Mark D. Pearlman, MD

The number of states that require notification to a woman who is identified on mammography as having heterogeneous (Breast Imaging-Reporting and Data System [BI-RADS] C) or extremely dense breasts (BI-RADS D) is growing. In fact, Michigan became the 22nd state to require such notification when its law went into effect on June 1, 2015. How do we advise our patients who come to us wondering what they should do with the new-found information?

Since supplemental imaging after normal mammography findings can result in false positives and potentially unnecessary biopsies or treatment, Kerlikowski and colleagues investigated for which patients supplemental screening could be beneficial. In other words, which patients are at highest risk for interval cancer (invasive cancer diagnosed within 12 months of a normal mammogram), as these women would be most likely to benefit from supplemental imaging that could potentially detect a tumor not identified on digital screening mammography.

Details of the study
The researchers included 831,455 digital screening mammography examinations performed among 365,426 women aged 40 to 74 years who did not have a history of breast cancer or breast implants and had complete information on demographic and breast health history. To calculate breast cancer risk, they used the Breast Cancer Surveillance Consortium (BCSC) 5-year risk model, which requires 5 risk factors: first-degree relatives with history of breast cancer, history of breast biopsy, BI-RADS breast density, and race/ethnicity. They used breast density to stratify women by risk for interval cancer within the next year and to identify women at increased 5-year risk for breast cancer.

In which patient populations are cases of interval cancer highest?
The authors found the interval cancer rates to exceed 1 case per 1,000 mammography examinations among:

The authors point out that, together, these 2 latter groups represent 24% of women aged 40 to 74 years with dense breasts, or 12% of women having screening mammography.

For women aged 40 to 49 years, interval cancer rates were less than 1 case per 1,000 examinations for all density categories. For 51% of these women with heterogeneously dense breasts, the 5-year risk of breast cancer was low to average (0% to 1.66%), with interval cancer rates of 0.58 to 0.63 per 1,000 examinations. For 52.5% of 40- to 49-year-old women with extremely dense breasts, the 5-year risk of breast cancer was low to average, with interval cancer rates of 0.72 to 0.89 cases per 1,000 examinations.

The interval cancer rate for women with scattered fibroglandular densities (BI-RADS B) and 5-year risk of 2.50% or greater was 0.90 cases per 1,000 mammography examinations.

Kerlikowski and colleagues conclude that breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. 

What this evidence means for practice
BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient–provider discussions about alternative screening strategies, as the study authors state. However, there remains a huge gap in our knowledge about whether supplemental imaging in any of these risk groups improved stage of diagnosis or breast cancer–specific mortality.

Nearly all national guidelines groups (US Preventive Services Task Force,¹ American College of Obstetricians and Gynecologists,² National Comprehensive Cancer Network,³ and the American Cancer Society⁴) concur that supplemental breast imaging should not be performed on women with dense breasts until there are reasonable data that demonstrate an improvement in stage of diagnosis or breast cancer mortality.
—Mark D. Pearlman, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The number of states that require notification to a woman who is identified on mammography as having heterogeneous (Breast Imaging-Reporting and Data System [BI-RADS] C) or extremely dense breasts (BI-RADS D) is growing. In fact, Michigan became the 22nd state to require such notification when its law went into effect on June 1, 2015. How do we advise our patients who come to us wondering what they should do with the new-found information?

Since supplemental imaging after normal mammography findings can result in false positives and potentially unnecessary biopsies or treatment, Kerlikowski and colleagues investigated for which patients supplemental screening could be beneficial. In other words, which patients are at highest risk for interval cancer (invasive cancer diagnosed within 12 months of a normal mammogram), as these women would be most likely to benefit from supplemental imaging that could potentially detect a tumor not identified on digital screening mammography.

Details of the study
The researchers included 831,455 digital screening mammography examinations performed among 365,426 women aged 40 to 74 years who did not have a history of breast cancer or breast implants and had complete information on demographic and breast health history. To calculate breast cancer risk, they used the Breast Cancer Surveillance Consortium (BCSC) 5-year risk model, which requires 5 risk factors: first-degree relatives with history of breast cancer, history of breast biopsy, BI-RADS breast density, and race/ethnicity. They used breast density to stratify women by risk for interval cancer within the next year and to identify women at increased 5-year risk for breast cancer.

In which patient populations are cases of interval cancer highest?
The authors found the interval cancer rates to exceed 1 case per 1,000 mammography examinations among:

The authors point out that, together, these 2 latter groups represent 24% of women aged 40 to 74 years with dense breasts, or 12% of women having screening mammography.

For women aged 40 to 49 years, interval cancer rates were less than 1 case per 1,000 examinations for all density categories. For 51% of these women with heterogeneously dense breasts, the 5-year risk of breast cancer was low to average (0% to 1.66%), with interval cancer rates of 0.58 to 0.63 per 1,000 examinations. For 52.5% of 40- to 49-year-old women with extremely dense breasts, the 5-year risk of breast cancer was low to average, with interval cancer rates of 0.72 to 0.89 cases per 1,000 examinations.

The interval cancer rate for women with scattered fibroglandular densities (BI-RADS B) and 5-year risk of 2.50% or greater was 0.90 cases per 1,000 mammography examinations.

Kerlikowski and colleagues conclude that breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. 

What this evidence means for practice
BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient–provider discussions about alternative screening strategies, as the study authors state. However, there remains a huge gap in our knowledge about whether supplemental imaging in any of these risk groups improved stage of diagnosis or breast cancer–specific mortality.

Nearly all national guidelines groups (US Preventive Services Task Force,¹ American College of Obstetricians and Gynecologists,² National Comprehensive Cancer Network,³ and the American Cancer Society⁴) concur that supplemental breast imaging should not be performed on women with dense breasts until there are reasonable data that demonstrate an improvement in stage of diagnosis or breast cancer mortality.
—Mark D. Pearlman, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

The number of states that require notification to a woman who is identified on mammography as having heterogeneous (Breast Imaging-Reporting and Data System [BI-RADS] C) or extremely dense breasts (BI-RADS D) is growing. In fact, Michigan became the 22nd state to require such notification when its law went into effect on June 1, 2015. How do we advise our patients who come to us wondering what they should do with the new-found information?

Since supplemental imaging after normal mammography findings can result in false positives and potentially unnecessary biopsies or treatment, Kerlikowski and colleagues investigated for which patients supplemental screening could be beneficial. In other words, which patients are at highest risk for interval cancer (invasive cancer diagnosed within 12 months of a normal mammogram), as these women would be most likely to benefit from supplemental imaging that could potentially detect a tumor not identified on digital screening mammography.

Details of the study
The researchers included 831,455 digital screening mammography examinations performed among 365,426 women aged 40 to 74 years who did not have a history of breast cancer or breast implants and had complete information on demographic and breast health history. To calculate breast cancer risk, they used the Breast Cancer Surveillance Consortium (BCSC) 5-year risk model, which requires 5 risk factors: first-degree relatives with history of breast cancer, history of breast biopsy, BI-RADS breast density, and race/ethnicity. They used breast density to stratify women by risk for interval cancer within the next year and to identify women at increased 5-year risk for breast cancer.

In which patient populations are cases of interval cancer highest?
The authors found the interval cancer rates to exceed 1 case per 1,000 mammography examinations among:

The authors point out that, together, these 2 latter groups represent 24% of women aged 40 to 74 years with dense breasts, or 12% of women having screening mammography.

For women aged 40 to 49 years, interval cancer rates were less than 1 case per 1,000 examinations for all density categories. For 51% of these women with heterogeneously dense breasts, the 5-year risk of breast cancer was low to average (0% to 1.66%), with interval cancer rates of 0.58 to 0.63 per 1,000 examinations. For 52.5% of 40- to 49-year-old women with extremely dense breasts, the 5-year risk of breast cancer was low to average, with interval cancer rates of 0.72 to 0.89 cases per 1,000 examinations.

The interval cancer rate for women with scattered fibroglandular densities (BI-RADS B) and 5-year risk of 2.50% or greater was 0.90 cases per 1,000 mammography examinations.

Kerlikowski and colleagues conclude that breast density should not be the sole criterion for deciding whether supplemental imaging is justified because not all women with dense breasts have high interval cancer rates. 

What this evidence means for practice
BCSC 5-year risk combined with BI-RADS breast density can identify women at high risk for interval cancer to inform patient–provider discussions about alternative screening strategies, as the study authors state. However, there remains a huge gap in our knowledge about whether supplemental imaging in any of these risk groups improved stage of diagnosis or breast cancer–specific mortality.

Nearly all national guidelines groups (US Preventive Services Task Force,¹ American College of Obstetricians and Gynecologists,² National Comprehensive Cancer Network,³ and the American Cancer Society⁴) concur that supplemental breast imaging should not be performed on women with dense breasts until there are reasonable data that demonstrate an improvement in stage of diagnosis or breast cancer mortality.
—Mark D. Pearlman, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Screening mammography in women with dense breasts (ie, containing more than 50% fibroglandular tissue) is challenging for two reasons:

Because nearly half of women in the United States undergoing screening mammography have dense breasts, it is vital that we provide them with accurate and useful counseling.

The challenge of managing women with dense breasts has become complicated by the fact that 21 states have passed laws requiring that women with dense breasts be informed through scripted messages of the decreased sensitivity of screening and increased risk of cancer and advised to
discuss with their provider whether additional testing (eg, with supplemental ultrasound) should be ordered. These laws may be well-intentioned, but they are problematic.

Although there are data documenting increased cancer detection with screening ultrasonography, there are no data currently available demonstrating that this increased detection adds value by improving important outcomes like disease-specific mortality. Further, the value proposition (improved outcomes/cost) of screening ultrasonography is unknown.

In this article, Sprague and colleagues attempt to fill this void by assessing the potential benefits, harms, and cost-effectivenessof supplemental ultrasonography following a negative screening mammogram for women with dense breasts.

Through the use of validated micro-simulation modeling, they calculate that the routine use of supplemental ultrasonography in women with dense breasts might result in 0.36 fewer deaths per 1,000 women screened. Compare this to 6 fewer deaths per 1,000 women undergoing screening mammography.

Moreover, the specificity of supplemental ultrasonography in this setting is poor, with 94% of recommended biopsies yielding benign findings (ie, positive predictive value of 6%).²

What this evidence means for practice
At present, there is little evidence that routine supplemental ultrasonography improves important outcomes such as disease-specific mortality at a rational cost. However, there may be hope on the horizon: Emerging data suggest that digital tomosynthesis as a primary screening modality may improve both specificity and sensitivity, compared with mammography, in women with dense breasts.

Initial experience with tomosynthesis demonstrates both fewer callbacks and improved cancer detection in women, compared with screening mammography.^3,4 However, the value proposition of this new technology will ultimately depend on a careful analysis of its effect on mortality and cost.
–Mark D. Pearlman, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Screening mammography in women with dense breasts (ie, containing more than 50% fibroglandular tissue) is challenging for two reasons:

Because nearly half of women in the United States undergoing screening mammography have dense breasts, it is vital that we provide them with accurate and useful counseling.

The challenge of managing women with dense breasts has become complicated by the fact that 21 states have passed laws requiring that women with dense breasts be informed through scripted messages of the decreased sensitivity of screening and increased risk of cancer and advised to
discuss with their provider whether additional testing (eg, with supplemental ultrasound) should be ordered. These laws may be well-intentioned, but they are problematic.

Although there are data documenting increased cancer detection with screening ultrasonography, there are no data currently available demonstrating that this increased detection adds value by improving important outcomes like disease-specific mortality. Further, the value proposition (improved outcomes/cost) of screening ultrasonography is unknown.

In this article, Sprague and colleagues attempt to fill this void by assessing the potential benefits, harms, and cost-effectivenessof supplemental ultrasonography following a negative screening mammogram for women with dense breasts.

Through the use of validated micro-simulation modeling, they calculate that the routine use of supplemental ultrasonography in women with dense breasts might result in 0.36 fewer deaths per 1,000 women screened. Compare this to 6 fewer deaths per 1,000 women undergoing screening mammography.

Moreover, the specificity of supplemental ultrasonography in this setting is poor, with 94% of recommended biopsies yielding benign findings (ie, positive predictive value of 6%).²

What this evidence means for practice
At present, there is little evidence that routine supplemental ultrasonography improves important outcomes such as disease-specific mortality at a rational cost. However, there may be hope on the horizon: Emerging data suggest that digital tomosynthesis as a primary screening modality may improve both specificity and sensitivity, compared with mammography, in women with dense breasts.

Initial experience with tomosynthesis demonstrates both fewer callbacks and improved cancer detection in women, compared with screening mammography.^3,4 However, the value proposition of this new technology will ultimately depend on a careful analysis of its effect on mortality and cost.
–Mark D. Pearlman, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Screening mammography in women with dense breasts (ie, containing more than 50% fibroglandular tissue) is challenging for two reasons:

Because nearly half of women in the United States undergoing screening mammography have dense breasts, it is vital that we provide them with accurate and useful counseling.

The challenge of managing women with dense breasts has become complicated by the fact that 21 states have passed laws requiring that women with dense breasts be informed through scripted messages of the decreased sensitivity of screening and increased risk of cancer and advised to
discuss with their provider whether additional testing (eg, with supplemental ultrasound) should be ordered. These laws may be well-intentioned, but they are problematic.

Although there are data documenting increased cancer detection with screening ultrasonography, there are no data currently available demonstrating that this increased detection adds value by improving important outcomes like disease-specific mortality. Further, the value proposition (improved outcomes/cost) of screening ultrasonography is unknown.

In this article, Sprague and colleagues attempt to fill this void by assessing the potential benefits, harms, and cost-effectivenessof supplemental ultrasonography following a negative screening mammogram for women with dense breasts.

Through the use of validated micro-simulation modeling, they calculate that the routine use of supplemental ultrasonography in women with dense breasts might result in 0.36 fewer deaths per 1,000 women screened. Compare this to 6 fewer deaths per 1,000 women undergoing screening mammography.

Moreover, the specificity of supplemental ultrasonography in this setting is poor, with 94% of recommended biopsies yielding benign findings (ie, positive predictive value of 6%).²

What this evidence means for practice
At present, there is little evidence that routine supplemental ultrasonography improves important outcomes such as disease-specific mortality at a rational cost. However, there may be hope on the horizon: Emerging data suggest that digital tomosynthesis as a primary screening modality may improve both specificity and sensitivity, compared with mammography, in women with dense breasts.

Initial experience with tomosynthesis demonstrates both fewer callbacks and improved cancer detection in women, compared with screening mammography.^3,4 However, the value proposition of this new technology will ultimately depend on a careful analysis of its effect on mortality and cost.
–Mark D. Pearlman, MD

Share your thoughts on this article! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

In 2009, the United States Preventive Services Task Force (USPSTF) released a controversial recommendation that breast cancer screening should routinely start at age 50 and be performed biennially.¹ The Task Force further stated that the determination to screen women before the age of 50 “should take patient context into account, including the patient’s values regarding specific benefits and harms.”¹

Although some professional societies have adopted this recommendation, others, including the American College of Obstetricians and Gynecologists (ACOG), have recommended that annual screening begin at age 40 in average-risk women.²

Related article: Is "overdiagnosis" of breast cancer common among women screened by mammography? Andrew M. Kaunitz, MD (January 2013)

With different professional societies lined up on both sides of this debate, practitioners and women remain confused about why different breast cancer screening guidelines exist in the United States.

Putting the study in context
A review of the data that informed the USPSTF recommendation demonstrate that routine screening mammography has similar efficacy in women in their fifth and sixth decade of life—a reduction in mortality of 16% and 15%, respectively.³ However, more mammograms need to be performed in women in their 40s than in women in their 50s to achieve that benefit. Moreover, because the specificity of screening mammography is less than ideal, about 10% of women are called back for additional imaging, and 10% of that population will undergo a biopsy. Only 30% of these biopsies will result in a diagnosis of cancer.

There has been considerable debate about the mortality improvement with routine screening mammography, including a nationwide administrative data review published in late 2012.⁴ This data-mining study suggested that routine screening mammography was only a minor contributor to the significant improvement in breast cancer mortality over the past 25 years.

Related article: Update on breast health Mark D. Pearlman, MD, and Jennifer L. Griffin Miller, MD, MPH (March 2013)

Details of the study
In this failure analysis from Massachusetts General Hospital and Brigham and Women’s Hospital, Webb and colleagues reviewed breast cancer deaths over 17 years (new breast cancer cases from 1990 through 1997, with cases followed through 2007). They compared the likelihood of death according to whether screening mammography had been performed in the preceding 2 years.

Of the 609 confirmed deaths from breast cancer, 71% occurred among unscreened women (ie, never screened or screening not done in the preceding 2 years). The median age at diagnosis of fatal cancers was 49 years, whereas women with breast cancer who ultimately died of other causes had a median age at diagnosis of 72 years.

Related article: Biennial vs annual mammography: How I manage my patients Andrew M. Kaunitz, MD (June 2013)

Webb and colleagues concluded: “Most deaths from breast cancer occur in unscreened women. To maximize mortality reduction and life-years gained, initiation of regular screening before age 50 years should be encouraged.”

WHAT THIS EVIDENCE MEANS FOR PRACTICE
The findings of Webb and colleagues are not surprising, given the already demonstrated reduction in breast cancer mortality with the use of routine screening mammography in women in their 40s. What is particularly interesting in this study is that the preponderance of breast cancer deaths occurred in younger women. Biologically, this may be explained by the more aggressive nature of breast cancer in younger women.⁵

This study provides additional support for the ACOG recommendation to routinely offer breast cancer screening with mammography for women aged 40 to 49 years.
--Mark D. Pearlman, MD

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

In 2009, the United States Preventive Services Task Force (USPSTF) released a controversial recommendation that breast cancer screening should routinely start at age 50 and be performed biennially.¹ The Task Force further stated that the determination to screen women before the age of 50 “should take patient context into account, including the patient’s values regarding specific benefits and harms.”¹

Although some professional societies have adopted this recommendation, others, including the American College of Obstetricians and Gynecologists (ACOG), have recommended that annual screening begin at age 40 in average-risk women.²

Related article: Is "overdiagnosis" of breast cancer common among women screened by mammography? Andrew M. Kaunitz, MD (January 2013)

With different professional societies lined up on both sides of this debate, practitioners and women remain confused about why different breast cancer screening guidelines exist in the United States.

Putting the study in context
A review of the data that informed the USPSTF recommendation demonstrate that routine screening mammography has similar efficacy in women in their fifth and sixth decade of life—a reduction in mortality of 16% and 15%, respectively.³ However, more mammograms need to be performed in women in their 40s than in women in their 50s to achieve that benefit. Moreover, because the specificity of screening mammography is less than ideal, about 10% of women are called back for additional imaging, and 10% of that population will undergo a biopsy. Only 30% of these biopsies will result in a diagnosis of cancer.

There has been considerable debate about the mortality improvement with routine screening mammography, including a nationwide administrative data review published in late 2012.⁴ This data-mining study suggested that routine screening mammography was only a minor contributor to the significant improvement in breast cancer mortality over the past 25 years.

Related article: Update on breast health Mark D. Pearlman, MD, and Jennifer L. Griffin Miller, MD, MPH (March 2013)

Details of the study
In this failure analysis from Massachusetts General Hospital and Brigham and Women’s Hospital, Webb and colleagues reviewed breast cancer deaths over 17 years (new breast cancer cases from 1990 through 1997, with cases followed through 2007). They compared the likelihood of death according to whether screening mammography had been performed in the preceding 2 years.

Of the 609 confirmed deaths from breast cancer, 71% occurred among unscreened women (ie, never screened or screening not done in the preceding 2 years). The median age at diagnosis of fatal cancers was 49 years, whereas women with breast cancer who ultimately died of other causes had a median age at diagnosis of 72 years.

Related article: Biennial vs annual mammography: How I manage my patients Andrew M. Kaunitz, MD (June 2013)

Webb and colleagues concluded: “Most deaths from breast cancer occur in unscreened women. To maximize mortality reduction and life-years gained, initiation of regular screening before age 50 years should be encouraged.”

WHAT THIS EVIDENCE MEANS FOR PRACTICE
The findings of Webb and colleagues are not surprising, given the already demonstrated reduction in breast cancer mortality with the use of routine screening mammography in women in their 40s. What is particularly interesting in this study is that the preponderance of breast cancer deaths occurred in younger women. Biologically, this may be explained by the more aggressive nature of breast cancer in younger women.⁵

This study provides additional support for the ACOG recommendation to routinely offer breast cancer screening with mammography for women aged 40 to 49 years.
--Mark D. Pearlman, MD

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

In 2009, the United States Preventive Services Task Force (USPSTF) released a controversial recommendation that breast cancer screening should routinely start at age 50 and be performed biennially.¹ The Task Force further stated that the determination to screen women before the age of 50 “should take patient context into account, including the patient’s values regarding specific benefits and harms.”¹

Although some professional societies have adopted this recommendation, others, including the American College of Obstetricians and Gynecologists (ACOG), have recommended that annual screening begin at age 40 in average-risk women.²

Related article: Is "overdiagnosis" of breast cancer common among women screened by mammography? Andrew M. Kaunitz, MD (January 2013)

With different professional societies lined up on both sides of this debate, practitioners and women remain confused about why different breast cancer screening guidelines exist in the United States.

Putting the study in context
A review of the data that informed the USPSTF recommendation demonstrate that routine screening mammography has similar efficacy in women in their fifth and sixth decade of life—a reduction in mortality of 16% and 15%, respectively.³ However, more mammograms need to be performed in women in their 40s than in women in their 50s to achieve that benefit. Moreover, because the specificity of screening mammography is less than ideal, about 10% of women are called back for additional imaging, and 10% of that population will undergo a biopsy. Only 30% of these biopsies will result in a diagnosis of cancer.

There has been considerable debate about the mortality improvement with routine screening mammography, including a nationwide administrative data review published in late 2012.⁴ This data-mining study suggested that routine screening mammography was only a minor contributor to the significant improvement in breast cancer mortality over the past 25 years.

Related article: Update on breast health Mark D. Pearlman, MD, and Jennifer L. Griffin Miller, MD, MPH (March 2013)

Details of the study
In this failure analysis from Massachusetts General Hospital and Brigham and Women’s Hospital, Webb and colleagues reviewed breast cancer deaths over 17 years (new breast cancer cases from 1990 through 1997, with cases followed through 2007). They compared the likelihood of death according to whether screening mammography had been performed in the preceding 2 years.

Of the 609 confirmed deaths from breast cancer, 71% occurred among unscreened women (ie, never screened or screening not done in the preceding 2 years). The median age at diagnosis of fatal cancers was 49 years, whereas women with breast cancer who ultimately died of other causes had a median age at diagnosis of 72 years.

Related article: Biennial vs annual mammography: How I manage my patients Andrew M. Kaunitz, MD (June 2013)

Webb and colleagues concluded: “Most deaths from breast cancer occur in unscreened women. To maximize mortality reduction and life-years gained, initiation of regular screening before age 50 years should be encouraged.”

WHAT THIS EVIDENCE MEANS FOR PRACTICE
The findings of Webb and colleagues are not surprising, given the already demonstrated reduction in breast cancer mortality with the use of routine screening mammography in women in their 40s. What is particularly interesting in this study is that the preponderance of breast cancer deaths occurred in younger women. Biologically, this may be explained by the more aggressive nature of breast cancer in younger women.⁵

This study provides additional support for the ACOG recommendation to routinely offer breast cancer screening with mammography for women aged 40 to 49 years.
--Mark D. Pearlman, MD

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

The effects of breast cancer on obstetric and gynecologic practices are pervasive. In this article, we touch on three aspects of breast cancer that are particularly relevant to the practicing ObGyn:

• the need to identify women at high risk for breast cancer and select those who would benefit from a discussion of the advantages and risks of chemoprophylaxis, which can reduce the likelihood of breast cancer by 50% or more
• the need for strategies to manage menopausal symptoms in the general population without increasing the risk of breast cancer. The traditional approach to this problem changed dramatically with the Women’s Health Initiative (WHI), which demonstrated an increased risk of breast cancer in women taking conjugated equine estrogen and progestin. The widely publicized initial findings of the estrogen-progestin arm of the WHI sharply contrast the equally relevant, somewhat unexpected, and less publicized results of the estrogen-alone arm, which demonstrated a substantial and statistically significant decrease in the incidence of breast cancer, even after estrogen was discontinued.
• the potential effects of breast cancer treatment on ovarian function in young women. This year, of the approximately 250,000 women who will be diagnosed with invasive breast cancer, more than 50,000 women will be of reproductive age. Most of these young women will require adjuvant chemotherapy; as a result, many will experience the premature onset of menopause. Along with the attendant loss of fertility these women will face, many will also develop distressing and life-altering menopausal symptoms. Management of these women before and after initiation of chemotherapy requires an understanding of both the expected effects of the chemotherapy and knowledge of how to actively manage these women with strategies to either prevent these events or to manage menopausal symptoms.

In women at normal risk for breast cancer, unopposed estrogen lowers the rate of the malignancy and the likelihood of mortality if the cancer occurs—but is not recommended as a prophylactic agent. Tamoxifen and other chemoprophylactic drugs can halve the rate of breast cancer in high-risk women but are not without drawbacks.

A look at the lower rate of breast cancer in the estrogen-alone arm of the WHI

Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13(5):476–486.

From 1993 through 1998, the WHI enrolled 10,739 postmenopausal women in the largest prospective trial evaluating the effect of hormone therapy (HT) on various clinical outcomes. The women were randomly allocated to three groups:

• conjugated estrogen with medroxyprogesterone acetate
• conjugated estrogen alone (in women with a prior hysterectomy)
• placebo.

The negative effects of estrogen plus progestin on the risk of breast cancer were the most widely discussed oucomes.¹ Shortly after the findings from this arm of the study were published, the use of HT in the United States declined dramatically and unequivocally.²

In 2012, WHI published the results of the estrogen-alone arm in the British cancer specialty journal Lancet Oncology. As shown in the TABLE below, the incidence of breast cancer was statistically significantly lower (23%) in the estrogen group than in the placebo group. Women who were treated with estrogen alone were also 63% less likely to die of breast cancer, and all-cause mortality was 38% lower; both of these findings were statistically significant. Not only was there a significant reduction in the incidence of invasive breast cancer while the subjects were taking estrogen, but that reduction continued for a median of 4.7 years of follow-up after discontinuation of estrogen.

Breast cancer incidence and mortality in the estrogen-only arm of the WHI, compared with placebo*

The incidence figure is somewhat remarkable (199 in the placebo group versus 151 in the estrogen-alone group) in that it was nearly the exact reverse of the estrogen-progestin arm of the WHI trial (199 in the estrogen/progestin group vs 150 in the placebo group).³

All breast cancer chemoprophylactic agents carry risks as well as benefits

Goss P, Ingle J, Ales-Martinez J, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364(25):2381–2391.

Cheung A, Tile L, Cardew S, et al. Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomized controlled trial. Lancet Oncol. 2012;13(3):275–284.

Vogel V, Costantino J, Wickerham L, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res. 2010;3(6):696–706.

The number of new cases of breast cancer in the United States last year reached nearly a quarter-million. Clearly, reducing this number remains an important goal.⁴ Chemoprevention—the use of medication to reduce cancer risk—may be offered to women who are at high risk of developing breast cancer.

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial, tamoxifen (a selective estrogen-receptor modulator) was shown to reduce the risk of invasive breast cancer by 49% in a high-risk population, resulting in the FDA approving tamoxifen as the first drug for breast cancer prevention.⁵ The P-1 trial was followed by the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial, which demonstrated relative equivalence between the two medications as cancer prevention agents in menopausal women.⁶ Serious side effects of these medications limit their use among eligible women, although raloxifene seems to be associated with fewer adverse events. In the update of the STAR trial with an average of 81 months of follow-up, the risk ratio for adverse events (raloxifene:tamoxifen) was 0.75 for thromboembolic events, 0.55 for endometrial cancer, and 0.19 for uterine hyperplasia.

Another drug used for cancer treatment has now entered the prevention scene. In 2011, the NCIC Clinical Trials Group Mammary Prevention.3 trial (NCIC CTG MAP.3) compared exemestane (an aromatase inhibitor) with placebo for menopausal women at high risk for breast cancer, demonstrating a 65% relative reduction in the incidence of invasive breast cancer. This study validated another option for cancer prevention in high-risk women, although its adoption is likely also to be limited by side effects, including vasomotor symptoms, a high rate of arthralgias, and vaginal dryness/dyspareunia. The greatest concern may be the potential effect on bone density. Though the rates of serious adverse events including fracture did not differ in the MAP.3 trial at 35 months of follow-up, women on exemestane had significantly larger losses of bone mineral density, compared with controls.

Managing the reproductive health concerns of young women with breast cancer

Azim H, Kroman N, Paesmans M, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol. 2013;31(1):73–79.

Howard-Anderson J, Ganz P, Bower J, Stanton A. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104(5):1386–1405.

Of the approximately 230,000 new cases of invasive breast cancer identified in 2011, 50,430 cases involved women less than 50 years of age.⁴ For these women, the diagnosis of cancer raises multifaceted concerns, including the physical changes that accompany breast cancer treatment, concerns about recurrence and mortality, and significant sexual and reproductive consequences of treatment that alters ovarian function. Pregnancy-associated breast cancers (breast cancers diagnosed during pregnancy, lactation, and for 12 months postpartum) represent a small subset of these cancers and occur in about 1 in 3,000 pregnancies. One might anticipate that this rate will increase as women continue to delay childbearing, because pregnancy-associated breast cancers are more common in older women.

In the review article by Howard-Anderson and colleagues, the importance of these reproductive health consequences in young women diagnosed with breast cancer is highlighted. The women who transition to menopause as a result of chemotherapy (reported to range from 33%–73%) experience more symptoms, including hot flashes, night sweats, breast pain, vaginal dryness, and lack of sexual desire. Sixty-one percent of women younger than 40 years at diagnosis reported that they were concerned about menopause, and 30% reported that this concern influenced their treatment decisions. Thirty-nine percent of women in this group had major concerns about treatment-associated infertility, and only half of the women studied felt that their fertility concerns were adequately addressed.

On a positive note, for women who successfully achieve pregnancy after breast cancer, pregnancy outcomes appear to be similar to those of their nonpregnant peers. In the study by Azim and colleagues, women who became pregnant after a breast cancer diagnosis had disease-free survival that was statistically similar to that of matched women who did not have subsequent pregnancies. In addition, this outcome did not differ based on estrogen/progesterone receptor status (ER/PR positive or negative).

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

The effects of breast cancer on obstetric and gynecologic practices are pervasive. In this article, we touch on three aspects of breast cancer that are particularly relevant to the practicing ObGyn:

• the need to identify women at high risk for breast cancer and select those who would benefit from a discussion of the advantages and risks of chemoprophylaxis, which can reduce the likelihood of breast cancer by 50% or more
• the need for strategies to manage menopausal symptoms in the general population without increasing the risk of breast cancer. The traditional approach to this problem changed dramatically with the Women’s Health Initiative (WHI), which demonstrated an increased risk of breast cancer in women taking conjugated equine estrogen and progestin. The widely publicized initial findings of the estrogen-progestin arm of the WHI sharply contrast the equally relevant, somewhat unexpected, and less publicized results of the estrogen-alone arm, which demonstrated a substantial and statistically significant decrease in the incidence of breast cancer, even after estrogen was discontinued.
• the potential effects of breast cancer treatment on ovarian function in young women. This year, of the approximately 250,000 women who will be diagnosed with invasive breast cancer, more than 50,000 women will be of reproductive age. Most of these young women will require adjuvant chemotherapy; as a result, many will experience the premature onset of menopause. Along with the attendant loss of fertility these women will face, many will also develop distressing and life-altering menopausal symptoms. Management of these women before and after initiation of chemotherapy requires an understanding of both the expected effects of the chemotherapy and knowledge of how to actively manage these women with strategies to either prevent these events or to manage menopausal symptoms.

In women at normal risk for breast cancer, unopposed estrogen lowers the rate of the malignancy and the likelihood of mortality if the cancer occurs—but is not recommended as a prophylactic agent. Tamoxifen and other chemoprophylactic drugs can halve the rate of breast cancer in high-risk women but are not without drawbacks.

A look at the lower rate of breast cancer in the estrogen-alone arm of the WHI

Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13(5):476–486.

From 1993 through 1998, the WHI enrolled 10,739 postmenopausal women in the largest prospective trial evaluating the effect of hormone therapy (HT) on various clinical outcomes. The women were randomly allocated to three groups:

• conjugated estrogen with medroxyprogesterone acetate
• conjugated estrogen alone (in women with a prior hysterectomy)
• placebo.

The negative effects of estrogen plus progestin on the risk of breast cancer were the most widely discussed oucomes.¹ Shortly after the findings from this arm of the study were published, the use of HT in the United States declined dramatically and unequivocally.²

In 2012, WHI published the results of the estrogen-alone arm in the British cancer specialty journal Lancet Oncology. As shown in the TABLE below, the incidence of breast cancer was statistically significantly lower (23%) in the estrogen group than in the placebo group. Women who were treated with estrogen alone were also 63% less likely to die of breast cancer, and all-cause mortality was 38% lower; both of these findings were statistically significant. Not only was there a significant reduction in the incidence of invasive breast cancer while the subjects were taking estrogen, but that reduction continued for a median of 4.7 years of follow-up after discontinuation of estrogen.

Breast cancer incidence and mortality in the estrogen-only arm of the WHI, compared with placebo*

The incidence figure is somewhat remarkable (199 in the placebo group versus 151 in the estrogen-alone group) in that it was nearly the exact reverse of the estrogen-progestin arm of the WHI trial (199 in the estrogen/progestin group vs 150 in the placebo group).³

All breast cancer chemoprophylactic agents carry risks as well as benefits

Goss P, Ingle J, Ales-Martinez J, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364(25):2381–2391.

Cheung A, Tile L, Cardew S, et al. Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomized controlled trial. Lancet Oncol. 2012;13(3):275–284.

Vogel V, Costantino J, Wickerham L, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res. 2010;3(6):696–706.

The number of new cases of breast cancer in the United States last year reached nearly a quarter-million. Clearly, reducing this number remains an important goal.⁴ Chemoprevention—the use of medication to reduce cancer risk—may be offered to women who are at high risk of developing breast cancer.

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial, tamoxifen (a selective estrogen-receptor modulator) was shown to reduce the risk of invasive breast cancer by 49% in a high-risk population, resulting in the FDA approving tamoxifen as the first drug for breast cancer prevention.⁵ The P-1 trial was followed by the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial, which demonstrated relative equivalence between the two medications as cancer prevention agents in menopausal women.⁶ Serious side effects of these medications limit their use among eligible women, although raloxifene seems to be associated with fewer adverse events. In the update of the STAR trial with an average of 81 months of follow-up, the risk ratio for adverse events (raloxifene:tamoxifen) was 0.75 for thromboembolic events, 0.55 for endometrial cancer, and 0.19 for uterine hyperplasia.

Another drug used for cancer treatment has now entered the prevention scene. In 2011, the NCIC Clinical Trials Group Mammary Prevention.3 trial (NCIC CTG MAP.3) compared exemestane (an aromatase inhibitor) with placebo for menopausal women at high risk for breast cancer, demonstrating a 65% relative reduction in the incidence of invasive breast cancer. This study validated another option for cancer prevention in high-risk women, although its adoption is likely also to be limited by side effects, including vasomotor symptoms, a high rate of arthralgias, and vaginal dryness/dyspareunia. The greatest concern may be the potential effect on bone density. Though the rates of serious adverse events including fracture did not differ in the MAP.3 trial at 35 months of follow-up, women on exemestane had significantly larger losses of bone mineral density, compared with controls.

Managing the reproductive health concerns of young women with breast cancer

Azim H, Kroman N, Paesmans M, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol. 2013;31(1):73–79.

Howard-Anderson J, Ganz P, Bower J, Stanton A. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104(5):1386–1405.

Of the approximately 230,000 new cases of invasive breast cancer identified in 2011, 50,430 cases involved women less than 50 years of age.⁴ For these women, the diagnosis of cancer raises multifaceted concerns, including the physical changes that accompany breast cancer treatment, concerns about recurrence and mortality, and significant sexual and reproductive consequences of treatment that alters ovarian function. Pregnancy-associated breast cancers (breast cancers diagnosed during pregnancy, lactation, and for 12 months postpartum) represent a small subset of these cancers and occur in about 1 in 3,000 pregnancies. One might anticipate that this rate will increase as women continue to delay childbearing, because pregnancy-associated breast cancers are more common in older women.

In the review article by Howard-Anderson and colleagues, the importance of these reproductive health consequences in young women diagnosed with breast cancer is highlighted. The women who transition to menopause as a result of chemotherapy (reported to range from 33%–73%) experience more symptoms, including hot flashes, night sweats, breast pain, vaginal dryness, and lack of sexual desire. Sixty-one percent of women younger than 40 years at diagnosis reported that they were concerned about menopause, and 30% reported that this concern influenced their treatment decisions. Thirty-nine percent of women in this group had major concerns about treatment-associated infertility, and only half of the women studied felt that their fertility concerns were adequately addressed.

On a positive note, for women who successfully achieve pregnancy after breast cancer, pregnancy outcomes appear to be similar to those of their nonpregnant peers. In the study by Azim and colleagues, women who became pregnant after a breast cancer diagnosis had disease-free survival that was statistically similar to that of matched women who did not have subsequent pregnancies. In addition, this outcome did not differ based on estrogen/progesterone receptor status (ER/PR positive or negative).

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

The effects of breast cancer on obstetric and gynecologic practices are pervasive. In this article, we touch on three aspects of breast cancer that are particularly relevant to the practicing ObGyn:

• the need to identify women at high risk for breast cancer and select those who would benefit from a discussion of the advantages and risks of chemoprophylaxis, which can reduce the likelihood of breast cancer by 50% or more
• the need for strategies to manage menopausal symptoms in the general population without increasing the risk of breast cancer. The traditional approach to this problem changed dramatically with the Women’s Health Initiative (WHI), which demonstrated an increased risk of breast cancer in women taking conjugated equine estrogen and progestin. The widely publicized initial findings of the estrogen-progestin arm of the WHI sharply contrast the equally relevant, somewhat unexpected, and less publicized results of the estrogen-alone arm, which demonstrated a substantial and statistically significant decrease in the incidence of breast cancer, even after estrogen was discontinued.
• the potential effects of breast cancer treatment on ovarian function in young women. This year, of the approximately 250,000 women who will be diagnosed with invasive breast cancer, more than 50,000 women will be of reproductive age. Most of these young women will require adjuvant chemotherapy; as a result, many will experience the premature onset of menopause. Along with the attendant loss of fertility these women will face, many will also develop distressing and life-altering menopausal symptoms. Management of these women before and after initiation of chemotherapy requires an understanding of both the expected effects of the chemotherapy and knowledge of how to actively manage these women with strategies to either prevent these events or to manage menopausal symptoms.

In women at normal risk for breast cancer, unopposed estrogen lowers the rate of the malignancy and the likelihood of mortality if the cancer occurs—but is not recommended as a prophylactic agent. Tamoxifen and other chemoprophylactic drugs can halve the rate of breast cancer in high-risk women but are not without drawbacks.

A look at the lower rate of breast cancer in the estrogen-alone arm of the WHI

Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012;13(5):476–486.

From 1993 through 1998, the WHI enrolled 10,739 postmenopausal women in the largest prospective trial evaluating the effect of hormone therapy (HT) on various clinical outcomes. The women were randomly allocated to three groups:

• conjugated estrogen with medroxyprogesterone acetate
• conjugated estrogen alone (in women with a prior hysterectomy)
• placebo.

The negative effects of estrogen plus progestin on the risk of breast cancer were the most widely discussed oucomes.¹ Shortly after the findings from this arm of the study were published, the use of HT in the United States declined dramatically and unequivocally.²

In 2012, WHI published the results of the estrogen-alone arm in the British cancer specialty journal Lancet Oncology. As shown in the TABLE below, the incidence of breast cancer was statistically significantly lower (23%) in the estrogen group than in the placebo group. Women who were treated with estrogen alone were also 63% less likely to die of breast cancer, and all-cause mortality was 38% lower; both of these findings were statistically significant. Not only was there a significant reduction in the incidence of invasive breast cancer while the subjects were taking estrogen, but that reduction continued for a median of 4.7 years of follow-up after discontinuation of estrogen.

Breast cancer incidence and mortality in the estrogen-only arm of the WHI, compared with placebo*

The incidence figure is somewhat remarkable (199 in the placebo group versus 151 in the estrogen-alone group) in that it was nearly the exact reverse of the estrogen-progestin arm of the WHI trial (199 in the estrogen/progestin group vs 150 in the placebo group).³

All breast cancer chemoprophylactic agents carry risks as well as benefits

Goss P, Ingle J, Ales-Martinez J, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364(25):2381–2391.

Cheung A, Tile L, Cardew S, et al. Bone density and structure in healthy postmenopausal women treated with exemestane for the primary prevention of breast cancer: a nested substudy of the MAP.3 randomized controlled trial. Lancet Oncol. 2012;13(3):275–284.

Vogel V, Costantino J, Wickerham L, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res. 2010;3(6):696–706.

The number of new cases of breast cancer in the United States last year reached nearly a quarter-million. Clearly, reducing this number remains an important goal.⁴ Chemoprevention—the use of medication to reduce cancer risk—may be offered to women who are at high risk of developing breast cancer.

In the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial, tamoxifen (a selective estrogen-receptor modulator) was shown to reduce the risk of invasive breast cancer by 49% in a high-risk population, resulting in the FDA approving tamoxifen as the first drug for breast cancer prevention.⁵ The P-1 trial was followed by the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial, which demonstrated relative equivalence between the two medications as cancer prevention agents in menopausal women.⁶ Serious side effects of these medications limit their use among eligible women, although raloxifene seems to be associated with fewer adverse events. In the update of the STAR trial with an average of 81 months of follow-up, the risk ratio for adverse events (raloxifene:tamoxifen) was 0.75 for thromboembolic events, 0.55 for endometrial cancer, and 0.19 for uterine hyperplasia.

Another drug used for cancer treatment has now entered the prevention scene. In 2011, the NCIC Clinical Trials Group Mammary Prevention.3 trial (NCIC CTG MAP.3) compared exemestane (an aromatase inhibitor) with placebo for menopausal women at high risk for breast cancer, demonstrating a 65% relative reduction in the incidence of invasive breast cancer. This study validated another option for cancer prevention in high-risk women, although its adoption is likely also to be limited by side effects, including vasomotor symptoms, a high rate of arthralgias, and vaginal dryness/dyspareunia. The greatest concern may be the potential effect on bone density. Though the rates of serious adverse events including fracture did not differ in the MAP.3 trial at 35 months of follow-up, women on exemestane had significantly larger losses of bone mineral density, compared with controls.

Managing the reproductive health concerns of young women with breast cancer

Azim H, Kroman N, Paesmans M, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol. 2013;31(1):73–79.

Howard-Anderson J, Ganz P, Bower J, Stanton A. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review. J Natl Cancer Inst. 2012;104(5):1386–1405.

Of the approximately 230,000 new cases of invasive breast cancer identified in 2011, 50,430 cases involved women less than 50 years of age.⁴ For these women, the diagnosis of cancer raises multifaceted concerns, including the physical changes that accompany breast cancer treatment, concerns about recurrence and mortality, and significant sexual and reproductive consequences of treatment that alters ovarian function. Pregnancy-associated breast cancers (breast cancers diagnosed during pregnancy, lactation, and for 12 months postpartum) represent a small subset of these cancers and occur in about 1 in 3,000 pregnancies. One might anticipate that this rate will increase as women continue to delay childbearing, because pregnancy-associated breast cancers are more common in older women.

In the review article by Howard-Anderson and colleagues, the importance of these reproductive health consequences in young women diagnosed with breast cancer is highlighted. The women who transition to menopause as a result of chemotherapy (reported to range from 33%–73%) experience more symptoms, including hot flashes, night sweats, breast pain, vaginal dryness, and lack of sexual desire. Sixty-one percent of women younger than 40 years at diagnosis reported that they were concerned about menopause, and 30% reported that this concern influenced their treatment decisions. Thirty-nine percent of women in this group had major concerns about treatment-associated infertility, and only half of the women studied felt that their fertility concerns were adequately addressed.

On a positive note, for women who successfully achieve pregnancy after breast cancer, pregnancy outcomes appear to be similar to those of their nonpregnant peers. In the study by Azim and colleagues, women who became pregnant after a breast cancer diagnosis had disease-free survival that was statistically similar to that of matched women who did not have subsequent pregnancies. In addition, this outcome did not differ based on estrogen/progesterone receptor status (ER/PR positive or negative).

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