawley OW. Accepting the existence of breast cancer overdiagnosis [published online ahead of print January 10, 2017]. Ann Intern Med. doi:10.7326/M16-2850.
- Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L. Screening for breast cancer: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2009;151(10):727-737.
Oral contraceptive use confers long-term cancer protection
New findings from a cohort study with more than 4 decades of follow-up show that, while women who have ever used combined oral contraceptives see an increased risk of breast and cervical cancer, the risk disappears within about 5 years after stopping, but a protective effect against colorectal, endometrial, and ovarian cancer persists for more than 30 years.
The findings provide an update to the General Practitioners’ Oral Contraception Study of a United Kingdom cohort recruited in the late 1960s.
The mean age was 70.2 years, most were white, and the mean follow-up was 40.7 years. Women who had used the pill did so a mean 3.66 years and used older, higher-estrogen formulations.
Compared with never users, users of oral contraception had a nonsignificant 4% reduced risk of any cancer. The incidence rate ratio for breast cancer was similar between ever users and nonusers (IRR 1.04; 99% CI, 0.91-1.17). Women who had used OCs saw significant reductions in colorectal (IRR, 0.81; 99% CI, 0.66-0.99), endometrial (IRR, 0.66; 99% CI, 0.48-0.89), ovarian (IRR, 0.67; 99% CI, 0.50-0.89), and lymphatic and hematopoietic cancers (IRR, 0.74; 0.58-0.94), compared with never users.
Lung cancer incidence was increased among ever users of OCs, but only in women who smoked at the time of recruitment.
“There was no evidence of new cancer risks appearing later in life among women who had used oral contraceptives,” the researchers wrote. “Thus, the overall balance of cancer risk among past users of oral contraceptives was neutral with the increased risks counterbalanced by the endometrial, ovarian, and colorectal cancer benefits that persist at least 30 years.”
The results, the researchers wrote, “provide strong evidence that most women do not expose themselves to long-term cancer harm if they choose to use oral contraception, indeed many are likely to be protected.”
The study was funded by the Royal College of General Practitioners, Medical Research Council, Imperial Cancer Research Fund, British Heart Foundation, Schering AG, Schering Health Care, Wyeth Ayerst International, Ortho Cilag, and Searle. The researchers reported having no conflicts of interest.
New findings from a cohort study with more than 4 decades of follow-up show that, while women who have ever used combined oral contraceptives see an increased risk of breast and cervical cancer, the risk disappears within about 5 years after stopping, but a protective effect against colorectal, endometrial, and ovarian cancer persists for more than 30 years.
The findings provide an update to the General Practitioners’ Oral Contraception Study of a United Kingdom cohort recruited in the late 1960s.
The mean age was 70.2 years, most were white, and the mean follow-up was 40.7 years. Women who had used the pill did so a mean 3.66 years and used older, higher-estrogen formulations.
Compared with never users, users of oral contraception had a nonsignificant 4% reduced risk of any cancer. The incidence rate ratio for breast cancer was similar between ever users and nonusers (IRR 1.04; 99% CI, 0.91-1.17). Women who had used OCs saw significant reductions in colorectal (IRR, 0.81; 99% CI, 0.66-0.99), endometrial (IRR, 0.66; 99% CI, 0.48-0.89), ovarian (IRR, 0.67; 99% CI, 0.50-0.89), and lymphatic and hematopoietic cancers (IRR, 0.74; 0.58-0.94), compared with never users.
Lung cancer incidence was increased among ever users of OCs, but only in women who smoked at the time of recruitment.
“There was no evidence of new cancer risks appearing later in life among women who had used oral contraceptives,” the researchers wrote. “Thus, the overall balance of cancer risk among past users of oral contraceptives was neutral with the increased risks counterbalanced by the endometrial, ovarian, and colorectal cancer benefits that persist at least 30 years.”
The results, the researchers wrote, “provide strong evidence that most women do not expose themselves to long-term cancer harm if they choose to use oral contraception, indeed many are likely to be protected.”
The study was funded by the Royal College of General Practitioners, Medical Research Council, Imperial Cancer Research Fund, British Heart Foundation, Schering AG, Schering Health Care, Wyeth Ayerst International, Ortho Cilag, and Searle. The researchers reported having no conflicts of interest.
New findings from a cohort study with more than 4 decades of follow-up show that, while women who have ever used combined oral contraceptives see an increased risk of breast and cervical cancer, the risk disappears within about 5 years after stopping, but a protective effect against colorectal, endometrial, and ovarian cancer persists for more than 30 years.
The findings provide an update to the General Practitioners’ Oral Contraception Study of a United Kingdom cohort recruited in the late 1960s.
The mean age was 70.2 years, most were white, and the mean follow-up was 40.7 years. Women who had used the pill did so a mean 3.66 years and used older, higher-estrogen formulations.
Compared with never users, users of oral contraception had a nonsignificant 4% reduced risk of any cancer. The incidence rate ratio for breast cancer was similar between ever users and nonusers (IRR 1.04; 99% CI, 0.91-1.17). Women who had used OCs saw significant reductions in colorectal (IRR, 0.81; 99% CI, 0.66-0.99), endometrial (IRR, 0.66; 99% CI, 0.48-0.89), ovarian (IRR, 0.67; 99% CI, 0.50-0.89), and lymphatic and hematopoietic cancers (IRR, 0.74; 0.58-0.94), compared with never users.
Lung cancer incidence was increased among ever users of OCs, but only in women who smoked at the time of recruitment.
“There was no evidence of new cancer risks appearing later in life among women who had used oral contraceptives,” the researchers wrote. “Thus, the overall balance of cancer risk among past users of oral contraceptives was neutral with the increased risks counterbalanced by the endometrial, ovarian, and colorectal cancer benefits that persist at least 30 years.”
The results, the researchers wrote, “provide strong evidence that most women do not expose themselves to long-term cancer harm if they choose to use oral contraception, indeed many are likely to be protected.”
The study was funded by the Royal College of General Practitioners, Medical Research Council, Imperial Cancer Research Fund, British Heart Foundation, Schering AG, Schering Health Care, Wyeth Ayerst International, Ortho Cilag, and Searle. The researchers reported having no conflicts of interest.
FROM THE AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
Key clinical point:
Major finding: At about 40 years of follow-up, women who had ever used combined OCs saw reduced incidence of colorectal (IRR, 0.81), endometrial (IRR, 0.66), ovarian (IRR, 0.67), and lymphatic and hematopoietic cancer (IRR, 0.74), compared with never users.
Data source: A prospective cohort study originally enrolling 46,000 women who were followed for up to 44 years.
Disclosures: The study was funded by the Royal College of General Practitioners, Medical Research Council, Imperial Cancer Research Fund, British Heart Foundation, Schering AG, Schering Health Care, Wyeth Ayerst International, Ortho Cilag, and Searle. The researchers reported having no conflicts of interest.
Scalp cooling reduces hair loss in 50% or more of women in separate studies
Scalp cooling resulted in significant reductions in hair loss in about half of all women who were treated before, during, and after chemotherapy for breast cancer in both the Scalp Cooling Alopecia Prevention (SCALP) randomized clinical trial and in a multicenter prospective cohort study.
However, the effects of the reduced alopecia on quality of life measures were mixed, according to the findings of the studies, which were published online in JAMA.
The findings of the multicenter SCALP trial are from a planned interim analysis of data from 95 women with breast cancer who were undergoing chemotherapy and who were randomized to undergo scalp cooling using the Orbis Paxman Hair Loss Prevention System (OPHLPS), and 47 controls. Successful hair preservation occurred in 50.5% of those in the scalp cooling group, compared with 0% of those in the control group – results which led to early study termination, reported Julie Nangia, MD, of Baylor College of Medicine, Houston, and her colleagues (JAMA 2017 Feb 14. doi: 10.1001/jama.2016.20939).
No serious adverse device-related events occurred in the cooling group, but there also were no significant differences between the groups with respect to changes in quality of life scales from baseline to chemotherapy cycle 4, the investigators found.
Study subjects were women with a mean age of 52.6 years who were receiving anthracycline-based chemotherapy (36%) or taxane-based chemotherapy (64%). Successful hair preservation was defined as grade 0 or 1 based on the Common Terminology Criteria for Adverse Events version 4.1 scale, representing no hair loss or less than 50% hair loss not requiring a wig, respectively. Five women had grade 0 hair loss, and 43 had grade 1 hair loss.
Quality of life was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-30), the Hospital Anxiety and Depression Scale (HADS), and a summary scale of the Body Image Scale. Changes in emotional and social functioning as measured using the EORTC-QLQ-30 did not differ between the groups, including among those with and without hair preservation, after four treatment cycles, and HADS anxiety and depression summary scores were normal both at baseline and after four cycles in both groups, regardless of hair preservation.
Patients will be followed for 5 years to assess for safety and overall survival, the investigators noted.
During a presentation of these findings at the San Antonio Breast Cancer Symposium in December, Dr. Nangia noted that the maker of the OPHLPS is seeking Food and Drug Administration clearance based on the findings, and if approved, the system would compete with the DigniCap (Dignitana AB), which has already received Food and Drug Administration clearance.*
The DigniCap was the device evaluated (at the time under an FDA investigational device exemption) in the prospective cohort study also published in JAMA.
In that study, 106 women receiving adjuvant or neoadjuvant chemotherapy for stage 1 or II breast cancer were treated with scalp cooling between August 2013 and October 2014, and, along with 16 control subjects, were followed for a median of 29.5 months. Self-estimated hair loss at 4 weeks after the last chemotherapy dose was 50% or less, based on the Dean scale (score of 0-2) in 67 of 101 evaluable patients in the scalp cooling group, vs. 0 of 16 in the control group, reported Dr. Hope S. Rugo, MD, of the Helen Diller Family Comprehensive Cancer Center, San Francisco, and her colleagues.
Five patients had no hair loss, and 62 had less than 50% hair loss, the investigators said (JAMA. 2017 Feb 14. doi: 10.1001/jama.2016.21038).
Three of five quality of life measures, as assessed using the EORTC-QLQ, were significantly better at 1 month after the end of chemotherapy vs. at baseline in the cooling group, compared with the control group. For example, 27.3% vs. 56.3% of treatment and control subjects, respectively, reported feeling less physically attractive. The results were similar among those with 50% or less hair loss vs. controls, they noted.
Adverse events associated with cooling included mild headache in four patients. Three patients discontinued treatment due to feeling cold.
The mean age of the women was 53 years. None of those in the treatment group received anthracyclines, thus further research is needed to assess scalp cooling outcomes after treatment with anthracycline regimens, the investigators said, noting that additional research is also needed to assess long-term measures of alopecia and adverse effects. Patients will be followed for a total of 5 years.
Taken together, the findings of these two studies suggest that increased use of scalp cooling is warranted, as it has the potential to both reduce a troublesome side effect of chemotherapy and to remove a common concern – and sometimes a deterrent – among women considering chemotherapy, according to Dawn L. Hershman, MD, of the Herbert Irving Comprehensive Cancer Center at Columbia University.
In an editorial, Dr. Hershman noted that adjuvant chemotherapy reduces the 10-year relative risk of death from breast cancer by about 35%, but that “a substantial number of women who are advised to undergo chemotherapy choose not to receive treatment because of concerns about adverse effects.”
About 50% of patients consider hair loss the most traumatic aspect of chemotherapy, and about 8% said they would decline chemotherapy because of concerns about hair loss, she said.
“Therefore an intervention that could reduce the adverse effects of chemotherapy may lead to improvement in the initiation and completion of therapy, in quality of life, and in survival outcomes,” she wrote (JAMA. 2017 Feb 14;317[6]:587-8).
At face value, the “reassuringly similar” findings from these two studies appear to represent a major step forward for improving the quality of life for individuals with cancer, she added, explaining that while the quality of life data suggest a limited effect, they should be interpreted with caution as the overall effects of the patients’ diagnoses, surgery, and treatment may have influenced the patient-reported outcomes, diminishing the likelihood of detecting differences in quality of life associated with lower rates of alopecia.
Further, the unblinded nature of the intervention may also bias patient-reported outcomes results, she said, adding that “better measures may be needed to capture the effect of treatments on outcomes that are meaningful to patients so that important adverse effects are fully captured in comparative clinical trials.”
Although questions about cost and coverage of scalp cooling remain, Dr. Hershman concluded that until chemotherapy is no longer necessary and some of the distressing adverse effects of cancer treatment can be avoided, interventions such as scalp cooling that can reduce or eliminate toxic effects will help ease the distress and may thereby improve outcomes for patients with breast cancer.
In a separate editorial, Howard (Jack) West, MD, of the Swedish Cancer Institute in Seattle, further notes that a “lingering concern” with respect to scalp cooling is “the speculated potential for increased scalp metastases ... owing to poor local circulation of chemotherapy.”
However, this has not been observed in studies to date, he noted (JAMA. 2017 Feb 14. doi: 10.1001/jamaoncol.2017.0051).
“While some may argue that we need long-term data on timing and patterns of recurrence as well as overall survival to ensure that there is no increased risk of scalp metastases or otherwise compromised outcomes for scalp cooling, there is no evidence thus far to suggest this,” he said, concluding that “it is arguable that growing attention on interventions to reduce chemotherapy-induced alopecia are reaching an inflection point that justifies far more widespread adoption.”
The SCALP trial was supported by Paxman Coolers Ltd. Dr. Nangia reported having no disclosures. The study by Dr. Rugo et al. was funded in part by Dignitana AB, the Laszlo Tauber Family Foundation, the Anne Moore Breast Cancer Research Fund, and the Friedman Family Foundation. Dr. Rugo, Dr. Hershman, and Dr. West reported having no disclosures.
*Correction, 4/5/17: An earlier version of this article misstated the device's FDA status.
Scalp cooling resulted in significant reductions in hair loss in about half of all women who were treated before, during, and after chemotherapy for breast cancer in both the Scalp Cooling Alopecia Prevention (SCALP) randomized clinical trial and in a multicenter prospective cohort study.
However, the effects of the reduced alopecia on quality of life measures were mixed, according to the findings of the studies, which were published online in JAMA.
The findings of the multicenter SCALP trial are from a planned interim analysis of data from 95 women with breast cancer who were undergoing chemotherapy and who were randomized to undergo scalp cooling using the Orbis Paxman Hair Loss Prevention System (OPHLPS), and 47 controls. Successful hair preservation occurred in 50.5% of those in the scalp cooling group, compared with 0% of those in the control group – results which led to early study termination, reported Julie Nangia, MD, of Baylor College of Medicine, Houston, and her colleagues (JAMA 2017 Feb 14. doi: 10.1001/jama.2016.20939).
No serious adverse device-related events occurred in the cooling group, but there also were no significant differences between the groups with respect to changes in quality of life scales from baseline to chemotherapy cycle 4, the investigators found.
Study subjects were women with a mean age of 52.6 years who were receiving anthracycline-based chemotherapy (36%) or taxane-based chemotherapy (64%). Successful hair preservation was defined as grade 0 or 1 based on the Common Terminology Criteria for Adverse Events version 4.1 scale, representing no hair loss or less than 50% hair loss not requiring a wig, respectively. Five women had grade 0 hair loss, and 43 had grade 1 hair loss.
Quality of life was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-30), the Hospital Anxiety and Depression Scale (HADS), and a summary scale of the Body Image Scale. Changes in emotional and social functioning as measured using the EORTC-QLQ-30 did not differ between the groups, including among those with and without hair preservation, after four treatment cycles, and HADS anxiety and depression summary scores were normal both at baseline and after four cycles in both groups, regardless of hair preservation.
Patients will be followed for 5 years to assess for safety and overall survival, the investigators noted.
During a presentation of these findings at the San Antonio Breast Cancer Symposium in December, Dr. Nangia noted that the maker of the OPHLPS is seeking Food and Drug Administration clearance based on the findings, and if approved, the system would compete with the DigniCap (Dignitana AB), which has already received Food and Drug Administration clearance.*
The DigniCap was the device evaluated (at the time under an FDA investigational device exemption) in the prospective cohort study also published in JAMA.
In that study, 106 women receiving adjuvant or neoadjuvant chemotherapy for stage 1 or II breast cancer were treated with scalp cooling between August 2013 and October 2014, and, along with 16 control subjects, were followed for a median of 29.5 months. Self-estimated hair loss at 4 weeks after the last chemotherapy dose was 50% or less, based on the Dean scale (score of 0-2) in 67 of 101 evaluable patients in the scalp cooling group, vs. 0 of 16 in the control group, reported Dr. Hope S. Rugo, MD, of the Helen Diller Family Comprehensive Cancer Center, San Francisco, and her colleagues.
Five patients had no hair loss, and 62 had less than 50% hair loss, the investigators said (JAMA. 2017 Feb 14. doi: 10.1001/jama.2016.21038).
Three of five quality of life measures, as assessed using the EORTC-QLQ, were significantly better at 1 month after the end of chemotherapy vs. at baseline in the cooling group, compared with the control group. For example, 27.3% vs. 56.3% of treatment and control subjects, respectively, reported feeling less physically attractive. The results were similar among those with 50% or less hair loss vs. controls, they noted.
Adverse events associated with cooling included mild headache in four patients. Three patients discontinued treatment due to feeling cold.
The mean age of the women was 53 years. None of those in the treatment group received anthracyclines, thus further research is needed to assess scalp cooling outcomes after treatment with anthracycline regimens, the investigators said, noting that additional research is also needed to assess long-term measures of alopecia and adverse effects. Patients will be followed for a total of 5 years.
Taken together, the findings of these two studies suggest that increased use of scalp cooling is warranted, as it has the potential to both reduce a troublesome side effect of chemotherapy and to remove a common concern – and sometimes a deterrent – among women considering chemotherapy, according to Dawn L. Hershman, MD, of the Herbert Irving Comprehensive Cancer Center at Columbia University.
In an editorial, Dr. Hershman noted that adjuvant chemotherapy reduces the 10-year relative risk of death from breast cancer by about 35%, but that “a substantial number of women who are advised to undergo chemotherapy choose not to receive treatment because of concerns about adverse effects.”
About 50% of patients consider hair loss the most traumatic aspect of chemotherapy, and about 8% said they would decline chemotherapy because of concerns about hair loss, she said.
“Therefore an intervention that could reduce the adverse effects of chemotherapy may lead to improvement in the initiation and completion of therapy, in quality of life, and in survival outcomes,” she wrote (JAMA. 2017 Feb 14;317[6]:587-8).
At face value, the “reassuringly similar” findings from these two studies appear to represent a major step forward for improving the quality of life for individuals with cancer, she added, explaining that while the quality of life data suggest a limited effect, they should be interpreted with caution as the overall effects of the patients’ diagnoses, surgery, and treatment may have influenced the patient-reported outcomes, diminishing the likelihood of detecting differences in quality of life associated with lower rates of alopecia.
Further, the unblinded nature of the intervention may also bias patient-reported outcomes results, she said, adding that “better measures may be needed to capture the effect of treatments on outcomes that are meaningful to patients so that important adverse effects are fully captured in comparative clinical trials.”
Although questions about cost and coverage of scalp cooling remain, Dr. Hershman concluded that until chemotherapy is no longer necessary and some of the distressing adverse effects of cancer treatment can be avoided, interventions such as scalp cooling that can reduce or eliminate toxic effects will help ease the distress and may thereby improve outcomes for patients with breast cancer.
In a separate editorial, Howard (Jack) West, MD, of the Swedish Cancer Institute in Seattle, further notes that a “lingering concern” with respect to scalp cooling is “the speculated potential for increased scalp metastases ... owing to poor local circulation of chemotherapy.”
However, this has not been observed in studies to date, he noted (JAMA. 2017 Feb 14. doi: 10.1001/jamaoncol.2017.0051).
“While some may argue that we need long-term data on timing and patterns of recurrence as well as overall survival to ensure that there is no increased risk of scalp metastases or otherwise compromised outcomes for scalp cooling, there is no evidence thus far to suggest this,” he said, concluding that “it is arguable that growing attention on interventions to reduce chemotherapy-induced alopecia are reaching an inflection point that justifies far more widespread adoption.”
The SCALP trial was supported by Paxman Coolers Ltd. Dr. Nangia reported having no disclosures. The study by Dr. Rugo et al. was funded in part by Dignitana AB, the Laszlo Tauber Family Foundation, the Anne Moore Breast Cancer Research Fund, and the Friedman Family Foundation. Dr. Rugo, Dr. Hershman, and Dr. West reported having no disclosures.
*Correction, 4/5/17: An earlier version of this article misstated the device's FDA status.
Scalp cooling resulted in significant reductions in hair loss in about half of all women who were treated before, during, and after chemotherapy for breast cancer in both the Scalp Cooling Alopecia Prevention (SCALP) randomized clinical trial and in a multicenter prospective cohort study.
However, the effects of the reduced alopecia on quality of life measures were mixed, according to the findings of the studies, which were published online in JAMA.
The findings of the multicenter SCALP trial are from a planned interim analysis of data from 95 women with breast cancer who were undergoing chemotherapy and who were randomized to undergo scalp cooling using the Orbis Paxman Hair Loss Prevention System (OPHLPS), and 47 controls. Successful hair preservation occurred in 50.5% of those in the scalp cooling group, compared with 0% of those in the control group – results which led to early study termination, reported Julie Nangia, MD, of Baylor College of Medicine, Houston, and her colleagues (JAMA 2017 Feb 14. doi: 10.1001/jama.2016.20939).
No serious adverse device-related events occurred in the cooling group, but there also were no significant differences between the groups with respect to changes in quality of life scales from baseline to chemotherapy cycle 4, the investigators found.
Study subjects were women with a mean age of 52.6 years who were receiving anthracycline-based chemotherapy (36%) or taxane-based chemotherapy (64%). Successful hair preservation was defined as grade 0 or 1 based on the Common Terminology Criteria for Adverse Events version 4.1 scale, representing no hair loss or less than 50% hair loss not requiring a wig, respectively. Five women had grade 0 hair loss, and 43 had grade 1 hair loss.
Quality of life was measured using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-30), the Hospital Anxiety and Depression Scale (HADS), and a summary scale of the Body Image Scale. Changes in emotional and social functioning as measured using the EORTC-QLQ-30 did not differ between the groups, including among those with and without hair preservation, after four treatment cycles, and HADS anxiety and depression summary scores were normal both at baseline and after four cycles in both groups, regardless of hair preservation.
Patients will be followed for 5 years to assess for safety and overall survival, the investigators noted.
During a presentation of these findings at the San Antonio Breast Cancer Symposium in December, Dr. Nangia noted that the maker of the OPHLPS is seeking Food and Drug Administration clearance based on the findings, and if approved, the system would compete with the DigniCap (Dignitana AB), which has already received Food and Drug Administration clearance.*
The DigniCap was the device evaluated (at the time under an FDA investigational device exemption) in the prospective cohort study also published in JAMA.
In that study, 106 women receiving adjuvant or neoadjuvant chemotherapy for stage 1 or II breast cancer were treated with scalp cooling between August 2013 and October 2014, and, along with 16 control subjects, were followed for a median of 29.5 months. Self-estimated hair loss at 4 weeks after the last chemotherapy dose was 50% or less, based on the Dean scale (score of 0-2) in 67 of 101 evaluable patients in the scalp cooling group, vs. 0 of 16 in the control group, reported Dr. Hope S. Rugo, MD, of the Helen Diller Family Comprehensive Cancer Center, San Francisco, and her colleagues.
Five patients had no hair loss, and 62 had less than 50% hair loss, the investigators said (JAMA. 2017 Feb 14. doi: 10.1001/jama.2016.21038).
Three of five quality of life measures, as assessed using the EORTC-QLQ, were significantly better at 1 month after the end of chemotherapy vs. at baseline in the cooling group, compared with the control group. For example, 27.3% vs. 56.3% of treatment and control subjects, respectively, reported feeling less physically attractive. The results were similar among those with 50% or less hair loss vs. controls, they noted.
Adverse events associated with cooling included mild headache in four patients. Three patients discontinued treatment due to feeling cold.
The mean age of the women was 53 years. None of those in the treatment group received anthracyclines, thus further research is needed to assess scalp cooling outcomes after treatment with anthracycline regimens, the investigators said, noting that additional research is also needed to assess long-term measures of alopecia and adverse effects. Patients will be followed for a total of 5 years.
Taken together, the findings of these two studies suggest that increased use of scalp cooling is warranted, as it has the potential to both reduce a troublesome side effect of chemotherapy and to remove a common concern – and sometimes a deterrent – among women considering chemotherapy, according to Dawn L. Hershman, MD, of the Herbert Irving Comprehensive Cancer Center at Columbia University.
In an editorial, Dr. Hershman noted that adjuvant chemotherapy reduces the 10-year relative risk of death from breast cancer by about 35%, but that “a substantial number of women who are advised to undergo chemotherapy choose not to receive treatment because of concerns about adverse effects.”
About 50% of patients consider hair loss the most traumatic aspect of chemotherapy, and about 8% said they would decline chemotherapy because of concerns about hair loss, she said.
“Therefore an intervention that could reduce the adverse effects of chemotherapy may lead to improvement in the initiation and completion of therapy, in quality of life, and in survival outcomes,” she wrote (JAMA. 2017 Feb 14;317[6]:587-8).
At face value, the “reassuringly similar” findings from these two studies appear to represent a major step forward for improving the quality of life for individuals with cancer, she added, explaining that while the quality of life data suggest a limited effect, they should be interpreted with caution as the overall effects of the patients’ diagnoses, surgery, and treatment may have influenced the patient-reported outcomes, diminishing the likelihood of detecting differences in quality of life associated with lower rates of alopecia.
Further, the unblinded nature of the intervention may also bias patient-reported outcomes results, she said, adding that “better measures may be needed to capture the effect of treatments on outcomes that are meaningful to patients so that important adverse effects are fully captured in comparative clinical trials.”
Although questions about cost and coverage of scalp cooling remain, Dr. Hershman concluded that until chemotherapy is no longer necessary and some of the distressing adverse effects of cancer treatment can be avoided, interventions such as scalp cooling that can reduce or eliminate toxic effects will help ease the distress and may thereby improve outcomes for patients with breast cancer.
In a separate editorial, Howard (Jack) West, MD, of the Swedish Cancer Institute in Seattle, further notes that a “lingering concern” with respect to scalp cooling is “the speculated potential for increased scalp metastases ... owing to poor local circulation of chemotherapy.”
However, this has not been observed in studies to date, he noted (JAMA. 2017 Feb 14. doi: 10.1001/jamaoncol.2017.0051).
“While some may argue that we need long-term data on timing and patterns of recurrence as well as overall survival to ensure that there is no increased risk of scalp metastases or otherwise compromised outcomes for scalp cooling, there is no evidence thus far to suggest this,” he said, concluding that “it is arguable that growing attention on interventions to reduce chemotherapy-induced alopecia are reaching an inflection point that justifies far more widespread adoption.”
The SCALP trial was supported by Paxman Coolers Ltd. Dr. Nangia reported having no disclosures. The study by Dr. Rugo et al. was funded in part by Dignitana AB, the Laszlo Tauber Family Foundation, the Anne Moore Breast Cancer Research Fund, and the Friedman Family Foundation. Dr. Rugo, Dr. Hershman, and Dr. West reported having no disclosures.
*Correction, 4/5/17: An earlier version of this article misstated the device's FDA status.
FROM JAMA
Key clinical point:
Major finding: About half of the treated women in both studies experienced reduced or no hair loss during chemotherapy.
Data source: A randomized clinical trial involving 142 women, and a prospective cohort study involving 122 women.
Disclosures: The SCALP trial was supported by Paxman Coolers Ltd. Dr. Nangia reported having no disclosures. The study by Dr. Rugo et al. was funded in part by Dignitana AB, the Laszlo Tauber Family Foundation, the Anne Moore Breast Cancer Research Fund, and the Friedman Family Foundation. Dr. Rugo, Dr. Hershman, and Dr. West reported having no disclosures.
Lipid-lowering meds benefit some breast cancer patients
Patients with early-stage, hormone-receptor positive breast cancer who used cholesterol-lowering medication at baseline of a long-term randomized study had more beneficial tumor characteristics and improved outcomes, compared with nonusers.
The findings come from an observation study of a randomized, phase III, double-blind trial conducted by the Breast International Group (BIG) known as BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. As reported online in the Feb. 13, 2017 issue of the Journal of Clinical Oncology, researchers measured systemic levels of total cholesterol and use of cholesterol-lowering medication at study entry and every 6 months up to 5.5 years. Endpoints of interest were disease-free survival, breast cancer–free interval, and distant recurrence–free interval.
Of the 789 patients who initiated cholesterol-lowering medication during endocrine therapy, most were assigned to letrozole monotherapy (318), followed by sequential tamoxifen-letrozole (189), letrozole-tamoxifen (176), and tamoxifen monotherapy (106).
The results showed that initiation of cholesterol-lowering medication during endocrine therapy was related to improved disease-free survival (hazard ratio 0.79; P = .01), breast cancer–free interval (HR, 0.76; P = .02), and distant recurrence–free interval (HR, 0.74; P = .03).
“The evidence from our observational study warrants consideration of a large, prospective, randomized clinical trial to confirm the value of CLM concomitant with endocrine treatment of breast cancer,” corresponding author Signe Borgquist, MD, PhD, of the division of oncology and pathology at Lund University, Sweden, and her associates concluded. “Further elucidation of the effect upon outcome of the clinical interaction between CLM and endocrine agents – both widely used by patients with breast cancer – will provide exclusive insight to future trial designs.”
The BIG 1-98 trial was supported by Novartis and coordinated by the International Breast Cancer Study Group (IBCSG). Of the 17 study authors, 7 reported having relevant financial disclosures.
[email protected]
Patients with early-stage, hormone-receptor positive breast cancer who used cholesterol-lowering medication at baseline of a long-term randomized study had more beneficial tumor characteristics and improved outcomes, compared with nonusers.
The findings come from an observation study of a randomized, phase III, double-blind trial conducted by the Breast International Group (BIG) known as BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. As reported online in the Feb. 13, 2017 issue of the Journal of Clinical Oncology, researchers measured systemic levels of total cholesterol and use of cholesterol-lowering medication at study entry and every 6 months up to 5.5 years. Endpoints of interest were disease-free survival, breast cancer–free interval, and distant recurrence–free interval.
Of the 789 patients who initiated cholesterol-lowering medication during endocrine therapy, most were assigned to letrozole monotherapy (318), followed by sequential tamoxifen-letrozole (189), letrozole-tamoxifen (176), and tamoxifen monotherapy (106).
The results showed that initiation of cholesterol-lowering medication during endocrine therapy was related to improved disease-free survival (hazard ratio 0.79; P = .01), breast cancer–free interval (HR, 0.76; P = .02), and distant recurrence–free interval (HR, 0.74; P = .03).
“The evidence from our observational study warrants consideration of a large, prospective, randomized clinical trial to confirm the value of CLM concomitant with endocrine treatment of breast cancer,” corresponding author Signe Borgquist, MD, PhD, of the division of oncology and pathology at Lund University, Sweden, and her associates concluded. “Further elucidation of the effect upon outcome of the clinical interaction between CLM and endocrine agents – both widely used by patients with breast cancer – will provide exclusive insight to future trial designs.”
The BIG 1-98 trial was supported by Novartis and coordinated by the International Breast Cancer Study Group (IBCSG). Of the 17 study authors, 7 reported having relevant financial disclosures.
[email protected]
Patients with early-stage, hormone-receptor positive breast cancer who used cholesterol-lowering medication at baseline of a long-term randomized study had more beneficial tumor characteristics and improved outcomes, compared with nonusers.
The findings come from an observation study of a randomized, phase III, double-blind trial conducted by the Breast International Group (BIG) known as BIG 1-98, which enrolled 8,010 postmenopausal women with early-stage, hormone receptor–positive invasive breast cancer from 1998 to 2003. As reported online in the Feb. 13, 2017 issue of the Journal of Clinical Oncology, researchers measured systemic levels of total cholesterol and use of cholesterol-lowering medication at study entry and every 6 months up to 5.5 years. Endpoints of interest were disease-free survival, breast cancer–free interval, and distant recurrence–free interval.
Of the 789 patients who initiated cholesterol-lowering medication during endocrine therapy, most were assigned to letrozole monotherapy (318), followed by sequential tamoxifen-letrozole (189), letrozole-tamoxifen (176), and tamoxifen monotherapy (106).
The results showed that initiation of cholesterol-lowering medication during endocrine therapy was related to improved disease-free survival (hazard ratio 0.79; P = .01), breast cancer–free interval (HR, 0.76; P = .02), and distant recurrence–free interval (HR, 0.74; P = .03).
“The evidence from our observational study warrants consideration of a large, prospective, randomized clinical trial to confirm the value of CLM concomitant with endocrine treatment of breast cancer,” corresponding author Signe Borgquist, MD, PhD, of the division of oncology and pathology at Lund University, Sweden, and her associates concluded. “Further elucidation of the effect upon outcome of the clinical interaction between CLM and endocrine agents – both widely used by patients with breast cancer – will provide exclusive insight to future trial designs.”
The BIG 1-98 trial was supported by Novartis and coordinated by the International Breast Cancer Study Group (IBCSG). Of the 17 study authors, 7 reported having relevant financial disclosures.
[email protected]
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Are Breast Cancer Patients Satisfied With Their Care?
Japan has a universal health care system with low copays and short wait times for appointments, including those with specialists. Yet patient satisfaction scores are low compared with those of other countries. Researchers from Juntendo Urayasu Hospital, a university hospital in a Tokyo suburb, conducted a study of 214 patients with breast cancer to find out which aspects of radiation oncology care might affect patient satisfaction. The survey included questions about overall treatment, time from diagnosis to treatment start, wait times in the hospital, and length of consultations.
In general, levels of satisfaction were high. However, wait time was significantly negatively associated with both overall satisfaction and satisfaction with the radiation oncologist. Wait time was just under an hour for an average 11-minute consultation. Although this was longer than the “notorious” Japanese situation of a “3 hours wait and 3 minutes consultation,” the researchers say, “We expect that an international audience will appreciate that even 11 minutes is an exceptionally short duration for a consultation visit with a specialist in radiation oncology.”
They note, though, a reasonable caveat. Anyone can walk into their hospital and, for an additional fee, see a specialist on the day they want, which can lead to extended wait times from sheer congestion. Their hospital’s chief breast cancer surgeon sees 60 to 70 patients a day; the radiation oncologist treats 500 to 600 patients a year without resident or trainee support. This situation is typical of Japanese university hospitals, the researchers add.
Related: Breast Cancer Treatment Among Rural and Urban Women at the Veterans Health Administration
Importantly, for Japanese patients, the researchers also included questions to measure patients’ opinions about sharing how they felt with their physicians. The level of sharing correlated with satisfaction, but the researchers point out that in Japan sharing feelings remains “challenging.” Their findings suggest, they say, that if this were improved, patients’ satisfaction might increase.
Japan has a universal health care system with low copays and short wait times for appointments, including those with specialists. Yet patient satisfaction scores are low compared with those of other countries. Researchers from Juntendo Urayasu Hospital, a university hospital in a Tokyo suburb, conducted a study of 214 patients with breast cancer to find out which aspects of radiation oncology care might affect patient satisfaction. The survey included questions about overall treatment, time from diagnosis to treatment start, wait times in the hospital, and length of consultations.
In general, levels of satisfaction were high. However, wait time was significantly negatively associated with both overall satisfaction and satisfaction with the radiation oncologist. Wait time was just under an hour for an average 11-minute consultation. Although this was longer than the “notorious” Japanese situation of a “3 hours wait and 3 minutes consultation,” the researchers say, “We expect that an international audience will appreciate that even 11 minutes is an exceptionally short duration for a consultation visit with a specialist in radiation oncology.”
They note, though, a reasonable caveat. Anyone can walk into their hospital and, for an additional fee, see a specialist on the day they want, which can lead to extended wait times from sheer congestion. Their hospital’s chief breast cancer surgeon sees 60 to 70 patients a day; the radiation oncologist treats 500 to 600 patients a year without resident or trainee support. This situation is typical of Japanese university hospitals, the researchers add.
Related: Breast Cancer Treatment Among Rural and Urban Women at the Veterans Health Administration
Importantly, for Japanese patients, the researchers also included questions to measure patients’ opinions about sharing how they felt with their physicians. The level of sharing correlated with satisfaction, but the researchers point out that in Japan sharing feelings remains “challenging.” Their findings suggest, they say, that if this were improved, patients’ satisfaction might increase.
Japan has a universal health care system with low copays and short wait times for appointments, including those with specialists. Yet patient satisfaction scores are low compared with those of other countries. Researchers from Juntendo Urayasu Hospital, a university hospital in a Tokyo suburb, conducted a study of 214 patients with breast cancer to find out which aspects of radiation oncology care might affect patient satisfaction. The survey included questions about overall treatment, time from diagnosis to treatment start, wait times in the hospital, and length of consultations.
In general, levels of satisfaction were high. However, wait time was significantly negatively associated with both overall satisfaction and satisfaction with the radiation oncologist. Wait time was just under an hour for an average 11-minute consultation. Although this was longer than the “notorious” Japanese situation of a “3 hours wait and 3 minutes consultation,” the researchers say, “We expect that an international audience will appreciate that even 11 minutes is an exceptionally short duration for a consultation visit with a specialist in radiation oncology.”
They note, though, a reasonable caveat. Anyone can walk into their hospital and, for an additional fee, see a specialist on the day they want, which can lead to extended wait times from sheer congestion. Their hospital’s chief breast cancer surgeon sees 60 to 70 patients a day; the radiation oncologist treats 500 to 600 patients a year without resident or trainee support. This situation is typical of Japanese university hospitals, the researchers add.
Related: Breast Cancer Treatment Among Rural and Urban Women at the Veterans Health Administration
Importantly, for Japanese patients, the researchers also included questions to measure patients’ opinions about sharing how they felt with their physicians. The level of sharing correlated with satisfaction, but the researchers point out that in Japan sharing feelings remains “challenging.” Their findings suggest, they say, that if this were improved, patients’ satisfaction might increase.
Optimal adjuvant endocrine therapy use in breast cancer remains elusive
Appropriate use of adjuvant endocrine therapy for breast cancer improved over a 10-year period, but optimal use has not been achieved, according to findings from a retrospective review of more than 980,000 women with stages I-III breast cancer.
As a result, an estimated 14,630 lives were unnecessarily lost during the study period, according to Bobby M. Daly, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.
Of the 981,729 women in the National Cancer Database from Jan. 1, 2004, to Dec. 31, 2013, who received all or part of their care at the reporting institution and who met eligibility criteria, 818,435 had hormone receptor positive (HR+) disease and 163,294 had hormone receptor negative (HR-) disease.
The percentage of HR+ patients receiving adjuvant endocrine therapy (AET) increased from 69.8% in 2004 to 82.4% in 2013 (annual percentage change, 1.51%), and the percentage of HR- patients decreased from 5.2% to 3.4% during the same time period (annual percentage change, -0.17%), the authors reported online Feb. 2 in JAMA Oncology (2017 Feb 2. doi: 10.1001jamaoncol.2016.6380).
Notably, receipt of AET varied significantly by age, race, geographic location, and receptor status. For example, more than 80% of those aged 50-69 years received AET, compared with 79.1% of those younger than age 40 years and 60.5% of those 80 years or older. African American and Hispanic patients were less likely than non-Hispanic white patients to receive AET (76.4% and 75.9% vs. 79.0%, respectively). The latter finding could be an important contributing factor to the racial disparity in breast cancer survival, the authors noted.
Facility factors also played a role in AET receipt; the rate of receipt varied substantially by facility volume and geographic location.
“We found that facilities in west south central states and low-volume institutions were more likely to misuse and underuse AET,” the investigators wrote, noting that these deficits could affect breast cancer mortality, as geographic differences in such mortality are well documented.
AET receipt also varied based on hormone receptor status, tumor size, and local treatment. Surgery and radiotherapy were the factors most significantly associated with appropriate AET receipt, with only 45% of those who underwent lumpectomy without radiotherapy receiving AET, compared with 90.1% of those receiving postmastectomy radiotherapy, 85.5% in those with postlumpectomy radiotherapy, and 73.2% of those with mastectomy alone.
Women included in this study were age 18 years or older (mean age, 60.8 years). Those undergoing surgery but receiving no neoadjuvant systemic treatment were eligible. Those with prior cancer diagnoses or with missing hormone receptor or AET status were excluded.
Based on recent trial results, the American Society of Clinical Oncology updated treatment guidelines in 2016 to recommend ovarian suppression for 5 years in combination with AET for high-risk premenopausal women, and AET alone both for women with stage I breast cancers that don’t warrant chemotherapy and for node-negative cancers of 1.0 cm or less.
“Similarly, the National Quality Forum (cancer measure 0220) endorsed tamoxifen or a third-generation aromatase inhibitor (considered or administered) within 1 year of diagnosis as a marker of quality care for patients with HR+ American Joint Committee on Cancer stage T1cN0M0, II, or III disease,” the researchers wrote. Studies demonstrated benefit with AET even in those with node-negative cancers of 1.0 cm or less, they added.
Improving adherence to these guidelines has lifesaving potential. In the current cohort, receipt of AET was associated with a 29% relative risk reduction in mortality, after adjusting for numerous patient, disease, and facility-related factors. This suggests that if all women with HR+ disease received AET in concordance with guidelines, 14,630 more lives would have been saved over the 10-year study period, the investigators said.
As for approaches that could help improve the appropriate use of AET, the findings of this cohort study support those from previous studies suggesting that a team-based approach is of benefit.
The finding that local treatments are key factors associated with appropriate AET use suggests that patients who undergo radiotherapy may be more likely to receive standard-of-care therapy in general, the authors explained, adding that “with more physicians involved in a patient’s care, these patients would be more likely to be recommended for guideline concordant care.
“Facilitation of multidisciplinary team-based care may help optimize guideline-concordant treatment by ensuring patients are not lost to follow-up and are recommended for evidence-based care,” the study authors concluded.
Their hope is that with the coming launch of the Medicare Access and Chip Reauthorization Act and value-based reimbursement, efforts will be made to close the quality gap affecting patients in certain age groups, racial minority groups, and geographic regions, and to thereby prevent the loss of lives.
MACRA may boost outcomes
In an interview, Dr. Daly said he believes the coming changes with respect to value-based reimbursement will indeed have an important impact on outcomes.
“The oncology care model, for example, mandates that physicians document that they are providing guideline-concordant care,” said Dr. Daly, assistant attending physician at Memorial Sloan Kettering Cancer Center. “There are also new technologies such as oncology clinical pathways ... that also try to ensure that all patients are receiving care according to guidelines.”
Further, the increasing use of team-based approaches to care and the incorporation of “tumor boards” might explain the growth in optimal AET usage seen in this cohort.
Dr. Daly said he was surprised to find that certain patient groups were being left behind, such as those with estrogen receptor-negative/progesterone receptor-positive disease, African American patients, and younger and older patients, who were less likely to receive AET.
“I think that helps us also focus on patient populations we can target to make sure they are receiving optimal care,” he said, stressing that the findings have important policy implications for figuring out why those patients are being left behind, and raising the standard of care for all patients.
“We are making great strides to providing appropriate guideline-concordant care for breast cancer patients, but there’s still room to improve,” he said.
Dr. Daly serves as a director of and receives compensation from Quadrant Holdings. Frontline Medical News is a subsidiary of Quadrant Holdings. Dr. Daly also reported financial relationships with CVS Health, Johnson & Johnson, McKesson, and Walgreens Boots Alliance.
Appropriate use of adjuvant endocrine therapy for breast cancer improved over a 10-year period, but optimal use has not been achieved, according to findings from a retrospective review of more than 980,000 women with stages I-III breast cancer.
As a result, an estimated 14,630 lives were unnecessarily lost during the study period, according to Bobby M. Daly, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.
Of the 981,729 women in the National Cancer Database from Jan. 1, 2004, to Dec. 31, 2013, who received all or part of their care at the reporting institution and who met eligibility criteria, 818,435 had hormone receptor positive (HR+) disease and 163,294 had hormone receptor negative (HR-) disease.
The percentage of HR+ patients receiving adjuvant endocrine therapy (AET) increased from 69.8% in 2004 to 82.4% in 2013 (annual percentage change, 1.51%), and the percentage of HR- patients decreased from 5.2% to 3.4% during the same time period (annual percentage change, -0.17%), the authors reported online Feb. 2 in JAMA Oncology (2017 Feb 2. doi: 10.1001jamaoncol.2016.6380).
Notably, receipt of AET varied significantly by age, race, geographic location, and receptor status. For example, more than 80% of those aged 50-69 years received AET, compared with 79.1% of those younger than age 40 years and 60.5% of those 80 years or older. African American and Hispanic patients were less likely than non-Hispanic white patients to receive AET (76.4% and 75.9% vs. 79.0%, respectively). The latter finding could be an important contributing factor to the racial disparity in breast cancer survival, the authors noted.
Facility factors also played a role in AET receipt; the rate of receipt varied substantially by facility volume and geographic location.
“We found that facilities in west south central states and low-volume institutions were more likely to misuse and underuse AET,” the investigators wrote, noting that these deficits could affect breast cancer mortality, as geographic differences in such mortality are well documented.
AET receipt also varied based on hormone receptor status, tumor size, and local treatment. Surgery and radiotherapy were the factors most significantly associated with appropriate AET receipt, with only 45% of those who underwent lumpectomy without radiotherapy receiving AET, compared with 90.1% of those receiving postmastectomy radiotherapy, 85.5% in those with postlumpectomy radiotherapy, and 73.2% of those with mastectomy alone.
Women included in this study were age 18 years or older (mean age, 60.8 years). Those undergoing surgery but receiving no neoadjuvant systemic treatment were eligible. Those with prior cancer diagnoses or with missing hormone receptor or AET status were excluded.
Based on recent trial results, the American Society of Clinical Oncology updated treatment guidelines in 2016 to recommend ovarian suppression for 5 years in combination with AET for high-risk premenopausal women, and AET alone both for women with stage I breast cancers that don’t warrant chemotherapy and for node-negative cancers of 1.0 cm or less.
“Similarly, the National Quality Forum (cancer measure 0220) endorsed tamoxifen or a third-generation aromatase inhibitor (considered or administered) within 1 year of diagnosis as a marker of quality care for patients with HR+ American Joint Committee on Cancer stage T1cN0M0, II, or III disease,” the researchers wrote. Studies demonstrated benefit with AET even in those with node-negative cancers of 1.0 cm or less, they added.
Improving adherence to these guidelines has lifesaving potential. In the current cohort, receipt of AET was associated with a 29% relative risk reduction in mortality, after adjusting for numerous patient, disease, and facility-related factors. This suggests that if all women with HR+ disease received AET in concordance with guidelines, 14,630 more lives would have been saved over the 10-year study period, the investigators said.
As for approaches that could help improve the appropriate use of AET, the findings of this cohort study support those from previous studies suggesting that a team-based approach is of benefit.
The finding that local treatments are key factors associated with appropriate AET use suggests that patients who undergo radiotherapy may be more likely to receive standard-of-care therapy in general, the authors explained, adding that “with more physicians involved in a patient’s care, these patients would be more likely to be recommended for guideline concordant care.
“Facilitation of multidisciplinary team-based care may help optimize guideline-concordant treatment by ensuring patients are not lost to follow-up and are recommended for evidence-based care,” the study authors concluded.
Their hope is that with the coming launch of the Medicare Access and Chip Reauthorization Act and value-based reimbursement, efforts will be made to close the quality gap affecting patients in certain age groups, racial minority groups, and geographic regions, and to thereby prevent the loss of lives.
MACRA may boost outcomes
In an interview, Dr. Daly said he believes the coming changes with respect to value-based reimbursement will indeed have an important impact on outcomes.
“The oncology care model, for example, mandates that physicians document that they are providing guideline-concordant care,” said Dr. Daly, assistant attending physician at Memorial Sloan Kettering Cancer Center. “There are also new technologies such as oncology clinical pathways ... that also try to ensure that all patients are receiving care according to guidelines.”
Further, the increasing use of team-based approaches to care and the incorporation of “tumor boards” might explain the growth in optimal AET usage seen in this cohort.
Dr. Daly said he was surprised to find that certain patient groups were being left behind, such as those with estrogen receptor-negative/progesterone receptor-positive disease, African American patients, and younger and older patients, who were less likely to receive AET.
“I think that helps us also focus on patient populations we can target to make sure they are receiving optimal care,” he said, stressing that the findings have important policy implications for figuring out why those patients are being left behind, and raising the standard of care for all patients.
“We are making great strides to providing appropriate guideline-concordant care for breast cancer patients, but there’s still room to improve,” he said.
Dr. Daly serves as a director of and receives compensation from Quadrant Holdings. Frontline Medical News is a subsidiary of Quadrant Holdings. Dr. Daly also reported financial relationships with CVS Health, Johnson & Johnson, McKesson, and Walgreens Boots Alliance.
Appropriate use of adjuvant endocrine therapy for breast cancer improved over a 10-year period, but optimal use has not been achieved, according to findings from a retrospective review of more than 980,000 women with stages I-III breast cancer.
As a result, an estimated 14,630 lives were unnecessarily lost during the study period, according to Bobby M. Daly, MD, of Memorial Sloan Kettering Cancer Center in New York, and his colleagues.
Of the 981,729 women in the National Cancer Database from Jan. 1, 2004, to Dec. 31, 2013, who received all or part of their care at the reporting institution and who met eligibility criteria, 818,435 had hormone receptor positive (HR+) disease and 163,294 had hormone receptor negative (HR-) disease.
The percentage of HR+ patients receiving adjuvant endocrine therapy (AET) increased from 69.8% in 2004 to 82.4% in 2013 (annual percentage change, 1.51%), and the percentage of HR- patients decreased from 5.2% to 3.4% during the same time period (annual percentage change, -0.17%), the authors reported online Feb. 2 in JAMA Oncology (2017 Feb 2. doi: 10.1001jamaoncol.2016.6380).
Notably, receipt of AET varied significantly by age, race, geographic location, and receptor status. For example, more than 80% of those aged 50-69 years received AET, compared with 79.1% of those younger than age 40 years and 60.5% of those 80 years or older. African American and Hispanic patients were less likely than non-Hispanic white patients to receive AET (76.4% and 75.9% vs. 79.0%, respectively). The latter finding could be an important contributing factor to the racial disparity in breast cancer survival, the authors noted.
Facility factors also played a role in AET receipt; the rate of receipt varied substantially by facility volume and geographic location.
“We found that facilities in west south central states and low-volume institutions were more likely to misuse and underuse AET,” the investigators wrote, noting that these deficits could affect breast cancer mortality, as geographic differences in such mortality are well documented.
AET receipt also varied based on hormone receptor status, tumor size, and local treatment. Surgery and radiotherapy were the factors most significantly associated with appropriate AET receipt, with only 45% of those who underwent lumpectomy without radiotherapy receiving AET, compared with 90.1% of those receiving postmastectomy radiotherapy, 85.5% in those with postlumpectomy radiotherapy, and 73.2% of those with mastectomy alone.
Women included in this study were age 18 years or older (mean age, 60.8 years). Those undergoing surgery but receiving no neoadjuvant systemic treatment were eligible. Those with prior cancer diagnoses or with missing hormone receptor or AET status were excluded.
Based on recent trial results, the American Society of Clinical Oncology updated treatment guidelines in 2016 to recommend ovarian suppression for 5 years in combination with AET for high-risk premenopausal women, and AET alone both for women with stage I breast cancers that don’t warrant chemotherapy and for node-negative cancers of 1.0 cm or less.
“Similarly, the National Quality Forum (cancer measure 0220) endorsed tamoxifen or a third-generation aromatase inhibitor (considered or administered) within 1 year of diagnosis as a marker of quality care for patients with HR+ American Joint Committee on Cancer stage T1cN0M0, II, or III disease,” the researchers wrote. Studies demonstrated benefit with AET even in those with node-negative cancers of 1.0 cm or less, they added.
Improving adherence to these guidelines has lifesaving potential. In the current cohort, receipt of AET was associated with a 29% relative risk reduction in mortality, after adjusting for numerous patient, disease, and facility-related factors. This suggests that if all women with HR+ disease received AET in concordance with guidelines, 14,630 more lives would have been saved over the 10-year study period, the investigators said.
As for approaches that could help improve the appropriate use of AET, the findings of this cohort study support those from previous studies suggesting that a team-based approach is of benefit.
The finding that local treatments are key factors associated with appropriate AET use suggests that patients who undergo radiotherapy may be more likely to receive standard-of-care therapy in general, the authors explained, adding that “with more physicians involved in a patient’s care, these patients would be more likely to be recommended for guideline concordant care.
“Facilitation of multidisciplinary team-based care may help optimize guideline-concordant treatment by ensuring patients are not lost to follow-up and are recommended for evidence-based care,” the study authors concluded.
Their hope is that with the coming launch of the Medicare Access and Chip Reauthorization Act and value-based reimbursement, efforts will be made to close the quality gap affecting patients in certain age groups, racial minority groups, and geographic regions, and to thereby prevent the loss of lives.
MACRA may boost outcomes
In an interview, Dr. Daly said he believes the coming changes with respect to value-based reimbursement will indeed have an important impact on outcomes.
“The oncology care model, for example, mandates that physicians document that they are providing guideline-concordant care,” said Dr. Daly, assistant attending physician at Memorial Sloan Kettering Cancer Center. “There are also new technologies such as oncology clinical pathways ... that also try to ensure that all patients are receiving care according to guidelines.”
Further, the increasing use of team-based approaches to care and the incorporation of “tumor boards” might explain the growth in optimal AET usage seen in this cohort.
Dr. Daly said he was surprised to find that certain patient groups were being left behind, such as those with estrogen receptor-negative/progesterone receptor-positive disease, African American patients, and younger and older patients, who were less likely to receive AET.
“I think that helps us also focus on patient populations we can target to make sure they are receiving optimal care,” he said, stressing that the findings have important policy implications for figuring out why those patients are being left behind, and raising the standard of care for all patients.
“We are making great strides to providing appropriate guideline-concordant care for breast cancer patients, but there’s still room to improve,” he said.
Dr. Daly serves as a director of and receives compensation from Quadrant Holdings. Frontline Medical News is a subsidiary of Quadrant Holdings. Dr. Daly also reported financial relationships with CVS Health, Johnson & Johnson, McKesson, and Walgreens Boots Alliance.
FROM JAMA ONCOLOGY
Key clinical point:
Major finding: Receipt of AET was associated with a 29% relative risk reduction in mortality; use of AET in concordance with guidelines would have saved an estimated 14,630 additional lives over 10 years.
Data source: A retrospective cohort study of 981,729 women with breast cancer.
Disclosures: Dr. Daly serves as a director of and receives compensation from Quadrant Holdings. Frontline Medical News is a subsidiary of Quadrant Holdings. Dr. Daly also reported financial relationships with CVS Health, Johnson & Johnson, McKesson, and Walgreens Boots Alliance.
START again shows safety of hypofractionated doses in early breast cancer
AMSTERDAM – Analyses of patient-reported outcomes in the UK START A and B trials show that radiation doses greater than 2 Gy to the supraclavicular fossa or axilla are safe and are associated with acceptable near- and late-term toxicities, trial investigators reported.
The START trials compared standard adjuvant radiation doses and schedules with accelerated, hypofractionated doses in women with early breast cancer.
At the annual San Antonio Breast Cancer Symposium in 2012, lead investigator John Yarnold, MD, professor of clinical oncology at the Institute of Cancer Research in London, reported that a 40-Gy, 15-fraction regimen was associated with fewer adverse events over 10 years of follow-up compared with a 50-Gy, 25-fraction regimen that was at the time the standard in the United States and the United Kingdom.
Here at an annual congress sponsored by the European Cancer Organisation, Dr. Yarnold reported that among 479 patients in the two trials who had lymphatic radiation, there were no significant differences in arm or shoulder pain, swelling, motion problems, or shoulder stiffness between patients who received conventional 2-Gy fractions for a total of 50 Gy, or lower total doses of radiation divided into fractions larger than 2 Gy.
“A post hoc analysis of outcomes in 479 patients treated with radiotherapy fractions larger than 2 Gy to the supraclavicular fossa and/or the axilla raise no concerns in terms of safety or patient acceptability, and it was for this reason that this schedule has been the standard for locoregional radiotherapy in the UK for some years now,” he said.
START (Standardization of Breast Radiotherapy) A enrolled 2,236 patients from 35 UK centers with breast cancer stages T 1-3, nodal stage N0-1, and no distant metastases (M0) and randomly assigned them to 50 Gy in 25 fractions of 2 Gy each over 5 weeks, 39.0 Gy in 13 fractions of 3.0 Gy over 5 weeks, and 41.6 Gy in 13 fractions of 3.2 Gy over 5 weeks.
In START B, 2,215 women were randomly assigned to the 50 Gy or 40 Gy regimens.
As reported in 2012, over a median follow-up of 9.3 years in START A, the 41.6-Gy regimen was similar in its adverse events profile compared with the 50-Gy dose (hazard ratio [HR] 0.94, and the lower-dose regimen also was comparable in efficacy, as measured by the rate of locoregional tumor relapse.
There were numerically but not significantly more relapses in the 39-Gy dose, however.
In START B, the 40-Gy dose was associated with significantly fewer adverse events over a median of 9.9 years of follow-up (HR 0.77). Efficacy was similar, although there was a nonsignificant trend toward superiority for the hypofractionated regimen.
In the post hoc analysis, the investigators looked at adverse events in 479 total patients in START A and B, 365 of whom had completed patient-reported outcome measures on the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer–Specific Quality of Life Questionnaire (QLQ-BR23).
A total of 262 patients in START A, and 103 in START B completed the questionnaires at 0, 6, 12, 24, and 60 months. Of these patients. The majority in each arm had radiation to the supraclavicular fossa only, and a minority had axilla radiation alone or in addition to supraclavicular fossa radiation.
In START B, 5-year patient reported outcomes of severity of 3 or 4 on a 4-point scale were low in each treatment arm, with arm or hand swelling reported in 10% of patients on 50 Gy, and 6% of patients on 40 Gy, and shoulder stiffness reported in 12% on the 50-Gy dose, vs. 15% on the 40-Gy dose.
Among all 479 patients with clinical assessments at 10 years, there were also no significant differences in either arm edema or shoulder stiffness between patients who received 50 Gy and those who received other, hypofractionated in each of the two trials.
The findings lend support to the Danish Breast Cancer Cooperative Group’s SKAGEN Trial 1, which is evaluating moderately hypofractionated locoregional adjuvant radiation therapy of early breast cancer combined with a simultaneous integrated boost in patients with an indication for boost, Dr. Yarnold said.
The UK START trials were supported by Cancer Research UK, the Medical Research Council, and the National Cancer Research Institute. Dr. Yarnold reported having no conflicts of interest.
AMSTERDAM – Analyses of patient-reported outcomes in the UK START A and B trials show that radiation doses greater than 2 Gy to the supraclavicular fossa or axilla are safe and are associated with acceptable near- and late-term toxicities, trial investigators reported.
The START trials compared standard adjuvant radiation doses and schedules with accelerated, hypofractionated doses in women with early breast cancer.
At the annual San Antonio Breast Cancer Symposium in 2012, lead investigator John Yarnold, MD, professor of clinical oncology at the Institute of Cancer Research in London, reported that a 40-Gy, 15-fraction regimen was associated with fewer adverse events over 10 years of follow-up compared with a 50-Gy, 25-fraction regimen that was at the time the standard in the United States and the United Kingdom.
Here at an annual congress sponsored by the European Cancer Organisation, Dr. Yarnold reported that among 479 patients in the two trials who had lymphatic radiation, there were no significant differences in arm or shoulder pain, swelling, motion problems, or shoulder stiffness between patients who received conventional 2-Gy fractions for a total of 50 Gy, or lower total doses of radiation divided into fractions larger than 2 Gy.
“A post hoc analysis of outcomes in 479 patients treated with radiotherapy fractions larger than 2 Gy to the supraclavicular fossa and/or the axilla raise no concerns in terms of safety or patient acceptability, and it was for this reason that this schedule has been the standard for locoregional radiotherapy in the UK for some years now,” he said.
START (Standardization of Breast Radiotherapy) A enrolled 2,236 patients from 35 UK centers with breast cancer stages T 1-3, nodal stage N0-1, and no distant metastases (M0) and randomly assigned them to 50 Gy in 25 fractions of 2 Gy each over 5 weeks, 39.0 Gy in 13 fractions of 3.0 Gy over 5 weeks, and 41.6 Gy in 13 fractions of 3.2 Gy over 5 weeks.
In START B, 2,215 women were randomly assigned to the 50 Gy or 40 Gy regimens.
As reported in 2012, over a median follow-up of 9.3 years in START A, the 41.6-Gy regimen was similar in its adverse events profile compared with the 50-Gy dose (hazard ratio [HR] 0.94, and the lower-dose regimen also was comparable in efficacy, as measured by the rate of locoregional tumor relapse.
There were numerically but not significantly more relapses in the 39-Gy dose, however.
In START B, the 40-Gy dose was associated with significantly fewer adverse events over a median of 9.9 years of follow-up (HR 0.77). Efficacy was similar, although there was a nonsignificant trend toward superiority for the hypofractionated regimen.
In the post hoc analysis, the investigators looked at adverse events in 479 total patients in START A and B, 365 of whom had completed patient-reported outcome measures on the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer–Specific Quality of Life Questionnaire (QLQ-BR23).
A total of 262 patients in START A, and 103 in START B completed the questionnaires at 0, 6, 12, 24, and 60 months. Of these patients. The majority in each arm had radiation to the supraclavicular fossa only, and a minority had axilla radiation alone or in addition to supraclavicular fossa radiation.
In START B, 5-year patient reported outcomes of severity of 3 or 4 on a 4-point scale were low in each treatment arm, with arm or hand swelling reported in 10% of patients on 50 Gy, and 6% of patients on 40 Gy, and shoulder stiffness reported in 12% on the 50-Gy dose, vs. 15% on the 40-Gy dose.
Among all 479 patients with clinical assessments at 10 years, there were also no significant differences in either arm edema or shoulder stiffness between patients who received 50 Gy and those who received other, hypofractionated in each of the two trials.
The findings lend support to the Danish Breast Cancer Cooperative Group’s SKAGEN Trial 1, which is evaluating moderately hypofractionated locoregional adjuvant radiation therapy of early breast cancer combined with a simultaneous integrated boost in patients with an indication for boost, Dr. Yarnold said.
The UK START trials were supported by Cancer Research UK, the Medical Research Council, and the National Cancer Research Institute. Dr. Yarnold reported having no conflicts of interest.
AMSTERDAM – Analyses of patient-reported outcomes in the UK START A and B trials show that radiation doses greater than 2 Gy to the supraclavicular fossa or axilla are safe and are associated with acceptable near- and late-term toxicities, trial investigators reported.
The START trials compared standard adjuvant radiation doses and schedules with accelerated, hypofractionated doses in women with early breast cancer.
At the annual San Antonio Breast Cancer Symposium in 2012, lead investigator John Yarnold, MD, professor of clinical oncology at the Institute of Cancer Research in London, reported that a 40-Gy, 15-fraction regimen was associated with fewer adverse events over 10 years of follow-up compared with a 50-Gy, 25-fraction regimen that was at the time the standard in the United States and the United Kingdom.
Here at an annual congress sponsored by the European Cancer Organisation, Dr. Yarnold reported that among 479 patients in the two trials who had lymphatic radiation, there were no significant differences in arm or shoulder pain, swelling, motion problems, or shoulder stiffness between patients who received conventional 2-Gy fractions for a total of 50 Gy, or lower total doses of radiation divided into fractions larger than 2 Gy.
“A post hoc analysis of outcomes in 479 patients treated with radiotherapy fractions larger than 2 Gy to the supraclavicular fossa and/or the axilla raise no concerns in terms of safety or patient acceptability, and it was for this reason that this schedule has been the standard for locoregional radiotherapy in the UK for some years now,” he said.
START (Standardization of Breast Radiotherapy) A enrolled 2,236 patients from 35 UK centers with breast cancer stages T 1-3, nodal stage N0-1, and no distant metastases (M0) and randomly assigned them to 50 Gy in 25 fractions of 2 Gy each over 5 weeks, 39.0 Gy in 13 fractions of 3.0 Gy over 5 weeks, and 41.6 Gy in 13 fractions of 3.2 Gy over 5 weeks.
In START B, 2,215 women were randomly assigned to the 50 Gy or 40 Gy regimens.
As reported in 2012, over a median follow-up of 9.3 years in START A, the 41.6-Gy regimen was similar in its adverse events profile compared with the 50-Gy dose (hazard ratio [HR] 0.94, and the lower-dose regimen also was comparable in efficacy, as measured by the rate of locoregional tumor relapse.
There were numerically but not significantly more relapses in the 39-Gy dose, however.
In START B, the 40-Gy dose was associated with significantly fewer adverse events over a median of 9.9 years of follow-up (HR 0.77). Efficacy was similar, although there was a nonsignificant trend toward superiority for the hypofractionated regimen.
In the post hoc analysis, the investigators looked at adverse events in 479 total patients in START A and B, 365 of whom had completed patient-reported outcome measures on the European Organization for Research and Treatment of Cancer (EORTC) Breast Cancer–Specific Quality of Life Questionnaire (QLQ-BR23).
A total of 262 patients in START A, and 103 in START B completed the questionnaires at 0, 6, 12, 24, and 60 months. Of these patients. The majority in each arm had radiation to the supraclavicular fossa only, and a minority had axilla radiation alone or in addition to supraclavicular fossa radiation.
In START B, 5-year patient reported outcomes of severity of 3 or 4 on a 4-point scale were low in each treatment arm, with arm or hand swelling reported in 10% of patients on 50 Gy, and 6% of patients on 40 Gy, and shoulder stiffness reported in 12% on the 50-Gy dose, vs. 15% on the 40-Gy dose.
Among all 479 patients with clinical assessments at 10 years, there were also no significant differences in either arm edema or shoulder stiffness between patients who received 50 Gy and those who received other, hypofractionated in each of the two trials.
The findings lend support to the Danish Breast Cancer Cooperative Group’s SKAGEN Trial 1, which is evaluating moderately hypofractionated locoregional adjuvant radiation therapy of early breast cancer combined with a simultaneous integrated boost in patients with an indication for boost, Dr. Yarnold said.
The UK START trials were supported by Cancer Research UK, the Medical Research Council, and the National Cancer Research Institute. Dr. Yarnold reported having no conflicts of interest.
AT ECCO2017
Key clinical point: Additional follow-up supports continued safety of hypofractionated radiation in early breast cancer.
Major finding: There were no significant differences in either patient-reported outcomes at 5 years or clinical assessments at 10 years in patients treated at 40-Gy or 50-Gy doses.
Data source: Post hoc analysis of 479 patients treated in the UK START A and B trials.
Disclosures: The UK START trials were supported by Cancer Research UK, the Medical Research Council, and the National Cancer Research Institute. Dr. Yarnold reported having no conflicts of interest..
Survival better with breast-conserving therapy for early cancers
AMSTERDAM – In real-life practice, women with early, localized breast cancer who underwent breast conserving therapy had better breast cancer–specific and overall survival compared with women who underwent mastectomy, according to investigators in the Netherlands.
Among nearly 130,000 patients treated over two different time periods, breast-conserving surgery and radiation (BCT) was associated with superior survival for women older than 50, patients who did not receive adjuvant chemotherapy, and those with comorbidities – irrespective of either hormonal or human epidermal growth factor receptor 2 (HER2) status, reported Mirelle Lagendijk, MD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands.
For patients 50 and younger, overall survival (OS), but not breast cancer–specific survival (BCSS), was superior with the more conservative approach.
“Breast conserving therapy in these identified subgroups seems to be the preferable treatment when both treatments are optional,” Dr. Lagendijk said at an annual congress sponsored by the European Cancer Organisation.
Although recent observational studies have shown survival with BCT to be at least equivalent for women with early stage disease, there is still a lack of sufficient data on BCSS, potential confounders such as systemic therapies and comorbidities, and on the relative effects of BCT or mastectomy on subgroups, she said.
The investigators drew data from the Netherlands Cancer Registry on 129,692 patients with early, primary invasive breast cancer without metastases other than to regional lymph nodes (T1-2NO-2MO).
They compared BCT to mastectomy for BCSS and OS in the population as a whole and in subgroups based on prognostic factors. They controlled for age, tumor and nodal stage, comorbidities, systemic therapy, hormone receptor and HER2 status, differentiation grade, morphology, year of treatment, axillary lymph node dissection, and contralateral breast cancer.
They divided patients into two treatment time periods. The older cohort consisted of 60,381 patients treated from 1999 through 2005, 48% of whom underwent mastectomy, with a median follow-up of 11.1 years, and 52% of whom had BCT, with a median follow-up of 12 years.
The more recent cohort consisted of 69,311 patients, 40% of whom had mastectomy with a median follow-up of 5.9 years, and 60% of whom had BCT with a median follow-up of 6.1 years.
In both time periods, deaths from all causes were lower among patients treated with BCT. In the older cohort, 13,960 of 28,968 patients (48.2%) who underwent mastectomy had died, compared with 8,915 of 31,413 patients (28.4%) who underwent BCT. In the more recent cohort, 5,504 of 27,731 (19.8%) of patients who had mastectomies had died, compared with 3,702 of 41,580 (8.9%) who underwent BCT.
“Irrespective of the time cohort and irrespective of the treatment, around 50% of the events were breast cancer related,” Dr. Lagendijk said.
BCSS was superior with BCT in each time cohort (log-rank P less than .001 for each). In the earlier cohort, BCT was significantly superior for BCSS across all disease stages; in the later cohort, it was significant for all but stages T1N1 and T1-2N2.
BCSS was superior for patients in all age categories in the early cohort, and for patients 50 and older in the later cohort.
“The final stratification performed for comorbidities present in the patients evaluated showed, surprisingly, that especially for those patients with comorbidity, there was significantly better breast cancer-specific survival when treated by breast conserving therapy as compared to a mastectomy,” Dr. Lagendijk said.
The investigators acknowledged that the study was limited by its retrospective design, potential confounding by severity, and the inability to show causal relationship between survival and treatment type.
Dutch health agencies sponsored the study. Dr. Lagendijk and Dr. Naredi reported no conflicts of interest.
AMSTERDAM – In real-life practice, women with early, localized breast cancer who underwent breast conserving therapy had better breast cancer–specific and overall survival compared with women who underwent mastectomy, according to investigators in the Netherlands.
Among nearly 130,000 patients treated over two different time periods, breast-conserving surgery and radiation (BCT) was associated with superior survival for women older than 50, patients who did not receive adjuvant chemotherapy, and those with comorbidities – irrespective of either hormonal or human epidermal growth factor receptor 2 (HER2) status, reported Mirelle Lagendijk, MD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands.
For patients 50 and younger, overall survival (OS), but not breast cancer–specific survival (BCSS), was superior with the more conservative approach.
“Breast conserving therapy in these identified subgroups seems to be the preferable treatment when both treatments are optional,” Dr. Lagendijk said at an annual congress sponsored by the European Cancer Organisation.
Although recent observational studies have shown survival with BCT to be at least equivalent for women with early stage disease, there is still a lack of sufficient data on BCSS, potential confounders such as systemic therapies and comorbidities, and on the relative effects of BCT or mastectomy on subgroups, she said.
The investigators drew data from the Netherlands Cancer Registry on 129,692 patients with early, primary invasive breast cancer without metastases other than to regional lymph nodes (T1-2NO-2MO).
They compared BCT to mastectomy for BCSS and OS in the population as a whole and in subgroups based on prognostic factors. They controlled for age, tumor and nodal stage, comorbidities, systemic therapy, hormone receptor and HER2 status, differentiation grade, morphology, year of treatment, axillary lymph node dissection, and contralateral breast cancer.
They divided patients into two treatment time periods. The older cohort consisted of 60,381 patients treated from 1999 through 2005, 48% of whom underwent mastectomy, with a median follow-up of 11.1 years, and 52% of whom had BCT, with a median follow-up of 12 years.
The more recent cohort consisted of 69,311 patients, 40% of whom had mastectomy with a median follow-up of 5.9 years, and 60% of whom had BCT with a median follow-up of 6.1 years.
In both time periods, deaths from all causes were lower among patients treated with BCT. In the older cohort, 13,960 of 28,968 patients (48.2%) who underwent mastectomy had died, compared with 8,915 of 31,413 patients (28.4%) who underwent BCT. In the more recent cohort, 5,504 of 27,731 (19.8%) of patients who had mastectomies had died, compared with 3,702 of 41,580 (8.9%) who underwent BCT.
“Irrespective of the time cohort and irrespective of the treatment, around 50% of the events were breast cancer related,” Dr. Lagendijk said.
BCSS was superior with BCT in each time cohort (log-rank P less than .001 for each). In the earlier cohort, BCT was significantly superior for BCSS across all disease stages; in the later cohort, it was significant for all but stages T1N1 and T1-2N2.
BCSS was superior for patients in all age categories in the early cohort, and for patients 50 and older in the later cohort.
“The final stratification performed for comorbidities present in the patients evaluated showed, surprisingly, that especially for those patients with comorbidity, there was significantly better breast cancer-specific survival when treated by breast conserving therapy as compared to a mastectomy,” Dr. Lagendijk said.
The investigators acknowledged that the study was limited by its retrospective design, potential confounding by severity, and the inability to show causal relationship between survival and treatment type.
Dutch health agencies sponsored the study. Dr. Lagendijk and Dr. Naredi reported no conflicts of interest.
AMSTERDAM – In real-life practice, women with early, localized breast cancer who underwent breast conserving therapy had better breast cancer–specific and overall survival compared with women who underwent mastectomy, according to investigators in the Netherlands.
Among nearly 130,000 patients treated over two different time periods, breast-conserving surgery and radiation (BCT) was associated with superior survival for women older than 50, patients who did not receive adjuvant chemotherapy, and those with comorbidities – irrespective of either hormonal or human epidermal growth factor receptor 2 (HER2) status, reported Mirelle Lagendijk, MD, of Erasmus Medical Center Cancer Institute in Rotterdam, the Netherlands.
For patients 50 and younger, overall survival (OS), but not breast cancer–specific survival (BCSS), was superior with the more conservative approach.
“Breast conserving therapy in these identified subgroups seems to be the preferable treatment when both treatments are optional,” Dr. Lagendijk said at an annual congress sponsored by the European Cancer Organisation.
Although recent observational studies have shown survival with BCT to be at least equivalent for women with early stage disease, there is still a lack of sufficient data on BCSS, potential confounders such as systemic therapies and comorbidities, and on the relative effects of BCT or mastectomy on subgroups, she said.
The investigators drew data from the Netherlands Cancer Registry on 129,692 patients with early, primary invasive breast cancer without metastases other than to regional lymph nodes (T1-2NO-2MO).
They compared BCT to mastectomy for BCSS and OS in the population as a whole and in subgroups based on prognostic factors. They controlled for age, tumor and nodal stage, comorbidities, systemic therapy, hormone receptor and HER2 status, differentiation grade, morphology, year of treatment, axillary lymph node dissection, and contralateral breast cancer.
They divided patients into two treatment time periods. The older cohort consisted of 60,381 patients treated from 1999 through 2005, 48% of whom underwent mastectomy, with a median follow-up of 11.1 years, and 52% of whom had BCT, with a median follow-up of 12 years.
The more recent cohort consisted of 69,311 patients, 40% of whom had mastectomy with a median follow-up of 5.9 years, and 60% of whom had BCT with a median follow-up of 6.1 years.
In both time periods, deaths from all causes were lower among patients treated with BCT. In the older cohort, 13,960 of 28,968 patients (48.2%) who underwent mastectomy had died, compared with 8,915 of 31,413 patients (28.4%) who underwent BCT. In the more recent cohort, 5,504 of 27,731 (19.8%) of patients who had mastectomies had died, compared with 3,702 of 41,580 (8.9%) who underwent BCT.
“Irrespective of the time cohort and irrespective of the treatment, around 50% of the events were breast cancer related,” Dr. Lagendijk said.
BCSS was superior with BCT in each time cohort (log-rank P less than .001 for each). In the earlier cohort, BCT was significantly superior for BCSS across all disease stages; in the later cohort, it was significant for all but stages T1N1 and T1-2N2.
BCSS was superior for patients in all age categories in the early cohort, and for patients 50 and older in the later cohort.
“The final stratification performed for comorbidities present in the patients evaluated showed, surprisingly, that especially for those patients with comorbidity, there was significantly better breast cancer-specific survival when treated by breast conserving therapy as compared to a mastectomy,” Dr. Lagendijk said.
The investigators acknowledged that the study was limited by its retrospective design, potential confounding by severity, and the inability to show causal relationship between survival and treatment type.
Dutch health agencies sponsored the study. Dr. Lagendijk and Dr. Naredi reported no conflicts of interest.
AT ECCO2017
Key clinical point: Breast cancer–specific survival and overall survival were better among women who had breast-conserving therapy (BCT) compared with mastectomy.
Major finding: BCT was associated with superior survival for women older than 50, patients who did not receive adjuvant chemotherapy, and those with comorbidities.
Data source: Retrospective registry data study of 129,692 women treated for early breast cancer in the Netherlands during 1999-2005 and 2006-2012.
Disclosures: Dutch health agencies sponsored the study. Dr. Langendijk and Dr. Naredi reported no conflicts of interest.