Neil Osterweil

There are significant racial disparities in the delivery of HER2-targeted therapy for breast cancer, investigators have found.

A review of Medicare beneficiaries with incident stage I-III HER2-positive breast cancer showed that black women were 25% less likely than white women to receive adjuvant trastuzumab (Herceptin) within a year of diagnosis, reported Dr. Katherine Reeder-Hayes and her colleagues at the University of North Carolina at Chapel Hill.

In addition, the investigators found that about one-half of Medicare-insured patients with HER2-positive tumors did not receive HER2-targeted therapy, despite the well-known clinical benefits in this population.

“These findings have several troubling implications. First, although this study did not examine survival outcomes, the low overall rates of use among patients with stage II and III disease raise concerns for widespread underuse of trastuzumab in this age group. Second, the racial findings suggest that the presence of a clear biologic predictor of treatment benefit, in this case the HER2 marker, does not mitigate the overall pattern of treatment disparity observed among black women with breast cancer,” they wrote (J Clin Oncol. 2016 April 11. doi: 10.1200/JCO.2015.65.8716).

The authors reviewed Surveillance, Epidemiology and End Results (SEER) Medicare data on 1,362 women with incidence stages I-III HER2-positive breast cancers in 2010 and 2011, and used insurance claims data to identify the use of adjuvant trastuzumab and chemotherapy agents within 12 months of diagnosis. The sample included 1,162 white women, 104 black women, and 96 women described as “other.”

The investigators found that just half of all white women (50%) and 40% of black women received at least some trastuzumab therapy.

In logistic regression analysis controlling for tumor characteristics, socioeconomic factors, and comorbidities, they found that compared with white women, black women had a risk ratio for receiving trastuzumab of 0.745 (P = .0097).

The investigators noted that in addition to the racial disparities, older women and those with more comorbidities were also less likely to get trastuzumab.

“However, given the sizeable benefit of trastuzumab, the overall aggressive biology of this subtype, and extensive literature documenting undertreatment of even healthy older patients, the hypothesis that age is used inappropriately to withhold trastuzumab-based therapy deserves further exploration,” they wrote.

The investigators called for the development of system-level interventions that can objectively identify patients eligible for HER2-targeted therapy, and for ongoing efforts to eradicate racial disparities in care.

The study was supported by grants from the National Institutes of Health and the University (NC) Cancer Research Fund.

There are significant racial disparities in the delivery of HER2-targeted therapy for breast cancer, investigators have found.

A review of Medicare beneficiaries with incident stage I-III HER2-positive breast cancer showed that black women were 25% less likely than white women to receive adjuvant trastuzumab (Herceptin) within a year of diagnosis, reported Dr. Katherine Reeder-Hayes and her colleagues at the University of North Carolina at Chapel Hill.

In addition, the investigators found that about one-half of Medicare-insured patients with HER2-positive tumors did not receive HER2-targeted therapy, despite the well-known clinical benefits in this population.

“These findings have several troubling implications. First, although this study did not examine survival outcomes, the low overall rates of use among patients with stage II and III disease raise concerns for widespread underuse of trastuzumab in this age group. Second, the racial findings suggest that the presence of a clear biologic predictor of treatment benefit, in this case the HER2 marker, does not mitigate the overall pattern of treatment disparity observed among black women with breast cancer,” they wrote (J Clin Oncol. 2016 April 11. doi: 10.1200/JCO.2015.65.8716).

The authors reviewed Surveillance, Epidemiology and End Results (SEER) Medicare data on 1,362 women with incidence stages I-III HER2-positive breast cancers in 2010 and 2011, and used insurance claims data to identify the use of adjuvant trastuzumab and chemotherapy agents within 12 months of diagnosis. The sample included 1,162 white women, 104 black women, and 96 women described as “other.”

The investigators found that just half of all white women (50%) and 40% of black women received at least some trastuzumab therapy.

In logistic regression analysis controlling for tumor characteristics, socioeconomic factors, and comorbidities, they found that compared with white women, black women had a risk ratio for receiving trastuzumab of 0.745 (P = .0097).

The investigators noted that in addition to the racial disparities, older women and those with more comorbidities were also less likely to get trastuzumab.

“However, given the sizeable benefit of trastuzumab, the overall aggressive biology of this subtype, and extensive literature documenting undertreatment of even healthy older patients, the hypothesis that age is used inappropriately to withhold trastuzumab-based therapy deserves further exploration,” they wrote.

The investigators called for the development of system-level interventions that can objectively identify patients eligible for HER2-targeted therapy, and for ongoing efforts to eradicate racial disparities in care.

The study was supported by grants from the National Institutes of Health and the University (NC) Cancer Research Fund.

There are significant racial disparities in the delivery of HER2-targeted therapy for breast cancer, investigators have found.

A review of Medicare beneficiaries with incident stage I-III HER2-positive breast cancer showed that black women were 25% less likely than white women to receive adjuvant trastuzumab (Herceptin) within a year of diagnosis, reported Dr. Katherine Reeder-Hayes and her colleagues at the University of North Carolina at Chapel Hill.

In addition, the investigators found that about one-half of Medicare-insured patients with HER2-positive tumors did not receive HER2-targeted therapy, despite the well-known clinical benefits in this population.

“These findings have several troubling implications. First, although this study did not examine survival outcomes, the low overall rates of use among patients with stage II and III disease raise concerns for widespread underuse of trastuzumab in this age group. Second, the racial findings suggest that the presence of a clear biologic predictor of treatment benefit, in this case the HER2 marker, does not mitigate the overall pattern of treatment disparity observed among black women with breast cancer,” they wrote (J Clin Oncol. 2016 April 11. doi: 10.1200/JCO.2015.65.8716).

The authors reviewed Surveillance, Epidemiology and End Results (SEER) Medicare data on 1,362 women with incidence stages I-III HER2-positive breast cancers in 2010 and 2011, and used insurance claims data to identify the use of adjuvant trastuzumab and chemotherapy agents within 12 months of diagnosis. The sample included 1,162 white women, 104 black women, and 96 women described as “other.”

The investigators found that just half of all white women (50%) and 40% of black women received at least some trastuzumab therapy.

In logistic regression analysis controlling for tumor characteristics, socioeconomic factors, and comorbidities, they found that compared with white women, black women had a risk ratio for receiving trastuzumab of 0.745 (P = .0097).

The investigators noted that in addition to the racial disparities, older women and those with more comorbidities were also less likely to get trastuzumab.

“However, given the sizeable benefit of trastuzumab, the overall aggressive biology of this subtype, and extensive literature documenting undertreatment of even healthy older patients, the hypothesis that age is used inappropriately to withhold trastuzumab-based therapy deserves further exploration,” they wrote.

The investigators called for the development of system-level interventions that can objectively identify patients eligible for HER2-targeted therapy, and for ongoing efforts to eradicate racial disparities in care.

The study was supported by grants from the National Institutes of Health and the University (NC) Cancer Research Fund.

HOLLYWOOD, FLA. –The remarkable changes that have occurred in the treatment of advanced malignant melanoma over the last several years are reflected in revised National Comprehensive Cancer Network guidelines.

“Gone are the days where our active agents were interferon and dacarbazine,” said Dr. John A. Thompson of the Fred Hutchinson Cancer Research Center, Seattle.

“We’ve seen the approval by the FDA of the PD-1-targeted agents and also molecular-targeted agents to treat patients with mutations in the BRAF gene, and the rate of change continues apace,” he said at the annual conference of the National Comprehensive Cancer Network.

Among the changes in the 2016 guidelines are the addition of high-dose ipilimumab (Yervoy) as an option for stage III (node-positive) disease, and intralesional talimogene laherparepvec (T-VEC) for primary treatment of stage III in-transit disease.

Guidelines for first-line systemic therapy for metastatic or unresectable disease recommend treatment based on evaluation of individual patients and include:

• Monotherapy with an anti-PD-1 (programmed death-1) agent, either pembrolizumab (Keytruda) or nivolumab (Opdivo) (category 1 recommendation).

• Targeted therapy for BRAF-mutated disease with combinations (preferred) of either dabrafenib (Tafinlar) and trametinib (Mekinist) or vemurafenib (Zelboraf)and cobimetinib (Cotellic); both are category 1 recommendations.

• Single-agent therapy with either vemurafenib or dabrafenib (category 1), or clinical trial.

For patients with disease progression or those who have had their maximum clinical benefit from BRAF-targeted therapy and good performance status (0-2), the guidelines recommend second-line or subsequent therapy with anti-PD-1 agents as above, ipilimumab, or a combination of nivolumab and ipilimumab.

The guidelines note, however, that “nivolumab/ipilimumab combination therapy is associated with improved relapse-free survival compared with single-agent nivolumab or ipilimumab, at the expense of significantly increased toxicity. Compared to single-agent therapy, the impact of nivolumab/ipilimumab combination therapy on overall survival is not known.”

Also recommended are targeted therapy with the BRAF-inhibitor combinations listed above (preferred) or single-agent therapy with vemurafenib or dabrafenib.

“In previously untreated patients with unresectable stage IIIC or stage IV disease, the combination of vemurafenib/cobimetinib was associated with improved PFS [progression-free survival] and response rate when compared to vemurafenib alone. The impact on overall survival compared to single-agent vemurafenib is unknown,” the guidelines state.

Other second-line options for patients with good performance status include high-dose interleukin-2 (not suitable for patients with inadequate organ reserve, poor performance status, or untreated or active brain metastases), biochemotherapy and cytotoxic agents (dacarbazine or temozolomide, and cisplatin or carboplatin, with or without vinblastine or nitrosourea, and IL-2 and interferon alfa-2b; paclitaxel, albumin-bound paclitaxel).

For patients with poor performance status (3-4) the guidelines call for best supportive care according to guidelines for palliative care.

Oncolytic immunotherapy

For treatment of recurrent disease, the guidelines newly recommend use of T-VEC, a genetically modified herpes simplex-1 virus that is injected intralesionally into accessible tumors. The attenuated virus does not kill healthy cells, but replicates in tumors and causes the cells to secrete granulocyte macrophage–colony stimulating factor (GM-CSF), leading to lysis of the tumor cells.

“It is hypothesized that the GM-CSF works with the immune system to boost a resident immune response against the destroyed melanoma cells and antigens that are released from this process,” Dr. Thompson said.

In a recent clinical trial (J Clin Oncol. 2015;33:2780-8), patients with injectable melanoma that was not surgically resectable were randomized to either intralesional T-VEC injections on week 0, 3, and then every 2 weeks (295 patients), or subcutaneous GM-CSF 125 mcg/m² on days 1 to 14 for every 28 days (141 patients).

T-VEC was associated with significantly more durables responses (16% vs. 2.1% for GM-CSF, P less than .001) and a significantly higher overall response rate (26.4% vs. 5.7%, respectively, P less than .001).

In the primary analysis in an intent-to-treat population, T-VEC had a borderline significant association with better overall survival (median 23.2 vs. 18.9 months, hazard ratio [HR] 0.70, log-rank P = .051).

In subanalyses of outcomes in patient subgroups, however, the benefits of T-VEC were seen in patients with stage IIIB IIIC, and IV M1a disease (HR 0.57, P less than .001), but not in patients with IV M1b or M1c disease. In addition, patients treated with T-VEC in first-line therapy had significantly better overall survival compared with GM-CSF (HR 0.50, P less than .001), but those who received it in second or subsequent lines of therapy saw no survival benefit from intralesional injection.

Future directions for the treatment of advanced melanoma include identification of predictive biomarkers to guide the choice of therapy, new immune agonist antibodies or checkpoint inhibitors to act in concert with PD-1 inhibitors, adaptive T-cell therapies, and lymphokines, cytokines, vaccines, and targeted therapies that can overcome mechanisms of resistance and work in combination with immunomodulators, Dr. Thompson said.

HOLLYWOOD, FLA. –The remarkable changes that have occurred in the treatment of advanced malignant melanoma over the last several years are reflected in revised National Comprehensive Cancer Network guidelines.

“Gone are the days where our active agents were interferon and dacarbazine,” said Dr. John A. Thompson of the Fred Hutchinson Cancer Research Center, Seattle.

“We’ve seen the approval by the FDA of the PD-1-targeted agents and also molecular-targeted agents to treat patients with mutations in the BRAF gene, and the rate of change continues apace,” he said at the annual conference of the National Comprehensive Cancer Network.

Among the changes in the 2016 guidelines are the addition of high-dose ipilimumab (Yervoy) as an option for stage III (node-positive) disease, and intralesional talimogene laherparepvec (T-VEC) for primary treatment of stage III in-transit disease.

Guidelines for first-line systemic therapy for metastatic or unresectable disease recommend treatment based on evaluation of individual patients and include:

• Monotherapy with an anti-PD-1 (programmed death-1) agent, either pembrolizumab (Keytruda) or nivolumab (Opdivo) (category 1 recommendation).

• Targeted therapy for BRAF-mutated disease with combinations (preferred) of either dabrafenib (Tafinlar) and trametinib (Mekinist) or vemurafenib (Zelboraf)and cobimetinib (Cotellic); both are category 1 recommendations.

• Single-agent therapy with either vemurafenib or dabrafenib (category 1), or clinical trial.

For patients with disease progression or those who have had their maximum clinical benefit from BRAF-targeted therapy and good performance status (0-2), the guidelines recommend second-line or subsequent therapy with anti-PD-1 agents as above, ipilimumab, or a combination of nivolumab and ipilimumab.

The guidelines note, however, that “nivolumab/ipilimumab combination therapy is associated with improved relapse-free survival compared with single-agent nivolumab or ipilimumab, at the expense of significantly increased toxicity. Compared to single-agent therapy, the impact of nivolumab/ipilimumab combination therapy on overall survival is not known.”

Also recommended are targeted therapy with the BRAF-inhibitor combinations listed above (preferred) or single-agent therapy with vemurafenib or dabrafenib.

“In previously untreated patients with unresectable stage IIIC or stage IV disease, the combination of vemurafenib/cobimetinib was associated with improved PFS [progression-free survival] and response rate when compared to vemurafenib alone. The impact on overall survival compared to single-agent vemurafenib is unknown,” the guidelines state.

Other second-line options for patients with good performance status include high-dose interleukin-2 (not suitable for patients with inadequate organ reserve, poor performance status, or untreated or active brain metastases), biochemotherapy and cytotoxic agents (dacarbazine or temozolomide, and cisplatin or carboplatin, with or without vinblastine or nitrosourea, and IL-2 and interferon alfa-2b; paclitaxel, albumin-bound paclitaxel).

For patients with poor performance status (3-4) the guidelines call for best supportive care according to guidelines for palliative care.

Oncolytic immunotherapy

For treatment of recurrent disease, the guidelines newly recommend use of T-VEC, a genetically modified herpes simplex-1 virus that is injected intralesionally into accessible tumors. The attenuated virus does not kill healthy cells, but replicates in tumors and causes the cells to secrete granulocyte macrophage–colony stimulating factor (GM-CSF), leading to lysis of the tumor cells.

“It is hypothesized that the GM-CSF works with the immune system to boost a resident immune response against the destroyed melanoma cells and antigens that are released from this process,” Dr. Thompson said.

In a recent clinical trial (J Clin Oncol. 2015;33:2780-8), patients with injectable melanoma that was not surgically resectable were randomized to either intralesional T-VEC injections on week 0, 3, and then every 2 weeks (295 patients), or subcutaneous GM-CSF 125 mcg/m² on days 1 to 14 for every 28 days (141 patients).

T-VEC was associated with significantly more durables responses (16% vs. 2.1% for GM-CSF, P less than .001) and a significantly higher overall response rate (26.4% vs. 5.7%, respectively, P less than .001).

In the primary analysis in an intent-to-treat population, T-VEC had a borderline significant association with better overall survival (median 23.2 vs. 18.9 months, hazard ratio [HR] 0.70, log-rank P = .051).

In subanalyses of outcomes in patient subgroups, however, the benefits of T-VEC were seen in patients with stage IIIB IIIC, and IV M1a disease (HR 0.57, P less than .001), but not in patients with IV M1b or M1c disease. In addition, patients treated with T-VEC in first-line therapy had significantly better overall survival compared with GM-CSF (HR 0.50, P less than .001), but those who received it in second or subsequent lines of therapy saw no survival benefit from intralesional injection.

Future directions for the treatment of advanced melanoma include identification of predictive biomarkers to guide the choice of therapy, new immune agonist antibodies or checkpoint inhibitors to act in concert with PD-1 inhibitors, adaptive T-cell therapies, and lymphokines, cytokines, vaccines, and targeted therapies that can overcome mechanisms of resistance and work in combination with immunomodulators, Dr. Thompson said.

HOLLYWOOD, FLA. –The remarkable changes that have occurred in the treatment of advanced malignant melanoma over the last several years are reflected in revised National Comprehensive Cancer Network guidelines.

“Gone are the days where our active agents were interferon and dacarbazine,” said Dr. John A. Thompson of the Fred Hutchinson Cancer Research Center, Seattle.

“We’ve seen the approval by the FDA of the PD-1-targeted agents and also molecular-targeted agents to treat patients with mutations in the BRAF gene, and the rate of change continues apace,” he said at the annual conference of the National Comprehensive Cancer Network.

Among the changes in the 2016 guidelines are the addition of high-dose ipilimumab (Yervoy) as an option for stage III (node-positive) disease, and intralesional talimogene laherparepvec (T-VEC) for primary treatment of stage III in-transit disease.

Guidelines for first-line systemic therapy for metastatic or unresectable disease recommend treatment based on evaluation of individual patients and include:

• Monotherapy with an anti-PD-1 (programmed death-1) agent, either pembrolizumab (Keytruda) or nivolumab (Opdivo) (category 1 recommendation).

• Targeted therapy for BRAF-mutated disease with combinations (preferred) of either dabrafenib (Tafinlar) and trametinib (Mekinist) or vemurafenib (Zelboraf)and cobimetinib (Cotellic); both are category 1 recommendations.

• Single-agent therapy with either vemurafenib or dabrafenib (category 1), or clinical trial.

For patients with disease progression or those who have had their maximum clinical benefit from BRAF-targeted therapy and good performance status (0-2), the guidelines recommend second-line or subsequent therapy with anti-PD-1 agents as above, ipilimumab, or a combination of nivolumab and ipilimumab.

The guidelines note, however, that “nivolumab/ipilimumab combination therapy is associated with improved relapse-free survival compared with single-agent nivolumab or ipilimumab, at the expense of significantly increased toxicity. Compared to single-agent therapy, the impact of nivolumab/ipilimumab combination therapy on overall survival is not known.”

Also recommended are targeted therapy with the BRAF-inhibitor combinations listed above (preferred) or single-agent therapy with vemurafenib or dabrafenib.

“In previously untreated patients with unresectable stage IIIC or stage IV disease, the combination of vemurafenib/cobimetinib was associated with improved PFS [progression-free survival] and response rate when compared to vemurafenib alone. The impact on overall survival compared to single-agent vemurafenib is unknown,” the guidelines state.

Other second-line options for patients with good performance status include high-dose interleukin-2 (not suitable for patients with inadequate organ reserve, poor performance status, or untreated or active brain metastases), biochemotherapy and cytotoxic agents (dacarbazine or temozolomide, and cisplatin or carboplatin, with or without vinblastine or nitrosourea, and IL-2 and interferon alfa-2b; paclitaxel, albumin-bound paclitaxel).

For patients with poor performance status (3-4) the guidelines call for best supportive care according to guidelines for palliative care.

Oncolytic immunotherapy

For treatment of recurrent disease, the guidelines newly recommend use of T-VEC, a genetically modified herpes simplex-1 virus that is injected intralesionally into accessible tumors. The attenuated virus does not kill healthy cells, but replicates in tumors and causes the cells to secrete granulocyte macrophage–colony stimulating factor (GM-CSF), leading to lysis of the tumor cells.

“It is hypothesized that the GM-CSF works with the immune system to boost a resident immune response against the destroyed melanoma cells and antigens that are released from this process,” Dr. Thompson said.

In a recent clinical trial (J Clin Oncol. 2015;33:2780-8), patients with injectable melanoma that was not surgically resectable were randomized to either intralesional T-VEC injections on week 0, 3, and then every 2 weeks (295 patients), or subcutaneous GM-CSF 125 mcg/m² on days 1 to 14 for every 28 days (141 patients).

T-VEC was associated with significantly more durables responses (16% vs. 2.1% for GM-CSF, P less than .001) and a significantly higher overall response rate (26.4% vs. 5.7%, respectively, P less than .001).

In the primary analysis in an intent-to-treat population, T-VEC had a borderline significant association with better overall survival (median 23.2 vs. 18.9 months, hazard ratio [HR] 0.70, log-rank P = .051).

In subanalyses of outcomes in patient subgroups, however, the benefits of T-VEC were seen in patients with stage IIIB IIIC, and IV M1a disease (HR 0.57, P less than .001), but not in patients with IV M1b or M1c disease. In addition, patients treated with T-VEC in first-line therapy had significantly better overall survival compared with GM-CSF (HR 0.50, P less than .001), but those who received it in second or subsequent lines of therapy saw no survival benefit from intralesional injection.

Future directions for the treatment of advanced melanoma include identification of predictive biomarkers to guide the choice of therapy, new immune agonist antibodies or checkpoint inhibitors to act in concert with PD-1 inhibitors, adaptive T-cell therapies, and lymphokines, cytokines, vaccines, and targeted therapies that can overcome mechanisms of resistance and work in combination with immunomodulators, Dr. Thompson said.

HOLLYWOOD, FLA. – No huge surprises here, but newly revised National Comprehensive Cancer Network guidelines for locoregional therapy of breast cancer help clarify the optimal use of adjuvant radiation.

For example, updates to the pages on principles of radiation therapy in invasive breast cancer contain new information on optimal dosing, fractionation, treatment planning, and techniques for minimizing radiation of surrounding normal tissues, noted Dr. Kilian E. Salerno, director of breast radiation and soft tissue/melanoma radiation at the Roswell Park Cancer Institute in Buffalo, New York.

“There are a number of treatment options, many more now than ever before,” she said at the annual conference of the National Comprehensive Cancer Network.

The guidelines emphasize the importance of individualized radiation therapy planning and delivery. A CT-based treatment plan can help clinicians choose target volumes and identify adjacent organs and tissues that may be at risk for radiation spill.

Recommended options for reducing radiation doses to adjacent tissues include deep breath holds and prone positioning so that the treated breast hangs down, helping to isolate it from the heart and lungs.

Whole breast irradiation

Whole breast irradiation is the standard for radiation therapy of early breast cancer following breast-conserving surgery, although partial breast irradiation, typically of lumpectomy cavities, is also commonly performed, Dr. Salerno said.

Boost radiation in conjunction with breast conserving therapy can be delivered via en face electron fields, photons, or brachytherapy; boost dosing to chest wall scar is usually treated with photons or electrons, the guidelines note.

The guidelines recommend weekly imaging to ensure that daily treatment setup is consistent, but caution against routine use of daily imaging.

For whole breast irradiation, the guidelines recommend either doses of 46-50 Gy divided into 23-25 fractions (conventional fractionation), or, preferably, hypofractionated radiation delivered in doses of 40-42.5 Gy over 15-16 fractions, with all doses given 5 days per week. Patients at higher risk for recurrence should receive boost doses to the tumor bed, typically at doses of 10-16 Gy delivered in 4-8 fractions.

The guidelines now favor hypofractionation based on long-term results from clinical trials conducted in Ontario, Canada, and in London.

In the Canadian trial (N Engl J Med. 2010;362:513-20), patients were treated with whole-breast irradiation at doses of 42.5 Gy in 16 fractions, with no boost dose.

In the Standardisation of Breast Radiotherapy B (START B) trial (Lancet Oncol. 14;11:1086-94), in London, patients received 40 Gy in 15 fractions without a boost dose.

Both trials showed that hypofractionation was associated with disease outcomes that were equivalent or better to those seen with conventional fractionation schedules, as well as equivalent or better cosmesis and adverse event profiles, Dr. Salerno said.

“This is for whole breast radiation; it is not to be routinely used in the post-mastectomy setting or when you’re treating regional nodes,” she said.

Accelerated partial breast irradiation

For accelerated partial breast irradiation (APBI), the guidelines recommend a hypofractionated schedule of 34 Gy divided into 10 fractions delivered twice daily for 5 days for brachytherapy, or 38.5 Gy in 10 twice daily fractions with external beam therapy to the tumor bed.

The NCCN guidelines for APBI are based on the American Society of Radiation Oncology (ASTRO) consensus statement for APBI. An updated statement is planned for 2017.

Omit radiation?

Results from the CALGB 9343 trial and other studies suggest that in selected women with lower risk for recurrence, radiation can be omitted without compromising survival. These include women aged 70 or older with small primary breast cancers, negative nodes, negative surgical margins, and hormone-receptor-positive disease who are treated with breast conserving surgery and go on to tamoxifen maintenance.

Post-mastectomy radiation

Following total mastectomy with surgical axillary staging, with our without reconstruction, the guidelines recommend specific steps based on the number of nodes involved and the tumor size and/or margin status.

Thus, women with four or more positive axillary nodes should receive radiation to the chest wall and infraclavicular region, supraclavicular area, internal mammary nodes, and any at-risk part of the axillary bed. If adjuvant chemotherapy is prescribed, radiation usually is given following chemotherapy completion.

For women with one to three positive axillary nodes, the guidelines urge clinicians to “strongly consider” treating them as they would women with four or more positive nodes. The same advice applies to women with negative nodes but tumors larger than 5 cm or positive surgical margins as defined by ink on tumor.

For patients with negative nodes, tumors 5 cm or smaller and negative but narrow margins (less than 1 mm), the guidelines recommend consideration of radiation to the chest wall. Patients with small tumors, no nodal involvement, and margins 1 mm or greater can be spared radiation therapy.

Recurrence

For women with local-only recurrence, the guidelines recommend mastectomy with axillary lymph node staging for those with recurrences after initial lumpectomy and radiation, or if the initial treatment was mastectomy with no radiation, surgical resection with radiation, or surgical resection alone for those women previously treated with mastectomy and radiation.

For regional or locoregional recurrences, the guidelines recommend that axillary recurrences be treated with surgery and radiation if possible, and that supraclavicular or internal mammary node recurrences be treated with radiation therapy, if possible.

HOLLYWOOD, FLA. – No huge surprises here, but newly revised National Comprehensive Cancer Network guidelines for locoregional therapy of breast cancer help clarify the optimal use of adjuvant radiation.

For example, updates to the pages on principles of radiation therapy in invasive breast cancer contain new information on optimal dosing, fractionation, treatment planning, and techniques for minimizing radiation of surrounding normal tissues, noted Dr. Kilian E. Salerno, director of breast radiation and soft tissue/melanoma radiation at the Roswell Park Cancer Institute in Buffalo, New York.

“There are a number of treatment options, many more now than ever before,” she said at the annual conference of the National Comprehensive Cancer Network.

The guidelines emphasize the importance of individualized radiation therapy planning and delivery. A CT-based treatment plan can help clinicians choose target volumes and identify adjacent organs and tissues that may be at risk for radiation spill.

Recommended options for reducing radiation doses to adjacent tissues include deep breath holds and prone positioning so that the treated breast hangs down, helping to isolate it from the heart and lungs.

Whole breast irradiation

Whole breast irradiation is the standard for radiation therapy of early breast cancer following breast-conserving surgery, although partial breast irradiation, typically of lumpectomy cavities, is also commonly performed, Dr. Salerno said.

Boost radiation in conjunction with breast conserving therapy can be delivered via en face electron fields, photons, or brachytherapy; boost dosing to chest wall scar is usually treated with photons or electrons, the guidelines note.

The guidelines recommend weekly imaging to ensure that daily treatment setup is consistent, but caution against routine use of daily imaging.

For whole breast irradiation, the guidelines recommend either doses of 46-50 Gy divided into 23-25 fractions (conventional fractionation), or, preferably, hypofractionated radiation delivered in doses of 40-42.5 Gy over 15-16 fractions, with all doses given 5 days per week. Patients at higher risk for recurrence should receive boost doses to the tumor bed, typically at doses of 10-16 Gy delivered in 4-8 fractions.

The guidelines now favor hypofractionation based on long-term results from clinical trials conducted in Ontario, Canada, and in London.

In the Canadian trial (N Engl J Med. 2010;362:513-20), patients were treated with whole-breast irradiation at doses of 42.5 Gy in 16 fractions, with no boost dose.

In the Standardisation of Breast Radiotherapy B (START B) trial (Lancet Oncol. 14;11:1086-94), in London, patients received 40 Gy in 15 fractions without a boost dose.

Both trials showed that hypofractionation was associated with disease outcomes that were equivalent or better to those seen with conventional fractionation schedules, as well as equivalent or better cosmesis and adverse event profiles, Dr. Salerno said.

“This is for whole breast radiation; it is not to be routinely used in the post-mastectomy setting or when you’re treating regional nodes,” she said.

Accelerated partial breast irradiation

For accelerated partial breast irradiation (APBI), the guidelines recommend a hypofractionated schedule of 34 Gy divided into 10 fractions delivered twice daily for 5 days for brachytherapy, or 38.5 Gy in 10 twice daily fractions with external beam therapy to the tumor bed.

The NCCN guidelines for APBI are based on the American Society of Radiation Oncology (ASTRO) consensus statement for APBI. An updated statement is planned for 2017.

Omit radiation?

Results from the CALGB 9343 trial and other studies suggest that in selected women with lower risk for recurrence, radiation can be omitted without compromising survival. These include women aged 70 or older with small primary breast cancers, negative nodes, negative surgical margins, and hormone-receptor-positive disease who are treated with breast conserving surgery and go on to tamoxifen maintenance.

Post-mastectomy radiation

Following total mastectomy with surgical axillary staging, with our without reconstruction, the guidelines recommend specific steps based on the number of nodes involved and the tumor size and/or margin status.

Thus, women with four or more positive axillary nodes should receive radiation to the chest wall and infraclavicular region, supraclavicular area, internal mammary nodes, and any at-risk part of the axillary bed. If adjuvant chemotherapy is prescribed, radiation usually is given following chemotherapy completion.

For women with one to three positive axillary nodes, the guidelines urge clinicians to “strongly consider” treating them as they would women with four or more positive nodes. The same advice applies to women with negative nodes but tumors larger than 5 cm or positive surgical margins as defined by ink on tumor.

For patients with negative nodes, tumors 5 cm or smaller and negative but narrow margins (less than 1 mm), the guidelines recommend consideration of radiation to the chest wall. Patients with small tumors, no nodal involvement, and margins 1 mm or greater can be spared radiation therapy.

Recurrence

For women with local-only recurrence, the guidelines recommend mastectomy with axillary lymph node staging for those with recurrences after initial lumpectomy and radiation, or if the initial treatment was mastectomy with no radiation, surgical resection with radiation, or surgical resection alone for those women previously treated with mastectomy and radiation.

For regional or locoregional recurrences, the guidelines recommend that axillary recurrences be treated with surgery and radiation if possible, and that supraclavicular or internal mammary node recurrences be treated with radiation therapy, if possible.

HOLLYWOOD, FLA. – No huge surprises here, but newly revised National Comprehensive Cancer Network guidelines for locoregional therapy of breast cancer help clarify the optimal use of adjuvant radiation.

For example, updates to the pages on principles of radiation therapy in invasive breast cancer contain new information on optimal dosing, fractionation, treatment planning, and techniques for minimizing radiation of surrounding normal tissues, noted Dr. Kilian E. Salerno, director of breast radiation and soft tissue/melanoma radiation at the Roswell Park Cancer Institute in Buffalo, New York.

“There are a number of treatment options, many more now than ever before,” she said at the annual conference of the National Comprehensive Cancer Network.

The guidelines emphasize the importance of individualized radiation therapy planning and delivery. A CT-based treatment plan can help clinicians choose target volumes and identify adjacent organs and tissues that may be at risk for radiation spill.

Recommended options for reducing radiation doses to adjacent tissues include deep breath holds and prone positioning so that the treated breast hangs down, helping to isolate it from the heart and lungs.

Whole breast irradiation

Whole breast irradiation is the standard for radiation therapy of early breast cancer following breast-conserving surgery, although partial breast irradiation, typically of lumpectomy cavities, is also commonly performed, Dr. Salerno said.

Boost radiation in conjunction with breast conserving therapy can be delivered via en face electron fields, photons, or brachytherapy; boost dosing to chest wall scar is usually treated with photons or electrons, the guidelines note.

The guidelines recommend weekly imaging to ensure that daily treatment setup is consistent, but caution against routine use of daily imaging.

For whole breast irradiation, the guidelines recommend either doses of 46-50 Gy divided into 23-25 fractions (conventional fractionation), or, preferably, hypofractionated radiation delivered in doses of 40-42.5 Gy over 15-16 fractions, with all doses given 5 days per week. Patients at higher risk for recurrence should receive boost doses to the tumor bed, typically at doses of 10-16 Gy delivered in 4-8 fractions.

The guidelines now favor hypofractionation based on long-term results from clinical trials conducted in Ontario, Canada, and in London.

In the Canadian trial (N Engl J Med. 2010;362:513-20), patients were treated with whole-breast irradiation at doses of 42.5 Gy in 16 fractions, with no boost dose.

In the Standardisation of Breast Radiotherapy B (START B) trial (Lancet Oncol. 14;11:1086-94), in London, patients received 40 Gy in 15 fractions without a boost dose.

Both trials showed that hypofractionation was associated with disease outcomes that were equivalent or better to those seen with conventional fractionation schedules, as well as equivalent or better cosmesis and adverse event profiles, Dr. Salerno said.

“This is for whole breast radiation; it is not to be routinely used in the post-mastectomy setting or when you’re treating regional nodes,” she said.

Accelerated partial breast irradiation

For accelerated partial breast irradiation (APBI), the guidelines recommend a hypofractionated schedule of 34 Gy divided into 10 fractions delivered twice daily for 5 days for brachytherapy, or 38.5 Gy in 10 twice daily fractions with external beam therapy to the tumor bed.

The NCCN guidelines for APBI are based on the American Society of Radiation Oncology (ASTRO) consensus statement for APBI. An updated statement is planned for 2017.

Omit radiation?

Results from the CALGB 9343 trial and other studies suggest that in selected women with lower risk for recurrence, radiation can be omitted without compromising survival. These include women aged 70 or older with small primary breast cancers, negative nodes, negative surgical margins, and hormone-receptor-positive disease who are treated with breast conserving surgery and go on to tamoxifen maintenance.

Post-mastectomy radiation

Following total mastectomy with surgical axillary staging, with our without reconstruction, the guidelines recommend specific steps based on the number of nodes involved and the tumor size and/or margin status.

Thus, women with four or more positive axillary nodes should receive radiation to the chest wall and infraclavicular region, supraclavicular area, internal mammary nodes, and any at-risk part of the axillary bed. If adjuvant chemotherapy is prescribed, radiation usually is given following chemotherapy completion.

For women with one to three positive axillary nodes, the guidelines urge clinicians to “strongly consider” treating them as they would women with four or more positive nodes. The same advice applies to women with negative nodes but tumors larger than 5 cm or positive surgical margins as defined by ink on tumor.

For patients with negative nodes, tumors 5 cm or smaller and negative but narrow margins (less than 1 mm), the guidelines recommend consideration of radiation to the chest wall. Patients with small tumors, no nodal involvement, and margins 1 mm or greater can be spared radiation therapy.

Recurrence

For women with local-only recurrence, the guidelines recommend mastectomy with axillary lymph node staging for those with recurrences after initial lumpectomy and radiation, or if the initial treatment was mastectomy with no radiation, surgical resection with radiation, or surgical resection alone for those women previously treated with mastectomy and radiation.

For regional or locoregional recurrences, the guidelines recommend that axillary recurrences be treated with surgery and radiation if possible, and that supraclavicular or internal mammary node recurrences be treated with radiation therapy, if possible.

HOLLYWOOD, FLA. – The latest updates to the National Comprehensive Cancer Network guidelines on breast cancer reflect a more nuanced approach to the use of systemic therapy in both the pre- and postoperative settings, with increasing emphasis on tailoring therapies to the unique clinical profiles of individual patients, according to Dr. William Gradishar.

The revised guidelines include new recommendations about preoperative endocrine and HER2-directed therapies, optimizing adjuvant endocrine therapy in both pre- and postmenopausal women, targeted agents as partner drugs for endocrine therapy in women with metastatic breast cancer, and recommendations about preservation of fertility in younger patients, said Dr. Gradishar, chair of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago.

“There have been some tweaks but I wouldn’t say major, major changes within the guidelines,” he said at the annual conference of the National Comprehensive Cancer Network.

Neoadjuvant therapy

One of the larger changes to this year’s guidelines is the addition of a page devoted to the principles of preoperative systemic therapy. The guidelines note that randomized clinical trials have shown similar long-term outcomes when patients receive the same treatment in either the pre- or post-op setting.

They add, however, that neoadjuvant systemic therapy “can render surgically inoperable tumors operable and offers potential benefits for patients with operable breast cancer. Importantly, preoperative systemic therapy can improve rates of breast conservation therapy eligibility and provides an opportunity to observe clinical and pathologic response to systemic therapy in an individual patient.”

The guidelines also note that a pathologic complete response to preoperative systemic therapy is predictive of “extremely favorable” disease-free and overall survival.

Patients who may be good candidates for neoadjuvant endocrine therapy include those with estrogen receptor–rich tumors (Allred score, 7 or 8), older postmenopausal women, and younger, premenopausal women with significant comorbidities that may make them poor candidates for chemotherapy, Dr. Gradishar said.

Adjuvant therapy

Regarding adjuvant therapy, the guidelines reflect data from recent clinical trials showing the benefits of both extended tamoxifen therapy, and for women who are premenopausal at diagnosis and are at high risk of recurrence, an aromatase inhibitor (AI) or steroidal aromatase inactivator plus ovarian suppression or ablation.

The recommendation to consider an AI and ovarian suppression in this population is based on data from the SOFT and TEXT trials (N Engl J Med. 2014; 371:107-18), which showed a significant reduction in the recurrence of hormone receptor–positive early breast cancer in premenopausal women treated with exemestane (Aromasin) and ovarian suppression, compared with tamoxifen and ovarian suppression.

Although data supporting the use of endocrine therapy and ovarian suppression are compelling, “we have to individualize our choice of which patient is appropriate for this, because there is a price to pay in terms of side effects, and we have to figure out if that balance is right for an individual patient,” Dr. Gradishar commented.

Anti-HER2 therapy

The guidelines state that patients with HER2-positive tumors should receive neoadjuvant systemic therapy with trastuzumab (Herceptin) for at least 9 weeks prior to surgery. For patients with stage T2 or greater or nodal status N1 or greater HER2-positive disease, a pertuzumab (Perjeta)-containing regimen may be considered.

Recurrent/Stage IV disease

Premenopausal women with recurrent or stage IV hormone receptor–positive disease should have ovarian ablation or suppression, and then be treated with a regimen for postmenopausal women, the guidelines say. Agents used in therapy for advanced disease have included a nonsteroidal or steroidal AI, a combination of exmestane and everolimus, palbociclib (Ibrance) plus letrozole (Femara), palbociclib plus fulvestrant, tamoxifen, or toremafine, megesterol acetate fluoxymesterone, or ethinyl estradiol.

The updated guidelines note that “a single study (S0226) in women with hormone receptor–positive breast cancer and no prior chemotherapy, biological therapy, or endocrine therapy for metastatic disease demonstrated that the addition of fulvestrant to anastrozole resulted in prolongation of time to progression. Subset analysis suggested that patients without prior adjuvant tamoxifen and more than 10 years since diagnosis experienced the greatest benefit. Two studies with similar design (FACT and SOFEA) demonstrated no advantage in time to progression with the addition of fulvestrant to anastrozole.”

Chemotherapy regimens for recurrent/metastatic breast cancer include various combination regimens, as well as single-agent therapy with anthracyclines, taxanes, antimetabolites, or microtubule inhibitors (all of the above preferred single agents), or with cyclophosphamide, carboplatin, docetaxel, albumin-bound paclitaxel, cisplatin, epirubicin, or ixabepilone.

For HER2-positive disease, preferred agents include pertuzumab and trastuzumab with either docetaxel (category 1 recommendation) or paclitaxel. Trastuzumab can also be combined with other agents such as paclitaxel with or without cisplatin, docetaxel, vinorelbine, or capecitabine.

For patients with recurrent HER2-positve disease with prior trastuzumab exposure, combinations may include lapatinin with capecitabine, or trastuzumab with capecitabine, lapatinib (without cytoxic therapy), or other agents.

Fertility preservation

Lastly, the revised guidelines note that all premenopausal patients should be informed about the potential effects of chemotherapy on fertility, with women who express the wish to have future pregnancies referred to fertility specialists. The options presented should be “based on patient specifics, disease stage, and biology (which determine the urgency and type and sequence of treatment). Timing and duration allowed for fertility preservation, options inclusive of oocyte and embryo cryopreservation as well as evolving technologies, and the probability of successful pregnancies subsequent to completion of breast cancer therapy are also to be discussed,” the guidelines say.

HOLLYWOOD, FLA. – The latest updates to the National Comprehensive Cancer Network guidelines on breast cancer reflect a more nuanced approach to the use of systemic therapy in both the pre- and postoperative settings, with increasing emphasis on tailoring therapies to the unique clinical profiles of individual patients, according to Dr. William Gradishar.

The revised guidelines include new recommendations about preoperative endocrine and HER2-directed therapies, optimizing adjuvant endocrine therapy in both pre- and postmenopausal women, targeted agents as partner drugs for endocrine therapy in women with metastatic breast cancer, and recommendations about preservation of fertility in younger patients, said Dr. Gradishar, chair of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago.

“There have been some tweaks but I wouldn’t say major, major changes within the guidelines,” he said at the annual conference of the National Comprehensive Cancer Network.

Neoadjuvant therapy

One of the larger changes to this year’s guidelines is the addition of a page devoted to the principles of preoperative systemic therapy. The guidelines note that randomized clinical trials have shown similar long-term outcomes when patients receive the same treatment in either the pre- or post-op setting.

They add, however, that neoadjuvant systemic therapy “can render surgically inoperable tumors operable and offers potential benefits for patients with operable breast cancer. Importantly, preoperative systemic therapy can improve rates of breast conservation therapy eligibility and provides an opportunity to observe clinical and pathologic response to systemic therapy in an individual patient.”

The guidelines also note that a pathologic complete response to preoperative systemic therapy is predictive of “extremely favorable” disease-free and overall survival.

Patients who may be good candidates for neoadjuvant endocrine therapy include those with estrogen receptor–rich tumors (Allred score, 7 or 8), older postmenopausal women, and younger, premenopausal women with significant comorbidities that may make them poor candidates for chemotherapy, Dr. Gradishar said.

Adjuvant therapy

Regarding adjuvant therapy, the guidelines reflect data from recent clinical trials showing the benefits of both extended tamoxifen therapy, and for women who are premenopausal at diagnosis and are at high risk of recurrence, an aromatase inhibitor (AI) or steroidal aromatase inactivator plus ovarian suppression or ablation.

The recommendation to consider an AI and ovarian suppression in this population is based on data from the SOFT and TEXT trials (N Engl J Med. 2014; 371:107-18), which showed a significant reduction in the recurrence of hormone receptor–positive early breast cancer in premenopausal women treated with exemestane (Aromasin) and ovarian suppression, compared with tamoxifen and ovarian suppression.

Although data supporting the use of endocrine therapy and ovarian suppression are compelling, “we have to individualize our choice of which patient is appropriate for this, because there is a price to pay in terms of side effects, and we have to figure out if that balance is right for an individual patient,” Dr. Gradishar commented.

Anti-HER2 therapy

The guidelines state that patients with HER2-positive tumors should receive neoadjuvant systemic therapy with trastuzumab (Herceptin) for at least 9 weeks prior to surgery. For patients with stage T2 or greater or nodal status N1 or greater HER2-positive disease, a pertuzumab (Perjeta)-containing regimen may be considered.

Recurrent/Stage IV disease

Premenopausal women with recurrent or stage IV hormone receptor–positive disease should have ovarian ablation or suppression, and then be treated with a regimen for postmenopausal women, the guidelines say. Agents used in therapy for advanced disease have included a nonsteroidal or steroidal AI, a combination of exmestane and everolimus, palbociclib (Ibrance) plus letrozole (Femara), palbociclib plus fulvestrant, tamoxifen, or toremafine, megesterol acetate fluoxymesterone, or ethinyl estradiol.

The updated guidelines note that “a single study (S0226) in women with hormone receptor–positive breast cancer and no prior chemotherapy, biological therapy, or endocrine therapy for metastatic disease demonstrated that the addition of fulvestrant to anastrozole resulted in prolongation of time to progression. Subset analysis suggested that patients without prior adjuvant tamoxifen and more than 10 years since diagnosis experienced the greatest benefit. Two studies with similar design (FACT and SOFEA) demonstrated no advantage in time to progression with the addition of fulvestrant to anastrozole.”

Chemotherapy regimens for recurrent/metastatic breast cancer include various combination regimens, as well as single-agent therapy with anthracyclines, taxanes, antimetabolites, or microtubule inhibitors (all of the above preferred single agents), or with cyclophosphamide, carboplatin, docetaxel, albumin-bound paclitaxel, cisplatin, epirubicin, or ixabepilone.

For HER2-positive disease, preferred agents include pertuzumab and trastuzumab with either docetaxel (category 1 recommendation) or paclitaxel. Trastuzumab can also be combined with other agents such as paclitaxel with or without cisplatin, docetaxel, vinorelbine, or capecitabine.

For patients with recurrent HER2-positve disease with prior trastuzumab exposure, combinations may include lapatinin with capecitabine, or trastuzumab with capecitabine, lapatinib (without cytoxic therapy), or other agents.

Fertility preservation

Lastly, the revised guidelines note that all premenopausal patients should be informed about the potential effects of chemotherapy on fertility, with women who express the wish to have future pregnancies referred to fertility specialists. The options presented should be “based on patient specifics, disease stage, and biology (which determine the urgency and type and sequence of treatment). Timing and duration allowed for fertility preservation, options inclusive of oocyte and embryo cryopreservation as well as evolving technologies, and the probability of successful pregnancies subsequent to completion of breast cancer therapy are also to be discussed,” the guidelines say.

HOLLYWOOD, FLA. – The latest updates to the National Comprehensive Cancer Network guidelines on breast cancer reflect a more nuanced approach to the use of systemic therapy in both the pre- and postoperative settings, with increasing emphasis on tailoring therapies to the unique clinical profiles of individual patients, according to Dr. William Gradishar.

The revised guidelines include new recommendations about preoperative endocrine and HER2-directed therapies, optimizing adjuvant endocrine therapy in both pre- and postmenopausal women, targeted agents as partner drugs for endocrine therapy in women with metastatic breast cancer, and recommendations about preservation of fertility in younger patients, said Dr. Gradishar, chair of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University in Chicago.

“There have been some tweaks but I wouldn’t say major, major changes within the guidelines,” he said at the annual conference of the National Comprehensive Cancer Network.

Neoadjuvant therapy

One of the larger changes to this year’s guidelines is the addition of a page devoted to the principles of preoperative systemic therapy. The guidelines note that randomized clinical trials have shown similar long-term outcomes when patients receive the same treatment in either the pre- or post-op setting.

They add, however, that neoadjuvant systemic therapy “can render surgically inoperable tumors operable and offers potential benefits for patients with operable breast cancer. Importantly, preoperative systemic therapy can improve rates of breast conservation therapy eligibility and provides an opportunity to observe clinical and pathologic response to systemic therapy in an individual patient.”

The guidelines also note that a pathologic complete response to preoperative systemic therapy is predictive of “extremely favorable” disease-free and overall survival.

Patients who may be good candidates for neoadjuvant endocrine therapy include those with estrogen receptor–rich tumors (Allred score, 7 or 8), older postmenopausal women, and younger, premenopausal women with significant comorbidities that may make them poor candidates for chemotherapy, Dr. Gradishar said.

Adjuvant therapy

Regarding adjuvant therapy, the guidelines reflect data from recent clinical trials showing the benefits of both extended tamoxifen therapy, and for women who are premenopausal at diagnosis and are at high risk of recurrence, an aromatase inhibitor (AI) or steroidal aromatase inactivator plus ovarian suppression or ablation.

The recommendation to consider an AI and ovarian suppression in this population is based on data from the SOFT and TEXT trials (N Engl J Med. 2014; 371:107-18), which showed a significant reduction in the recurrence of hormone receptor–positive early breast cancer in premenopausal women treated with exemestane (Aromasin) and ovarian suppression, compared with tamoxifen and ovarian suppression.

Although data supporting the use of endocrine therapy and ovarian suppression are compelling, “we have to individualize our choice of which patient is appropriate for this, because there is a price to pay in terms of side effects, and we have to figure out if that balance is right for an individual patient,” Dr. Gradishar commented.

Anti-HER2 therapy

The guidelines state that patients with HER2-positive tumors should receive neoadjuvant systemic therapy with trastuzumab (Herceptin) for at least 9 weeks prior to surgery. For patients with stage T2 or greater or nodal status N1 or greater HER2-positive disease, a pertuzumab (Perjeta)-containing regimen may be considered.

Recurrent/Stage IV disease

Premenopausal women with recurrent or stage IV hormone receptor–positive disease should have ovarian ablation or suppression, and then be treated with a regimen for postmenopausal women, the guidelines say. Agents used in therapy for advanced disease have included a nonsteroidal or steroidal AI, a combination of exmestane and everolimus, palbociclib (Ibrance) plus letrozole (Femara), palbociclib plus fulvestrant, tamoxifen, or toremafine, megesterol acetate fluoxymesterone, or ethinyl estradiol.

The updated guidelines note that “a single study (S0226) in women with hormone receptor–positive breast cancer and no prior chemotherapy, biological therapy, or endocrine therapy for metastatic disease demonstrated that the addition of fulvestrant to anastrozole resulted in prolongation of time to progression. Subset analysis suggested that patients without prior adjuvant tamoxifen and more than 10 years since diagnosis experienced the greatest benefit. Two studies with similar design (FACT and SOFEA) demonstrated no advantage in time to progression with the addition of fulvestrant to anastrozole.”

Chemotherapy regimens for recurrent/metastatic breast cancer include various combination regimens, as well as single-agent therapy with anthracyclines, taxanes, antimetabolites, or microtubule inhibitors (all of the above preferred single agents), or with cyclophosphamide, carboplatin, docetaxel, albumin-bound paclitaxel, cisplatin, epirubicin, or ixabepilone.

For HER2-positive disease, preferred agents include pertuzumab and trastuzumab with either docetaxel (category 1 recommendation) or paclitaxel. Trastuzumab can also be combined with other agents such as paclitaxel with or without cisplatin, docetaxel, vinorelbine, or capecitabine.

For patients with recurrent HER2-positve disease with prior trastuzumab exposure, combinations may include lapatinin with capecitabine, or trastuzumab with capecitabine, lapatinib (without cytoxic therapy), or other agents.

Fertility preservation

Lastly, the revised guidelines note that all premenopausal patients should be informed about the potential effects of chemotherapy on fertility, with women who express the wish to have future pregnancies referred to fertility specialists. The options presented should be “based on patient specifics, disease stage, and biology (which determine the urgency and type and sequence of treatment). Timing and duration allowed for fertility preservation, options inclusive of oocyte and embryo cryopreservation as well as evolving technologies, and the probability of successful pregnancies subsequent to completion of breast cancer therapy are also to be discussed,” the guidelines say.

BOSTON – With art supplies and “mystery” sutures, a team of investigators has determined that immediate intraoperative inking of lumpectomy specimens appears to be a better method than suture placement for orienting specimens for pathology, a finding that could reduce re-excisions.

“Intraoperative specimen suturing appears to be inaccurate for margin identification, and additional means by the surgeon to improve the accuracy are needed. This could be either immediate inking or routine excision of shave margins, either at the original surgery or when you go back for re-excision, to take all the margins instead of one specific margin,” Dr. Angel Arnaout, a breast surgeon at the University of Ottawa, Ont., said at the annual Society of Surgical Oncology Cancer Symposium.

She presented results of the randomized, blinded SMART (Specimen Margin Assessment Technique) trial comparing suture placement with intraoperative inking within the same surgical specimen.

Positive resection margins during breast-conserving surgery are associated with a twofold increase in the risk of ipsilateral tumor recurrence, and require re-excision or conversion to mastectomy. Re-excisions rates range from 25% to 45%, but in the majority of cases – 53% to 65% – no additional disease is found, Dr. Arnaout said.

In addition to adding to patient distress, re-excisions diminish cosmetic results because they take additional tissue, and delay the start of adjuvant breast cancer therapy, she noted.

Surgeons typically orient specimens for pathologists by placing two or three sutures in the center of the margin surfaces or, less frequently, by intraoperative marking of the margins with ink. But in transit from the OR to the pathology lab, specimens often flatten or “pancake” under their own weight, making it challenging for the pathologist to identify the originally marked margins.

To test whether suturing or inking is better at identifying the extent of tumors during breast-conserving surgery, the investigators devised a strategy using benign breast tissue removed during prophylactic mastectomy or reduction mammoplasty.

The surgeons first performed a sham lumpectomy within the tissue. They then painted the specimen margins in the OR using a phospholuminescent paint obtained from an art supply store. The paint dries clear and colorless, but glows in different colors under black light. By using the paint, carefully selected so as not to interfere with pathology staining, the investigators were able to blind the pathologists to the actual orientation of the margins.

While the tissue was still in the OR, the surgeons then placed two or three orienting sutures in customary locations, plus a third, “mystery” suture at a location known only to the surgeon.

In the pathology lab, the assistant was asked to look at the sutures and outline in black ink the edges of the margins using the sutures for guidance.

The specimen was then examined under black light to determine the degree of discordance between surgeons and pathologist for identification of margins using the suture and painting methods (primary outcome), and to evaluate the discrepancy in the extent of margin surface areas as identified by the surgeons and the pathologists (secondary outcome).

“We asked breast surgeons ‘what would be a clinically significant discordance rate for you?’ and most of them said between 10% and 20%, so we looked for a 15% discordance rate as being clinically significant between the two margin assessment techniques,” Dr. Arnaout said.

They found that the overall discordance in the location of the mystery suture between surgeons and pathologists was similar whether the samples contained two or three location sutures, with discordance rates of 46% (34 of 75 samples) for two sutures, and 47% (41 of 88 samples) for three sutures.

For the secondary outcome of discordance in the extent of margins, they found that pathologists tended to estimate the mean surface of the anterior and posterior margins to be significantly larger than the surgeons did (P less than .01), while significantly underestimating the superior, inferior, and lateral margins (P less than .01 for superior and inferior, and P = .04 for lateral margins).

Examination under black light showed that often two or three additional margins would be included by the surgeon within what the pathologist had identified as the anterior margin.

“This has implications for the surgeon and for the patient,” Dr. Arnaout said. “For most of us that do lumpectomies that go from skin down to chest wall, if an anterior margin or posterior margin is positive, a lot of times we would fight not to go back because we would say there is no further room for re-excision.”

But if the tumor is within what is actually the superior margin but labeled by the pathologist as an anterior margin, the patient may miss an opportunity for successful re-excision, she explained.

The study was limited by the fact that the sham lumpectomy specimens did not contain skin or muscle, which would have allowed for more accurate margin orientation in an actual operative setting; by lack of compression of specimens with small nonpalpable lesions in containers, which further distorts specimens; and by the use of smaller lumpectomy specimens than normally obtained during cancer surgery, which could have resulted in overestimation of the discordance that might occur when larger specimens are taken, Dr. Arnaout said.

“The conclusion of our study is that specimen margin orientation really should be defined by the surgeon who knows the original shape and orientation of the tissue during surgery, and not to rely on the pathology to reorient based on some sutures placed in the centers of the specimens without defining the extent of the surface area of each of the margins,” she said.

The Canadian Cancer Society Research Institute and the Canadian Surgical Research Fund supported the study. Dr. Arnaout and coauthors reported no conflicts of interest.

BOSTON – With art supplies and “mystery” sutures, a team of investigators has determined that immediate intraoperative inking of lumpectomy specimens appears to be a better method than suture placement for orienting specimens for pathology, a finding that could reduce re-excisions.

“Intraoperative specimen suturing appears to be inaccurate for margin identification, and additional means by the surgeon to improve the accuracy are needed. This could be either immediate inking or routine excision of shave margins, either at the original surgery or when you go back for re-excision, to take all the margins instead of one specific margin,” Dr. Angel Arnaout, a breast surgeon at the University of Ottawa, Ont., said at the annual Society of Surgical Oncology Cancer Symposium.

She presented results of the randomized, blinded SMART (Specimen Margin Assessment Technique) trial comparing suture placement with intraoperative inking within the same surgical specimen.

Positive resection margins during breast-conserving surgery are associated with a twofold increase in the risk of ipsilateral tumor recurrence, and require re-excision or conversion to mastectomy. Re-excisions rates range from 25% to 45%, but in the majority of cases – 53% to 65% – no additional disease is found, Dr. Arnaout said.

In addition to adding to patient distress, re-excisions diminish cosmetic results because they take additional tissue, and delay the start of adjuvant breast cancer therapy, she noted.

Surgeons typically orient specimens for pathologists by placing two or three sutures in the center of the margin surfaces or, less frequently, by intraoperative marking of the margins with ink. But in transit from the OR to the pathology lab, specimens often flatten or “pancake” under their own weight, making it challenging for the pathologist to identify the originally marked margins.

To test whether suturing or inking is better at identifying the extent of tumors during breast-conserving surgery, the investigators devised a strategy using benign breast tissue removed during prophylactic mastectomy or reduction mammoplasty.

The surgeons first performed a sham lumpectomy within the tissue. They then painted the specimen margins in the OR using a phospholuminescent paint obtained from an art supply store. The paint dries clear and colorless, but glows in different colors under black light. By using the paint, carefully selected so as not to interfere with pathology staining, the investigators were able to blind the pathologists to the actual orientation of the margins.

While the tissue was still in the OR, the surgeons then placed two or three orienting sutures in customary locations, plus a third, “mystery” suture at a location known only to the surgeon.

In the pathology lab, the assistant was asked to look at the sutures and outline in black ink the edges of the margins using the sutures for guidance.

The specimen was then examined under black light to determine the degree of discordance between surgeons and pathologist for identification of margins using the suture and painting methods (primary outcome), and to evaluate the discrepancy in the extent of margin surface areas as identified by the surgeons and the pathologists (secondary outcome).

“We asked breast surgeons ‘what would be a clinically significant discordance rate for you?’ and most of them said between 10% and 20%, so we looked for a 15% discordance rate as being clinically significant between the two margin assessment techniques,” Dr. Arnaout said.

They found that the overall discordance in the location of the mystery suture between surgeons and pathologists was similar whether the samples contained two or three location sutures, with discordance rates of 46% (34 of 75 samples) for two sutures, and 47% (41 of 88 samples) for three sutures.

For the secondary outcome of discordance in the extent of margins, they found that pathologists tended to estimate the mean surface of the anterior and posterior margins to be significantly larger than the surgeons did (P less than .01), while significantly underestimating the superior, inferior, and lateral margins (P less than .01 for superior and inferior, and P = .04 for lateral margins).

Examination under black light showed that often two or three additional margins would be included by the surgeon within what the pathologist had identified as the anterior margin.

“This has implications for the surgeon and for the patient,” Dr. Arnaout said. “For most of us that do lumpectomies that go from skin down to chest wall, if an anterior margin or posterior margin is positive, a lot of times we would fight not to go back because we would say there is no further room for re-excision.”

But if the tumor is within what is actually the superior margin but labeled by the pathologist as an anterior margin, the patient may miss an opportunity for successful re-excision, she explained.

The study was limited by the fact that the sham lumpectomy specimens did not contain skin or muscle, which would have allowed for more accurate margin orientation in an actual operative setting; by lack of compression of specimens with small nonpalpable lesions in containers, which further distorts specimens; and by the use of smaller lumpectomy specimens than normally obtained during cancer surgery, which could have resulted in overestimation of the discordance that might occur when larger specimens are taken, Dr. Arnaout said.

“The conclusion of our study is that specimen margin orientation really should be defined by the surgeon who knows the original shape and orientation of the tissue during surgery, and not to rely on the pathology to reorient based on some sutures placed in the centers of the specimens without defining the extent of the surface area of each of the margins,” she said.

The Canadian Cancer Society Research Institute and the Canadian Surgical Research Fund supported the study. Dr. Arnaout and coauthors reported no conflicts of interest.

BOSTON – With art supplies and “mystery” sutures, a team of investigators has determined that immediate intraoperative inking of lumpectomy specimens appears to be a better method than suture placement for orienting specimens for pathology, a finding that could reduce re-excisions.

“Intraoperative specimen suturing appears to be inaccurate for margin identification, and additional means by the surgeon to improve the accuracy are needed. This could be either immediate inking or routine excision of shave margins, either at the original surgery or when you go back for re-excision, to take all the margins instead of one specific margin,” Dr. Angel Arnaout, a breast surgeon at the University of Ottawa, Ont., said at the annual Society of Surgical Oncology Cancer Symposium.

She presented results of the randomized, blinded SMART (Specimen Margin Assessment Technique) trial comparing suture placement with intraoperative inking within the same surgical specimen.

Positive resection margins during breast-conserving surgery are associated with a twofold increase in the risk of ipsilateral tumor recurrence, and require re-excision or conversion to mastectomy. Re-excisions rates range from 25% to 45%, but in the majority of cases – 53% to 65% – no additional disease is found, Dr. Arnaout said.

In addition to adding to patient distress, re-excisions diminish cosmetic results because they take additional tissue, and delay the start of adjuvant breast cancer therapy, she noted.

Surgeons typically orient specimens for pathologists by placing two or three sutures in the center of the margin surfaces or, less frequently, by intraoperative marking of the margins with ink. But in transit from the OR to the pathology lab, specimens often flatten or “pancake” under their own weight, making it challenging for the pathologist to identify the originally marked margins.

To test whether suturing or inking is better at identifying the extent of tumors during breast-conserving surgery, the investigators devised a strategy using benign breast tissue removed during prophylactic mastectomy or reduction mammoplasty.

The surgeons first performed a sham lumpectomy within the tissue. They then painted the specimen margins in the OR using a phospholuminescent paint obtained from an art supply store. The paint dries clear and colorless, but glows in different colors under black light. By using the paint, carefully selected so as not to interfere with pathology staining, the investigators were able to blind the pathologists to the actual orientation of the margins.

While the tissue was still in the OR, the surgeons then placed two or three orienting sutures in customary locations, plus a third, “mystery” suture at a location known only to the surgeon.

In the pathology lab, the assistant was asked to look at the sutures and outline in black ink the edges of the margins using the sutures for guidance.

The specimen was then examined under black light to determine the degree of discordance between surgeons and pathologist for identification of margins using the suture and painting methods (primary outcome), and to evaluate the discrepancy in the extent of margin surface areas as identified by the surgeons and the pathologists (secondary outcome).

“We asked breast surgeons ‘what would be a clinically significant discordance rate for you?’ and most of them said between 10% and 20%, so we looked for a 15% discordance rate as being clinically significant between the two margin assessment techniques,” Dr. Arnaout said.

They found that the overall discordance in the location of the mystery suture between surgeons and pathologists was similar whether the samples contained two or three location sutures, with discordance rates of 46% (34 of 75 samples) for two sutures, and 47% (41 of 88 samples) for three sutures.

For the secondary outcome of discordance in the extent of margins, they found that pathologists tended to estimate the mean surface of the anterior and posterior margins to be significantly larger than the surgeons did (P less than .01), while significantly underestimating the superior, inferior, and lateral margins (P less than .01 for superior and inferior, and P = .04 for lateral margins).

Examination under black light showed that often two or three additional margins would be included by the surgeon within what the pathologist had identified as the anterior margin.

“This has implications for the surgeon and for the patient,” Dr. Arnaout said. “For most of us that do lumpectomies that go from skin down to chest wall, if an anterior margin or posterior margin is positive, a lot of times we would fight not to go back because we would say there is no further room for re-excision.”

But if the tumor is within what is actually the superior margin but labeled by the pathologist as an anterior margin, the patient may miss an opportunity for successful re-excision, she explained.

The study was limited by the fact that the sham lumpectomy specimens did not contain skin or muscle, which would have allowed for more accurate margin orientation in an actual operative setting; by lack of compression of specimens with small nonpalpable lesions in containers, which further distorts specimens; and by the use of smaller lumpectomy specimens than normally obtained during cancer surgery, which could have resulted in overestimation of the discordance that might occur when larger specimens are taken, Dr. Arnaout said.

“The conclusion of our study is that specimen margin orientation really should be defined by the surgeon who knows the original shape and orientation of the tissue during surgery, and not to rely on the pathology to reorient based on some sutures placed in the centers of the specimens without defining the extent of the surface area of each of the margins,” she said.

The Canadian Cancer Society Research Institute and the Canadian Surgical Research Fund supported the study. Dr. Arnaout and coauthors reported no conflicts of interest.

BOSTON – The risk that a person living in the United States will become infected with HIV in his or her lifetime is declining compared with a decade ago, but the risk remains quite high among blacks and Hispanics/Latinos, investigators from the Centers for Disease Control and Prevention caution.

In fact, an estimated one in two black men who have sex with men (MSM) and one in four Hispanic/Latino MSM will be diagnosed with HIV within their lifetimes, reported CDC investigator Dr. Kristen Hess, at a media briefing and in an oral session at the 2016 Conference on Retroviruses and Opportunistic Infections.

“In the current analysis, we estimated that the overall lifetime risk is 1 in 99, which is reduced from 1 in 78 in the previous estimate [2004-2005]. However, there are vast disparities that still persist,” she said.

Estimates of lifetime risk are frequently used by epidemiologists to compare the burden of diseases such as cancer across populations, but are infrequently used for estimating lifetime risk of HIV infection, Dr. Hess said.

“The advantage to using lifetime risk is that it is more easily understood by the general population. Therefore, it could be a useful tool for clinicians, outreach workers, and policy makers,” she said in her podium presentation.

Previous estimates of lifetime HIV infection risk were based on data from 2004 and 2005, before data from all 50 states were available, leading the investigators to calculate new estimates based on more current information.

They drew on the National HIV Surveillance System for information about HIV diagnosis, mortality data from the National Center for Health Statistics, and U.S. Census data on population size by age, race/ethnicity, and state. The study covered the years 2009 through 2013.

The investigators used the number of HIV diagnoses and the number of non-HIV deaths to calculate the probability of a diagnosis of HIV at a given age and applied the probabilities to a hypothetical cohort to determine risk estimates.

They defined lifetime risk as” the cumulative probability of being diagnosed with HIV from birth.”

The lifetime risk of an HIV diagnosis for MSM varied widely by race/ethnicity. Overall, 1 in 64 men will be diagnosed with HIV during his lifetime, with the risk highest for black men at 1 in 20, followed by Hispanics at 1 in 48, native Hawaiian or other Pacific Islanders (NHOPI) at 1 in 82, American Indian/Alaskan Natives (AI/AN) at 1 in 129, whites at 1 in 132, and Asians with the lowest risk at 1 in 174.

For women the risks were considerably lower overall at 1 in 227. However, African American women had the same level of risk as Hispanic MSM (1 in 48). Risks for other racial/ethnic groups among women are: Hispanics, 1 in 227; NHOPI, 1 in 385; AI/AN, 1 in 399; whites, 1 in 880; and Asians, 1 in 883.

Lifetime risk from age 13 of an HIV diagnosis by risk group was highest among MSM, at 1 in 6, followed by female injectable drug users (1 in 23), male injectable drug users (1 in 36), heterosexual women (1 in 241), and heterosexual men (1 in 473).

Among MSM, the risk was highest for black men (1 in 2), followed by Hispanic/Latino (1 in 4), NHOPI (1 in 7), white (1 in 11), AI/AN (1 in 12) and Asians (1 in 14).

The overall lifetime risk of an HIV diagnosis among the U.S. population as a whole was 1 in 99. The area with the highest lifetime risk was Washington, D.C., with a risk of 1 in 13. Dr. Hess cautioned that the D.C. is a city, not a state, which could skew comparisons. The states with the highest lifetime HIV infection risk were Maryland, Georgia, and Florida, and in general, the highest lifetime risks were in the South.

The lowest overall risk was in North Dakota, at 1 in 670.

The investigators noted that their study was limited by its reliance on diagnosis rather than incidence data and may thus underestimate some risk categories because infection may occur several years before a diagnosis. Additionally, death certificates may be missing HIV information, she said.

“One of the goals of National HIV/AIDS strategy is to reduce disparities. Lifetime risk highlights work that still needs to be done and could be used to track progress toward this goal,” Dr. Hess said.

The study was supported by the CDC. Dr. Hess is a CDC employee.

BOSTON – The risk that a person living in the United States will become infected with HIV in his or her lifetime is declining compared with a decade ago, but the risk remains quite high among blacks and Hispanics/Latinos, investigators from the Centers for Disease Control and Prevention caution.

In fact, an estimated one in two black men who have sex with men (MSM) and one in four Hispanic/Latino MSM will be diagnosed with HIV within their lifetimes, reported CDC investigator Dr. Kristen Hess, at a media briefing and in an oral session at the 2016 Conference on Retroviruses and Opportunistic Infections.

“In the current analysis, we estimated that the overall lifetime risk is 1 in 99, which is reduced from 1 in 78 in the previous estimate [2004-2005]. However, there are vast disparities that still persist,” she said.

Estimates of lifetime risk are frequently used by epidemiologists to compare the burden of diseases such as cancer across populations, but are infrequently used for estimating lifetime risk of HIV infection, Dr. Hess said.

“The advantage to using lifetime risk is that it is more easily understood by the general population. Therefore, it could be a useful tool for clinicians, outreach workers, and policy makers,” she said in her podium presentation.

Previous estimates of lifetime HIV infection risk were based on data from 2004 and 2005, before data from all 50 states were available, leading the investigators to calculate new estimates based on more current information.

They drew on the National HIV Surveillance System for information about HIV diagnosis, mortality data from the National Center for Health Statistics, and U.S. Census data on population size by age, race/ethnicity, and state. The study covered the years 2009 through 2013.

The investigators used the number of HIV diagnoses and the number of non-HIV deaths to calculate the probability of a diagnosis of HIV at a given age and applied the probabilities to a hypothetical cohort to determine risk estimates.

They defined lifetime risk as” the cumulative probability of being diagnosed with HIV from birth.”

The lifetime risk of an HIV diagnosis for MSM varied widely by race/ethnicity. Overall, 1 in 64 men will be diagnosed with HIV during his lifetime, with the risk highest for black men at 1 in 20, followed by Hispanics at 1 in 48, native Hawaiian or other Pacific Islanders (NHOPI) at 1 in 82, American Indian/Alaskan Natives (AI/AN) at 1 in 129, whites at 1 in 132, and Asians with the lowest risk at 1 in 174.

For women the risks were considerably lower overall at 1 in 227. However, African American women had the same level of risk as Hispanic MSM (1 in 48). Risks for other racial/ethnic groups among women are: Hispanics, 1 in 227; NHOPI, 1 in 385; AI/AN, 1 in 399; whites, 1 in 880; and Asians, 1 in 883.

Lifetime risk from age 13 of an HIV diagnosis by risk group was highest among MSM, at 1 in 6, followed by female injectable drug users (1 in 23), male injectable drug users (1 in 36), heterosexual women (1 in 241), and heterosexual men (1 in 473).

Among MSM, the risk was highest for black men (1 in 2), followed by Hispanic/Latino (1 in 4), NHOPI (1 in 7), white (1 in 11), AI/AN (1 in 12) and Asians (1 in 14).

The overall lifetime risk of an HIV diagnosis among the U.S. population as a whole was 1 in 99. The area with the highest lifetime risk was Washington, D.C., with a risk of 1 in 13. Dr. Hess cautioned that the D.C. is a city, not a state, which could skew comparisons. The states with the highest lifetime HIV infection risk were Maryland, Georgia, and Florida, and in general, the highest lifetime risks were in the South.

The lowest overall risk was in North Dakota, at 1 in 670.

The investigators noted that their study was limited by its reliance on diagnosis rather than incidence data and may thus underestimate some risk categories because infection may occur several years before a diagnosis. Additionally, death certificates may be missing HIV information, she said.

“One of the goals of National HIV/AIDS strategy is to reduce disparities. Lifetime risk highlights work that still needs to be done and could be used to track progress toward this goal,” Dr. Hess said.

The study was supported by the CDC. Dr. Hess is a CDC employee.

BOSTON – The risk that a person living in the United States will become infected with HIV in his or her lifetime is declining compared with a decade ago, but the risk remains quite high among blacks and Hispanics/Latinos, investigators from the Centers for Disease Control and Prevention caution.

In fact, an estimated one in two black men who have sex with men (MSM) and one in four Hispanic/Latino MSM will be diagnosed with HIV within their lifetimes, reported CDC investigator Dr. Kristen Hess, at a media briefing and in an oral session at the 2016 Conference on Retroviruses and Opportunistic Infections.

“In the current analysis, we estimated that the overall lifetime risk is 1 in 99, which is reduced from 1 in 78 in the previous estimate [2004-2005]. However, there are vast disparities that still persist,” she said.

Estimates of lifetime risk are frequently used by epidemiologists to compare the burden of diseases such as cancer across populations, but are infrequently used for estimating lifetime risk of HIV infection, Dr. Hess said.

“The advantage to using lifetime risk is that it is more easily understood by the general population. Therefore, it could be a useful tool for clinicians, outreach workers, and policy makers,” she said in her podium presentation.

Previous estimates of lifetime HIV infection risk were based on data from 2004 and 2005, before data from all 50 states were available, leading the investigators to calculate new estimates based on more current information.

They drew on the National HIV Surveillance System for information about HIV diagnosis, mortality data from the National Center for Health Statistics, and U.S. Census data on population size by age, race/ethnicity, and state. The study covered the years 2009 through 2013.

The investigators used the number of HIV diagnoses and the number of non-HIV deaths to calculate the probability of a diagnosis of HIV at a given age and applied the probabilities to a hypothetical cohort to determine risk estimates.

They defined lifetime risk as” the cumulative probability of being diagnosed with HIV from birth.”

The lifetime risk of an HIV diagnosis for MSM varied widely by race/ethnicity. Overall, 1 in 64 men will be diagnosed with HIV during his lifetime, with the risk highest for black men at 1 in 20, followed by Hispanics at 1 in 48, native Hawaiian or other Pacific Islanders (NHOPI) at 1 in 82, American Indian/Alaskan Natives (AI/AN) at 1 in 129, whites at 1 in 132, and Asians with the lowest risk at 1 in 174.

For women the risks were considerably lower overall at 1 in 227. However, African American women had the same level of risk as Hispanic MSM (1 in 48). Risks for other racial/ethnic groups among women are: Hispanics, 1 in 227; NHOPI, 1 in 385; AI/AN, 1 in 399; whites, 1 in 880; and Asians, 1 in 883.

Lifetime risk from age 13 of an HIV diagnosis by risk group was highest among MSM, at 1 in 6, followed by female injectable drug users (1 in 23), male injectable drug users (1 in 36), heterosexual women (1 in 241), and heterosexual men (1 in 473).

Among MSM, the risk was highest for black men (1 in 2), followed by Hispanic/Latino (1 in 4), NHOPI (1 in 7), white (1 in 11), AI/AN (1 in 12) and Asians (1 in 14).

The overall lifetime risk of an HIV diagnosis among the U.S. population as a whole was 1 in 99. The area with the highest lifetime risk was Washington, D.C., with a risk of 1 in 13. Dr. Hess cautioned that the D.C. is a city, not a state, which could skew comparisons. The states with the highest lifetime HIV infection risk were Maryland, Georgia, and Florida, and in general, the highest lifetime risks were in the South.

The lowest overall risk was in North Dakota, at 1 in 670.

The investigators noted that their study was limited by its reliance on diagnosis rather than incidence data and may thus underestimate some risk categories because infection may occur several years before a diagnosis. Additionally, death certificates may be missing HIV information, she said.

“One of the goals of National HIV/AIDS strategy is to reduce disparities. Lifetime risk highlights work that still needs to be done and could be used to track progress toward this goal,” Dr. Hess said.

The study was supported by the CDC. Dr. Hess is a CDC employee.