Breast Cancer

SAN FRANCISCO – Two surgeons working in tandem, one on each side of the patient, can significantly reduce the total operative time for bilateral mastectomies without compromising safety or quality of results, according to a study presented at the 2015 ASCO Breast Cancer Symposium.

A review of records on consecutive cases of bilateral mastectomy with tissue expander reconstruction (BMTR) showed that mean overall surgery time (start of incision to closure) was about 23 minutes shorter when two surgeons were working at once, and mean general surgery time (start of incision to end of mastectomy procedure) was 41 minutes shorter with two surgeons vs. a solo operator, reported Dr. Suniti Nimbkar of the department of surgery at Brigham and Women’s Hospital, Boston.

Neil Osterweil/Frontline Medical News

“We did find that there was a significant reduction in time when two surgeons work together, and that reduction is particularly emphasized when you have a patient who is larger, perhaps a heavier patient, and when you have to do more extensive surgery,” she said in an interview at the symposium.

Dual surgeons did take slightly longer to perform the reconstructive surgery portion of the procedure, however.

Effective cosurgery is like a healthy marriage or a successful restaurant kitchen, with partners learning how to anticipate each other’s needs, knowing when to lend a hand, and intuitively grasping when to get out of the way, Dr. Nimbkar suggested.

“As two surgeons work together more and more, they just inevitably grow together in how they operate. I know for example that my direct partner and I operate very similarly, whereas sometimes if I do a cosurgery with a second surgeon that I don’t always operate with we have to work together to understand each other’s approach,” she said.

The investigators scanned the charts of 116 consecutive women who underwent BMTR done by eight breast surgeons at their center, looking for potential differences in operative time and 30-day postoperative complications. In all, 67 of the procedures were cosurgeries, and 49 were done by a single surgeon.

They found that in bivariate analysis, mean general surgery time was 75.8 minutes for the surgical duos, compared with 116.8 minutes for the solo surgeons (P less than .0001). Overall surgery time was also shorter, at 255.2 minutes vs. 278.3 minutes, respectively (P = .005).

Although there were numerically more complications among patients of cosurgeons, there was no statistically significant difference in postoperative complications rates between the twin and singleton surgeons.

A linear regression model showed that factors significantly associated with general surgery time were cosurgeries (P less than .0001), total breast weight (P =.03) and axillary dissection (P = .0003).

The authors noted that although two surgeons cut operative times significantly, the amount of time savings was not proportional to what they expected.

“We also want to know if the plastic surgeons are happy with the results if there are two different surgeons. Do they feel that there is too much of a difference in the way the mastectomy comes out, or is it something they’re fine with? So one of the next steps we’re going to take is to survey the plastic surgeons as to whether they’re comfortable with what we’re doing or if they have ideas about how we can be more uniform,” Dr. Nimbkar said.

SAN FRANCISCO – Two surgeons working in tandem, one on each side of the patient, can significantly reduce the total operative time for bilateral mastectomies without compromising safety or quality of results, according to a study presented at the 2015 ASCO Breast Cancer Symposium.

A review of records on consecutive cases of bilateral mastectomy with tissue expander reconstruction (BMTR) showed that mean overall surgery time (start of incision to closure) was about 23 minutes shorter when two surgeons were working at once, and mean general surgery time (start of incision to end of mastectomy procedure) was 41 minutes shorter with two surgeons vs. a solo operator, reported Dr. Suniti Nimbkar of the department of surgery at Brigham and Women’s Hospital, Boston.

Neil Osterweil/Frontline Medical News

“We did find that there was a significant reduction in time when two surgeons work together, and that reduction is particularly emphasized when you have a patient who is larger, perhaps a heavier patient, and when you have to do more extensive surgery,” she said in an interview at the symposium.

Dual surgeons did take slightly longer to perform the reconstructive surgery portion of the procedure, however.

Effective cosurgery is like a healthy marriage or a successful restaurant kitchen, with partners learning how to anticipate each other’s needs, knowing when to lend a hand, and intuitively grasping when to get out of the way, Dr. Nimbkar suggested.

“As two surgeons work together more and more, they just inevitably grow together in how they operate. I know for example that my direct partner and I operate very similarly, whereas sometimes if I do a cosurgery with a second surgeon that I don’t always operate with we have to work together to understand each other’s approach,” she said.

The investigators scanned the charts of 116 consecutive women who underwent BMTR done by eight breast surgeons at their center, looking for potential differences in operative time and 30-day postoperative complications. In all, 67 of the procedures were cosurgeries, and 49 were done by a single surgeon.

They found that in bivariate analysis, mean general surgery time was 75.8 minutes for the surgical duos, compared with 116.8 minutes for the solo surgeons (P less than .0001). Overall surgery time was also shorter, at 255.2 minutes vs. 278.3 minutes, respectively (P = .005).

Although there were numerically more complications among patients of cosurgeons, there was no statistically significant difference in postoperative complications rates between the twin and singleton surgeons.

A linear regression model showed that factors significantly associated with general surgery time were cosurgeries (P less than .0001), total breast weight (P =.03) and axillary dissection (P = .0003).

The authors noted that although two surgeons cut operative times significantly, the amount of time savings was not proportional to what they expected.

“We also want to know if the plastic surgeons are happy with the results if there are two different surgeons. Do they feel that there is too much of a difference in the way the mastectomy comes out, or is it something they’re fine with? So one of the next steps we’re going to take is to survey the plastic surgeons as to whether they’re comfortable with what we’re doing or if they have ideas about how we can be more uniform,” Dr. Nimbkar said.

SAN FRANCISCO – Two surgeons working in tandem, one on each side of the patient, can significantly reduce the total operative time for bilateral mastectomies without compromising safety or quality of results, according to a study presented at the 2015 ASCO Breast Cancer Symposium.

A review of records on consecutive cases of bilateral mastectomy with tissue expander reconstruction (BMTR) showed that mean overall surgery time (start of incision to closure) was about 23 minutes shorter when two surgeons were working at once, and mean general surgery time (start of incision to end of mastectomy procedure) was 41 minutes shorter with two surgeons vs. a solo operator, reported Dr. Suniti Nimbkar of the department of surgery at Brigham and Women’s Hospital, Boston.

Neil Osterweil/Frontline Medical News

“We did find that there was a significant reduction in time when two surgeons work together, and that reduction is particularly emphasized when you have a patient who is larger, perhaps a heavier patient, and when you have to do more extensive surgery,” she said in an interview at the symposium.

Dual surgeons did take slightly longer to perform the reconstructive surgery portion of the procedure, however.

Effective cosurgery is like a healthy marriage or a successful restaurant kitchen, with partners learning how to anticipate each other’s needs, knowing when to lend a hand, and intuitively grasping when to get out of the way, Dr. Nimbkar suggested.

“As two surgeons work together more and more, they just inevitably grow together in how they operate. I know for example that my direct partner and I operate very similarly, whereas sometimes if I do a cosurgery with a second surgeon that I don’t always operate with we have to work together to understand each other’s approach,” she said.

The investigators scanned the charts of 116 consecutive women who underwent BMTR done by eight breast surgeons at their center, looking for potential differences in operative time and 30-day postoperative complications. In all, 67 of the procedures were cosurgeries, and 49 were done by a single surgeon.

They found that in bivariate analysis, mean general surgery time was 75.8 minutes for the surgical duos, compared with 116.8 minutes for the solo surgeons (P less than .0001). Overall surgery time was also shorter, at 255.2 minutes vs. 278.3 minutes, respectively (P = .005).

Although there were numerically more complications among patients of cosurgeons, there was no statistically significant difference in postoperative complications rates between the twin and singleton surgeons.

A linear regression model showed that factors significantly associated with general surgery time were cosurgeries (P less than .0001), total breast weight (P =.03) and axillary dissection (P = .0003).

The authors noted that although two surgeons cut operative times significantly, the amount of time savings was not proportional to what they expected.

“We also want to know if the plastic surgeons are happy with the results if there are two different surgeons. Do they feel that there is too much of a difference in the way the mastectomy comes out, or is it something they’re fine with? So one of the next steps we’re going to take is to survey the plastic surgeons as to whether they’re comfortable with what we’re doing or if they have ideas about how we can be more uniform,” Dr. Nimbkar said.

Augmenting digital screening mammography with computer-aided detection failed to improve diagnostic accuracy in every performance measure and every subgroup of women studied in a series of 625,625 exams performed across the United States during a 7-year period, according to a report published online Sept. 28 in JAMA Internal Medicine.

In fact, the sensitivity of mammography was actually decreased by computer-aided detection (CAD) in a subgroup of radiologists who practiced at some sites that used CAD and others that did not.

“CAD is a technology that does not seem to warrant added compensation beyond coverage of the mammographic examination,” wrote Dr. Constance D. Lehman of the department of radiology, Massachusetts General Hospital and the Avon Comprehensive Breast Evaluation Center, both in Boston. “The results of our comprehensive study lend no support for continued reimbursement for CAD as a method to increase mammography performance or improve patient outcomes.”

Measuring the real-world impact of CAD on mammographic accuracy has been difficult and has yielded inconsistent and contradictory findings; most studies to date have been relatively small, have focused on older women only, or haven’t taken into account the early part of radiologists’ learning curves. To circumvent these problems, the investigators pooled data from five mammographic registries to include more than 625,000 full-field digital mammograms, included a demographically diverse population of women aged 40-89 years, and excluded the first year of CAD use for every radiologist in the study.

They assessed outcomes after routine screening mammography with CAD (495,818) or without CAD (129,807), which were interpreted by 271 radiologists. Breast cancer was diagnosed in 3,159 women within 1 year of these screening mammograms.

The overall sensitivity of mammography was 85.3% with CAD and 87.3% without it; sensitivity for invasive cancer was 82.1% with CAD and 85.0% without it, all of which are nonsignificant differences. Also similar were mammography’s specificity, at 91.6% with CAD and 91.4% without CAD.

The overall cancer detection rate was exactly the same regardless of the use of CAD, at 4.1 cancers per 1,000 women screened. And the invasive cancer detection rate was nearly the same, at 2.9 cancers with CAD versus 3.0 cancers without CAD (JAMA Intern Med. 2015 Sep 28. doi:10.1001/jamainternmed.2015.5231).

Also, diagnostic accuracy was the same with or without CAD regardless of patient age, patient ethnicity, breast density, patient menopausal status, family history, or interval since the last mammogram. In the subgroup of 107 radiologists who sometimes used CAD and sometimes did not, the use of CAD actually decreased the sensitivity of mammography (83.3% with CAD and 89.6% without CAD).

“Given that the evidence of the current application of CAD in community practice does not show an improvement in diagnostic accuracy, we question the policy of continuing to charge for a technology that provides no established benefits to women,” Dr. Lehman and her associates wrote.

But the researchers noted that CAD may offer advantages beyond diagnostic accuracy, such as improved work flow or shorter times spent assessing faint calcifications. CAD also may be useful in guiding treatment decisions, perhaps reducing unnecessary biopsies of lesions that have specific benign features or ensuring biopsy of lesions that have specific malignant features, they added.

The study was supported by the National Cancer Institute, the Breast Cancer Surveillance Consortium, several state public health departments, and cancer registries throughout the United States. Dr. Lehman reported receiving grant support from General Electric Healthcare and serving as a member of the company’s Comparative Effectiveness Research Advisory Board.

Augmenting digital screening mammography with computer-aided detection failed to improve diagnostic accuracy in every performance measure and every subgroup of women studied in a series of 625,625 exams performed across the United States during a 7-year period, according to a report published online Sept. 28 in JAMA Internal Medicine.

In fact, the sensitivity of mammography was actually decreased by computer-aided detection (CAD) in a subgroup of radiologists who practiced at some sites that used CAD and others that did not.

“CAD is a technology that does not seem to warrant added compensation beyond coverage of the mammographic examination,” wrote Dr. Constance D. Lehman of the department of radiology, Massachusetts General Hospital and the Avon Comprehensive Breast Evaluation Center, both in Boston. “The results of our comprehensive study lend no support for continued reimbursement for CAD as a method to increase mammography performance or improve patient outcomes.”

Measuring the real-world impact of CAD on mammographic accuracy has been difficult and has yielded inconsistent and contradictory findings; most studies to date have been relatively small, have focused on older women only, or haven’t taken into account the early part of radiologists’ learning curves. To circumvent these problems, the investigators pooled data from five mammographic registries to include more than 625,000 full-field digital mammograms, included a demographically diverse population of women aged 40-89 years, and excluded the first year of CAD use for every radiologist in the study.

They assessed outcomes after routine screening mammography with CAD (495,818) or without CAD (129,807), which were interpreted by 271 radiologists. Breast cancer was diagnosed in 3,159 women within 1 year of these screening mammograms.

The overall sensitivity of mammography was 85.3% with CAD and 87.3% without it; sensitivity for invasive cancer was 82.1% with CAD and 85.0% without it, all of which are nonsignificant differences. Also similar were mammography’s specificity, at 91.6% with CAD and 91.4% without CAD.

The overall cancer detection rate was exactly the same regardless of the use of CAD, at 4.1 cancers per 1,000 women screened. And the invasive cancer detection rate was nearly the same, at 2.9 cancers with CAD versus 3.0 cancers without CAD (JAMA Intern Med. 2015 Sep 28. doi:10.1001/jamainternmed.2015.5231).

Also, diagnostic accuracy was the same with or without CAD regardless of patient age, patient ethnicity, breast density, patient menopausal status, family history, or interval since the last mammogram. In the subgroup of 107 radiologists who sometimes used CAD and sometimes did not, the use of CAD actually decreased the sensitivity of mammography (83.3% with CAD and 89.6% without CAD).

“Given that the evidence of the current application of CAD in community practice does not show an improvement in diagnostic accuracy, we question the policy of continuing to charge for a technology that provides no established benefits to women,” Dr. Lehman and her associates wrote.

But the researchers noted that CAD may offer advantages beyond diagnostic accuracy, such as improved work flow or shorter times spent assessing faint calcifications. CAD also may be useful in guiding treatment decisions, perhaps reducing unnecessary biopsies of lesions that have specific benign features or ensuring biopsy of lesions that have specific malignant features, they added.

The study was supported by the National Cancer Institute, the Breast Cancer Surveillance Consortium, several state public health departments, and cancer registries throughout the United States. Dr. Lehman reported receiving grant support from General Electric Healthcare and serving as a member of the company’s Comparative Effectiveness Research Advisory Board.

Augmenting digital screening mammography with computer-aided detection failed to improve diagnostic accuracy in every performance measure and every subgroup of women studied in a series of 625,625 exams performed across the United States during a 7-year period, according to a report published online Sept. 28 in JAMA Internal Medicine.

In fact, the sensitivity of mammography was actually decreased by computer-aided detection (CAD) in a subgroup of radiologists who practiced at some sites that used CAD and others that did not.

“CAD is a technology that does not seem to warrant added compensation beyond coverage of the mammographic examination,” wrote Dr. Constance D. Lehman of the department of radiology, Massachusetts General Hospital and the Avon Comprehensive Breast Evaluation Center, both in Boston. “The results of our comprehensive study lend no support for continued reimbursement for CAD as a method to increase mammography performance or improve patient outcomes.”

Measuring the real-world impact of CAD on mammographic accuracy has been difficult and has yielded inconsistent and contradictory findings; most studies to date have been relatively small, have focused on older women only, or haven’t taken into account the early part of radiologists’ learning curves. To circumvent these problems, the investigators pooled data from five mammographic registries to include more than 625,000 full-field digital mammograms, included a demographically diverse population of women aged 40-89 years, and excluded the first year of CAD use for every radiologist in the study.

They assessed outcomes after routine screening mammography with CAD (495,818) or without CAD (129,807), which were interpreted by 271 radiologists. Breast cancer was diagnosed in 3,159 women within 1 year of these screening mammograms.

The overall sensitivity of mammography was 85.3% with CAD and 87.3% without it; sensitivity for invasive cancer was 82.1% with CAD and 85.0% without it, all of which are nonsignificant differences. Also similar were mammography’s specificity, at 91.6% with CAD and 91.4% without CAD.

The overall cancer detection rate was exactly the same regardless of the use of CAD, at 4.1 cancers per 1,000 women screened. And the invasive cancer detection rate was nearly the same, at 2.9 cancers with CAD versus 3.0 cancers without CAD (JAMA Intern Med. 2015 Sep 28. doi:10.1001/jamainternmed.2015.5231).

Also, diagnostic accuracy was the same with or without CAD regardless of patient age, patient ethnicity, breast density, patient menopausal status, family history, or interval since the last mammogram. In the subgroup of 107 radiologists who sometimes used CAD and sometimes did not, the use of CAD actually decreased the sensitivity of mammography (83.3% with CAD and 89.6% without CAD).

“Given that the evidence of the current application of CAD in community practice does not show an improvement in diagnostic accuracy, we question the policy of continuing to charge for a technology that provides no established benefits to women,” Dr. Lehman and her associates wrote.

But the researchers noted that CAD may offer advantages beyond diagnostic accuracy, such as improved work flow or shorter times spent assessing faint calcifications. CAD also may be useful in guiding treatment decisions, perhaps reducing unnecessary biopsies of lesions that have specific benign features or ensuring biopsy of lesions that have specific malignant features, they added.

The study was supported by the National Cancer Institute, the Breast Cancer Surveillance Consortium, several state public health departments, and cancer registries throughout the United States. Dr. Lehman reported receiving grant support from General Electric Healthcare and serving as a member of the company’s Comparative Effectiveness Research Advisory Board.

SAN FRANCISCO – Using multiplatform profiling, potentially targetable biomarker aberrations were identified in a large sample of tumors taken from older breast cancer patients, reported researchers at the 2015 Breast Cancer Symposium.

In this cross sectional study, 1,189 tumors were collected from breast cancer patients between the ages of 70-97 years, and the samples were assayed for potential targetable biomarkers, and then the findings were compared with samples obtained from younger patients.

“Most of the differences we found were in triple negative patients, and they are related to PIK3CA mutations,” said study author Dr. Paula Pohlmann, from the Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington.

“Also, I am very puzzled that the BRCA1 mutations were not found in older triple negative patients, as compared with the younger patients,” she noted. “Even taking into account the limitations of the study, it was still interesting.”

ERBB2 mutations were identified in non-amplifed breast cancers and less frequently in amplified ones. “And another interesting point was that both PD-1 and PD-L1 positivity by immunohistochemistry were found in all groups, and not only triple negative,” said Dr. Pohlmann. “The checkpoints are similar for both older and younger populations.”

Dr. Pohlmann explained that while she expected to see the PD-1 and PD-L1 positivity, it is worth mentioning since all the treatments focusing on PD-1 and PD-L1 in breast cancer are with triple negative disease. “But we found this expression in Her2 positive and hormone receptor positive disease.”

However, she emphasized that this doesn’t mean that they are necessarily a target. “If they will respond to that therapy, we don’t know, that’s a different story, but the markers are there,” Dr. Pohlmann said.

In this study a total of 1,189 tumors were collected from breast cancer patients (male= 21/female = 1,168) who were aged 70 years and older. The tumors were analyzed (breast biopsy n = 512; metastatic site n = 677), and of 1,088 tumors with available immunohistochemistry (IHC) of ER, PR and IHC and/or in situ hybridization (ISH) of HER2, 613 (56%) were HR+/HER2-, 72 (7%) were HR+/HER2+, 346 (32%) were triple negative, and 57 (5%) were HR-/HER2+.

Overall, 39 of 47 genes that were sequenced carried mutations with frequencies ranging from 0.2% to 37%. The highest mutation rates were seen in PIK3CA (37%), TP53 (37%), BRCA2 (12%), PTEN (5.8%), AKT1 (4.2%), cMET (3.9%), ERBB2 (3.5%), BRCA1 (3.3%), and ATM (3.2%).

Among 13 patients with ERBB2 mutation, 3 had it amplified. PD-L1 expression on tumor cells was detected in 13% of tumors and PD-1 expression on tumor-infiltrating lymphocytes was seen in 46%, but the triple negative subtype had the highest expression: 20% and 60%, respectively.

The researchers also noted that TOPO1, TLE3, AR, TOP2A, and SPARC were overexpressed in 61%, 58%, 55%, 51%, and 37% of tumors, respectively. These observations suggest that there is potential sensitivity to irinotecan, taxanes, anthracyclines, and nab-paclitaxel.

In addition, TS, RRM1, and ERCC1 were under-expressed in 69%, 69%, and 53% of tumors, respectively, which suggests that there may be potential sensitivity to fluoropyrimidines, gemcitabine, and platinums

“This study provides key elements for the design of clinical trials focusing on geriatric patient population, particularly in the subgroup of triple negative breast cancer,” said Dr. Pohlmann. “In addition, ERBB2 abnormalities in older patients may also warrant further investigation.”

Dr. Charles E. Geyer, Jr., of Virginia Commonwealth University Massey Cancer Center, Richmond, in his discussion of the paper, pointed out that while there were some differences in the groups, it wasn’t clear that they are clinically significant differences. “The most interesting were PD-1 and PD-L1, which were in higher numbers than are being reported.”

But the data from this study suggest that focus needs to be on inclusion of geriatric patients in targeted therapy trials, he said.

He also noted that in general, patients frequently have some unrealistic expectations when it comes to genetic testing. “The advocacy often gets a little ahead of the science,” Dr. Geyer said.

SAN FRANCISCO – Using multiplatform profiling, potentially targetable biomarker aberrations were identified in a large sample of tumors taken from older breast cancer patients, reported researchers at the 2015 Breast Cancer Symposium.

In this cross sectional study, 1,189 tumors were collected from breast cancer patients between the ages of 70-97 years, and the samples were assayed for potential targetable biomarkers, and then the findings were compared with samples obtained from younger patients.

“Most of the differences we found were in triple negative patients, and they are related to PIK3CA mutations,” said study author Dr. Paula Pohlmann, from the Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington.

“Also, I am very puzzled that the BRCA1 mutations were not found in older triple negative patients, as compared with the younger patients,” she noted. “Even taking into account the limitations of the study, it was still interesting.”

ERBB2 mutations were identified in non-amplifed breast cancers and less frequently in amplified ones. “And another interesting point was that both PD-1 and PD-L1 positivity by immunohistochemistry were found in all groups, and not only triple negative,” said Dr. Pohlmann. “The checkpoints are similar for both older and younger populations.”

Dr. Pohlmann explained that while she expected to see the PD-1 and PD-L1 positivity, it is worth mentioning since all the treatments focusing on PD-1 and PD-L1 in breast cancer are with triple negative disease. “But we found this expression in Her2 positive and hormone receptor positive disease.”

However, she emphasized that this doesn’t mean that they are necessarily a target. “If they will respond to that therapy, we don’t know, that’s a different story, but the markers are there,” Dr. Pohlmann said.

In this study a total of 1,189 tumors were collected from breast cancer patients (male= 21/female = 1,168) who were aged 70 years and older. The tumors were analyzed (breast biopsy n = 512; metastatic site n = 677), and of 1,088 tumors with available immunohistochemistry (IHC) of ER, PR and IHC and/or in situ hybridization (ISH) of HER2, 613 (56%) were HR+/HER2-, 72 (7%) were HR+/HER2+, 346 (32%) were triple negative, and 57 (5%) were HR-/HER2+.

Overall, 39 of 47 genes that were sequenced carried mutations with frequencies ranging from 0.2% to 37%. The highest mutation rates were seen in PIK3CA (37%), TP53 (37%), BRCA2 (12%), PTEN (5.8%), AKT1 (4.2%), cMET (3.9%), ERBB2 (3.5%), BRCA1 (3.3%), and ATM (3.2%).

Among 13 patients with ERBB2 mutation, 3 had it amplified. PD-L1 expression on tumor cells was detected in 13% of tumors and PD-1 expression on tumor-infiltrating lymphocytes was seen in 46%, but the triple negative subtype had the highest expression: 20% and 60%, respectively.

The researchers also noted that TOPO1, TLE3, AR, TOP2A, and SPARC were overexpressed in 61%, 58%, 55%, 51%, and 37% of tumors, respectively. These observations suggest that there is potential sensitivity to irinotecan, taxanes, anthracyclines, and nab-paclitaxel.

In addition, TS, RRM1, and ERCC1 were under-expressed in 69%, 69%, and 53% of tumors, respectively, which suggests that there may be potential sensitivity to fluoropyrimidines, gemcitabine, and platinums

“This study provides key elements for the design of clinical trials focusing on geriatric patient population, particularly in the subgroup of triple negative breast cancer,” said Dr. Pohlmann. “In addition, ERBB2 abnormalities in older patients may also warrant further investigation.”

Dr. Charles E. Geyer, Jr., of Virginia Commonwealth University Massey Cancer Center, Richmond, in his discussion of the paper, pointed out that while there were some differences in the groups, it wasn’t clear that they are clinically significant differences. “The most interesting were PD-1 and PD-L1, which were in higher numbers than are being reported.”

But the data from this study suggest that focus needs to be on inclusion of geriatric patients in targeted therapy trials, he said.

He also noted that in general, patients frequently have some unrealistic expectations when it comes to genetic testing. “The advocacy often gets a little ahead of the science,” Dr. Geyer said.

SAN FRANCISCO – Using multiplatform profiling, potentially targetable biomarker aberrations were identified in a large sample of tumors taken from older breast cancer patients, reported researchers at the 2015 Breast Cancer Symposium.

In this cross sectional study, 1,189 tumors were collected from breast cancer patients between the ages of 70-97 years, and the samples were assayed for potential targetable biomarkers, and then the findings were compared with samples obtained from younger patients.

“Most of the differences we found were in triple negative patients, and they are related to PIK3CA mutations,” said study author Dr. Paula Pohlmann, from the Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington.

“Also, I am very puzzled that the BRCA1 mutations were not found in older triple negative patients, as compared with the younger patients,” she noted. “Even taking into account the limitations of the study, it was still interesting.”

ERBB2 mutations were identified in non-amplifed breast cancers and less frequently in amplified ones. “And another interesting point was that both PD-1 and PD-L1 positivity by immunohistochemistry were found in all groups, and not only triple negative,” said Dr. Pohlmann. “The checkpoints are similar for both older and younger populations.”

Dr. Pohlmann explained that while she expected to see the PD-1 and PD-L1 positivity, it is worth mentioning since all the treatments focusing on PD-1 and PD-L1 in breast cancer are with triple negative disease. “But we found this expression in Her2 positive and hormone receptor positive disease.”

However, she emphasized that this doesn’t mean that they are necessarily a target. “If they will respond to that therapy, we don’t know, that’s a different story, but the markers are there,” Dr. Pohlmann said.

In this study a total of 1,189 tumors were collected from breast cancer patients (male= 21/female = 1,168) who were aged 70 years and older. The tumors were analyzed (breast biopsy n = 512; metastatic site n = 677), and of 1,088 tumors with available immunohistochemistry (IHC) of ER, PR and IHC and/or in situ hybridization (ISH) of HER2, 613 (56%) were HR+/HER2-, 72 (7%) were HR+/HER2+, 346 (32%) were triple negative, and 57 (5%) were HR-/HER2+.

Overall, 39 of 47 genes that were sequenced carried mutations with frequencies ranging from 0.2% to 37%. The highest mutation rates were seen in PIK3CA (37%), TP53 (37%), BRCA2 (12%), PTEN (5.8%), AKT1 (4.2%), cMET (3.9%), ERBB2 (3.5%), BRCA1 (3.3%), and ATM (3.2%).

Among 13 patients with ERBB2 mutation, 3 had it amplified. PD-L1 expression on tumor cells was detected in 13% of tumors and PD-1 expression on tumor-infiltrating lymphocytes was seen in 46%, but the triple negative subtype had the highest expression: 20% and 60%, respectively.

The researchers also noted that TOPO1, TLE3, AR, TOP2A, and SPARC were overexpressed in 61%, 58%, 55%, 51%, and 37% of tumors, respectively. These observations suggest that there is potential sensitivity to irinotecan, taxanes, anthracyclines, and nab-paclitaxel.

In addition, TS, RRM1, and ERCC1 were under-expressed in 69%, 69%, and 53% of tumors, respectively, which suggests that there may be potential sensitivity to fluoropyrimidines, gemcitabine, and platinums

“This study provides key elements for the design of clinical trials focusing on geriatric patient population, particularly in the subgroup of triple negative breast cancer,” said Dr. Pohlmann. “In addition, ERBB2 abnormalities in older patients may also warrant further investigation.”

Dr. Charles E. Geyer, Jr., of Virginia Commonwealth University Massey Cancer Center, Richmond, in his discussion of the paper, pointed out that while there were some differences in the groups, it wasn’t clear that they are clinically significant differences. “The most interesting were PD-1 and PD-L1, which were in higher numbers than are being reported.”

But the data from this study suggest that focus needs to be on inclusion of geriatric patients in targeted therapy trials, he said.

He also noted that in general, patients frequently have some unrealistic expectations when it comes to genetic testing. “The advocacy often gets a little ahead of the science,” Dr. Geyer said.

SAN FRANCISCO – Breast cancer surgery within 30 days of neoadjuvant chemotherapy appears to be safe, with no significant increase in risk of postoperative complications compared with surgery performed in women who did not receive chemotherapy.

An analysis of data on more than 3,500 patients who underwent surgery for invasive breast cancer after receiving neoadjuvant chemotherapy showed that in an analysis adjusted to better balance patient characteristics, there were no significant differences in postoperative complication rates for patients who received chemotherapy and those who did not, reported Dr. Erin Cordeiro from the Ottawa Hospital in Ontario, Canada, and associates, at a breast cancer symposium sponsored jointly by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology.

“I really think this should put to rest the concern that surgeons might have about neoadjuvant chemotherapy particularly because this [study] compressed people within 30 days of the surgery date,” commented Dr. Charles E. Geyer, Jr., from the Virginia Commonwealth University School of Medicine in Richmond. Dr. Geyer was the invited discussant.

The use of neoadjuvant chemotherapy in the treatment of patients with breast cancer continues to increase, growing from 14% in 2006, to 20% in 2011, Dr. Cordeiro said.

But because myelosuppression, particularly neutropenia, is a common side of chemotherapy, surgeons are often concerned that operating too soon after a patient completes a course of chemotherapy could result in increased post-operative complications, she said.

To determine whether neoadjuvant chemotherapy would increase the proportion of overall 30-day postoperative complications among patients undergoing surgery for invasive breast cancer, Dr. Cordeiro drew on the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, which contains validated, risk-adjusted surgical outcomes data from more than 600 hospitals in 49 states, Canada, and Europe.

She identified data on 67,685 patients who underwent surgery for invasive breast cancer from 2005 through 2012. Of this group, 3,624 (5.5%) had received neoadjuvant chemotherapy. Investigators excludedpPatients with high-risk comorbidities and those who underwent other surgery concurrent with breast surgery (e.g., oophorectomy).

In unadjusted analysis, the rate of a composite of overall 30-day post-operative complications, the primary outcome, was 4.9% for patients who had undergone neoadjuvant chemotherapy, compared with 3.7% for patients who did not and this difference was significant (P= .0003). The higher rate among patient who had received chemotherapy recently was largely due to infections, Dr. Cordeiro said.

However, in a multivariate analysis adjusted for propensity score – a measure of the probability of receiving neoeadjuvant chemotherapy by age, diabetes, chronic obstructive pulmonary disease, hypertension, bilateral surgery, and/or year of surgery – the differences between patients who underwent neoadjuvant chemo and those who did not vanished (odds ratio 1.16; 95% confidence interval, 0.98-1.36).

Dr. Cordeiro acknowledged that the study was limited by the use of retrospective data, a lack of knowledge of exactly when chemotherapy was stopped in relation to the surgery data, lack of data on which regimens were used, and no information about prophylatic antibiotics or thromboprophylaxis.

The investigators plan to perform additional subgroup analyses to determine whether there might be differences in complication rates in patients who did or did not receive neoadjuvant chemo by type of breast surgery (breast-conserving vs. mastectomy), type of axillary surgery (sentinel node biopsy vs. axillary lymph node dissection) or among patients who undergo immediate reconstruction.

The study was presented as a poster and in an oral abstract session.

SAN FRANCISCO – Breast cancer surgery within 30 days of neoadjuvant chemotherapy appears to be safe, with no significant increase in risk of postoperative complications compared with surgery performed in women who did not receive chemotherapy.

An analysis of data on more than 3,500 patients who underwent surgery for invasive breast cancer after receiving neoadjuvant chemotherapy showed that in an analysis adjusted to better balance patient characteristics, there were no significant differences in postoperative complication rates for patients who received chemotherapy and those who did not, reported Dr. Erin Cordeiro from the Ottawa Hospital in Ontario, Canada, and associates, at a breast cancer symposium sponsored jointly by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology.

“I really think this should put to rest the concern that surgeons might have about neoadjuvant chemotherapy particularly because this [study] compressed people within 30 days of the surgery date,” commented Dr. Charles E. Geyer, Jr., from the Virginia Commonwealth University School of Medicine in Richmond. Dr. Geyer was the invited discussant.

The use of neoadjuvant chemotherapy in the treatment of patients with breast cancer continues to increase, growing from 14% in 2006, to 20% in 2011, Dr. Cordeiro said.

But because myelosuppression, particularly neutropenia, is a common side of chemotherapy, surgeons are often concerned that operating too soon after a patient completes a course of chemotherapy could result in increased post-operative complications, she said.

To determine whether neoadjuvant chemotherapy would increase the proportion of overall 30-day postoperative complications among patients undergoing surgery for invasive breast cancer, Dr. Cordeiro drew on the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, which contains validated, risk-adjusted surgical outcomes data from more than 600 hospitals in 49 states, Canada, and Europe.

She identified data on 67,685 patients who underwent surgery for invasive breast cancer from 2005 through 2012. Of this group, 3,624 (5.5%) had received neoadjuvant chemotherapy. Investigators excludedpPatients with high-risk comorbidities and those who underwent other surgery concurrent with breast surgery (e.g., oophorectomy).

In unadjusted analysis, the rate of a composite of overall 30-day post-operative complications, the primary outcome, was 4.9% for patients who had undergone neoadjuvant chemotherapy, compared with 3.7% for patients who did not and this difference was significant (P= .0003). The higher rate among patient who had received chemotherapy recently was largely due to infections, Dr. Cordeiro said.

However, in a multivariate analysis adjusted for propensity score – a measure of the probability of receiving neoeadjuvant chemotherapy by age, diabetes, chronic obstructive pulmonary disease, hypertension, bilateral surgery, and/or year of surgery – the differences between patients who underwent neoadjuvant chemo and those who did not vanished (odds ratio 1.16; 95% confidence interval, 0.98-1.36).

Dr. Cordeiro acknowledged that the study was limited by the use of retrospective data, a lack of knowledge of exactly when chemotherapy was stopped in relation to the surgery data, lack of data on which regimens were used, and no information about prophylatic antibiotics or thromboprophylaxis.

The investigators plan to perform additional subgroup analyses to determine whether there might be differences in complication rates in patients who did or did not receive neoadjuvant chemo by type of breast surgery (breast-conserving vs. mastectomy), type of axillary surgery (sentinel node biopsy vs. axillary lymph node dissection) or among patients who undergo immediate reconstruction.

The study was presented as a poster and in an oral abstract session.

SAN FRANCISCO – Breast cancer surgery within 30 days of neoadjuvant chemotherapy appears to be safe, with no significant increase in risk of postoperative complications compared with surgery performed in women who did not receive chemotherapy.

An analysis of data on more than 3,500 patients who underwent surgery for invasive breast cancer after receiving neoadjuvant chemotherapy showed that in an analysis adjusted to better balance patient characteristics, there were no significant differences in postoperative complication rates for patients who received chemotherapy and those who did not, reported Dr. Erin Cordeiro from the Ottawa Hospital in Ontario, Canada, and associates, at a breast cancer symposium sponsored jointly by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology.

“I really think this should put to rest the concern that surgeons might have about neoadjuvant chemotherapy particularly because this [study] compressed people within 30 days of the surgery date,” commented Dr. Charles E. Geyer, Jr., from the Virginia Commonwealth University School of Medicine in Richmond. Dr. Geyer was the invited discussant.

The use of neoadjuvant chemotherapy in the treatment of patients with breast cancer continues to increase, growing from 14% in 2006, to 20% in 2011, Dr. Cordeiro said.

But because myelosuppression, particularly neutropenia, is a common side of chemotherapy, surgeons are often concerned that operating too soon after a patient completes a course of chemotherapy could result in increased post-operative complications, she said.

To determine whether neoadjuvant chemotherapy would increase the proportion of overall 30-day postoperative complications among patients undergoing surgery for invasive breast cancer, Dr. Cordeiro drew on the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, which contains validated, risk-adjusted surgical outcomes data from more than 600 hospitals in 49 states, Canada, and Europe.

She identified data on 67,685 patients who underwent surgery for invasive breast cancer from 2005 through 2012. Of this group, 3,624 (5.5%) had received neoadjuvant chemotherapy. Investigators excludedpPatients with high-risk comorbidities and those who underwent other surgery concurrent with breast surgery (e.g., oophorectomy).

In unadjusted analysis, the rate of a composite of overall 30-day post-operative complications, the primary outcome, was 4.9% for patients who had undergone neoadjuvant chemotherapy, compared with 3.7% for patients who did not and this difference was significant (P= .0003). The higher rate among patient who had received chemotherapy recently was largely due to infections, Dr. Cordeiro said.

However, in a multivariate analysis adjusted for propensity score – a measure of the probability of receiving neoeadjuvant chemotherapy by age, diabetes, chronic obstructive pulmonary disease, hypertension, bilateral surgery, and/or year of surgery – the differences between patients who underwent neoadjuvant chemo and those who did not vanished (odds ratio 1.16; 95% confidence interval, 0.98-1.36).

Dr. Cordeiro acknowledged that the study was limited by the use of retrospective data, a lack of knowledge of exactly when chemotherapy was stopped in relation to the surgery data, lack of data on which regimens were used, and no information about prophylatic antibiotics or thromboprophylaxis.

The investigators plan to perform additional subgroup analyses to determine whether there might be differences in complication rates in patients who did or did not receive neoadjuvant chemo by type of breast surgery (breast-conserving vs. mastectomy), type of axillary surgery (sentinel node biopsy vs. axillary lymph node dissection) or among patients who undergo immediate reconstruction.

The study was presented as a poster and in an oral abstract session.

SAN FRANCISCO – Many younger women diagnosed with triple-negative breast cancers do not get tested for BRCA, despite guideline recommendations, investigators report.

Among 173 women with triple-negative tumors -- lacking the HER2, estrogen and progesterone receptors –17% of those who should have been tested for BRCA according to National Comprehensive Cancer Network (NCCN) guidelines, were not tested.

Women less likely to be tested were those 55 years or older, African Americans, those who list Medicaid as their primary form of insurance, and those with stage 3 disease, reported Staci Aubry, a 4th-year medical student at Rush University Medical Center in Chicago, and her associates.

In an interview, Ms. Aubry said that some of the women who were eligible for genetic testing under the guidelines simply declined it.

“Often patients, if they didn’t have a daughter or if they were older and were in the 50 to 60 [year-old] range, even though they’re still included in the NCCN guidelines to be screened, still refused to be tested,” she said.

NCCN guidelines on genetic and familial high-risk assessment for breast and ovarian cancer susceptibility recommend BRCA genetic testing for all women below age 60 years who are diagnosed with triple-negative breast cancer.

“Some histopathologic features have reported to occur more frequently in breast cancers characterized by a BRCA1 or BRCA2 mutation. For example, several studies have shown that BRCA1 breast cancer is more likely to be characterized as ER-/PR-negative and HER2-negative (i.e., “triple negative”), the guidelines note.

To see whether clinicians were adhering to this recommendation, the investigators searched the Commission on Cancer registry tumor database for cases of triple-negative breast cancers diagnosed from 2006 through 2013.

They identified 173 patients, 105 of whom were younger than 60 and thus recommended for screening. Of this group, 87 (83%) were tested for BRCA, and 15 were found to be BRCA positive, but the remaining 18 patients (17%) were not tested.

When the authors looked at demographic and clinical factors that might have accounted for the differences between women who were tested for the gene and those who were not, four factors stood out. Women who did not get tested were more likely to be 55 or older (P = .002), African American (P = .001), Medicaid insured (P = .021) or to have American Joint Commission on Cancer stage 3 disease (P = .014).

“The main message for clinicians is to be aware that these disparities exist, and keep in mind that these four groups – people who are under Medicaid insurance, between 55 and 60 years of age, African American, or who have higher disease stage – should be targeted for screening,” Ms. Aubry said.

SAN FRANCISCO – Many younger women diagnosed with triple-negative breast cancers do not get tested for BRCA, despite guideline recommendations, investigators report.

Among 173 women with triple-negative tumors -- lacking the HER2, estrogen and progesterone receptors –17% of those who should have been tested for BRCA according to National Comprehensive Cancer Network (NCCN) guidelines, were not tested.

Women less likely to be tested were those 55 years or older, African Americans, those who list Medicaid as their primary form of insurance, and those with stage 3 disease, reported Staci Aubry, a 4th-year medical student at Rush University Medical Center in Chicago, and her associates.

In an interview, Ms. Aubry said that some of the women who were eligible for genetic testing under the guidelines simply declined it.

“Often patients, if they didn’t have a daughter or if they were older and were in the 50 to 60 [year-old] range, even though they’re still included in the NCCN guidelines to be screened, still refused to be tested,” she said.

NCCN guidelines on genetic and familial high-risk assessment for breast and ovarian cancer susceptibility recommend BRCA genetic testing for all women below age 60 years who are diagnosed with triple-negative breast cancer.

“Some histopathologic features have reported to occur more frequently in breast cancers characterized by a BRCA1 or BRCA2 mutation. For example, several studies have shown that BRCA1 breast cancer is more likely to be characterized as ER-/PR-negative and HER2-negative (i.e., “triple negative”), the guidelines note.

To see whether clinicians were adhering to this recommendation, the investigators searched the Commission on Cancer registry tumor database for cases of triple-negative breast cancers diagnosed from 2006 through 2013.

They identified 173 patients, 105 of whom were younger than 60 and thus recommended for screening. Of this group, 87 (83%) were tested for BRCA, and 15 were found to be BRCA positive, but the remaining 18 patients (17%) were not tested.

When the authors looked at demographic and clinical factors that might have accounted for the differences between women who were tested for the gene and those who were not, four factors stood out. Women who did not get tested were more likely to be 55 or older (P = .002), African American (P = .001), Medicaid insured (P = .021) or to have American Joint Commission on Cancer stage 3 disease (P = .014).

“The main message for clinicians is to be aware that these disparities exist, and keep in mind that these four groups – people who are under Medicaid insurance, between 55 and 60 years of age, African American, or who have higher disease stage – should be targeted for screening,” Ms. Aubry said.

SAN FRANCISCO – Many younger women diagnosed with triple-negative breast cancers do not get tested for BRCA, despite guideline recommendations, investigators report.

Among 173 women with triple-negative tumors -- lacking the HER2, estrogen and progesterone receptors –17% of those who should have been tested for BRCA according to National Comprehensive Cancer Network (NCCN) guidelines, were not tested.

Women less likely to be tested were those 55 years or older, African Americans, those who list Medicaid as their primary form of insurance, and those with stage 3 disease, reported Staci Aubry, a 4th-year medical student at Rush University Medical Center in Chicago, and her associates.

In an interview, Ms. Aubry said that some of the women who were eligible for genetic testing under the guidelines simply declined it.

“Often patients, if they didn’t have a daughter or if they were older and were in the 50 to 60 [year-old] range, even though they’re still included in the NCCN guidelines to be screened, still refused to be tested,” she said.

NCCN guidelines on genetic and familial high-risk assessment for breast and ovarian cancer susceptibility recommend BRCA genetic testing for all women below age 60 years who are diagnosed with triple-negative breast cancer.

“Some histopathologic features have reported to occur more frequently in breast cancers characterized by a BRCA1 or BRCA2 mutation. For example, several studies have shown that BRCA1 breast cancer is more likely to be characterized as ER-/PR-negative and HER2-negative (i.e., “triple negative”), the guidelines note.

To see whether clinicians were adhering to this recommendation, the investigators searched the Commission on Cancer registry tumor database for cases of triple-negative breast cancers diagnosed from 2006 through 2013.

They identified 173 patients, 105 of whom were younger than 60 and thus recommended for screening. Of this group, 87 (83%) were tested for BRCA, and 15 were found to be BRCA positive, but the remaining 18 patients (17%) were not tested.

When the authors looked at demographic and clinical factors that might have accounted for the differences between women who were tested for the gene and those who were not, four factors stood out. Women who did not get tested were more likely to be 55 or older (P = .002), African American (P = .001), Medicaid insured (P = .021) or to have American Joint Commission on Cancer stage 3 disease (P = .014).

“The main message for clinicians is to be aware that these disparities exist, and keep in mind that these four groups – people who are under Medicaid insurance, between 55 and 60 years of age, African American, or who have higher disease stage – should be targeted for screening,” Ms. Aubry said.

SAN FRANCISCO – A woman’s age at biopsy and the number of atypical hyperplasia foci appear to be good predictors of risk for subsequent breast cancer, investigators say.

A review of pathology records and medical history on more than 13,000 women with benign breast disease showed that a predictive model including age and atypia effectively identified those women with atypical hyperplasia at highest risk for developing breast cancer, reported Dr. Amy C. Degnim from the Mayo Clinic in Rochester, Minnesota.

“In our country, approximately 10% of all benign breast biopsies are showing atypical hyperplasia, and with about a million women who undergo biopsy every year, this about 100,000 women every year who are diagnosed with atypical hyperplasia. These women are known to have an increased risk of breast cancer,” Dr. Degnim said at a breast symposium here jointly sponsored by the American Society of Clinical Oncology, American Society For Radiation Oncology, and Society of Surgical Oncology.

Current risk prediction models such as the Breast Cancer Risk Assessment Tool and IBIS Breast Cancer Risk Evaluation Tool tend to underestimate or overestimate risk of breast cancer in women with atypical hyperplasia, prompting the investigators to explore developing a reliable prediction tool, she said

The investigators identified a cohort of 13,538 women diagnosed with benign breast disease at the Mayo Clinic from 1967 through 2001, and they found data on 699 with atypical hyperplasia confirmed by pathology review blinded to outcomes. They collected data on clinical and histologic features and identified breast cancer event through review of medical records and questionnaires.

In addition to the Mayo patients used to develop the model, the authors tested it in a validation sample of 461 women with atypical hyperplasia treated at Vanderibilt University in Nashville, Tennessee.

They rounded up data on potential contributors to a risk-prediction model using Lasso-identified variables that they then plugged into a Cox regression model.

They found that of all possible co-variates, including body-mass index at biopsy, age at menarche, indication for biopsy, number of live births, breastfeeding, family features, and histologic features such as involution or calcifications, only the age at biopsy and number of foci of atypical hyperplasia remained as robust predictors for breast cancer risk.

They then tested the model on data from the 699 women in the development set, who had had a total of 142 breast cancer events over a median follow-up of 8.1 years, and in the external validation set of 461 women who had a total of 114 breast cancer events over a median follow-up of 11.4 years.

They found that the concordance between the prediction model and the actual outcomes at 5, 10, and 30 years was 0.607. 0.633, and 0.607, respectively, for the development set.

The model performed a little less well for the validation set, with 5-, 10-, and 30-year concordance of 0.557, 0.584, and 0.557.

Based on their findings, they developed a risk-prediction table showing relative risk for women by age and number of foci (1, 2, or 3 or more). For example, the table shows a 5-year absolute risk of 9.69% for a woman 70-74 years in age at the time of biopsy with 3 or more foci of atypia, compared with just 4.5% for a woman of the same age with only 1 focus. There are risk prediction tables for 5-, 10-, and 30-year absolute risk.

In her commentary on the study, Dr. A. Marilyn Leitch from the University of Texas Southwestern Medical Center in Dallas, noted that the risk-prediction model relies on specific detail in the pathology report for the description of the number of foci of atypical hyperplasia.

“This model can provide estimates that are more informative to the patient than ‘4.5 times risk of breast cancer.’ However, while a high score might motivate a patient for intervention, most patients in the less than 20% risk category, and so we may not have as much persuasion from this model,” she said.

SAN FRANCISCO – A woman’s age at biopsy and the number of atypical hyperplasia foci appear to be good predictors of risk for subsequent breast cancer, investigators say.

A review of pathology records and medical history on more than 13,000 women with benign breast disease showed that a predictive model including age and atypia effectively identified those women with atypical hyperplasia at highest risk for developing breast cancer, reported Dr. Amy C. Degnim from the Mayo Clinic in Rochester, Minnesota.

“In our country, approximately 10% of all benign breast biopsies are showing atypical hyperplasia, and with about a million women who undergo biopsy every year, this about 100,000 women every year who are diagnosed with atypical hyperplasia. These women are known to have an increased risk of breast cancer,” Dr. Degnim said at a breast symposium here jointly sponsored by the American Society of Clinical Oncology, American Society For Radiation Oncology, and Society of Surgical Oncology.

Current risk prediction models such as the Breast Cancer Risk Assessment Tool and IBIS Breast Cancer Risk Evaluation Tool tend to underestimate or overestimate risk of breast cancer in women with atypical hyperplasia, prompting the investigators to explore developing a reliable prediction tool, she said

The investigators identified a cohort of 13,538 women diagnosed with benign breast disease at the Mayo Clinic from 1967 through 2001, and they found data on 699 with atypical hyperplasia confirmed by pathology review blinded to outcomes. They collected data on clinical and histologic features and identified breast cancer event through review of medical records and questionnaires.

In addition to the Mayo patients used to develop the model, the authors tested it in a validation sample of 461 women with atypical hyperplasia treated at Vanderibilt University in Nashville, Tennessee.

They rounded up data on potential contributors to a risk-prediction model using Lasso-identified variables that they then plugged into a Cox regression model.

They found that of all possible co-variates, including body-mass index at biopsy, age at menarche, indication for biopsy, number of live births, breastfeeding, family features, and histologic features such as involution or calcifications, only the age at biopsy and number of foci of atypical hyperplasia remained as robust predictors for breast cancer risk.

They then tested the model on data from the 699 women in the development set, who had had a total of 142 breast cancer events over a median follow-up of 8.1 years, and in the external validation set of 461 women who had a total of 114 breast cancer events over a median follow-up of 11.4 years.

They found that the concordance between the prediction model and the actual outcomes at 5, 10, and 30 years was 0.607. 0.633, and 0.607, respectively, for the development set.

The model performed a little less well for the validation set, with 5-, 10-, and 30-year concordance of 0.557, 0.584, and 0.557.

Based on their findings, they developed a risk-prediction table showing relative risk for women by age and number of foci (1, 2, or 3 or more). For example, the table shows a 5-year absolute risk of 9.69% for a woman 70-74 years in age at the time of biopsy with 3 or more foci of atypia, compared with just 4.5% for a woman of the same age with only 1 focus. There are risk prediction tables for 5-, 10-, and 30-year absolute risk.

In her commentary on the study, Dr. A. Marilyn Leitch from the University of Texas Southwestern Medical Center in Dallas, noted that the risk-prediction model relies on specific detail in the pathology report for the description of the number of foci of atypical hyperplasia.

“This model can provide estimates that are more informative to the patient than ‘4.5 times risk of breast cancer.’ However, while a high score might motivate a patient for intervention, most patients in the less than 20% risk category, and so we may not have as much persuasion from this model,” she said.

SAN FRANCISCO – A woman’s age at biopsy and the number of atypical hyperplasia foci appear to be good predictors of risk for subsequent breast cancer, investigators say.

A review of pathology records and medical history on more than 13,000 women with benign breast disease showed that a predictive model including age and atypia effectively identified those women with atypical hyperplasia at highest risk for developing breast cancer, reported Dr. Amy C. Degnim from the Mayo Clinic in Rochester, Minnesota.

“In our country, approximately 10% of all benign breast biopsies are showing atypical hyperplasia, and with about a million women who undergo biopsy every year, this about 100,000 women every year who are diagnosed with atypical hyperplasia. These women are known to have an increased risk of breast cancer,” Dr. Degnim said at a breast symposium here jointly sponsored by the American Society of Clinical Oncology, American Society For Radiation Oncology, and Society of Surgical Oncology.

Current risk prediction models such as the Breast Cancer Risk Assessment Tool and IBIS Breast Cancer Risk Evaluation Tool tend to underestimate or overestimate risk of breast cancer in women with atypical hyperplasia, prompting the investigators to explore developing a reliable prediction tool, she said

The investigators identified a cohort of 13,538 women diagnosed with benign breast disease at the Mayo Clinic from 1967 through 2001, and they found data on 699 with atypical hyperplasia confirmed by pathology review blinded to outcomes. They collected data on clinical and histologic features and identified breast cancer event through review of medical records and questionnaires.

In addition to the Mayo patients used to develop the model, the authors tested it in a validation sample of 461 women with atypical hyperplasia treated at Vanderibilt University in Nashville, Tennessee.

They rounded up data on potential contributors to a risk-prediction model using Lasso-identified variables that they then plugged into a Cox regression model.

They found that of all possible co-variates, including body-mass index at biopsy, age at menarche, indication for biopsy, number of live births, breastfeeding, family features, and histologic features such as involution or calcifications, only the age at biopsy and number of foci of atypical hyperplasia remained as robust predictors for breast cancer risk.

They then tested the model on data from the 699 women in the development set, who had had a total of 142 breast cancer events over a median follow-up of 8.1 years, and in the external validation set of 461 women who had a total of 114 breast cancer events over a median follow-up of 11.4 years.

They found that the concordance between the prediction model and the actual outcomes at 5, 10, and 30 years was 0.607. 0.633, and 0.607, respectively, for the development set.

The model performed a little less well for the validation set, with 5-, 10-, and 30-year concordance of 0.557, 0.584, and 0.557.

Based on their findings, they developed a risk-prediction table showing relative risk for women by age and number of foci (1, 2, or 3 or more). For example, the table shows a 5-year absolute risk of 9.69% for a woman 70-74 years in age at the time of biopsy with 3 or more foci of atypia, compared with just 4.5% for a woman of the same age with only 1 focus. There are risk prediction tables for 5-, 10-, and 30-year absolute risk.

In her commentary on the study, Dr. A. Marilyn Leitch from the University of Texas Southwestern Medical Center in Dallas, noted that the risk-prediction model relies on specific detail in the pathology report for the description of the number of foci of atypical hyperplasia.

“This model can provide estimates that are more informative to the patient than ‘4.5 times risk of breast cancer.’ However, while a high score might motivate a patient for intervention, most patients in the less than 20% risk category, and so we may not have as much persuasion from this model,” she said.

SAN FRANCISCO – Molecular subtyping of breast tumors with an 80-gene panel appears to be a better predictor of response or resistance to neoadjuvant therapy than do standard techniques and may identify patients who could benefit from dual HER-2 blockade, according to data presented by investigators.

In a prospective trial, molecular subtyping with the BluePrint 80-gene profile (Agendia) classified 23% of tumors into a different subgroup than did immunohistochemical staining and fluorescent in-situ hybridization (IHC/FISH) and identified a sub-group of so-called triple-positive tumors (positive for the HER-2, estrogen and progresterone receptors) with luminal features.

“This triple-positive, 80-gene luminal subtype, is relatively resistant to neoadjuvant chemotherapy with trastuzumab [Herceptin] alone. Pertuzumab [Perjeta] overcame resistance to chemotherapy with trastuzumab in a substantial proportion of the triple-positive 80-gene luminal subtype,” said Dr. Peter Beitsch from the Dallas (Texas) Surgical group, in an oral session at a breast cancer meeting sponsored jointly by the American Society of Clinical Oncology, American Society of Radiation Oncology, and Society of Surgical Oncology. The data were also presented in a poster session.

“This trial was about 4 years long, and over the course of the trial, we saw the triple-positive luminal group get more and more pathologically complete responses, and we finally figured it out. What had happened was that about midway through the trial, pertuzumab became the standard,” Dr. Beitsch said in an interview.

The investigators used the gene profile to subtype tumors from 889 women from the ages of 18 years through 90 years with histologically proven breast cancer who had not yet undergone excision biopsy, axillary dissection, or breast cancer therapy.

Patients were treated with neoadjuvant therapy at the discretion of their oncologists, provided that the regimen was peer-reviewed or accepted by the National Comprehensive Cancer Network.

As noted before, 23% of tumors were classified into a different subgroup than those assigned by ICH/FISH.

The gene profile re-classified 82 of 167 patients (49%) who were classified by IHC/FISH as triple-positive as BluePrint luminal instead. In this subgroup of patients, the pathologic complete response (pCR) rate was 17%. In contrast, of the 72 patients (43%) classified as triple-positive by IHC/FISH and as BluePrint HER2 by the gene profile, the pCR rate was 59%, a statistically significantly better response rate than patients with the BluePrint luminal designation (P = .0001).

The remaining 13 patients (8%) were reclassified as BluePrint basal.

“We looked at the patients who were triple-positive, luminal subtype, and they had an absymal [chance of achieving pathologic complete response] with just trastuzumab and chemotherapy, but, you add in pertuzumab, and it goes up 10-fold,” Dr. Beitsch said.

“Using this particular molecular platform may indeed allow us to better categorize patients over what ICH alone is able to do,” said Dr. William J. Gradishar from the Lurie Comprehensive Cancer Center at Northwestern University in Chicago, Illinois, the invited discussant.

He noted that therapy guided by intrinsic subtype could be even more potent and might result in superior outcomes.

“Of course, in the end, the only way we’re going to be able to definitively address this is by rigorously looking at this in a prospective manner,” he said.

SAN FRANCISCO – Molecular subtyping of breast tumors with an 80-gene panel appears to be a better predictor of response or resistance to neoadjuvant therapy than do standard techniques and may identify patients who could benefit from dual HER-2 blockade, according to data presented by investigators.

In a prospective trial, molecular subtyping with the BluePrint 80-gene profile (Agendia) classified 23% of tumors into a different subgroup than did immunohistochemical staining and fluorescent in-situ hybridization (IHC/FISH) and identified a sub-group of so-called triple-positive tumors (positive for the HER-2, estrogen and progresterone receptors) with luminal features.

“This triple-positive, 80-gene luminal subtype, is relatively resistant to neoadjuvant chemotherapy with trastuzumab [Herceptin] alone. Pertuzumab [Perjeta] overcame resistance to chemotherapy with trastuzumab in a substantial proportion of the triple-positive 80-gene luminal subtype,” said Dr. Peter Beitsch from the Dallas (Texas) Surgical group, in an oral session at a breast cancer meeting sponsored jointly by the American Society of Clinical Oncology, American Society of Radiation Oncology, and Society of Surgical Oncology. The data were also presented in a poster session.

“This trial was about 4 years long, and over the course of the trial, we saw the triple-positive luminal group get more and more pathologically complete responses, and we finally figured it out. What had happened was that about midway through the trial, pertuzumab became the standard,” Dr. Beitsch said in an interview.

The investigators used the gene profile to subtype tumors from 889 women from the ages of 18 years through 90 years with histologically proven breast cancer who had not yet undergone excision biopsy, axillary dissection, or breast cancer therapy.

Patients were treated with neoadjuvant therapy at the discretion of their oncologists, provided that the regimen was peer-reviewed or accepted by the National Comprehensive Cancer Network.

As noted before, 23% of tumors were classified into a different subgroup than those assigned by ICH/FISH.

The gene profile re-classified 82 of 167 patients (49%) who were classified by IHC/FISH as triple-positive as BluePrint luminal instead. In this subgroup of patients, the pathologic complete response (pCR) rate was 17%. In contrast, of the 72 patients (43%) classified as triple-positive by IHC/FISH and as BluePrint HER2 by the gene profile, the pCR rate was 59%, a statistically significantly better response rate than patients with the BluePrint luminal designation (P = .0001).

The remaining 13 patients (8%) were reclassified as BluePrint basal.

“We looked at the patients who were triple-positive, luminal subtype, and they had an absymal [chance of achieving pathologic complete response] with just trastuzumab and chemotherapy, but, you add in pertuzumab, and it goes up 10-fold,” Dr. Beitsch said.

“Using this particular molecular platform may indeed allow us to better categorize patients over what ICH alone is able to do,” said Dr. William J. Gradishar from the Lurie Comprehensive Cancer Center at Northwestern University in Chicago, Illinois, the invited discussant.

He noted that therapy guided by intrinsic subtype could be even more potent and might result in superior outcomes.

“Of course, in the end, the only way we’re going to be able to definitively address this is by rigorously looking at this in a prospective manner,” he said.

SAN FRANCISCO – Molecular subtyping of breast tumors with an 80-gene panel appears to be a better predictor of response or resistance to neoadjuvant therapy than do standard techniques and may identify patients who could benefit from dual HER-2 blockade, according to data presented by investigators.

In a prospective trial, molecular subtyping with the BluePrint 80-gene profile (Agendia) classified 23% of tumors into a different subgroup than did immunohistochemical staining and fluorescent in-situ hybridization (IHC/FISH) and identified a sub-group of so-called triple-positive tumors (positive for the HER-2, estrogen and progresterone receptors) with luminal features.

“This triple-positive, 80-gene luminal subtype, is relatively resistant to neoadjuvant chemotherapy with trastuzumab [Herceptin] alone. Pertuzumab [Perjeta] overcame resistance to chemotherapy with trastuzumab in a substantial proportion of the triple-positive 80-gene luminal subtype,” said Dr. Peter Beitsch from the Dallas (Texas) Surgical group, in an oral session at a breast cancer meeting sponsored jointly by the American Society of Clinical Oncology, American Society of Radiation Oncology, and Society of Surgical Oncology. The data were also presented in a poster session.

“This trial was about 4 years long, and over the course of the trial, we saw the triple-positive luminal group get more and more pathologically complete responses, and we finally figured it out. What had happened was that about midway through the trial, pertuzumab became the standard,” Dr. Beitsch said in an interview.

The investigators used the gene profile to subtype tumors from 889 women from the ages of 18 years through 90 years with histologically proven breast cancer who had not yet undergone excision biopsy, axillary dissection, or breast cancer therapy.

Patients were treated with neoadjuvant therapy at the discretion of their oncologists, provided that the regimen was peer-reviewed or accepted by the National Comprehensive Cancer Network.

As noted before, 23% of tumors were classified into a different subgroup than those assigned by ICH/FISH.

The gene profile re-classified 82 of 167 patients (49%) who were classified by IHC/FISH as triple-positive as BluePrint luminal instead. In this subgroup of patients, the pathologic complete response (pCR) rate was 17%. In contrast, of the 72 patients (43%) classified as triple-positive by IHC/FISH and as BluePrint HER2 by the gene profile, the pCR rate was 59%, a statistically significantly better response rate than patients with the BluePrint luminal designation (P = .0001).

The remaining 13 patients (8%) were reclassified as BluePrint basal.

“We looked at the patients who were triple-positive, luminal subtype, and they had an absymal [chance of achieving pathologic complete response] with just trastuzumab and chemotherapy, but, you add in pertuzumab, and it goes up 10-fold,” Dr. Beitsch said.

“Using this particular molecular platform may indeed allow us to better categorize patients over what ICH alone is able to do,” said Dr. William J. Gradishar from the Lurie Comprehensive Cancer Center at Northwestern University in Chicago, Illinois, the invited discussant.

He noted that therapy guided by intrinsic subtype could be even more potent and might result in superior outcomes.

“Of course, in the end, the only way we’re going to be able to definitively address this is by rigorously looking at this in a prospective manner,” he said.

SAN FRANCISCO – MRI-screening may improve the detection of biologically relevant breast cancer in women who are at average-risk, and reduce the interval-cancer rate down to 0%, at a low false-positive rate, say the authors of a new study presented at the 2015 Breast Cancer Symposium.

In this cohort of heavily pre-screened women at average risk, the additional cancer yield achieved through MRI was high, at 15.8 cases per 1,000 women screened, and the added cancers diagnosed by MRI tended to be of high nuclear grade.

“MRI improves the detection of small high grade cancers in women at average risk, to the extent that the interval cancer rate was zero,” said Dr. Christiane Kuhl, of the University of Aachen, Germany.

“Between 30% and 50% of cancers identified in women who undergo screening mammography are not detected by mammography,” she said during her presentation.

Breast cancer continues to be the main or second most important cause of cancer death in women, and is the main cause of life years lost in women. “Which tells you that the main problem with mammography screening is not overdiagnosis,” she said. “The main problem is actually underdiagnois of disease.”

Breast MRI is currently recommended for screening women who are at a high-risk of breast-cancer, but despite decades of mammographic screening, breast cancer continues to cause high mortality for women who are deemed to be at an average risk of the disease. These data suggest that there is a need for improved methods of early diagnosis in this population.

Dr. Kuhl and her colleagues investigated the utility of supplemental MRI-screening of women who carry an average-risk of breast-cancer, and they conducted a prospective observational cohort-study that assessed the use of MRI screening in this population. The participants were in the usual age range for screening-mammography (40-70 years).

The women underwent dynamic contrast-enhanced MRI of the breast in addition to mammography every 12, 24, or 36 months, plus follow-up of 2 years to establish a standard-of-reference. The cohort included 2,120 women who underwent a total 3,861 MRI screenings.

Breast-cancer was diagnosed in 61 women (DCIS: 20, invasive: 41), and the rate of interval cancers was 0%, irrespective of screening interval. Of these women, 48 were diagnosed at prevalence-screening by MRI alone (supplemental cancer detection rate: 22.6 cases per 1,000 women screened. In addition, 13 women were diagnosed with breast-cancer in 1,741 incidence-screening-rounds collected over 4,887 women-years. A total 12 of these 13 incident cancers were diagnosed by screening-MRI alone (supplemental cancer detection rate was 6.9 per 1,000), one by MRI and mammography, and none were by mammography alone.

The authors also found that the supplemental cancer detection rate was independent of mammographic breast density. Invasive cancers were small, with a mean size of 8mm. They were node-negative in 93.4%, ER/PR-negative in 32.8%, and de-differentiated in 41.7% at prevalence, and 46% at incidence-screening. The specificity of MRI-screening was 97.1%, while false positive rate was 2.9%.

In a discussion of the paper, Dr. A. Marilyn Leitch, of the University of Texas Southwestern Medical Center, Dallas, pointed out that this was a selected population with negative mammograms. But is it possible to “apply MRI at longer intervals, say every 3 years, without initial mammography as a screening tool, in average risk women?” she asked

One of her concerns, however, is that “we hear all the time about the high false positive rates with MRI,” and they are generally higher than was reported in this study. “MRI also detects lesions that might drive patients to avoid breast conserving surgery, and there can be unreasonable costs for screening and work up of false positives.”

Screening guidelines from the USPSTF say that evidence for replacing mammography with MRI is lacking and the balance of benefit versus harms cannot be determined. “Even more ‘liberal’ guidelines from the American Cancer Society reserve MRI for high risk patients.”

What is needed is a clinical trial, she summarized, that will compare screening MRI at 3 year intervals to tomosynthesis mammogram annually in average risk women.

SAN FRANCISCO – MRI-screening may improve the detection of biologically relevant breast cancer in women who are at average-risk, and reduce the interval-cancer rate down to 0%, at a low false-positive rate, say the authors of a new study presented at the 2015 Breast Cancer Symposium.

In this cohort of heavily pre-screened women at average risk, the additional cancer yield achieved through MRI was high, at 15.8 cases per 1,000 women screened, and the added cancers diagnosed by MRI tended to be of high nuclear grade.

“MRI improves the detection of small high grade cancers in women at average risk, to the extent that the interval cancer rate was zero,” said Dr. Christiane Kuhl, of the University of Aachen, Germany.

“Between 30% and 50% of cancers identified in women who undergo screening mammography are not detected by mammography,” she said during her presentation.

Breast cancer continues to be the main or second most important cause of cancer death in women, and is the main cause of life years lost in women. “Which tells you that the main problem with mammography screening is not overdiagnosis,” she said. “The main problem is actually underdiagnois of disease.”

Breast MRI is currently recommended for screening women who are at a high-risk of breast-cancer, but despite decades of mammographic screening, breast cancer continues to cause high mortality for women who are deemed to be at an average risk of the disease. These data suggest that there is a need for improved methods of early diagnosis in this population.

Dr. Kuhl and her colleagues investigated the utility of supplemental MRI-screening of women who carry an average-risk of breast-cancer, and they conducted a prospective observational cohort-study that assessed the use of MRI screening in this population. The participants were in the usual age range for screening-mammography (40-70 years).

The women underwent dynamic contrast-enhanced MRI of the breast in addition to mammography every 12, 24, or 36 months, plus follow-up of 2 years to establish a standard-of-reference. The cohort included 2,120 women who underwent a total 3,861 MRI screenings.

Breast-cancer was diagnosed in 61 women (DCIS: 20, invasive: 41), and the rate of interval cancers was 0%, irrespective of screening interval. Of these women, 48 were diagnosed at prevalence-screening by MRI alone (supplemental cancer detection rate: 22.6 cases per 1,000 women screened. In addition, 13 women were diagnosed with breast-cancer in 1,741 incidence-screening-rounds collected over 4,887 women-years. A total 12 of these 13 incident cancers were diagnosed by screening-MRI alone (supplemental cancer detection rate was 6.9 per 1,000), one by MRI and mammography, and none were by mammography alone.

The authors also found that the supplemental cancer detection rate was independent of mammographic breast density. Invasive cancers were small, with a mean size of 8mm. They were node-negative in 93.4%, ER/PR-negative in 32.8%, and de-differentiated in 41.7% at prevalence, and 46% at incidence-screening. The specificity of MRI-screening was 97.1%, while false positive rate was 2.9%.

In a discussion of the paper, Dr. A. Marilyn Leitch, of the University of Texas Southwestern Medical Center, Dallas, pointed out that this was a selected population with negative mammograms. But is it possible to “apply MRI at longer intervals, say every 3 years, without initial mammography as a screening tool, in average risk women?” she asked

One of her concerns, however, is that “we hear all the time about the high false positive rates with MRI,” and they are generally higher than was reported in this study. “MRI also detects lesions that might drive patients to avoid breast conserving surgery, and there can be unreasonable costs for screening and work up of false positives.”

Screening guidelines from the USPSTF say that evidence for replacing mammography with MRI is lacking and the balance of benefit versus harms cannot be determined. “Even more ‘liberal’ guidelines from the American Cancer Society reserve MRI for high risk patients.”

What is needed is a clinical trial, she summarized, that will compare screening MRI at 3 year intervals to tomosynthesis mammogram annually in average risk women.

SAN FRANCISCO – MRI-screening may improve the detection of biologically relevant breast cancer in women who are at average-risk, and reduce the interval-cancer rate down to 0%, at a low false-positive rate, say the authors of a new study presented at the 2015 Breast Cancer Symposium.

In this cohort of heavily pre-screened women at average risk, the additional cancer yield achieved through MRI was high, at 15.8 cases per 1,000 women screened, and the added cancers diagnosed by MRI tended to be of high nuclear grade.

“MRI improves the detection of small high grade cancers in women at average risk, to the extent that the interval cancer rate was zero,” said Dr. Christiane Kuhl, of the University of Aachen, Germany.

“Between 30% and 50% of cancers identified in women who undergo screening mammography are not detected by mammography,” she said during her presentation.

Breast cancer continues to be the main or second most important cause of cancer death in women, and is the main cause of life years lost in women. “Which tells you that the main problem with mammography screening is not overdiagnosis,” she said. “The main problem is actually underdiagnois of disease.”

Breast MRI is currently recommended for screening women who are at a high-risk of breast-cancer, but despite decades of mammographic screening, breast cancer continues to cause high mortality for women who are deemed to be at an average risk of the disease. These data suggest that there is a need for improved methods of early diagnosis in this population.

Dr. Kuhl and her colleagues investigated the utility of supplemental MRI-screening of women who carry an average-risk of breast-cancer, and they conducted a prospective observational cohort-study that assessed the use of MRI screening in this population. The participants were in the usual age range for screening-mammography (40-70 years).

The women underwent dynamic contrast-enhanced MRI of the breast in addition to mammography every 12, 24, or 36 months, plus follow-up of 2 years to establish a standard-of-reference. The cohort included 2,120 women who underwent a total 3,861 MRI screenings.

Breast-cancer was diagnosed in 61 women (DCIS: 20, invasive: 41), and the rate of interval cancers was 0%, irrespective of screening interval. Of these women, 48 were diagnosed at prevalence-screening by MRI alone (supplemental cancer detection rate: 22.6 cases per 1,000 women screened. In addition, 13 women were diagnosed with breast-cancer in 1,741 incidence-screening-rounds collected over 4,887 women-years. A total 12 of these 13 incident cancers were diagnosed by screening-MRI alone (supplemental cancer detection rate was 6.9 per 1,000), one by MRI and mammography, and none were by mammography alone.

The authors also found that the supplemental cancer detection rate was independent of mammographic breast density. Invasive cancers were small, with a mean size of 8mm. They were node-negative in 93.4%, ER/PR-negative in 32.8%, and de-differentiated in 41.7% at prevalence, and 46% at incidence-screening. The specificity of MRI-screening was 97.1%, while false positive rate was 2.9%.

In a discussion of the paper, Dr. A. Marilyn Leitch, of the University of Texas Southwestern Medical Center, Dallas, pointed out that this was a selected population with negative mammograms. But is it possible to “apply MRI at longer intervals, say every 3 years, without initial mammography as a screening tool, in average risk women?” she asked

One of her concerns, however, is that “we hear all the time about the high false positive rates with MRI,” and they are generally higher than was reported in this study. “MRI also detects lesions that might drive patients to avoid breast conserving surgery, and there can be unreasonable costs for screening and work up of false positives.”

Screening guidelines from the USPSTF say that evidence for replacing mammography with MRI is lacking and the balance of benefit versus harms cannot be determined. “Even more ‘liberal’ guidelines from the American Cancer Society reserve MRI for high risk patients.”

What is needed is a clinical trial, she summarized, that will compare screening MRI at 3 year intervals to tomosynthesis mammogram annually in average risk women.

SAN FRANCISCO – The use of aromatase inhibitors (AIs) in the adjuvant setting appears to delay the development of contralateral breast cancer, and this effect was particularly prevalent among breast cancer patients who were BRCA positive, according to findings presented here at the 2015 Breast Cancer Symposium.

“AI use was suggestive of a decreased risk in all patients with a P value of .08, which was not statistically significant,” said Dr. Maryam Nemati Shafaee, from the University of Texas M.D. Anderson Cancer Center, Houston, who presented the results of her study. “However among patients with BRCA mutation, AI use was significantly associated with a smaller hazard of developing contralateral breast cancer with a P value of .04.”

“This may give these patients an option other than prophylactic mastectomy,” she said.

The risk of contralateral breast cancer in women who are carriers of BRCA1 and 2 mutations is up to 64%. Those with estrogen receptor positive (ER+) disease are offered tamoxifen or AIs adjuvantly. Some studies have suggested that tamoxifen might be able to reduce the risk of contralateral breast cancer in this population, but results have been conflicting.

“There is no final conclusion on the use of tamoxifen in preventing contralateral breast cancer in BRCA mutation carriers,” said Dr. Shafee, “And there are no such data on the effect of AIs.”

Dr. Shafee and her colleagues identified 2,520 patients known to carry a BRCA mutation from a prospectively maintained database, and, of that number, 486 breast cancer patients with known BRCA status were included in the final analysis.

Of these patients, the majority were diagnosed under the age of 50 years, and the majority had not undergone prophylactic mastectomy. Most patients had received tamoxifen only (60%), 21% had received tamoxifen and AIs sequentially, and 16% had received AIs only.

The median follow up 8.6 years.

Upon univariate analysis, only BRCA status was associated with a risk of contralateral breast cancer (P= .04). “Interestingly AI use was suggestive to lead to decreased risk (P value of .08) but did not reach statistical significance,” said Dr. Shafee.

In multivariate analysis, BRCA status was significantly associated with an increased risk of contralateral breast cancer. AI was again suggestive of a decreased risk (P= .08).

BRCA mutation status was also significantly associated with shorter time to the development of contralateral breast cancer (P= .047), compared with patients who were BRCA negative. AI treatment was marginally significantly associated with time to the development of contralateral breast cancer (P= .088), as compared with patients who didn’t receive this treatment. Those who received AI therapy had a smaller hazard of cancer development in the other breast.

The effect on risk of cancer in the second breast was not statistically associated with age, HER2 status, TNM stage, and tamoxifen use.

Dr. Shafee noted that the study had several limitations, one being the relatively small sample size of BRCA 1&2 mutation carriers with hormone positive tumors. “Validation of our findings based on a larger cohort of BRCA mutation carriers who have received endocrine therapy in adjuvant setting is recommended,” she said.

Dr. William J. Gradishar, of the Lurie COmprehensive Cancer Center of Northwestern University, Chicago, noted that while the data are impressive, he agreed with Dr. Shafee that the “numbers are simply too small to make any sweeping recommendations based on these data.”

In his discussion of the popular, he also posed the question if these patients are really a reflection of BRCA mutation carriers, being that they are largely ER+. “The conclusions are intriguing and value further evaluation, and I would caution the use of this broadly in this use of individuals,” noted Dr. Gradishar.

SAN FRANCISCO – The use of aromatase inhibitors (AIs) in the adjuvant setting appears to delay the development of contralateral breast cancer, and this effect was particularly prevalent among breast cancer patients who were BRCA positive, according to findings presented here at the 2015 Breast Cancer Symposium.

“AI use was suggestive of a decreased risk in all patients with a P value of .08, which was not statistically significant,” said Dr. Maryam Nemati Shafaee, from the University of Texas M.D. Anderson Cancer Center, Houston, who presented the results of her study. “However among patients with BRCA mutation, AI use was significantly associated with a smaller hazard of developing contralateral breast cancer with a P value of .04.”

“This may give these patients an option other than prophylactic mastectomy,” she said.

The risk of contralateral breast cancer in women who are carriers of BRCA1 and 2 mutations is up to 64%. Those with estrogen receptor positive (ER+) disease are offered tamoxifen or AIs adjuvantly. Some studies have suggested that tamoxifen might be able to reduce the risk of contralateral breast cancer in this population, but results have been conflicting.

“There is no final conclusion on the use of tamoxifen in preventing contralateral breast cancer in BRCA mutation carriers,” said Dr. Shafee, “And there are no such data on the effect of AIs.”

Dr. Shafee and her colleagues identified 2,520 patients known to carry a BRCA mutation from a prospectively maintained database, and, of that number, 486 breast cancer patients with known BRCA status were included in the final analysis.

Of these patients, the majority were diagnosed under the age of 50 years, and the majority had not undergone prophylactic mastectomy. Most patients had received tamoxifen only (60%), 21% had received tamoxifen and AIs sequentially, and 16% had received AIs only.

The median follow up 8.6 years.

Upon univariate analysis, only BRCA status was associated with a risk of contralateral breast cancer (P= .04). “Interestingly AI use was suggestive to lead to decreased risk (P value of .08) but did not reach statistical significance,” said Dr. Shafee.

In multivariate analysis, BRCA status was significantly associated with an increased risk of contralateral breast cancer. AI was again suggestive of a decreased risk (P= .08).

BRCA mutation status was also significantly associated with shorter time to the development of contralateral breast cancer (P= .047), compared with patients who were BRCA negative. AI treatment was marginally significantly associated with time to the development of contralateral breast cancer (P= .088), as compared with patients who didn’t receive this treatment. Those who received AI therapy had a smaller hazard of cancer development in the other breast.

The effect on risk of cancer in the second breast was not statistically associated with age, HER2 status, TNM stage, and tamoxifen use.

Dr. Shafee noted that the study had several limitations, one being the relatively small sample size of BRCA 1&2 mutation carriers with hormone positive tumors. “Validation of our findings based on a larger cohort of BRCA mutation carriers who have received endocrine therapy in adjuvant setting is recommended,” she said.

Dr. William J. Gradishar, of the Lurie COmprehensive Cancer Center of Northwestern University, Chicago, noted that while the data are impressive, he agreed with Dr. Shafee that the “numbers are simply too small to make any sweeping recommendations based on these data.”

In his discussion of the popular, he also posed the question if these patients are really a reflection of BRCA mutation carriers, being that they are largely ER+. “The conclusions are intriguing and value further evaluation, and I would caution the use of this broadly in this use of individuals,” noted Dr. Gradishar.

SAN FRANCISCO – The use of aromatase inhibitors (AIs) in the adjuvant setting appears to delay the development of contralateral breast cancer, and this effect was particularly prevalent among breast cancer patients who were BRCA positive, according to findings presented here at the 2015 Breast Cancer Symposium.

“AI use was suggestive of a decreased risk in all patients with a P value of .08, which was not statistically significant,” said Dr. Maryam Nemati Shafaee, from the University of Texas M.D. Anderson Cancer Center, Houston, who presented the results of her study. “However among patients with BRCA mutation, AI use was significantly associated with a smaller hazard of developing contralateral breast cancer with a P value of .04.”

“This may give these patients an option other than prophylactic mastectomy,” she said.

The risk of contralateral breast cancer in women who are carriers of BRCA1 and 2 mutations is up to 64%. Those with estrogen receptor positive (ER+) disease are offered tamoxifen or AIs adjuvantly. Some studies have suggested that tamoxifen might be able to reduce the risk of contralateral breast cancer in this population, but results have been conflicting.

“There is no final conclusion on the use of tamoxifen in preventing contralateral breast cancer in BRCA mutation carriers,” said Dr. Shafee, “And there are no such data on the effect of AIs.”

Dr. Shafee and her colleagues identified 2,520 patients known to carry a BRCA mutation from a prospectively maintained database, and, of that number, 486 breast cancer patients with known BRCA status were included in the final analysis.

Of these patients, the majority were diagnosed under the age of 50 years, and the majority had not undergone prophylactic mastectomy. Most patients had received tamoxifen only (60%), 21% had received tamoxifen and AIs sequentially, and 16% had received AIs only.

The median follow up 8.6 years.

Upon univariate analysis, only BRCA status was associated with a risk of contralateral breast cancer (P= .04). “Interestingly AI use was suggestive to lead to decreased risk (P value of .08) but did not reach statistical significance,” said Dr. Shafee.

In multivariate analysis, BRCA status was significantly associated with an increased risk of contralateral breast cancer. AI was again suggestive of a decreased risk (P= .08).

BRCA mutation status was also significantly associated with shorter time to the development of contralateral breast cancer (P= .047), compared with patients who were BRCA negative. AI treatment was marginally significantly associated with time to the development of contralateral breast cancer (P= .088), as compared with patients who didn’t receive this treatment. Those who received AI therapy had a smaller hazard of cancer development in the other breast.

The effect on risk of cancer in the second breast was not statistically associated with age, HER2 status, TNM stage, and tamoxifen use.

Dr. Shafee noted that the study had several limitations, one being the relatively small sample size of BRCA 1&2 mutation carriers with hormone positive tumors. “Validation of our findings based on a larger cohort of BRCA mutation carriers who have received endocrine therapy in adjuvant setting is recommended,” she said.

Dr. William J. Gradishar, of the Lurie COmprehensive Cancer Center of Northwestern University, Chicago, noted that while the data are impressive, he agreed with Dr. Shafee that the “numbers are simply too small to make any sweeping recommendations based on these data.”

In his discussion of the popular, he also posed the question if these patients are really a reflection of BRCA mutation carriers, being that they are largely ER+. “The conclusions are intriguing and value further evaluation, and I would caution the use of this broadly in this use of individuals,” noted Dr. Gradishar.