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Cardiac monitoring falls short in elderly breast cancer patients given trastuzumab
Nearly two-thirds of older women receiving trastuzumab for breast cancer do not get adequate cardiac monitoring, despite the known risks for cardiotoxicity, investigators reported.
Only 36% of 2,203 patients with a median age of 72 years who received trastuzumab (Herceptin)-based adjuvant therapy had adequate cardiac monitoring, based on a review (J. Clin. Oncol 2015 May 11 [doi:10.1200/JCO.2014.58.9465]).
“Our study shows that cardiac monitoring is an area that requires improvement. Actions to increase the rates of cardiac monitoring in this vulnerable population are needed, and adequate cardiac monitoring among trastuzumab-treated patients should be considered a marker of quality of care. Efforts to further disseminate current guidelines should be a priority for our hospitals, training programs, and medical societies,” wrote Dr. Mariana Chavez-MacGregor and colleagues from the University of Texas MD Anderson Cancer Center in Houston.
The authors reviewed Medicare data on patients aged 66 years and older with stage I-III breast cancer treated with trastuzumab-based therapy. They found that 79% of the patients had a baseline cardiac evaluation and that 68% had cardiac tests within 4 months of starting on therapy. Only 43% of patients, however, received subsequent monitoring once every 4 months as recommended in treatment guidelines, and only 36% received optimal monitoring with baseline exam and scheduled follow-up evaluations, the researchers reported.
In multivariable models controlling for demographic/socioeconomic factors (age, race, marital status, education, income, urban/rural residence), clinical stage, comorbidities, and anthracycline and taxane use, factors associated with the likelihood of getting optimal monitoring included more recent year of diagnosis, anthracycline exposure, female prescribing physician, and physician age. Physicians who graduated from medical school after 1990 were significantly more likely to recommend monitoring.
“We estimated the relative contributions of physician and patient-level effects to the variance of the observation; 15.3% of the variance in the adequacy of cardiac monitoring was attributable to physician factors, and only 5.2% of the variance was attributable to measured patient factors,” the authors wrote.
Dr. Chavez-MacGregor disclosed financial relationships with Genomic Health, Roche, and Novartis.
Nearly two-thirds of older women receiving trastuzumab for breast cancer do not get adequate cardiac monitoring, despite the known risks for cardiotoxicity, investigators reported.
Only 36% of 2,203 patients with a median age of 72 years who received trastuzumab (Herceptin)-based adjuvant therapy had adequate cardiac monitoring, based on a review (J. Clin. Oncol 2015 May 11 [doi:10.1200/JCO.2014.58.9465]).
“Our study shows that cardiac monitoring is an area that requires improvement. Actions to increase the rates of cardiac monitoring in this vulnerable population are needed, and adequate cardiac monitoring among trastuzumab-treated patients should be considered a marker of quality of care. Efforts to further disseminate current guidelines should be a priority for our hospitals, training programs, and medical societies,” wrote Dr. Mariana Chavez-MacGregor and colleagues from the University of Texas MD Anderson Cancer Center in Houston.
The authors reviewed Medicare data on patients aged 66 years and older with stage I-III breast cancer treated with trastuzumab-based therapy. They found that 79% of the patients had a baseline cardiac evaluation and that 68% had cardiac tests within 4 months of starting on therapy. Only 43% of patients, however, received subsequent monitoring once every 4 months as recommended in treatment guidelines, and only 36% received optimal monitoring with baseline exam and scheduled follow-up evaluations, the researchers reported.
In multivariable models controlling for demographic/socioeconomic factors (age, race, marital status, education, income, urban/rural residence), clinical stage, comorbidities, and anthracycline and taxane use, factors associated with the likelihood of getting optimal monitoring included more recent year of diagnosis, anthracycline exposure, female prescribing physician, and physician age. Physicians who graduated from medical school after 1990 were significantly more likely to recommend monitoring.
“We estimated the relative contributions of physician and patient-level effects to the variance of the observation; 15.3% of the variance in the adequacy of cardiac monitoring was attributable to physician factors, and only 5.2% of the variance was attributable to measured patient factors,” the authors wrote.
Dr. Chavez-MacGregor disclosed financial relationships with Genomic Health, Roche, and Novartis.
Nearly two-thirds of older women receiving trastuzumab for breast cancer do not get adequate cardiac monitoring, despite the known risks for cardiotoxicity, investigators reported.
Only 36% of 2,203 patients with a median age of 72 years who received trastuzumab (Herceptin)-based adjuvant therapy had adequate cardiac monitoring, based on a review (J. Clin. Oncol 2015 May 11 [doi:10.1200/JCO.2014.58.9465]).
“Our study shows that cardiac monitoring is an area that requires improvement. Actions to increase the rates of cardiac monitoring in this vulnerable population are needed, and adequate cardiac monitoring among trastuzumab-treated patients should be considered a marker of quality of care. Efforts to further disseminate current guidelines should be a priority for our hospitals, training programs, and medical societies,” wrote Dr. Mariana Chavez-MacGregor and colleagues from the University of Texas MD Anderson Cancer Center in Houston.
The authors reviewed Medicare data on patients aged 66 years and older with stage I-III breast cancer treated with trastuzumab-based therapy. They found that 79% of the patients had a baseline cardiac evaluation and that 68% had cardiac tests within 4 months of starting on therapy. Only 43% of patients, however, received subsequent monitoring once every 4 months as recommended in treatment guidelines, and only 36% received optimal monitoring with baseline exam and scheduled follow-up evaluations, the researchers reported.
In multivariable models controlling for demographic/socioeconomic factors (age, race, marital status, education, income, urban/rural residence), clinical stage, comorbidities, and anthracycline and taxane use, factors associated with the likelihood of getting optimal monitoring included more recent year of diagnosis, anthracycline exposure, female prescribing physician, and physician age. Physicians who graduated from medical school after 1990 were significantly more likely to recommend monitoring.
“We estimated the relative contributions of physician and patient-level effects to the variance of the observation; 15.3% of the variance in the adequacy of cardiac monitoring was attributable to physician factors, and only 5.2% of the variance was attributable to measured patient factors,” the authors wrote.
Dr. Chavez-MacGregor disclosed financial relationships with Genomic Health, Roche, and Novartis.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Older patients on trastuzumab-based adjuvant therapy require baseline and regular cardiac monitoring.
Major finding: Only 36% of women aged 66 years and older received optimal monitoring during trastuzumab-based therapy.
Data source: Review of SEER-Medicare and Texas Cancer Registry Medicare data on 2,203 women with a mean age of 72 years.
Disclosures: Dr. Chavez-MacGregor disclosed financial relationships with Genomic Health, Roche, and Novartis.
ASA: Radiation lowers local recurrence risk for DCIS patients with close or positive margins
SAN DIEGO – Radiation may benefit women with ductal carcinoma in situ (DCIS) who have breast-conserving surgery if their tumor margins are close or positive; however, wide tumor margins alone also may convey the same protection from local recurrence, Dr. Kimberly Van Zee reported at the annual meeting of the American Surgical Association.
Dr. Van Zee and her colleagues on the breast surgery service at New York’s Sloan Kettering Cancer Center examined the data from a large institutional database of DCIS patients to assess the relative benefit of radiation for various margin widths. They discovered that after adjusting for the other variables, patients with the widest tumor margins saw very little reduction in risk of 10-year recurrence when radiation was added – only 6%. However, this was still a significant difference and represented a hazard ratio of 0.54. Radiation gave patients with positive margins an absolute 18% risk reduction, for a hazard ratio of 0.10.
“We know that radiation reduces risk in all subsets of women with DCIS undergoing breast-conserving surgery,” she said. “But we really wanted to evaluate the relationship between margin width and recurrence and find the best margin width for DCIS with breast-conserving surgery.”
Over 20% of breast cancers are DCIS, and though overall mortality is low, as many as one in three patients will have local recurrence of their cancer. Radiation reduces the risk of local recurrence by about 50%, but it does not reduce the already low mortality associated with DCIS, she said.
Since radiation for DCIS may be associated with an increased risk for cardiovascular disease and certain rare malignancies, Dr. Van Zee said she and her colleagues were interested in identifying those women who were already at low risk for recurrence and would see little increased benefit from radiation.
Dr. Van Zee and her associates conducted a retrospective review of a prospectively collected database of women with DCIS who received treatment at Sloan Kettering Cancer Center between 1978 and 2010. The database contained multiple patient- and procedure-specific variables that were also factored into multivariable analysis in order to evaluate the relationships between margin width and recurrence, and to account for the contribution of radiation to reducing the risk of recurrence in women who received breast-conserving surgery for DCIS.
Overall, the database contained data for nearly 3,000 patients. Of the 2,996 studied, 72% were over the age of 50 and about 67% were postmenopausal. In 87% of cases, the diagnosis was made radiologically rather than clinically, and 60% of the patients had low or intermediate nuclear grade disease.
Dr. Van Zee and her colleagues assessed the 10-year recurrence rate for the 2,788 women whose excision margin width was known. Only 3% of these women had positive margins, and 75% had margin widths greater than 2 mm.
On multivariable analysis, wider margin width was associated with a significantly decreased 10-year risk of recurrence, but only for individuals who had not received radiation (P less than .0001). The hazard ratios for recurrence became progressively lower as margins widened, dropping to 0.31 for a margin of 10 mm or more.
Dr. Van Zee noted that the study was limited by its retrospective nature and the relatively small number of cases with positive margins. Also, cases with positive or close margins usually had more limited or focal disease at the margins, so recurrence rate estimates for this group may have underestimated risk of recurrence for those who had more significant disease.
During the discussion following her presentation, Dr. Van Zee noted that multiple factors are related to the risk of local recurrence, and that nomograms exist to help calculate risk and guide the decision to recommend radiation in women with close margins.
Dr. Patrick Borgen, chairman of the department of surgery at Maimonides Medical Center, New York, remarked that “biology beats technique. A growing wealth of information exists that there is a reservoir of DCIS that will progress so slowly as not to be significant. Is the next step in refining our approach better class prediction using genomic profiling?”
Dr. Van Zee agreed that genomic profiling will play a role, but noted that a study comparing DCIS score and multiple clinical variables would be expensive and archival pathology specimens would be difficult to obtain. Studies will mostly have to be prospective, she said.
The complete manuscript of this study and its presentation at the American Surgical Association’s 135th Annual Meeting, April 2015, in San Diego, California, are anticipated to be published in the Annals of Surgery pending editorial review.
This article was updated May 11, 2015.
SAN DIEGO – Radiation may benefit women with ductal carcinoma in situ (DCIS) who have breast-conserving surgery if their tumor margins are close or positive; however, wide tumor margins alone also may convey the same protection from local recurrence, Dr. Kimberly Van Zee reported at the annual meeting of the American Surgical Association.
Dr. Van Zee and her colleagues on the breast surgery service at New York’s Sloan Kettering Cancer Center examined the data from a large institutional database of DCIS patients to assess the relative benefit of radiation for various margin widths. They discovered that after adjusting for the other variables, patients with the widest tumor margins saw very little reduction in risk of 10-year recurrence when radiation was added – only 6%. However, this was still a significant difference and represented a hazard ratio of 0.54. Radiation gave patients with positive margins an absolute 18% risk reduction, for a hazard ratio of 0.10.
“We know that radiation reduces risk in all subsets of women with DCIS undergoing breast-conserving surgery,” she said. “But we really wanted to evaluate the relationship between margin width and recurrence and find the best margin width for DCIS with breast-conserving surgery.”
Over 20% of breast cancers are DCIS, and though overall mortality is low, as many as one in three patients will have local recurrence of their cancer. Radiation reduces the risk of local recurrence by about 50%, but it does not reduce the already low mortality associated with DCIS, she said.
Since radiation for DCIS may be associated with an increased risk for cardiovascular disease and certain rare malignancies, Dr. Van Zee said she and her colleagues were interested in identifying those women who were already at low risk for recurrence and would see little increased benefit from radiation.
Dr. Van Zee and her associates conducted a retrospective review of a prospectively collected database of women with DCIS who received treatment at Sloan Kettering Cancer Center between 1978 and 2010. The database contained multiple patient- and procedure-specific variables that were also factored into multivariable analysis in order to evaluate the relationships between margin width and recurrence, and to account for the contribution of radiation to reducing the risk of recurrence in women who received breast-conserving surgery for DCIS.
Overall, the database contained data for nearly 3,000 patients. Of the 2,996 studied, 72% were over the age of 50 and about 67% were postmenopausal. In 87% of cases, the diagnosis was made radiologically rather than clinically, and 60% of the patients had low or intermediate nuclear grade disease.
Dr. Van Zee and her colleagues assessed the 10-year recurrence rate for the 2,788 women whose excision margin width was known. Only 3% of these women had positive margins, and 75% had margin widths greater than 2 mm.
On multivariable analysis, wider margin width was associated with a significantly decreased 10-year risk of recurrence, but only for individuals who had not received radiation (P less than .0001). The hazard ratios for recurrence became progressively lower as margins widened, dropping to 0.31 for a margin of 10 mm or more.
Dr. Van Zee noted that the study was limited by its retrospective nature and the relatively small number of cases with positive margins. Also, cases with positive or close margins usually had more limited or focal disease at the margins, so recurrence rate estimates for this group may have underestimated risk of recurrence for those who had more significant disease.
During the discussion following her presentation, Dr. Van Zee noted that multiple factors are related to the risk of local recurrence, and that nomograms exist to help calculate risk and guide the decision to recommend radiation in women with close margins.
Dr. Patrick Borgen, chairman of the department of surgery at Maimonides Medical Center, New York, remarked that “biology beats technique. A growing wealth of information exists that there is a reservoir of DCIS that will progress so slowly as not to be significant. Is the next step in refining our approach better class prediction using genomic profiling?”
Dr. Van Zee agreed that genomic profiling will play a role, but noted that a study comparing DCIS score and multiple clinical variables would be expensive and archival pathology specimens would be difficult to obtain. Studies will mostly have to be prospective, she said.
The complete manuscript of this study and its presentation at the American Surgical Association’s 135th Annual Meeting, April 2015, in San Diego, California, are anticipated to be published in the Annals of Surgery pending editorial review.
This article was updated May 11, 2015.
SAN DIEGO – Radiation may benefit women with ductal carcinoma in situ (DCIS) who have breast-conserving surgery if their tumor margins are close or positive; however, wide tumor margins alone also may convey the same protection from local recurrence, Dr. Kimberly Van Zee reported at the annual meeting of the American Surgical Association.
Dr. Van Zee and her colleagues on the breast surgery service at New York’s Sloan Kettering Cancer Center examined the data from a large institutional database of DCIS patients to assess the relative benefit of radiation for various margin widths. They discovered that after adjusting for the other variables, patients with the widest tumor margins saw very little reduction in risk of 10-year recurrence when radiation was added – only 6%. However, this was still a significant difference and represented a hazard ratio of 0.54. Radiation gave patients with positive margins an absolute 18% risk reduction, for a hazard ratio of 0.10.
“We know that radiation reduces risk in all subsets of women with DCIS undergoing breast-conserving surgery,” she said. “But we really wanted to evaluate the relationship between margin width and recurrence and find the best margin width for DCIS with breast-conserving surgery.”
Over 20% of breast cancers are DCIS, and though overall mortality is low, as many as one in three patients will have local recurrence of their cancer. Radiation reduces the risk of local recurrence by about 50%, but it does not reduce the already low mortality associated with DCIS, she said.
Since radiation for DCIS may be associated with an increased risk for cardiovascular disease and certain rare malignancies, Dr. Van Zee said she and her colleagues were interested in identifying those women who were already at low risk for recurrence and would see little increased benefit from radiation.
Dr. Van Zee and her associates conducted a retrospective review of a prospectively collected database of women with DCIS who received treatment at Sloan Kettering Cancer Center between 1978 and 2010. The database contained multiple patient- and procedure-specific variables that were also factored into multivariable analysis in order to evaluate the relationships between margin width and recurrence, and to account for the contribution of radiation to reducing the risk of recurrence in women who received breast-conserving surgery for DCIS.
Overall, the database contained data for nearly 3,000 patients. Of the 2,996 studied, 72% were over the age of 50 and about 67% were postmenopausal. In 87% of cases, the diagnosis was made radiologically rather than clinically, and 60% of the patients had low or intermediate nuclear grade disease.
Dr. Van Zee and her colleagues assessed the 10-year recurrence rate for the 2,788 women whose excision margin width was known. Only 3% of these women had positive margins, and 75% had margin widths greater than 2 mm.
On multivariable analysis, wider margin width was associated with a significantly decreased 10-year risk of recurrence, but only for individuals who had not received radiation (P less than .0001). The hazard ratios for recurrence became progressively lower as margins widened, dropping to 0.31 for a margin of 10 mm or more.
Dr. Van Zee noted that the study was limited by its retrospective nature and the relatively small number of cases with positive margins. Also, cases with positive or close margins usually had more limited or focal disease at the margins, so recurrence rate estimates for this group may have underestimated risk of recurrence for those who had more significant disease.
During the discussion following her presentation, Dr. Van Zee noted that multiple factors are related to the risk of local recurrence, and that nomograms exist to help calculate risk and guide the decision to recommend radiation in women with close margins.
Dr. Patrick Borgen, chairman of the department of surgery at Maimonides Medical Center, New York, remarked that “biology beats technique. A growing wealth of information exists that there is a reservoir of DCIS that will progress so slowly as not to be significant. Is the next step in refining our approach better class prediction using genomic profiling?”
Dr. Van Zee agreed that genomic profiling will play a role, but noted that a study comparing DCIS score and multiple clinical variables would be expensive and archival pathology specimens would be difficult to obtain. Studies will mostly have to be prospective, she said.
The complete manuscript of this study and its presentation at the American Surgical Association’s 135th Annual Meeting, April 2015, in San Diego, California, are anticipated to be published in the Annals of Surgery pending editorial review.
This article was updated May 11, 2015.
AT THE ASA ANNUAL MEETING
Key clinical point: Ductal carcinoma in situ patients with close or positive tumor margins may benefit more from radiation.
Major finding: Radiation gave patients with positive margins an absolute 18% risk reduction, for a hazard ratio of 0.10.
Data source: Retrospective review of a prospective database of DCIS patients undergoing breast-conserving surgery from 1978 to 2010.
Disclosures: The authors reported no disclosures.
Mammographic breast density is a strong risk factor for breast cancer
Breast density is a strong, prevalent, and potentially modifiable risk factor for breast cancer, which makes it of special interest to clinicians whose jobs involve breast cancer risk prediction. That was the theme of a talk by Karla Kerlikowske, MD, of the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco. Dr. Kerlikowske delivered the John I. Brewer Memorial Lecture May 3 at the 2015 Annual Clinical Meeting of the American College of Obstetricians and Gynecologists in San Francisco.
Mammographic breast density is a radiologic term, Dr. Kerlikowske explained. “The only way to really know someone’s breast density is if they have a mammogram.” The whiter the mammogram, the denser the breast. The darker the mammogram, the fattier the breast.
According to the American College of Radiology, the following 4 categories of breast composition are defined by the “visually estimated” content of fibroglandular-density tissue within the breasts:
A. The breasts are almost entirely fatty.
B. There are scattered areas of fibroglandular density.
C. The breasts are heterogeneously dense, which may obscure small masses.
D. The breasts are extremely dense, which lowers the specificity of mammography.
Categories C and D signify dense breasts, which contain a high degree of collagen, epithelial cells, and stroma. In the United States, more than 25 million women are thought to have dense breasts.
Women who have a family history of breast cancer are more likely to have dense breasts. And women who have dense breasts have an elevated risk of breast cancer. They also have a higher risk of advanced disease, as well as a higher risk of large, high-grade, and lymph node-positive tumors, said Dr. Kerlikowske.
Breast-density legislation is increasing
Twenty-two states now have laws mandating that women found to have heterogeneously dense or extremely dense breasts be notified of their status, said Dr. Kerlikowske. That prompts the question: How should these patients be managed?
Breast density declines with age. Breast density also is influenced by body mass index (BMI). As BMI increases, density declines.
Breast density also can be affected by medications, such as hormone therapy and tamoxifen, Dr. Kerlikowske said.
For example, breast density declines about 1% to 2% per year in postmenopause. In postmenopausal women who take estrogen alone, breast density increases slightly. “But the real increase is for people who take estrogen plus progestin,” said Dr. Kerlikowske. “It’s thought that the progestin component is what increases breast density.” Estrogen-progestin therapy confers the same risk of breast cancer as that faced by a premenopausal woman with dense breasts.
As for tamoxifen, it reduces breast density by 2% to 3% per year in postmenopausal women, Dr. Kerlikowske said. “People who have a decrease of more than 10% in breast density are those who have a reduction in breast cancer.” If a woman doesn’t have that reduction with tamoxifen—about half of women don’t—there is no reduction in breast cancer mortality.
“There’s some thought that you should look at mammograms during the first year of tamoxifen use and, if you don’t see a change, consider switching to another medication,” said Dr. Kerlikowske.
More frequent mammograms and supplemental imaging are options for detecting cancers early. Among the modalities that have been studied in this regard are ultrasonography, tomosynthesis, and breast magnetic resonance imaging (MRI).
“If you do more tests, such as ultrasound, you will definitely find additional lesions,” said Dr. Kerlikowske. “There’s no question. But what are the harms?”
The biopsy rate almost doubles after ultrasonography, compared with mammography. And the number needed to screen to detect cancer is fairly high. For mammography, that number is about 250. For ultrasonography, tomosynthesis, and breast MRI, it is higher.
Tomosynthesis is more cost-effective than supplemental ultrasonography because it decreases the number of false positives, Dr. Kerlikowske said.
What’s the bottom line?
Not every woman with dense breasts is at high risk for breast cancer, said Dr. Kerlikowske. And although breast density is prevalent, it is potentially modifiable.
Nevertheless, breast density confers an elevated risk of breast cancer and can also mask tumors. Women with dense breasts likely should avoid the use of postmenopausal hormone therapy. They also may be candidates for more frequent mammography and/or supplemental imaging.
The Breast Cancer Surveillance Consortium (BCSC) Risk Calculator is the only tool that incorporates breast density. In the works is a new model that also incorporates benign breast disease.
Risk-prediction tool considers density and other factors
A risk-prediction tool from the Breast Cancer Surveillance Consortium (BCSC) is the only model to incorporate breast density. The BCSC Risk Calculator is available free of charge for the iPhone and iPad (an Android version is in the works). The tool takes 5 factors into consideration in estimating a woman’s 5-year risk of developing invasive breast cancer:
• age
• race/ethnicity
• breast density
• family history of breast cancer (first-degree relative)
• personal history of breast biopsy.
The tool is designed for use by health professionals. It is not appropriate for determining risk in women younger than 35 years or older than 79 years; women with a previous diagnosis of breast cancer, lobular carcinoma in situ, ductal carcinoma in situ, or atypical ductal hyperplasia; or women who have undergone breast augmentation. Other risk-prediction models are more appropriate for women with a BRCA mutation.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
Breast density is a strong, prevalent, and potentially modifiable risk factor for breast cancer, which makes it of special interest to clinicians whose jobs involve breast cancer risk prediction. That was the theme of a talk by Karla Kerlikowske, MD, of the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco. Dr. Kerlikowske delivered the John I. Brewer Memorial Lecture May 3 at the 2015 Annual Clinical Meeting of the American College of Obstetricians and Gynecologists in San Francisco.
Mammographic breast density is a radiologic term, Dr. Kerlikowske explained. “The only way to really know someone’s breast density is if they have a mammogram.” The whiter the mammogram, the denser the breast. The darker the mammogram, the fattier the breast.
According to the American College of Radiology, the following 4 categories of breast composition are defined by the “visually estimated” content of fibroglandular-density tissue within the breasts:
A. The breasts are almost entirely fatty.
B. There are scattered areas of fibroglandular density.
C. The breasts are heterogeneously dense, which may obscure small masses.
D. The breasts are extremely dense, which lowers the specificity of mammography.
Categories C and D signify dense breasts, which contain a high degree of collagen, epithelial cells, and stroma. In the United States, more than 25 million women are thought to have dense breasts.
Women who have a family history of breast cancer are more likely to have dense breasts. And women who have dense breasts have an elevated risk of breast cancer. They also have a higher risk of advanced disease, as well as a higher risk of large, high-grade, and lymph node-positive tumors, said Dr. Kerlikowske.
Breast-density legislation is increasing
Twenty-two states now have laws mandating that women found to have heterogeneously dense or extremely dense breasts be notified of their status, said Dr. Kerlikowske. That prompts the question: How should these patients be managed?
Breast density declines with age. Breast density also is influenced by body mass index (BMI). As BMI increases, density declines.
Breast density also can be affected by medications, such as hormone therapy and tamoxifen, Dr. Kerlikowske said.
For example, breast density declines about 1% to 2% per year in postmenopause. In postmenopausal women who take estrogen alone, breast density increases slightly. “But the real increase is for people who take estrogen plus progestin,” said Dr. Kerlikowske. “It’s thought that the progestin component is what increases breast density.” Estrogen-progestin therapy confers the same risk of breast cancer as that faced by a premenopausal woman with dense breasts.
As for tamoxifen, it reduces breast density by 2% to 3% per year in postmenopausal women, Dr. Kerlikowske said. “People who have a decrease of more than 10% in breast density are those who have a reduction in breast cancer.” If a woman doesn’t have that reduction with tamoxifen—about half of women don’t—there is no reduction in breast cancer mortality.
“There’s some thought that you should look at mammograms during the first year of tamoxifen use and, if you don’t see a change, consider switching to another medication,” said Dr. Kerlikowske.
More frequent mammograms and supplemental imaging are options for detecting cancers early. Among the modalities that have been studied in this regard are ultrasonography, tomosynthesis, and breast magnetic resonance imaging (MRI).
“If you do more tests, such as ultrasound, you will definitely find additional lesions,” said Dr. Kerlikowske. “There’s no question. But what are the harms?”
The biopsy rate almost doubles after ultrasonography, compared with mammography. And the number needed to screen to detect cancer is fairly high. For mammography, that number is about 250. For ultrasonography, tomosynthesis, and breast MRI, it is higher.
Tomosynthesis is more cost-effective than supplemental ultrasonography because it decreases the number of false positives, Dr. Kerlikowske said.
What’s the bottom line?
Not every woman with dense breasts is at high risk for breast cancer, said Dr. Kerlikowske. And although breast density is prevalent, it is potentially modifiable.
Nevertheless, breast density confers an elevated risk of breast cancer and can also mask tumors. Women with dense breasts likely should avoid the use of postmenopausal hormone therapy. They also may be candidates for more frequent mammography and/or supplemental imaging.
The Breast Cancer Surveillance Consortium (BCSC) Risk Calculator is the only tool that incorporates breast density. In the works is a new model that also incorporates benign breast disease.
Risk-prediction tool considers density and other factors
A risk-prediction tool from the Breast Cancer Surveillance Consortium (BCSC) is the only model to incorporate breast density. The BCSC Risk Calculator is available free of charge for the iPhone and iPad (an Android version is in the works). The tool takes 5 factors into consideration in estimating a woman’s 5-year risk of developing invasive breast cancer:
• age
• race/ethnicity
• breast density
• family history of breast cancer (first-degree relative)
• personal history of breast biopsy.
The tool is designed for use by health professionals. It is not appropriate for determining risk in women younger than 35 years or older than 79 years; women with a previous diagnosis of breast cancer, lobular carcinoma in situ, ductal carcinoma in situ, or atypical ductal hyperplasia; or women who have undergone breast augmentation. Other risk-prediction models are more appropriate for women with a BRCA mutation.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
Breast density is a strong, prevalent, and potentially modifiable risk factor for breast cancer, which makes it of special interest to clinicians whose jobs involve breast cancer risk prediction. That was the theme of a talk by Karla Kerlikowske, MD, of the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco. Dr. Kerlikowske delivered the John I. Brewer Memorial Lecture May 3 at the 2015 Annual Clinical Meeting of the American College of Obstetricians and Gynecologists in San Francisco.
Mammographic breast density is a radiologic term, Dr. Kerlikowske explained. “The only way to really know someone’s breast density is if they have a mammogram.” The whiter the mammogram, the denser the breast. The darker the mammogram, the fattier the breast.
According to the American College of Radiology, the following 4 categories of breast composition are defined by the “visually estimated” content of fibroglandular-density tissue within the breasts:
A. The breasts are almost entirely fatty.
B. There are scattered areas of fibroglandular density.
C. The breasts are heterogeneously dense, which may obscure small masses.
D. The breasts are extremely dense, which lowers the specificity of mammography.
Categories C and D signify dense breasts, which contain a high degree of collagen, epithelial cells, and stroma. In the United States, more than 25 million women are thought to have dense breasts.
Women who have a family history of breast cancer are more likely to have dense breasts. And women who have dense breasts have an elevated risk of breast cancer. They also have a higher risk of advanced disease, as well as a higher risk of large, high-grade, and lymph node-positive tumors, said Dr. Kerlikowske.
Breast-density legislation is increasing
Twenty-two states now have laws mandating that women found to have heterogeneously dense or extremely dense breasts be notified of their status, said Dr. Kerlikowske. That prompts the question: How should these patients be managed?
Breast density declines with age. Breast density also is influenced by body mass index (BMI). As BMI increases, density declines.
Breast density also can be affected by medications, such as hormone therapy and tamoxifen, Dr. Kerlikowske said.
For example, breast density declines about 1% to 2% per year in postmenopause. In postmenopausal women who take estrogen alone, breast density increases slightly. “But the real increase is for people who take estrogen plus progestin,” said Dr. Kerlikowske. “It’s thought that the progestin component is what increases breast density.” Estrogen-progestin therapy confers the same risk of breast cancer as that faced by a premenopausal woman with dense breasts.
As for tamoxifen, it reduces breast density by 2% to 3% per year in postmenopausal women, Dr. Kerlikowske said. “People who have a decrease of more than 10% in breast density are those who have a reduction in breast cancer.” If a woman doesn’t have that reduction with tamoxifen—about half of women don’t—there is no reduction in breast cancer mortality.
“There’s some thought that you should look at mammograms during the first year of tamoxifen use and, if you don’t see a change, consider switching to another medication,” said Dr. Kerlikowske.
More frequent mammograms and supplemental imaging are options for detecting cancers early. Among the modalities that have been studied in this regard are ultrasonography, tomosynthesis, and breast magnetic resonance imaging (MRI).
“If you do more tests, such as ultrasound, you will definitely find additional lesions,” said Dr. Kerlikowske. “There’s no question. But what are the harms?”
The biopsy rate almost doubles after ultrasonography, compared with mammography. And the number needed to screen to detect cancer is fairly high. For mammography, that number is about 250. For ultrasonography, tomosynthesis, and breast MRI, it is higher.
Tomosynthesis is more cost-effective than supplemental ultrasonography because it decreases the number of false positives, Dr. Kerlikowske said.
What’s the bottom line?
Not every woman with dense breasts is at high risk for breast cancer, said Dr. Kerlikowske. And although breast density is prevalent, it is potentially modifiable.
Nevertheless, breast density confers an elevated risk of breast cancer and can also mask tumors. Women with dense breasts likely should avoid the use of postmenopausal hormone therapy. They also may be candidates for more frequent mammography and/or supplemental imaging.
The Breast Cancer Surveillance Consortium (BCSC) Risk Calculator is the only tool that incorporates breast density. In the works is a new model that also incorporates benign breast disease.
Risk-prediction tool considers density and other factors
A risk-prediction tool from the Breast Cancer Surveillance Consortium (BCSC) is the only model to incorporate breast density. The BCSC Risk Calculator is available free of charge for the iPhone and iPad (an Android version is in the works). The tool takes 5 factors into consideration in estimating a woman’s 5-year risk of developing invasive breast cancer:
• age
• race/ethnicity
• breast density
• family history of breast cancer (first-degree relative)
• personal history of breast biopsy.
The tool is designed for use by health professionals. It is not appropriate for determining risk in women younger than 35 years or older than 79 years; women with a previous diagnosis of breast cancer, lobular carcinoma in situ, ductal carcinoma in situ, or atypical ductal hyperplasia; or women who have undergone breast augmentation. Other risk-prediction models are more appropriate for women with a BRCA mutation.
Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.
Omega-3 fatty acids similar to placebo for aromatase inhibitor–induced musculoskeletal pain
Aromatase inhibitor-induced arthralgia substantially improved in women who received omega-3 fatty acid capsules, as well as in those who took placebo, according to a study published online May 4 in the Journal of Clinical Oncology.
Brief Pain Inventory (BPI) worst pain scores were significantly lower than were baseline scores after treatment with O3-FAs and placebo. On the 10-point scale, the median scores reported by women taking O3-FAs were lower by 1.69, 1.74, and 2.23 at 6, 12, and 24 weeks, respectively (P < .001). For those taking placebo, the scores also were significantly lower: 1.36, 1.50, and 1.81 points at 6, 12, and 24 weeks respectively (P < .001). Differences between the groups were not significant, reported Dr. Dawn Hershman of the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, and associates (J. Clin. Onc. 2015 May 4 [doi: 10.1200/JCO.2014.59.5595]).
“The improvement in symptoms in both the treatment and placebo groups was unexpected. The magnitude of the expected placebo effect reported in the literature can vary from 6% to 59% and can be higher in symptom-management studies. We found an effect >50%,” Dr. Hershman and associates wrote.
The large placebo effect may have resulted from a number of factors, including the natural history of arthralgia (which can improve over time), the soy/corn oil ingredients in the placebo capsule, or O3-FA contamination in the placebo arm due to supplementation by patients.
There are no proven therapies for AI-associated arthralgia, and its mechanism is unclear. Evidence suggests that inflammation may play a role. Given that studies have shown O3-FAs may benefit symptoms of rheumatoid arthritis, this multicenter, placebo controlled trial evaluated whether O3-FAs reduce pain and stiffness in 249 women undergoing adjuvant AI therapy for early-stage breast cancer.
At week 12, patients who received O3-FAs had significantly decreased serum triglyceride levels (–22.1 mg/dL, P < .001) and increased HDL (2.9 mg/dL, P < .007). Triglyceride and HDL levels for the placebo arm did not significantly change, which suggests that O3-FA contamination in the placebo arm was not a factor in the high placebo effect. Other serum measures (cholesterol, CRP, and LDL) did not significantly change for either group, Dr. Hershman and associates said.
The placebo effect is related to patient expectations and perceptions of treatment. It is heightened with a supportive patient-provider relationship and typically diminished in blinded clinical trials where patients do not know if they are receiving the active drug. However, in clinical trials that have evaluated symptom management, substantial placebo effects were more common. This observation points to the importance of placebo-controlled, randomized trials vs. uncontrolled trials for symptom management therapies.
The larger-than-expected placebo response in the Hershman et. al. study may have resulted from several factors, including O3-FA supplementation causing placebo contamination, ingredients within the placebo capsule, the natural history of AIMSS, and patient selection.
Because O3-FAs are readily available as supplements, placebo contamination should be considered. The authors examined a surrogate marker for exposure, longitudinal change in triglycerides, and found only the active arm had decreased triglyceride levels. This observation suggests that participants in the placebo arm were not significantly exposed to O3-FAs.
The ingredients of the placebo capsule, soybean oil or other components, may have contributed to symptom improvement. If AIMSS is related to estrogen deprivation, estrogenic compounds in the placebo may have affected symptoms.
Previous studies indicate that many patients do not spontaneously improve over time, as would be the case if the natural history of AIMSS accounted for the high placebo effect.
Regarding the patients enrolled in the study, there is no way to definitively determine if their pain and stiffness was caused by AIs; distinguishing between AIMSS and worsening of osteoarthritis in this patient population with high baseline joint pain is difficult. It is possible that patients with preexisting musculoskeletal pain not related to AIs participated in this study, particularly since there is a low perceived toxicity of the drug.
Patients enrolled in this trial may have experienced symptom improvement solely due to the expectation of benefit by participation in the trial. A similar placebo response was reported in a controlled trial of modafinil for fatigue.
The results of this well-conducted SWOG trial clearly demonstrate that acknowledging and controlling for placebo effects is crucial to high-quality research in the field of symptom management.
Dr. N. Lynn Henry is assistant professor in the division of hematology/oncology, department of internal medicine, at the University of Michigan, Ann Arbor. Dr. Jennifer Griggs is professor of medicine in the division of hematology/oncology and director of the breast cancer survivorship program at the University of Michigan Comprehensive Cancer Center, Ann Arbor. Dr. Henry reported receiving research funding from Sanofi-Aventis, BioMarin, and Celldex. These comments were taken from an editorial accompanying the report by Hershman et al. (J. Clin. Onc. 2015 May 4 [doi:10.1200/JCO.2015.61.1004]).
The placebo effect is related to patient expectations and perceptions of treatment. It is heightened with a supportive patient-provider relationship and typically diminished in blinded clinical trials where patients do not know if they are receiving the active drug. However, in clinical trials that have evaluated symptom management, substantial placebo effects were more common. This observation points to the importance of placebo-controlled, randomized trials vs. uncontrolled trials for symptom management therapies.
The larger-than-expected placebo response in the Hershman et. al. study may have resulted from several factors, including O3-FA supplementation causing placebo contamination, ingredients within the placebo capsule, the natural history of AIMSS, and patient selection.
Because O3-FAs are readily available as supplements, placebo contamination should be considered. The authors examined a surrogate marker for exposure, longitudinal change in triglycerides, and found only the active arm had decreased triglyceride levels. This observation suggests that participants in the placebo arm were not significantly exposed to O3-FAs.
The ingredients of the placebo capsule, soybean oil or other components, may have contributed to symptom improvement. If AIMSS is related to estrogen deprivation, estrogenic compounds in the placebo may have affected symptoms.
Previous studies indicate that many patients do not spontaneously improve over time, as would be the case if the natural history of AIMSS accounted for the high placebo effect.
Regarding the patients enrolled in the study, there is no way to definitively determine if their pain and stiffness was caused by AIs; distinguishing between AIMSS and worsening of osteoarthritis in this patient population with high baseline joint pain is difficult. It is possible that patients with preexisting musculoskeletal pain not related to AIs participated in this study, particularly since there is a low perceived toxicity of the drug.
Patients enrolled in this trial may have experienced symptom improvement solely due to the expectation of benefit by participation in the trial. A similar placebo response was reported in a controlled trial of modafinil for fatigue.
The results of this well-conducted SWOG trial clearly demonstrate that acknowledging and controlling for placebo effects is crucial to high-quality research in the field of symptom management.
Dr. N. Lynn Henry is assistant professor in the division of hematology/oncology, department of internal medicine, at the University of Michigan, Ann Arbor. Dr. Jennifer Griggs is professor of medicine in the division of hematology/oncology and director of the breast cancer survivorship program at the University of Michigan Comprehensive Cancer Center, Ann Arbor. Dr. Henry reported receiving research funding from Sanofi-Aventis, BioMarin, and Celldex. These comments were taken from an editorial accompanying the report by Hershman et al. (J. Clin. Onc. 2015 May 4 [doi:10.1200/JCO.2015.61.1004]).
The placebo effect is related to patient expectations and perceptions of treatment. It is heightened with a supportive patient-provider relationship and typically diminished in blinded clinical trials where patients do not know if they are receiving the active drug. However, in clinical trials that have evaluated symptom management, substantial placebo effects were more common. This observation points to the importance of placebo-controlled, randomized trials vs. uncontrolled trials for symptom management therapies.
The larger-than-expected placebo response in the Hershman et. al. study may have resulted from several factors, including O3-FA supplementation causing placebo contamination, ingredients within the placebo capsule, the natural history of AIMSS, and patient selection.
Because O3-FAs are readily available as supplements, placebo contamination should be considered. The authors examined a surrogate marker for exposure, longitudinal change in triglycerides, and found only the active arm had decreased triglyceride levels. This observation suggests that participants in the placebo arm were not significantly exposed to O3-FAs.
The ingredients of the placebo capsule, soybean oil or other components, may have contributed to symptom improvement. If AIMSS is related to estrogen deprivation, estrogenic compounds in the placebo may have affected symptoms.
Previous studies indicate that many patients do not spontaneously improve over time, as would be the case if the natural history of AIMSS accounted for the high placebo effect.
Regarding the patients enrolled in the study, there is no way to definitively determine if their pain and stiffness was caused by AIs; distinguishing between AIMSS and worsening of osteoarthritis in this patient population with high baseline joint pain is difficult. It is possible that patients with preexisting musculoskeletal pain not related to AIs participated in this study, particularly since there is a low perceived toxicity of the drug.
Patients enrolled in this trial may have experienced symptom improvement solely due to the expectation of benefit by participation in the trial. A similar placebo response was reported in a controlled trial of modafinil for fatigue.
The results of this well-conducted SWOG trial clearly demonstrate that acknowledging and controlling for placebo effects is crucial to high-quality research in the field of symptom management.
Dr. N. Lynn Henry is assistant professor in the division of hematology/oncology, department of internal medicine, at the University of Michigan, Ann Arbor. Dr. Jennifer Griggs is professor of medicine in the division of hematology/oncology and director of the breast cancer survivorship program at the University of Michigan Comprehensive Cancer Center, Ann Arbor. Dr. Henry reported receiving research funding from Sanofi-Aventis, BioMarin, and Celldex. These comments were taken from an editorial accompanying the report by Hershman et al. (J. Clin. Onc. 2015 May 4 [doi:10.1200/JCO.2015.61.1004]).
Aromatase inhibitor-induced arthralgia substantially improved in women who received omega-3 fatty acid capsules, as well as in those who took placebo, according to a study published online May 4 in the Journal of Clinical Oncology.
Brief Pain Inventory (BPI) worst pain scores were significantly lower than were baseline scores after treatment with O3-FAs and placebo. On the 10-point scale, the median scores reported by women taking O3-FAs were lower by 1.69, 1.74, and 2.23 at 6, 12, and 24 weeks, respectively (P < .001). For those taking placebo, the scores also were significantly lower: 1.36, 1.50, and 1.81 points at 6, 12, and 24 weeks respectively (P < .001). Differences between the groups were not significant, reported Dr. Dawn Hershman of the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, and associates (J. Clin. Onc. 2015 May 4 [doi: 10.1200/JCO.2014.59.5595]).
“The improvement in symptoms in both the treatment and placebo groups was unexpected. The magnitude of the expected placebo effect reported in the literature can vary from 6% to 59% and can be higher in symptom-management studies. We found an effect >50%,” Dr. Hershman and associates wrote.
The large placebo effect may have resulted from a number of factors, including the natural history of arthralgia (which can improve over time), the soy/corn oil ingredients in the placebo capsule, or O3-FA contamination in the placebo arm due to supplementation by patients.
There are no proven therapies for AI-associated arthralgia, and its mechanism is unclear. Evidence suggests that inflammation may play a role. Given that studies have shown O3-FAs may benefit symptoms of rheumatoid arthritis, this multicenter, placebo controlled trial evaluated whether O3-FAs reduce pain and stiffness in 249 women undergoing adjuvant AI therapy for early-stage breast cancer.
At week 12, patients who received O3-FAs had significantly decreased serum triglyceride levels (–22.1 mg/dL, P < .001) and increased HDL (2.9 mg/dL, P < .007). Triglyceride and HDL levels for the placebo arm did not significantly change, which suggests that O3-FA contamination in the placebo arm was not a factor in the high placebo effect. Other serum measures (cholesterol, CRP, and LDL) did not significantly change for either group, Dr. Hershman and associates said.
Aromatase inhibitor-induced arthralgia substantially improved in women who received omega-3 fatty acid capsules, as well as in those who took placebo, according to a study published online May 4 in the Journal of Clinical Oncology.
Brief Pain Inventory (BPI) worst pain scores were significantly lower than were baseline scores after treatment with O3-FAs and placebo. On the 10-point scale, the median scores reported by women taking O3-FAs were lower by 1.69, 1.74, and 2.23 at 6, 12, and 24 weeks, respectively (P < .001). For those taking placebo, the scores also were significantly lower: 1.36, 1.50, and 1.81 points at 6, 12, and 24 weeks respectively (P < .001). Differences between the groups were not significant, reported Dr. Dawn Hershman of the Herbert Irving Comprehensive Cancer Center, Columbia University, New York, and associates (J. Clin. Onc. 2015 May 4 [doi: 10.1200/JCO.2014.59.5595]).
“The improvement in symptoms in both the treatment and placebo groups was unexpected. The magnitude of the expected placebo effect reported in the literature can vary from 6% to 59% and can be higher in symptom-management studies. We found an effect >50%,” Dr. Hershman and associates wrote.
The large placebo effect may have resulted from a number of factors, including the natural history of arthralgia (which can improve over time), the soy/corn oil ingredients in the placebo capsule, or O3-FA contamination in the placebo arm due to supplementation by patients.
There are no proven therapies for AI-associated arthralgia, and its mechanism is unclear. Evidence suggests that inflammation may play a role. Given that studies have shown O3-FAs may benefit symptoms of rheumatoid arthritis, this multicenter, placebo controlled trial evaluated whether O3-FAs reduce pain and stiffness in 249 women undergoing adjuvant AI therapy for early-stage breast cancer.
At week 12, patients who received O3-FAs had significantly decreased serum triglyceride levels (–22.1 mg/dL, P < .001) and increased HDL (2.9 mg/dL, P < .007). Triglyceride and HDL levels for the placebo arm did not significantly change, which suggests that O3-FA contamination in the placebo arm was not a factor in the high placebo effect. Other serum measures (cholesterol, CRP, and LDL) did not significantly change for either group, Dr. Hershman and associates said.
Key clinical point: Patients who received omega-3 fatty acid (O3-FA) capsules, as well as those who received placebo, had significant, sustained improvement in aromatase inhibitor-induced musculoskeletal pain.
Major finding: Mean observed Brief Pain Inventory worst pain scores for the O3-FA arm and the placebo arm were about 50% lower (1.74 and 1.49 points lower, respectively) than baseline scores after 12 weeks.
Data source: A multicenter, placebo controlled trial evaluating the effect of O3-FAs in 249 women with a history of breast cancer who had muscle pain and stiffness subsequent to the initiation of AI treatment.
Disclosures: Dr. Hershman reported having no disclosures. His coauthors reported ties to several industry sources.
AACR: Targeted combo active in triple-negative breast cancer, ovarian cancer
Combining the poly(ADP-ribose) polymerase inhibitor olaparib and the investigational P13K inhibitor BKM 120 was safe and active in triple-negative breast cancer and ovarian cancer in a phase I trial.
Patients with both BRCA-mutant and BRCA-wildtype breast cancer responded to the combination. One patient with germline BRCA-wildtype triple-negative breast cancer (TNBC) and lung metastases had a partial response and remained on treatment for 20 cycles, or nearly 2 years, study author Dr. Ursula Matulonis reported at the annual meeting of the American Association for Cancer Research.
Rationale for the study lay in data from mouse models showing that combination olaparib and BKM120 was more effective than either drug alone in BRCA-mutant breast cancer and BRCA-wildtype TNBC. Similarities also exist between high-grade serous ovarian cancer and TNBC, including an association with germline BRCA mutations, sensitivity to platinum agents, and high copy number alteration rates, she said in a press briefing at the meeting.
Olaparib (Lynparza), a PARP (poly [ADP-ribose] polymerase) inhibitor, was approved in the United States in December 2014 for treating BRCA-positive advanced ovarian cancer.
The phase I, dose-escalation study enrolled 70 patients with a diagnosis of recurrent high-grade serous ovarian cancer or TNBC but also allowed documented germline BRCA mutation carriers regardless of histology.
The histology was high-grade serous in 90% of the 46 ovarian cancer patients, while 2% had high-grade endometrioid disease, 4% carcinosarcoma, and 4% poorly differentiated carcinoma. Most of the 24 breast cancer patients (63%) had TNBC, while 29% had estrogen receptor–positive/progesterone receptor–positive disease and 8% had ER+/PR– breast cancer.
Germline BRCA mutations were present in 77% of ovarian and 58% of breast cancer patients. The median age in the two groups was 60 years and 47.5 years, respectively. Prior PARP or P13kinase pathway inhibitors were allowed during dose escalation.
Among ovarian cancer patients, 12 (26%) had a partial response and 22 (48%) had stable disease. Responses were similar in the breast cancer group, with 5 (21%) partial responses and 12 (50%) patients with stable disease, said Dr. Matulonis of the Dana-Farber Cancer Center and Harvard Medical School, both in Boston.
Ten dosing regimens were evaluated in the study, beginning with an initial dose of BKM120 60 mg once daily and olaparib 100 mg twice daily, both given orally on a continuous basis. This elicited two dose-limiting toxicities (DLTs) – grade 3 hyperglycemia and grade 3 transaminitis – and prompted the investigators to back down to dose levels of 40 mg and 50 mg, respectively.
No DLTs occurred until dosing reached BKM120 60 mg and olaparib 300 mg, at which point one grade-4 transaminitis and one grade-3 depression were reported in cycle 2, she said. Dose levels of 50 mg and 300 mg, respectively, were selected for the expansion cohort.
As for why the two DLTs occurred at the initial dose but the same doses were later used without incident, Dr. Matulonis said that one of the patients with a DLT fell out of well-controlled diabetes and the other had liver metastases that accelerated during treatment.
Overall, the most common nonhematologic toxicities of any grade were nausea (79.4%), fatigue (66%), and hyperglycemia (40%). Related hematologic toxicities of any grade were anemia in 23.5%, neutropenia in 12%, and thrombocytopenia and leukopenia, both in 10% of patients.
“Combinations of biologic agents will require establishment of target patient populations using biomarkers in order to predict sensitivity as well as determine mechanisms of resistance,” Dr. Matulonis concluded.
Next-generation sequencing is ongoing for BKM120/olaparib patients and mechanisms of response and resistance are being studied in human ovarian mouse models, she added.
The study was funded by Stand Up to Cancer, the Kathryn Fox Samway Foundation, and participating centers. Olaparib was provided by AstraZeneca and BKM120 by Novartis. Dr. Matulonis reported research funding from AstraZeneca, as well as renumeration for attending a speaker’s bureau.
On Twitter @pwendl
Combining the poly(ADP-ribose) polymerase inhibitor olaparib and the investigational P13K inhibitor BKM 120 was safe and active in triple-negative breast cancer and ovarian cancer in a phase I trial.
Patients with both BRCA-mutant and BRCA-wildtype breast cancer responded to the combination. One patient with germline BRCA-wildtype triple-negative breast cancer (TNBC) and lung metastases had a partial response and remained on treatment for 20 cycles, or nearly 2 years, study author Dr. Ursula Matulonis reported at the annual meeting of the American Association for Cancer Research.
Rationale for the study lay in data from mouse models showing that combination olaparib and BKM120 was more effective than either drug alone in BRCA-mutant breast cancer and BRCA-wildtype TNBC. Similarities also exist between high-grade serous ovarian cancer and TNBC, including an association with germline BRCA mutations, sensitivity to platinum agents, and high copy number alteration rates, she said in a press briefing at the meeting.
Olaparib (Lynparza), a PARP (poly [ADP-ribose] polymerase) inhibitor, was approved in the United States in December 2014 for treating BRCA-positive advanced ovarian cancer.
The phase I, dose-escalation study enrolled 70 patients with a diagnosis of recurrent high-grade serous ovarian cancer or TNBC but also allowed documented germline BRCA mutation carriers regardless of histology.
The histology was high-grade serous in 90% of the 46 ovarian cancer patients, while 2% had high-grade endometrioid disease, 4% carcinosarcoma, and 4% poorly differentiated carcinoma. Most of the 24 breast cancer patients (63%) had TNBC, while 29% had estrogen receptor–positive/progesterone receptor–positive disease and 8% had ER+/PR– breast cancer.
Germline BRCA mutations were present in 77% of ovarian and 58% of breast cancer patients. The median age in the two groups was 60 years and 47.5 years, respectively. Prior PARP or P13kinase pathway inhibitors were allowed during dose escalation.
Among ovarian cancer patients, 12 (26%) had a partial response and 22 (48%) had stable disease. Responses were similar in the breast cancer group, with 5 (21%) partial responses and 12 (50%) patients with stable disease, said Dr. Matulonis of the Dana-Farber Cancer Center and Harvard Medical School, both in Boston.
Ten dosing regimens were evaluated in the study, beginning with an initial dose of BKM120 60 mg once daily and olaparib 100 mg twice daily, both given orally on a continuous basis. This elicited two dose-limiting toxicities (DLTs) – grade 3 hyperglycemia and grade 3 transaminitis – and prompted the investigators to back down to dose levels of 40 mg and 50 mg, respectively.
No DLTs occurred until dosing reached BKM120 60 mg and olaparib 300 mg, at which point one grade-4 transaminitis and one grade-3 depression were reported in cycle 2, she said. Dose levels of 50 mg and 300 mg, respectively, were selected for the expansion cohort.
As for why the two DLTs occurred at the initial dose but the same doses were later used without incident, Dr. Matulonis said that one of the patients with a DLT fell out of well-controlled diabetes and the other had liver metastases that accelerated during treatment.
Overall, the most common nonhematologic toxicities of any grade were nausea (79.4%), fatigue (66%), and hyperglycemia (40%). Related hematologic toxicities of any grade were anemia in 23.5%, neutropenia in 12%, and thrombocytopenia and leukopenia, both in 10% of patients.
“Combinations of biologic agents will require establishment of target patient populations using biomarkers in order to predict sensitivity as well as determine mechanisms of resistance,” Dr. Matulonis concluded.
Next-generation sequencing is ongoing for BKM120/olaparib patients and mechanisms of response and resistance are being studied in human ovarian mouse models, she added.
The study was funded by Stand Up to Cancer, the Kathryn Fox Samway Foundation, and participating centers. Olaparib was provided by AstraZeneca and BKM120 by Novartis. Dr. Matulonis reported research funding from AstraZeneca, as well as renumeration for attending a speaker’s bureau.
On Twitter @pwendl
Combining the poly(ADP-ribose) polymerase inhibitor olaparib and the investigational P13K inhibitor BKM 120 was safe and active in triple-negative breast cancer and ovarian cancer in a phase I trial.
Patients with both BRCA-mutant and BRCA-wildtype breast cancer responded to the combination. One patient with germline BRCA-wildtype triple-negative breast cancer (TNBC) and lung metastases had a partial response and remained on treatment for 20 cycles, or nearly 2 years, study author Dr. Ursula Matulonis reported at the annual meeting of the American Association for Cancer Research.
Rationale for the study lay in data from mouse models showing that combination olaparib and BKM120 was more effective than either drug alone in BRCA-mutant breast cancer and BRCA-wildtype TNBC. Similarities also exist between high-grade serous ovarian cancer and TNBC, including an association with germline BRCA mutations, sensitivity to platinum agents, and high copy number alteration rates, she said in a press briefing at the meeting.
Olaparib (Lynparza), a PARP (poly [ADP-ribose] polymerase) inhibitor, was approved in the United States in December 2014 for treating BRCA-positive advanced ovarian cancer.
The phase I, dose-escalation study enrolled 70 patients with a diagnosis of recurrent high-grade serous ovarian cancer or TNBC but also allowed documented germline BRCA mutation carriers regardless of histology.
The histology was high-grade serous in 90% of the 46 ovarian cancer patients, while 2% had high-grade endometrioid disease, 4% carcinosarcoma, and 4% poorly differentiated carcinoma. Most of the 24 breast cancer patients (63%) had TNBC, while 29% had estrogen receptor–positive/progesterone receptor–positive disease and 8% had ER+/PR– breast cancer.
Germline BRCA mutations were present in 77% of ovarian and 58% of breast cancer patients. The median age in the two groups was 60 years and 47.5 years, respectively. Prior PARP or P13kinase pathway inhibitors were allowed during dose escalation.
Among ovarian cancer patients, 12 (26%) had a partial response and 22 (48%) had stable disease. Responses were similar in the breast cancer group, with 5 (21%) partial responses and 12 (50%) patients with stable disease, said Dr. Matulonis of the Dana-Farber Cancer Center and Harvard Medical School, both in Boston.
Ten dosing regimens were evaluated in the study, beginning with an initial dose of BKM120 60 mg once daily and olaparib 100 mg twice daily, both given orally on a continuous basis. This elicited two dose-limiting toxicities (DLTs) – grade 3 hyperglycemia and grade 3 transaminitis – and prompted the investigators to back down to dose levels of 40 mg and 50 mg, respectively.
No DLTs occurred until dosing reached BKM120 60 mg and olaparib 300 mg, at which point one grade-4 transaminitis and one grade-3 depression were reported in cycle 2, she said. Dose levels of 50 mg and 300 mg, respectively, were selected for the expansion cohort.
As for why the two DLTs occurred at the initial dose but the same doses were later used without incident, Dr. Matulonis said that one of the patients with a DLT fell out of well-controlled diabetes and the other had liver metastases that accelerated during treatment.
Overall, the most common nonhematologic toxicities of any grade were nausea (79.4%), fatigue (66%), and hyperglycemia (40%). Related hematologic toxicities of any grade were anemia in 23.5%, neutropenia in 12%, and thrombocytopenia and leukopenia, both in 10% of patients.
“Combinations of biologic agents will require establishment of target patient populations using biomarkers in order to predict sensitivity as well as determine mechanisms of resistance,” Dr. Matulonis concluded.
Next-generation sequencing is ongoing for BKM120/olaparib patients and mechanisms of response and resistance are being studied in human ovarian mouse models, she added.
The study was funded by Stand Up to Cancer, the Kathryn Fox Samway Foundation, and participating centers. Olaparib was provided by AstraZeneca and BKM120 by Novartis. Dr. Matulonis reported research funding from AstraZeneca, as well as renumeration for attending a speaker’s bureau.
On Twitter @pwendl
FROM THE AACR ANNUAL MEETING
Key clinical point: Combining the PARP inhibitor olaparib and the investigational P13K inhibitor BKM 120 is safe and active in triple-negative breast cancer and ovarian cancer in early studies.
Major finding: Partial responses occurred in 26% of patients with ovarian cancer and 21% with breast cancer.
Data source: Phase I study in 70 women with ovarian cancer or breast cancer.
Disclosures: The study was funded by Stand Up to Cancer, the Kathryn Fox Samway Foundation, and participating centers. Olaparib was provided by AstraZeneca and BKM120 by Novartis. Dr. Matulonis reported research funding from AstraZeneca, as well as renumeration for attending a speaker’s bureau.
David Henry's JCSO podcast, April 2015
In this month’s podcast for The Journal of Community and Supportive Oncology, Dr David Henry highlights two Original Reports, one on the effectiveness and safety of ipilimumab therapy in advanced melanoma, and another on the feasibility of implementing a community-based randomized trial of yoga for women who are undergoing chemotherapy for breast cancer. Also in the line-up are a Review article on sleep disorders in patients with cancer; a Community Translations examination of palonosetron and netupitant for the prevention of chemotherapy-induced nausea and vomiting in cancer patients; and Case Reports on distant skin metastases as primary presentation of gastric cancer, and sarcoidosis, complete heart block, and warm autoimmune hemolytic anemia in a young woman. The bimonthly New Therapies feature focuses on hard-to-treat tumors, specifically, glioblastoma, bone sarcoma, and liver cancer.
In this month’s podcast for The Journal of Community and Supportive Oncology, Dr David Henry highlights two Original Reports, one on the effectiveness and safety of ipilimumab therapy in advanced melanoma, and another on the feasibility of implementing a community-based randomized trial of yoga for women who are undergoing chemotherapy for breast cancer. Also in the line-up are a Review article on sleep disorders in patients with cancer; a Community Translations examination of palonosetron and netupitant for the prevention of chemotherapy-induced nausea and vomiting in cancer patients; and Case Reports on distant skin metastases as primary presentation of gastric cancer, and sarcoidosis, complete heart block, and warm autoimmune hemolytic anemia in a young woman. The bimonthly New Therapies feature focuses on hard-to-treat tumors, specifically, glioblastoma, bone sarcoma, and liver cancer.
In this month’s podcast for The Journal of Community and Supportive Oncology, Dr David Henry highlights two Original Reports, one on the effectiveness and safety of ipilimumab therapy in advanced melanoma, and another on the feasibility of implementing a community-based randomized trial of yoga for women who are undergoing chemotherapy for breast cancer. Also in the line-up are a Review article on sleep disorders in patients with cancer; a Community Translations examination of palonosetron and netupitant for the prevention of chemotherapy-induced nausea and vomiting in cancer patients; and Case Reports on distant skin metastases as primary presentation of gastric cancer, and sarcoidosis, complete heart block, and warm autoimmune hemolytic anemia in a young woman. The bimonthly New Therapies feature focuses on hard-to-treat tumors, specifically, glioblastoma, bone sarcoma, and liver cancer.
Exercise pumps up chemotherapy completion rates for breast cancer patients
Compared with usual care, a moderate- to high-intensity exercise intervention had beneficial effects on chemotherapy completion rates, symptom burden, and return-to-work rates among women with breast cancer who were undergoing adjuvant chemotherapy, according to a study published online April 27 in the Journal of Clinical Oncology.
For the multicenter Physical Exercise During Adjuvant Chemotherapy Effectiveness Study (PACES), 230 women (mean age 51 years) with breast cancer who were undergoing adjuvant chemotherapy were randomized to participate in a high- to moderate-intensity exercise program supervised by physical therapists (n = 76), a low-intensity home-based program (n = 77), or the usual care group (n = 77).
Dose adjustments in the chemotherapy regimen were less frequent in the moderate- to high-intensity exercise group (12%) than in the usual care or low-intensity groups (both 34%, P = .002). Patients in the exercise interventions were more likely to return to work by the 6-month follow up than those with usual care, wrote Ms. Hanna van Waart, a doctoral candidate at the Netherlands Cancer Institute, Amsterdam, and colleagues (J. Clin. Oncol. 2015 Apr. 27 [doi:10.1200/JCO.2014.59.1081]).
“This not only has financial implications, but also carries meaning in terms of quality of life and a sense of return to normalcy,” they wrote.
At completion of chemotherapy, patients from both activity groups reported significantly better physical functioning, less nausea and vomiting, and less pain than did those in the usual care group.
Compared with usual care, a moderate- to high-intensity exercise intervention had beneficial effects on chemotherapy completion rates, symptom burden, and return-to-work rates among women with breast cancer who were undergoing adjuvant chemotherapy, according to a study published online April 27 in the Journal of Clinical Oncology.
For the multicenter Physical Exercise During Adjuvant Chemotherapy Effectiveness Study (PACES), 230 women (mean age 51 years) with breast cancer who were undergoing adjuvant chemotherapy were randomized to participate in a high- to moderate-intensity exercise program supervised by physical therapists (n = 76), a low-intensity home-based program (n = 77), or the usual care group (n = 77).
Dose adjustments in the chemotherapy regimen were less frequent in the moderate- to high-intensity exercise group (12%) than in the usual care or low-intensity groups (both 34%, P = .002). Patients in the exercise interventions were more likely to return to work by the 6-month follow up than those with usual care, wrote Ms. Hanna van Waart, a doctoral candidate at the Netherlands Cancer Institute, Amsterdam, and colleagues (J. Clin. Oncol. 2015 Apr. 27 [doi:10.1200/JCO.2014.59.1081]).
“This not only has financial implications, but also carries meaning in terms of quality of life and a sense of return to normalcy,” they wrote.
At completion of chemotherapy, patients from both activity groups reported significantly better physical functioning, less nausea and vomiting, and less pain than did those in the usual care group.
Compared with usual care, a moderate- to high-intensity exercise intervention had beneficial effects on chemotherapy completion rates, symptom burden, and return-to-work rates among women with breast cancer who were undergoing adjuvant chemotherapy, according to a study published online April 27 in the Journal of Clinical Oncology.
For the multicenter Physical Exercise During Adjuvant Chemotherapy Effectiveness Study (PACES), 230 women (mean age 51 years) with breast cancer who were undergoing adjuvant chemotherapy were randomized to participate in a high- to moderate-intensity exercise program supervised by physical therapists (n = 76), a low-intensity home-based program (n = 77), or the usual care group (n = 77).
Dose adjustments in the chemotherapy regimen were less frequent in the moderate- to high-intensity exercise group (12%) than in the usual care or low-intensity groups (both 34%, P = .002). Patients in the exercise interventions were more likely to return to work by the 6-month follow up than those with usual care, wrote Ms. Hanna van Waart, a doctoral candidate at the Netherlands Cancer Institute, Amsterdam, and colleagues (J. Clin. Oncol. 2015 Apr. 27 [doi:10.1200/JCO.2014.59.1081]).
“This not only has financial implications, but also carries meaning in terms of quality of life and a sense of return to normalcy,” they wrote.
At completion of chemotherapy, patients from both activity groups reported significantly better physical functioning, less nausea and vomiting, and less pain than did those in the usual care group.
Key clinical point: Moderate- to high-intensity exercise during adjuvant chemotherapy improves completion rates. Low-intensity physical activity resulted in less pronounced benefits.
Major finding: Dose adjustments in the chemotherapy regimen were less frequent in the moderate- to high-intensity exercise group (12%) than in the usual care or low-intensity groups (both 34%, P = .002).
Data source: PACES, a controlled multicenter study that randomized 230 patients with breast cancer to participate in high- to moderate-intensity (n = 76) or low intensity (n = 77) exercise or usual care (n = 77) while undergoing adjuvant chemotherapy.
Disclosures: Dr. van Waart reported having no disclosures. Two of her coauthors reported ties to several industry sources.
Contamination prompts voluntary injectables recall
Mylan N.V. has announced a voluntary recall of specific lots of injectable products for conditions including rheumatoid arthritis, severe psoriasis, lung cancer, breast cancer, ovarian cancer, and acute nonlymphocytic leukemia because foreign particles were observed during testing of retention samples, according to a statement issued by the company on April 23.
The specific lot numbers can be found on the company’s website.
Affected products include methotrexate injection, USP 25 mg/mL, which is indicated for adult rheumatoid arthritis, severe psoriasis, and some neoplastic diseases. According to Mylan, the contaminated lot was distributed in the United States between Jan. 16, 2014, and March 25, 2014.
Other recalled injectable products include gemcitabine, USP 200 mg, an intravenous product for ovarian cancer, breast cancer, non–small cell lung cancer, and pancreatic cancer; carboplatin 10 mg/mL, indicated for advanced ovarian cancer; and cytarabine, indicated for remission induction in acute nonlymphocytic leukemia in adults and children. The lots for these products were distributed in the United States in various periods of several months during 2014.
The recall is being conducted with the knowledge of the Food and Drug Administration, and any adverse events or quality problems should be reported to the FDA’s MedWatch adverse event reporting program.
Mylan N.V. has announced a voluntary recall of specific lots of injectable products for conditions including rheumatoid arthritis, severe psoriasis, lung cancer, breast cancer, ovarian cancer, and acute nonlymphocytic leukemia because foreign particles were observed during testing of retention samples, according to a statement issued by the company on April 23.
The specific lot numbers can be found on the company’s website.
Affected products include methotrexate injection, USP 25 mg/mL, which is indicated for adult rheumatoid arthritis, severe psoriasis, and some neoplastic diseases. According to Mylan, the contaminated lot was distributed in the United States between Jan. 16, 2014, and March 25, 2014.
Other recalled injectable products include gemcitabine, USP 200 mg, an intravenous product for ovarian cancer, breast cancer, non–small cell lung cancer, and pancreatic cancer; carboplatin 10 mg/mL, indicated for advanced ovarian cancer; and cytarabine, indicated for remission induction in acute nonlymphocytic leukemia in adults and children. The lots for these products were distributed in the United States in various periods of several months during 2014.
The recall is being conducted with the knowledge of the Food and Drug Administration, and any adverse events or quality problems should be reported to the FDA’s MedWatch adverse event reporting program.
Mylan N.V. has announced a voluntary recall of specific lots of injectable products for conditions including rheumatoid arthritis, severe psoriasis, lung cancer, breast cancer, ovarian cancer, and acute nonlymphocytic leukemia because foreign particles were observed during testing of retention samples, according to a statement issued by the company on April 23.
The specific lot numbers can be found on the company’s website.
Affected products include methotrexate injection, USP 25 mg/mL, which is indicated for adult rheumatoid arthritis, severe psoriasis, and some neoplastic diseases. According to Mylan, the contaminated lot was distributed in the United States between Jan. 16, 2014, and March 25, 2014.
Other recalled injectable products include gemcitabine, USP 200 mg, an intravenous product for ovarian cancer, breast cancer, non–small cell lung cancer, and pancreatic cancer; carboplatin 10 mg/mL, indicated for advanced ovarian cancer; and cytarabine, indicated for remission induction in acute nonlymphocytic leukemia in adults and children. The lots for these products were distributed in the United States in various periods of several months during 2014.
The recall is being conducted with the knowledge of the Food and Drug Administration, and any adverse events or quality problems should be reported to the FDA’s MedWatch adverse event reporting program.
Oophorectomy improves survival after breast cancer in BRCA1 carriers
Women with breast cancer and BRCA1 mutations had a lower risk of mortality if they underwent oophorectomy, and the benefit was apparent beyond age 50, investigators reported online April 23 in JAMA Oncology.
In the entire cohort that included women with BRCA1 and BRCA2 mutations, breast cancer–related mortality was reduced 56%, and all-cause mortality (including 9 deaths due to ovarian cancer) was reduced 65% with oophorectomy (adjusted HR, 0.35; 95% CI, 0.22-0.56; P < .001).
Dr. Kelly Metcalfe of the Women’s College Research Institute, Toronto, and her colleagues provided evidence in support of BRCA1 testing in women with early-stage breast cancer at the time of diagnosis.
“The data presented here suggest that oophorectomy should be discussed with the patient [with a BRCA1 mutation] shortly after diagnosis. We recommend that the operation be performed in the first year of treatment to maximize the benefit,” the investigators wrote (JAMA Oncol. 2015 Apr. 23 [doi:10.1001/jamaoncol.2015.0658]).
The historical cohort study evaluated 676 women with BRCA1 or BRCA2 mutations and early-stage breast cancer diagnosed between 1975 and 2008. In order to examine the impact of subsequent oophorectomy on mortality risk due to breast cancer, a requirement for inclusion was that both ovaries be intact at the time of diagnosis. The subsequent oophorectomy group included 345 women.
Among the women who underwent oophorectomy, women with a BRCA1 mutation had a significantly reduced risk of breast cancer–related death, but the association was not significant for those with BRCA2 mutations. However, the number of BRCA2 carriers was much smaller than the number of BRCA1 carriers, and the 95% CI range was wide (0.23-1.43). A larger sample is required to determine the strength of an association.
Regardless of BRCA1/2 mutation status, in patients with estrogen receptor–negative breast cancer, oophorectomy had a protective effect (HR, 0.07; 95% CI, 0.01-0.51; P = .009).
Among 14 women over age 50 with estrogen receptor–negative cancer who did not undergo oophorectomy, 3 (21%) died; of the 15 who underwent the surgery, none died. Based on this finding, and a previous study indicating a protective effect of oophorectomy on the risk of primary breast cancer in women over 50, the researchers concluded that “the postmenopausal ovary remains active in terms of androgen production and that this affects cancer risk and progression, either directly or through aromatization to estrogen.”
Women with breast cancer and BRCA1 mutations had a lower risk of mortality if they underwent oophorectomy, and the benefit was apparent beyond age 50, investigators reported online April 23 in JAMA Oncology.
In the entire cohort that included women with BRCA1 and BRCA2 mutations, breast cancer–related mortality was reduced 56%, and all-cause mortality (including 9 deaths due to ovarian cancer) was reduced 65% with oophorectomy (adjusted HR, 0.35; 95% CI, 0.22-0.56; P < .001).
Dr. Kelly Metcalfe of the Women’s College Research Institute, Toronto, and her colleagues provided evidence in support of BRCA1 testing in women with early-stage breast cancer at the time of diagnosis.
“The data presented here suggest that oophorectomy should be discussed with the patient [with a BRCA1 mutation] shortly after diagnosis. We recommend that the operation be performed in the first year of treatment to maximize the benefit,” the investigators wrote (JAMA Oncol. 2015 Apr. 23 [doi:10.1001/jamaoncol.2015.0658]).
The historical cohort study evaluated 676 women with BRCA1 or BRCA2 mutations and early-stage breast cancer diagnosed between 1975 and 2008. In order to examine the impact of subsequent oophorectomy on mortality risk due to breast cancer, a requirement for inclusion was that both ovaries be intact at the time of diagnosis. The subsequent oophorectomy group included 345 women.
Among the women who underwent oophorectomy, women with a BRCA1 mutation had a significantly reduced risk of breast cancer–related death, but the association was not significant for those with BRCA2 mutations. However, the number of BRCA2 carriers was much smaller than the number of BRCA1 carriers, and the 95% CI range was wide (0.23-1.43). A larger sample is required to determine the strength of an association.
Regardless of BRCA1/2 mutation status, in patients with estrogen receptor–negative breast cancer, oophorectomy had a protective effect (HR, 0.07; 95% CI, 0.01-0.51; P = .009).
Among 14 women over age 50 with estrogen receptor–negative cancer who did not undergo oophorectomy, 3 (21%) died; of the 15 who underwent the surgery, none died. Based on this finding, and a previous study indicating a protective effect of oophorectomy on the risk of primary breast cancer in women over 50, the researchers concluded that “the postmenopausal ovary remains active in terms of androgen production and that this affects cancer risk and progression, either directly or through aromatization to estrogen.”
Women with breast cancer and BRCA1 mutations had a lower risk of mortality if they underwent oophorectomy, and the benefit was apparent beyond age 50, investigators reported online April 23 in JAMA Oncology.
In the entire cohort that included women with BRCA1 and BRCA2 mutations, breast cancer–related mortality was reduced 56%, and all-cause mortality (including 9 deaths due to ovarian cancer) was reduced 65% with oophorectomy (adjusted HR, 0.35; 95% CI, 0.22-0.56; P < .001).
Dr. Kelly Metcalfe of the Women’s College Research Institute, Toronto, and her colleagues provided evidence in support of BRCA1 testing in women with early-stage breast cancer at the time of diagnosis.
“The data presented here suggest that oophorectomy should be discussed with the patient [with a BRCA1 mutation] shortly after diagnosis. We recommend that the operation be performed in the first year of treatment to maximize the benefit,” the investigators wrote (JAMA Oncol. 2015 Apr. 23 [doi:10.1001/jamaoncol.2015.0658]).
The historical cohort study evaluated 676 women with BRCA1 or BRCA2 mutations and early-stage breast cancer diagnosed between 1975 and 2008. In order to examine the impact of subsequent oophorectomy on mortality risk due to breast cancer, a requirement for inclusion was that both ovaries be intact at the time of diagnosis. The subsequent oophorectomy group included 345 women.
Among the women who underwent oophorectomy, women with a BRCA1 mutation had a significantly reduced risk of breast cancer–related death, but the association was not significant for those with BRCA2 mutations. However, the number of BRCA2 carriers was much smaller than the number of BRCA1 carriers, and the 95% CI range was wide (0.23-1.43). A larger sample is required to determine the strength of an association.
Regardless of BRCA1/2 mutation status, in patients with estrogen receptor–negative breast cancer, oophorectomy had a protective effect (HR, 0.07; 95% CI, 0.01-0.51; P = .009).
Among 14 women over age 50 with estrogen receptor–negative cancer who did not undergo oophorectomy, 3 (21%) died; of the 15 who underwent the surgery, none died. Based on this finding, and a previous study indicating a protective effect of oophorectomy on the risk of primary breast cancer in women over 50, the researchers concluded that “the postmenopausal ovary remains active in terms of androgen production and that this affects cancer risk and progression, either directly or through aromatization to estrogen.”
FROM JAMA ONCOLOGY
Key clinical point: Oophorectomy significantly improved the prognosis of women with breast cancer and a BRCA1 mutation.
Major finding: The adjusted hazard ratio for breast cancer mortality in women with a BRCA1 mutation who had breast cancer and a subsequent oophorectomy was 0.38 (95% CI, 0.19-0.077; P = .007).
Data source: The retrospective cohort study evaluated 676 women with BRCA1 or BRCA2 mutations and breast cancer diagnosed from 1975 to 2008.
Disclosures: Dr. Kelly Metcalfe reported having no disclosures. The research was funded by the Canadian Breast Cancer Foundation.
Feasibility of implementing a community-based randomized trial of yoga for women undergoing chemotherapy for breast cancer
Background Treatment-related symptoms and decreased health-related quality of life (HRQoL) frequently occur during chemotherapy for breast cancer. Although research findings suggest that yoga can reduce symptoms and improve HRQoL after treatment, potential benefits of yoga during chemotherapy have received minimal attention.
Objective To estimate accrual, adherence, study retention, and preliminary efficacy of a yoga intervention compared with an active control group for breast cancer patients during chemotherapy.
Methods Women with stage I-III breast cancer were recruited from 3 community cancer clinics and randomized to 10 weeks of gentle yoga or wellness education. Depressive symptoms, fatigue, sleep, and HRQoL were assessed at baseline, mid-intervention (Week 5), and after intervention (Week 10).
Results 40 women aged 29-83 years (median, 48 years; 88% white) were randomized to yoga (n = 22) or wellness education (n = 18). The groups did not differ significantly on baseline characteristics, adherence, or study retention. Participant feedback was positive and comparable between groups. Meaningful within-group differences were identified for sleep adequacy and quantity in yoga participants and for somnolence in wellness-education participants.
Limitations Small sample size and lack of a usual-care control group.
Conclusions This study established feasibility of a community-based randomized trial of yoga and an active comparison group for women undergoing chemotherapy for breast cancer. Preliminary efficacy estimates suggest that yoga improves sleep adequacy. Symptom severity and interference remained stable during chemotherapy for the yoga group and showed a trend toward increasing in the control group. The study highlighted obstacles to multisite yoga research during cancer treatment.
Funding/sponsorship National Cancer Institute (3U10 CA081851, PI: Shaw; R25 CA122061, PI: Avis); Translational Science Institute, Wake Forest School of Medicine
Click on the PDF icon at the top of this introduction to read the full article.
Background Treatment-related symptoms and decreased health-related quality of life (HRQoL) frequently occur during chemotherapy for breast cancer. Although research findings suggest that yoga can reduce symptoms and improve HRQoL after treatment, potential benefits of yoga during chemotherapy have received minimal attention.
Objective To estimate accrual, adherence, study retention, and preliminary efficacy of a yoga intervention compared with an active control group for breast cancer patients during chemotherapy.
Methods Women with stage I-III breast cancer were recruited from 3 community cancer clinics and randomized to 10 weeks of gentle yoga or wellness education. Depressive symptoms, fatigue, sleep, and HRQoL were assessed at baseline, mid-intervention (Week 5), and after intervention (Week 10).
Results 40 women aged 29-83 years (median, 48 years; 88% white) were randomized to yoga (n = 22) or wellness education (n = 18). The groups did not differ significantly on baseline characteristics, adherence, or study retention. Participant feedback was positive and comparable between groups. Meaningful within-group differences were identified for sleep adequacy and quantity in yoga participants and for somnolence in wellness-education participants.
Limitations Small sample size and lack of a usual-care control group.
Conclusions This study established feasibility of a community-based randomized trial of yoga and an active comparison group for women undergoing chemotherapy for breast cancer. Preliminary efficacy estimates suggest that yoga improves sleep adequacy. Symptom severity and interference remained stable during chemotherapy for the yoga group and showed a trend toward increasing in the control group. The study highlighted obstacles to multisite yoga research during cancer treatment.
Funding/sponsorship National Cancer Institute (3U10 CA081851, PI: Shaw; R25 CA122061, PI: Avis); Translational Science Institute, Wake Forest School of Medicine
Click on the PDF icon at the top of this introduction to read the full article.
Background Treatment-related symptoms and decreased health-related quality of life (HRQoL) frequently occur during chemotherapy for breast cancer. Although research findings suggest that yoga can reduce symptoms and improve HRQoL after treatment, potential benefits of yoga during chemotherapy have received minimal attention.
Objective To estimate accrual, adherence, study retention, and preliminary efficacy of a yoga intervention compared with an active control group for breast cancer patients during chemotherapy.
Methods Women with stage I-III breast cancer were recruited from 3 community cancer clinics and randomized to 10 weeks of gentle yoga or wellness education. Depressive symptoms, fatigue, sleep, and HRQoL were assessed at baseline, mid-intervention (Week 5), and after intervention (Week 10).
Results 40 women aged 29-83 years (median, 48 years; 88% white) were randomized to yoga (n = 22) or wellness education (n = 18). The groups did not differ significantly on baseline characteristics, adherence, or study retention. Participant feedback was positive and comparable between groups. Meaningful within-group differences were identified for sleep adequacy and quantity in yoga participants and for somnolence in wellness-education participants.
Limitations Small sample size and lack of a usual-care control group.
Conclusions This study established feasibility of a community-based randomized trial of yoga and an active comparison group for women undergoing chemotherapy for breast cancer. Preliminary efficacy estimates suggest that yoga improves sleep adequacy. Symptom severity and interference remained stable during chemotherapy for the yoga group and showed a trend toward increasing in the control group. The study highlighted obstacles to multisite yoga research during cancer treatment.
Funding/sponsorship National Cancer Institute (3U10 CA081851, PI: Shaw; R25 CA122061, PI: Avis); Translational Science Institute, Wake Forest School of Medicine
Click on the PDF icon at the top of this introduction to read the full article.