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.

SAN FRANCISCO – Tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor increase the risk of a fatal adverse event in cancer patients, but the absolute rate is still low, investigators concluded from a meta-analysis of 10 randomized trials with a total of 4,679 patients.

Trial participants given sorafenib (Nexavar), sunitinib (Sutent), or pazopanib (Votrient) were more than twice as likely to die from an adverse event as were peers given control treatment, said lead investigator Dr. Christopher J. Richards of the Beth Israel Deaconess Medical Center in Boston. Yet, the rate was still less than 2%.

"Our analysis may underestimate the true incidence of fatal adverse events, as study patients may be healthier than the general population exposed to these drugs," he noted at the Genitourinary Cancers Symposium. But that said, "all three of the study drugs have been shown in various randomized controlled trials to improve clinical outcomes compared to traditional therapies."

Discussant Dr. Thomas E. Hutson of the Baylor Sammons Cancer Center in Dallas commented, "I feel confident that everyone or almost everyone in the room today would agree with me that our current therapy benefit outweighs the risk associated with the treatment."

Moreover, even among the new targeted agents, the 1.5% rate seen with the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) in the meta-analysis "compares very favorably" with the rate of 2.9% seen previously with bevacizumab (Avastin), another VEGF-targeted therapy, in a similar analysis (JAMA 2011;305:487-94).

"Targeted therapies have real toxicities, and these toxicities include a low risk of death – a risk of death not much different than other therapies used for kidney and other cancer types," Dr. Hutson asserted. "If anything, this meta-analysis shows us that close monitoring is going to be essential for optimal use of these agents."

In the study, Dr. Richards and his colleagues identified 10 randomized controlled phase II or III trials in which patients received any of three VEGFR TKIs approved by the Food and Drug Administration for cancer treatment as of February 2011: sorafenib, sunitinib, or pazopanib. The control groups were usually treated with a placebo, but in some cases with chemotherapy or immunotherapy.

The enrolled patients had a variety of malignancies: renal cell carcinoma, hepatocellular carcinoma, melanoma, non–small cell lung cancer, breast cancer, and pancreatic neuroendocrine tumor. "All patients included in the studies had good performance status and had adequate baseline cardiac, hematologic, and renal function at the time of study entry," Dr. Richards pointed out.

In a pooled analysis, relative to control treatment, VEGFR TKI treatment was associated with a 2.23-fold increased risk of fatal adverse events (P = .02). But even so, the absolute rate of such events was just 1.5%, compared with 0.7% with the control treatment.

In stratified analyses, there was no significant difference in the relative risks across the three agents or the relative risks for renal cell carcinoma vs. other types of cancer.

The most common fatal adverse events in the trials overall (considering both control and VEGFR TKI arms) were hemorrhage (48% of the total), myocardial infarction (15%), and hepatic failure (10%). These events "occurred in both the placebo and control groups as well as study groups," Dr. Richards noted.

He acknowledged that limitations of the study included the fact that the analysis used study-level instead of patient-level data, which may have resulted in confounding, and that it did not have adequate power to detect differences between the three VEGFR TKIs, although they all have a similar mechanism of action.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Richards disclosed that he had no relevant conflicts of interest. Dr. Hutson disclosed that he is a consultant to and receives honoraria from Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx, Pfizer, and Wyeth, and that he receives research funding from GlaxoSmithKline, Pfizer, and Wyeth.

SAN FRANCISCO – Tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor increase the risk of a fatal adverse event in cancer patients, but the absolute rate is still low, investigators concluded from a meta-analysis of 10 randomized trials with a total of 4,679 patients.

Trial participants given sorafenib (Nexavar), sunitinib (Sutent), or pazopanib (Votrient) were more than twice as likely to die from an adverse event as were peers given control treatment, said lead investigator Dr. Christopher J. Richards of the Beth Israel Deaconess Medical Center in Boston. Yet, the rate was still less than 2%.

"Our analysis may underestimate the true incidence of fatal adverse events, as study patients may be healthier than the general population exposed to these drugs," he noted at the Genitourinary Cancers Symposium. But that said, "all three of the study drugs have been shown in various randomized controlled trials to improve clinical outcomes compared to traditional therapies."

Discussant Dr. Thomas E. Hutson of the Baylor Sammons Cancer Center in Dallas commented, "I feel confident that everyone or almost everyone in the room today would agree with me that our current therapy benefit outweighs the risk associated with the treatment."

Moreover, even among the new targeted agents, the 1.5% rate seen with the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) in the meta-analysis "compares very favorably" with the rate of 2.9% seen previously with bevacizumab (Avastin), another VEGF-targeted therapy, in a similar analysis (JAMA 2011;305:487-94).

"Targeted therapies have real toxicities, and these toxicities include a low risk of death – a risk of death not much different than other therapies used for kidney and other cancer types," Dr. Hutson asserted. "If anything, this meta-analysis shows us that close monitoring is going to be essential for optimal use of these agents."

In the study, Dr. Richards and his colleagues identified 10 randomized controlled phase II or III trials in which patients received any of three VEGFR TKIs approved by the Food and Drug Administration for cancer treatment as of February 2011: sorafenib, sunitinib, or pazopanib. The control groups were usually treated with a placebo, but in some cases with chemotherapy or immunotherapy.

The enrolled patients had a variety of malignancies: renal cell carcinoma, hepatocellular carcinoma, melanoma, non–small cell lung cancer, breast cancer, and pancreatic neuroendocrine tumor. "All patients included in the studies had good performance status and had adequate baseline cardiac, hematologic, and renal function at the time of study entry," Dr. Richards pointed out.

In a pooled analysis, relative to control treatment, VEGFR TKI treatment was associated with a 2.23-fold increased risk of fatal adverse events (P = .02). But even so, the absolute rate of such events was just 1.5%, compared with 0.7% with the control treatment.

In stratified analyses, there was no significant difference in the relative risks across the three agents or the relative risks for renal cell carcinoma vs. other types of cancer.

The most common fatal adverse events in the trials overall (considering both control and VEGFR TKI arms) were hemorrhage (48% of the total), myocardial infarction (15%), and hepatic failure (10%). These events "occurred in both the placebo and control groups as well as study groups," Dr. Richards noted.

He acknowledged that limitations of the study included the fact that the analysis used study-level instead of patient-level data, which may have resulted in confounding, and that it did not have adequate power to detect differences between the three VEGFR TKIs, although they all have a similar mechanism of action.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Richards disclosed that he had no relevant conflicts of interest. Dr. Hutson disclosed that he is a consultant to and receives honoraria from Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx, Pfizer, and Wyeth, and that he receives research funding from GlaxoSmithKline, Pfizer, and Wyeth.

SAN FRANCISCO – Tyrosine kinase inhibitors that target the vascular endothelial growth factor receptor increase the risk of a fatal adverse event in cancer patients, but the absolute rate is still low, investigators concluded from a meta-analysis of 10 randomized trials with a total of 4,679 patients.

Trial participants given sorafenib (Nexavar), sunitinib (Sutent), or pazopanib (Votrient) were more than twice as likely to die from an adverse event as were peers given control treatment, said lead investigator Dr. Christopher J. Richards of the Beth Israel Deaconess Medical Center in Boston. Yet, the rate was still less than 2%.

"Our analysis may underestimate the true incidence of fatal adverse events, as study patients may be healthier than the general population exposed to these drugs," he noted at the Genitourinary Cancers Symposium. But that said, "all three of the study drugs have been shown in various randomized controlled trials to improve clinical outcomes compared to traditional therapies."

Discussant Dr. Thomas E. Hutson of the Baylor Sammons Cancer Center in Dallas commented, "I feel confident that everyone or almost everyone in the room today would agree with me that our current therapy benefit outweighs the risk associated with the treatment."

Moreover, even among the new targeted agents, the 1.5% rate seen with the vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) in the meta-analysis "compares very favorably" with the rate of 2.9% seen previously with bevacizumab (Avastin), another VEGF-targeted therapy, in a similar analysis (JAMA 2011;305:487-94).

"Targeted therapies have real toxicities, and these toxicities include a low risk of death – a risk of death not much different than other therapies used for kidney and other cancer types," Dr. Hutson asserted. "If anything, this meta-analysis shows us that close monitoring is going to be essential for optimal use of these agents."

In the study, Dr. Richards and his colleagues identified 10 randomized controlled phase II or III trials in which patients received any of three VEGFR TKIs approved by the Food and Drug Administration for cancer treatment as of February 2011: sorafenib, sunitinib, or pazopanib. The control groups were usually treated with a placebo, but in some cases with chemotherapy or immunotherapy.

The enrolled patients had a variety of malignancies: renal cell carcinoma, hepatocellular carcinoma, melanoma, non–small cell lung cancer, breast cancer, and pancreatic neuroendocrine tumor. "All patients included in the studies had good performance status and had adequate baseline cardiac, hematologic, and renal function at the time of study entry," Dr. Richards pointed out.

In a pooled analysis, relative to control treatment, VEGFR TKI treatment was associated with a 2.23-fold increased risk of fatal adverse events (P = .02). But even so, the absolute rate of such events was just 1.5%, compared with 0.7% with the control treatment.

In stratified analyses, there was no significant difference in the relative risks across the three agents or the relative risks for renal cell carcinoma vs. other types of cancer.

The most common fatal adverse events in the trials overall (considering both control and VEGFR TKI arms) were hemorrhage (48% of the total), myocardial infarction (15%), and hepatic failure (10%). These events "occurred in both the placebo and control groups as well as study groups," Dr. Richards noted.

He acknowledged that limitations of the study included the fact that the analysis used study-level instead of patient-level data, which may have resulted in confounding, and that it did not have adequate power to detect differences between the three VEGFR TKIs, although they all have a similar mechanism of action.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Dr. Richards disclosed that he had no relevant conflicts of interest. Dr. Hutson disclosed that he is a consultant to and receives honoraria from Bayer, Genentech, GlaxoSmithKline, Novartis, Onyx, Pfizer, and Wyeth, and that he receives research funding from GlaxoSmithKline, Pfizer, and Wyeth.

The American College of Obstetricians and Gynecologists advises that selective serotonin reuptake inhibitors, or SSRIs, can safely be used to treat hot flashes in some women with breast cancer.

And women who are able to become pregnant following breast cancer treatment can do so without increasing the risk of disease recurrence, according to the college.

The advice, published online Feb. 21 in Obstetrics and Gynecology as Practice Bulletin No. 126, is part of the college’s comprehensive new clinical guideline on the gynecological management of women who are being treated for – or who have been treated for – breast cancer (Obstet. Gynecol. 2012;119:666-82).

The guideline, which cites evidence from 166 published sources, covers such diverse issues as vasomotor symptoms; vaginal atrophy; contraception and fertility; uterine evaluation; and the treatment and prevention of bone loss in the context of current treatment regimens, which may include chemotherapy, hormonal treatments, radiation, and surgery.

"More and more women are living with breast cancer, and breast cancer treatments – particularly the hormonal therapies – have gynecological side effects," Dr. Mindy E. Goldman, lead author of the guideline, said in an interview.

"Ob.gyns. need to be aware of how these drugs work and know about any of the gynecological side effects," said Dr. Goldman, who is director of women’s cancer care for the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco.

For managing vasomotor symptoms such as hot flashes, the guideline recommends that – because hormonal therapy is generally contraindicated in women with hormone-positive breast cancer – an SSRI, an SNRI (serotonin norepinephrine reuptake inhibitor), or gabapentin be used instead. For women on tamoxifen, an SNRI is a better choice than an SSRI, because it avoids a potential interaction.

One SNRI, venlafaxine, was shown in randomized clinical trials to provide significant relief at low doses (75 mg) among women who had been treated for breast cancer. Gabapentin, an anticonvulsant used to control neuropathic pain in breast cancer patients, also helps relieve vasomotor symptoms at low doses, and may improve sleep quality. Pregabalin, a drug in the same class as gabapentin, also was seen as helpful, as was clonidine.

None of these medicines is licensed in the United States for the treatment of hot flashes.

Because chemotherapy, ovarian suppression, and aromatase inhibitors contribute to bone loss and increase fracture risk, the guideline recommends that pharmacologic therapy with bisphosphonates be considered for women who have T scores between –1.5 and –2.0, and be strongly considered for women with T scores less than –2.0, or who have a 10-year risk greater than 20% for a major fracture, or a 10-year hip fracture risk greater than 3%. Zoledronic acid was seen as a strong option among the bisphosphonates, and although raloxifene was generally well tolerated, vasomotor symptoms are among its reported adverse effects.

The guideline also recommends annual monitoring of women whose risks of bone loss significantly change as a result of treatment (for example, premenopausal women being treated with aromatase inhibitors). And vitamin D levels should be checked in women with breast cancer.

Up to 40% of women with breast cancer have severe vaginal dryness, and the topical hormonal creams, suppositories, and vaginal rings commonly used to treat vaginal dryness and atrophy have not been shown to be safe in women with breast cancer. Preference should be given to nonhormonal vaginal moisturizers, with hormonal treatments used on a short-term basis when nonhormonal options have failed. Testosterone supplementation, in patches or creams, remains without enough breast safety data to support it.

Contraceptives that are appropriate for women with breast cancer include barrier methods, the copper intrauterine device, and sterilization. Hormonal methods are contraindicated in women with breast cancer and are considered a risk even for women who have been cancer free for 5 or more years.

One exception may be the levonorgestrel-releasing intrauterine system, in which systemic absorption of levonorgestrel is minimal. However, the system has not been thoroughly studied with regard to long-term breast risk and should be considered only on a case-by-case basis, the guideline states.

Pregnancy following breast cancer treatment has not been shown to increase the risk of recurrence or mortality, according to a recent meta-analysis cited in the guideline (Eur. J. Cancer 2011;47:74-83).

But chemotherapy can compromise fertility, and 5-year use of tamoxifen may diminish a woman’s ovarian reserve before she may safely conceive. Therefore, many women of childbearing age will have difficulty becoming pregnant after treatment, and a fertility consultation at diagnosis is recommended so that advance planning can take place.

In vitro fertilization (IVF) with embryo cryopreservation is seen as a strong option for preserving the potential to have a child; however, there is concern that ovarian stimulation in IVF could cause proliferation of breast cancer cells, leading some practitioners to recommend natural cycle (nonstimulated) IVF.

It is not clear whether ovarian suppression during cancer treatment preserves fertility, according to the guideline. Tamoxifen as an ovarian stimulant has been investigated and has shown promise in treating women whose fertility has been compromised as a result of breast cancer treatment. Although the aromatase inhibitor letrozole cannot be used in premenopausal women as a breast cancer treatment, it may be used in combination with gonadotropins as a fertility agent following treatment.

Finally, routine endometrial biopsy and uterine ultrasonography are not recommended for postmenopausal women taking tamoxifen without evidence of vaginal bleeding, as ultrasound has been associated with a significant false-positive rate leading to unnecessary invasive diagnostic procedures.

However, for women on tamoxifen who experience vaginal bleeding, an endometrial evaluation – including biopsy and follow-up of possible uterine structural anomalies – is essential, the guideline states.

The members of the Committee on Practice Bulletins–Gynecology who wrote the guideline reported no relevant conflicts of interest.

The American College of Obstetricians and Gynecologists advises that selective serotonin reuptake inhibitors, or SSRIs, can safely be used to treat hot flashes in some women with breast cancer.

And women who are able to become pregnant following breast cancer treatment can do so without increasing the risk of disease recurrence, according to the college.

The advice, published online Feb. 21 in Obstetrics and Gynecology as Practice Bulletin No. 126, is part of the college’s comprehensive new clinical guideline on the gynecological management of women who are being treated for – or who have been treated for – breast cancer (Obstet. Gynecol. 2012;119:666-82).

The guideline, which cites evidence from 166 published sources, covers such diverse issues as vasomotor symptoms; vaginal atrophy; contraception and fertility; uterine evaluation; and the treatment and prevention of bone loss in the context of current treatment regimens, which may include chemotherapy, hormonal treatments, radiation, and surgery.

"More and more women are living with breast cancer, and breast cancer treatments – particularly the hormonal therapies – have gynecological side effects," Dr. Mindy E. Goldman, lead author of the guideline, said in an interview.

"Ob.gyns. need to be aware of how these drugs work and know about any of the gynecological side effects," said Dr. Goldman, who is director of women’s cancer care for the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco.

For managing vasomotor symptoms such as hot flashes, the guideline recommends that – because hormonal therapy is generally contraindicated in women with hormone-positive breast cancer – an SSRI, an SNRI (serotonin norepinephrine reuptake inhibitor), or gabapentin be used instead. For women on tamoxifen, an SNRI is a better choice than an SSRI, because it avoids a potential interaction.

One SNRI, venlafaxine, was shown in randomized clinical trials to provide significant relief at low doses (75 mg) among women who had been treated for breast cancer. Gabapentin, an anticonvulsant used to control neuropathic pain in breast cancer patients, also helps relieve vasomotor symptoms at low doses, and may improve sleep quality. Pregabalin, a drug in the same class as gabapentin, also was seen as helpful, as was clonidine.

None of these medicines is licensed in the United States for the treatment of hot flashes.

Because chemotherapy, ovarian suppression, and aromatase inhibitors contribute to bone loss and increase fracture risk, the guideline recommends that pharmacologic therapy with bisphosphonates be considered for women who have T scores between –1.5 and –2.0, and be strongly considered for women with T scores less than –2.0, or who have a 10-year risk greater than 20% for a major fracture, or a 10-year hip fracture risk greater than 3%. Zoledronic acid was seen as a strong option among the bisphosphonates, and although raloxifene was generally well tolerated, vasomotor symptoms are among its reported adverse effects.

The guideline also recommends annual monitoring of women whose risks of bone loss significantly change as a result of treatment (for example, premenopausal women being treated with aromatase inhibitors). And vitamin D levels should be checked in women with breast cancer.

Up to 40% of women with breast cancer have severe vaginal dryness, and the topical hormonal creams, suppositories, and vaginal rings commonly used to treat vaginal dryness and atrophy have not been shown to be safe in women with breast cancer. Preference should be given to nonhormonal vaginal moisturizers, with hormonal treatments used on a short-term basis when nonhormonal options have failed. Testosterone supplementation, in patches or creams, remains without enough breast safety data to support it.

Contraceptives that are appropriate for women with breast cancer include barrier methods, the copper intrauterine device, and sterilization. Hormonal methods are contraindicated in women with breast cancer and are considered a risk even for women who have been cancer free for 5 or more years.

One exception may be the levonorgestrel-releasing intrauterine system, in which systemic absorption of levonorgestrel is minimal. However, the system has not been thoroughly studied with regard to long-term breast risk and should be considered only on a case-by-case basis, the guideline states.

Pregnancy following breast cancer treatment has not been shown to increase the risk of recurrence or mortality, according to a recent meta-analysis cited in the guideline (Eur. J. Cancer 2011;47:74-83).

But chemotherapy can compromise fertility, and 5-year use of tamoxifen may diminish a woman’s ovarian reserve before she may safely conceive. Therefore, many women of childbearing age will have difficulty becoming pregnant after treatment, and a fertility consultation at diagnosis is recommended so that advance planning can take place.

In vitro fertilization (IVF) with embryo cryopreservation is seen as a strong option for preserving the potential to have a child; however, there is concern that ovarian stimulation in IVF could cause proliferation of breast cancer cells, leading some practitioners to recommend natural cycle (nonstimulated) IVF.

It is not clear whether ovarian suppression during cancer treatment preserves fertility, according to the guideline. Tamoxifen as an ovarian stimulant has been investigated and has shown promise in treating women whose fertility has been compromised as a result of breast cancer treatment. Although the aromatase inhibitor letrozole cannot be used in premenopausal women as a breast cancer treatment, it may be used in combination with gonadotropins as a fertility agent following treatment.

Finally, routine endometrial biopsy and uterine ultrasonography are not recommended for postmenopausal women taking tamoxifen without evidence of vaginal bleeding, as ultrasound has been associated with a significant false-positive rate leading to unnecessary invasive diagnostic procedures.

However, for women on tamoxifen who experience vaginal bleeding, an endometrial evaluation – including biopsy and follow-up of possible uterine structural anomalies – is essential, the guideline states.

The members of the Committee on Practice Bulletins–Gynecology who wrote the guideline reported no relevant conflicts of interest.

The American College of Obstetricians and Gynecologists advises that selective serotonin reuptake inhibitors, or SSRIs, can safely be used to treat hot flashes in some women with breast cancer.

And women who are able to become pregnant following breast cancer treatment can do so without increasing the risk of disease recurrence, according to the college.

The advice, published online Feb. 21 in Obstetrics and Gynecology as Practice Bulletin No. 126, is part of the college’s comprehensive new clinical guideline on the gynecological management of women who are being treated for – or who have been treated for – breast cancer (Obstet. Gynecol. 2012;119:666-82).

The guideline, which cites evidence from 166 published sources, covers such diverse issues as vasomotor symptoms; vaginal atrophy; contraception and fertility; uterine evaluation; and the treatment and prevention of bone loss in the context of current treatment regimens, which may include chemotherapy, hormonal treatments, radiation, and surgery.

"More and more women are living with breast cancer, and breast cancer treatments – particularly the hormonal therapies – have gynecological side effects," Dr. Mindy E. Goldman, lead author of the guideline, said in an interview.

"Ob.gyns. need to be aware of how these drugs work and know about any of the gynecological side effects," said Dr. Goldman, who is director of women’s cancer care for the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco.

For managing vasomotor symptoms such as hot flashes, the guideline recommends that – because hormonal therapy is generally contraindicated in women with hormone-positive breast cancer – an SSRI, an SNRI (serotonin norepinephrine reuptake inhibitor), or gabapentin be used instead. For women on tamoxifen, an SNRI is a better choice than an SSRI, because it avoids a potential interaction.

One SNRI, venlafaxine, was shown in randomized clinical trials to provide significant relief at low doses (75 mg) among women who had been treated for breast cancer. Gabapentin, an anticonvulsant used to control neuropathic pain in breast cancer patients, also helps relieve vasomotor symptoms at low doses, and may improve sleep quality. Pregabalin, a drug in the same class as gabapentin, also was seen as helpful, as was clonidine.

None of these medicines is licensed in the United States for the treatment of hot flashes.

Because chemotherapy, ovarian suppression, and aromatase inhibitors contribute to bone loss and increase fracture risk, the guideline recommends that pharmacologic therapy with bisphosphonates be considered for women who have T scores between –1.5 and –2.0, and be strongly considered for women with T scores less than –2.0, or who have a 10-year risk greater than 20% for a major fracture, or a 10-year hip fracture risk greater than 3%. Zoledronic acid was seen as a strong option among the bisphosphonates, and although raloxifene was generally well tolerated, vasomotor symptoms are among its reported adverse effects.

The guideline also recommends annual monitoring of women whose risks of bone loss significantly change as a result of treatment (for example, premenopausal women being treated with aromatase inhibitors). And vitamin D levels should be checked in women with breast cancer.

Up to 40% of women with breast cancer have severe vaginal dryness, and the topical hormonal creams, suppositories, and vaginal rings commonly used to treat vaginal dryness and atrophy have not been shown to be safe in women with breast cancer. Preference should be given to nonhormonal vaginal moisturizers, with hormonal treatments used on a short-term basis when nonhormonal options have failed. Testosterone supplementation, in patches or creams, remains without enough breast safety data to support it.

Contraceptives that are appropriate for women with breast cancer include barrier methods, the copper intrauterine device, and sterilization. Hormonal methods are contraindicated in women with breast cancer and are considered a risk even for women who have been cancer free for 5 or more years.

One exception may be the levonorgestrel-releasing intrauterine system, in which systemic absorption of levonorgestrel is minimal. However, the system has not been thoroughly studied with regard to long-term breast risk and should be considered only on a case-by-case basis, the guideline states.

Pregnancy following breast cancer treatment has not been shown to increase the risk of recurrence or mortality, according to a recent meta-analysis cited in the guideline (Eur. J. Cancer 2011;47:74-83).

But chemotherapy can compromise fertility, and 5-year use of tamoxifen may diminish a woman’s ovarian reserve before she may safely conceive. Therefore, many women of childbearing age will have difficulty becoming pregnant after treatment, and a fertility consultation at diagnosis is recommended so that advance planning can take place.

In vitro fertilization (IVF) with embryo cryopreservation is seen as a strong option for preserving the potential to have a child; however, there is concern that ovarian stimulation in IVF could cause proliferation of breast cancer cells, leading some practitioners to recommend natural cycle (nonstimulated) IVF.

It is not clear whether ovarian suppression during cancer treatment preserves fertility, according to the guideline. Tamoxifen as an ovarian stimulant has been investigated and has shown promise in treating women whose fertility has been compromised as a result of breast cancer treatment. Although the aromatase inhibitor letrozole cannot be used in premenopausal women as a breast cancer treatment, it may be used in combination with gonadotropins as a fertility agent following treatment.

Finally, routine endometrial biopsy and uterine ultrasonography are not recommended for postmenopausal women taking tamoxifen without evidence of vaginal bleeding, as ultrasound has been associated with a significant false-positive rate leading to unnecessary invasive diagnostic procedures.

However, for women on tamoxifen who experience vaginal bleeding, an endometrial evaluation – including biopsy and follow-up of possible uterine structural anomalies – is essential, the guideline states.

The members of the Committee on Practice Bulletins–Gynecology who wrote the guideline reported no relevant conflicts of interest.

England’s clinical and cost-effectiveness agency has said that it would not recommend lapatinib or trastuzumab with aromatase inhibitors as first-line treatments for postmenopausal women with HER2 positive metastatic breast cancer.

The new negative draft guidance follows previous negative guidance, issued in July 2011, and a subsequent appeal by Roche, the manufacturer of trastuzumab (Herceptin). While an independent panel upheld parts of Roche’s appeal in November, the National Institute for Health and Clinical Excellence nonetheless rejected both treatments once more, citing cost concerns and unclear overall survival evidence for this patient group.

In clinical trial results evaluated by NICE, lapatinib plus an aromatase inhibitor was associated with progression-free survival of 5.2 months, and trastuzumab plus an aromatase inhibitor with 2.4 months; however, NICE said that there was insufficient evidence of an overall survival gain with either treatment.

While NICE has never before issued guidance on lapatinib (Tyverb and Tykerb, GlaxoSmithKline) for any indication, trastuzumab is currently recommended by NICE for the treatment of HER2 positive gastric cancer and for two groups of women with breast cancer: those whose tumors overexpress HER2 at levels of 3+ who have not had chemotherapy for metastatic breast cancer and for whom anthracycline is inappropriate (for this group, trastuzumab is recommended in combination with paclitaxel); and those who have early-stage HER2 positive breast cancer following surgery and chemotherapy.

Lapatinib and trastuzumab combined with aromatase inhibitors are being assessed as treatments for women only when chemotherapy is deemed unsuitable.

Trastuzumab, a humanized monoclonal antibody directed against HER2, is administered as an intravenous infusion of 4 mg/kg, followed by a weekly maintenance dose of 2 mg/kg until disease progression (or an alternative schedule of 8 mg/kg followed by 3-weekly doses of 6 mg/kg). NICE estimates the cost of treatment with trastuzumab plus the aromatase inhibitor anastrozole to be between £26,000 and £27,000, depending on the dosing schedule.

Lapatinib, an oral medication, is administered in six tablets totaling 1,500 mg/day. Treatment with lapatinib plus the aromatase inhibitor letrozole is estimated at about £28,000.

NICE said that the estimated incremental cost effectiveness ratio for lapatinib plus letrozole, compared with letrozole alone, is about £74,400 per quality-adjusted life year gained. Trastuzumab plus anastrozole, compared with anastrozole alone, is estimated at £51,000 per QALY gained. Both estimates surpass NICE’s cost-effectiveness caps.

England’s clinical and cost-effectiveness agency has said that it would not recommend lapatinib or trastuzumab with aromatase inhibitors as first-line treatments for postmenopausal women with HER2 positive metastatic breast cancer.

The new negative draft guidance follows previous negative guidance, issued in July 2011, and a subsequent appeal by Roche, the manufacturer of trastuzumab (Herceptin). While an independent panel upheld parts of Roche’s appeal in November, the National Institute for Health and Clinical Excellence nonetheless rejected both treatments once more, citing cost concerns and unclear overall survival evidence for this patient group.

In clinical trial results evaluated by NICE, lapatinib plus an aromatase inhibitor was associated with progression-free survival of 5.2 months, and trastuzumab plus an aromatase inhibitor with 2.4 months; however, NICE said that there was insufficient evidence of an overall survival gain with either treatment.

While NICE has never before issued guidance on lapatinib (Tyverb and Tykerb, GlaxoSmithKline) for any indication, trastuzumab is currently recommended by NICE for the treatment of HER2 positive gastric cancer and for two groups of women with breast cancer: those whose tumors overexpress HER2 at levels of 3+ who have not had chemotherapy for metastatic breast cancer and for whom anthracycline is inappropriate (for this group, trastuzumab is recommended in combination with paclitaxel); and those who have early-stage HER2 positive breast cancer following surgery and chemotherapy.

Lapatinib and trastuzumab combined with aromatase inhibitors are being assessed as treatments for women only when chemotherapy is deemed unsuitable.

Trastuzumab, a humanized monoclonal antibody directed against HER2, is administered as an intravenous infusion of 4 mg/kg, followed by a weekly maintenance dose of 2 mg/kg until disease progression (or an alternative schedule of 8 mg/kg followed by 3-weekly doses of 6 mg/kg). NICE estimates the cost of treatment with trastuzumab plus the aromatase inhibitor anastrozole to be between £26,000 and £27,000, depending on the dosing schedule.

Lapatinib, an oral medication, is administered in six tablets totaling 1,500 mg/day. Treatment with lapatinib plus the aromatase inhibitor letrozole is estimated at about £28,000.

NICE said that the estimated incremental cost effectiveness ratio for lapatinib plus letrozole, compared with letrozole alone, is about £74,400 per quality-adjusted life year gained. Trastuzumab plus anastrozole, compared with anastrozole alone, is estimated at £51,000 per QALY gained. Both estimates surpass NICE’s cost-effectiveness caps.

England’s clinical and cost-effectiveness agency has said that it would not recommend lapatinib or trastuzumab with aromatase inhibitors as first-line treatments for postmenopausal women with HER2 positive metastatic breast cancer.

The new negative draft guidance follows previous negative guidance, issued in July 2011, and a subsequent appeal by Roche, the manufacturer of trastuzumab (Herceptin). While an independent panel upheld parts of Roche’s appeal in November, the National Institute for Health and Clinical Excellence nonetheless rejected both treatments once more, citing cost concerns and unclear overall survival evidence for this patient group.

In clinical trial results evaluated by NICE, lapatinib plus an aromatase inhibitor was associated with progression-free survival of 5.2 months, and trastuzumab plus an aromatase inhibitor with 2.4 months; however, NICE said that there was insufficient evidence of an overall survival gain with either treatment.

While NICE has never before issued guidance on lapatinib (Tyverb and Tykerb, GlaxoSmithKline) for any indication, trastuzumab is currently recommended by NICE for the treatment of HER2 positive gastric cancer and for two groups of women with breast cancer: those whose tumors overexpress HER2 at levels of 3+ who have not had chemotherapy for metastatic breast cancer and for whom anthracycline is inappropriate (for this group, trastuzumab is recommended in combination with paclitaxel); and those who have early-stage HER2 positive breast cancer following surgery and chemotherapy.

Lapatinib and trastuzumab combined with aromatase inhibitors are being assessed as treatments for women only when chemotherapy is deemed unsuitable.

Trastuzumab, a humanized monoclonal antibody directed against HER2, is administered as an intravenous infusion of 4 mg/kg, followed by a weekly maintenance dose of 2 mg/kg until disease progression (or an alternative schedule of 8 mg/kg followed by 3-weekly doses of 6 mg/kg). NICE estimates the cost of treatment with trastuzumab plus the aromatase inhibitor anastrozole to be between £26,000 and £27,000, depending on the dosing schedule.

Lapatinib, an oral medication, is administered in six tablets totaling 1,500 mg/day. Treatment with lapatinib plus the aromatase inhibitor letrozole is estimated at about £28,000.

NICE said that the estimated incremental cost effectiveness ratio for lapatinib plus letrozole, compared with letrozole alone, is about £74,400 per quality-adjusted life year gained. Trastuzumab plus anastrozole, compared with anastrozole alone, is estimated at £51,000 per QALY gained. Both estimates surpass NICE’s cost-effectiveness caps.

A prospective study has confirmed that Lynch syndrome, an inherited disorder that predisposes to many types of cancer, significantly raises the risk of both breast cancer and pancreatic cancer.

The trial is the first to "find a strong association between breast cancer and Lynch syndrome," said senior author and genetic epidemiologist Mark A. Jenkins, Ph.D., of the centre for molecular, environmental, genetic, and analytic epidemiology at the University of Melbourne.

Risk of breast cancer was fourfold higher for the Lynch syndrome patients, compared with the general population. The syndrome is known to increase the risk for a wide variety of other cancers, including colon cancer. Patients are typically advised to begin colonoscopies at an earlier age and repeat them more often than does the general population.

The new findings suggest that women with the syndrome might also benefit from enhanced breast cancer screening, but "further clarification of the risk of breast cancer for women at various ages is needed to determine the recommended age for mammography ... and to determine whether additional tests such as MRI are warranted," Dr. Jenkins said.

The researchers also found an 11-fold increase in pancreatic cancers among the Lynch syndrome patients. Although elevated risk of this cancer has long been suspected, the evidence from previous studies has been inconsistent. The results were published online Feb. 13 in the Journal of Clinical Oncology.

The autosomal dominant disorder, detected with a blood test, is caused by a mutation in one of four DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6, or PMS2. The estimated carrier frequency in the population ranges from 1 in 360 to 1 in 3,010 individuals, depending on whether all four specific mutations, or fewer than four, are included in the calculations.

Family members without the mutation, however, do not have a greater risk for cancer, and do not need more intensive screening than does the general population – something that has been unclear until now.

The investigators followed 446 mutation carriers and 1,029 noncarrier relatives recruited from the Colon Cancer Family Registry in 1997-2010. Almost all study subjects (96%) were white, and slightly more than half were female. At recruitment, mean age ranged from 40 to 50 years for the different subgroups. The registry includes subjects from the United States, Canada, Australia, and New Zealand.

After a median follow-up of 5 years, mutation carriers had a 20-fold greater risk of colorectal cancer, a 31-fold greater risk of endometrial cancer, a 19-fold higher risk of ovarian cancer, an 11-fold greater risk of renal cancer, and a 10-fold greater risk of stomach and bladder cancers, compared with the general population. The increase in risk for breast and pancreatic cancer was 4-fold and 11-fold, respectively.

For each cancer type, the increased rate in mutation carriers was highly significant, with P values ranging from .009 to less than .001. In addition, the Lynch syndrome patients’ cancer diagnoses typically came at an earlier age than it did in the general population. (J. Clin. Oncol. 2012 Feb. 13 [doi:10.1200/JCO.2011.39.5590]).

"Estimates of site-specific cancer risks for MMR gene mutation carriers inform optimal clinical management," the researchers noted. "Screening colonoscopy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy have the potential to decrease the risk of colorectal cancer, endometrial cancer, and ovarian cancer, respectively."

"Eventually, we expect that the management of cancer risk, including the choice and timing of screening, will be able to be tailored to the specific underlying gene mutation in a person with Lynch syndrome." However, there are no data demonstrating that screening for cancers other than colorectal "is beneficial, in part due to the absence of effective screening tests," Dr. Jenkins and colleagues wrote.

The authors said that they have no relevant conflicts of interest. The study was funded by the National Cancer Institute.

A prospective study has confirmed that Lynch syndrome, an inherited disorder that predisposes to many types of cancer, significantly raises the risk of both breast cancer and pancreatic cancer.

The trial is the first to "find a strong association between breast cancer and Lynch syndrome," said senior author and genetic epidemiologist Mark A. Jenkins, Ph.D., of the centre for molecular, environmental, genetic, and analytic epidemiology at the University of Melbourne.

Risk of breast cancer was fourfold higher for the Lynch syndrome patients, compared with the general population. The syndrome is known to increase the risk for a wide variety of other cancers, including colon cancer. Patients are typically advised to begin colonoscopies at an earlier age and repeat them more often than does the general population.

The new findings suggest that women with the syndrome might also benefit from enhanced breast cancer screening, but "further clarification of the risk of breast cancer for women at various ages is needed to determine the recommended age for mammography ... and to determine whether additional tests such as MRI are warranted," Dr. Jenkins said.

The researchers also found an 11-fold increase in pancreatic cancers among the Lynch syndrome patients. Although elevated risk of this cancer has long been suspected, the evidence from previous studies has been inconsistent. The results were published online Feb. 13 in the Journal of Clinical Oncology.

The autosomal dominant disorder, detected with a blood test, is caused by a mutation in one of four DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6, or PMS2. The estimated carrier frequency in the population ranges from 1 in 360 to 1 in 3,010 individuals, depending on whether all four specific mutations, or fewer than four, are included in the calculations.

Family members without the mutation, however, do not have a greater risk for cancer, and do not need more intensive screening than does the general population – something that has been unclear until now.

The investigators followed 446 mutation carriers and 1,029 noncarrier relatives recruited from the Colon Cancer Family Registry in 1997-2010. Almost all study subjects (96%) were white, and slightly more than half were female. At recruitment, mean age ranged from 40 to 50 years for the different subgroups. The registry includes subjects from the United States, Canada, Australia, and New Zealand.

After a median follow-up of 5 years, mutation carriers had a 20-fold greater risk of colorectal cancer, a 31-fold greater risk of endometrial cancer, a 19-fold higher risk of ovarian cancer, an 11-fold greater risk of renal cancer, and a 10-fold greater risk of stomach and bladder cancers, compared with the general population. The increase in risk for breast and pancreatic cancer was 4-fold and 11-fold, respectively.

For each cancer type, the increased rate in mutation carriers was highly significant, with P values ranging from .009 to less than .001. In addition, the Lynch syndrome patients’ cancer diagnoses typically came at an earlier age than it did in the general population. (J. Clin. Oncol. 2012 Feb. 13 [doi:10.1200/JCO.2011.39.5590]).

"Estimates of site-specific cancer risks for MMR gene mutation carriers inform optimal clinical management," the researchers noted. "Screening colonoscopy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy have the potential to decrease the risk of colorectal cancer, endometrial cancer, and ovarian cancer, respectively."

"Eventually, we expect that the management of cancer risk, including the choice and timing of screening, will be able to be tailored to the specific underlying gene mutation in a person with Lynch syndrome." However, there are no data demonstrating that screening for cancers other than colorectal "is beneficial, in part due to the absence of effective screening tests," Dr. Jenkins and colleagues wrote.

The authors said that they have no relevant conflicts of interest. The study was funded by the National Cancer Institute.

A prospective study has confirmed that Lynch syndrome, an inherited disorder that predisposes to many types of cancer, significantly raises the risk of both breast cancer and pancreatic cancer.

The trial is the first to "find a strong association between breast cancer and Lynch syndrome," said senior author and genetic epidemiologist Mark A. Jenkins, Ph.D., of the centre for molecular, environmental, genetic, and analytic epidemiology at the University of Melbourne.

Risk of breast cancer was fourfold higher for the Lynch syndrome patients, compared with the general population. The syndrome is known to increase the risk for a wide variety of other cancers, including colon cancer. Patients are typically advised to begin colonoscopies at an earlier age and repeat them more often than does the general population.

The new findings suggest that women with the syndrome might also benefit from enhanced breast cancer screening, but "further clarification of the risk of breast cancer for women at various ages is needed to determine the recommended age for mammography ... and to determine whether additional tests such as MRI are warranted," Dr. Jenkins said.

The researchers also found an 11-fold increase in pancreatic cancers among the Lynch syndrome patients. Although elevated risk of this cancer has long been suspected, the evidence from previous studies has been inconsistent. The results were published online Feb. 13 in the Journal of Clinical Oncology.

The autosomal dominant disorder, detected with a blood test, is caused by a mutation in one of four DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6, or PMS2. The estimated carrier frequency in the population ranges from 1 in 360 to 1 in 3,010 individuals, depending on whether all four specific mutations, or fewer than four, are included in the calculations.

Family members without the mutation, however, do not have a greater risk for cancer, and do not need more intensive screening than does the general population – something that has been unclear until now.

The investigators followed 446 mutation carriers and 1,029 noncarrier relatives recruited from the Colon Cancer Family Registry in 1997-2010. Almost all study subjects (96%) were white, and slightly more than half were female. At recruitment, mean age ranged from 40 to 50 years for the different subgroups. The registry includes subjects from the United States, Canada, Australia, and New Zealand.

After a median follow-up of 5 years, mutation carriers had a 20-fold greater risk of colorectal cancer, a 31-fold greater risk of endometrial cancer, a 19-fold higher risk of ovarian cancer, an 11-fold greater risk of renal cancer, and a 10-fold greater risk of stomach and bladder cancers, compared with the general population. The increase in risk for breast and pancreatic cancer was 4-fold and 11-fold, respectively.

For each cancer type, the increased rate in mutation carriers was highly significant, with P values ranging from .009 to less than .001. In addition, the Lynch syndrome patients’ cancer diagnoses typically came at an earlier age than it did in the general population. (J. Clin. Oncol. 2012 Feb. 13 [doi:10.1200/JCO.2011.39.5590]).

"Estimates of site-specific cancer risks for MMR gene mutation carriers inform optimal clinical management," the researchers noted. "Screening colonoscopy, prophylactic hysterectomy, and bilateral salpingo-oophorectomy have the potential to decrease the risk of colorectal cancer, endometrial cancer, and ovarian cancer, respectively."

"Eventually, we expect that the management of cancer risk, including the choice and timing of screening, will be able to be tailored to the specific underlying gene mutation in a person with Lynch syndrome." However, there are no data demonstrating that screening for cancers other than colorectal "is beneficial, in part due to the absence of effective screening tests," Dr. Jenkins and colleagues wrote.

The authors said that they have no relevant conflicts of interest. The study was funded by the National Cancer Institute.