SABCS 2011

SAN ANTONIO – A new meta-analysis challenges the notion that breast cancer risk is inversely related to serum vitamin D level.

The meta-analysis included 16 published studies deemed by investigators to have made the grade in terms of scientific rigor. In 10 studies, vitamin D was measured before diagnosis of breast cancer, while in the other 6 studies, blood samples were gathered for measurement of vitamin D only after the diagnosis.

When data from all 16 studies were pooled, lower vitamin D levels were associated with a significant 1.5-fold increased rate of breast cancer (P less than .001). So far so good for the theory that low vitamin D might be causally related to breast cancer, and by extension for the corollary that vitamin D supplementation might be an effective option for breast cancer prevention.

However, a major difficulty with this line of thinking arose when the two groups of studies were analyzed separately, Dr. Eitan Amir explained at the San Antonio Breast Cancer Symposium.

Indeed, only 1 of the 10 studies in which vitamin D was measured before diagnosis of breast cancer showed a significant relationship between low levels of vitamin D and subsequent increased likelihood of the malignancy.

In contrast, all six studies in which serum vitamin D was measured following diagnosis of breast cancer showed a significant inverse relationship. In the pooled analysis of these six studies, lower serum vitamin D was associated with a highly significant, 2.63-fold increased likelihood of breast cancer (P less than .001), according to Dr. Amir of the University of Toronto.

Breast cancer cells have been shown to express vitamin D catalytic enzymes that may interfere with accurate measurement of serum levels of the vitamin, added Dr. Amir.

Dr. Amir declared having no relevant financial interests.

SAN ANTONIO – A new meta-analysis challenges the notion that breast cancer risk is inversely related to serum vitamin D level.

The meta-analysis included 16 published studies deemed by investigators to have made the grade in terms of scientific rigor. In 10 studies, vitamin D was measured before diagnosis of breast cancer, while in the other 6 studies, blood samples were gathered for measurement of vitamin D only after the diagnosis.

When data from all 16 studies were pooled, lower vitamin D levels were associated with a significant 1.5-fold increased rate of breast cancer (P less than .001). So far so good for the theory that low vitamin D might be causally related to breast cancer, and by extension for the corollary that vitamin D supplementation might be an effective option for breast cancer prevention.

However, a major difficulty with this line of thinking arose when the two groups of studies were analyzed separately, Dr. Eitan Amir explained at the San Antonio Breast Cancer Symposium.

Indeed, only 1 of the 10 studies in which vitamin D was measured before diagnosis of breast cancer showed a significant relationship between low levels of vitamin D and subsequent increased likelihood of the malignancy.

In contrast, all six studies in which serum vitamin D was measured following diagnosis of breast cancer showed a significant inverse relationship. In the pooled analysis of these six studies, lower serum vitamin D was associated with a highly significant, 2.63-fold increased likelihood of breast cancer (P less than .001), according to Dr. Amir of the University of Toronto.

Breast cancer cells have been shown to express vitamin D catalytic enzymes that may interfere with accurate measurement of serum levels of the vitamin, added Dr. Amir.

Dr. Amir declared having no relevant financial interests.

SAN ANTONIO – A new meta-analysis challenges the notion that breast cancer risk is inversely related to serum vitamin D level.

The meta-analysis included 16 published studies deemed by investigators to have made the grade in terms of scientific rigor. In 10 studies, vitamin D was measured before diagnosis of breast cancer, while in the other 6 studies, blood samples were gathered for measurement of vitamin D only after the diagnosis.

When data from all 16 studies were pooled, lower vitamin D levels were associated with a significant 1.5-fold increased rate of breast cancer (P less than .001). So far so good for the theory that low vitamin D might be causally related to breast cancer, and by extension for the corollary that vitamin D supplementation might be an effective option for breast cancer prevention.

However, a major difficulty with this line of thinking arose when the two groups of studies were analyzed separately, Dr. Eitan Amir explained at the San Antonio Breast Cancer Symposium.

Indeed, only 1 of the 10 studies in which vitamin D was measured before diagnosis of breast cancer showed a significant relationship between low levels of vitamin D and subsequent increased likelihood of the malignancy.

In contrast, all six studies in which serum vitamin D was measured following diagnosis of breast cancer showed a significant inverse relationship. In the pooled analysis of these six studies, lower serum vitamin D was associated with a highly significant, 2.63-fold increased likelihood of breast cancer (P less than .001), according to Dr. Amir of the University of Toronto.

Breast cancer cells have been shown to express vitamin D catalytic enzymes that may interfere with accurate measurement of serum levels of the vitamin, added Dr. Amir.

Dr. Amir declared having no relevant financial interests.

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.

SAN ANTONIO – Universal testing with the 21-gene Oncotype DX assay at diagnosis of estrogen receptor–positive breast cancer could save $330.8 million annually in the United States through avoidance of ineffective chemotherapy, according to a retrospective study involving analysis of nearly 200,000 estrogen receptor-positive tumor samples.

"We believe a low risk score on the assay is presently the most reliable biomarker for a chemotherapy-resistant phenotype. And we believe that the excess harm of chemotherapy outweighs the potential benefit of chemotherapy for those patients," Dr. Joseph Ragaz declared at the San Antonio Breast Cancer Symposium.

His analysis of tumor samples from 196,967 estrogen receptor–positive breast cancer patients in assay parent company Genomic Health’s database showed that a low 10-year recurrence risk score on the Oncotype DX assay – that is, a score of less than 18 – was more common among patients with axillary node–positive women than node-negative women. A low risk score was present in 59% of the nearly 14,000 patients with node-positive disease, compared with 54% of those with node-negative disease.

Prior major retrospective studies have shown no significant benefit of adjuvant chemotherapy in estrogen receptor–positive breast cancer patients with a low risk score on the assay, regardless of whether they had node-positive (Lancet Oncology 2010;11:55-65) or node-negative disease (J. Clin. Oncol. 2006;24:3726-34).

With an estimated 225,000 new cases of breast cancer per year in the United States, there are 94,500 patients who are estrogen receptor–positive and could be considered candidates for chemotherapy according to current widespread practice. At an estimated cost of chemotherapy of $15,000 per patient and $4,000 per Oncotype DX assay, avoidance of chemotherapy in all such patients who have a low risk score on the assay would save $330.8 million annually in the United States, according to Dr. Ragaz of the University of British Columbia, Vancouver.

In light of these data, he argued that both ethics and economics dictate universal Oncotype DX testing should be done in all estrogen receptor–positive breast cancer patients who are candidates for chemotherapy, regardless of their axillary node status. Moreover, practice guidelines should be revised to avoid chemotherapy in all patients with a low risk score, regardless of nodal status.

"Until prospective randomized trials confirm chemotherapy benefit among low risk score patients, its use among these chemotherapy-resistant cases should be considered investigational," Dr. Ragaz asserted.

"Pretty strong stuff," said session chair Dr. Thomas J. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

"You’re suggesting that we should really change our whole way of practice, and everyone who’s estrogen receptor–positive should have the Oncotype DX, and that should be the basis on which we give chemotherapy," he said as Dr. Ragaz nodded in agreement.

It’s a proposal with considerable appeal, Dr. Smith said. Not only would it save one-third of a billion dollars annually in avoided ineffective chemotherapy – at a time when oncology is increasingly drawing criticism for wasteful spending – but women with a low risk score would also be spared the associated chemotherapy toxicities. Not to mention the patient inconvenience and travel time entailed in a year’s worth of adjuvant chemotherapy. Indeed, this strategy would generate considerable additional savings in terms of the large carbon footprint it would erase, he added.

Yet there might be a much less expensive alternative to the Oncotype DX assay that could accomplish the same thing, according to Dr. Smith. He cited a recent retrospective study by investigators at the University of London, who analyzed tumor specimens from 1,125 estrogen receptor–positive breast cancer patients who participated in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

The investigators compared the predictive accuracy of the Oncotype DX assay in terms of the end point of distant recurrence with that of a score derived from four standard immunohistochemical (IHC) tests for estrogen-, progesterone-, and HER2-receptor status along with the tumor marker Ki-67. The London group called this four-test panel the IHC4. The predictive accuracy of the two tests was essentially the same (J. Clin. Oncol. 2011;29:4273-8). Yet the cost of the IHC4 is but a small fraction of the $4,000-plus for the proprietary Oncotype DX assay.

"Hopefully this can be replicated very quickly. It might actually be an alternative that would be much less expensive," Dr. Smith commented.

Audience member Dr. Laura J. Esserman rose to say the entire California state university system-wide breast health program is planning to adopt the IHC4.

"It’s cheap and gives you just about the same information as the Oncotype DX. The key is to see that physicians will then follow that information, and that’s something that’s under our control. We can spare people therapies that are toxic and don’t help them," said Dr. Esserman, director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco.

Dr. Ragaz said that while he believes the IHC4 has potential, it has not been prospectively validated as a predictor of benefit from chemotherapy.

And Dr. Simon D.H. Holt, who presented a favorable cost-effectiveness analysis of the Oncotype DX assay in clinical practice in the United Kingdom, cautioned that Ki-67 assay results vary considerably between laboratories.

"There are problems with Ki-67. One of the great advantages of Oncotype DX is its central laboratory with extremely tight quality assurance. It’s very repeatable. At the moment, in my opinion, it’s certainly the best thing on the market," said Dr. Holt of Prince Philip Hospital in Llanelli, Wales.

Genomic Health supported the study. Dr Ragaz, Dr. Smith, and Dr. Holt declared having no relevant financial relationships.

SAN ANTONIO – Acupuncture for the reduction of aromatase inhibitor–related musculoskeletal symptoms in breast cancer patients proved a disappointment in an interim analysis of a double-blind, randomized, sham-controlled, multicenter clinical trial.

Both real and sham acupuncture turned out to provide similar reductions in the Health Assessment Questionnaire Disability Index (HAQ-DI), the primary study end point. The two groups also experienced similar improvement in scores on a pain visual analog scale after eight weekly real or sham treatment sessions, Dr. Ting Bao reported at the San Antonio Breast Cancer Symposium.

©Liang Zhang/iStockphoto.com

The double-blind randomized trial included 47 postmenopausal women with early-stage breast cancer who were experiencing musculoskeletal symptoms related to aromatase inhibitor use. None of the patients had received acupuncture in the previous year.

The acupuncture group received eight weekly sessions targeting 15 acupuncture points. The control group got a sham acupuncture procedure at 14 non-acupuncture points. The sham therapy utilized the Park Sham Device, which consists of a nonpenetrating, retractable acupuncture needle and an adhesive tube. From a median baseline HAQ-DI score of 0.75, 8 of 23 patients in the real acupuncture group achieved the minimum clinically important improvement, predefined as a 0.22-point reduction. So did 13 of 24 women in the sham acupuncture group.

Pain scores on a visual analog scale improved to a similar extent in the two study arms, from a baseline median of 50 out of a possible 100 to 41 in the real acupuncture group and 36 in the sham group.

When the blinded patients were asked to guess their treatment assignment, 55% in each group did so accurately, according to Dr. Bao, a medical oncologist and licensed acupuncturist at the University of Maryland Greenebaum Cancer Center, Baltimore.

Plasma estradiol levels remained undetectable in most patients during the study period.

No significant side effects were noted in either study arm.

About half of breast cancer patients on adjuvant aromatase inhibitor therapy experience musculoskeletal symptoms. These side effects can be sufficiently debilitating as to lead to poor compliance or even treatment discontinuation.

Among the possible explanations for the negative results in this study are that the HAQ-DI may not be a sufficiently sensitive tool to detect small differences in effectiveness between real and sham acupuncture, and that sham acupuncture may not be an inert procedure, Dr. Bao said.

Although this randomized trial originally was scheduled to enroll 100 patients, it was halted early for futility based on the interim results.

The study was funded by a Komen grant and an ASCO Young Investigator Award. Dr. Bao declared having no financial conflicts.

SAN ANTONIO – Acupuncture for the reduction of aromatase inhibitor–related musculoskeletal symptoms in breast cancer patients proved a disappointment in an interim analysis of a double-blind, randomized, sham-controlled, multicenter clinical trial.

Both real and sham acupuncture turned out to provide similar reductions in the Health Assessment Questionnaire Disability Index (HAQ-DI), the primary study end point. The two groups also experienced similar improvement in scores on a pain visual analog scale after eight weekly real or sham treatment sessions, Dr. Ting Bao reported at the San Antonio Breast Cancer Symposium.

©Liang Zhang/iStockphoto.com

The double-blind randomized trial included 47 postmenopausal women with early-stage breast cancer who were experiencing musculoskeletal symptoms related to aromatase inhibitor use. None of the patients had received acupuncture in the previous year.

The acupuncture group received eight weekly sessions targeting 15 acupuncture points. The control group got a sham acupuncture procedure at 14 non-acupuncture points. The sham therapy utilized the Park Sham Device, which consists of a nonpenetrating, retractable acupuncture needle and an adhesive tube. From a median baseline HAQ-DI score of 0.75, 8 of 23 patients in the real acupuncture group achieved the minimum clinically important improvement, predefined as a 0.22-point reduction. So did 13 of 24 women in the sham acupuncture group.

Pain scores on a visual analog scale improved to a similar extent in the two study arms, from a baseline median of 50 out of a possible 100 to 41 in the real acupuncture group and 36 in the sham group.

When the blinded patients were asked to guess their treatment assignment, 55% in each group did so accurately, according to Dr. Bao, a medical oncologist and licensed acupuncturist at the University of Maryland Greenebaum Cancer Center, Baltimore.

Plasma estradiol levels remained undetectable in most patients during the study period.

No significant side effects were noted in either study arm.

About half of breast cancer patients on adjuvant aromatase inhibitor therapy experience musculoskeletal symptoms. These side effects can be sufficiently debilitating as to lead to poor compliance or even treatment discontinuation.

Among the possible explanations for the negative results in this study are that the HAQ-DI may not be a sufficiently sensitive tool to detect small differences in effectiveness between real and sham acupuncture, and that sham acupuncture may not be an inert procedure, Dr. Bao said.

Although this randomized trial originally was scheduled to enroll 100 patients, it was halted early for futility based on the interim results.

The study was funded by a Komen grant and an ASCO Young Investigator Award. Dr. Bao declared having no financial conflicts.

SAN ANTONIO – Acupuncture for the reduction of aromatase inhibitor–related musculoskeletal symptoms in breast cancer patients proved a disappointment in an interim analysis of a double-blind, randomized, sham-controlled, multicenter clinical trial.

Both real and sham acupuncture turned out to provide similar reductions in the Health Assessment Questionnaire Disability Index (HAQ-DI), the primary study end point. The two groups also experienced similar improvement in scores on a pain visual analog scale after eight weekly real or sham treatment sessions, Dr. Ting Bao reported at the San Antonio Breast Cancer Symposium.

©Liang Zhang/iStockphoto.com

The double-blind randomized trial included 47 postmenopausal women with early-stage breast cancer who were experiencing musculoskeletal symptoms related to aromatase inhibitor use. None of the patients had received acupuncture in the previous year.

The acupuncture group received eight weekly sessions targeting 15 acupuncture points. The control group got a sham acupuncture procedure at 14 non-acupuncture points. The sham therapy utilized the Park Sham Device, which consists of a nonpenetrating, retractable acupuncture needle and an adhesive tube. From a median baseline HAQ-DI score of 0.75, 8 of 23 patients in the real acupuncture group achieved the minimum clinically important improvement, predefined as a 0.22-point reduction. So did 13 of 24 women in the sham acupuncture group.

Pain scores on a visual analog scale improved to a similar extent in the two study arms, from a baseline median of 50 out of a possible 100 to 41 in the real acupuncture group and 36 in the sham group.

When the blinded patients were asked to guess their treatment assignment, 55% in each group did so accurately, according to Dr. Bao, a medical oncologist and licensed acupuncturist at the University of Maryland Greenebaum Cancer Center, Baltimore.

Plasma estradiol levels remained undetectable in most patients during the study period.

No significant side effects were noted in either study arm.

About half of breast cancer patients on adjuvant aromatase inhibitor therapy experience musculoskeletal symptoms. These side effects can be sufficiently debilitating as to lead to poor compliance or even treatment discontinuation.

Among the possible explanations for the negative results in this study are that the HAQ-DI may not be a sufficiently sensitive tool to detect small differences in effectiveness between real and sham acupuncture, and that sham acupuncture may not be an inert procedure, Dr. Bao said.

Although this randomized trial originally was scheduled to enroll 100 patients, it was halted early for futility based on the interim results.

The study was funded by a Komen grant and an ASCO Young Investigator Award. Dr. Bao declared having no financial conflicts.

SAN ANTONIO – Diagnosis of diabetes within the prior 4 years was independently associated with breast cancer in a Swedish case-control study.

Dr. Håkan Olsson reported at the San Antonio Breast Cancer Symposium on all 2,724 women diagnosed with breast cancer in southern Sweden during 2005-2007 and 20,542 matched controls. He and his coworkers were interested in how the malignancy is related to diabetes, obesity, and serum lipid levels.

In a multivariate analysis adjusted for obesity, serum lipids, and other potential confounders, the breast cancer patients were 37% more likely than controls to have been diagnosed with diabetes during the previous 4 years. Yet diabetes diagnosed 4-10 years previously was not associated with a significant increase in breast cancer, said Dr. Olsson, professor of oncology and cancer epidemiology at Lund (Sweden) University.

The most likely explanation for the finding that only relatively recently diagnosed diabetes was linked to increased risk of breast cancer is that the diabetic hormonal milieu doesn’t initiate breast tumors, but rather it promotes the growth of tumors that are already established but dormant. This would be analogous to the relationship between hormone replacement therapy and breast cancer, where the Early Breast Cancer Trialists’ Collaborative Group has demonstrated that it’s only present use, not past use, that increases the risk of malignancy, he observed.

Dr. Olsson and coworkers also looked at the relationship between diabetes and all other types of cancer among patients in the comprehensive regional cancer registry. They found that three other types of cancer in addition to breast cancer were associated with a significantly increased likelihood of prior diagnosis of diabetes compared to controls: pancreatic cancer, with a 2.36-fold increased rate; liver cancer, with a 3.43-fold increased odds; and colon cancer, with a 1.49-fold increase.

Dr. Olsson and coworkers also looked at the relationship between the antidiabetic medications metformin and glargine and cancer risk among all patients in the cancer registry, not just those with breast cancer. Use of the long-acting insulin analog glargine, which is quite common among Swedish type 2 diabetic patients, was associated with a 2.88-fold increased overall cancer risk. In contrast, metformin use was associated with an 8% reduction in overall cancer risk, although this association didn’t achieve statistical significance, unlike the relationship between glargine and overall cancer.

An association between glargine and increased cancer risk has also been noted in several other studies, according to Dr. Olsson.

In the southern Swedish breast cancer cohort, obesity after age 60 was independently associated with a 55% increased likelihood of breast cancer after controlling for diabetes and other factors in a multivariate analysis. However, obesity in women under age 60 was associated with a nonsignificant 41% reduction in breast cancer.

To Dr. Olsson’s surprise, the investigators found that hypercholesterolemia was independently associated with a 27% reduction in the prevalence of breast cancer. In other words, significantly fewer breast cancer patients had a high cholesterol level compared with the general population. This is a novel finding that requires confirmation in other data sets, he added.

The relationship between metformin and breast cancer is under study in the large, prospective, phase III, double-blind, randomized MA 32 clinical trial led by the National Cancer Institute of Canada Clinical Trials Group. More than 1,000 nondiabetic patients with early-stage breast cancer have been randomized to metformin or placebo. Key end points in the MA 32 study include overall and disease-free survival. Results are about 5 years off.

Dr. Olsson’s study was funded by the Southern Sweden Health Care Region. He declared having no relevant financial relationships.

SAN ANTONIO – Diagnosis of diabetes within the prior 4 years was independently associated with breast cancer in a Swedish case-control study.

Dr. Håkan Olsson reported at the San Antonio Breast Cancer Symposium on all 2,724 women diagnosed with breast cancer in southern Sweden during 2005-2007 and 20,542 matched controls. He and his coworkers were interested in how the malignancy is related to diabetes, obesity, and serum lipid levels.

In a multivariate analysis adjusted for obesity, serum lipids, and other potential confounders, the breast cancer patients were 37% more likely than controls to have been diagnosed with diabetes during the previous 4 years. Yet diabetes diagnosed 4-10 years previously was not associated with a significant increase in breast cancer, said Dr. Olsson, professor of oncology and cancer epidemiology at Lund (Sweden) University.

The most likely explanation for the finding that only relatively recently diagnosed diabetes was linked to increased risk of breast cancer is that the diabetic hormonal milieu doesn’t initiate breast tumors, but rather it promotes the growth of tumors that are already established but dormant. This would be analogous to the relationship between hormone replacement therapy and breast cancer, where the Early Breast Cancer Trialists’ Collaborative Group has demonstrated that it’s only present use, not past use, that increases the risk of malignancy, he observed.

Dr. Olsson and coworkers also looked at the relationship between diabetes and all other types of cancer among patients in the comprehensive regional cancer registry. They found that three other types of cancer in addition to breast cancer were associated with a significantly increased likelihood of prior diagnosis of diabetes compared to controls: pancreatic cancer, with a 2.36-fold increased rate; liver cancer, with a 3.43-fold increased odds; and colon cancer, with a 1.49-fold increase.

Dr. Olsson and coworkers also looked at the relationship between the antidiabetic medications metformin and glargine and cancer risk among all patients in the cancer registry, not just those with breast cancer. Use of the long-acting insulin analog glargine, which is quite common among Swedish type 2 diabetic patients, was associated with a 2.88-fold increased overall cancer risk. In contrast, metformin use was associated with an 8% reduction in overall cancer risk, although this association didn’t achieve statistical significance, unlike the relationship between glargine and overall cancer.

An association between glargine and increased cancer risk has also been noted in several other studies, according to Dr. Olsson.

In the southern Swedish breast cancer cohort, obesity after age 60 was independently associated with a 55% increased likelihood of breast cancer after controlling for diabetes and other factors in a multivariate analysis. However, obesity in women under age 60 was associated with a nonsignificant 41% reduction in breast cancer.

To Dr. Olsson’s surprise, the investigators found that hypercholesterolemia was independently associated with a 27% reduction in the prevalence of breast cancer. In other words, significantly fewer breast cancer patients had a high cholesterol level compared with the general population. This is a novel finding that requires confirmation in other data sets, he added.

The relationship between metformin and breast cancer is under study in the large, prospective, phase III, double-blind, randomized MA 32 clinical trial led by the National Cancer Institute of Canada Clinical Trials Group. More than 1,000 nondiabetic patients with early-stage breast cancer have been randomized to metformin or placebo. Key end points in the MA 32 study include overall and disease-free survival. Results are about 5 years off.

Dr. Olsson’s study was funded by the Southern Sweden Health Care Region. He declared having no relevant financial relationships.

SAN ANTONIO – Diagnosis of diabetes within the prior 4 years was independently associated with breast cancer in a Swedish case-control study.

Dr. Håkan Olsson reported at the San Antonio Breast Cancer Symposium on all 2,724 women diagnosed with breast cancer in southern Sweden during 2005-2007 and 20,542 matched controls. He and his coworkers were interested in how the malignancy is related to diabetes, obesity, and serum lipid levels.

In a multivariate analysis adjusted for obesity, serum lipids, and other potential confounders, the breast cancer patients were 37% more likely than controls to have been diagnosed with diabetes during the previous 4 years. Yet diabetes diagnosed 4-10 years previously was not associated with a significant increase in breast cancer, said Dr. Olsson, professor of oncology and cancer epidemiology at Lund (Sweden) University.

The most likely explanation for the finding that only relatively recently diagnosed diabetes was linked to increased risk of breast cancer is that the diabetic hormonal milieu doesn’t initiate breast tumors, but rather it promotes the growth of tumors that are already established but dormant. This would be analogous to the relationship between hormone replacement therapy and breast cancer, where the Early Breast Cancer Trialists’ Collaborative Group has demonstrated that it’s only present use, not past use, that increases the risk of malignancy, he observed.

Dr. Olsson and coworkers also looked at the relationship between diabetes and all other types of cancer among patients in the comprehensive regional cancer registry. They found that three other types of cancer in addition to breast cancer were associated with a significantly increased likelihood of prior diagnosis of diabetes compared to controls: pancreatic cancer, with a 2.36-fold increased rate; liver cancer, with a 3.43-fold increased odds; and colon cancer, with a 1.49-fold increase.

Dr. Olsson and coworkers also looked at the relationship between the antidiabetic medications metformin and glargine and cancer risk among all patients in the cancer registry, not just those with breast cancer. Use of the long-acting insulin analog glargine, which is quite common among Swedish type 2 diabetic patients, was associated with a 2.88-fold increased overall cancer risk. In contrast, metformin use was associated with an 8% reduction in overall cancer risk, although this association didn’t achieve statistical significance, unlike the relationship between glargine and overall cancer.

An association between glargine and increased cancer risk has also been noted in several other studies, according to Dr. Olsson.

In the southern Swedish breast cancer cohort, obesity after age 60 was independently associated with a 55% increased likelihood of breast cancer after controlling for diabetes and other factors in a multivariate analysis. However, obesity in women under age 60 was associated with a nonsignificant 41% reduction in breast cancer.

To Dr. Olsson’s surprise, the investigators found that hypercholesterolemia was independently associated with a 27% reduction in the prevalence of breast cancer. In other words, significantly fewer breast cancer patients had a high cholesterol level compared with the general population. This is a novel finding that requires confirmation in other data sets, he added.

The relationship between metformin and breast cancer is under study in the large, prospective, phase III, double-blind, randomized MA 32 clinical trial led by the National Cancer Institute of Canada Clinical Trials Group. More than 1,000 nondiabetic patients with early-stage breast cancer have been randomized to metformin or placebo. Key end points in the MA 32 study include overall and disease-free survival. Results are about 5 years off.

Dr. Olsson’s study was funded by the Southern Sweden Health Care Region. He declared having no relevant financial relationships.

SAN ANTONIO – Pregnancy-associated breast cancer carries a relatively poor prognosis regardless of whether the malignancy is diagnosed during pregnancy or post partum, a meta-analysis has shown.

The meta-analysis included 29 matched case-control studies totaling 3,529 women with pregnancy-associated breast cancer – defined as breast cancer diagnosed during pregnancy or within 1 year afterward – and 36,914 controls whose breast cancer was unrelated to pregnancy.

This is believed to be the largest-ever meta-analysis addressing the prognosis of pregnancy-associated breast cancer, a relatively rare disease, Dr. Hatem A. Azim Jr. reported at the annual San Antonio Breast Cancer Symposium. In addition to the published reports, Dr. Azim and coauthors contacted the various study investigators to obtain unpublished data.

Women with pregnancy-associated breast cancer had a significantly greater risk of death than did controls, Dr. Azim and colleagues found: In a multivariate analysis, pregnancy increased the overall mortality rate by 46%. This held true even after adjustment for differences in tumor size, nodal status, and systemic therapy, according to Dr. Azim of the Jules Bordet Institute at the Free University of Brussels.

The secondary outcome measure in the meta-analysis was disease-free survival. Patients with pregnancy-associated breast cancer had a 59% increased risk of relapse compared with women with nonpregnancy-related breast cancer.

Roughly 6% of breast cancers are diagnosed in women before the age of 40, and of those only about 10% are diagnosed during pregnancy or within a year after. The relative rarity of this condition precludes conducting definitive large prospective clinical trials addressing patient prognosis.

Despite the rarity of pregnancy-associated breast cancer, however, it’s an important condition for a couple of reasons: The incidence of pregnancy-associated breast cancer is increasing because of the popular trend for delay of childbirth until later in life, and the condition poses a thorny therapeutic challenge because of the poor prognosis.

Dr. Azim reported no relevant financial disclosures.

SAN ANTONIO – Pregnancy-associated breast cancer carries a relatively poor prognosis regardless of whether the malignancy is diagnosed during pregnancy or post partum, a meta-analysis has shown.

The meta-analysis included 29 matched case-control studies totaling 3,529 women with pregnancy-associated breast cancer – defined as breast cancer diagnosed during pregnancy or within 1 year afterward – and 36,914 controls whose breast cancer was unrelated to pregnancy.

This is believed to be the largest-ever meta-analysis addressing the prognosis of pregnancy-associated breast cancer, a relatively rare disease, Dr. Hatem A. Azim Jr. reported at the annual San Antonio Breast Cancer Symposium. In addition to the published reports, Dr. Azim and coauthors contacted the various study investigators to obtain unpublished data.

Women with pregnancy-associated breast cancer had a significantly greater risk of death than did controls, Dr. Azim and colleagues found: In a multivariate analysis, pregnancy increased the overall mortality rate by 46%. This held true even after adjustment for differences in tumor size, nodal status, and systemic therapy, according to Dr. Azim of the Jules Bordet Institute at the Free University of Brussels.

The secondary outcome measure in the meta-analysis was disease-free survival. Patients with pregnancy-associated breast cancer had a 59% increased risk of relapse compared with women with nonpregnancy-related breast cancer.

Roughly 6% of breast cancers are diagnosed in women before the age of 40, and of those only about 10% are diagnosed during pregnancy or within a year after. The relative rarity of this condition precludes conducting definitive large prospective clinical trials addressing patient prognosis.

Despite the rarity of pregnancy-associated breast cancer, however, it’s an important condition for a couple of reasons: The incidence of pregnancy-associated breast cancer is increasing because of the popular trend for delay of childbirth until later in life, and the condition poses a thorny therapeutic challenge because of the poor prognosis.

Dr. Azim reported no relevant financial disclosures.

SAN ANTONIO – Pregnancy-associated breast cancer carries a relatively poor prognosis regardless of whether the malignancy is diagnosed during pregnancy or post partum, a meta-analysis has shown.

The meta-analysis included 29 matched case-control studies totaling 3,529 women with pregnancy-associated breast cancer – defined as breast cancer diagnosed during pregnancy or within 1 year afterward – and 36,914 controls whose breast cancer was unrelated to pregnancy.

This is believed to be the largest-ever meta-analysis addressing the prognosis of pregnancy-associated breast cancer, a relatively rare disease, Dr. Hatem A. Azim Jr. reported at the annual San Antonio Breast Cancer Symposium. In addition to the published reports, Dr. Azim and coauthors contacted the various study investigators to obtain unpublished data.

Women with pregnancy-associated breast cancer had a significantly greater risk of death than did controls, Dr. Azim and colleagues found: In a multivariate analysis, pregnancy increased the overall mortality rate by 46%. This held true even after adjustment for differences in tumor size, nodal status, and systemic therapy, according to Dr. Azim of the Jules Bordet Institute at the Free University of Brussels.

The secondary outcome measure in the meta-analysis was disease-free survival. Patients with pregnancy-associated breast cancer had a 59% increased risk of relapse compared with women with nonpregnancy-related breast cancer.

Roughly 6% of breast cancers are diagnosed in women before the age of 40, and of those only about 10% are diagnosed during pregnancy or within a year after. The relative rarity of this condition precludes conducting definitive large prospective clinical trials addressing patient prognosis.

Despite the rarity of pregnancy-associated breast cancer, however, it’s an important condition for a couple of reasons: The incidence of pregnancy-associated breast cancer is increasing because of the popular trend for delay of childbirth until later in life, and the condition poses a thorny therapeutic challenge because of the poor prognosis.

Dr. Azim reported no relevant financial disclosures.

SAN ANTONIO – The guideline-recommended practice of routinely measuring left ventricular ejection fraction before anthracycline-based chemotherapy to screen out patients at increased risk for treatment-induced heart failure has come under fire as unproductive and financially wasteful.

It’s a practice endorsed by the American Heart Association and American College of Cardiology, enshrined in Food and Drug Administration labeling, required as part of most U.S. clinical trials, and common in community-based oncology practice.

Yet there are no data to support the utility of this practice as a screening tool aimed at minimizing heart failure induced by anthracycline-based chemotherapy, according to a report at the San Antonio Breast Cancer Symposium.

Dr. Seema M. Policepatil of the Gundersen Lutheran Medical Foundation, La Crosse, Wis., and colleagues presented a retrospective study that suggested routine cardiac ejection fraction screening under these circumstances is without merit. The study included 466 patients with early-stage, HER2-negative invasive breast cancer who were under consideration for anthracycline-based chemotherapy as part of their initial therapy. None had prior heart failure.

Left ventricular ejection fraction (LVEF) was measured by echocardiography, nuclear imaging, or MRI prior to chemotherapy in 241 of the patients. This reflects institutional practice: at Gundersen, pretreatment assessment of cardiac pump function is common but not uniform.

One of the 241 patients was found to have asymptomatic left ventricular dysfunction, with a screening ejection fraction of 48%, and she therefore didn’t receive anthracycline-based chemotherapy. Thus, modification of the treatment strategy in response to screening of ejection fraction occurred only rarely.

In addition, nine patients – six who had pretreatment cardiac imaging and three who did not – skipped the chemotherapy, either because of physician or patient preference or participation in clinical trials.

During a mean 5 years of follow-up, 3 of the remaining 456 women were diagnosed with heart failure: 2 among those with a pretreatment LVEF measurement, and 1 among those without it. That’s an acceptably low 0.7% event rate, she declared.

Current practice guidelines recommending pretreatment LVEF measurement are based upon expert consensus. It’s time to incorporate the available evidence, which in the case of the Gundersen experience doesn’t support the practice, Dr. Policepatil continued.

Assuming that nationally half of all patients with early-stage HER2-negative breast cancer undergo measurement of their LV ejection fraction before getting chemotherapy, eliminating this routine practice would save $7 million to $17 million annually based upon Medicare and Medicaid reimbursement rates, the physician added.

This study was funded by the Center for Cancer and Blood Disorders at the Gundersen Lutheran Medical Foundation. Dr. Policepatil declared having no financial conflicts.

SAN ANTONIO – The guideline-recommended practice of routinely measuring left ventricular ejection fraction before anthracycline-based chemotherapy to screen out patients at increased risk for treatment-induced heart failure has come under fire as unproductive and financially wasteful.

It’s a practice endorsed by the American Heart Association and American College of Cardiology, enshrined in Food and Drug Administration labeling, required as part of most U.S. clinical trials, and common in community-based oncology practice.

Yet there are no data to support the utility of this practice as a screening tool aimed at minimizing heart failure induced by anthracycline-based chemotherapy, according to a report at the San Antonio Breast Cancer Symposium.

Dr. Seema M. Policepatil of the Gundersen Lutheran Medical Foundation, La Crosse, Wis., and colleagues presented a retrospective study that suggested routine cardiac ejection fraction screening under these circumstances is without merit. The study included 466 patients with early-stage, HER2-negative invasive breast cancer who were under consideration for anthracycline-based chemotherapy as part of their initial therapy. None had prior heart failure.

Left ventricular ejection fraction (LVEF) was measured by echocardiography, nuclear imaging, or MRI prior to chemotherapy in 241 of the patients. This reflects institutional practice: at Gundersen, pretreatment assessment of cardiac pump function is common but not uniform.

One of the 241 patients was found to have asymptomatic left ventricular dysfunction, with a screening ejection fraction of 48%, and she therefore didn’t receive anthracycline-based chemotherapy. Thus, modification of the treatment strategy in response to screening of ejection fraction occurred only rarely.

In addition, nine patients – six who had pretreatment cardiac imaging and three who did not – skipped the chemotherapy, either because of physician or patient preference or participation in clinical trials.

During a mean 5 years of follow-up, 3 of the remaining 456 women were diagnosed with heart failure: 2 among those with a pretreatment LVEF measurement, and 1 among those without it. That’s an acceptably low 0.7% event rate, she declared.

Current practice guidelines recommending pretreatment LVEF measurement are based upon expert consensus. It’s time to incorporate the available evidence, which in the case of the Gundersen experience doesn’t support the practice, Dr. Policepatil continued.

Assuming that nationally half of all patients with early-stage HER2-negative breast cancer undergo measurement of their LV ejection fraction before getting chemotherapy, eliminating this routine practice would save $7 million to $17 million annually based upon Medicare and Medicaid reimbursement rates, the physician added.

This study was funded by the Center for Cancer and Blood Disorders at the Gundersen Lutheran Medical Foundation. Dr. Policepatil declared having no financial conflicts.

SAN ANTONIO – The guideline-recommended practice of routinely measuring left ventricular ejection fraction before anthracycline-based chemotherapy to screen out patients at increased risk for treatment-induced heart failure has come under fire as unproductive and financially wasteful.

It’s a practice endorsed by the American Heart Association and American College of Cardiology, enshrined in Food and Drug Administration labeling, required as part of most U.S. clinical trials, and common in community-based oncology practice.

Yet there are no data to support the utility of this practice as a screening tool aimed at minimizing heart failure induced by anthracycline-based chemotherapy, according to a report at the San Antonio Breast Cancer Symposium.

Dr. Seema M. Policepatil of the Gundersen Lutheran Medical Foundation, La Crosse, Wis., and colleagues presented a retrospective study that suggested routine cardiac ejection fraction screening under these circumstances is without merit. The study included 466 patients with early-stage, HER2-negative invasive breast cancer who were under consideration for anthracycline-based chemotherapy as part of their initial therapy. None had prior heart failure.

Left ventricular ejection fraction (LVEF) was measured by echocardiography, nuclear imaging, or MRI prior to chemotherapy in 241 of the patients. This reflects institutional practice: at Gundersen, pretreatment assessment of cardiac pump function is common but not uniform.

One of the 241 patients was found to have asymptomatic left ventricular dysfunction, with a screening ejection fraction of 48%, and she therefore didn’t receive anthracycline-based chemotherapy. Thus, modification of the treatment strategy in response to screening of ejection fraction occurred only rarely.

In addition, nine patients – six who had pretreatment cardiac imaging and three who did not – skipped the chemotherapy, either because of physician or patient preference or participation in clinical trials.

During a mean 5 years of follow-up, 3 of the remaining 456 women were diagnosed with heart failure: 2 among those with a pretreatment LVEF measurement, and 1 among those without it. That’s an acceptably low 0.7% event rate, she declared.

Current practice guidelines recommending pretreatment LVEF measurement are based upon expert consensus. It’s time to incorporate the available evidence, which in the case of the Gundersen experience doesn’t support the practice, Dr. Policepatil continued.

Assuming that nationally half of all patients with early-stage HER2-negative breast cancer undergo measurement of their LV ejection fraction before getting chemotherapy, eliminating this routine practice would save $7 million to $17 million annually based upon Medicare and Medicaid reimbursement rates, the physician added.

This study was funded by the Center for Cancer and Blood Disorders at the Gundersen Lutheran Medical Foundation. Dr. Policepatil declared having no financial conflicts.

SAN ANTONIO – Breast cancer patients have an increased prevalence of autoimmune thyroid disease, according to a comprehensive meta-analysis incorporating 26 published studies.

That being said, the cause of this strong association remains to be determined by future longitudinal studies. In the interim, the take-home message from this meta-analysis is that it’s useful to screen women with breast cancer for autoimmune thyroid disease, Dr. Prue Hardefeldt observed at the San Antonio Breast Cancer Symposium.

The pooled analysis demonstrated that breast cancer patients were 2.92-fold more likely to have autoimmune thyroiditis than controls without breast disease. In addition, they were 2.02-fold more likely to be positive for antithyroid antibodies, and they had a 2.26-fold greater prevalence of goiter, according to Dr. Hardefeldt of the Whitely-Martin Research Center at the University of Sydney.

Breast cancer patients were also 50%-80% more likely than other women to be either hyper- or hypothyroid; however, these trends didn’t achieve statistical significance.

She declared having no financial conflicts.

SAN ANTONIO – Breast cancer patients have an increased prevalence of autoimmune thyroid disease, according to a comprehensive meta-analysis incorporating 26 published studies.

That being said, the cause of this strong association remains to be determined by future longitudinal studies. In the interim, the take-home message from this meta-analysis is that it’s useful to screen women with breast cancer for autoimmune thyroid disease, Dr. Prue Hardefeldt observed at the San Antonio Breast Cancer Symposium.

The pooled analysis demonstrated that breast cancer patients were 2.92-fold more likely to have autoimmune thyroiditis than controls without breast disease. In addition, they were 2.02-fold more likely to be positive for antithyroid antibodies, and they had a 2.26-fold greater prevalence of goiter, according to Dr. Hardefeldt of the Whitely-Martin Research Center at the University of Sydney.

Breast cancer patients were also 50%-80% more likely than other women to be either hyper- or hypothyroid; however, these trends didn’t achieve statistical significance.

She declared having no financial conflicts.

SAN ANTONIO – Breast cancer patients have an increased prevalence of autoimmune thyroid disease, according to a comprehensive meta-analysis incorporating 26 published studies.

That being said, the cause of this strong association remains to be determined by future longitudinal studies. In the interim, the take-home message from this meta-analysis is that it’s useful to screen women with breast cancer for autoimmune thyroid disease, Dr. Prue Hardefeldt observed at the San Antonio Breast Cancer Symposium.

The pooled analysis demonstrated that breast cancer patients were 2.92-fold more likely to have autoimmune thyroiditis than controls without breast disease. In addition, they were 2.02-fold more likely to be positive for antithyroid antibodies, and they had a 2.26-fold greater prevalence of goiter, according to Dr. Hardefeldt of the Whitely-Martin Research Center at the University of Sydney.

Breast cancer patients were also 50%-80% more likely than other women to be either hyper- or hypothyroid; however, these trends didn’t achieve statistical significance.

She declared having no financial conflicts.

SAN ANTONIO – BRCA mutation carriers can be separated into subgroups at low and sharply increased risks of developing contralateral breast cancer following a first breast cancer, a Dutch study suggests.

The key predictive variables identified in the BOSOM (Breast Cancer Outcome Study of Mutation) carriers were the patient’s age at diagnosis of the first breast cancer and whether or not the tumor was triple negative – that is, estrogen receptor–, progesterone receptor– and HER2 receptor–negative, Alexandra J. van den Broek reported at the annual meeting.

The BOSOM study analysis included 5,065 consecutive women diagnosed with breast cancer before age 50 at 10 Dutch hospitals during 1970-2003, all of whom were tested for BRCA mutations. The prevalence of BRCA1 mutations was 3%, while another 1% had a BRCA2 mutation.

The cumulative 10-year risk of developing contralateral breast cancer (CBC) was 6% in women with no BRCA mutations, 11% with a BRCA2 mutation, and 20% in those with a BRCA1 mutation.

The subgroup of BRCA mutation carriers at greatest risk for CBC consisted of those whose first breast cancer was diagnosed before age 41. They had a 26% rate of CBC during the next 10 years. That was nearly eightfold greater than the nearly 4% figure in the low-risk subgroup, which comprised BRCA mutation carriers with a non–triple-negative cancer diagnosed at age 41-50 years, said Ms. van den Broek, a doctoral candidate in epidemiology at the Netherlands Cancer Institute, Amsterdam.

The other high-risk subgroup of BRCA mutation carriers consisted of women with a triple-negative first breast cancer diagnosed at age 41-50 years, she added. Their 10-year cumulative risk was 15%.

The number of BRCA mutation carriers in this consecutive series of breast cancer patients was fairly small, so the BOSOM results require confirmation in other data sets. If that’s forthcoming, a change in practice guidelines for prophylaxis and screening in following breast cancer patients with a BRCA mutation will be warranted, Ms. van den Broek asserted.

The study was sponsored by the Dutch Cancer Society. Ms. van den Broek declared having no financial conflicts.

SAN ANTONIO – BRCA mutation carriers can be separated into subgroups at low and sharply increased risks of developing contralateral breast cancer following a first breast cancer, a Dutch study suggests.

The key predictive variables identified in the BOSOM (Breast Cancer Outcome Study of Mutation) carriers were the patient’s age at diagnosis of the first breast cancer and whether or not the tumor was triple negative – that is, estrogen receptor–, progesterone receptor– and HER2 receptor–negative, Alexandra J. van den Broek reported at the annual meeting.

The BOSOM study analysis included 5,065 consecutive women diagnosed with breast cancer before age 50 at 10 Dutch hospitals during 1970-2003, all of whom were tested for BRCA mutations. The prevalence of BRCA1 mutations was 3%, while another 1% had a BRCA2 mutation.

The cumulative 10-year risk of developing contralateral breast cancer (CBC) was 6% in women with no BRCA mutations, 11% with a BRCA2 mutation, and 20% in those with a BRCA1 mutation.

The subgroup of BRCA mutation carriers at greatest risk for CBC consisted of those whose first breast cancer was diagnosed before age 41. They had a 26% rate of CBC during the next 10 years. That was nearly eightfold greater than the nearly 4% figure in the low-risk subgroup, which comprised BRCA mutation carriers with a non–triple-negative cancer diagnosed at age 41-50 years, said Ms. van den Broek, a doctoral candidate in epidemiology at the Netherlands Cancer Institute, Amsterdam.

The other high-risk subgroup of BRCA mutation carriers consisted of women with a triple-negative first breast cancer diagnosed at age 41-50 years, she added. Their 10-year cumulative risk was 15%.

The number of BRCA mutation carriers in this consecutive series of breast cancer patients was fairly small, so the BOSOM results require confirmation in other data sets. If that’s forthcoming, a change in practice guidelines for prophylaxis and screening in following breast cancer patients with a BRCA mutation will be warranted, Ms. van den Broek asserted.

The study was sponsored by the Dutch Cancer Society. Ms. van den Broek declared having no financial conflicts.

SAN ANTONIO – BRCA mutation carriers can be separated into subgroups at low and sharply increased risks of developing contralateral breast cancer following a first breast cancer, a Dutch study suggests.

The key predictive variables identified in the BOSOM (Breast Cancer Outcome Study of Mutation) carriers were the patient’s age at diagnosis of the first breast cancer and whether or not the tumor was triple negative – that is, estrogen receptor–, progesterone receptor– and HER2 receptor–negative, Alexandra J. van den Broek reported at the annual meeting.

The BOSOM study analysis included 5,065 consecutive women diagnosed with breast cancer before age 50 at 10 Dutch hospitals during 1970-2003, all of whom were tested for BRCA mutations. The prevalence of BRCA1 mutations was 3%, while another 1% had a BRCA2 mutation.

The cumulative 10-year risk of developing contralateral breast cancer (CBC) was 6% in women with no BRCA mutations, 11% with a BRCA2 mutation, and 20% in those with a BRCA1 mutation.

The subgroup of BRCA mutation carriers at greatest risk for CBC consisted of those whose first breast cancer was diagnosed before age 41. They had a 26% rate of CBC during the next 10 years. That was nearly eightfold greater than the nearly 4% figure in the low-risk subgroup, which comprised BRCA mutation carriers with a non–triple-negative cancer diagnosed at age 41-50 years, said Ms. van den Broek, a doctoral candidate in epidemiology at the Netherlands Cancer Institute, Amsterdam.

The other high-risk subgroup of BRCA mutation carriers consisted of women with a triple-negative first breast cancer diagnosed at age 41-50 years, she added. Their 10-year cumulative risk was 15%.

The number of BRCA mutation carriers in this consecutive series of breast cancer patients was fairly small, so the BOSOM results require confirmation in other data sets. If that’s forthcoming, a change in practice guidelines for prophylaxis and screening in following breast cancer patients with a BRCA mutation will be warranted, Ms. van den Broek asserted.

The study was sponsored by the Dutch Cancer Society. Ms. van den Broek declared having no financial conflicts.

SAN ANTONIO – Bilateral oophorectomy in women younger than age 45 is associated with a subsequent doubled prevalence of osteoporosis and a similarly elevated rate of arthritis, compared with women with intact ovaries.

These findings from a new analysis of the Third National Health and Nutrition Examination Survey (NHANES III) had a further twist: The likelihood of having low bone mineral density and/or arthritis was even greater in the subgroup of women not on hormone replacement therapy following their surgically-induced abrupt menopause, Anne Marie McCarthy said at the San Antonio Breast Cancer Symposium.

"The implication of our findings is that women who’ve had their ovaries removed at a young age can now be informed about their risk for bone loss over the long term. However, additional studies are needed to determine the frequency of monitoring for osteoporosis and the appropriateness of various preventive strategies in women who’ve had their ovaries removed," according to Ms. McCarthy, a doctoral candidate in epidemiology at Johns Hopkins University, Baltimore.

The bone mineral density analysis included 3,660 women who underwent femoral neck bone density measurement by dual energy x-ray as part of their participation in NHANES III, which was conducted in a U.S. nationally representative sample in 1988-1994.

The age-standardized mean femoral neck bone density was significantly lower in women with oophorectomy before age 45 than in those with intact ovaries: 0.711 compared with 0.743 g/m² (P = .017). Moreover, in a multivariate logistic regression analysis, women with early oophorectomy had an adjusted 1.78-fold increased likelihood of having osteoporosis, compared with women with intact ovaries. Upon exclusion of hormone replacement therapy users, the odds climbed even higher so that oophorectomy before age 45 was associated with a 2.92-fold increased likelihood of osteoporosis, she reported.

The Johns Hopkins investigators are now in the midst of a study in which they’re measuring bone mineral density before and after prophylactic oophorectomy in women who carry high-risk BRCA mutations.

The arthritis analysis included 4,039 women. Those who had undergone oophorectomy were significantly more likely to report having been informed by a physician that they have arthritis, by a margin of 45.4% to 32.1% (P less than .001). Among the subset of women with oophorectomy before age 45, the prevalence of arthritis was even higher at 47.7%. In a multivariate analysis, women with oophorectomy when they were younger than 45 had a 1.78-fold increased odds of arthritis compared with those with intact ovaries. If they didn’t use hormone replacement therapy, however, those odds rose to 1.99-fold.

Because the investigators didn’t study the NHANES III participants’ actual medical records, they were unable to say what specific forms of arthritis were more prevalent in the early oophorectomy group. Also, since to Ms. McCarthy’s knowledge this is the first-ever study linking oophorectomy to arthritis, this association needs confirmation by others. There are animal data supporting such a link, she noted.

"One possible mechanism is that we think estrogen is important for the health of cartilage, so losing estrogen can lead to inflammation and damage of cartilage, perhaps," Ms. McCarthy speculated.

Prophylactic bilateral oophorectomy is a widely accepted procedure to reduce the risks of breast and ovarian cancer in BRCA mutation carriers. But this indication actually accounts for only a small fraction of oophorectomies performed in this country. About 600,000 women per year undergo hysterectomy for indications including fibroids, abnormal bleeding, endometriosis, and uterine prolapse, according to the Centers for Disease Control and Prevention, and about half of them have both ovaries removed at that time to prevent ovarian cancer.

NHANES III was conducted by the CDC. Ms. McCarthy said she had no relevant financial disclosures.

SAN ANTONIO – Bilateral oophorectomy in women younger than age 45 is associated with a subsequent doubled prevalence of osteoporosis and a similarly elevated rate of arthritis, compared with women with intact ovaries.

These findings from a new analysis of the Third National Health and Nutrition Examination Survey (NHANES III) had a further twist: The likelihood of having low bone mineral density and/or arthritis was even greater in the subgroup of women not on hormone replacement therapy following their surgically-induced abrupt menopause, Anne Marie McCarthy said at the San Antonio Breast Cancer Symposium.

"The implication of our findings is that women who’ve had their ovaries removed at a young age can now be informed about their risk for bone loss over the long term. However, additional studies are needed to determine the frequency of monitoring for osteoporosis and the appropriateness of various preventive strategies in women who’ve had their ovaries removed," according to Ms. McCarthy, a doctoral candidate in epidemiology at Johns Hopkins University, Baltimore.

The bone mineral density analysis included 3,660 women who underwent femoral neck bone density measurement by dual energy x-ray as part of their participation in NHANES III, which was conducted in a U.S. nationally representative sample in 1988-1994.

The age-standardized mean femoral neck bone density was significantly lower in women with oophorectomy before age 45 than in those with intact ovaries: 0.711 compared with 0.743 g/m² (P = .017). Moreover, in a multivariate logistic regression analysis, women with early oophorectomy had an adjusted 1.78-fold increased likelihood of having osteoporosis, compared with women with intact ovaries. Upon exclusion of hormone replacement therapy users, the odds climbed even higher so that oophorectomy before age 45 was associated with a 2.92-fold increased likelihood of osteoporosis, she reported.

The Johns Hopkins investigators are now in the midst of a study in which they’re measuring bone mineral density before and after prophylactic oophorectomy in women who carry high-risk BRCA mutations.

The arthritis analysis included 4,039 women. Those who had undergone oophorectomy were significantly more likely to report having been informed by a physician that they have arthritis, by a margin of 45.4% to 32.1% (P less than .001). Among the subset of women with oophorectomy before age 45, the prevalence of arthritis was even higher at 47.7%. In a multivariate analysis, women with oophorectomy when they were younger than 45 had a 1.78-fold increased odds of arthritis compared with those with intact ovaries. If they didn’t use hormone replacement therapy, however, those odds rose to 1.99-fold.

Because the investigators didn’t study the NHANES III participants’ actual medical records, they were unable to say what specific forms of arthritis were more prevalent in the early oophorectomy group. Also, since to Ms. McCarthy’s knowledge this is the first-ever study linking oophorectomy to arthritis, this association needs confirmation by others. There are animal data supporting such a link, she noted.

"One possible mechanism is that we think estrogen is important for the health of cartilage, so losing estrogen can lead to inflammation and damage of cartilage, perhaps," Ms. McCarthy speculated.

Prophylactic bilateral oophorectomy is a widely accepted procedure to reduce the risks of breast and ovarian cancer in BRCA mutation carriers. But this indication actually accounts for only a small fraction of oophorectomies performed in this country. About 600,000 women per year undergo hysterectomy for indications including fibroids, abnormal bleeding, endometriosis, and uterine prolapse, according to the Centers for Disease Control and Prevention, and about half of them have both ovaries removed at that time to prevent ovarian cancer.

NHANES III was conducted by the CDC. Ms. McCarthy said she had no relevant financial disclosures.

SAN ANTONIO – Bilateral oophorectomy in women younger than age 45 is associated with a subsequent doubled prevalence of osteoporosis and a similarly elevated rate of arthritis, compared with women with intact ovaries.

These findings from a new analysis of the Third National Health and Nutrition Examination Survey (NHANES III) had a further twist: The likelihood of having low bone mineral density and/or arthritis was even greater in the subgroup of women not on hormone replacement therapy following their surgically-induced abrupt menopause, Anne Marie McCarthy said at the San Antonio Breast Cancer Symposium.

"The implication of our findings is that women who’ve had their ovaries removed at a young age can now be informed about their risk for bone loss over the long term. However, additional studies are needed to determine the frequency of monitoring for osteoporosis and the appropriateness of various preventive strategies in women who’ve had their ovaries removed," according to Ms. McCarthy, a doctoral candidate in epidemiology at Johns Hopkins University, Baltimore.

The bone mineral density analysis included 3,660 women who underwent femoral neck bone density measurement by dual energy x-ray as part of their participation in NHANES III, which was conducted in a U.S. nationally representative sample in 1988-1994.

The age-standardized mean femoral neck bone density was significantly lower in women with oophorectomy before age 45 than in those with intact ovaries: 0.711 compared with 0.743 g/m² (P = .017). Moreover, in a multivariate logistic regression analysis, women with early oophorectomy had an adjusted 1.78-fold increased likelihood of having osteoporosis, compared with women with intact ovaries. Upon exclusion of hormone replacement therapy users, the odds climbed even higher so that oophorectomy before age 45 was associated with a 2.92-fold increased likelihood of osteoporosis, she reported.

The Johns Hopkins investigators are now in the midst of a study in which they’re measuring bone mineral density before and after prophylactic oophorectomy in women who carry high-risk BRCA mutations.

The arthritis analysis included 4,039 women. Those who had undergone oophorectomy were significantly more likely to report having been informed by a physician that they have arthritis, by a margin of 45.4% to 32.1% (P less than .001). Among the subset of women with oophorectomy before age 45, the prevalence of arthritis was even higher at 47.7%. In a multivariate analysis, women with oophorectomy when they were younger than 45 had a 1.78-fold increased odds of arthritis compared with those with intact ovaries. If they didn’t use hormone replacement therapy, however, those odds rose to 1.99-fold.

Because the investigators didn’t study the NHANES III participants’ actual medical records, they were unable to say what specific forms of arthritis were more prevalent in the early oophorectomy group. Also, since to Ms. McCarthy’s knowledge this is the first-ever study linking oophorectomy to arthritis, this association needs confirmation by others. There are animal data supporting such a link, she noted.

"One possible mechanism is that we think estrogen is important for the health of cartilage, so losing estrogen can lead to inflammation and damage of cartilage, perhaps," Ms. McCarthy speculated.

Prophylactic bilateral oophorectomy is a widely accepted procedure to reduce the risks of breast and ovarian cancer in BRCA mutation carriers. But this indication actually accounts for only a small fraction of oophorectomies performed in this country. About 600,000 women per year undergo hysterectomy for indications including fibroids, abnormal bleeding, endometriosis, and uterine prolapse, according to the Centers for Disease Control and Prevention, and about half of them have both ovaries removed at that time to prevent ovarian cancer.

NHANES III was conducted by the CDC. Ms. McCarthy said she had no relevant financial disclosures.

SAN ANTONIO – Treatment with atorvastatin did not significantly change mammographic density after 1 year in a small randomized phase III study of premenopausal women at high risk for breast cancer.

While statins are widely used to prevent cardiovascular disease, it has been suggested that these drugs also may have a role in breast cancer prevention. Statin users are estimated to have a 30%-70% lower incidence of breast cancer, compared with nonusers, according to Dr. Marie E. Wood, professor of medicine and director of the familial cancer program at the University of Vermont, Burlington, and her coinvestigators.

A total of 63 premenopausal women were randomized to receive either 40 mg of atorvastatin (Lipitor) or placebo daily for a year. At the end of that time the investigators found no association between change in breast density and atorvastatin use in a multivariable linear regression analysis adjusted for age and body mass index. The data were presented in poster form at the San Antonio Breast Cancer Symposium.

The women had a mean age of 44 years and a mean body mass index (BMI) of 26.4 kg/m². Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS), which is a standardized qualitative assessment of mammographic breast density with four categories.

Four percent of women had fatty-replaced breast tissue, 29% had scattered fibroglandular densities, 56% had heterogeneously dense breasts, and 11% had extremely dense breast tissue.

A total of 26% of women withdrew from the study – four because of side effects (headache, back pain, joint pain), six because of abnormal laboratory values, and the remainder for other reasons.

Baseline to 12-month changes in breast density were measured in all patients on a continuous scale using the visual analog scale method. Mean density at study entry was 31.6% and 32.4% at the end of treatment. Because of the skewed distribution of breast density change, a Wilcoxon signed-rank test was performed to determine if the change in breast density varied with treatment. No statistically significant difference was observed between the two treatment groups (P = .89).

Premenopausal women with regular menstrual cycles (four cycles in past 6 months) were eligible if they were at least 35 years of age and at increased risk of developing breast cancer. Increased risk was defined as having at least one of the following: a prior biopsy demonstrating atypical hyperplasia or lobular carcinoma in situ; BRCA1/2 mutation carrier (or mutation is in a family member); 5-year Gail Model Risk of greater than1.66%; a strong family history of breast and/or ovarian cancer; a prior history of breast cancer (ductal carcinoma in situ and stage 0-IIIb) and at least 1 year off of all therapy; and a history of chemoradiotherapy treatment for Hodgkin’s disease.

Women were excluded if they had a history of stage IV breast cancer or ovarian cancer; were already taking statins; were taking HRT, tamoxifen, raloxifene, an aromatase inhibitor; or were participating in another chemoprevention trial.

The researchers urged caution in interpreting the data, given the small sample size, slow accrual, wide variation in the mammographic density in this population, and the fact that mammograms were done during the transition to digital mammography.

"While the primary aim of this study was not met, we have shown that biomarker studies can be done in a multi-institutional setting ... Additional biomarker evaluation may prove informative," they wrote

Dr. Wood and her associates are currently analyzing the effect of a daily statin vs. placebo on markers of breast cancer risk, including mammographic density, serum markers (IGF-1), and tissue markers (atypia and Ki67).

This study is sponsored by the Breast Cancer Research Foundation and the Cancer and Leukemia Group B. The researchers reported that they have no relevant disclosures.

SAN ANTONIO – Treatment with atorvastatin did not significantly change mammographic density after 1 year in a small randomized phase III study of premenopausal women at high risk for breast cancer.

While statins are widely used to prevent cardiovascular disease, it has been suggested that these drugs also may have a role in breast cancer prevention. Statin users are estimated to have a 30%-70% lower incidence of breast cancer, compared with nonusers, according to Dr. Marie E. Wood, professor of medicine and director of the familial cancer program at the University of Vermont, Burlington, and her coinvestigators.

A total of 63 premenopausal women were randomized to receive either 40 mg of atorvastatin (Lipitor) or placebo daily for a year. At the end of that time the investigators found no association between change in breast density and atorvastatin use in a multivariable linear regression analysis adjusted for age and body mass index. The data were presented in poster form at the San Antonio Breast Cancer Symposium.

The women had a mean age of 44 years and a mean body mass index (BMI) of 26.4 kg/m². Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS), which is a standardized qualitative assessment of mammographic breast density with four categories.

Four percent of women had fatty-replaced breast tissue, 29% had scattered fibroglandular densities, 56% had heterogeneously dense breasts, and 11% had extremely dense breast tissue.

A total of 26% of women withdrew from the study – four because of side effects (headache, back pain, joint pain), six because of abnormal laboratory values, and the remainder for other reasons.

Baseline to 12-month changes in breast density were measured in all patients on a continuous scale using the visual analog scale method. Mean density at study entry was 31.6% and 32.4% at the end of treatment. Because of the skewed distribution of breast density change, a Wilcoxon signed-rank test was performed to determine if the change in breast density varied with treatment. No statistically significant difference was observed between the two treatment groups (P = .89).

Premenopausal women with regular menstrual cycles (four cycles in past 6 months) were eligible if they were at least 35 years of age and at increased risk of developing breast cancer. Increased risk was defined as having at least one of the following: a prior biopsy demonstrating atypical hyperplasia or lobular carcinoma in situ; BRCA1/2 mutation carrier (or mutation is in a family member); 5-year Gail Model Risk of greater than1.66%; a strong family history of breast and/or ovarian cancer; a prior history of breast cancer (ductal carcinoma in situ and stage 0-IIIb) and at least 1 year off of all therapy; and a history of chemoradiotherapy treatment for Hodgkin’s disease.

Women were excluded if they had a history of stage IV breast cancer or ovarian cancer; were already taking statins; were taking HRT, tamoxifen, raloxifene, an aromatase inhibitor; or were participating in another chemoprevention trial.

The researchers urged caution in interpreting the data, given the small sample size, slow accrual, wide variation in the mammographic density in this population, and the fact that mammograms were done during the transition to digital mammography.

"While the primary aim of this study was not met, we have shown that biomarker studies can be done in a multi-institutional setting ... Additional biomarker evaluation may prove informative," they wrote

Dr. Wood and her associates are currently analyzing the effect of a daily statin vs. placebo on markers of breast cancer risk, including mammographic density, serum markers (IGF-1), and tissue markers (atypia and Ki67).

This study is sponsored by the Breast Cancer Research Foundation and the Cancer and Leukemia Group B. The researchers reported that they have no relevant disclosures.

SAN ANTONIO – Treatment with atorvastatin did not significantly change mammographic density after 1 year in a small randomized phase III study of premenopausal women at high risk for breast cancer.

While statins are widely used to prevent cardiovascular disease, it has been suggested that these drugs also may have a role in breast cancer prevention. Statin users are estimated to have a 30%-70% lower incidence of breast cancer, compared with nonusers, according to Dr. Marie E. Wood, professor of medicine and director of the familial cancer program at the University of Vermont, Burlington, and her coinvestigators.

A total of 63 premenopausal women were randomized to receive either 40 mg of atorvastatin (Lipitor) or placebo daily for a year. At the end of that time the investigators found no association between change in breast density and atorvastatin use in a multivariable linear regression analysis adjusted for age and body mass index. The data were presented in poster form at the San Antonio Breast Cancer Symposium.

The women had a mean age of 44 years and a mean body mass index (BMI) of 26.4 kg/m². Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS), which is a standardized qualitative assessment of mammographic breast density with four categories.

Four percent of women had fatty-replaced breast tissue, 29% had scattered fibroglandular densities, 56% had heterogeneously dense breasts, and 11% had extremely dense breast tissue.

A total of 26% of women withdrew from the study – four because of side effects (headache, back pain, joint pain), six because of abnormal laboratory values, and the remainder for other reasons.

Baseline to 12-month changes in breast density were measured in all patients on a continuous scale using the visual analog scale method. Mean density at study entry was 31.6% and 32.4% at the end of treatment. Because of the skewed distribution of breast density change, a Wilcoxon signed-rank test was performed to determine if the change in breast density varied with treatment. No statistically significant difference was observed between the two treatment groups (P = .89).

Premenopausal women with regular menstrual cycles (four cycles in past 6 months) were eligible if they were at least 35 years of age and at increased risk of developing breast cancer. Increased risk was defined as having at least one of the following: a prior biopsy demonstrating atypical hyperplasia or lobular carcinoma in situ; BRCA1/2 mutation carrier (or mutation is in a family member); 5-year Gail Model Risk of greater than1.66%; a strong family history of breast and/or ovarian cancer; a prior history of breast cancer (ductal carcinoma in situ and stage 0-IIIb) and at least 1 year off of all therapy; and a history of chemoradiotherapy treatment for Hodgkin’s disease.

Women were excluded if they had a history of stage IV breast cancer or ovarian cancer; were already taking statins; were taking HRT, tamoxifen, raloxifene, an aromatase inhibitor; or were participating in another chemoprevention trial.

The researchers urged caution in interpreting the data, given the small sample size, slow accrual, wide variation in the mammographic density in this population, and the fact that mammograms were done during the transition to digital mammography.

"While the primary aim of this study was not met, we have shown that biomarker studies can be done in a multi-institutional setting ... Additional biomarker evaluation may prove informative," they wrote

Dr. Wood and her associates are currently analyzing the effect of a daily statin vs. placebo on markers of breast cancer risk, including mammographic density, serum markers (IGF-1), and tissue markers (atypia and Ki67).

This study is sponsored by the Breast Cancer Research Foundation and the Cancer and Leukemia Group B. The researchers reported that they have no relevant disclosures.