Breast Cancer

AMSTERDAM – Axillary radiotherapy appears to be a safe and effective alternative to completion axillary lymph node dissection (cALND) for selected patients who have early invasive breast cancer with sentinel lymph node metastasis, a randomized phase III trial showed.

After a mean of just over 8 years of follow-up, there were no significant differences in breast cancer recurrence, overall survival (OS), disease-free survival (DFS), or breast cancer deaths between patients treated with cALND or axillary radiotherapy, reported Akos Savolt, MD, PhD, of the National Institute of Oncology in Budapest.

“This trial has changed our everyday practice about the optimal care of the axilla,” he said at an annual congress sponsored by the European Cancer Organisation.

An estimated 25%-50% of patients with positive sentinel lymph nodes will have disease that extends to other lymph nodes, and for these patients, cALND is the standard of care.

But patients for whom metastasis is limited to the sentinel lymph node are unlikely to benefit from more extensive dissections, and for these patients, the proven benefits of cALND must be weighed against the significant complications associated with the procedure, including lymphedema, arm pain, nerve injury, shoulder dysfunction, and paresthesias, Dr. Savolt noted.

The OTOASOR (Optimal Treatment of the Axilla – Surgery or Radiotherapy) trial was a single-center study designed to see whether axillary radiotherapy could be noninferior to cALND for preventing recurrence and breast cancer deaths.

From mid-2002 through mid-2009,the investigators enrolled women with primary invasive breast cancer (tumors 3 cm or smaller and no clinically detected lymph node metastases), and randomized them prior to surgery to receive either cALND or axillary radiotherapy at a dose of 50 Gy. Patients also received adjuvant therapy as per institutional guidelines.

A total of 474 patients were evaluable for follow-up: 244 assigned to cALND and 230 assigned to radiotherapy. In all, 94 patients assigned to cALND (38.5%) were found to have additional lymph node metastases.

At a mean follow-up of 97 months, 2% of women in the cALND group had experienced an axillary recurrence (the primary endpoint), compared with 1.7% in the axillary radiation arm.

Overall survival was also similar between the groups, at 77.9% vs. 84.8%, respectively, as was disease-free survival, at 72.1% and 77.4%; neither comparison yielded statistically significant results.

There were also no between-group differences in the percentage of patients alive with recurrence, breast cancer deaths (13.9% of patients in the cALND arm vs. 8.7 in the radiation arm), or deaths from other causes (8.2% vs. 6.5%, respectively).

In contrast, however, 15.3% of patients assigned to cALND reported lymphedema, paresthesia, swelling, arm pain, or shoulder mobility problems, compared with 4.7% treated with radiotherapy. There were no significant differences in quality of life as assessed by standard instruments, however.

The study was supported by the Hungarian National Institute of Oncology. Dr. Savolt and colleagues reported no competing interests.

[email protected]

AMSTERDAM – Axillary radiotherapy appears to be a safe and effective alternative to completion axillary lymph node dissection (cALND) for selected patients who have early invasive breast cancer with sentinel lymph node metastasis, a randomized phase III trial showed.

After a mean of just over 8 years of follow-up, there were no significant differences in breast cancer recurrence, overall survival (OS), disease-free survival (DFS), or breast cancer deaths between patients treated with cALND or axillary radiotherapy, reported Akos Savolt, MD, PhD, of the National Institute of Oncology in Budapest.

“This trial has changed our everyday practice about the optimal care of the axilla,” he said at an annual congress sponsored by the European Cancer Organisation.

An estimated 25%-50% of patients with positive sentinel lymph nodes will have disease that extends to other lymph nodes, and for these patients, cALND is the standard of care.

But patients for whom metastasis is limited to the sentinel lymph node are unlikely to benefit from more extensive dissections, and for these patients, the proven benefits of cALND must be weighed against the significant complications associated with the procedure, including lymphedema, arm pain, nerve injury, shoulder dysfunction, and paresthesias, Dr. Savolt noted.

The OTOASOR (Optimal Treatment of the Axilla – Surgery or Radiotherapy) trial was a single-center study designed to see whether axillary radiotherapy could be noninferior to cALND for preventing recurrence and breast cancer deaths.

From mid-2002 through mid-2009,the investigators enrolled women with primary invasive breast cancer (tumors 3 cm or smaller and no clinically detected lymph node metastases), and randomized them prior to surgery to receive either cALND or axillary radiotherapy at a dose of 50 Gy. Patients also received adjuvant therapy as per institutional guidelines.

A total of 474 patients were evaluable for follow-up: 244 assigned to cALND and 230 assigned to radiotherapy. In all, 94 patients assigned to cALND (38.5%) were found to have additional lymph node metastases.

At a mean follow-up of 97 months, 2% of women in the cALND group had experienced an axillary recurrence (the primary endpoint), compared with 1.7% in the axillary radiation arm.

Overall survival was also similar between the groups, at 77.9% vs. 84.8%, respectively, as was disease-free survival, at 72.1% and 77.4%; neither comparison yielded statistically significant results.

There were also no between-group differences in the percentage of patients alive with recurrence, breast cancer deaths (13.9% of patients in the cALND arm vs. 8.7 in the radiation arm), or deaths from other causes (8.2% vs. 6.5%, respectively).

In contrast, however, 15.3% of patients assigned to cALND reported lymphedema, paresthesia, swelling, arm pain, or shoulder mobility problems, compared with 4.7% treated with radiotherapy. There were no significant differences in quality of life as assessed by standard instruments, however.

The study was supported by the Hungarian National Institute of Oncology. Dr. Savolt and colleagues reported no competing interests.

[email protected]

AMSTERDAM – Axillary radiotherapy appears to be a safe and effective alternative to completion axillary lymph node dissection (cALND) for selected patients who have early invasive breast cancer with sentinel lymph node metastasis, a randomized phase III trial showed.

After a mean of just over 8 years of follow-up, there were no significant differences in breast cancer recurrence, overall survival (OS), disease-free survival (DFS), or breast cancer deaths between patients treated with cALND or axillary radiotherapy, reported Akos Savolt, MD, PhD, of the National Institute of Oncology in Budapest.

“This trial has changed our everyday practice about the optimal care of the axilla,” he said at an annual congress sponsored by the European Cancer Organisation.

An estimated 25%-50% of patients with positive sentinel lymph nodes will have disease that extends to other lymph nodes, and for these patients, cALND is the standard of care.

But patients for whom metastasis is limited to the sentinel lymph node are unlikely to benefit from more extensive dissections, and for these patients, the proven benefits of cALND must be weighed against the significant complications associated with the procedure, including lymphedema, arm pain, nerve injury, shoulder dysfunction, and paresthesias, Dr. Savolt noted.

The OTOASOR (Optimal Treatment of the Axilla – Surgery or Radiotherapy) trial was a single-center study designed to see whether axillary radiotherapy could be noninferior to cALND for preventing recurrence and breast cancer deaths.

From mid-2002 through mid-2009,the investigators enrolled women with primary invasive breast cancer (tumors 3 cm or smaller and no clinically detected lymph node metastases), and randomized them prior to surgery to receive either cALND or axillary radiotherapy at a dose of 50 Gy. Patients also received adjuvant therapy as per institutional guidelines.

A total of 474 patients were evaluable for follow-up: 244 assigned to cALND and 230 assigned to radiotherapy. In all, 94 patients assigned to cALND (38.5%) were found to have additional lymph node metastases.

At a mean follow-up of 97 months, 2% of women in the cALND group had experienced an axillary recurrence (the primary endpoint), compared with 1.7% in the axillary radiation arm.

Overall survival was also similar between the groups, at 77.9% vs. 84.8%, respectively, as was disease-free survival, at 72.1% and 77.4%; neither comparison yielded statistically significant results.

There were also no between-group differences in the percentage of patients alive with recurrence, breast cancer deaths (13.9% of patients in the cALND arm vs. 8.7 in the radiation arm), or deaths from other causes (8.2% vs. 6.5%, respectively).

In contrast, however, 15.3% of patients assigned to cALND reported lymphedema, paresthesia, swelling, arm pain, or shoulder mobility problems, compared with 4.7% treated with radiotherapy. There were no significant differences in quality of life as assessed by standard instruments, however.

The study was supported by the Hungarian National Institute of Oncology. Dr. Savolt and colleagues reported no competing interests.

[email protected]

The Patient Protection and Affordable Care Act of 2010 (ACA) intended that women have access to critical preventive health services without a copay or deductible. The Institute of Medicine (IOM) was asked to help identify those critical preventive women’s health services. In 2011, the IOM Committee on Preventive Services for Women recommended that all women have access to 9 preventive services, among them¹:

• screening for gestational diabetes mellitus (GDM)
• human papilloma virus testing
• contraceptive methods and counseling
• well-woman visits.

The Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services agreed to update the recommended preventive services every 5 years.

In March 2016, HRSA entered into a 5-year cooperative agreement with the American College of Obstetricians and Gynecologists (ACOG) to update the guidelines and to develop additional recommendations to enhance women’s health.² ACOG launched the Women’s Preventive Services Initiative (WPSI) to develop the 2016 update.

The 5-year grant with HRSA will address many more preventive health services for women across their lifespan as well as implementation strategies so that women receive consistent and appropriate care, regardless of the health care provider’s specialty. The WPSI recognizes that the selection of a provider for well-woman care will be determined as much by a woman’s needs and preferences as by her access to health care services and health plan availability.

The WPSI draft recommendations were released for public comment in September 2016,² and HRSA approved the recommendations in December 2016.³ In this editorial, I provide a look at which organizations comprise the WPSI and a summary of the 9 recommended preventive health services.

Who makes up the Women’s Preventive Services Initiative?

The WPSI is a collaboration between professional societies and consumer organizations. The goal of the WPSI is “to promote health over the course of a woman’s lifetime through disease prevention and preventive healthcare.” The WPSI advisory panel provides oversight to the effort and the multidisciplinary steering committee develops the recommendations. The WPSI advisory panel includes leaders and experts from 4 major professional organizations, whose members provide the majority of women’s health care in the United States:

• ACOG
• American College of Physicians (ACP)
• American Academy of Family Physicians (AAFP)
• National Association of Nurse Practitioners in Women’s Health (NPWH).

The multidisciplinary steering committee includes the members of the advisory panel, representatives from 17 professional and consumer organizations, a patient representative, and representatives from 6 federal agencies. The WPSI is currently chaired by Jeanne Conry, MD, PhD, past president of ACOG. The steering committee used evidence-based best practices to develop the guidelines and relied heavily on the foundation provided by the 2011 IOM report.¹

The 9 WPSI recommendations

Much of the text below is directly quoted from the final recommendations. When a recommendation is paraphrased it is not placed in quotations.

Recommendation 1: Breast cancer screening for average-risk women

“Average-risk women should initiate mammography screening for breast cancer no earlier than age 40 and no later than age 50 years. Screeningmammography should occur at least biennially and as frequently as annually. Screening should continue through at least age 74 years and age alone should not be the basis to stop screening.”

Decisions about when to initiate screening for women between 40 and 50 years of age, how often to screen, and when to stop screening should be based on shared decision making involving the woman and her clinician.

Recommendation 2: Breastfeeding services and supplies

Women should be provided “comprehensive lactation support services including counseling, education and breast feeding equipment and supplies during the antenatal, perinatal, and postpartum periods.” These services will support the successful initiation and maintenance of breastfeeding. Women should have access to double electric breast pumps.

Recommendation 3: Screening for cervical cancer

Average-risk women should initiate cervical cancer screening with cervical cytology at age 21 years and have cervical cytology testing every 3 years from 21 to 29 years of age. “Cotesting with cytology and human papillomavirus (HPV) testing is not recommended for women younger than 30 years. Women aged 30 to 65 years should be screened with cytology and HPV testing every 5 years or cytology alone every 3 years.” Women who have received the HPV vaccine should be screened using these guidelines. Cervical cancer screening is not recommended for women younger than 21 years or older than 65 years who have had adequate prior screening and are not at high risk for cervical cancer. Cervical cancer screening is also not recommended for women who have had a hysterectomy with removal of the cervix and no personal history of cervical intraepithelial neoplasia grade 2 or 3 within the past 20 years.

Recommendation 4: Contraception

Adolescent and adult women should have access to the full range of US Food and Drug Administration–approved female-controlled contraceptives to prevent unintended pregnancy and improve birth outcomes. Multiple visits with a clinician may be needed to select an optimal contraceptive.

Recommendation 5: Screening for gestational diabetes mellitus

Pregnant women should be screened for GDM between 24 and 28 weeks’ gestation to prevent adverse birth outcomes. Screening should be performed with a “50 gm oral glucose challenge test followed by a 3-hour 100 gm oral glucose tolerance test” if the results on the initial oral glucose tolerance test are abnormal. This testing sequence has high sensitivity and specificity. Women with risk factors for diabetes mellitus should be screened for diabetes at the first prenatal visit using current best clinical practice.

Recommendation 6: Screening for human immunodeficiency virus (HIV) infection

Adolescents and women should receive education and risk assessment for HIV annually and should be tested for HIV at least once during their lifetime. Based on assessed risk, screening annually may be appropriate. “Screening for HIV is recommended for all pregnant women upon initiation of prenatal care with retesting during pregnancy based on risk factors. Rapid HIV testing is recommended for pregnant women who present in active labor with an undocumented HIV status.” Risk-based screening does not identify approximately 20% of HIV-infected people. Hence screening annually may be reasonable.

Recommendation 7: Screening for interpersonal and domestic violence

All adolescents and women should be screened annually for both interpersonal violence (IPV) and domestic violence (DV). Intervention services should be available to all adolescents and women. IPV and DV are prevalent problems, and they are often undetected by clinicians. Hence annual screening is recommended.

Recommendation 8: Counseling for sexually transmitted infections

Adolescents and women should be assessed for sexually transmittedinfection (STI) risk. Risk factors include:

• “age younger than 25 years,
• a recent STI,
• a new sex partner,
• multiple partners,
• a partner with concurrent partners,
• a partner with an STI, and
• a lack of or inconsistent condom use.”

Women at increased risk for an STI should receive behavioral counseling.

Recommendation 9: Well-woman preventive visits

Women should “receive at least one preventive care visit per year beginning in adolescence and continuing across the lifespan to ensure that the recommended preventive services including preconception and many services necessary for prenatal and interconception care are obtained. The primary purpose of these visits is the delivery and coordination of recommended preventive services as determined by age and risk factors.”

I plan on using these recommendations to guide my practice

Historically, many high-profile expert professional groups have developed their own women’s health services guidelines. The proliferation of conflicting guidelines confused both patients and clinicians. Dueling guidelines likely undermine public health because they result in confusion among patients and inconsistent care across the many disciplines that provide medical services to women.

The proliferation of conflicting guidelines for mammography screening for breast cancer is a good example of how dueling guidelines can undermine public health (TABLE).⁴⁻⁷ The WPSI has done a great service to women and clinicians by creating a shared framework for consistently providing critical services across a woman’s entire life. I plan on using these recommendations to guide my practice. Patients and clinicians will greatly benefit from the exceptionally thoughtful women’s preventive services guidelines provided by the WPSI.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The Patient Protection and Affordable Care Act of 2010 (ACA) intended that women have access to critical preventive health services without a copay or deductible. The Institute of Medicine (IOM) was asked to help identify those critical preventive women’s health services. In 2011, the IOM Committee on Preventive Services for Women recommended that all women have access to 9 preventive services, among them¹:

• screening for gestational diabetes mellitus (GDM)
• human papilloma virus testing
• contraceptive methods and counseling
• well-woman visits.

The Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services agreed to update the recommended preventive services every 5 years.

In March 2016, HRSA entered into a 5-year cooperative agreement with the American College of Obstetricians and Gynecologists (ACOG) to update the guidelines and to develop additional recommendations to enhance women’s health.² ACOG launched the Women’s Preventive Services Initiative (WPSI) to develop the 2016 update.

The 5-year grant with HRSA will address many more preventive health services for women across their lifespan as well as implementation strategies so that women receive consistent and appropriate care, regardless of the health care provider’s specialty. The WPSI recognizes that the selection of a provider for well-woman care will be determined as much by a woman’s needs and preferences as by her access to health care services and health plan availability.

The WPSI draft recommendations were released for public comment in September 2016,² and HRSA approved the recommendations in December 2016.³ In this editorial, I provide a look at which organizations comprise the WPSI and a summary of the 9 recommended preventive health services.

Who makes up the Women’s Preventive Services Initiative?

The WPSI is a collaboration between professional societies and consumer organizations. The goal of the WPSI is “to promote health over the course of a woman’s lifetime through disease prevention and preventive healthcare.” The WPSI advisory panel provides oversight to the effort and the multidisciplinary steering committee develops the recommendations. The WPSI advisory panel includes leaders and experts from 4 major professional organizations, whose members provide the majority of women’s health care in the United States:

• ACOG
• American College of Physicians (ACP)
• American Academy of Family Physicians (AAFP)
• National Association of Nurse Practitioners in Women’s Health (NPWH).

The multidisciplinary steering committee includes the members of the advisory panel, representatives from 17 professional and consumer organizations, a patient representative, and representatives from 6 federal agencies. The WPSI is currently chaired by Jeanne Conry, MD, PhD, past president of ACOG. The steering committee used evidence-based best practices to develop the guidelines and relied heavily on the foundation provided by the 2011 IOM report.¹

The 9 WPSI recommendations

Much of the text below is directly quoted from the final recommendations. When a recommendation is paraphrased it is not placed in quotations.

Recommendation 1: Breast cancer screening for average-risk women

“Average-risk women should initiate mammography screening for breast cancer no earlier than age 40 and no later than age 50 years. Screeningmammography should occur at least biennially and as frequently as annually. Screening should continue through at least age 74 years and age alone should not be the basis to stop screening.”

Decisions about when to initiate screening for women between 40 and 50 years of age, how often to screen, and when to stop screening should be based on shared decision making involving the woman and her clinician.

Recommendation 2: Breastfeeding services and supplies

Women should be provided “comprehensive lactation support services including counseling, education and breast feeding equipment and supplies during the antenatal, perinatal, and postpartum periods.” These services will support the successful initiation and maintenance of breastfeeding. Women should have access to double electric breast pumps.

Recommendation 3: Screening for cervical cancer

Average-risk women should initiate cervical cancer screening with cervical cytology at age 21 years and have cervical cytology testing every 3 years from 21 to 29 years of age. “Cotesting with cytology and human papillomavirus (HPV) testing is not recommended for women younger than 30 years. Women aged 30 to 65 years should be screened with cytology and HPV testing every 5 years or cytology alone every 3 years.” Women who have received the HPV vaccine should be screened using these guidelines. Cervical cancer screening is not recommended for women younger than 21 years or older than 65 years who have had adequate prior screening and are not at high risk for cervical cancer. Cervical cancer screening is also not recommended for women who have had a hysterectomy with removal of the cervix and no personal history of cervical intraepithelial neoplasia grade 2 or 3 within the past 20 years.

Recommendation 4: Contraception

Adolescent and adult women should have access to the full range of US Food and Drug Administration–approved female-controlled contraceptives to prevent unintended pregnancy and improve birth outcomes. Multiple visits with a clinician may be needed to select an optimal contraceptive.

Recommendation 5: Screening for gestational diabetes mellitus

Pregnant women should be screened for GDM between 24 and 28 weeks’ gestation to prevent adverse birth outcomes. Screening should be performed with a “50 gm oral glucose challenge test followed by a 3-hour 100 gm oral glucose tolerance test” if the results on the initial oral glucose tolerance test are abnormal. This testing sequence has high sensitivity and specificity. Women with risk factors for diabetes mellitus should be screened for diabetes at the first prenatal visit using current best clinical practice.

Recommendation 6: Screening for human immunodeficiency virus (HIV) infection

Adolescents and women should receive education and risk assessment for HIV annually and should be tested for HIV at least once during their lifetime. Based on assessed risk, screening annually may be appropriate. “Screening for HIV is recommended for all pregnant women upon initiation of prenatal care with retesting during pregnancy based on risk factors. Rapid HIV testing is recommended for pregnant women who present in active labor with an undocumented HIV status.” Risk-based screening does not identify approximately 20% of HIV-infected people. Hence screening annually may be reasonable.

Recommendation 7: Screening for interpersonal and domestic violence

All adolescents and women should be screened annually for both interpersonal violence (IPV) and domestic violence (DV). Intervention services should be available to all adolescents and women. IPV and DV are prevalent problems, and they are often undetected by clinicians. Hence annual screening is recommended.

Recommendation 8: Counseling for sexually transmitted infections

Adolescents and women should be assessed for sexually transmittedinfection (STI) risk. Risk factors include:

• “age younger than 25 years,
• a recent STI,
• a new sex partner,
• multiple partners,
• a partner with concurrent partners,
• a partner with an STI, and
• a lack of or inconsistent condom use.”

Women at increased risk for an STI should receive behavioral counseling.

Recommendation 9: Well-woman preventive visits

Women should “receive at least one preventive care visit per year beginning in adolescence and continuing across the lifespan to ensure that the recommended preventive services including preconception and many services necessary for prenatal and interconception care are obtained. The primary purpose of these visits is the delivery and coordination of recommended preventive services as determined by age and risk factors.”

I plan on using these recommendations to guide my practice

Historically, many high-profile expert professional groups have developed their own women’s health services guidelines. The proliferation of conflicting guidelines confused both patients and clinicians. Dueling guidelines likely undermine public health because they result in confusion among patients and inconsistent care across the many disciplines that provide medical services to women.

The proliferation of conflicting guidelines for mammography screening for breast cancer is a good example of how dueling guidelines can undermine public health (TABLE).⁴⁻⁷ The WPSI has done a great service to women and clinicians by creating a shared framework for consistently providing critical services across a woman’s entire life. I plan on using these recommendations to guide my practice. Patients and clinicians will greatly benefit from the exceptionally thoughtful women’s preventive services guidelines provided by the WPSI.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The Patient Protection and Affordable Care Act of 2010 (ACA) intended that women have access to critical preventive health services without a copay or deductible. The Institute of Medicine (IOM) was asked to help identify those critical preventive women’s health services. In 2011, the IOM Committee on Preventive Services for Women recommended that all women have access to 9 preventive services, among them¹:

• screening for gestational diabetes mellitus (GDM)
• human papilloma virus testing
• contraceptive methods and counseling
• well-woman visits.

The Health Resources and Services Administration (HRSA) of the US Department of Health and Human Services agreed to update the recommended preventive services every 5 years.

In March 2016, HRSA entered into a 5-year cooperative agreement with the American College of Obstetricians and Gynecologists (ACOG) to update the guidelines and to develop additional recommendations to enhance women’s health.² ACOG launched the Women’s Preventive Services Initiative (WPSI) to develop the 2016 update.

The 5-year grant with HRSA will address many more preventive health services for women across their lifespan as well as implementation strategies so that women receive consistent and appropriate care, regardless of the health care provider’s specialty. The WPSI recognizes that the selection of a provider for well-woman care will be determined as much by a woman’s needs and preferences as by her access to health care services and health plan availability.

The WPSI draft recommendations were released for public comment in September 2016,² and HRSA approved the recommendations in December 2016.³ In this editorial, I provide a look at which organizations comprise the WPSI and a summary of the 9 recommended preventive health services.

Who makes up the Women’s Preventive Services Initiative?

The WPSI is a collaboration between professional societies and consumer organizations. The goal of the WPSI is “to promote health over the course of a woman’s lifetime through disease prevention and preventive healthcare.” The WPSI advisory panel provides oversight to the effort and the multidisciplinary steering committee develops the recommendations. The WPSI advisory panel includes leaders and experts from 4 major professional organizations, whose members provide the majority of women’s health care in the United States:

• ACOG
• American College of Physicians (ACP)
• American Academy of Family Physicians (AAFP)
• National Association of Nurse Practitioners in Women’s Health (NPWH).

The multidisciplinary steering committee includes the members of the advisory panel, representatives from 17 professional and consumer organizations, a patient representative, and representatives from 6 federal agencies. The WPSI is currently chaired by Jeanne Conry, MD, PhD, past president of ACOG. The steering committee used evidence-based best practices to develop the guidelines and relied heavily on the foundation provided by the 2011 IOM report.¹

The 9 WPSI recommendations

Much of the text below is directly quoted from the final recommendations. When a recommendation is paraphrased it is not placed in quotations.

Recommendation 1: Breast cancer screening for average-risk women

“Average-risk women should initiate mammography screening for breast cancer no earlier than age 40 and no later than age 50 years. Screeningmammography should occur at least biennially and as frequently as annually. Screening should continue through at least age 74 years and age alone should not be the basis to stop screening.”

Decisions about when to initiate screening for women between 40 and 50 years of age, how often to screen, and when to stop screening should be based on shared decision making involving the woman and her clinician.

Recommendation 2: Breastfeeding services and supplies

Women should be provided “comprehensive lactation support services including counseling, education and breast feeding equipment and supplies during the antenatal, perinatal, and postpartum periods.” These services will support the successful initiation and maintenance of breastfeeding. Women should have access to double electric breast pumps.

Recommendation 3: Screening for cervical cancer

Average-risk women should initiate cervical cancer screening with cervical cytology at age 21 years and have cervical cytology testing every 3 years from 21 to 29 years of age. “Cotesting with cytology and human papillomavirus (HPV) testing is not recommended for women younger than 30 years. Women aged 30 to 65 years should be screened with cytology and HPV testing every 5 years or cytology alone every 3 years.” Women who have received the HPV vaccine should be screened using these guidelines. Cervical cancer screening is not recommended for women younger than 21 years or older than 65 years who have had adequate prior screening and are not at high risk for cervical cancer. Cervical cancer screening is also not recommended for women who have had a hysterectomy with removal of the cervix and no personal history of cervical intraepithelial neoplasia grade 2 or 3 within the past 20 years.

Recommendation 4: Contraception

Adolescent and adult women should have access to the full range of US Food and Drug Administration–approved female-controlled contraceptives to prevent unintended pregnancy and improve birth outcomes. Multiple visits with a clinician may be needed to select an optimal contraceptive.

Recommendation 5: Screening for gestational diabetes mellitus

Pregnant women should be screened for GDM between 24 and 28 weeks’ gestation to prevent adverse birth outcomes. Screening should be performed with a “50 gm oral glucose challenge test followed by a 3-hour 100 gm oral glucose tolerance test” if the results on the initial oral glucose tolerance test are abnormal. This testing sequence has high sensitivity and specificity. Women with risk factors for diabetes mellitus should be screened for diabetes at the first prenatal visit using current best clinical practice.

Recommendation 6: Screening for human immunodeficiency virus (HIV) infection

Adolescents and women should receive education and risk assessment for HIV annually and should be tested for HIV at least once during their lifetime. Based on assessed risk, screening annually may be appropriate. “Screening for HIV is recommended for all pregnant women upon initiation of prenatal care with retesting during pregnancy based on risk factors. Rapid HIV testing is recommended for pregnant women who present in active labor with an undocumented HIV status.” Risk-based screening does not identify approximately 20% of HIV-infected people. Hence screening annually may be reasonable.

Recommendation 7: Screening for interpersonal and domestic violence

All adolescents and women should be screened annually for both interpersonal violence (IPV) and domestic violence (DV). Intervention services should be available to all adolescents and women. IPV and DV are prevalent problems, and they are often undetected by clinicians. Hence annual screening is recommended.

Recommendation 8: Counseling for sexually transmitted infections

Adolescents and women should be assessed for sexually transmittedinfection (STI) risk. Risk factors include:

• “age younger than 25 years,
• a recent STI,
• a new sex partner,
• multiple partners,
• a partner with concurrent partners,
• a partner with an STI, and
• a lack of or inconsistent condom use.”

Women at increased risk for an STI should receive behavioral counseling.

Recommendation 9: Well-woman preventive visits

Women should “receive at least one preventive care visit per year beginning in adolescence and continuing across the lifespan to ensure that the recommended preventive services including preconception and many services necessary for prenatal and interconception care are obtained. The primary purpose of these visits is the delivery and coordination of recommended preventive services as determined by age and risk factors.”

I plan on using these recommendations to guide my practice

Historically, many high-profile expert professional groups have developed their own women’s health services guidelines. The proliferation of conflicting guidelines confused both patients and clinicians. Dueling guidelines likely undermine public health because they result in confusion among patients and inconsistent care across the many disciplines that provide medical services to women.

The proliferation of conflicting guidelines for mammography screening for breast cancer is a good example of how dueling guidelines can undermine public health (TABLE).⁴⁻⁷ The WPSI has done a great service to women and clinicians by creating a shared framework for consistently providing critical services across a woman’s entire life. I plan on using these recommendations to guide my practice. Patients and clinicians will greatly benefit from the exceptionally thoughtful women’s preventive services guidelines provided by the WPSI.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The Residual Cancer Burden (RCB), a standardized measure of residual disease in pathologic resection specimens following neoadjuvant chemotherapy, was found to be prognostic of long-term survival across all three phenotypic subtypes when it was applied to five breast cancer cohorts totaling 1,158 patients from a single institution, investigators report in the Journal of Clinical Oncology.

If the findings of this retrospective cohort analysis are validated in other cohorts, it would indicate that assessing patients’ RCB index could add “meaningful information to pretreatement clinical and pathologic information and posttreatment yp stage [American Joint Commission on Cancer stage],” said W. Fraser Symmans, MD, of the University of Texas M.D. Anderson Cancer Center, Houston, and his associates.

Residual disease is categorized into four groups: an index of zero (RCB-0) reflects a complete pathologic response to neoadjuvant treatment, RCB-I indicates minimal residual disease, RCB-II indicates moderate residual disease, and RCB-III indicates extensive residual disease. The investigators reviewed pathology specimens to determine the RCB index in a cohort of 219 patients followed for 13 years, a cohort of 262 patients followed for 9 years, a cohort of 342 patients followed for 7 years, a cohort of 132 patients followed for more than 16 years, and a cohort of 203 patients followed for 7 years.

They found that the RCB index predicted the risk of relapse or death across all five cohorts, regardless of other clinical and pathologic variables such as tumor stage or grade, patient age, and type of surgery (J Clin Oncol. 2017 Jan 30. doi: 10.1200/JCO.2015.63.1010).

RCB also was predictive regardless of whether patients had triple-negative disease, HR-positive/HER2-negative disease, HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide alone, or HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide plus trastuzumab.

In two especially high-risk groups of patients – those with triple-negative breast cancer and those with HER2-positive breast cancer – RCB was the only or the most important predictor of survival. Approximately half of the patients with triple-negative disease had an index of RCB-0 or RCB-I and a good prognosis, while those with an RCB-II or RCB-III index had poor survival, Dr. Symmans and his associates said.

The Residual Cancer Burden (RCB), a standardized measure of residual disease in pathologic resection specimens following neoadjuvant chemotherapy, was found to be prognostic of long-term survival across all three phenotypic subtypes when it was applied to five breast cancer cohorts totaling 1,158 patients from a single institution, investigators report in the Journal of Clinical Oncology.

If the findings of this retrospective cohort analysis are validated in other cohorts, it would indicate that assessing patients’ RCB index could add “meaningful information to pretreatement clinical and pathologic information and posttreatment yp stage [American Joint Commission on Cancer stage],” said W. Fraser Symmans, MD, of the University of Texas M.D. Anderson Cancer Center, Houston, and his associates.

Residual disease is categorized into four groups: an index of zero (RCB-0) reflects a complete pathologic response to neoadjuvant treatment, RCB-I indicates minimal residual disease, RCB-II indicates moderate residual disease, and RCB-III indicates extensive residual disease. The investigators reviewed pathology specimens to determine the RCB index in a cohort of 219 patients followed for 13 years, a cohort of 262 patients followed for 9 years, a cohort of 342 patients followed for 7 years, a cohort of 132 patients followed for more than 16 years, and a cohort of 203 patients followed for 7 years.

They found that the RCB index predicted the risk of relapse or death across all five cohorts, regardless of other clinical and pathologic variables such as tumor stage or grade, patient age, and type of surgery (J Clin Oncol. 2017 Jan 30. doi: 10.1200/JCO.2015.63.1010).

RCB also was predictive regardless of whether patients had triple-negative disease, HR-positive/HER2-negative disease, HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide alone, or HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide plus trastuzumab.

In two especially high-risk groups of patients – those with triple-negative breast cancer and those with HER2-positive breast cancer – RCB was the only or the most important predictor of survival. Approximately half of the patients with triple-negative disease had an index of RCB-0 or RCB-I and a good prognosis, while those with an RCB-II or RCB-III index had poor survival, Dr. Symmans and his associates said.

The Residual Cancer Burden (RCB), a standardized measure of residual disease in pathologic resection specimens following neoadjuvant chemotherapy, was found to be prognostic of long-term survival across all three phenotypic subtypes when it was applied to five breast cancer cohorts totaling 1,158 patients from a single institution, investigators report in the Journal of Clinical Oncology.

If the findings of this retrospective cohort analysis are validated in other cohorts, it would indicate that assessing patients’ RCB index could add “meaningful information to pretreatement clinical and pathologic information and posttreatment yp stage [American Joint Commission on Cancer stage],” said W. Fraser Symmans, MD, of the University of Texas M.D. Anderson Cancer Center, Houston, and his associates.

Residual disease is categorized into four groups: an index of zero (RCB-0) reflects a complete pathologic response to neoadjuvant treatment, RCB-I indicates minimal residual disease, RCB-II indicates moderate residual disease, and RCB-III indicates extensive residual disease. The investigators reviewed pathology specimens to determine the RCB index in a cohort of 219 patients followed for 13 years, a cohort of 262 patients followed for 9 years, a cohort of 342 patients followed for 7 years, a cohort of 132 patients followed for more than 16 years, and a cohort of 203 patients followed for 7 years.

They found that the RCB index predicted the risk of relapse or death across all five cohorts, regardless of other clinical and pathologic variables such as tumor stage or grade, patient age, and type of surgery (J Clin Oncol. 2017 Jan 30. doi: 10.1200/JCO.2015.63.1010).

RCB also was predictive regardless of whether patients had triple-negative disease, HR-positive/HER2-negative disease, HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide alone, or HER2-positive disease treated with paclitaxel plus combined fluorouracil, doxorubicin, and cyclophosphamide plus trastuzumab.

In two especially high-risk groups of patients – those with triple-negative breast cancer and those with HER2-positive breast cancer – RCB was the only or the most important predictor of survival. Approximately half of the patients with triple-negative disease had an index of RCB-0 or RCB-I and a good prognosis, while those with an RCB-II or RCB-III index had poor survival, Dr. Symmans and his associates said.

The risk of acute coronary events following radiotherapy for breast cancer is better predicted by the volume of the left ventricle that received 5 Gy than by the mean dose of radiation to the heart, according to a Dutch investigation of 910 women who underwent radiation treatment following breast-conserving surgery.

The finding follows up a 2013 report that found that the risk of acute coronary events (ACE) after breast cancer (BC) radiation could be predicted by the mean radiation heart dose (MHD), the presence of cardiac risk factors, and age (N Engl J Med. 2013 Mar 14;368[11]:987-98. doi: 0.1056/NEJMoa1209825).

The new study validated those findings, but also found that risk prediction was better when mean heart dose (MHD) was replaced by the volume of the left ventricle receiving 5 Gy (LV-V5); the substitution improved the c-statistic to 0.80 (95% confidence interval, 0.72-0.88). Using a weighted ACE risk score based on baseline diabetes, hypertension, and ischemic event history – instead of the risk factor yes-or-no approach from 2013 – further improved predictive power, with a c-statistic of 0.83 (95% CI, 0.75-0.91). Anything over a c-statistic of 0.8 is considered strong; 0.5 is chance, 1.0 is perfect prediction.

For instance, a 70-year-old woman with an LV-V5 of 50% and no cardiac risk factors had an excess ACE risk in the new system of 2.52% within 9 years of radiotherapy (RT). If she had a history of ischemic heart disease, the excess risk increased to 8.42%, the investigators said (J Clin Oncol. 2017 Jan 17. doi: 10.1200/JCO.2016.69.8480).

“Model performance was significantly improved by replacing MHD with LV-V5 and using the weighted ACE risk score.” However, “because we were not able to externally validate the LV-V5 model, this model” requires validation “before it can be used in routine clinical practice,” said investigators, led by Veerle van den Bogaard, MD, of the University of Groningen, the Netherlands.

The women were a median of 59 years old, and they were followed for a median of 7.6 years, with a range of 0.1-10.1 years. Radiation dose information was derived from CT planning scans. The median MHD was 2.37 Gy.

Thirty patients (3.3%) had an ACE, defined as myocardial infarction, coronary revascularization, or death due to ischemic heart disease; 17 had events in the first 5 years. The 5- and 9-year cumulative ACE incidences were 1.9% and 3.9%. Ten of the 30 women died from their cardiac complication.

The model predicted a cumulative ACE incidence at 9 years of 3.5%, which was in line with the observed rate of 3.9%. The excess cumulative risk related to RT was 1.13%. Overall, about 10 patients had an ACE that could be attributed to RT. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6-35.0; P = .042). The findings were consistent with the 2013 study.

ACE incidence was not significantly associated with the maximum dose of radiation to the heart.

LV-V5 was the most important prognostic dose-volume parameter associated with the cumulative incidence of ACE, with a hazard ratio of 1.016 (95% CI, 1.002-1.030; P = .016). “Because of this strong association, we chose to include LV-V5 in the model,” the investigators said.

There was no external funding. The lead investigator had no disclosures, but two authors reported institutional research funding from Philips, Roche, and other companies. One was an advisor and speaker for IBA.
 

[email protected]

The risk of acute coronary events following radiotherapy for breast cancer is better predicted by the volume of the left ventricle that received 5 Gy than by the mean dose of radiation to the heart, according to a Dutch investigation of 910 women who underwent radiation treatment following breast-conserving surgery.

The finding follows up a 2013 report that found that the risk of acute coronary events (ACE) after breast cancer (BC) radiation could be predicted by the mean radiation heart dose (MHD), the presence of cardiac risk factors, and age (N Engl J Med. 2013 Mar 14;368[11]:987-98. doi: 0.1056/NEJMoa1209825).

The new study validated those findings, but also found that risk prediction was better when mean heart dose (MHD) was replaced by the volume of the left ventricle receiving 5 Gy (LV-V5); the substitution improved the c-statistic to 0.80 (95% confidence interval, 0.72-0.88). Using a weighted ACE risk score based on baseline diabetes, hypertension, and ischemic event history – instead of the risk factor yes-or-no approach from 2013 – further improved predictive power, with a c-statistic of 0.83 (95% CI, 0.75-0.91). Anything over a c-statistic of 0.8 is considered strong; 0.5 is chance, 1.0 is perfect prediction.

For instance, a 70-year-old woman with an LV-V5 of 50% and no cardiac risk factors had an excess ACE risk in the new system of 2.52% within 9 years of radiotherapy (RT). If she had a history of ischemic heart disease, the excess risk increased to 8.42%, the investigators said (J Clin Oncol. 2017 Jan 17. doi: 10.1200/JCO.2016.69.8480).

“Model performance was significantly improved by replacing MHD with LV-V5 and using the weighted ACE risk score.” However, “because we were not able to externally validate the LV-V5 model, this model” requires validation “before it can be used in routine clinical practice,” said investigators, led by Veerle van den Bogaard, MD, of the University of Groningen, the Netherlands.

The women were a median of 59 years old, and they were followed for a median of 7.6 years, with a range of 0.1-10.1 years. Radiation dose information was derived from CT planning scans. The median MHD was 2.37 Gy.

Thirty patients (3.3%) had an ACE, defined as myocardial infarction, coronary revascularization, or death due to ischemic heart disease; 17 had events in the first 5 years. The 5- and 9-year cumulative ACE incidences were 1.9% and 3.9%. Ten of the 30 women died from their cardiac complication.

The model predicted a cumulative ACE incidence at 9 years of 3.5%, which was in line with the observed rate of 3.9%. The excess cumulative risk related to RT was 1.13%. Overall, about 10 patients had an ACE that could be attributed to RT. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6-35.0; P = .042). The findings were consistent with the 2013 study.

ACE incidence was not significantly associated with the maximum dose of radiation to the heart.

LV-V5 was the most important prognostic dose-volume parameter associated with the cumulative incidence of ACE, with a hazard ratio of 1.016 (95% CI, 1.002-1.030; P = .016). “Because of this strong association, we chose to include LV-V5 in the model,” the investigators said.

There was no external funding. The lead investigator had no disclosures, but two authors reported institutional research funding from Philips, Roche, and other companies. One was an advisor and speaker for IBA.
 

[email protected]

The risk of acute coronary events following radiotherapy for breast cancer is better predicted by the volume of the left ventricle that received 5 Gy than by the mean dose of radiation to the heart, according to a Dutch investigation of 910 women who underwent radiation treatment following breast-conserving surgery.

The finding follows up a 2013 report that found that the risk of acute coronary events (ACE) after breast cancer (BC) radiation could be predicted by the mean radiation heart dose (MHD), the presence of cardiac risk factors, and age (N Engl J Med. 2013 Mar 14;368[11]:987-98. doi: 0.1056/NEJMoa1209825).

The new study validated those findings, but also found that risk prediction was better when mean heart dose (MHD) was replaced by the volume of the left ventricle receiving 5 Gy (LV-V5); the substitution improved the c-statistic to 0.80 (95% confidence interval, 0.72-0.88). Using a weighted ACE risk score based on baseline diabetes, hypertension, and ischemic event history – instead of the risk factor yes-or-no approach from 2013 – further improved predictive power, with a c-statistic of 0.83 (95% CI, 0.75-0.91). Anything over a c-statistic of 0.8 is considered strong; 0.5 is chance, 1.0 is perfect prediction.

For instance, a 70-year-old woman with an LV-V5 of 50% and no cardiac risk factors had an excess ACE risk in the new system of 2.52% within 9 years of radiotherapy (RT). If she had a history of ischemic heart disease, the excess risk increased to 8.42%, the investigators said (J Clin Oncol. 2017 Jan 17. doi: 10.1200/JCO.2016.69.8480).

“Model performance was significantly improved by replacing MHD with LV-V5 and using the weighted ACE risk score.” However, “because we were not able to externally validate the LV-V5 model, this model” requires validation “before it can be used in routine clinical practice,” said investigators, led by Veerle van den Bogaard, MD, of the University of Groningen, the Netherlands.

The women were a median of 59 years old, and they were followed for a median of 7.6 years, with a range of 0.1-10.1 years. Radiation dose information was derived from CT planning scans. The median MHD was 2.37 Gy.

Thirty patients (3.3%) had an ACE, defined as myocardial infarction, coronary revascularization, or death due to ischemic heart disease; 17 had events in the first 5 years. The 5- and 9-year cumulative ACE incidences were 1.9% and 3.9%. Ten of the 30 women died from their cardiac complication.

The model predicted a cumulative ACE incidence at 9 years of 3.5%, which was in line with the observed rate of 3.9%. The excess cumulative risk related to RT was 1.13%. Overall, about 10 patients had an ACE that could be attributed to RT. The cumulative incidence of ACE increased by 16.5% per Gy (95% CI, 0.6-35.0; P = .042). The findings were consistent with the 2013 study.

ACE incidence was not significantly associated with the maximum dose of radiation to the heart.

LV-V5 was the most important prognostic dose-volume parameter associated with the cumulative incidence of ACE, with a hazard ratio of 1.016 (95% CI, 1.002-1.030; P = .016). “Because of this strong association, we chose to include LV-V5 in the model,” the investigators said.

There was no external funding. The lead investigator had no disclosures, but two authors reported institutional research funding from Philips, Roche, and other companies. One was an advisor and speaker for IBA.
 

[email protected]

SAN ANTONIO – Circulating microRNAs may predict treatment response in HER2-positive breast cancer patients treated with neoadjuvant therapy, according to findings from the randomized phase III NeoALTTO trial.

Specifically, four circulating tumor microRNA signatures were found to predict pathologic complete response to specific treatments at specific time points in a “testing set” of patients from the study, Serena Di Cosimo, MD, of Istituto Nazionale dei Tumori, Milan, reported at the San Antonio Breast Cancer Symposium.

Overall results from the trial, which were reported in 2012 (The Lancet. 379[9816]:633-40) showed that the combination of lapatinib and trastuzumab significantly improved rates of pathologic complete response, compared with either drug alone in patients with HER2-positive early breast cancer, and the authors concluded that dual inhibition of HER2 might be a valid approach in such patients in the neoadjuvant treatment setting.

For the current analysis of NeoALTTO data, microRNA from plasma samples from 435 women – 141 treated with lapatinib, 151 treated with trastuzumab, and 143 treated with a combination of the two – were monitored longitudinally, as NeoALTTO “was done thinking about future translational studies, so blood samples were collected prospectively at baseline, after 2 weeks of treatment, at surgery, and at the time of relapse,” she noted.

Potential microRNAs associated with pathologic complete response were identified for each treatment arm and time point, and a multivariate model was used to identify specific signatures and their predictive capability.

A total of 30 microRNAs and 6 microRNA signatures were found to be predict pathologic complete response in a “training population,” and the predictive ability of 4 of those was confirmed in the testing set for lapatinib at baseline (area under the curve [AUC] = .86), lapatinib after 2 weeks (AUC = .71), trastuzumab after 2 weeks (AUC=.81), and lapatinib and trastuzumab after 2 weeks (AUC = .67), Dr. Di Cosimo said.

“Results obtained early post treatment are of special value,” she said, explaining that “women with unfavorable microRNA signatures can be expected to have poor response after just 2 weeks of treatment.”

The findings are of note because a significant proportion of breast cancer patients treated in the neoadjuvant setting do not achieve pathologic complete response and have an increased risk of relapse after surgery. Further, there is a lack of reliable predictors of response to help guide therapy in clinical practice, Dr. Ci Cosimo said.

“This is the first evidence of the potential of circulating microRNAs to discriminate between responsive and unresponsive HER2+ breast cancer patients,” she said.

At present, the signatures, overall, have been associated with pathologic complete response, but not event-free survival. However, one microRNA signature (140-5p) appeared to be associated with event-free survival after 2 weeks among patients treated with trastuzumab, she said, adding that functional studies are ongoing to investigate the biological role of microRNAs, and independent validation studies are planned.

Dr. Di Cosimo reported having no disclosures.

[email protected]

SAN ANTONIO – Circulating microRNAs may predict treatment response in HER2-positive breast cancer patients treated with neoadjuvant therapy, according to findings from the randomized phase III NeoALTTO trial.

Specifically, four circulating tumor microRNA signatures were found to predict pathologic complete response to specific treatments at specific time points in a “testing set” of patients from the study, Serena Di Cosimo, MD, of Istituto Nazionale dei Tumori, Milan, reported at the San Antonio Breast Cancer Symposium.

Overall results from the trial, which were reported in 2012 (The Lancet. 379[9816]:633-40) showed that the combination of lapatinib and trastuzumab significantly improved rates of pathologic complete response, compared with either drug alone in patients with HER2-positive early breast cancer, and the authors concluded that dual inhibition of HER2 might be a valid approach in such patients in the neoadjuvant treatment setting.

For the current analysis of NeoALTTO data, microRNA from plasma samples from 435 women – 141 treated with lapatinib, 151 treated with trastuzumab, and 143 treated with a combination of the two – were monitored longitudinally, as NeoALTTO “was done thinking about future translational studies, so blood samples were collected prospectively at baseline, after 2 weeks of treatment, at surgery, and at the time of relapse,” she noted.

Potential microRNAs associated with pathologic complete response were identified for each treatment arm and time point, and a multivariate model was used to identify specific signatures and their predictive capability.

A total of 30 microRNAs and 6 microRNA signatures were found to be predict pathologic complete response in a “training population,” and the predictive ability of 4 of those was confirmed in the testing set for lapatinib at baseline (area under the curve [AUC] = .86), lapatinib after 2 weeks (AUC = .71), trastuzumab after 2 weeks (AUC=.81), and lapatinib and trastuzumab after 2 weeks (AUC = .67), Dr. Di Cosimo said.

“Results obtained early post treatment are of special value,” she said, explaining that “women with unfavorable microRNA signatures can be expected to have poor response after just 2 weeks of treatment.”

The findings are of note because a significant proportion of breast cancer patients treated in the neoadjuvant setting do not achieve pathologic complete response and have an increased risk of relapse after surgery. Further, there is a lack of reliable predictors of response to help guide therapy in clinical practice, Dr. Ci Cosimo said.

“This is the first evidence of the potential of circulating microRNAs to discriminate between responsive and unresponsive HER2+ breast cancer patients,” she said.

At present, the signatures, overall, have been associated with pathologic complete response, but not event-free survival. However, one microRNA signature (140-5p) appeared to be associated with event-free survival after 2 weeks among patients treated with trastuzumab, she said, adding that functional studies are ongoing to investigate the biological role of microRNAs, and independent validation studies are planned.

Dr. Di Cosimo reported having no disclosures.

[email protected]

SAN ANTONIO – Circulating microRNAs may predict treatment response in HER2-positive breast cancer patients treated with neoadjuvant therapy, according to findings from the randomized phase III NeoALTTO trial.

Specifically, four circulating tumor microRNA signatures were found to predict pathologic complete response to specific treatments at specific time points in a “testing set” of patients from the study, Serena Di Cosimo, MD, of Istituto Nazionale dei Tumori, Milan, reported at the San Antonio Breast Cancer Symposium.

Overall results from the trial, which were reported in 2012 (The Lancet. 379[9816]:633-40) showed that the combination of lapatinib and trastuzumab significantly improved rates of pathologic complete response, compared with either drug alone in patients with HER2-positive early breast cancer, and the authors concluded that dual inhibition of HER2 might be a valid approach in such patients in the neoadjuvant treatment setting.

For the current analysis of NeoALTTO data, microRNA from plasma samples from 435 women – 141 treated with lapatinib, 151 treated with trastuzumab, and 143 treated with a combination of the two – were monitored longitudinally, as NeoALTTO “was done thinking about future translational studies, so blood samples were collected prospectively at baseline, after 2 weeks of treatment, at surgery, and at the time of relapse,” she noted.

Potential microRNAs associated with pathologic complete response were identified for each treatment arm and time point, and a multivariate model was used to identify specific signatures and their predictive capability.

A total of 30 microRNAs and 6 microRNA signatures were found to be predict pathologic complete response in a “training population,” and the predictive ability of 4 of those was confirmed in the testing set for lapatinib at baseline (area under the curve [AUC] = .86), lapatinib after 2 weeks (AUC = .71), trastuzumab after 2 weeks (AUC=.81), and lapatinib and trastuzumab after 2 weeks (AUC = .67), Dr. Di Cosimo said.

“Results obtained early post treatment are of special value,” she said, explaining that “women with unfavorable microRNA signatures can be expected to have poor response after just 2 weeks of treatment.”

The findings are of note because a significant proportion of breast cancer patients treated in the neoadjuvant setting do not achieve pathologic complete response and have an increased risk of relapse after surgery. Further, there is a lack of reliable predictors of response to help guide therapy in clinical practice, Dr. Ci Cosimo said.

“This is the first evidence of the potential of circulating microRNAs to discriminate between responsive and unresponsive HER2+ breast cancer patients,” she said.

At present, the signatures, overall, have been associated with pathologic complete response, but not event-free survival. However, one microRNA signature (140-5p) appeared to be associated with event-free survival after 2 weeks among patients treated with trastuzumab, she said, adding that functional studies are ongoing to investigate the biological role of microRNAs, and independent validation studies are planned.

Dr. Di Cosimo reported having no disclosures.

[email protected]

SAN ANTONIO – Circulating tumor cells are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy, according to findings from an international meta-analysis of individual patient data.

The cells (CTCs), which can be measured using a Food and Drug Administration–approved assay, are known to seed distant metastases and to be prognostic before and during therapy for patients with metastatic breast cancer, and prognostic before adjuvant therapy for patients with nonmetastatic breast cancer.

However, findings in the neoadjuvant setting have been variable, Francois-Clement Bidard, MD, of Institut Curie, Paris, reported at the San Antonio Breast Cancer Symposium.

In the study (the international meta-analysis of circulating tumor cell detection in early breast cancer patients treated by neoadjuvant chemotherapy, or IMENEO), CTCs were useful, independent of pathologic complete response, for predicting overall survival and distant disease-free survival in the neoadjuvant setting. Further, IMENEO showed for the first time that CTCs also predict locoregional relapse-free survival,

Based on the analysis of data from 2,156 patients from 21 studies and 16 centers in 10 countries, the CTC positivity rates using thresholds of one or more, two or more, and five or more, respectively, were 25%, 13%, and 6% in 1,574 patients tested at baseline, 17%, 6%, and 3% in 290 tested after neoadjuvant chemotherapy, 15%, 5%, and 1% in 1,200 tested before surgery, and 11%, 4%, and 1% in 285 tested after surgery, Dr. Bidard said.

Prior to neoadjuvant chemotherapy, at least one CTC was found in 19%, 22%, 24%, 29% and 41% of cT1, T2, T3, T4a-c, and T4d breast cancers, respectively, and this was marginally associated with hormone receptor negativity, he said, noting that later CTC detection rates were not associated with any patient baseline characteristics.

Nearly one in four patients (24%) achieved pathologic complete response, but this was not associated at any time point with CTC count.

For the primary study endpoint of overall survival, a significant association was found with the presence of at least two CTCs at baseline (hazard ratio, 2.6 for two CTCs; 3.84 for three to four CTCs; and 6.25 for five or more CTCs). Similar associations were found for distant disease-free survival (hazard ratios, 2.4, 3.4, and 5.0, respectively) and for locoregional relapse-free interval with two CTCs and five or more CTCs (hazard ratios, 2.4 and 4.2, respectively).

Similar results were found using later time points, such as after the start of neoadjuvant chemotherapy or before surgery, he said.

On multivariate analysis, baseline CTC detection using any of the thresholds remained an independent predictor of overall and distant disease-free survival and locoregional relapse-free interval when considered together with pathologic complete response, cT, cN, and tumor subtype, suggesting that CTC measurement adds value to comprehensive prognostic models.

That is, they complement rather than duplicate usual prognostic factors and pathologic complete response rates to better predict outcomes in patients with early breast cancer in the neoadjuvant setting, Dr. Bidard said.

This study was supported by a research grant from Janssen Diagnostics. Dr. Bidard reported having no disclosures.

[email protected]

SAN ANTONIO – Circulating tumor cells are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy, according to findings from an international meta-analysis of individual patient data.

The cells (CTCs), which can be measured using a Food and Drug Administration–approved assay, are known to seed distant metastases and to be prognostic before and during therapy for patients with metastatic breast cancer, and prognostic before adjuvant therapy for patients with nonmetastatic breast cancer.

However, findings in the neoadjuvant setting have been variable, Francois-Clement Bidard, MD, of Institut Curie, Paris, reported at the San Antonio Breast Cancer Symposium.

In the study (the international meta-analysis of circulating tumor cell detection in early breast cancer patients treated by neoadjuvant chemotherapy, or IMENEO), CTCs were useful, independent of pathologic complete response, for predicting overall survival and distant disease-free survival in the neoadjuvant setting. Further, IMENEO showed for the first time that CTCs also predict locoregional relapse-free survival,

Based on the analysis of data from 2,156 patients from 21 studies and 16 centers in 10 countries, the CTC positivity rates using thresholds of one or more, two or more, and five or more, respectively, were 25%, 13%, and 6% in 1,574 patients tested at baseline, 17%, 6%, and 3% in 290 tested after neoadjuvant chemotherapy, 15%, 5%, and 1% in 1,200 tested before surgery, and 11%, 4%, and 1% in 285 tested after surgery, Dr. Bidard said.

Prior to neoadjuvant chemotherapy, at least one CTC was found in 19%, 22%, 24%, 29% and 41% of cT1, T2, T3, T4a-c, and T4d breast cancers, respectively, and this was marginally associated with hormone receptor negativity, he said, noting that later CTC detection rates were not associated with any patient baseline characteristics.

Nearly one in four patients (24%) achieved pathologic complete response, but this was not associated at any time point with CTC count.

For the primary study endpoint of overall survival, a significant association was found with the presence of at least two CTCs at baseline (hazard ratio, 2.6 for two CTCs; 3.84 for three to four CTCs; and 6.25 for five or more CTCs). Similar associations were found for distant disease-free survival (hazard ratios, 2.4, 3.4, and 5.0, respectively) and for locoregional relapse-free interval with two CTCs and five or more CTCs (hazard ratios, 2.4 and 4.2, respectively).

Similar results were found using later time points, such as after the start of neoadjuvant chemotherapy or before surgery, he said.

On multivariate analysis, baseline CTC detection using any of the thresholds remained an independent predictor of overall and distant disease-free survival and locoregional relapse-free interval when considered together with pathologic complete response, cT, cN, and tumor subtype, suggesting that CTC measurement adds value to comprehensive prognostic models.

That is, they complement rather than duplicate usual prognostic factors and pathologic complete response rates to better predict outcomes in patients with early breast cancer in the neoadjuvant setting, Dr. Bidard said.

This study was supported by a research grant from Janssen Diagnostics. Dr. Bidard reported having no disclosures.

[email protected]

SAN ANTONIO – Circulating tumor cells are a useful prognostic biomarker in early breast cancer patients treated with neoadjuvant chemotherapy, according to findings from an international meta-analysis of individual patient data.

The cells (CTCs), which can be measured using a Food and Drug Administration–approved assay, are known to seed distant metastases and to be prognostic before and during therapy for patients with metastatic breast cancer, and prognostic before adjuvant therapy for patients with nonmetastatic breast cancer.

However, findings in the neoadjuvant setting have been variable, Francois-Clement Bidard, MD, of Institut Curie, Paris, reported at the San Antonio Breast Cancer Symposium.

In the study (the international meta-analysis of circulating tumor cell detection in early breast cancer patients treated by neoadjuvant chemotherapy, or IMENEO), CTCs were useful, independent of pathologic complete response, for predicting overall survival and distant disease-free survival in the neoadjuvant setting. Further, IMENEO showed for the first time that CTCs also predict locoregional relapse-free survival,

Based on the analysis of data from 2,156 patients from 21 studies and 16 centers in 10 countries, the CTC positivity rates using thresholds of one or more, two or more, and five or more, respectively, were 25%, 13%, and 6% in 1,574 patients tested at baseline, 17%, 6%, and 3% in 290 tested after neoadjuvant chemotherapy, 15%, 5%, and 1% in 1,200 tested before surgery, and 11%, 4%, and 1% in 285 tested after surgery, Dr. Bidard said.

Prior to neoadjuvant chemotherapy, at least one CTC was found in 19%, 22%, 24%, 29% and 41% of cT1, T2, T3, T4a-c, and T4d breast cancers, respectively, and this was marginally associated with hormone receptor negativity, he said, noting that later CTC detection rates were not associated with any patient baseline characteristics.

Nearly one in four patients (24%) achieved pathologic complete response, but this was not associated at any time point with CTC count.

For the primary study endpoint of overall survival, a significant association was found with the presence of at least two CTCs at baseline (hazard ratio, 2.6 for two CTCs; 3.84 for three to four CTCs; and 6.25 for five or more CTCs). Similar associations were found for distant disease-free survival (hazard ratios, 2.4, 3.4, and 5.0, respectively) and for locoregional relapse-free interval with two CTCs and five or more CTCs (hazard ratios, 2.4 and 4.2, respectively).

Similar results were found using later time points, such as after the start of neoadjuvant chemotherapy or before surgery, he said.

On multivariate analysis, baseline CTC detection using any of the thresholds remained an independent predictor of overall and distant disease-free survival and locoregional relapse-free interval when considered together with pathologic complete response, cT, cN, and tumor subtype, suggesting that CTC measurement adds value to comprehensive prognostic models.

That is, they complement rather than duplicate usual prognostic factors and pathologic complete response rates to better predict outcomes in patients with early breast cancer in the neoadjuvant setting, Dr. Bidard said.

This study was supported by a research grant from Janssen Diagnostics. Dr. Bidard reported having no disclosures.

[email protected]

Triage to chemotherapy using a Ki67-based Preoperative Endocrine Prognostic Index (PEPI), which also integrates residual disease burden, appears useful for deescalating adjuvant treatment after neoadjuvant aromatase inhibitor (AI) therapy for breast cancer, investigators report in the Journal of Clinical Oncology.

Only 4 of 109 patients (3.7%) in the American College of Surgeons Oncology Group Z1031B trial with a PEPI score of 0 relapsed after a median of 5.5 years (and were therefore unlikely to benefit from adjuvant chemotherapy), compared with 49 (14.4%) of 341 patients with a PEPI score greater than 0 (recurrence hazard ratio, 0.27), reported Matthew J. Ellis, MD, of Baylor College of Medicine, Houston, and his associates.

[email protected]

Triage to chemotherapy using a Ki67-based Preoperative Endocrine Prognostic Index (PEPI), which also integrates residual disease burden, appears useful for deescalating adjuvant treatment after neoadjuvant aromatase inhibitor (AI) therapy for breast cancer, investigators report in the Journal of Clinical Oncology.

Only 4 of 109 patients (3.7%) in the American College of Surgeons Oncology Group Z1031B trial with a PEPI score of 0 relapsed after a median of 5.5 years (and were therefore unlikely to benefit from adjuvant chemotherapy), compared with 49 (14.4%) of 341 patients with a PEPI score greater than 0 (recurrence hazard ratio, 0.27), reported Matthew J. Ellis, MD, of Baylor College of Medicine, Houston, and his associates.

[email protected]

Triage to chemotherapy using a Ki67-based Preoperative Endocrine Prognostic Index (PEPI), which also integrates residual disease burden, appears useful for deescalating adjuvant treatment after neoadjuvant aromatase inhibitor (AI) therapy for breast cancer, investigators report in the Journal of Clinical Oncology.

Only 4 of 109 patients (3.7%) in the American College of Surgeons Oncology Group Z1031B trial with a PEPI score of 0 relapsed after a median of 5.5 years (and were therefore unlikely to benefit from adjuvant chemotherapy), compared with 49 (14.4%) of 341 patients with a PEPI score greater than 0 (recurrence hazard ratio, 0.27), reported Matthew J. Ellis, MD, of Baylor College of Medicine, Houston, and his associates.

[email protected]

SAN ANTONIO – PARPi 7, BRCAness, and MammaPrint high1/(ultra)high2 signatures could help predict response to combination therapy with the poly ADP ribose polymerase (PARP) inhibitors veliparib and carboplatin among high-risk breast cancer patients and thereby improve patient care, according to findings from the I-SPY 2 clinical trial.

“I-SPY 2 is a phase II adaptively randomized neoadjuvant clinical trial with a shared control arm where patients receive standard neoadjuvant chemotherapy, and up to 4 simultaneous investigational arms. The primary endpoint of the trial is pathologic complete response, or pCR. The goal is to match therapies with the most responsive breast cancer subtypes,” Denise M. Wolf, PhD, of the University of California, San Francisco, explained at the San Antonio Breast Cancer Symposium.

The current analysis of I-Spy 2 data focuses on veliparib/carboplatin (VC), and the subtypes Dr. Wolf mentioned are defined by hormone receptor (HR) and HER2 expression, and by MammaPrint high1 or (ultra)high2 risk status, which, “roughly speaking, is a further stratification of the poor prognosis group into high- and extra-high-risk groups,” she said.

“This arm was open to HER2-negative patients, and graduated successfully in the triple-negative subset,” she noted, explaining that “agents or combinations graduate for efficacy if they reach 85% predicted probability of success in a subsequent phase III trial in the most responsive patient subset.”

The biomarker component of the trial aimed to evaluate biomarkers associated with the mechanisms of action of each investigational agent along with the predefined subsets.

Although the findings require verification in a larger trial, Dr. Wolf and her colleagues found that three biomarkers – the PARPi 7 gene signature, the 77-gene BRCAness signature (which both relate to DNA damage repair deficiency), and the MammaPrint high1 and (ultra)high2 risk categories – were each moderately correlated with treatment response in 72 patients receiving veliparib/carboplatin (VC), but not in 44 controls, and that the treatment-biomarker interactions retained statistical significance after adjusting for hormone receptor status.

“And so we asked the question, ‘Are these signatures identifying the same patients – and if not, might there be a way to combine them to identify a subset of patients who are especially likely to respond to VC?’” she said.

Further analysis showed that even though each of the biomarkers was a predictor of response, the biomarkers did not appear to identify exactly the same patients, therefore combining them might be of benefit.

“We did this using a simple voting scheme to combine pairs of biomarkers,” she said, adding that if the two paired biomarkers predicted resistance, the biomarker also predicted resistance. If only 1 predicted resistance, the combination predicted resistance, and only if both biomarkers predicted sensitivity did the combination predict sensitivity.

In the graduated triple-negative subset, for example, the 40% of patients who were PARPi 7–high and MammaPrint high2 (the two biomarkers most predictive of response) a dramatic separation was seen in the pCR probability curves, with an estimated pCR of 79% with VC treatment vs. 23% in the control arm.

“In contrast, triple-negative patients who were negative for one or more of the sensitivity markers had nearly overlapping probability response curves, from which we conclude that nearly all of the specific sensitivity to VC seen in the triple-negative patients is found in that subset who are positive for both sensitivity markers,” she said.

Additionally, although only 9% of HR-positive/HER2-negative patients were PARPi 7-high and MammaPrint high2, those patients also appeared to be more responsive to VC vs. the control arm (49% vs. 15%).

The results also demonstrate the value of an exploratory voting method for combining multiple biomarkers for the same treatment, Dr. Wolf noted.

However, the findings are limited by the small sample size and need to be evaluated in larger trials, and the biomarkers also need to be evaluated in carboplatin-only arms in order to “tease out whether the biomarkers are really specific to a PARP inhibitor with carboplatin or whether they might also apply to carboplatin alone.

“Our ongoing and future work is to develop predictive biomarkers for other I-Spy 2 agents,” she said.

Dr. Wolf reported having no disclosures.

[email protected]

SAN ANTONIO – PARPi 7, BRCAness, and MammaPrint high1/(ultra)high2 signatures could help predict response to combination therapy with the poly ADP ribose polymerase (PARP) inhibitors veliparib and carboplatin among high-risk breast cancer patients and thereby improve patient care, according to findings from the I-SPY 2 clinical trial.

“I-SPY 2 is a phase II adaptively randomized neoadjuvant clinical trial with a shared control arm where patients receive standard neoadjuvant chemotherapy, and up to 4 simultaneous investigational arms. The primary endpoint of the trial is pathologic complete response, or pCR. The goal is to match therapies with the most responsive breast cancer subtypes,” Denise M. Wolf, PhD, of the University of California, San Francisco, explained at the San Antonio Breast Cancer Symposium.

The current analysis of I-Spy 2 data focuses on veliparib/carboplatin (VC), and the subtypes Dr. Wolf mentioned are defined by hormone receptor (HR) and HER2 expression, and by MammaPrint high1 or (ultra)high2 risk status, which, “roughly speaking, is a further stratification of the poor prognosis group into high- and extra-high-risk groups,” she said.

“This arm was open to HER2-negative patients, and graduated successfully in the triple-negative subset,” she noted, explaining that “agents or combinations graduate for efficacy if they reach 85% predicted probability of success in a subsequent phase III trial in the most responsive patient subset.”

The biomarker component of the trial aimed to evaluate biomarkers associated with the mechanisms of action of each investigational agent along with the predefined subsets.

Although the findings require verification in a larger trial, Dr. Wolf and her colleagues found that three biomarkers – the PARPi 7 gene signature, the 77-gene BRCAness signature (which both relate to DNA damage repair deficiency), and the MammaPrint high1 and (ultra)high2 risk categories – were each moderately correlated with treatment response in 72 patients receiving veliparib/carboplatin (VC), but not in 44 controls, and that the treatment-biomarker interactions retained statistical significance after adjusting for hormone receptor status.

“And so we asked the question, ‘Are these signatures identifying the same patients – and if not, might there be a way to combine them to identify a subset of patients who are especially likely to respond to VC?’” she said.

Further analysis showed that even though each of the biomarkers was a predictor of response, the biomarkers did not appear to identify exactly the same patients, therefore combining them might be of benefit.

“We did this using a simple voting scheme to combine pairs of biomarkers,” she said, adding that if the two paired biomarkers predicted resistance, the biomarker also predicted resistance. If only 1 predicted resistance, the combination predicted resistance, and only if both biomarkers predicted sensitivity did the combination predict sensitivity.

In the graduated triple-negative subset, for example, the 40% of patients who were PARPi 7–high and MammaPrint high2 (the two biomarkers most predictive of response) a dramatic separation was seen in the pCR probability curves, with an estimated pCR of 79% with VC treatment vs. 23% in the control arm.

“In contrast, triple-negative patients who were negative for one or more of the sensitivity markers had nearly overlapping probability response curves, from which we conclude that nearly all of the specific sensitivity to VC seen in the triple-negative patients is found in that subset who are positive for both sensitivity markers,” she said.

Additionally, although only 9% of HR-positive/HER2-negative patients were PARPi 7-high and MammaPrint high2, those patients also appeared to be more responsive to VC vs. the control arm (49% vs. 15%).

The results also demonstrate the value of an exploratory voting method for combining multiple biomarkers for the same treatment, Dr. Wolf noted.

However, the findings are limited by the small sample size and need to be evaluated in larger trials, and the biomarkers also need to be evaluated in carboplatin-only arms in order to “tease out whether the biomarkers are really specific to a PARP inhibitor with carboplatin or whether they might also apply to carboplatin alone.

“Our ongoing and future work is to develop predictive biomarkers for other I-Spy 2 agents,” she said.

Dr. Wolf reported having no disclosures.

[email protected]

SAN ANTONIO – PARPi 7, BRCAness, and MammaPrint high1/(ultra)high2 signatures could help predict response to combination therapy with the poly ADP ribose polymerase (PARP) inhibitors veliparib and carboplatin among high-risk breast cancer patients and thereby improve patient care, according to findings from the I-SPY 2 clinical trial.

“I-SPY 2 is a phase II adaptively randomized neoadjuvant clinical trial with a shared control arm where patients receive standard neoadjuvant chemotherapy, and up to 4 simultaneous investigational arms. The primary endpoint of the trial is pathologic complete response, or pCR. The goal is to match therapies with the most responsive breast cancer subtypes,” Denise M. Wolf, PhD, of the University of California, San Francisco, explained at the San Antonio Breast Cancer Symposium.

The current analysis of I-Spy 2 data focuses on veliparib/carboplatin (VC), and the subtypes Dr. Wolf mentioned are defined by hormone receptor (HR) and HER2 expression, and by MammaPrint high1 or (ultra)high2 risk status, which, “roughly speaking, is a further stratification of the poor prognosis group into high- and extra-high-risk groups,” she said.

“This arm was open to HER2-negative patients, and graduated successfully in the triple-negative subset,” she noted, explaining that “agents or combinations graduate for efficacy if they reach 85% predicted probability of success in a subsequent phase III trial in the most responsive patient subset.”

The biomarker component of the trial aimed to evaluate biomarkers associated with the mechanisms of action of each investigational agent along with the predefined subsets.

Although the findings require verification in a larger trial, Dr. Wolf and her colleagues found that three biomarkers – the PARPi 7 gene signature, the 77-gene BRCAness signature (which both relate to DNA damage repair deficiency), and the MammaPrint high1 and (ultra)high2 risk categories – were each moderately correlated with treatment response in 72 patients receiving veliparib/carboplatin (VC), but not in 44 controls, and that the treatment-biomarker interactions retained statistical significance after adjusting for hormone receptor status.

“And so we asked the question, ‘Are these signatures identifying the same patients – and if not, might there be a way to combine them to identify a subset of patients who are especially likely to respond to VC?’” she said.

Further analysis showed that even though each of the biomarkers was a predictor of response, the biomarkers did not appear to identify exactly the same patients, therefore combining them might be of benefit.

“We did this using a simple voting scheme to combine pairs of biomarkers,” she said, adding that if the two paired biomarkers predicted resistance, the biomarker also predicted resistance. If only 1 predicted resistance, the combination predicted resistance, and only if both biomarkers predicted sensitivity did the combination predict sensitivity.

In the graduated triple-negative subset, for example, the 40% of patients who were PARPi 7–high and MammaPrint high2 (the two biomarkers most predictive of response) a dramatic separation was seen in the pCR probability curves, with an estimated pCR of 79% with VC treatment vs. 23% in the control arm.

“In contrast, triple-negative patients who were negative for one or more of the sensitivity markers had nearly overlapping probability response curves, from which we conclude that nearly all of the specific sensitivity to VC seen in the triple-negative patients is found in that subset who are positive for both sensitivity markers,” she said.

Additionally, although only 9% of HR-positive/HER2-negative patients were PARPi 7-high and MammaPrint high2, those patients also appeared to be more responsive to VC vs. the control arm (49% vs. 15%).

The results also demonstrate the value of an exploratory voting method for combining multiple biomarkers for the same treatment, Dr. Wolf noted.

However, the findings are limited by the small sample size and need to be evaluated in larger trials, and the biomarkers also need to be evaluated in carboplatin-only arms in order to “tease out whether the biomarkers are really specific to a PARP inhibitor with carboplatin or whether they might also apply to carboplatin alone.

“Our ongoing and future work is to develop predictive biomarkers for other I-Spy 2 agents,” she said.

Dr. Wolf reported having no disclosures.

[email protected]

Background The importance of social support for cancer patients has been established in previous studies. However, much of the existing research has identified associations between general measures of social support and various health indicators. Nevertheless, some research has begun to suggest the utility of more nuanced understandings of how patients receive and use social support.

Objective To examine the roles of nondirective (ie, support that accepts recipients’ feelings and is cooperative with their plans) and directive support (ie, support that prescribes “correct” choices and feelings) as well as social support needs and desires among patients with advanced breast cancer.

Methods We conducted semi-structured interviews (qualitative method) with 8 patients with stage IV breast cancer to collect qualitative information about the disease-related challenges they faced, the support they received from their families and medical teams, and the appropriateness of directive and nondirective support. In addition, we used the 14-item Hospital Anxiety and Depression Scale (HADS) to assess clinically relevant cut-offs for anxiety and depression and the 16-item Social Support Inventory to assess the provision of nondirective and directive social support to the patients (quantitative method).

Results Qualitative findings suggested that there was considerable variability among patients’ reports of social support provided by family, friends, and the medical team. From the qualitative data, patients reported directive support as more useful in times of acute need and emphasized the importance of supportive systems rather than supportive persons in providing emotional support. From the quantitative data, patients reported nondirective support as more typical of support received from both family and medical teams than directive support. On the HADS, 1 patient had a score of 9 on the anxiety subscale, above the score of 7 that is for mild anxiety. No patients scored above the criterion for mild depression, also a score of 7.

Limitations Very small sample limits the ability to generalize findings.

Conclusions The right type of support for patients with advanced breast cancer is contingent on a range of variables, which suggests that the key characteristic of support may not be any particular feature, but the nuanced adjustment of its content and style of delivery to the patient’s circumstances.

Funding Peers for Progress

Click on the PDF icon at the top of this introduction to read the full article.

Background The importance of social support for cancer patients has been established in previous studies. However, much of the existing research has identified associations between general measures of social support and various health indicators. Nevertheless, some research has begun to suggest the utility of more nuanced understandings of how patients receive and use social support.

Objective To examine the roles of nondirective (ie, support that accepts recipients’ feelings and is cooperative with their plans) and directive support (ie, support that prescribes “correct” choices and feelings) as well as social support needs and desires among patients with advanced breast cancer.

Methods We conducted semi-structured interviews (qualitative method) with 8 patients with stage IV breast cancer to collect qualitative information about the disease-related challenges they faced, the support they received from their families and medical teams, and the appropriateness of directive and nondirective support. In addition, we used the 14-item Hospital Anxiety and Depression Scale (HADS) to assess clinically relevant cut-offs for anxiety and depression and the 16-item Social Support Inventory to assess the provision of nondirective and directive social support to the patients (quantitative method).

Results Qualitative findings suggested that there was considerable variability among patients’ reports of social support provided by family, friends, and the medical team. From the qualitative data, patients reported directive support as more useful in times of acute need and emphasized the importance of supportive systems rather than supportive persons in providing emotional support. From the quantitative data, patients reported nondirective support as more typical of support received from both family and medical teams than directive support. On the HADS, 1 patient had a score of 9 on the anxiety subscale, above the score of 7 that is for mild anxiety. No patients scored above the criterion for mild depression, also a score of 7.

Limitations Very small sample limits the ability to generalize findings.

Conclusions The right type of support for patients with advanced breast cancer is contingent on a range of variables, which suggests that the key characteristic of support may not be any particular feature, but the nuanced adjustment of its content and style of delivery to the patient’s circumstances.

Funding Peers for Progress

Click on the PDF icon at the top of this introduction to read the full article.

Background The importance of social support for cancer patients has been established in previous studies. However, much of the existing research has identified associations between general measures of social support and various health indicators. Nevertheless, some research has begun to suggest the utility of more nuanced understandings of how patients receive and use social support.

Objective To examine the roles of nondirective (ie, support that accepts recipients’ feelings and is cooperative with their plans) and directive support (ie, support that prescribes “correct” choices and feelings) as well as social support needs and desires among patients with advanced breast cancer.

Methods We conducted semi-structured interviews (qualitative method) with 8 patients with stage IV breast cancer to collect qualitative information about the disease-related challenges they faced, the support they received from their families and medical teams, and the appropriateness of directive and nondirective support. In addition, we used the 14-item Hospital Anxiety and Depression Scale (HADS) to assess clinically relevant cut-offs for anxiety and depression and the 16-item Social Support Inventory to assess the provision of nondirective and directive social support to the patients (quantitative method).

Results Qualitative findings suggested that there was considerable variability among patients’ reports of social support provided by family, friends, and the medical team. From the qualitative data, patients reported directive support as more useful in times of acute need and emphasized the importance of supportive systems rather than supportive persons in providing emotional support. From the quantitative data, patients reported nondirective support as more typical of support received from both family and medical teams than directive support. On the HADS, 1 patient had a score of 9 on the anxiety subscale, above the score of 7 that is for mild anxiety. No patients scored above the criterion for mild depression, also a score of 7.

Limitations Very small sample limits the ability to generalize findings.

Conclusions The right type of support for patients with advanced breast cancer is contingent on a range of variables, which suggests that the key characteristic of support may not be any particular feature, but the nuanced adjustment of its content and style of delivery to the patient’s circumstances.

Funding Peers for Progress

Click on the PDF icon at the top of this introduction to read the full article.

Women with breast cancer are much less likely to opt for contralateral prophylactic mastectomies if they know it won’t prolong their lives, according to a survey of 2,402 women with unilateral stage 0-II breast cancer.

Contralateral prophylactic mastectomy (CPM) – removing the healthy breast along with the cancerous one – is on the rise for early-stage, unilateral breast cancer because of “celebrity exposure and publicity,” said investigators led by Reshma Jagsi, MD, of the University of Michigan, Ann Arbor (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4749).

CPM might make sense for women at genetic risk for breast cancer, like actress Angelina Jolie – who made headlines in 2013 when she opted for double mastectomy – but the survey found that nearly one in five women with no genetic risks also opted for CPM when their surgeons made no recommendation either way.

When surgeons advised against the procedure, the number fell to about 2%. Meanwhile, many women said their surgeons stayed silent on the issue, which is a problem, according to the investigators.

Overall, about 44% of women in the survey considered CPM, but just 38% of them said they knew that CPM didn’t improve survival for all women with breast cancer.

“Some patients may pursue CPM for cosmetic symmetry or other reasons. However, it is not clear that average-risk patients who choose CPM truly understand that it will not improve their survival or alter recurrence risk,” the investigators noted.

Surgeons’ knowledge and communication practices could be targets for quality improvement interventions, the investigators wrote. “Our findings should motivate surgeons to broach these difficult conversations with their patients, to make their recommendations clear, and to promote patients’ peace of mind by emphasizing how other treatments complement surgery to reduce the risk of both tumor recurrence and subsequent cancer development,” they said.

Women in the study were identified through the Surveillance Epidemiology and End Results (SEER) registries of Los Angeles County and Georgia. They were 62 years old, on average. CPM was associated with younger age, white race, higher educational level, family history, and private insurance.

The National Institutes of Health supported the study. Dr. Jagsi reported having no disclosures. A coauthor reported research funding from Myriad Genetics, Invitae, Ambry Genetics, GeneDx, and Genomic Health.

[email protected]

Women with breast cancer are much less likely to opt for contralateral prophylactic mastectomies if they know it won’t prolong their lives, according to a survey of 2,402 women with unilateral stage 0-II breast cancer.

Contralateral prophylactic mastectomy (CPM) – removing the healthy breast along with the cancerous one – is on the rise for early-stage, unilateral breast cancer because of “celebrity exposure and publicity,” said investigators led by Reshma Jagsi, MD, of the University of Michigan, Ann Arbor (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4749).

CPM might make sense for women at genetic risk for breast cancer, like actress Angelina Jolie – who made headlines in 2013 when she opted for double mastectomy – but the survey found that nearly one in five women with no genetic risks also opted for CPM when their surgeons made no recommendation either way.

When surgeons advised against the procedure, the number fell to about 2%. Meanwhile, many women said their surgeons stayed silent on the issue, which is a problem, according to the investigators.

Overall, about 44% of women in the survey considered CPM, but just 38% of them said they knew that CPM didn’t improve survival for all women with breast cancer.

“Some patients may pursue CPM for cosmetic symmetry or other reasons. However, it is not clear that average-risk patients who choose CPM truly understand that it will not improve their survival or alter recurrence risk,” the investigators noted.

Surgeons’ knowledge and communication practices could be targets for quality improvement interventions, the investigators wrote. “Our findings should motivate surgeons to broach these difficult conversations with their patients, to make their recommendations clear, and to promote patients’ peace of mind by emphasizing how other treatments complement surgery to reduce the risk of both tumor recurrence and subsequent cancer development,” they said.

Women in the study were identified through the Surveillance Epidemiology and End Results (SEER) registries of Los Angeles County and Georgia. They were 62 years old, on average. CPM was associated with younger age, white race, higher educational level, family history, and private insurance.

The National Institutes of Health supported the study. Dr. Jagsi reported having no disclosures. A coauthor reported research funding from Myriad Genetics, Invitae, Ambry Genetics, GeneDx, and Genomic Health.

[email protected]

Women with breast cancer are much less likely to opt for contralateral prophylactic mastectomies if they know it won’t prolong their lives, according to a survey of 2,402 women with unilateral stage 0-II breast cancer.

Contralateral prophylactic mastectomy (CPM) – removing the healthy breast along with the cancerous one – is on the rise for early-stage, unilateral breast cancer because of “celebrity exposure and publicity,” said investigators led by Reshma Jagsi, MD, of the University of Michigan, Ann Arbor (JAMA Surg. 2016 Dec 21. doi: 10.1001/jamasurg.2016.4749).

CPM might make sense for women at genetic risk for breast cancer, like actress Angelina Jolie – who made headlines in 2013 when she opted for double mastectomy – but the survey found that nearly one in five women with no genetic risks also opted for CPM when their surgeons made no recommendation either way.

When surgeons advised against the procedure, the number fell to about 2%. Meanwhile, many women said their surgeons stayed silent on the issue, which is a problem, according to the investigators.

Overall, about 44% of women in the survey considered CPM, but just 38% of them said they knew that CPM didn’t improve survival for all women with breast cancer.

“Some patients may pursue CPM for cosmetic symmetry or other reasons. However, it is not clear that average-risk patients who choose CPM truly understand that it will not improve their survival or alter recurrence risk,” the investigators noted.

Surgeons’ knowledge and communication practices could be targets for quality improvement interventions, the investigators wrote. “Our findings should motivate surgeons to broach these difficult conversations with their patients, to make their recommendations clear, and to promote patients’ peace of mind by emphasizing how other treatments complement surgery to reduce the risk of both tumor recurrence and subsequent cancer development,” they said.

Women in the study were identified through the Surveillance Epidemiology and End Results (SEER) registries of Los Angeles County and Georgia. They were 62 years old, on average. CPM was associated with younger age, white race, higher educational level, family history, and private insurance.

The National Institutes of Health supported the study. Dr. Jagsi reported having no disclosures. A coauthor reported research funding from Myriad Genetics, Invitae, Ambry Genetics, GeneDx, and Genomic Health.

[email protected]