Breast Cancer

A frequent challenge facing clinicians who manage breast cancer survivors is identifying treatment options to attenuate hot flushes and night sweats without resorting to estrogen, which is contraindicated because it can induce cancer growth.

Variables associated with a high prevalence of hot flushes in this population:

• age at diagnosis (>50 years)
• abrupt discontinuation of estrogen therapy at diagnosis
• induction of premature menopause by therapy (i.e., chemotherapy and surgical or medical ovarian ablation)
• induction of estrogen deficiency symptoms by chemotherapy (e.g., tamoxifen or an aromatase inhibitor).

There are no FDA-approved nonhormonal pharmaceutical options to alleviate bothersome hot flushes that accompany breast cancer treatment and the menopausal transition, whether spontaneous or induced. Moreover, meaningful guidance from published trials is limited by the small number of enrolled subjects and short duration of study (i.e., ≤12 weeks).

How hot flushes happen

According to Freedman, body temperature is regulated over a range called the thermo-neutral zone.^1,2 Reduced or fluctuating ovarian hormones are believed to narrow the thermoregulatory zone such that variations in core body temperature trigger heat loss mechanisms. A narrowed thermoregulatory zone has been associated with increased norepinephrine.

Clonidine, an α-2 adrenergic agonist, decreases norepinephrine and has been found to reduce hot flushes. Other nonhormonal agents that have been found to be at least partially effective in reducing hot flushes include SSRI and SNRI antidepressants, which enhance central serotonin and norepinephrine activity. Gabapentin has also proved to be effective.

Potential adverse events or negative side effects, such as insomnia, weight gain, drowsiness, and sedation, need to be taken into account when evaluating the benefits of pharmaceutical options.

We want to hear from you! Tell us what you think.

A frequent challenge facing clinicians who manage breast cancer survivors is identifying treatment options to attenuate hot flushes and night sweats without resorting to estrogen, which is contraindicated because it can induce cancer growth.

Variables associated with a high prevalence of hot flushes in this population:

• age at diagnosis (>50 years)
• abrupt discontinuation of estrogen therapy at diagnosis
• induction of premature menopause by therapy (i.e., chemotherapy and surgical or medical ovarian ablation)
• induction of estrogen deficiency symptoms by chemotherapy (e.g., tamoxifen or an aromatase inhibitor).

There are no FDA-approved nonhormonal pharmaceutical options to alleviate bothersome hot flushes that accompany breast cancer treatment and the menopausal transition, whether spontaneous or induced. Moreover, meaningful guidance from published trials is limited by the small number of enrolled subjects and short duration of study (i.e., ≤12 weeks).

How hot flushes happen

According to Freedman, body temperature is regulated over a range called the thermo-neutral zone.^1,2 Reduced or fluctuating ovarian hormones are believed to narrow the thermoregulatory zone such that variations in core body temperature trigger heat loss mechanisms. A narrowed thermoregulatory zone has been associated with increased norepinephrine.

Clonidine, an α-2 adrenergic agonist, decreases norepinephrine and has been found to reduce hot flushes. Other nonhormonal agents that have been found to be at least partially effective in reducing hot flushes include SSRI and SNRI antidepressants, which enhance central serotonin and norepinephrine activity. Gabapentin has also proved to be effective.

Potential adverse events or negative side effects, such as insomnia, weight gain, drowsiness, and sedation, need to be taken into account when evaluating the benefits of pharmaceutical options.

We want to hear from you! Tell us what you think.

A frequent challenge facing clinicians who manage breast cancer survivors is identifying treatment options to attenuate hot flushes and night sweats without resorting to estrogen, which is contraindicated because it can induce cancer growth.

Variables associated with a high prevalence of hot flushes in this population:

• age at diagnosis (>50 years)
• abrupt discontinuation of estrogen therapy at diagnosis
• induction of premature menopause by therapy (i.e., chemotherapy and surgical or medical ovarian ablation)
• induction of estrogen deficiency symptoms by chemotherapy (e.g., tamoxifen or an aromatase inhibitor).

There are no FDA-approved nonhormonal pharmaceutical options to alleviate bothersome hot flushes that accompany breast cancer treatment and the menopausal transition, whether spontaneous or induced. Moreover, meaningful guidance from published trials is limited by the small number of enrolled subjects and short duration of study (i.e., ≤12 weeks).

How hot flushes happen

According to Freedman, body temperature is regulated over a range called the thermo-neutral zone.^1,2 Reduced or fluctuating ovarian hormones are believed to narrow the thermoregulatory zone such that variations in core body temperature trigger heat loss mechanisms. A narrowed thermoregulatory zone has been associated with increased norepinephrine.

Clonidine, an α-2 adrenergic agonist, decreases norepinephrine and has been found to reduce hot flushes. Other nonhormonal agents that have been found to be at least partially effective in reducing hot flushes include SSRI and SNRI antidepressants, which enhance central serotonin and norepinephrine activity. Gabapentin has also proved to be effective.

Potential adverse events or negative side effects, such as insomnia, weight gain, drowsiness, and sedation, need to be taken into account when evaluating the benefits of pharmaceutical options.

We want to hear from you! Tell us what you think.

Updated results for the ABCSG Trial 12 continue to show disease-free and overall survival benefits 2 years after stopping adjuvant endocrine treatment with zoledronic acid, Dr. Michael Gnant explains.

Updated results for the ABCSG Trial 12 continue to show disease-free and overall survival benefits 2 years after stopping adjuvant endocrine treatment with zoledronic acid, Dr. Michael Gnant explains.

Updated results for the ABCSG Trial 12 continue to show disease-free and overall survival benefits 2 years after stopping adjuvant endocrine treatment with zoledronic acid, Dr. Michael Gnant explains.

Zoledronic acid failed to improve disease-free survival when added to adjuvant chemotherapy for women with stage II/III breast cancer, in the highly anticipated AZURE phase III trial.

Zoledronic acid failed to improve disease-free survival when added to adjuvant chemotherapy for women with stage II/III breast cancer, in the highly anticipated AZURE phase III trial.

Zoledronic acid failed to improve disease-free survival when added to adjuvant chemotherapy for women with stage II/III breast cancer, in the highly anticipated AZURE phase III trial.

Screening rates among fully insured women fall far short of guidelines, explains Dr. Milayna Subar, with half of women failing to get regular mammograms.

Screening rates among fully insured women fall far short of guidelines, explains Dr. Milayna Subar, with half of women failing to get regular mammograms.

Screening rates among fully insured women fall far short of guidelines, explains Dr. Milayna Subar, with half of women failing to get regular mammograms.

The 10-year follow-up data from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial continue to show that the adjuvant anastrozole significantly reduces the rate of breast cancer recurrence and secondary primary breast cancer in comparison with tamoxifen in postmenopausal, hormone receptor-positive patients, Dr. Aman Buzdar explains.

The 10-year follow-up data from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial continue to show that the adjuvant anastrozole significantly reduces the rate of breast cancer recurrence and secondary primary breast cancer in comparison with tamoxifen in postmenopausal, hormone receptor-positive patients, Dr. Aman Buzdar explains.

The 10-year follow-up data from the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial continue to show that the adjuvant anastrozole significantly reduces the rate of breast cancer recurrence and secondary primary breast cancer in comparison with tamoxifen in postmenopausal, hormone receptor-positive patients, Dr. Aman Buzdar explains.

Because a collaborative approach to early diagnosis and treatment has dramatically improved outcomes, breast cancer in many cases has become a chronic disease, Dr. Jennifer C. Obel says.

Because a collaborative approach to early diagnosis and treatment has dramatically improved outcomes, breast cancer in many cases has become a chronic disease, Dr. Jennifer C. Obel says.

Because a collaborative approach to early diagnosis and treatment has dramatically improved outcomes, breast cancer in many cases has become a chronic disease, Dr. Jennifer C. Obel says.

Real-world results of screening mammography in women aged 40-49 years give more data for clinicians to discuss with their patients, Dr. Jennifer Obel says. 

Real-world results of screening mammography in women aged 40-49 years give more data for clinicians to discuss with their patients, Dr. Jennifer Obel says. 

Real-world results of screening mammography in women aged 40-49 years give more data for clinicians to discuss with their patients, Dr. Jennifer Obel says. 

Women with triple-negative breast cancer and a BRCA mutation had better relapse-free survival in a study of 77 patients, Dr. Ana Maria Gonzalez-Angulo reports.

Women with triple-negative breast cancer and a BRCA mutation had better relapse-free survival in a study of 77 patients, Dr. Ana Maria Gonzalez-Angulo reports.

Women with triple-negative breast cancer and a BRCA mutation had better relapse-free survival in a study of 77 patients, Dr. Ana Maria Gonzalez-Angulo reports.

In its 2009 assessment of the benefits of screening mammography among women 50 to 69 years old, the US Preventive Services Task Force (USPSTF) estimated that the modality reduces mortality from breast cancer by 14% to 32%. However, that estimate is based on studies conducted more than 20 years ago.¹

In 1996, some parts of Norway began to offer screening mammography. By 2005, screening had become universally available in the country, with more than 75% of the eligible population participating. During that decade, Norway also established multidisciplinary teams to improve the management of women given a diagnosis of breast cancer.

To determine the effects of modern screening, investigators in Norway compared breast cancer mortality in four groups:

• women who lived, from 1996 through 2005, in counties in that country that offered mammography screening
• those who lived, from 1986 through 1995, in these same counties
• those who lived, from 1996 through 2005, in counties that did not offer screening
• those who lived, from 1986 through 1995, in these same counties.

The impact of the combination of mammography screening and multidisciplinary management of breast cancer cases was a 10% reduction in breast cancer mortality. Women who did not undergo mammography screening but whose cancers were treated according to the new paradigm experienced an 8% reduction in breast cancer mortality. That suggests that the reduction in mortality that can be attributed solely to screening mammography is a surprisingly low 2%. In other words, mammography may prevent as few as 2.4 deaths for every 100,000 person-years.

Although these numbers may appear to be strikingly low, the authors point out that they are consistent with those from Britain’s national screening program.

Can the low figures be good news?

Although some practitioners may view these data with confusion or even hostility, I see the findings of this study as good news: We have improved our treatment of breast cancer so dramatically over the past few decades that the benefits of early diagnosis have become attenuated. As an editorial accompanying the Norwegian study postulates, “It is quite plausible that screening mammography was more effective in the past than it is now. If women with new breast lumps now present earlier for evaluation, the benefit of screening will be less. If treatment of clinically detected breast cancer (i.e., tumors that are detected by means other than screening) has now improved, the benefit of screening will be less. Thus, the increased awareness about the importance of promptly seeking care for overt breast abnormalities (there is no debate about diagnostic mammography) and the widespread use of adjuvant therapy may have combined to make screening now less important.”²

What about women under 50?

Breast cancer is uncommon in women in their 40s, and screening mammograms are associated with a high rate of false-positive results and unnecessary additional imaging and biopsies in this age group. In late 2009, these observations led the USPSTF to recommend against routinely screening women 40 to 49 years old.³

Now, a study from Sweden provides data that contradict that position.⁴ In Sweden, a screening-mammography program was initiated for women 40 to 74 years old between 1986 and 1997. In 1987 and 1988, national guidelines were revised to allow counties that faced financial challenges to curtail screening for women younger than 50 years. At that time, about 50% of Swedish counties discontinued screening of younger women. The remaining counties continued screening women in their 40s at intervals ranging from 18 to 24 months.

From 1986 through 2005, 803 women died from breast cancer that was diagnosed when they were 40 to 49 years old and who were screened by mammography (7.3 million person-years). During the same period, 1,238 women died from breast cancer that was diagnosed when they were 40 to 49 years old and who were not screened by mammography (8.8 million person-years).

Investigators calculated the odds ratio (OR) for fatal breast cancer among women who were screened in their 40s: 0.71 (95% confidence interval [CI], 0.62–0.80). They also estimated that, over a 10-year period (roughly six screening mammograms), one case of fatal breast cancer was prevented among every 1,252 women screened.

Picture remains a bit murky

Coming less than a year after the aforementioned USPSTF recommendations against screening women under 50, and right on the heels of the Norwegian study minimizing the value of screening in women 50 to 69 years old, these new data have ignited controversy.

Unlike their Norwegian counterparts, Swedish investigators failed to report mortality rates, making interpretation of the data difficult. Nor did they detail the health costs of mammograms among women in their 40s.

Note: For more on the debate over screening mammography, see Dr. Kaunitz’s earlier commentary on the subject, “I’ve been rethinking my zeal for breast cancer screening,” in the December 2009 issue of OBG Management, and Dr. Robert L. Barbieri’s distinctive viewpoint, “Access to screening mammography: Priceless,” in the January 2010 issue at obgmanagement.com.

We want to hear from you! Tell us what you think.

In its 2009 assessment of the benefits of screening mammography among women 50 to 69 years old, the US Preventive Services Task Force (USPSTF) estimated that the modality reduces mortality from breast cancer by 14% to 32%. However, that estimate is based on studies conducted more than 20 years ago.¹

In 1996, some parts of Norway began to offer screening mammography. By 2005, screening had become universally available in the country, with more than 75% of the eligible population participating. During that decade, Norway also established multidisciplinary teams to improve the management of women given a diagnosis of breast cancer.

To determine the effects of modern screening, investigators in Norway compared breast cancer mortality in four groups:

• women who lived, from 1996 through 2005, in counties in that country that offered mammography screening
• those who lived, from 1986 through 1995, in these same counties
• those who lived, from 1996 through 2005, in counties that did not offer screening
• those who lived, from 1986 through 1995, in these same counties.

The impact of the combination of mammography screening and multidisciplinary management of breast cancer cases was a 10% reduction in breast cancer mortality. Women who did not undergo mammography screening but whose cancers were treated according to the new paradigm experienced an 8% reduction in breast cancer mortality. That suggests that the reduction in mortality that can be attributed solely to screening mammography is a surprisingly low 2%. In other words, mammography may prevent as few as 2.4 deaths for every 100,000 person-years.

Although these numbers may appear to be strikingly low, the authors point out that they are consistent with those from Britain’s national screening program.

Can the low figures be good news?

Although some practitioners may view these data with confusion or even hostility, I see the findings of this study as good news: We have improved our treatment of breast cancer so dramatically over the past few decades that the benefits of early diagnosis have become attenuated. As an editorial accompanying the Norwegian study postulates, “It is quite plausible that screening mammography was more effective in the past than it is now. If women with new breast lumps now present earlier for evaluation, the benefit of screening will be less. If treatment of clinically detected breast cancer (i.e., tumors that are detected by means other than screening) has now improved, the benefit of screening will be less. Thus, the increased awareness about the importance of promptly seeking care for overt breast abnormalities (there is no debate about diagnostic mammography) and the widespread use of adjuvant therapy may have combined to make screening now less important.”²

What about women under 50?

Breast cancer is uncommon in women in their 40s, and screening mammograms are associated with a high rate of false-positive results and unnecessary additional imaging and biopsies in this age group. In late 2009, these observations led the USPSTF to recommend against routinely screening women 40 to 49 years old.³

Now, a study from Sweden provides data that contradict that position.⁴ In Sweden, a screening-mammography program was initiated for women 40 to 74 years old between 1986 and 1997. In 1987 and 1988, national guidelines were revised to allow counties that faced financial challenges to curtail screening for women younger than 50 years. At that time, about 50% of Swedish counties discontinued screening of younger women. The remaining counties continued screening women in their 40s at intervals ranging from 18 to 24 months.

From 1986 through 2005, 803 women died from breast cancer that was diagnosed when they were 40 to 49 years old and who were screened by mammography (7.3 million person-years). During the same period, 1,238 women died from breast cancer that was diagnosed when they were 40 to 49 years old and who were not screened by mammography (8.8 million person-years).

Investigators calculated the odds ratio (OR) for fatal breast cancer among women who were screened in their 40s: 0.71 (95% confidence interval [CI], 0.62–0.80). They also estimated that, over a 10-year period (roughly six screening mammograms), one case of fatal breast cancer was prevented among every 1,252 women screened.

Picture remains a bit murky

Coming less than a year after the aforementioned USPSTF recommendations against screening women under 50, and right on the heels of the Norwegian study minimizing the value of screening in women 50 to 69 years old, these new data have ignited controversy.

Unlike their Norwegian counterparts, Swedish investigators failed to report mortality rates, making interpretation of the data difficult. Nor did they detail the health costs of mammograms among women in their 40s.

Note: For more on the debate over screening mammography, see Dr. Kaunitz’s earlier commentary on the subject, “I’ve been rethinking my zeal for breast cancer screening,” in the December 2009 issue of OBG Management, and Dr. Robert L. Barbieri’s distinctive viewpoint, “Access to screening mammography: Priceless,” in the January 2010 issue at obgmanagement.com.

We want to hear from you! Tell us what you think.

In its 2009 assessment of the benefits of screening mammography among women 50 to 69 years old, the US Preventive Services Task Force (USPSTF) estimated that the modality reduces mortality from breast cancer by 14% to 32%. However, that estimate is based on studies conducted more than 20 years ago.¹

In 1996, some parts of Norway began to offer screening mammography. By 2005, screening had become universally available in the country, with more than 75% of the eligible population participating. During that decade, Norway also established multidisciplinary teams to improve the management of women given a diagnosis of breast cancer.

To determine the effects of modern screening, investigators in Norway compared breast cancer mortality in four groups:

• women who lived, from 1996 through 2005, in counties in that country that offered mammography screening
• those who lived, from 1986 through 1995, in these same counties
• those who lived, from 1996 through 2005, in counties that did not offer screening
• those who lived, from 1986 through 1995, in these same counties.

The impact of the combination of mammography screening and multidisciplinary management of breast cancer cases was a 10% reduction in breast cancer mortality. Women who did not undergo mammography screening but whose cancers were treated according to the new paradigm experienced an 8% reduction in breast cancer mortality. That suggests that the reduction in mortality that can be attributed solely to screening mammography is a surprisingly low 2%. In other words, mammography may prevent as few as 2.4 deaths for every 100,000 person-years.

Although these numbers may appear to be strikingly low, the authors point out that they are consistent with those from Britain’s national screening program.

Can the low figures be good news?

Although some practitioners may view these data with confusion or even hostility, I see the findings of this study as good news: We have improved our treatment of breast cancer so dramatically over the past few decades that the benefits of early diagnosis have become attenuated. As an editorial accompanying the Norwegian study postulates, “It is quite plausible that screening mammography was more effective in the past than it is now. If women with new breast lumps now present earlier for evaluation, the benefit of screening will be less. If treatment of clinically detected breast cancer (i.e., tumors that are detected by means other than screening) has now improved, the benefit of screening will be less. Thus, the increased awareness about the importance of promptly seeking care for overt breast abnormalities (there is no debate about diagnostic mammography) and the widespread use of adjuvant therapy may have combined to make screening now less important.”²

What about women under 50?

Breast cancer is uncommon in women in their 40s, and screening mammograms are associated with a high rate of false-positive results and unnecessary additional imaging and biopsies in this age group. In late 2009, these observations led the USPSTF to recommend against routinely screening women 40 to 49 years old.³

Now, a study from Sweden provides data that contradict that position.⁴ In Sweden, a screening-mammography program was initiated for women 40 to 74 years old between 1986 and 1997. In 1987 and 1988, national guidelines were revised to allow counties that faced financial challenges to curtail screening for women younger than 50 years. At that time, about 50% of Swedish counties discontinued screening of younger women. The remaining counties continued screening women in their 40s at intervals ranging from 18 to 24 months.

From 1986 through 2005, 803 women died from breast cancer that was diagnosed when they were 40 to 49 years old and who were screened by mammography (7.3 million person-years). During the same period, 1,238 women died from breast cancer that was diagnosed when they were 40 to 49 years old and who were not screened by mammography (8.8 million person-years).

Investigators calculated the odds ratio (OR) for fatal breast cancer among women who were screened in their 40s: 0.71 (95% confidence interval [CI], 0.62–0.80). They also estimated that, over a 10-year period (roughly six screening mammograms), one case of fatal breast cancer was prevented among every 1,252 women screened.

Picture remains a bit murky

Coming less than a year after the aforementioned USPSTF recommendations against screening women under 50, and right on the heels of the Norwegian study minimizing the value of screening in women 50 to 69 years old, these new data have ignited controversy.

Unlike their Norwegian counterparts, Swedish investigators failed to report mortality rates, making interpretation of the data difficult. Nor did they detail the health costs of mammograms among women in their 40s.

Note: For more on the debate over screening mammography, see Dr. Kaunitz’s earlier commentary on the subject, “I’ve been rethinking my zeal for breast cancer screening,” in the December 2009 issue of OBG Management, and Dr. Robert L. Barbieri’s distinctive viewpoint, “Access to screening mammography: Priceless,” in the January 2010 issue at obgmanagement.com.

We want to hear from you! Tell us what you think.