The introduction of widespread screening mammography in Norway was associated with an estimated 15%-25% "overdiagnosis" of breast cancer there, according to a report in the April 3 issue of the Annals of Internal Medicine.

This finding is consistent with those of previous studies in other countries, which estimated rates of overdiagnosis ranging from 0% to 54%, with randomized controlled trials tending to estimate it at approximately 30%, investigators said.

The result of this study in Norway adds to the evidence that "overdiagnosis and unnecessary treatment of nonfatal cancer creates a substantial ethical and clinical dilemma and may cast doubt on whether mammography screening programs should exist," said Dr. Mette Kalager of the department of epidemiology, Harvard School of Public Health, Boston, and her associates.

Screening mammography was uncommon in Norway until a national, state-funded program began in 1996. Screening mammography was then implemented gradually, in different geographic areas, over the course of 10 years. Since 2005, all women in Norway aged 50-69 years have been invited to participate in mammographic screening every 2 years, and approximately 77% of them do so.

"This staggered implementation allowed comparison of contemporaneous trends in breast cancer incidence in areas with and without mammography screening," as well as the comparison of current and historical trends in incidence. This in turn gave the researchers two analytic methods for calculating estimates of overdiagnosis.

They defined overdiagnosis as the percentage of cases of cancer that would not have become clinically apparent in a woman’s lifetime without screening. It refers to cases of breast cancer that would be diagnosed and treated without yielding any possible survival benefit – cases in which the tumor would never have progressed to a clinical stage or in which the woman would die from other causes before the breast cancer became evident.

The study population comprised 39,888 women diagnosed as having invasive breast cancer in 1996-2005, including 27,238 who were aged 50-79 years at diagnosis. A total of 7,793 women were diagnosed after the introduction of routine screening.

In fully adjusted analyses using the first method of estimating, 15%-20% of the cases of breast cancer found on screening mammography – that is, between 1,169 and 1,948 women – were overdiagnosed. In an analysis using the second method of estimating, 18%-25% of cases were overdiagnosed.

Thus, the overall rate of overdiagnosis in this study was 15%-25%, Dr. Kalager and her colleagues said (Ann. Intern. Med. 2012;156:491-9).

Moreover, the proportion of advanced-stage breast cancers decreased over time to the same degree among screened and unscreened women, while the proportion of stage I breast cancers markedly increased only among screened women. This indicates that the cancers being found on screening mammography were almost entirely early-stage, low-risk tumors.

"Our findings suggest that enhanced awareness is probably the reason for the reduction of late-stage cancer, not screening," the investigators noted.

Extrapolating their findings, they added that "after 10 years of biennial mammography screening, for every 2,500 women invited, 6-10 women have been overdiagnosed, 20 women are diagnosed with breast cancer ... and one death from breast cancer has been prevented.

"To put it differently, if 2,500 women are invited to undergo mammography screening over 10 years, 2,470-2,474 women will not be diagnosed with breast cancer, 2,499 will not die of breast cancer, but 6-10 women will be overdiagnosed," they said.

This study was supported by the Research Council of Norway and Frontier Science. Dr. Kalager and her coauthors had no relevant disclosures.

The introduction of widespread screening mammography in Norway was associated with an estimated 15%-25% "overdiagnosis" of breast cancer there, according to a report in the April 3 issue of the Annals of Internal Medicine.

This finding is consistent with those of previous studies in other countries, which estimated rates of overdiagnosis ranging from 0% to 54%, with randomized controlled trials tending to estimate it at approximately 30%, investigators said.

The result of this study in Norway adds to the evidence that "overdiagnosis and unnecessary treatment of nonfatal cancer creates a substantial ethical and clinical dilemma and may cast doubt on whether mammography screening programs should exist," said Dr. Mette Kalager of the department of epidemiology, Harvard School of Public Health, Boston, and her associates.

Screening mammography was uncommon in Norway until a national, state-funded program began in 1996. Screening mammography was then implemented gradually, in different geographic areas, over the course of 10 years. Since 2005, all women in Norway aged 50-69 years have been invited to participate in mammographic screening every 2 years, and approximately 77% of them do so.

"This staggered implementation allowed comparison of contemporaneous trends in breast cancer incidence in areas with and without mammography screening," as well as the comparison of current and historical trends in incidence. This in turn gave the researchers two analytic methods for calculating estimates of overdiagnosis.

They defined overdiagnosis as the percentage of cases of cancer that would not have become clinically apparent in a woman’s lifetime without screening. It refers to cases of breast cancer that would be diagnosed and treated without yielding any possible survival benefit – cases in which the tumor would never have progressed to a clinical stage or in which the woman would die from other causes before the breast cancer became evident.

The study population comprised 39,888 women diagnosed as having invasive breast cancer in 1996-2005, including 27,238 who were aged 50-79 years at diagnosis. A total of 7,793 women were diagnosed after the introduction of routine screening.

In fully adjusted analyses using the first method of estimating, 15%-20% of the cases of breast cancer found on screening mammography – that is, between 1,169 and 1,948 women – were overdiagnosed. In an analysis using the second method of estimating, 18%-25% of cases were overdiagnosed.

Thus, the overall rate of overdiagnosis in this study was 15%-25%, Dr. Kalager and her colleagues said (Ann. Intern. Med. 2012;156:491-9).

Moreover, the proportion of advanced-stage breast cancers decreased over time to the same degree among screened and unscreened women, while the proportion of stage I breast cancers markedly increased only among screened women. This indicates that the cancers being found on screening mammography were almost entirely early-stage, low-risk tumors.

"Our findings suggest that enhanced awareness is probably the reason for the reduction of late-stage cancer, not screening," the investigators noted.

Extrapolating their findings, they added that "after 10 years of biennial mammography screening, for every 2,500 women invited, 6-10 women have been overdiagnosed, 20 women are diagnosed with breast cancer ... and one death from breast cancer has been prevented.

"To put it differently, if 2,500 women are invited to undergo mammography screening over 10 years, 2,470-2,474 women will not be diagnosed with breast cancer, 2,499 will not die of breast cancer, but 6-10 women will be overdiagnosed," they said.

This study was supported by the Research Council of Norway and Frontier Science. Dr. Kalager and her coauthors had no relevant disclosures.

The introduction of widespread screening mammography in Norway was associated with an estimated 15%-25% "overdiagnosis" of breast cancer there, according to a report in the April 3 issue of the Annals of Internal Medicine.

This finding is consistent with those of previous studies in other countries, which estimated rates of overdiagnosis ranging from 0% to 54%, with randomized controlled trials tending to estimate it at approximately 30%, investigators said.

The result of this study in Norway adds to the evidence that "overdiagnosis and unnecessary treatment of nonfatal cancer creates a substantial ethical and clinical dilemma and may cast doubt on whether mammography screening programs should exist," said Dr. Mette Kalager of the department of epidemiology, Harvard School of Public Health, Boston, and her associates.

Screening mammography was uncommon in Norway until a national, state-funded program began in 1996. Screening mammography was then implemented gradually, in different geographic areas, over the course of 10 years. Since 2005, all women in Norway aged 50-69 years have been invited to participate in mammographic screening every 2 years, and approximately 77% of them do so.

"This staggered implementation allowed comparison of contemporaneous trends in breast cancer incidence in areas with and without mammography screening," as well as the comparison of current and historical trends in incidence. This in turn gave the researchers two analytic methods for calculating estimates of overdiagnosis.

They defined overdiagnosis as the percentage of cases of cancer that would not have become clinically apparent in a woman’s lifetime without screening. It refers to cases of breast cancer that would be diagnosed and treated without yielding any possible survival benefit – cases in which the tumor would never have progressed to a clinical stage or in which the woman would die from other causes before the breast cancer became evident.

The study population comprised 39,888 women diagnosed as having invasive breast cancer in 1996-2005, including 27,238 who were aged 50-79 years at diagnosis. A total of 7,793 women were diagnosed after the introduction of routine screening.

In fully adjusted analyses using the first method of estimating, 15%-20% of the cases of breast cancer found on screening mammography – that is, between 1,169 and 1,948 women – were overdiagnosed. In an analysis using the second method of estimating, 18%-25% of cases were overdiagnosed.

Thus, the overall rate of overdiagnosis in this study was 15%-25%, Dr. Kalager and her colleagues said (Ann. Intern. Med. 2012;156:491-9).

Moreover, the proportion of advanced-stage breast cancers decreased over time to the same degree among screened and unscreened women, while the proportion of stage I breast cancers markedly increased only among screened women. This indicates that the cancers being found on screening mammography were almost entirely early-stage, low-risk tumors.

"Our findings suggest that enhanced awareness is probably the reason for the reduction of late-stage cancer, not screening," the investigators noted.

Extrapolating their findings, they added that "after 10 years of biennial mammography screening, for every 2,500 women invited, 6-10 women have been overdiagnosed, 20 women are diagnosed with breast cancer ... and one death from breast cancer has been prevented.

"To put it differently, if 2,500 women are invited to undergo mammography screening over 10 years, 2,470-2,474 women will not be diagnosed with breast cancer, 2,499 will not die of breast cancer, but 6-10 women will be overdiagnosed," they said.

This study was supported by the Research Council of Norway and Frontier Science. Dr. Kalager and her coauthors had no relevant disclosures.

Chemotherapy doses should be tailored for obese cancer patients based on their actual body weight, not their ideal body weight, according to a new practice guideline from the American Society of Clinical Oncology.

There is no evidence that full-weight-based chemotherapy doses cause greater toxicity than adjusted doses, and concerns about "overdosing" obese cancer patients are unfounded, a panel of experts wrote in a report published online April 2 in the Journal of Clinical Oncology.

A systematic review of the literature showed that many overweight and obese cancer patients continue to receive underdoses of intravenous and oral cytotoxic drugs because of "considerable uncertainty among physicians about optimal dose selection," even though research has confirmed that full-weight-based dosing is both safe and crucial to the patients’ survival.

"Many oncologists continue to use either ideal body weight or adjusted ideal body weight, or to cap the body surface area at, for example, 2.0 m², rather than use actual body weight to calculate body surface area," said Dr. Jennifer J. Griggs of the University of Michigan, Ann Arbor, and her associates on the expert panel for ASCO’s new practice guideline.

As a result, chemotherapy dosing varies widely in overweight and obese patients, with as many as 40% receiving less than optimal dosing. This "may explain, in part, the significantly higher cancer mortality observed in overweight and obese individuals," they noted.

"With the incidence of obesity at an all-time high in the United States, as well as in other developed and developing nations, oncologists face this issue more than ever before," Dr. Griggs added in a press statement accompanying release of the guideline.

The ASCO guideline panel reviewed all the randomized clinical trials, meta-analyses, and clinical practice guidelines of other organizations concerning cytotoxic oral or IV chemotherapy dosing approaches for overweight or obese patients with cancer, excluding leukemias. Since there have been no prospective randomized studies directly comparing full-weight-based dose selection against other types of dose selection, they had to rely primarily on subgroup analyses and registry data.

Most of the studies concerned breast, ovarian, colon, and lung cancers, the authors said. As little data in the literature addressed dosing for novel agents such as tyrosine kinase inhibitors, immunotherapies such as interleukin-2 or interferon, or monoclonal antibodies, the guideline did not address these agents.

A summary of the guideline (J. Clin. Oncol. 2012 [doi:10.1200/JCO.2011.39.9436]) lists these key recommendations:

• Actual body weight should be used to select cytotoxic chemotherapy doses, regardless of obesity status. There is no evidence that either short- or long-term toxicity is increased with this approach.

• Use the same strategy in obese patients as in other patients for dose reductions, taking into account the type and severity of toxicity, any comorbid conditions, and whether the aim of treatment is cure or palliation. There is no evidence that greater dose reductions are needed for obese patients. Also, consider resuming the full-weight-based dose for subsequent chemotherapy cycles, especially if a possible cause of toxicity (such as impaired renal or liver function) has resolved.

• Consider fixed dosing only with select cytotoxic agents for which maximal dosing limits have been established, such as vincristine, carboplatin, or bleomycin.

• Calculate body surface area using any of the standard formulas currently available. There is no evidence to support using one formula over any other.

• Further research is needed into the pharmacokinetics and pharmacogenetics of chemotherapy dosing for obese patients, who have been excluded from many anticancer drug trials.

The guideline also emphasizes that physicians may need to fully discuss this issue with patients and caregivers, stressing that higher doses are needed in obese patients for the chemotherapy to be effective and reassuring them that toxicity is not expected to be any greater at proportionally higher doses.

"Communication with other health care providers is also warranted. Pharmacists and nursing professionals who are accustomed to limiting chemotherapy doses for obese patients should be informed of the existing evidence. IV and oral doses may be prepackaged for patients of normal weight, but appropriate dosing should be delivered, regardless of doses contained within a given vial. Arbitrary capping based on drug procurement is unacceptable (e.g., 1 vs. 1.5 vials)," the guideline stated.

Clinicians also should be aware that since rates of obesity are higher in black patients, Hispanic patients, and patients of lower socioeconomic status, these groups are harmed the most by underdosing and may benefit the most when full-weight-based dosing is adopted.

"This guideline should ease fears about administering chemotherapy based on actual body weight to otherwise healthy obese patients with cancer," Dr. Gary H. Lyman, cochair of the expert panel that drafted the guideline, said in a press statement.

"While chemotherapy dose for an obese patient may be larger than some physicians are accustomed to, they can rest assured that the risk of toxicity associated with chemotherapy dosing based on actual body weight is no greater in obese patients than in nonobese patients with cancer," said Dr. Lyman, a professor of medicine in the division of medical oncology at Duke University, Durham, N.C.

The full practice guideline, along with additional information on methodology and clinical resources, is available at ASCO’s website. For additional patient information, click here.

No financial conflicts of interest were reported.

Chemotherapy doses should be tailored for obese cancer patients based on their actual body weight, not their ideal body weight, according to a new practice guideline from the American Society of Clinical Oncology.

There is no evidence that full-weight-based chemotherapy doses cause greater toxicity than adjusted doses, and concerns about "overdosing" obese cancer patients are unfounded, a panel of experts wrote in a report published online April 2 in the Journal of Clinical Oncology.

A systematic review of the literature showed that many overweight and obese cancer patients continue to receive underdoses of intravenous and oral cytotoxic drugs because of "considerable uncertainty among physicians about optimal dose selection," even though research has confirmed that full-weight-based dosing is both safe and crucial to the patients’ survival.

"Many oncologists continue to use either ideal body weight or adjusted ideal body weight, or to cap the body surface area at, for example, 2.0 m², rather than use actual body weight to calculate body surface area," said Dr. Jennifer J. Griggs of the University of Michigan, Ann Arbor, and her associates on the expert panel for ASCO’s new practice guideline.

As a result, chemotherapy dosing varies widely in overweight and obese patients, with as many as 40% receiving less than optimal dosing. This "may explain, in part, the significantly higher cancer mortality observed in overweight and obese individuals," they noted.

"With the incidence of obesity at an all-time high in the United States, as well as in other developed and developing nations, oncologists face this issue more than ever before," Dr. Griggs added in a press statement accompanying release of the guideline.

The ASCO guideline panel reviewed all the randomized clinical trials, meta-analyses, and clinical practice guidelines of other organizations concerning cytotoxic oral or IV chemotherapy dosing approaches for overweight or obese patients with cancer, excluding leukemias. Since there have been no prospective randomized studies directly comparing full-weight-based dose selection against other types of dose selection, they had to rely primarily on subgroup analyses and registry data.

Most of the studies concerned breast, ovarian, colon, and lung cancers, the authors said. As little data in the literature addressed dosing for novel agents such as tyrosine kinase inhibitors, immunotherapies such as interleukin-2 or interferon, or monoclonal antibodies, the guideline did not address these agents.

A summary of the guideline (J. Clin. Oncol. 2012 [doi:10.1200/JCO.2011.39.9436]) lists these key recommendations:

• Actual body weight should be used to select cytotoxic chemotherapy doses, regardless of obesity status. There is no evidence that either short- or long-term toxicity is increased with this approach.

• Use the same strategy in obese patients as in other patients for dose reductions, taking into account the type and severity of toxicity, any comorbid conditions, and whether the aim of treatment is cure or palliation. There is no evidence that greater dose reductions are needed for obese patients. Also, consider resuming the full-weight-based dose for subsequent chemotherapy cycles, especially if a possible cause of toxicity (such as impaired renal or liver function) has resolved.

• Consider fixed dosing only with select cytotoxic agents for which maximal dosing limits have been established, such as vincristine, carboplatin, or bleomycin.

• Calculate body surface area using any of the standard formulas currently available. There is no evidence to support using one formula over any other.

• Further research is needed into the pharmacokinetics and pharmacogenetics of chemotherapy dosing for obese patients, who have been excluded from many anticancer drug trials.

The guideline also emphasizes that physicians may need to fully discuss this issue with patients and caregivers, stressing that higher doses are needed in obese patients for the chemotherapy to be effective and reassuring them that toxicity is not expected to be any greater at proportionally higher doses.

"Communication with other health care providers is also warranted. Pharmacists and nursing professionals who are accustomed to limiting chemotherapy doses for obese patients should be informed of the existing evidence. IV and oral doses may be prepackaged for patients of normal weight, but appropriate dosing should be delivered, regardless of doses contained within a given vial. Arbitrary capping based on drug procurement is unacceptable (e.g., 1 vs. 1.5 vials)," the guideline stated.

Clinicians also should be aware that since rates of obesity are higher in black patients, Hispanic patients, and patients of lower socioeconomic status, these groups are harmed the most by underdosing and may benefit the most when full-weight-based dosing is adopted.

"This guideline should ease fears about administering chemotherapy based on actual body weight to otherwise healthy obese patients with cancer," Dr. Gary H. Lyman, cochair of the expert panel that drafted the guideline, said in a press statement.

"While chemotherapy dose for an obese patient may be larger than some physicians are accustomed to, they can rest assured that the risk of toxicity associated with chemotherapy dosing based on actual body weight is no greater in obese patients than in nonobese patients with cancer," said Dr. Lyman, a professor of medicine in the division of medical oncology at Duke University, Durham, N.C.

The full practice guideline, along with additional information on methodology and clinical resources, is available at ASCO’s website. For additional patient information, click here.

No financial conflicts of interest were reported.

Chemotherapy doses should be tailored for obese cancer patients based on their actual body weight, not their ideal body weight, according to a new practice guideline from the American Society of Clinical Oncology.

There is no evidence that full-weight-based chemotherapy doses cause greater toxicity than adjusted doses, and concerns about "overdosing" obese cancer patients are unfounded, a panel of experts wrote in a report published online April 2 in the Journal of Clinical Oncology.

A systematic review of the literature showed that many overweight and obese cancer patients continue to receive underdoses of intravenous and oral cytotoxic drugs because of "considerable uncertainty among physicians about optimal dose selection," even though research has confirmed that full-weight-based dosing is both safe and crucial to the patients’ survival.

"Many oncologists continue to use either ideal body weight or adjusted ideal body weight, or to cap the body surface area at, for example, 2.0 m², rather than use actual body weight to calculate body surface area," said Dr. Jennifer J. Griggs of the University of Michigan, Ann Arbor, and her associates on the expert panel for ASCO’s new practice guideline.

As a result, chemotherapy dosing varies widely in overweight and obese patients, with as many as 40% receiving less than optimal dosing. This "may explain, in part, the significantly higher cancer mortality observed in overweight and obese individuals," they noted.

"With the incidence of obesity at an all-time high in the United States, as well as in other developed and developing nations, oncologists face this issue more than ever before," Dr. Griggs added in a press statement accompanying release of the guideline.

The ASCO guideline panel reviewed all the randomized clinical trials, meta-analyses, and clinical practice guidelines of other organizations concerning cytotoxic oral or IV chemotherapy dosing approaches for overweight or obese patients with cancer, excluding leukemias. Since there have been no prospective randomized studies directly comparing full-weight-based dose selection against other types of dose selection, they had to rely primarily on subgroup analyses and registry data.

Most of the studies concerned breast, ovarian, colon, and lung cancers, the authors said. As little data in the literature addressed dosing for novel agents such as tyrosine kinase inhibitors, immunotherapies such as interleukin-2 or interferon, or monoclonal antibodies, the guideline did not address these agents.

A summary of the guideline (J. Clin. Oncol. 2012 [doi:10.1200/JCO.2011.39.9436]) lists these key recommendations:

• Actual body weight should be used to select cytotoxic chemotherapy doses, regardless of obesity status. There is no evidence that either short- or long-term toxicity is increased with this approach.

• Use the same strategy in obese patients as in other patients for dose reductions, taking into account the type and severity of toxicity, any comorbid conditions, and whether the aim of treatment is cure or palliation. There is no evidence that greater dose reductions are needed for obese patients. Also, consider resuming the full-weight-based dose for subsequent chemotherapy cycles, especially if a possible cause of toxicity (such as impaired renal or liver function) has resolved.

• Consider fixed dosing only with select cytotoxic agents for which maximal dosing limits have been established, such as vincristine, carboplatin, or bleomycin.

• Calculate body surface area using any of the standard formulas currently available. There is no evidence to support using one formula over any other.

• Further research is needed into the pharmacokinetics and pharmacogenetics of chemotherapy dosing for obese patients, who have been excluded from many anticancer drug trials.

The guideline also emphasizes that physicians may need to fully discuss this issue with patients and caregivers, stressing that higher doses are needed in obese patients for the chemotherapy to be effective and reassuring them that toxicity is not expected to be any greater at proportionally higher doses.

"Communication with other health care providers is also warranted. Pharmacists and nursing professionals who are accustomed to limiting chemotherapy doses for obese patients should be informed of the existing evidence. IV and oral doses may be prepackaged for patients of normal weight, but appropriate dosing should be delivered, regardless of doses contained within a given vial. Arbitrary capping based on drug procurement is unacceptable (e.g., 1 vs. 1.5 vials)," the guideline stated.

Clinicians also should be aware that since rates of obesity are higher in black patients, Hispanic patients, and patients of lower socioeconomic status, these groups are harmed the most by underdosing and may benefit the most when full-weight-based dosing is adopted.

"This guideline should ease fears about administering chemotherapy based on actual body weight to otherwise healthy obese patients with cancer," Dr. Gary H. Lyman, cochair of the expert panel that drafted the guideline, said in a press statement.

"While chemotherapy dose for an obese patient may be larger than some physicians are accustomed to, they can rest assured that the risk of toxicity associated with chemotherapy dosing based on actual body weight is no greater in obese patients than in nonobese patients with cancer," said Dr. Lyman, a professor of medicine in the division of medical oncology at Duke University, Durham, N.C.

The full practice guideline, along with additional information on methodology and clinical resources, is available at ASCO’s website. For additional patient information, click here.

No financial conflicts of interest were reported.

CHICAGO – Long-term use of estrogen-only therapy increases the risk of postmenopausal women developing breast cancer, according to new data from the Nurses’ Health Study.

The finding, reported April 1 by Dr. Wendy Chen at the annual meeting of the American Association for Cancer Research, suggests that opting for progesterone-free hormone therapy for the treatment of menopause symptoms should not be considered the risk-free alternative to combination progesterone plus estrogen formulations.

Still, the absolute risks were small. During the study’s 1.57 million person-years of follow-up from 1980 through 2008, 5,631 incident invasive breast cancers were diagnosed and 884 of the women died of breast cancer.

To evaluate the breast cancer risk associated with long-term use of both combined and estrogen-only hormone therapy, Dr. Chen of Brigham and Women’s Hospital in Boston and her colleagues evaluated data collected over 28 years through the Nurses’ Health Study. Of the 121,700 study participants who were aged 30-55 years in 1976, women who used estrogen-only therapy for 10.0-14.9 years and for 15.0-19.9 years had, respectively, a 22% and 43% increased risk of developing breast cancer relative to those women not on hormone therapy (HT).

"Our data also confirmed the previously reported increased risk associated with combined hormone therapy," Dr. Chen stated, noting that women in the study who used progesterone plus estrogen for 10-14.9 years had an 88% increased risk of developing breast cancer relative to those not on HT and the risk increased to more than twofold in women using it for up to 20 years. Further, the risk of developing breast cancer does not appear to plateau over time, but rather continues to increase. "The longer women use [HT]. The higher their risk," she said.

In a separate analysis, the investigators restricted the study population to healthy, active postmenopausal women 50-79 years with an intact uterus – the same population observed in the Women’s Health Initiative. "What we saw was a decline in breast cancer risk among women using estrogen-only therapy for less than 10 years, but an increased risk among those women using estrogen for 15-20 years," Dr. Chen said.

Importantly, although breast cancer incidence was increased in the HT groups, "there was no increase in the risk of fatal breast cancer, either with combined or estrogen-only therapy," Dr. Chen stressed. "This is something we are continuing to investigate."

The findings have the potential to increase the confusion regarding HT and to perhaps reignite the hormone therapy debate, Dr. Chen acknowledged in an interview. However, they should be considered in their proper context. "While the relative risk of developing breast cancer in increased, the absolute risk associated with [HT] are low," she said.

The observed effects associated with HT were stronger for estrogen receptor–positive tumors and among thinner women, Dr. Chen noted, adding that the results were similar when limited to women who underwent regular breast cancer screening.

The study was funded by the National Cancer Institute. Dr. Chen disclosed no financial conflicts of interest.

CHICAGO – Long-term use of estrogen-only therapy increases the risk of postmenopausal women developing breast cancer, according to new data from the Nurses’ Health Study.

The finding, reported April 1 by Dr. Wendy Chen at the annual meeting of the American Association for Cancer Research, suggests that opting for progesterone-free hormone therapy for the treatment of menopause symptoms should not be considered the risk-free alternative to combination progesterone plus estrogen formulations.

Still, the absolute risks were small. During the study’s 1.57 million person-years of follow-up from 1980 through 2008, 5,631 incident invasive breast cancers were diagnosed and 884 of the women died of breast cancer.

To evaluate the breast cancer risk associated with long-term use of both combined and estrogen-only hormone therapy, Dr. Chen of Brigham and Women’s Hospital in Boston and her colleagues evaluated data collected over 28 years through the Nurses’ Health Study. Of the 121,700 study participants who were aged 30-55 years in 1976, women who used estrogen-only therapy for 10.0-14.9 years and for 15.0-19.9 years had, respectively, a 22% and 43% increased risk of developing breast cancer relative to those women not on hormone therapy (HT).

"Our data also confirmed the previously reported increased risk associated with combined hormone therapy," Dr. Chen stated, noting that women in the study who used progesterone plus estrogen for 10-14.9 years had an 88% increased risk of developing breast cancer relative to those not on HT and the risk increased to more than twofold in women using it for up to 20 years. Further, the risk of developing breast cancer does not appear to plateau over time, but rather continues to increase. "The longer women use [HT]. The higher their risk," she said.

In a separate analysis, the investigators restricted the study population to healthy, active postmenopausal women 50-79 years with an intact uterus – the same population observed in the Women’s Health Initiative. "What we saw was a decline in breast cancer risk among women using estrogen-only therapy for less than 10 years, but an increased risk among those women using estrogen for 15-20 years," Dr. Chen said.

Importantly, although breast cancer incidence was increased in the HT groups, "there was no increase in the risk of fatal breast cancer, either with combined or estrogen-only therapy," Dr. Chen stressed. "This is something we are continuing to investigate."

The findings have the potential to increase the confusion regarding HT and to perhaps reignite the hormone therapy debate, Dr. Chen acknowledged in an interview. However, they should be considered in their proper context. "While the relative risk of developing breast cancer in increased, the absolute risk associated with [HT] are low," she said.

The observed effects associated with HT were stronger for estrogen receptor–positive tumors and among thinner women, Dr. Chen noted, adding that the results were similar when limited to women who underwent regular breast cancer screening.

The study was funded by the National Cancer Institute. Dr. Chen disclosed no financial conflicts of interest.

CHICAGO – Long-term use of estrogen-only therapy increases the risk of postmenopausal women developing breast cancer, according to new data from the Nurses’ Health Study.

The finding, reported April 1 by Dr. Wendy Chen at the annual meeting of the American Association for Cancer Research, suggests that opting for progesterone-free hormone therapy for the treatment of menopause symptoms should not be considered the risk-free alternative to combination progesterone plus estrogen formulations.

Still, the absolute risks were small. During the study’s 1.57 million person-years of follow-up from 1980 through 2008, 5,631 incident invasive breast cancers were diagnosed and 884 of the women died of breast cancer.

To evaluate the breast cancer risk associated with long-term use of both combined and estrogen-only hormone therapy, Dr. Chen of Brigham and Women’s Hospital in Boston and her colleagues evaluated data collected over 28 years through the Nurses’ Health Study. Of the 121,700 study participants who were aged 30-55 years in 1976, women who used estrogen-only therapy for 10.0-14.9 years and for 15.0-19.9 years had, respectively, a 22% and 43% increased risk of developing breast cancer relative to those women not on hormone therapy (HT).

"Our data also confirmed the previously reported increased risk associated with combined hormone therapy," Dr. Chen stated, noting that women in the study who used progesterone plus estrogen for 10-14.9 years had an 88% increased risk of developing breast cancer relative to those not on HT and the risk increased to more than twofold in women using it for up to 20 years. Further, the risk of developing breast cancer does not appear to plateau over time, but rather continues to increase. "The longer women use [HT]. The higher their risk," she said.

In a separate analysis, the investigators restricted the study population to healthy, active postmenopausal women 50-79 years with an intact uterus – the same population observed in the Women’s Health Initiative. "What we saw was a decline in breast cancer risk among women using estrogen-only therapy for less than 10 years, but an increased risk among those women using estrogen for 15-20 years," Dr. Chen said.

Importantly, although breast cancer incidence was increased in the HT groups, "there was no increase in the risk of fatal breast cancer, either with combined or estrogen-only therapy," Dr. Chen stressed. "This is something we are continuing to investigate."

The findings have the potential to increase the confusion regarding HT and to perhaps reignite the hormone therapy debate, Dr. Chen acknowledged in an interview. However, they should be considered in their proper context. "While the relative risk of developing breast cancer in increased, the absolute risk associated with [HT] are low," she said.

The observed effects associated with HT were stronger for estrogen receptor–positive tumors and among thinner women, Dr. Chen noted, adding that the results were similar when limited to women who underwent regular breast cancer screening.

The study was funded by the National Cancer Institute. Dr. Chen disclosed no financial conflicts of interest.

ORLANDO  – Triple-negative breast tumors are notorious for their ability to evade hormonal agents and targeted therapies. But a subset of these intractable tumors expresses androgen receptors, and may be vulnerable to antiandrogen drugs, investigators suggested at the symposium of the Society of Surgical Oncology.

An evaluation of cancerous and normal breast tissues from 94 patients with triple-negative breast tumors (lacking estrogen-, progesterone-, and HER2-receptor expression), showed that the androgen receptor (AR) was expressed in 23% of tumors, reported Dr. Barbara Pockaj of the Mayo Clinic in Scottsdale, Ariz., and colleagues.

AR–positive cancers occurred more frequently in older patients and were significantly associated with lymph node metastases, compared with AR-negative, triple-negative breast cancers in this small study, she said.

There was a trend toward higher tumor stage at diagnosis among patients with AR-positive tumors, but AR-positive and AR-negative patients did not differ significantly in overall or recurrence-free survival, said Dr. Pockaj.

Previous studies have suggested that 10%-43% of triple-negative breast cancers bear the androgen receptor, but the antibodies and methods used for characterizing the presence of the receptor varied significantly, making it difficult to nail down actual numbers, Dr. Pockaj said.

The investigators examined 177 tissue biopsy cores from 94 patients with triple-negative breast cancer to see whether AR-receptor expression correlated with patient and tumor factors and survival, and where expression of the receptors in different tissues from the same patients correlated with tumor progression.

The receptor was expressed in 88% of normal breast tissues in the samples, a proportion identical to that of the estrogen receptor in normal tissues from the same patients.

AR expression was detected in all 6 of 6 adjacent DCIS (ductal carcinoma in situ) samples from AR-positive patients, and in 9 of 15 DCIS samples from patients with AR-negative cancer.

All lymph node metastases from AR-positive patients were also positive, whereas no lymph node metastases from AR-negative patients were found to express the androgen receptor.

There were no significant differences between AR-positive and -negative patients in tumor grade, angiolymphatic invasion, TNM (tumor, node, metastasis) stage, or tumor size. In contrast, 16 of the 72 (22%) of the AR-negative patients had lymph node metastases, compared with 10 of 22 (46%) AR-positive patients (P = .033).

There were no significant differences in locoregional recurrences, overall survival, or disease-specific survival between positive and negative patients.

Among all 94 patients, however, the presence of lymph node metastases was associated with a significantly worse recurrence-free survival (hazard ratio, 5.502; P = .017). Chemotherapy significantly reduced that risk (HR, 0.099; P = .0004).

In multivariate analysis, the investigators found that AR expression was associated with older age (63 years vs. 57 years; P = .051) and with the presence of lymph nodes metastases (P = .033).

Although larger studies are needed, the data suggest that AR-positive, triple-negative breast cancer "has unique clinical behavior and may need different treatment," Dr. Pockaj said.

A phase II, open-label trial of the antiandrogen bicalutamide (Casodex) in patients with AR-positive, estrogen- and progesterone-receptor–negative, metastatic breast cancer is currently underway in eight U.S. cancer centers.

The current study was supported by the Translational Genomics Research Institute, Phoenix, and the Mayo Clinic, Scottsdale, Ariz. Dr. Pockaj is an employee of the Mayo Clinic.

ORLANDO  – Triple-negative breast tumors are notorious for their ability to evade hormonal agents and targeted therapies. But a subset of these intractable tumors expresses androgen receptors, and may be vulnerable to antiandrogen drugs, investigators suggested at the symposium of the Society of Surgical Oncology.

An evaluation of cancerous and normal breast tissues from 94 patients with triple-negative breast tumors (lacking estrogen-, progesterone-, and HER2-receptor expression), showed that the androgen receptor (AR) was expressed in 23% of tumors, reported Dr. Barbara Pockaj of the Mayo Clinic in Scottsdale, Ariz., and colleagues.

AR–positive cancers occurred more frequently in older patients and were significantly associated with lymph node metastases, compared with AR-negative, triple-negative breast cancers in this small study, she said.

There was a trend toward higher tumor stage at diagnosis among patients with AR-positive tumors, but AR-positive and AR-negative patients did not differ significantly in overall or recurrence-free survival, said Dr. Pockaj.

Previous studies have suggested that 10%-43% of triple-negative breast cancers bear the androgen receptor, but the antibodies and methods used for characterizing the presence of the receptor varied significantly, making it difficult to nail down actual numbers, Dr. Pockaj said.

The investigators examined 177 tissue biopsy cores from 94 patients with triple-negative breast cancer to see whether AR-receptor expression correlated with patient and tumor factors and survival, and where expression of the receptors in different tissues from the same patients correlated with tumor progression.

The receptor was expressed in 88% of normal breast tissues in the samples, a proportion identical to that of the estrogen receptor in normal tissues from the same patients.

AR expression was detected in all 6 of 6 adjacent DCIS (ductal carcinoma in situ) samples from AR-positive patients, and in 9 of 15 DCIS samples from patients with AR-negative cancer.

All lymph node metastases from AR-positive patients were also positive, whereas no lymph node metastases from AR-negative patients were found to express the androgen receptor.

There were no significant differences between AR-positive and -negative patients in tumor grade, angiolymphatic invasion, TNM (tumor, node, metastasis) stage, or tumor size. In contrast, 16 of the 72 (22%) of the AR-negative patients had lymph node metastases, compared with 10 of 22 (46%) AR-positive patients (P = .033).

There were no significant differences in locoregional recurrences, overall survival, or disease-specific survival between positive and negative patients.

Among all 94 patients, however, the presence of lymph node metastases was associated with a significantly worse recurrence-free survival (hazard ratio, 5.502; P = .017). Chemotherapy significantly reduced that risk (HR, 0.099; P = .0004).

In multivariate analysis, the investigators found that AR expression was associated with older age (63 years vs. 57 years; P = .051) and with the presence of lymph nodes metastases (P = .033).

Although larger studies are needed, the data suggest that AR-positive, triple-negative breast cancer "has unique clinical behavior and may need different treatment," Dr. Pockaj said.

A phase II, open-label trial of the antiandrogen bicalutamide (Casodex) in patients with AR-positive, estrogen- and progesterone-receptor–negative, metastatic breast cancer is currently underway in eight U.S. cancer centers.

The current study was supported by the Translational Genomics Research Institute, Phoenix, and the Mayo Clinic, Scottsdale, Ariz. Dr. Pockaj is an employee of the Mayo Clinic.

ORLANDO  – Triple-negative breast tumors are notorious for their ability to evade hormonal agents and targeted therapies. But a subset of these intractable tumors expresses androgen receptors, and may be vulnerable to antiandrogen drugs, investigators suggested at the symposium of the Society of Surgical Oncology.

An evaluation of cancerous and normal breast tissues from 94 patients with triple-negative breast tumors (lacking estrogen-, progesterone-, and HER2-receptor expression), showed that the androgen receptor (AR) was expressed in 23% of tumors, reported Dr. Barbara Pockaj of the Mayo Clinic in Scottsdale, Ariz., and colleagues.

AR–positive cancers occurred more frequently in older patients and were significantly associated with lymph node metastases, compared with AR-negative, triple-negative breast cancers in this small study, she said.

There was a trend toward higher tumor stage at diagnosis among patients with AR-positive tumors, but AR-positive and AR-negative patients did not differ significantly in overall or recurrence-free survival, said Dr. Pockaj.

Previous studies have suggested that 10%-43% of triple-negative breast cancers bear the androgen receptor, but the antibodies and methods used for characterizing the presence of the receptor varied significantly, making it difficult to nail down actual numbers, Dr. Pockaj said.

The investigators examined 177 tissue biopsy cores from 94 patients with triple-negative breast cancer to see whether AR-receptor expression correlated with patient and tumor factors and survival, and where expression of the receptors in different tissues from the same patients correlated with tumor progression.

The receptor was expressed in 88% of normal breast tissues in the samples, a proportion identical to that of the estrogen receptor in normal tissues from the same patients.

AR expression was detected in all 6 of 6 adjacent DCIS (ductal carcinoma in situ) samples from AR-positive patients, and in 9 of 15 DCIS samples from patients with AR-negative cancer.

All lymph node metastases from AR-positive patients were also positive, whereas no lymph node metastases from AR-negative patients were found to express the androgen receptor.

There were no significant differences between AR-positive and -negative patients in tumor grade, angiolymphatic invasion, TNM (tumor, node, metastasis) stage, or tumor size. In contrast, 16 of the 72 (22%) of the AR-negative patients had lymph node metastases, compared with 10 of 22 (46%) AR-positive patients (P = .033).

There were no significant differences in locoregional recurrences, overall survival, or disease-specific survival between positive and negative patients.

Among all 94 patients, however, the presence of lymph node metastases was associated with a significantly worse recurrence-free survival (hazard ratio, 5.502; P = .017). Chemotherapy significantly reduced that risk (HR, 0.099; P = .0004).

In multivariate analysis, the investigators found that AR expression was associated with older age (63 years vs. 57 years; P = .051) and with the presence of lymph nodes metastases (P = .033).

Although larger studies are needed, the data suggest that AR-positive, triple-negative breast cancer "has unique clinical behavior and may need different treatment," Dr. Pockaj said.

A phase II, open-label trial of the antiandrogen bicalutamide (Casodex) in patients with AR-positive, estrogen- and progesterone-receptor–negative, metastatic breast cancer is currently underway in eight U.S. cancer centers.

The current study was supported by the Translational Genomics Research Institute, Phoenix, and the Mayo Clinic, Scottsdale, Ariz. Dr. Pockaj is an employee of the Mayo Clinic.

ORLANDO – Anastrozole led the pack in a new analysis of a clinical trial that found neoadjuvant aromatase inhibitor therapies can shrink large, endocrine-rich tumors in postmenopausal women scheduled for mastectomy.

Half of these women were able to have successful breast-conserving surgery instead, lead author Dr. John A. Olson Jr. reported at a symposium sponsored by the Society of Surgical Oncology. Conversion rates ranged from 25% to 70.4%, based on tumor stage and the aromatase inhibitor (AI) that was used.

"Even in the absence of a randomized clinical trial, we feel it’s reasonable to consider neoadjuvant endocrine therapy for selected women who desire breast-conserving surgery," said Dr. Olson, who recently joined the University of Maryland, Baltimore, as chief of its division of general and oncologic surgery. He had been at Duke University in Durham, N.C.

Among all patients initially considered inoperable or mastectomy candidates, breast-conserving surgery was made possible in 48.2% of those on exemestane (Aromasin), 43.1% of those on letrozole (Femara), and 64.7% of those on anastrozole (Arimidex), reported Dr. Olson. The differences between these AIs were not statistically significant, however, and he noted that the study was not powered to detect differences among the individual drugs by surgical assignment.

The phase III American College of Surgeons Oncology Group (ACOSOG) Z1031 trial randomized 377 women with stage II or III estrogen-receptor (ER)-positive breast cancer. This analysis addressed 163 women who were considered to have inoperable disease or were scheduled for mastectomy. Treatment-naïve women with stage T2 through T4c with any nodal involvement but not metastases and palpable tumors greater than 2 cm were enrolled.

Women in the trial received 16-18 weeks of neoadjuvant exemestane 25 mg daily, letrozole 2.5 mg, or anastrozole 1 mg. Following surgery, they continued on AI therapy where possible, and received adjuvant radiotherapy and chemotherapy at the treating physician’s discretion. The overall clinical tumor response rate to neoadjuvant AI therapy was 69% (258 of 374 patients).

At the end of AI therapy, 91 (56%) of the 163 women classified as having inoperable disease or requiring a mastectomy at baseline were considered to be suitable candidates for a breast-conserving procedure. The remaining 72 were assigned to mastectomy. One-third of women who underwent breast-conserving surgery after AI therapy required additional surgery to ensure adequate resection margins, Dr. Olson noted.

Eleven of the women assigned to breast conservation eventually had a mastectomy, for a total mastectomy-to-breast-conserving surgery conversion rate of 51%. Conversely, 4 (5%) of the women scheduled for mastectomy at the end of neoadjuvant therapy went on to a breast-conserving procedure.

Among 189 considered eligible for breast-conserving surgery before treatment, 17 were recommended for mastectomy following AI therapy, and 16 went on to undergo it, while 1 had a breast-conserving procedure instead.

Of the 172 recommended for conservation surgery after neoadjuvant treatment, 16 went on to mastectomy, and 156 had the recommended conservation surgery. In all, 64 of the 172 patients (37%) required re-excision for inadequate margins on the first go-round.

In a breakdown by drug and tumor type, 70.4% of women with T2 tumors on either exemestane or anastrozole had successful conversion to breast conservation, compared with 55.2% of patients on letrozole. Among patients with T3 tumors, 25% of those on exemestane went on to breast-conserving surgery, compared with 28.6% of those on letrozole and 60% of those on anastrozole. Of those with higher tumor stages (T4a-c), exemestane accounted for 28.6% of conversions, compared with 37.5% for letrozole and 50% for anastrozole.

The investigators performed a multivariate analysis controlling for clinical T and N stage, surgical impression, assigned treatment arm, tumor size, and tumor response to therapy. This analysis revealed that the factors significantly predicting conversion to breast-conserving operations were clinical stage T2 (odds ratio, 2.11; P = .0364) and smaller vs. larger tumors (OR, 4.03; P = .006) for those not larger than 2.0 cm in their largest dimension prior to surgery compared with tumors 5.1 cm or greater. Intermediate-size tumors (2.1-5.0 cm) trended toward but did not reach significance.

"Importantly, there was no tumor feature or clinical factor that predicted the change in surgical plan. This shows that biological response to the aromatase inhibitor was the driver of the final surgical procedure chosen," Dr. Olson said.

The overall incidence of pathologic stage 1 disease following surgery was 24.3% among mastectomy patients and 44.8% in conservation surgery patients; this difference was not significant.

"The relatively high incidence of stage I disease following AI therapy suggests significant downstaging of this group of patients who presented with clinical stage II or III disease," Dr. Olson said.

However, the high rate of T1 tumors in women who had a mastectomy suggests that presurgical staging for women who have neoadjuvant therapy could stand improvement, he noted.

Following the presentation, Dr. Monica Morrow, chief of the breast surgical service at Memorial Sloan-Kettering Cancer Center in New York suggested that the study may not be considering the appropriate duration of neoadjuvant therapy.

"We give this like it’s chemotherapy for 4 months, when we know that it takes a long time to achieve maximum benefit in the adjuvant setting, so would it make more sense to treat people to response plateau, if your goal was downstaging to breast conservation?" she said.

Dr. Morrow was not involved in the study, but she moderated the session in which it was presented.

The study was supported by the National Cancer Institute, the Breast Cancer Research Foundation, Pfizer, AstraZeneca, and Novartis. Dr. Olson and Dr. Morrow reported that they had no relevant financial disclosures.

ORLANDO – Anastrozole led the pack in a new analysis of a clinical trial that found neoadjuvant aromatase inhibitor therapies can shrink large, endocrine-rich tumors in postmenopausal women scheduled for mastectomy.

Half of these women were able to have successful breast-conserving surgery instead, lead author Dr. John A. Olson Jr. reported at a symposium sponsored by the Society of Surgical Oncology. Conversion rates ranged from 25% to 70.4%, based on tumor stage and the aromatase inhibitor (AI) that was used.

"Even in the absence of a randomized clinical trial, we feel it’s reasonable to consider neoadjuvant endocrine therapy for selected women who desire breast-conserving surgery," said Dr. Olson, who recently joined the University of Maryland, Baltimore, as chief of its division of general and oncologic surgery. He had been at Duke University in Durham, N.C.

Among all patients initially considered inoperable or mastectomy candidates, breast-conserving surgery was made possible in 48.2% of those on exemestane (Aromasin), 43.1% of those on letrozole (Femara), and 64.7% of those on anastrozole (Arimidex), reported Dr. Olson. The differences between these AIs were not statistically significant, however, and he noted that the study was not powered to detect differences among the individual drugs by surgical assignment.

The phase III American College of Surgeons Oncology Group (ACOSOG) Z1031 trial randomized 377 women with stage II or III estrogen-receptor (ER)-positive breast cancer. This analysis addressed 163 women who were considered to have inoperable disease or were scheduled for mastectomy. Treatment-naïve women with stage T2 through T4c with any nodal involvement but not metastases and palpable tumors greater than 2 cm were enrolled.

Women in the trial received 16-18 weeks of neoadjuvant exemestane 25 mg daily, letrozole 2.5 mg, or anastrozole 1 mg. Following surgery, they continued on AI therapy where possible, and received adjuvant radiotherapy and chemotherapy at the treating physician’s discretion. The overall clinical tumor response rate to neoadjuvant AI therapy was 69% (258 of 374 patients).

At the end of AI therapy, 91 (56%) of the 163 women classified as having inoperable disease or requiring a mastectomy at baseline were considered to be suitable candidates for a breast-conserving procedure. The remaining 72 were assigned to mastectomy. One-third of women who underwent breast-conserving surgery after AI therapy required additional surgery to ensure adequate resection margins, Dr. Olson noted.

Eleven of the women assigned to breast conservation eventually had a mastectomy, for a total mastectomy-to-breast-conserving surgery conversion rate of 51%. Conversely, 4 (5%) of the women scheduled for mastectomy at the end of neoadjuvant therapy went on to a breast-conserving procedure.

Among 189 considered eligible for breast-conserving surgery before treatment, 17 were recommended for mastectomy following AI therapy, and 16 went on to undergo it, while 1 had a breast-conserving procedure instead.

Of the 172 recommended for conservation surgery after neoadjuvant treatment, 16 went on to mastectomy, and 156 had the recommended conservation surgery. In all, 64 of the 172 patients (37%) required re-excision for inadequate margins on the first go-round.

In a breakdown by drug and tumor type, 70.4% of women with T2 tumors on either exemestane or anastrozole had successful conversion to breast conservation, compared with 55.2% of patients on letrozole. Among patients with T3 tumors, 25% of those on exemestane went on to breast-conserving surgery, compared with 28.6% of those on letrozole and 60% of those on anastrozole. Of those with higher tumor stages (T4a-c), exemestane accounted for 28.6% of conversions, compared with 37.5% for letrozole and 50% for anastrozole.

The investigators performed a multivariate analysis controlling for clinical T and N stage, surgical impression, assigned treatment arm, tumor size, and tumor response to therapy. This analysis revealed that the factors significantly predicting conversion to breast-conserving operations were clinical stage T2 (odds ratio, 2.11; P = .0364) and smaller vs. larger tumors (OR, 4.03; P = .006) for those not larger than 2.0 cm in their largest dimension prior to surgery compared with tumors 5.1 cm or greater. Intermediate-size tumors (2.1-5.0 cm) trended toward but did not reach significance.

"Importantly, there was no tumor feature or clinical factor that predicted the change in surgical plan. This shows that biological response to the aromatase inhibitor was the driver of the final surgical procedure chosen," Dr. Olson said.

The overall incidence of pathologic stage 1 disease following surgery was 24.3% among mastectomy patients and 44.8% in conservation surgery patients; this difference was not significant.

"The relatively high incidence of stage I disease following AI therapy suggests significant downstaging of this group of patients who presented with clinical stage II or III disease," Dr. Olson said.

However, the high rate of T1 tumors in women who had a mastectomy suggests that presurgical staging for women who have neoadjuvant therapy could stand improvement, he noted.

Following the presentation, Dr. Monica Morrow, chief of the breast surgical service at Memorial Sloan-Kettering Cancer Center in New York suggested that the study may not be considering the appropriate duration of neoadjuvant therapy.

"We give this like it’s chemotherapy for 4 months, when we know that it takes a long time to achieve maximum benefit in the adjuvant setting, so would it make more sense to treat people to response plateau, if your goal was downstaging to breast conservation?" she said.

Dr. Morrow was not involved in the study, but she moderated the session in which it was presented.

The study was supported by the National Cancer Institute, the Breast Cancer Research Foundation, Pfizer, AstraZeneca, and Novartis. Dr. Olson and Dr. Morrow reported that they had no relevant financial disclosures.

ORLANDO – Anastrozole led the pack in a new analysis of a clinical trial that found neoadjuvant aromatase inhibitor therapies can shrink large, endocrine-rich tumors in postmenopausal women scheduled for mastectomy.

Half of these women were able to have successful breast-conserving surgery instead, lead author Dr. John A. Olson Jr. reported at a symposium sponsored by the Society of Surgical Oncology. Conversion rates ranged from 25% to 70.4%, based on tumor stage and the aromatase inhibitor (AI) that was used.

"Even in the absence of a randomized clinical trial, we feel it’s reasonable to consider neoadjuvant endocrine therapy for selected women who desire breast-conserving surgery," said Dr. Olson, who recently joined the University of Maryland, Baltimore, as chief of its division of general and oncologic surgery. He had been at Duke University in Durham, N.C.

Among all patients initially considered inoperable or mastectomy candidates, breast-conserving surgery was made possible in 48.2% of those on exemestane (Aromasin), 43.1% of those on letrozole (Femara), and 64.7% of those on anastrozole (Arimidex), reported Dr. Olson. The differences between these AIs were not statistically significant, however, and he noted that the study was not powered to detect differences among the individual drugs by surgical assignment.

The phase III American College of Surgeons Oncology Group (ACOSOG) Z1031 trial randomized 377 women with stage II or III estrogen-receptor (ER)-positive breast cancer. This analysis addressed 163 women who were considered to have inoperable disease or were scheduled for mastectomy. Treatment-naïve women with stage T2 through T4c with any nodal involvement but not metastases and palpable tumors greater than 2 cm were enrolled.

Women in the trial received 16-18 weeks of neoadjuvant exemestane 25 mg daily, letrozole 2.5 mg, or anastrozole 1 mg. Following surgery, they continued on AI therapy where possible, and received adjuvant radiotherapy and chemotherapy at the treating physician’s discretion. The overall clinical tumor response rate to neoadjuvant AI therapy was 69% (258 of 374 patients).

At the end of AI therapy, 91 (56%) of the 163 women classified as having inoperable disease or requiring a mastectomy at baseline were considered to be suitable candidates for a breast-conserving procedure. The remaining 72 were assigned to mastectomy. One-third of women who underwent breast-conserving surgery after AI therapy required additional surgery to ensure adequate resection margins, Dr. Olson noted.

Eleven of the women assigned to breast conservation eventually had a mastectomy, for a total mastectomy-to-breast-conserving surgery conversion rate of 51%. Conversely, 4 (5%) of the women scheduled for mastectomy at the end of neoadjuvant therapy went on to a breast-conserving procedure.

Among 189 considered eligible for breast-conserving surgery before treatment, 17 were recommended for mastectomy following AI therapy, and 16 went on to undergo it, while 1 had a breast-conserving procedure instead.

Of the 172 recommended for conservation surgery after neoadjuvant treatment, 16 went on to mastectomy, and 156 had the recommended conservation surgery. In all, 64 of the 172 patients (37%) required re-excision for inadequate margins on the first go-round.

In a breakdown by drug and tumor type, 70.4% of women with T2 tumors on either exemestane or anastrozole had successful conversion to breast conservation, compared with 55.2% of patients on letrozole. Among patients with T3 tumors, 25% of those on exemestane went on to breast-conserving surgery, compared with 28.6% of those on letrozole and 60% of those on anastrozole. Of those with higher tumor stages (T4a-c), exemestane accounted for 28.6% of conversions, compared with 37.5% for letrozole and 50% for anastrozole.

The investigators performed a multivariate analysis controlling for clinical T and N stage, surgical impression, assigned treatment arm, tumor size, and tumor response to therapy. This analysis revealed that the factors significantly predicting conversion to breast-conserving operations were clinical stage T2 (odds ratio, 2.11; P = .0364) and smaller vs. larger tumors (OR, 4.03; P = .006) for those not larger than 2.0 cm in their largest dimension prior to surgery compared with tumors 5.1 cm or greater. Intermediate-size tumors (2.1-5.0 cm) trended toward but did not reach significance.

"Importantly, there was no tumor feature or clinical factor that predicted the change in surgical plan. This shows that biological response to the aromatase inhibitor was the driver of the final surgical procedure chosen," Dr. Olson said.

The overall incidence of pathologic stage 1 disease following surgery was 24.3% among mastectomy patients and 44.8% in conservation surgery patients; this difference was not significant.

"The relatively high incidence of stage I disease following AI therapy suggests significant downstaging of this group of patients who presented with clinical stage II or III disease," Dr. Olson said.

However, the high rate of T1 tumors in women who had a mastectomy suggests that presurgical staging for women who have neoadjuvant therapy could stand improvement, he noted.

Following the presentation, Dr. Monica Morrow, chief of the breast surgical service at Memorial Sloan-Kettering Cancer Center in New York suggested that the study may not be considering the appropriate duration of neoadjuvant therapy.

"We give this like it’s chemotherapy for 4 months, when we know that it takes a long time to achieve maximum benefit in the adjuvant setting, so would it make more sense to treat people to response plateau, if your goal was downstaging to breast conservation?" she said.

Dr. Morrow was not involved in the study, but she moderated the session in which it was presented.

The study was supported by the National Cancer Institute, the Breast Cancer Research Foundation, Pfizer, AstraZeneca, and Novartis. Dr. Olson and Dr. Morrow reported that they had no relevant financial disclosures.

More than one in four women who were later diagnosed with breast cancer had a combined state anxiety and depressive symptoms, and this helped predict quality of life, state anxiety, depressive symptoms, and fatigue at 12 and 24 months after surgery, according to a multicenter prospective study reported in the February 2012 issue of the Journal of Affective Disorders.

Incidence of breast cancer in Europe is 88/100,000 individuals, with survival rates of 24.3/100,000. A recent study estimated that 16.3% of cancer patients have clinical depression and 20.7% have all types of depression, respectively. However, few studies address the relationship between baseline anxiety and/or depression and quality of life.

So, Lotje van Esch, a doctoral candidate at the Center of Research on Psychology and Somatic Diseases at Tilburg University in the Netherlands, and her coauthors began to investigate state anxiety (namely, the level of momentary anxiety), depressive symptoms, and combined state anxiety and depressive symptoms (CADS) the relationship to quality of life, fatigue, and mood at 12 and 24 months after surgery in women with breast cancer (J. Affect. Disord. 2012;136:895-901).

They recruited 1,501 women referred by the national screening program or their general practitioners to six hospitals. These women, who had not yet received a diagnosis, completed a set of questionnaires that measured state anxiety, the presence and degree of depressive symptoms over the previous week, fatigue, quality of life, personality trait neuroticism, and trait anxiety.

Among these subjects, 407 women (27% of all subjects) were diagnosed with breast cancer, and 111 (28% of those diagnosed with cancer) had CADS at baseline. These patients completed questionnaires again at 12 and 24 months after surgery, although 75 dropped out between baseline and 12 months, and 24 dropped out between 12 and 14 months. The researchers also gathered demographic data and medical information on disease stage at diagnosis, type of operation and adjuvant treatment, such as chemotherapy, radiotherapy, or hormone treatment.

Of the remaining 332 patients who were in the study at 12 months, 14% had CADS, the results show. And, 10% of the remaining 246 patients had CADS at 24 months, and 10% had CADS at 12 and 24 months, respectively.

And, 10% of the remaining 246 patients at 24 months, 10% had CADS at 12 and 24 months, respectively.

At 12 and 24 months, 21% of the group had elevated depressive symptoms, and 20% had state anxiety. Of the group that had CADS at baseline, a greater percentage had elevated levels of anxiety, depressive symptoms, and CADS at 12 and 24 months than did the group that did not have CADS at baseline.

"[The] CADS group had elevated levels of state anxiety, depressive symptoms, and CADS at all follow-up measure moments in the 2 years after baseline, compared with the non-CADS group," the researchers said. "In both groups, these scores decreased over time but, after 24 months, the CADS, state anxiety, and depressive symptoms scores of the CADS group were still about three times as high as the scores in the non-CADS group. This implies that the CADS group experienced considerably more anxiety and/or depressive symptoms even 24 months after surgery."

On further analysis, the researchers found that CADS and neuroticism were both significant predictors of patients’ quality of life, fatigue, depressive symptoms, and state anxiety at 12 and 24 months after surgery, the researchers found.

The findings in this study suggest that clinicians use questionnaires or screening instruments to identify those women with a higher score on state anxiety and depressive symptom, the researchers say, and that they should do so as soon as possible when diagnosing and treating breast cancer. "Only by identifying this group of patients, tailored psychological care can be accomplished," they add.

The study’s strength was its prospective multicenter and longitudinal design. A limitation, however, was that some data were not available because some patients dropped out, and because some women were included less than 2 years earlier. Also, those who dropped out often cited a high stress level, meaning that anxiety levels might have been higher in the patients who did not participate.

The authors had no conflicts of interest to declare, and there were no study sponsors.

More than one in four women who were later diagnosed with breast cancer had a combined state anxiety and depressive symptoms, and this helped predict quality of life, state anxiety, depressive symptoms, and fatigue at 12 and 24 months after surgery, according to a multicenter prospective study reported in the February 2012 issue of the Journal of Affective Disorders.

Incidence of breast cancer in Europe is 88/100,000 individuals, with survival rates of 24.3/100,000. A recent study estimated that 16.3% of cancer patients have clinical depression and 20.7% have all types of depression, respectively. However, few studies address the relationship between baseline anxiety and/or depression and quality of life.

So, Lotje van Esch, a doctoral candidate at the Center of Research on Psychology and Somatic Diseases at Tilburg University in the Netherlands, and her coauthors began to investigate state anxiety (namely, the level of momentary anxiety), depressive symptoms, and combined state anxiety and depressive symptoms (CADS) the relationship to quality of life, fatigue, and mood at 12 and 24 months after surgery in women with breast cancer (J. Affect. Disord. 2012;136:895-901).

They recruited 1,501 women referred by the national screening program or their general practitioners to six hospitals. These women, who had not yet received a diagnosis, completed a set of questionnaires that measured state anxiety, the presence and degree of depressive symptoms over the previous week, fatigue, quality of life, personality trait neuroticism, and trait anxiety.

Among these subjects, 407 women (27% of all subjects) were diagnosed with breast cancer, and 111 (28% of those diagnosed with cancer) had CADS at baseline. These patients completed questionnaires again at 12 and 24 months after surgery, although 75 dropped out between baseline and 12 months, and 24 dropped out between 12 and 14 months. The researchers also gathered demographic data and medical information on disease stage at diagnosis, type of operation and adjuvant treatment, such as chemotherapy, radiotherapy, or hormone treatment.

Of the remaining 332 patients who were in the study at 12 months, 14% had CADS, the results show. And, 10% of the remaining 246 patients had CADS at 24 months, and 10% had CADS at 12 and 24 months, respectively.

And, 10% of the remaining 246 patients at 24 months, 10% had CADS at 12 and 24 months, respectively.

At 12 and 24 months, 21% of the group had elevated depressive symptoms, and 20% had state anxiety. Of the group that had CADS at baseline, a greater percentage had elevated levels of anxiety, depressive symptoms, and CADS at 12 and 24 months than did the group that did not have CADS at baseline.

"[The] CADS group had elevated levels of state anxiety, depressive symptoms, and CADS at all follow-up measure moments in the 2 years after baseline, compared with the non-CADS group," the researchers said. "In both groups, these scores decreased over time but, after 24 months, the CADS, state anxiety, and depressive symptoms scores of the CADS group were still about three times as high as the scores in the non-CADS group. This implies that the CADS group experienced considerably more anxiety and/or depressive symptoms even 24 months after surgery."

On further analysis, the researchers found that CADS and neuroticism were both significant predictors of patients’ quality of life, fatigue, depressive symptoms, and state anxiety at 12 and 24 months after surgery, the researchers found.

The findings in this study suggest that clinicians use questionnaires or screening instruments to identify those women with a higher score on state anxiety and depressive symptom, the researchers say, and that they should do so as soon as possible when diagnosing and treating breast cancer. "Only by identifying this group of patients, tailored psychological care can be accomplished," they add.

The study’s strength was its prospective multicenter and longitudinal design. A limitation, however, was that some data were not available because some patients dropped out, and because some women were included less than 2 years earlier. Also, those who dropped out often cited a high stress level, meaning that anxiety levels might have been higher in the patients who did not participate.

The authors had no conflicts of interest to declare, and there were no study sponsors.

More than one in four women who were later diagnosed with breast cancer had a combined state anxiety and depressive symptoms, and this helped predict quality of life, state anxiety, depressive symptoms, and fatigue at 12 and 24 months after surgery, according to a multicenter prospective study reported in the February 2012 issue of the Journal of Affective Disorders.

Incidence of breast cancer in Europe is 88/100,000 individuals, with survival rates of 24.3/100,000. A recent study estimated that 16.3% of cancer patients have clinical depression and 20.7% have all types of depression, respectively. However, few studies address the relationship between baseline anxiety and/or depression and quality of life.

So, Lotje van Esch, a doctoral candidate at the Center of Research on Psychology and Somatic Diseases at Tilburg University in the Netherlands, and her coauthors began to investigate state anxiety (namely, the level of momentary anxiety), depressive symptoms, and combined state anxiety and depressive symptoms (CADS) the relationship to quality of life, fatigue, and mood at 12 and 24 months after surgery in women with breast cancer (J. Affect. Disord. 2012;136:895-901).

They recruited 1,501 women referred by the national screening program or their general practitioners to six hospitals. These women, who had not yet received a diagnosis, completed a set of questionnaires that measured state anxiety, the presence and degree of depressive symptoms over the previous week, fatigue, quality of life, personality trait neuroticism, and trait anxiety.

Among these subjects, 407 women (27% of all subjects) were diagnosed with breast cancer, and 111 (28% of those diagnosed with cancer) had CADS at baseline. These patients completed questionnaires again at 12 and 24 months after surgery, although 75 dropped out between baseline and 12 months, and 24 dropped out between 12 and 14 months. The researchers also gathered demographic data and medical information on disease stage at diagnosis, type of operation and adjuvant treatment, such as chemotherapy, radiotherapy, or hormone treatment.

Of the remaining 332 patients who were in the study at 12 months, 14% had CADS, the results show. And, 10% of the remaining 246 patients had CADS at 24 months, and 10% had CADS at 12 and 24 months, respectively.

And, 10% of the remaining 246 patients at 24 months, 10% had CADS at 12 and 24 months, respectively.

At 12 and 24 months, 21% of the group had elevated depressive symptoms, and 20% had state anxiety. Of the group that had CADS at baseline, a greater percentage had elevated levels of anxiety, depressive symptoms, and CADS at 12 and 24 months than did the group that did not have CADS at baseline.

"[The] CADS group had elevated levels of state anxiety, depressive symptoms, and CADS at all follow-up measure moments in the 2 years after baseline, compared with the non-CADS group," the researchers said. "In both groups, these scores decreased over time but, after 24 months, the CADS, state anxiety, and depressive symptoms scores of the CADS group were still about three times as high as the scores in the non-CADS group. This implies that the CADS group experienced considerably more anxiety and/or depressive symptoms even 24 months after surgery."

On further analysis, the researchers found that CADS and neuroticism were both significant predictors of patients’ quality of life, fatigue, depressive symptoms, and state anxiety at 12 and 24 months after surgery, the researchers found.

The findings in this study suggest that clinicians use questionnaires or screening instruments to identify those women with a higher score on state anxiety and depressive symptom, the researchers say, and that they should do so as soon as possible when diagnosing and treating breast cancer. "Only by identifying this group of patients, tailored psychological care can be accomplished," they add.

The study’s strength was its prospective multicenter and longitudinal design. A limitation, however, was that some data were not available because some patients dropped out, and because some women were included less than 2 years earlier. Also, those who dropped out often cited a high stress level, meaning that anxiety levels might have been higher in the patients who did not participate.

The authors had no conflicts of interest to declare, and there were no study sponsors.

In a study of postmenopausal women who had undergone hysterectomy, the use of unopposed estrogen significantly reduced the incidence of invasive breast cancer for up to 5 years after they stopped taking the hormone, according to a report published online March 7 in the Lancet Oncology.

For study subjects who did develop breast cancer, estrogen use reduced breast-cancer mortality and all-cause mortality, Garnet L. Anderson, Ph.D., and her associates reported in an extended follow-up study of 7,645 participants in the Women’s Health Initiative (WHI).

"Our findings ... provide reassurance about breast cancer safety for postmenopausal women with [a] previous hysterectomy who receive unopposed estrogen to reduce climacteric symptoms," they noted.

The WHI, a multicenter, randomized clinical trial involving more than 10,000 women, compared outcomes between those who took conjugated equine estrogen and those who took a matching placebo.

The intervention phase of the WHI was terminated early in February 2004, after a mean follow-up of 7 years. Approximately 78% of the study subjects – 3,778 who had been randomly assigned to receive estrogen and 3,867 to receive placebo – agreed to extended follow-up until August 2009, for a total median follow-up of 11.8 years.

At this final assessment, women who had taken estrogen for a median of 6 years during the intervention phase had an overall incidence of invasive breast cancer of 0.27% per year (151 cases), which was significantly lower than the 0.35% per year rate (199 cases) among women who had taken placebo, said Dr. Anderson of the Fred Hutchinson Cancer Research Center, Seattle, and her colleagues.

"The continued, postintervention effect of estrogen on breast cancer incidence is akin to that reported for other hormone-targeted drugs shown to reduce breast cancer incidence," the investigators said (Lancet Oncol. 2012 March 7 [doi:10.1016/S1470-2045(12)70075-x]).

Estrogen was associated with a reduced risk of developing infiltrating ductal carcinoma but not infiltrating lobular cancers. It also decreased the risk of human epidermal growth factor receptor 2 (HER-2)–negative tumors but not HER-2–positive tumors, and appeared to reduce the risk of small and node-negative cancers but not large (2 cm or larger) or node-positive cancers. However, these differences among tumor subtypes did not reach statistical significance.

Among the study subjects who did develop breast cancer, those in the estrogen group were significantly less likely to die of any cause (30 deaths, for a mortality of 0.046% per year) than were those in the placebo group (50 deaths, for a mortality of 0.076% per year).

Breast-cancer-specific mortality also was significantly lower in the estrogen recipients (6 deaths, for a mortality of 0.009% per year) than in the placebo recipients (16 deaths, for a mortality of 0.024% per year).

However, the number of deaths was small, limiting the strength of these associations, Dr. Anderson and her associates noted.

These protective effects appeared to be restricted to women who had a lower risk for breast cancer. They did not apply to women with a history of benign breast disease or those with a first-degree family history of breast cancer.

In subgroup analyses, estrogen’s protective effects showed no interactions with patient age, body mass index, oophorectomy status, years since the onset of menopause, previous estrogen use, or the presence of vasomotor symptoms.

The WHI was limited in that it assessed "only one dose and schedule of oral conjugated equine estrogens; whether these findings apply to lower doses, other estrogen preparations, or longer durations of use is not known," the researchers noted.

They reported no relevant financial disclosures. The WHI was supported by the National Heart, Lung, and Blood Institute; the National Institutes of Health; the Department of Health and Human Services; and Wyeth. One of Dr. Anderson’s associates reported ties to AstraZeneca, Novartis, Amgen, and Pfizer. Dr. Anderson and the other investigators said they had no relevant financial disclosures.

In a study of postmenopausal women who had undergone hysterectomy, the use of unopposed estrogen significantly reduced the incidence of invasive breast cancer for up to 5 years after they stopped taking the hormone, according to a report published online March 7 in the Lancet Oncology.

For study subjects who did develop breast cancer, estrogen use reduced breast-cancer mortality and all-cause mortality, Garnet L. Anderson, Ph.D., and her associates reported in an extended follow-up study of 7,645 participants in the Women’s Health Initiative (WHI).

"Our findings ... provide reassurance about breast cancer safety for postmenopausal women with [a] previous hysterectomy who receive unopposed estrogen to reduce climacteric symptoms," they noted.

The WHI, a multicenter, randomized clinical trial involving more than 10,000 women, compared outcomes between those who took conjugated equine estrogen and those who took a matching placebo.

The intervention phase of the WHI was terminated early in February 2004, after a mean follow-up of 7 years. Approximately 78% of the study subjects – 3,778 who had been randomly assigned to receive estrogen and 3,867 to receive placebo – agreed to extended follow-up until August 2009, for a total median follow-up of 11.8 years.

At this final assessment, women who had taken estrogen for a median of 6 years during the intervention phase had an overall incidence of invasive breast cancer of 0.27% per year (151 cases), which was significantly lower than the 0.35% per year rate (199 cases) among women who had taken placebo, said Dr. Anderson of the Fred Hutchinson Cancer Research Center, Seattle, and her colleagues.

"The continued, postintervention effect of estrogen on breast cancer incidence is akin to that reported for other hormone-targeted drugs shown to reduce breast cancer incidence," the investigators said (Lancet Oncol. 2012 March 7 [doi:10.1016/S1470-2045(12)70075-x]).

Estrogen was associated with a reduced risk of developing infiltrating ductal carcinoma but not infiltrating lobular cancers. It also decreased the risk of human epidermal growth factor receptor 2 (HER-2)–negative tumors but not HER-2–positive tumors, and appeared to reduce the risk of small and node-negative cancers but not large (2 cm or larger) or node-positive cancers. However, these differences among tumor subtypes did not reach statistical significance.

Among the study subjects who did develop breast cancer, those in the estrogen group were significantly less likely to die of any cause (30 deaths, for a mortality of 0.046% per year) than were those in the placebo group (50 deaths, for a mortality of 0.076% per year).

Breast-cancer-specific mortality also was significantly lower in the estrogen recipients (6 deaths, for a mortality of 0.009% per year) than in the placebo recipients (16 deaths, for a mortality of 0.024% per year).

However, the number of deaths was small, limiting the strength of these associations, Dr. Anderson and her associates noted.

These protective effects appeared to be restricted to women who had a lower risk for breast cancer. They did not apply to women with a history of benign breast disease or those with a first-degree family history of breast cancer.

In subgroup analyses, estrogen’s protective effects showed no interactions with patient age, body mass index, oophorectomy status, years since the onset of menopause, previous estrogen use, or the presence of vasomotor symptoms.

The WHI was limited in that it assessed "only one dose and schedule of oral conjugated equine estrogens; whether these findings apply to lower doses, other estrogen preparations, or longer durations of use is not known," the researchers noted.

They reported no relevant financial disclosures. The WHI was supported by the National Heart, Lung, and Blood Institute; the National Institutes of Health; the Department of Health and Human Services; and Wyeth. One of Dr. Anderson’s associates reported ties to AstraZeneca, Novartis, Amgen, and Pfizer. Dr. Anderson and the other investigators said they had no relevant financial disclosures.

In a study of postmenopausal women who had undergone hysterectomy, the use of unopposed estrogen significantly reduced the incidence of invasive breast cancer for up to 5 years after they stopped taking the hormone, according to a report published online March 7 in the Lancet Oncology.

For study subjects who did develop breast cancer, estrogen use reduced breast-cancer mortality and all-cause mortality, Garnet L. Anderson, Ph.D., and her associates reported in an extended follow-up study of 7,645 participants in the Women’s Health Initiative (WHI).

"Our findings ... provide reassurance about breast cancer safety for postmenopausal women with [a] previous hysterectomy who receive unopposed estrogen to reduce climacteric symptoms," they noted.

The WHI, a multicenter, randomized clinical trial involving more than 10,000 women, compared outcomes between those who took conjugated equine estrogen and those who took a matching placebo.

The intervention phase of the WHI was terminated early in February 2004, after a mean follow-up of 7 years. Approximately 78% of the study subjects – 3,778 who had been randomly assigned to receive estrogen and 3,867 to receive placebo – agreed to extended follow-up until August 2009, for a total median follow-up of 11.8 years.

At this final assessment, women who had taken estrogen for a median of 6 years during the intervention phase had an overall incidence of invasive breast cancer of 0.27% per year (151 cases), which was significantly lower than the 0.35% per year rate (199 cases) among women who had taken placebo, said Dr. Anderson of the Fred Hutchinson Cancer Research Center, Seattle, and her colleagues.

"The continued, postintervention effect of estrogen on breast cancer incidence is akin to that reported for other hormone-targeted drugs shown to reduce breast cancer incidence," the investigators said (Lancet Oncol. 2012 March 7 [doi:10.1016/S1470-2045(12)70075-x]).

Estrogen was associated with a reduced risk of developing infiltrating ductal carcinoma but not infiltrating lobular cancers. It also decreased the risk of human epidermal growth factor receptor 2 (HER-2)–negative tumors but not HER-2–positive tumors, and appeared to reduce the risk of small and node-negative cancers but not large (2 cm or larger) or node-positive cancers. However, these differences among tumor subtypes did not reach statistical significance.

Among the study subjects who did develop breast cancer, those in the estrogen group were significantly less likely to die of any cause (30 deaths, for a mortality of 0.046% per year) than were those in the placebo group (50 deaths, for a mortality of 0.076% per year).

Breast-cancer-specific mortality also was significantly lower in the estrogen recipients (6 deaths, for a mortality of 0.009% per year) than in the placebo recipients (16 deaths, for a mortality of 0.024% per year).

However, the number of deaths was small, limiting the strength of these associations, Dr. Anderson and her associates noted.

These protective effects appeared to be restricted to women who had a lower risk for breast cancer. They did not apply to women with a history of benign breast disease or those with a first-degree family history of breast cancer.

In subgroup analyses, estrogen’s protective effects showed no interactions with patient age, body mass index, oophorectomy status, years since the onset of menopause, previous estrogen use, or the presence of vasomotor symptoms.

The WHI was limited in that it assessed "only one dose and schedule of oral conjugated equine estrogens; whether these findings apply to lower doses, other estrogen preparations, or longer durations of use is not known," the researchers noted.

They reported no relevant financial disclosures. The WHI was supported by the National Heart, Lung, and Blood Institute; the National Institutes of Health; the Department of Health and Human Services; and Wyeth. One of Dr. Anderson’s associates reported ties to AstraZeneca, Novartis, Amgen, and Pfizer. Dr. Anderson and the other investigators said they had no relevant financial disclosures.

Axitinib in renal cell carcinoma, pertuzumab plus trastuzumab and docetaxel in HER2-positive metastatic breast cancer, and models for including psychosocial services into community oncology practices are featured in the February podcast of Community Oncology, hosted by Editor-in-Chief Dr. David Henry.

Axitinib in renal cell carcinoma, pertuzumab plus trastuzumab and docetaxel in HER2-positive metastatic breast cancer, and models for including psychosocial services into community oncology practices are featured in the February podcast of Community Oncology, hosted by Editor-in-Chief Dr. David Henry.

Axitinib in renal cell carcinoma, pertuzumab plus trastuzumab and docetaxel in HER2-positive metastatic breast cancer, and models for including psychosocial services into community oncology practices are featured in the February podcast of Community Oncology, hosted by Editor-in-Chief Dr. David Henry.