Breast Cancer

Hormonal contraception (HC) has long been utilized safely in this country for a variety of indications, including pregnancy prevention, timing pregnancy appropriately, management of symptoms (dysmenorrhea, irregular menstrual cycles, heavy menstrual bleeding), and to prevent serious diseases (such as ovarian cancer, uterine cancer, osteoporosis in women with premature menopause). Like most prescription medications, there are potential adverse effects. With HC, side effects such as venous thromboembolism, a slight increase in liver cancer, and a possible increase in breast cancer risk have long been recognized.

Danish study compared HC use with breast cancer risk
In the December 7, 2017, issue of New England Journal of Medicine,¹ investigators in Denmark published a study of women using HC (oral, transdermal, intravaginal routes, and levonorgestrel intrauterine device [LNG-IUD]) and breast cancer risk compared with women who did not use HC. This retrospective observational country-wide study was very large (1.8 million women followed over an average of 10.9 years), which allowed for the detection of even small changes in breast cancer risk.

Putting results in perspective
It is important to point out that this is an observational study, and small effect sizes (1 in 7,600) should be interpreted with caution. Observational studies can introduce many different types of bias (prescribing bias, confounding bias, etc). Of note, while the LNG-IUD was associated with a small increased risk of breast cancer (relative risk [RR], 1.21; 95% confidence interval [CI], 1.11-1.33]), the higher dose continuous progestin administration (medroxyprogesterone) was not (RR, 0.95; 95% CI, 0.40-2.29).¹

Nonetheless, providing patients with a balanced summary of this new study along with other published and reliable information about HC that conveys both benefits and risks is important to assure that each woman makes a decision regarding HC that achieves her health and life goals. See "Counseling talking points" below.

Bottom line

This recent study demonstrated that in Denmark, a woman's risk of developing breast cancer is very slightly elevated on HC¹:

• 1 in 7,690 users overall
• 1 in 50,000 women older than age 35 years.

By comparison, the risk of maternal mortality in the United States is 1 in 3,788.² A substantial reduction in HC use would likely increase unintended and mistimed pregnancies with a potential substantial negative impact on quality of life and personal/societal cost.

The best available data indicate that a woman's risk of developing any cancer is slightly less on HC than not on HC, even with this incremental breast cancer increase.^3,4

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

Hormonal contraception (HC) has long been utilized safely in this country for a variety of indications, including pregnancy prevention, timing pregnancy appropriately, management of symptoms (dysmenorrhea, irregular menstrual cycles, heavy menstrual bleeding), and to prevent serious diseases (such as ovarian cancer, uterine cancer, osteoporosis in women with premature menopause). Like most prescription medications, there are potential adverse effects. With HC, side effects such as venous thromboembolism, a slight increase in liver cancer, and a possible increase in breast cancer risk have long been recognized.

Danish study compared HC use with breast cancer risk
In the December 7, 2017, issue of New England Journal of Medicine,¹ investigators in Denmark published a study of women using HC (oral, transdermal, intravaginal routes, and levonorgestrel intrauterine device [LNG-IUD]) and breast cancer risk compared with women who did not use HC. This retrospective observational country-wide study was very large (1.8 million women followed over an average of 10.9 years), which allowed for the detection of even small changes in breast cancer risk.

Putting results in perspective
It is important to point out that this is an observational study, and small effect sizes (1 in 7,600) should be interpreted with caution. Observational studies can introduce many different types of bias (prescribing bias, confounding bias, etc). Of note, while the LNG-IUD was associated with a small increased risk of breast cancer (relative risk [RR], 1.21; 95% confidence interval [CI], 1.11-1.33]), the higher dose continuous progestin administration (medroxyprogesterone) was not (RR, 0.95; 95% CI, 0.40-2.29).¹

Nonetheless, providing patients with a balanced summary of this new study along with other published and reliable information about HC that conveys both benefits and risks is important to assure that each woman makes a decision regarding HC that achieves her health and life goals. See "Counseling talking points" below.

Bottom line

This recent study demonstrated that in Denmark, a woman's risk of developing breast cancer is very slightly elevated on HC¹:

• 1 in 7,690 users overall
• 1 in 50,000 women older than age 35 years.

By comparison, the risk of maternal mortality in the United States is 1 in 3,788.² A substantial reduction in HC use would likely increase unintended and mistimed pregnancies with a potential substantial negative impact on quality of life and personal/societal cost.

The best available data indicate that a woman's risk of developing any cancer is slightly less on HC than not on HC, even with this incremental breast cancer increase.^3,4

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

Hormonal contraception (HC) has long been utilized safely in this country for a variety of indications, including pregnancy prevention, timing pregnancy appropriately, management of symptoms (dysmenorrhea, irregular menstrual cycles, heavy menstrual bleeding), and to prevent serious diseases (such as ovarian cancer, uterine cancer, osteoporosis in women with premature menopause). Like most prescription medications, there are potential adverse effects. With HC, side effects such as venous thromboembolism, a slight increase in liver cancer, and a possible increase in breast cancer risk have long been recognized.

Danish study compared HC use with breast cancer risk
In the December 7, 2017, issue of New England Journal of Medicine,¹ investigators in Denmark published a study of women using HC (oral, transdermal, intravaginal routes, and levonorgestrel intrauterine device [LNG-IUD]) and breast cancer risk compared with women who did not use HC. This retrospective observational country-wide study was very large (1.8 million women followed over an average of 10.9 years), which allowed for the detection of even small changes in breast cancer risk.

Putting results in perspective
It is important to point out that this is an observational study, and small effect sizes (1 in 7,600) should be interpreted with caution. Observational studies can introduce many different types of bias (prescribing bias, confounding bias, etc). Of note, while the LNG-IUD was associated with a small increased risk of breast cancer (relative risk [RR], 1.21; 95% confidence interval [CI], 1.11-1.33]), the higher dose continuous progestin administration (medroxyprogesterone) was not (RR, 0.95; 95% CI, 0.40-2.29).¹

Nonetheless, providing patients with a balanced summary of this new study along with other published and reliable information about HC that conveys both benefits and risks is important to assure that each woman makes a decision regarding HC that achieves her health and life goals. See "Counseling talking points" below.

Bottom line

This recent study demonstrated that in Denmark, a woman's risk of developing breast cancer is very slightly elevated on HC¹:

• 1 in 7,690 users overall
• 1 in 50,000 women older than age 35 years.

By comparison, the risk of maternal mortality in the United States is 1 in 3,788.² A substantial reduction in HC use would likely increase unintended and mistimed pregnancies with a potential substantial negative impact on quality of life and personal/societal cost.

The best available data indicate that a woman's risk of developing any cancer is slightly less on HC than not on HC, even with this incremental breast cancer increase.^3,4

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

SAN FRANCISCO – Pembrolizumab immunotherapy with multi-site stereotactic body radiotherapy (SBRT) appears to be a safe and effective treatment in patients with advanced solid tumors, according to findings from a phase 1 study.

Of 79 patients with metastatic solid tumors who progressed on standard treatment and who were enrolled in the study, 68 underwent multi-site SBRT, received at least one cycle of pembrolizumab (Keytruda), and had imaging follow-up. The overall objective response rate in those 68 patients was 13.2%, Jeffrey Lemons, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

[email protected]

SOURCE: Lemons J et al., ASCO-SITC abstract #20.

SAN FRANCISCO – Pembrolizumab immunotherapy with multi-site stereotactic body radiotherapy (SBRT) appears to be a safe and effective treatment in patients with advanced solid tumors, according to findings from a phase 1 study.

Of 79 patients with metastatic solid tumors who progressed on standard treatment and who were enrolled in the study, 68 underwent multi-site SBRT, received at least one cycle of pembrolizumab (Keytruda), and had imaging follow-up. The overall objective response rate in those 68 patients was 13.2%, Jeffrey Lemons, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

[email protected]

SOURCE: Lemons J et al., ASCO-SITC abstract #20.

SAN FRANCISCO – Pembrolizumab immunotherapy with multi-site stereotactic body radiotherapy (SBRT) appears to be a safe and effective treatment in patients with advanced solid tumors, according to findings from a phase 1 study.

Of 79 patients with metastatic solid tumors who progressed on standard treatment and who were enrolled in the study, 68 underwent multi-site SBRT, received at least one cycle of pembrolizumab (Keytruda), and had imaging follow-up. The overall objective response rate in those 68 patients was 13.2%, Jeffrey Lemons, MD, reported at the ASCO-SITC Clinical Immuno-Oncology Symposium.

[email protected]

SOURCE: Lemons J et al., ASCO-SITC abstract #20.

More women received recommended mammograms after cost sharing for the service was eliminated under the Affordable Care Act, a study shows.

In health plans that eliminated cost sharing, such as copays, deductibles, or other out-of-pocket costs, the rate of biennial screening mammography increased from 60% in the 2-year period before the cost-sharing elimination to 65% in the 2-year period following the new regulation, according to an analysis in the New England Journal of Medicine.

John Foxx/Thinkstock

The findings extend that of past studies that show older women who need mammograms are sensitive to out-of-pocket costs and the presence of supplemental coverage, the authors conclude. If the cost-sharing provisions of the ACA are rescinded, the results also “raise concern that fewer older women will receive recommended breast-cancer screening.”

However, the authors also note that since mammogram rates in the health plans that eliminated cost sharing remained below those in plans with full coverage and less than three-quarters of women in control plans received biennial breast cancer screenings, that “the removal of out-of-pocket payments alone may not raise screening rates to desired levels.”

[email protected]

SOURCE: Trivedi A et al. N Engl J Med. 2018 Jan 18;378:262-9.
 

More women received recommended mammograms after cost sharing for the service was eliminated under the Affordable Care Act, a study shows.

In health plans that eliminated cost sharing, such as copays, deductibles, or other out-of-pocket costs, the rate of biennial screening mammography increased from 60% in the 2-year period before the cost-sharing elimination to 65% in the 2-year period following the new regulation, according to an analysis in the New England Journal of Medicine.

John Foxx/Thinkstock

The findings extend that of past studies that show older women who need mammograms are sensitive to out-of-pocket costs and the presence of supplemental coverage, the authors conclude. If the cost-sharing provisions of the ACA are rescinded, the results also “raise concern that fewer older women will receive recommended breast-cancer screening.”

However, the authors also note that since mammogram rates in the health plans that eliminated cost sharing remained below those in plans with full coverage and less than three-quarters of women in control plans received biennial breast cancer screenings, that “the removal of out-of-pocket payments alone may not raise screening rates to desired levels.”

[email protected]

SOURCE: Trivedi A et al. N Engl J Med. 2018 Jan 18;378:262-9.
 

More women received recommended mammograms after cost sharing for the service was eliminated under the Affordable Care Act, a study shows.

In health plans that eliminated cost sharing, such as copays, deductibles, or other out-of-pocket costs, the rate of biennial screening mammography increased from 60% in the 2-year period before the cost-sharing elimination to 65% in the 2-year period following the new regulation, according to an analysis in the New England Journal of Medicine.

John Foxx/Thinkstock

The findings extend that of past studies that show older women who need mammograms are sensitive to out-of-pocket costs and the presence of supplemental coverage, the authors conclude. If the cost-sharing provisions of the ACA are rescinded, the results also “raise concern that fewer older women will receive recommended breast-cancer screening.”

However, the authors also note that since mammogram rates in the health plans that eliminated cost sharing remained below those in plans with full coverage and less than three-quarters of women in control plans received biennial breast cancer screenings, that “the removal of out-of-pocket payments alone may not raise screening rates to desired levels.”

[email protected]

SOURCE: Trivedi A et al. N Engl J Med. 2018 Jan 18;378:262-9.
 

Imagine a single blood test that would cost less than $500 and could screen for at least eight cancer types.

It’s early days for the technology, called CancerSEEK, but the test had a sensitivity of 69%-98%, depending on the cancer type, and a specificity of 99% in a cohort of 1,005 patients with stage I-III cancers and 850 healthy controls, wrote Joshua D. Cohen of the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins University, Baltimore, and his colleagues. The report was published in Science.

SilverV/Thinkstock

CancerSEEK tests for mutations in 2,001 genomic positions and eight proteins. The researchers examined a 61-amplicon panel with each amplicon analyzing an average of 33 base pairs within a gene. They theorized the test could detect between 41% and 95% of the cancers in the Catalog of Somatic Mutations in Cancer dataset. They next used multiplex-PCR techniques to minimize errors associated with large sequencing and identified protein biomarkers for early stage cancers that may not release detectable ctDNA.

The researchers used the technology to examine blood samples from 1,005 patients with stage I (20%), stage II (49%), or stage III (31%) cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast prior to undergoing neoadjuvant chemotherapy. Participants had a median age of 64 years (range of 22-93 years). The healthy controls did not have a history of cancer, chronic kidney disease, autoimmune disease, or high-grade dysplasia.

SOURCE: Cohen JD et al., Science 2018 Jan 18. doi: 10.1126/science.aar3247.

Imagine a single blood test that would cost less than $500 and could screen for at least eight cancer types.

It’s early days for the technology, called CancerSEEK, but the test had a sensitivity of 69%-98%, depending on the cancer type, and a specificity of 99% in a cohort of 1,005 patients with stage I-III cancers and 850 healthy controls, wrote Joshua D. Cohen of the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins University, Baltimore, and his colleagues. The report was published in Science.

SilverV/Thinkstock

CancerSEEK tests for mutations in 2,001 genomic positions and eight proteins. The researchers examined a 61-amplicon panel with each amplicon analyzing an average of 33 base pairs within a gene. They theorized the test could detect between 41% and 95% of the cancers in the Catalog of Somatic Mutations in Cancer dataset. They next used multiplex-PCR techniques to minimize errors associated with large sequencing and identified protein biomarkers for early stage cancers that may not release detectable ctDNA.

The researchers used the technology to examine blood samples from 1,005 patients with stage I (20%), stage II (49%), or stage III (31%) cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast prior to undergoing neoadjuvant chemotherapy. Participants had a median age of 64 years (range of 22-93 years). The healthy controls did not have a history of cancer, chronic kidney disease, autoimmune disease, or high-grade dysplasia.

SOURCE: Cohen JD et al., Science 2018 Jan 18. doi: 10.1126/science.aar3247.

Imagine a single blood test that would cost less than $500 and could screen for at least eight cancer types.

It’s early days for the technology, called CancerSEEK, but the test had a sensitivity of 69%-98%, depending on the cancer type, and a specificity of 99% in a cohort of 1,005 patients with stage I-III cancers and 850 healthy controls, wrote Joshua D. Cohen of the Ludwig Center for Cancer Genetics and Therapeutics at Johns Hopkins University, Baltimore, and his colleagues. The report was published in Science.

SilverV/Thinkstock

CancerSEEK tests for mutations in 2,001 genomic positions and eight proteins. The researchers examined a 61-amplicon panel with each amplicon analyzing an average of 33 base pairs within a gene. They theorized the test could detect between 41% and 95% of the cancers in the Catalog of Somatic Mutations in Cancer dataset. They next used multiplex-PCR techniques to minimize errors associated with large sequencing and identified protein biomarkers for early stage cancers that may not release detectable ctDNA.

The researchers used the technology to examine blood samples from 1,005 patients with stage I (20%), stage II (49%), or stage III (31%) cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast prior to undergoing neoadjuvant chemotherapy. Participants had a median age of 64 years (range of 22-93 years). The healthy controls did not have a history of cancer, chronic kidney disease, autoimmune disease, or high-grade dysplasia.

SOURCE: Cohen JD et al., Science 2018 Jan 18. doi: 10.1126/science.aar3247.

For women with young-onset breast cancer, presence of a BRCA mutation did not significantly impact survival, according to results of the Prospective Outcomes in Sporadic versus Hereditary breast cancer (POSH) study.

BRCA-positive and BRCA-negative women had similar overall survival at 2 years, 5 years, and 10 years after diagnosis, according to lead author Ellen R. Copson, MD, a senior lecturer in medical oncology in the cancer sciences division, University of Southampton (England) and her study coauthors.

SOURCE: Copson et al. Lancet Oncol. 2018 Jan 11 doi: 10.1016/S1470-2045(17)30891-4.

For women with young-onset breast cancer, presence of a BRCA mutation did not significantly impact survival, according to results of the Prospective Outcomes in Sporadic versus Hereditary breast cancer (POSH) study.

BRCA-positive and BRCA-negative women had similar overall survival at 2 years, 5 years, and 10 years after diagnosis, according to lead author Ellen R. Copson, MD, a senior lecturer in medical oncology in the cancer sciences division, University of Southampton (England) and her study coauthors.

SOURCE: Copson et al. Lancet Oncol. 2018 Jan 11 doi: 10.1016/S1470-2045(17)30891-4.

For women with young-onset breast cancer, presence of a BRCA mutation did not significantly impact survival, according to results of the Prospective Outcomes in Sporadic versus Hereditary breast cancer (POSH) study.

BRCA-positive and BRCA-negative women had similar overall survival at 2 years, 5 years, and 10 years after diagnosis, according to lead author Ellen R. Copson, MD, a senior lecturer in medical oncology in the cancer sciences division, University of Southampton (England) and her study coauthors.

SOURCE: Copson et al. Lancet Oncol. 2018 Jan 11 doi: 10.1016/S1470-2045(17)30891-4.

The Food and Drug Administration has approved the PARP inhibitor olaparib for the treatment of patients with germline BRCA-positive, HER2-negative metastatic breast cancer who have previously received chemotherapy.

This is the first PARP inhibitor approved to treat breast cancer and the first approval for treatment of patients with metastatic breast cancer who have a BRCA gene mutation, the FDA said in a press statement.

The FDA also expanded approval of the companion diagnostic, BRACAnalysis CDx, to include the detection of BRCA mutations in blood samples from patients with breast cancer.

A capsule form of olaparib (Lynparza) was first approved in 2014 for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. In August 2017, the FDA granted regular approval to olaparib tablets for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. Olaparib tablets and capsules are not interchangeable. Olaparib capsules are being phased out of the U.S. market and will be available only through the Lynparza Specialty Pharmacy Network, the FDA said.

Approval for the treatment of breast cancer was based on a 2.8 month improvement in progression-free survival with olaparib vs standard chemotherapy in the phase 3 OlympiAD trial of 302 previously treated patients with BRCA-positive, HER2-negative breast cancer. Results of the trial were presented at ASCO 2017 and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2017 Jun 4. doi: 10.1056/NEJMoa1706450).

Common side effects of olaparib include anemia, neutropenia, leukopenia, nausea, fatigue, vomiting, nasopharyngitis, respiratory tract infection, influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and stomatitis.

Severe side effects include development of myelodysplastic syndrome/acute myeloid leukemia and pneumonitis. Women should be advised of the potential risk to the fetus and to use effective contraception, the FDA said.

The FDA granted the approval of olaparib to AstraZeneca Pharmaceuticals LP and the approval of the BRACAnalysis CDx to Myriad Genetic Laboratories, Inc.

[email protected]

The Food and Drug Administration has approved the PARP inhibitor olaparib for the treatment of patients with germline BRCA-positive, HER2-negative metastatic breast cancer who have previously received chemotherapy.

This is the first PARP inhibitor approved to treat breast cancer and the first approval for treatment of patients with metastatic breast cancer who have a BRCA gene mutation, the FDA said in a press statement.

The FDA also expanded approval of the companion diagnostic, BRACAnalysis CDx, to include the detection of BRCA mutations in blood samples from patients with breast cancer.

A capsule form of olaparib (Lynparza) was first approved in 2014 for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. In August 2017, the FDA granted regular approval to olaparib tablets for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. Olaparib tablets and capsules are not interchangeable. Olaparib capsules are being phased out of the U.S. market and will be available only through the Lynparza Specialty Pharmacy Network, the FDA said.

Approval for the treatment of breast cancer was based on a 2.8 month improvement in progression-free survival with olaparib vs standard chemotherapy in the phase 3 OlympiAD trial of 302 previously treated patients with BRCA-positive, HER2-negative breast cancer. Results of the trial were presented at ASCO 2017 and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2017 Jun 4. doi: 10.1056/NEJMoa1706450).

Common side effects of olaparib include anemia, neutropenia, leukopenia, nausea, fatigue, vomiting, nasopharyngitis, respiratory tract infection, influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and stomatitis.

Severe side effects include development of myelodysplastic syndrome/acute myeloid leukemia and pneumonitis. Women should be advised of the potential risk to the fetus and to use effective contraception, the FDA said.

The FDA granted the approval of olaparib to AstraZeneca Pharmaceuticals LP and the approval of the BRACAnalysis CDx to Myriad Genetic Laboratories, Inc.

[email protected]

The Food and Drug Administration has approved the PARP inhibitor olaparib for the treatment of patients with germline BRCA-positive, HER2-negative metastatic breast cancer who have previously received chemotherapy.

This is the first PARP inhibitor approved to treat breast cancer and the first approval for treatment of patients with metastatic breast cancer who have a BRCA gene mutation, the FDA said in a press statement.

The FDA also expanded approval of the companion diagnostic, BRACAnalysis CDx, to include the detection of BRCA mutations in blood samples from patients with breast cancer.

A capsule form of olaparib (Lynparza) was first approved in 2014 for the treatment of patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. In August 2017, the FDA granted regular approval to olaparib tablets for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy. Olaparib tablets and capsules are not interchangeable. Olaparib capsules are being phased out of the U.S. market and will be available only through the Lynparza Specialty Pharmacy Network, the FDA said.

Approval for the treatment of breast cancer was based on a 2.8 month improvement in progression-free survival with olaparib vs standard chemotherapy in the phase 3 OlympiAD trial of 302 previously treated patients with BRCA-positive, HER2-negative breast cancer. Results of the trial were presented at ASCO 2017 and simultaneously published in the New England Journal of Medicine (N Engl J Med. 2017 Jun 4. doi: 10.1056/NEJMoa1706450).

Common side effects of olaparib include anemia, neutropenia, leukopenia, nausea, fatigue, vomiting, nasopharyngitis, respiratory tract infection, influenza, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and stomatitis.

Severe side effects include development of myelodysplastic syndrome/acute myeloid leukemia and pneumonitis. Women should be advised of the potential risk to the fetus and to use effective contraception, the FDA said.

The FDA granted the approval of olaparib to AstraZeneca Pharmaceuticals LP and the approval of the BRACAnalysis CDx to Myriad Genetic Laboratories, Inc.

[email protected]

Chronic pain after breast reconstruction surgery is a common complaint, but its considerable incidence means that the operation itself may not be to blame, according to a study of almost 2,000 women recruited from the Mastectomy Reconstructive Outcomes Consortium (MROC).

In the February issue of The Breast, investigators from the University of Michigan, Ann Arbor and Memorial Sloan Kettering Cancer Center, New York, wrote that almost half of the study subjects had some level of pain before their operations and that, at 2 years afterward, their pain had increased but not in a clinically meaningful way. This finding is consistent with earlier research, which investigators noted found that “one-fourth to one-half of women who undergo postmastectomy report persistent pain months and years after surgery.”

“Average clinical pain severity was strikingly similar for preoperative and postoperative assessments,” said lead author Randy S. Roth, PhD, of the University of Michigan, and his coauthors. “Postoperative levels of pain, acute postoperative pain and (marginally) level of depression held consistent relationship at 2-year follow-up with all outcome measures.”

The prospective, multicenter cohort study of 1,996 women was undertaken over 5 years. Most patients had immediate (92.7%) and bilateral (53.8%) reconstruction; 47.6% had sentinel lymph node biopsy and 25.9% had axillary lymph node dissection. Most had no adjuvant therapy: 70.3% received no radiation and 52.7% no chemotherapy.

At 2 years, the Numerical Pain Rating Scale (NPRS) measured what Dr. Roth and his coauthors called a “significant increase in pain intensity” – from an average rating of 1.1 to 1.2, an increase of 9%. However, the absolute change and standard deviation (1.7 for both intervals) “suggest that this was not a clinically meaningful change.” The researchers also recorded more complaints of bodily discomfort after 2 years, “but the statistical parameters again indicate little clinically meaningful differences from preoperative status.”

Pain ratings measured with the McGill Pain Questionnaire showed a significant decrease in the MPQ affective pain rating, from 1.6 preoperatively to 0.8 at 2 years (P less than .001), and virtually no change in the MPQ sensory rating, from 3.2 to 3.1.

The researchers drew some conclusions about demographic profiles and pain after breast reconstruction. Older age was associated with more severe pain on NPRS, and higher body mass index was linked with chronic postsurgical pain for the MPQ sensory rating, NPRS score, and body discomfort scores.

Treatment characteristics associated with chronic postsurgical pain (CPSP) include radiation therapy during or after reconstruction and chemotherapy before reconstruction. Chemotherapy during or after reconstruction was associated with higher MPQ affective rating scores at 2 years (P = .011), as was chemotherapy both before and during or after reconstruction (P = .001). The latter also was linked to higher NPRS scores (P = .0015).

The type of surgery also was a factor in CPSP, the researchers wrote. Both MPQ sensory and affective ratings were higher in women who had free transverse flap surgery, or deep or superficial inferior epigastric perforator surgery than in women who had tissue expander/implant reconstruction. Lymph node status and timing of surgery had no impact on chronic pain.

One noteworthy finding, Dr. Roth and his coauthors wrote, is that “careful examination of our data suggests that CPSP following breast reconstruction may be of less clinical concern as a direct consequence of breast reconstruction than suggested by previous investigations of major surgery, including mastectomy and breast reconstruction.” Future studies of chronic postsurgical pain in breast reconstruction “will require greater methodological rigor” to reach more sound conclusions to use in patient counseling.

Dr. Roth and his coauthors had no financial relationships to disclose.

SOURCE: Roth RS et al. Breast 2018;37:119-25.

Chronic pain after breast reconstruction surgery is a common complaint, but its considerable incidence means that the operation itself may not be to blame, according to a study of almost 2,000 women recruited from the Mastectomy Reconstructive Outcomes Consortium (MROC).

In the February issue of The Breast, investigators from the University of Michigan, Ann Arbor and Memorial Sloan Kettering Cancer Center, New York, wrote that almost half of the study subjects had some level of pain before their operations and that, at 2 years afterward, their pain had increased but not in a clinically meaningful way. This finding is consistent with earlier research, which investigators noted found that “one-fourth to one-half of women who undergo postmastectomy report persistent pain months and years after surgery.”

“Average clinical pain severity was strikingly similar for preoperative and postoperative assessments,” said lead author Randy S. Roth, PhD, of the University of Michigan, and his coauthors. “Postoperative levels of pain, acute postoperative pain and (marginally) level of depression held consistent relationship at 2-year follow-up with all outcome measures.”

The prospective, multicenter cohort study of 1,996 women was undertaken over 5 years. Most patients had immediate (92.7%) and bilateral (53.8%) reconstruction; 47.6% had sentinel lymph node biopsy and 25.9% had axillary lymph node dissection. Most had no adjuvant therapy: 70.3% received no radiation and 52.7% no chemotherapy.

At 2 years, the Numerical Pain Rating Scale (NPRS) measured what Dr. Roth and his coauthors called a “significant increase in pain intensity” – from an average rating of 1.1 to 1.2, an increase of 9%. However, the absolute change and standard deviation (1.7 for both intervals) “suggest that this was not a clinically meaningful change.” The researchers also recorded more complaints of bodily discomfort after 2 years, “but the statistical parameters again indicate little clinically meaningful differences from preoperative status.”

Pain ratings measured with the McGill Pain Questionnaire showed a significant decrease in the MPQ affective pain rating, from 1.6 preoperatively to 0.8 at 2 years (P less than .001), and virtually no change in the MPQ sensory rating, from 3.2 to 3.1.

The researchers drew some conclusions about demographic profiles and pain after breast reconstruction. Older age was associated with more severe pain on NPRS, and higher body mass index was linked with chronic postsurgical pain for the MPQ sensory rating, NPRS score, and body discomfort scores.

Treatment characteristics associated with chronic postsurgical pain (CPSP) include radiation therapy during or after reconstruction and chemotherapy before reconstruction. Chemotherapy during or after reconstruction was associated with higher MPQ affective rating scores at 2 years (P = .011), as was chemotherapy both before and during or after reconstruction (P = .001). The latter also was linked to higher NPRS scores (P = .0015).

The type of surgery also was a factor in CPSP, the researchers wrote. Both MPQ sensory and affective ratings were higher in women who had free transverse flap surgery, or deep or superficial inferior epigastric perforator surgery than in women who had tissue expander/implant reconstruction. Lymph node status and timing of surgery had no impact on chronic pain.

One noteworthy finding, Dr. Roth and his coauthors wrote, is that “careful examination of our data suggests that CPSP following breast reconstruction may be of less clinical concern as a direct consequence of breast reconstruction than suggested by previous investigations of major surgery, including mastectomy and breast reconstruction.” Future studies of chronic postsurgical pain in breast reconstruction “will require greater methodological rigor” to reach more sound conclusions to use in patient counseling.

Dr. Roth and his coauthors had no financial relationships to disclose.

SOURCE: Roth RS et al. Breast 2018;37:119-25.

Chronic pain after breast reconstruction surgery is a common complaint, but its considerable incidence means that the operation itself may not be to blame, according to a study of almost 2,000 women recruited from the Mastectomy Reconstructive Outcomes Consortium (MROC).

In the February issue of The Breast, investigators from the University of Michigan, Ann Arbor and Memorial Sloan Kettering Cancer Center, New York, wrote that almost half of the study subjects had some level of pain before their operations and that, at 2 years afterward, their pain had increased but not in a clinically meaningful way. This finding is consistent with earlier research, which investigators noted found that “one-fourth to one-half of women who undergo postmastectomy report persistent pain months and years after surgery.”

“Average clinical pain severity was strikingly similar for preoperative and postoperative assessments,” said lead author Randy S. Roth, PhD, of the University of Michigan, and his coauthors. “Postoperative levels of pain, acute postoperative pain and (marginally) level of depression held consistent relationship at 2-year follow-up with all outcome measures.”

The prospective, multicenter cohort study of 1,996 women was undertaken over 5 years. Most patients had immediate (92.7%) and bilateral (53.8%) reconstruction; 47.6% had sentinel lymph node biopsy and 25.9% had axillary lymph node dissection. Most had no adjuvant therapy: 70.3% received no radiation and 52.7% no chemotherapy.

At 2 years, the Numerical Pain Rating Scale (NPRS) measured what Dr. Roth and his coauthors called a “significant increase in pain intensity” – from an average rating of 1.1 to 1.2, an increase of 9%. However, the absolute change and standard deviation (1.7 for both intervals) “suggest that this was not a clinically meaningful change.” The researchers also recorded more complaints of bodily discomfort after 2 years, “but the statistical parameters again indicate little clinically meaningful differences from preoperative status.”

Pain ratings measured with the McGill Pain Questionnaire showed a significant decrease in the MPQ affective pain rating, from 1.6 preoperatively to 0.8 at 2 years (P less than .001), and virtually no change in the MPQ sensory rating, from 3.2 to 3.1.

The researchers drew some conclusions about demographic profiles and pain after breast reconstruction. Older age was associated with more severe pain on NPRS, and higher body mass index was linked with chronic postsurgical pain for the MPQ sensory rating, NPRS score, and body discomfort scores.

Treatment characteristics associated with chronic postsurgical pain (CPSP) include radiation therapy during or after reconstruction and chemotherapy before reconstruction. Chemotherapy during or after reconstruction was associated with higher MPQ affective rating scores at 2 years (P = .011), as was chemotherapy both before and during or after reconstruction (P = .001). The latter also was linked to higher NPRS scores (P = .0015).

The type of surgery also was a factor in CPSP, the researchers wrote. Both MPQ sensory and affective ratings were higher in women who had free transverse flap surgery, or deep or superficial inferior epigastric perforator surgery than in women who had tissue expander/implant reconstruction. Lymph node status and timing of surgery had no impact on chronic pain.

One noteworthy finding, Dr. Roth and his coauthors wrote, is that “careful examination of our data suggests that CPSP following breast reconstruction may be of less clinical concern as a direct consequence of breast reconstruction than suggested by previous investigations of major surgery, including mastectomy and breast reconstruction.” Future studies of chronic postsurgical pain in breast reconstruction “will require greater methodological rigor” to reach more sound conclusions to use in patient counseling.

Dr. Roth and his coauthors had no financial relationships to disclose.

SOURCE: Roth RS et al. Breast 2018;37:119-25.

Decreases in breast cancer mortality between 2000 and 2012 were associated with advances in screening and adjuvant therapy but varied by breast cancer molecular subtype, according to a simulation modeling study.

The estimated rate of reduction in overall breast cancer mortality in 2000 was 37% from an estimated baseline rate of 64 deaths per 100,000 women, with 44% and 56% of that associated with screening and treatment, respectively. In 2012 the estimated reduction was 49% from an estimated baseline rate of 63 per 100,000 women, with 37% and 63% associated with screening and treatment, respectively (estimated 12% difference in 2012 vs. 2000), Sylvia K. Plevritis, PhD, of Stanford (Calif.) University and her colleagues reported in JAMA.

Screening and treatment were estimated to contribute to the reductions at varying rates. For example, the relative contributions of screening vs. treatment were 36% vs. 64% for ER+/ERBB2– disease; 31% vs. 69% for ER+/ERBB2+ disease; 40% vs. 60% for ER–/ERBB2+ disease; and 48% vs. 52% for ER–/ERBB2– disease.

The model-based analysis provides clinically relevant insights about the contributions of screening and treatment to reductions in breast cancer mortality by molecular subtype, showing a greater relative contribution of treatment in 2012 overall and for all subtypes except ER–/ERBB2– disease, the authors said.

“Because ER+ cancers are the most prevalent and this group is expected to increase with time, additional advances for this subtype could have the largest effect on reducing the overall population burden of breast cancer,” they noted.

This study was supported by grants from the National Cancer Institute and the American Cancer Society. Dr. Plevritis reported consulting for GRAIL.

[email protected]

SOURCE: Plevritis S et al. JAMA. 2018 Jan 9;319(2):154-64. doi: 10.1001/jama.2017.19130.

.
 

Decreases in breast cancer mortality between 2000 and 2012 were associated with advances in screening and adjuvant therapy but varied by breast cancer molecular subtype, according to a simulation modeling study.

The estimated rate of reduction in overall breast cancer mortality in 2000 was 37% from an estimated baseline rate of 64 deaths per 100,000 women, with 44% and 56% of that associated with screening and treatment, respectively. In 2012 the estimated reduction was 49% from an estimated baseline rate of 63 per 100,000 women, with 37% and 63% associated with screening and treatment, respectively (estimated 12% difference in 2012 vs. 2000), Sylvia K. Plevritis, PhD, of Stanford (Calif.) University and her colleagues reported in JAMA.

Screening and treatment were estimated to contribute to the reductions at varying rates. For example, the relative contributions of screening vs. treatment were 36% vs. 64% for ER+/ERBB2– disease; 31% vs. 69% for ER+/ERBB2+ disease; 40% vs. 60% for ER–/ERBB2+ disease; and 48% vs. 52% for ER–/ERBB2– disease.

The model-based analysis provides clinically relevant insights about the contributions of screening and treatment to reductions in breast cancer mortality by molecular subtype, showing a greater relative contribution of treatment in 2012 overall and for all subtypes except ER–/ERBB2– disease, the authors said.

“Because ER+ cancers are the most prevalent and this group is expected to increase with time, additional advances for this subtype could have the largest effect on reducing the overall population burden of breast cancer,” they noted.

This study was supported by grants from the National Cancer Institute and the American Cancer Society. Dr. Plevritis reported consulting for GRAIL.

[email protected]

SOURCE: Plevritis S et al. JAMA. 2018 Jan 9;319(2):154-64. doi: 10.1001/jama.2017.19130.

.
 

Decreases in breast cancer mortality between 2000 and 2012 were associated with advances in screening and adjuvant therapy but varied by breast cancer molecular subtype, according to a simulation modeling study.

The estimated rate of reduction in overall breast cancer mortality in 2000 was 37% from an estimated baseline rate of 64 deaths per 100,000 women, with 44% and 56% of that associated with screening and treatment, respectively. In 2012 the estimated reduction was 49% from an estimated baseline rate of 63 per 100,000 women, with 37% and 63% associated with screening and treatment, respectively (estimated 12% difference in 2012 vs. 2000), Sylvia K. Plevritis, PhD, of Stanford (Calif.) University and her colleagues reported in JAMA.

Screening and treatment were estimated to contribute to the reductions at varying rates. For example, the relative contributions of screening vs. treatment were 36% vs. 64% for ER+/ERBB2– disease; 31% vs. 69% for ER+/ERBB2+ disease; 40% vs. 60% for ER–/ERBB2+ disease; and 48% vs. 52% for ER–/ERBB2– disease.

The model-based analysis provides clinically relevant insights about the contributions of screening and treatment to reductions in breast cancer mortality by molecular subtype, showing a greater relative contribution of treatment in 2012 overall and for all subtypes except ER–/ERBB2– disease, the authors said.

“Because ER+ cancers are the most prevalent and this group is expected to increase with time, additional advances for this subtype could have the largest effect on reducing the overall population burden of breast cancer,” they noted.

This study was supported by grants from the National Cancer Institute and the American Cancer Society. Dr. Plevritis reported consulting for GRAIL.

[email protected]

SOURCE: Plevritis S et al. JAMA. 2018 Jan 9;319(2):154-64. doi: 10.1001/jama.2017.19130.

.
 

SAN ANTONIO – Adjuvant endocrine therapies improve outcomes of premenopausal breast cancer in the long term, with absolute benefit varying somewhat by therapy and by patient and disease characteristics, according to planned updates of a pair of pivotal phase 3 trials.

The trials – TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) – are coordinated by the International Breast Cancer Study Group and together randomized more than 5,000 premenopausal women with early hormone receptor–positive breast cancer to 5 years of various types of adjuvant endocrine therapy. Their initial results, reported several years ago, form part of treatment guidelines that are used worldwide.

Clinical implications

These updates, along with other emerging data, can be used to optimize endocrine therapy for younger women with breast cancer, according to invited discussant Ann H. Partridge, MD, of Dana Farber Cancer Institute in Boston.

“For higher-risk disease, we should be considering OFS. At this point in time, I don’t think HER2 status alone should drive this decision,” she commented. “If you are getting OFS, what do we do, AI versus tamoxifen? Well, we do see a large improvement in disease-free survival [with AIs], so many women will want to use AIs. Yet tamoxifen is still reasonable, especially in light of the survival data.”

Data on switch strategies and extended-duration therapy are generally lacking at present for the premenopausal population, Dr. Partridge noted. “That’s something that we still need to extrapolate from data that’s predominantly in postmenopausal women.”

Another compelling question is whether OFS can be used instead of chemo for some patients. “We are increasingly recognizing that women with higher-risk anatomy and lower-risk biology having endocrine-responsive tumors may get more bang for the buck from the optimizing of hormonal therapy, and chemo may not add much,” she said.

Both short- and long-term toxicities of the various endocrine therapies and, for aromatase inhibitors, the potential for breakthrough (return of estradiol levels to premenopausal levels) also need to be considered, Dr. Partridge stressed. “And ultimately, patient preference and tolerance are key. After all, the best treatment is the one the patient will take.”

“We need to follow these women on TEXT and SOFT very long term. It would be a crime not to follow these women further out,” she maintained. “We need to conduct real-world comparative effectiveness research to understand the risks and benefits of OFS more fully in our survivors. Then, as we start to suppress more ovaries in more women with breast cancer, we need to be aware clinically of these risks, and we need to share this awareness with their primary care providers because we need to optimize in particular their cardiovascular risk factors, and screen and treat for potential comorbidities that they may be at higher risk for.”
 

Joint TEXT and SOFT update

Initial results of the joint TEXT and SOFT analysis, reported after a median follow-up of 5.7 years, showed that exemestane plus OFS was superior to tamoxifen plus OFS for the primary outcome, providing a significant 3.8% absolute gain in 5-year disease-free survival (N Engl J Med. 2014;371:107-18).

The updated joint analysis, now with a median follow-up of 9 years and based on data from 4,690 women, showed that the 8-year rate of disease-free survival was 86.8% with exemestane plus OFS versus 82.8% with tamoxifen plus OFS (hazard ratio, 0.77; P = .0006), for a similar absolute benefit of 4.0%, reported Prudence Francis, MD, of the University of Melbourne, head of Medical Oncology in the Breast Service at the Peter MacCallum Cancer Centre, Melbourne.

In stratified analysis, absolute benefit tended to be greater among women in TEXT who received chemotherapy (6.0%); intermediate among women in TEXT who did not receive chemotherapy (3.7%) and women in SOFT who received prior chemotherapy (3.7%); and less among women in SOFT who did not receive chemotherapy (1.9%).

Exemestane plus OFS was also superior to tamoxifen plus OFS in terms of breast cancer–free interval, with an absolute 4.1% benefit (P = .0002), and distant recurrence–free interval, with an absolute 2.1% benefit (P = .02). Overall survival did not differ significantly between arms.

Among the 86% of patients with HER2-negative disease, exemestane plus OFS netted an absolute disease-free survival gain of 5.4% and an absolute distant recurrence–free interval gain of 3.4%. There was a consistent relative treatment benefit across subgroups, but larger absolute benefit, on the order of 5%-9%, in women given chemotherapy and in those younger than 35 years.

“Results for the HER2-positive subgroup require further investigation,” Dr. Francis said. “The trials enrolled both before and after the routine use of adjuvant trastuzumab, and a significant proportion of the patients with HER2-positive breast cancer did not receive adjuvant HER2-targeted therapy.”

In the entire joint-analysis population, exemestane plus OFS was associated with higher rates of musculoskeletal events of grade 3 or 4 (11% vs. 6%) and osteoporosis of grade 2-4 (15% vs. 7%), while tamoxifen plus OFS was associated with a higher rate of thrombosis/embolism of grade 2-4 (2.3% vs. 1.2%) and more cases of endometrial cancer (9 vs. 4 cases). At 4 years, early discontinuation of oral endocrine therapy was greater for exemestane than for tamoxifen (25% vs. 19%).

“After longer follow-up, with a median of 9 years, the combined analysis results confirm a statistically significant improvement in disease outcomes with exemestane plus ovarian suppression. As is critical given the long natural history of estrogen receptor–positive breast cancer, follow-up in these trials is currently continuing,” Dr. Francis summarized.

“To optimally translate the observed absolute trial improvements into clinical practice, oncologists need to discuss and weigh the potential benefits and toxicities in each individual patient who is premenopausal with hormone receptor–positive breast cancer,” she recommended.

Session attendee Hope S. Rugo, MD, of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, noted that exemestane had superior benefit despite the 25% rate of early discontinuation. “I wonder if one of the interpretations of that, given the toxicity of this therapy for very young women, is that we need some but maybe not so much. Maybe they don’t need 5 years altogether,” she said.

“The fact that they stopped their assigned endocrine therapy doesn’t mean that they didn’t continue any therapy. They may have switched over to tamoxifen or they may have decided they wanted to have a baby or there may have been many other things,” Dr. Francis replied, noting that analyses sorting out the reasons for early discontinuation are planned.

Session attendee Mark E. Sherman, MD, of the Mayo Clinic, Jacksonville, Fla., asked, “Do you have any ability to test for tamoxifen metabolites? It’s possible that a third to a half of patients got reduced benefit from that drug.”

Banked samples are available and a substudy is planned, according to Dr. Francis. “We haven’t got data on that yet, but yes, we are analyzing that.”
 

SOFT update

Initial results of the SOFT trial, reported after a median follow-up of 5.6 years, showed that adding OFS to tamoxifen did not significantly improve disease-free survival over tamoxifen alone in the entire trial population (N Engl J Med. 2015;372:436-46). However, there was benefit for women who received chemotherapy and remained premenopausal.

The updated SOFT analysis, now with a median follow-up of 8 years, focused mainly on the 1,018 women given tamoxifen alone and the 1,015 women given tamoxifen plus OFS. (Another 1,014 women were given exemestane plus OFS.)

“SOFT is now positive for its primary endpoint,” reported first author Gini Fleming, MD, director of the Medical Oncology Breast Program and medical oncology director of Gynecologic Oncology at University of Chicago Medicine. The 8-year disease-free survival rate was 83.2% with tamoxifen plus OFS, compared with 78.9% with tamoxifen alone (HR, 0.76; P = .009), corresponding to a 4.2% gain in this outcome. The relative benefit was identical whether patients had received chemotherapy or not, but absolute benefit was greater for those who had (5.3%), as well as for patients younger than 35 years (8.7%).

In addition, exemestane plus OFS was superior to tamoxifen alone (85.9% vs. 78.9%; HR, 0.65), with an absolute benefit of 7.0%. Again, absolute benefit was more pronounced among women who had received prior chemotherapy (9.0%) or were younger than 35 years (13.1%).

The relative disease-free survival benefit of tamoxifen plus OFS over tamoxifen alone was similar across most subgroups stratified by disease characteristics, but patients with HER2-positive disease derived greater relative benefit from the combination as compared with their HER2-negative counterparts (P = .04 for interaction). “When we look at the combination of exemestane plus OFS versus tamoxifen, this heterogeneity is no longer seen,” Dr. Fleming noted.

In the entire trial population, there was no significant benefit of tamoxifen plus OFS over tamoxifen alone for distant recurrence-free interval and a small, significant absolute 1.9% gain in overall survival.

“The cohort who had elected to receive no prior chemotherapy did exceedingly well regardless of therapy,” she said, with little difference in overall survival across the three arms. “There were only 24 deaths total in this cohort, and 12 of those deaths were in the setting of no distant recurrence.”

On the other hand, among the women who received chemotherapy, there were significant absolute overall survival benefits of 4.3% with tamoxifen plus OFS and 2.1% with exemestane plus OFS, over tamoxifen alone. “This late emergence of an overall survival benefit is consistent with the time course of events in estrogen receptor–positive breast cancer,” Dr. Fleming commented.

The proportion of patients who stopped their oral endocrine therapy early was 22.5% with tamoxifen alone and 18.5% with tamoxifen plus OFS. (It was 27.8% with exemestane plus OFS.) “Almost a quarter of the patients on either tamoxifen arm were using extended oral endocrine therapy at 6 years or later prior to any disease progression. Only about 12% of patients in the exemestane group were doing so,” she noted.

There were more cases of endometrial cancer with tamoxifen alone than with tamoxifen plus OFS (7 vs. 4 cases). Thrombosis/embolism of grade 2-4 occurred in 2.2% of each group (and 0.9% of the exemestane plus OFS group). Musculoskeletal symptoms of grade 3 or 4 occurred in 6.7% of patients with tamoxifen alone and 5.9% with tamoxifen plus OFS, but 12.0% with exemestane plus OFS. Respective rates of osteoporosis grade 2-4 were 3.9%, 6.1%, and 11.9%.

“The addition of OFS to tamoxifen significantly improves disease-free survival at 8 years’ median follow-up, and disease-free survival benefits are further improved by the use of exemestane plus OFS,” Dr. Fleming summarized. “Follow-up, which is critically important given the long natural history of ER-positive disease, continues.”

Session attendee Matthew P. Goetz, MD, of the Mayo Clinic, Rochester, Minn., commented, “For the primary endpoint, I was looking at the tail for tamoxifen. It seemed that there was a relatively rapid drop-off between year 5 and this 8-year follow-up. Have you looked carefully to see whether there is a difference between those who stayed on their therapy versus those who went off it per protocol? That is, extended versus not extended? The question is whether there is a carry-over effect, if you will, that is different in those with OFS versus those not.”

“The percent who went on to extended therapy between the tamoxifen and the tamoxifen plus OFS was fairly similar,” Dr. Fleming replied. “But the answer is no, we have not yet done any sort of per protocol analysis.”

Session attendee Steven Vogl, MD, of Montefiore Medical Center, New York, commented, “I worry about your control group. I’m worried, first, how many of your tamoxifen patients lost their menses and became postmenopausal in those 5 years? And of those, why didn’t they switch to an aromatase inhibitor? Only 25% of the patients continued after the 5 years according to your slide, and all of those patients should either have stayed on tamoxifen or switched to an aromatase inhibitor, now probably for 2 years at least.”

“We have not yet looked at data for who became amenorrheic during treatment, although we have it. However, it’s certainly possible to become amenorrheic on tamoxifen and not be postmenopausal, and we didn’t regularly collect estradiol levels on any but the very small subset of women in the SOFT-S trial. So I don’t know that we have exactly the data that you’re looking for,” Dr. Fleming said. “Many of these women are obviously at very, very low risk and have done well with 5 years of tamoxifen alone, and I don’t know, even given current guidelines, that extended tamoxifen would add a lot to that.”

Finally, session attendee Richard Gray, professor of medical statistics at the University of Oxford (England), wondered, “What is the certainty that follow-up will happen? Because obviously, prolonged follow-up is expensive and there are controversies about that. But this would be the one study you would really want to have 15- and 20-year data on.”

“We are working very, very hard on that,” Dr. Fleming replied. “NCI granted additional funds to institutions for prolonging follow-up, and IBCSG has been ceaselessly working to look for funding to continue it. So I think it’s relatively certain that it will happen.”

Dr. Francis disclosed that she has received fees for non-CME services from AstraZeneca and has given an overseas lecture for Pfizer. Dr. Fleming disclosed that she had no relevant financial relationships with commercial interests. The trials received financial support from Pfizer and Ipsen.

SOURCES: Francis et al. SABCS Abstract GS4-02; Fleming et al. SABCS Abstract GS4-03
 

SAN ANTONIO – Adjuvant endocrine therapies improve outcomes of premenopausal breast cancer in the long term, with absolute benefit varying somewhat by therapy and by patient and disease characteristics, according to planned updates of a pair of pivotal phase 3 trials.

The trials – TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) – are coordinated by the International Breast Cancer Study Group and together randomized more than 5,000 premenopausal women with early hormone receptor–positive breast cancer to 5 years of various types of adjuvant endocrine therapy. Their initial results, reported several years ago, form part of treatment guidelines that are used worldwide.

Clinical implications

These updates, along with other emerging data, can be used to optimize endocrine therapy for younger women with breast cancer, according to invited discussant Ann H. Partridge, MD, of Dana Farber Cancer Institute in Boston.

“For higher-risk disease, we should be considering OFS. At this point in time, I don’t think HER2 status alone should drive this decision,” she commented. “If you are getting OFS, what do we do, AI versus tamoxifen? Well, we do see a large improvement in disease-free survival [with AIs], so many women will want to use AIs. Yet tamoxifen is still reasonable, especially in light of the survival data.”

Data on switch strategies and extended-duration therapy are generally lacking at present for the premenopausal population, Dr. Partridge noted. “That’s something that we still need to extrapolate from data that’s predominantly in postmenopausal women.”

Another compelling question is whether OFS can be used instead of chemo for some patients. “We are increasingly recognizing that women with higher-risk anatomy and lower-risk biology having endocrine-responsive tumors may get more bang for the buck from the optimizing of hormonal therapy, and chemo may not add much,” she said.

Both short- and long-term toxicities of the various endocrine therapies and, for aromatase inhibitors, the potential for breakthrough (return of estradiol levels to premenopausal levels) also need to be considered, Dr. Partridge stressed. “And ultimately, patient preference and tolerance are key. After all, the best treatment is the one the patient will take.”

“We need to follow these women on TEXT and SOFT very long term. It would be a crime not to follow these women further out,” she maintained. “We need to conduct real-world comparative effectiveness research to understand the risks and benefits of OFS more fully in our survivors. Then, as we start to suppress more ovaries in more women with breast cancer, we need to be aware clinically of these risks, and we need to share this awareness with their primary care providers because we need to optimize in particular their cardiovascular risk factors, and screen and treat for potential comorbidities that they may be at higher risk for.”
 

Joint TEXT and SOFT update

Initial results of the joint TEXT and SOFT analysis, reported after a median follow-up of 5.7 years, showed that exemestane plus OFS was superior to tamoxifen plus OFS for the primary outcome, providing a significant 3.8% absolute gain in 5-year disease-free survival (N Engl J Med. 2014;371:107-18).

The updated joint analysis, now with a median follow-up of 9 years and based on data from 4,690 women, showed that the 8-year rate of disease-free survival was 86.8% with exemestane plus OFS versus 82.8% with tamoxifen plus OFS (hazard ratio, 0.77; P = .0006), for a similar absolute benefit of 4.0%, reported Prudence Francis, MD, of the University of Melbourne, head of Medical Oncology in the Breast Service at the Peter MacCallum Cancer Centre, Melbourne.

In stratified analysis, absolute benefit tended to be greater among women in TEXT who received chemotherapy (6.0%); intermediate among women in TEXT who did not receive chemotherapy (3.7%) and women in SOFT who received prior chemotherapy (3.7%); and less among women in SOFT who did not receive chemotherapy (1.9%).

Exemestane plus OFS was also superior to tamoxifen plus OFS in terms of breast cancer–free interval, with an absolute 4.1% benefit (P = .0002), and distant recurrence–free interval, with an absolute 2.1% benefit (P = .02). Overall survival did not differ significantly between arms.

Among the 86% of patients with HER2-negative disease, exemestane plus OFS netted an absolute disease-free survival gain of 5.4% and an absolute distant recurrence–free interval gain of 3.4%. There was a consistent relative treatment benefit across subgroups, but larger absolute benefit, on the order of 5%-9%, in women given chemotherapy and in those younger than 35 years.

“Results for the HER2-positive subgroup require further investigation,” Dr. Francis said. “The trials enrolled both before and after the routine use of adjuvant trastuzumab, and a significant proportion of the patients with HER2-positive breast cancer did not receive adjuvant HER2-targeted therapy.”

In the entire joint-analysis population, exemestane plus OFS was associated with higher rates of musculoskeletal events of grade 3 or 4 (11% vs. 6%) and osteoporosis of grade 2-4 (15% vs. 7%), while tamoxifen plus OFS was associated with a higher rate of thrombosis/embolism of grade 2-4 (2.3% vs. 1.2%) and more cases of endometrial cancer (9 vs. 4 cases). At 4 years, early discontinuation of oral endocrine therapy was greater for exemestane than for tamoxifen (25% vs. 19%).

“After longer follow-up, with a median of 9 years, the combined analysis results confirm a statistically significant improvement in disease outcomes with exemestane plus ovarian suppression. As is critical given the long natural history of estrogen receptor–positive breast cancer, follow-up in these trials is currently continuing,” Dr. Francis summarized.

“To optimally translate the observed absolute trial improvements into clinical practice, oncologists need to discuss and weigh the potential benefits and toxicities in each individual patient who is premenopausal with hormone receptor–positive breast cancer,” she recommended.

Session attendee Hope S. Rugo, MD, of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, noted that exemestane had superior benefit despite the 25% rate of early discontinuation. “I wonder if one of the interpretations of that, given the toxicity of this therapy for very young women, is that we need some but maybe not so much. Maybe they don’t need 5 years altogether,” she said.

“The fact that they stopped their assigned endocrine therapy doesn’t mean that they didn’t continue any therapy. They may have switched over to tamoxifen or they may have decided they wanted to have a baby or there may have been many other things,” Dr. Francis replied, noting that analyses sorting out the reasons for early discontinuation are planned.

Session attendee Mark E. Sherman, MD, of the Mayo Clinic, Jacksonville, Fla., asked, “Do you have any ability to test for tamoxifen metabolites? It’s possible that a third to a half of patients got reduced benefit from that drug.”

Banked samples are available and a substudy is planned, according to Dr. Francis. “We haven’t got data on that yet, but yes, we are analyzing that.”
 

SOFT update

Initial results of the SOFT trial, reported after a median follow-up of 5.6 years, showed that adding OFS to tamoxifen did not significantly improve disease-free survival over tamoxifen alone in the entire trial population (N Engl J Med. 2015;372:436-46). However, there was benefit for women who received chemotherapy and remained premenopausal.

The updated SOFT analysis, now with a median follow-up of 8 years, focused mainly on the 1,018 women given tamoxifen alone and the 1,015 women given tamoxifen plus OFS. (Another 1,014 women were given exemestane plus OFS.)

“SOFT is now positive for its primary endpoint,” reported first author Gini Fleming, MD, director of the Medical Oncology Breast Program and medical oncology director of Gynecologic Oncology at University of Chicago Medicine. The 8-year disease-free survival rate was 83.2% with tamoxifen plus OFS, compared with 78.9% with tamoxifen alone (HR, 0.76; P = .009), corresponding to a 4.2% gain in this outcome. The relative benefit was identical whether patients had received chemotherapy or not, but absolute benefit was greater for those who had (5.3%), as well as for patients younger than 35 years (8.7%).

In addition, exemestane plus OFS was superior to tamoxifen alone (85.9% vs. 78.9%; HR, 0.65), with an absolute benefit of 7.0%. Again, absolute benefit was more pronounced among women who had received prior chemotherapy (9.0%) or were younger than 35 years (13.1%).

The relative disease-free survival benefit of tamoxifen plus OFS over tamoxifen alone was similar across most subgroups stratified by disease characteristics, but patients with HER2-positive disease derived greater relative benefit from the combination as compared with their HER2-negative counterparts (P = .04 for interaction). “When we look at the combination of exemestane plus OFS versus tamoxifen, this heterogeneity is no longer seen,” Dr. Fleming noted.

In the entire trial population, there was no significant benefit of tamoxifen plus OFS over tamoxifen alone for distant recurrence-free interval and a small, significant absolute 1.9% gain in overall survival.

“The cohort who had elected to receive no prior chemotherapy did exceedingly well regardless of therapy,” she said, with little difference in overall survival across the three arms. “There were only 24 deaths total in this cohort, and 12 of those deaths were in the setting of no distant recurrence.”

On the other hand, among the women who received chemotherapy, there were significant absolute overall survival benefits of 4.3% with tamoxifen plus OFS and 2.1% with exemestane plus OFS, over tamoxifen alone. “This late emergence of an overall survival benefit is consistent with the time course of events in estrogen receptor–positive breast cancer,” Dr. Fleming commented.

The proportion of patients who stopped their oral endocrine therapy early was 22.5% with tamoxifen alone and 18.5% with tamoxifen plus OFS. (It was 27.8% with exemestane plus OFS.) “Almost a quarter of the patients on either tamoxifen arm were using extended oral endocrine therapy at 6 years or later prior to any disease progression. Only about 12% of patients in the exemestane group were doing so,” she noted.

There were more cases of endometrial cancer with tamoxifen alone than with tamoxifen plus OFS (7 vs. 4 cases). Thrombosis/embolism of grade 2-4 occurred in 2.2% of each group (and 0.9% of the exemestane plus OFS group). Musculoskeletal symptoms of grade 3 or 4 occurred in 6.7% of patients with tamoxifen alone and 5.9% with tamoxifen plus OFS, but 12.0% with exemestane plus OFS. Respective rates of osteoporosis grade 2-4 were 3.9%, 6.1%, and 11.9%.

“The addition of OFS to tamoxifen significantly improves disease-free survival at 8 years’ median follow-up, and disease-free survival benefits are further improved by the use of exemestane plus OFS,” Dr. Fleming summarized. “Follow-up, which is critically important given the long natural history of ER-positive disease, continues.”

Session attendee Matthew P. Goetz, MD, of the Mayo Clinic, Rochester, Minn., commented, “For the primary endpoint, I was looking at the tail for tamoxifen. It seemed that there was a relatively rapid drop-off between year 5 and this 8-year follow-up. Have you looked carefully to see whether there is a difference between those who stayed on their therapy versus those who went off it per protocol? That is, extended versus not extended? The question is whether there is a carry-over effect, if you will, that is different in those with OFS versus those not.”

“The percent who went on to extended therapy between the tamoxifen and the tamoxifen plus OFS was fairly similar,” Dr. Fleming replied. “But the answer is no, we have not yet done any sort of per protocol analysis.”

Session attendee Steven Vogl, MD, of Montefiore Medical Center, New York, commented, “I worry about your control group. I’m worried, first, how many of your tamoxifen patients lost their menses and became postmenopausal in those 5 years? And of those, why didn’t they switch to an aromatase inhibitor? Only 25% of the patients continued after the 5 years according to your slide, and all of those patients should either have stayed on tamoxifen or switched to an aromatase inhibitor, now probably for 2 years at least.”

“We have not yet looked at data for who became amenorrheic during treatment, although we have it. However, it’s certainly possible to become amenorrheic on tamoxifen and not be postmenopausal, and we didn’t regularly collect estradiol levels on any but the very small subset of women in the SOFT-S trial. So I don’t know that we have exactly the data that you’re looking for,” Dr. Fleming said. “Many of these women are obviously at very, very low risk and have done well with 5 years of tamoxifen alone, and I don’t know, even given current guidelines, that extended tamoxifen would add a lot to that.”

Finally, session attendee Richard Gray, professor of medical statistics at the University of Oxford (England), wondered, “What is the certainty that follow-up will happen? Because obviously, prolonged follow-up is expensive and there are controversies about that. But this would be the one study you would really want to have 15- and 20-year data on.”

“We are working very, very hard on that,” Dr. Fleming replied. “NCI granted additional funds to institutions for prolonging follow-up, and IBCSG has been ceaselessly working to look for funding to continue it. So I think it’s relatively certain that it will happen.”

Dr. Francis disclosed that she has received fees for non-CME services from AstraZeneca and has given an overseas lecture for Pfizer. Dr. Fleming disclosed that she had no relevant financial relationships with commercial interests. The trials received financial support from Pfizer and Ipsen.

SOURCES: Francis et al. SABCS Abstract GS4-02; Fleming et al. SABCS Abstract GS4-03
 

SAN ANTONIO – Adjuvant endocrine therapies improve outcomes of premenopausal breast cancer in the long term, with absolute benefit varying somewhat by therapy and by patient and disease characteristics, according to planned updates of a pair of pivotal phase 3 trials.

The trials – TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) – are coordinated by the International Breast Cancer Study Group and together randomized more than 5,000 premenopausal women with early hormone receptor–positive breast cancer to 5 years of various types of adjuvant endocrine therapy. Their initial results, reported several years ago, form part of treatment guidelines that are used worldwide.

Clinical implications

These updates, along with other emerging data, can be used to optimize endocrine therapy for younger women with breast cancer, according to invited discussant Ann H. Partridge, MD, of Dana Farber Cancer Institute in Boston.

“For higher-risk disease, we should be considering OFS. At this point in time, I don’t think HER2 status alone should drive this decision,” she commented. “If you are getting OFS, what do we do, AI versus tamoxifen? Well, we do see a large improvement in disease-free survival [with AIs], so many women will want to use AIs. Yet tamoxifen is still reasonable, especially in light of the survival data.”

Data on switch strategies and extended-duration therapy are generally lacking at present for the premenopausal population, Dr. Partridge noted. “That’s something that we still need to extrapolate from data that’s predominantly in postmenopausal women.”

Another compelling question is whether OFS can be used instead of chemo for some patients. “We are increasingly recognizing that women with higher-risk anatomy and lower-risk biology having endocrine-responsive tumors may get more bang for the buck from the optimizing of hormonal therapy, and chemo may not add much,” she said.

Both short- and long-term toxicities of the various endocrine therapies and, for aromatase inhibitors, the potential for breakthrough (return of estradiol levels to premenopausal levels) also need to be considered, Dr. Partridge stressed. “And ultimately, patient preference and tolerance are key. After all, the best treatment is the one the patient will take.”

“We need to follow these women on TEXT and SOFT very long term. It would be a crime not to follow these women further out,” she maintained. “We need to conduct real-world comparative effectiveness research to understand the risks and benefits of OFS more fully in our survivors. Then, as we start to suppress more ovaries in more women with breast cancer, we need to be aware clinically of these risks, and we need to share this awareness with their primary care providers because we need to optimize in particular their cardiovascular risk factors, and screen and treat for potential comorbidities that they may be at higher risk for.”
 

Joint TEXT and SOFT update

Initial results of the joint TEXT and SOFT analysis, reported after a median follow-up of 5.7 years, showed that exemestane plus OFS was superior to tamoxifen plus OFS for the primary outcome, providing a significant 3.8% absolute gain in 5-year disease-free survival (N Engl J Med. 2014;371:107-18).

The updated joint analysis, now with a median follow-up of 9 years and based on data from 4,690 women, showed that the 8-year rate of disease-free survival was 86.8% with exemestane plus OFS versus 82.8% with tamoxifen plus OFS (hazard ratio, 0.77; P = .0006), for a similar absolute benefit of 4.0%, reported Prudence Francis, MD, of the University of Melbourne, head of Medical Oncology in the Breast Service at the Peter MacCallum Cancer Centre, Melbourne.

In stratified analysis, absolute benefit tended to be greater among women in TEXT who received chemotherapy (6.0%); intermediate among women in TEXT who did not receive chemotherapy (3.7%) and women in SOFT who received prior chemotherapy (3.7%); and less among women in SOFT who did not receive chemotherapy (1.9%).

Exemestane plus OFS was also superior to tamoxifen plus OFS in terms of breast cancer–free interval, with an absolute 4.1% benefit (P = .0002), and distant recurrence–free interval, with an absolute 2.1% benefit (P = .02). Overall survival did not differ significantly between arms.

Among the 86% of patients with HER2-negative disease, exemestane plus OFS netted an absolute disease-free survival gain of 5.4% and an absolute distant recurrence–free interval gain of 3.4%. There was a consistent relative treatment benefit across subgroups, but larger absolute benefit, on the order of 5%-9%, in women given chemotherapy and in those younger than 35 years.

“Results for the HER2-positive subgroup require further investigation,” Dr. Francis said. “The trials enrolled both before and after the routine use of adjuvant trastuzumab, and a significant proportion of the patients with HER2-positive breast cancer did not receive adjuvant HER2-targeted therapy.”

In the entire joint-analysis population, exemestane plus OFS was associated with higher rates of musculoskeletal events of grade 3 or 4 (11% vs. 6%) and osteoporosis of grade 2-4 (15% vs. 7%), while tamoxifen plus OFS was associated with a higher rate of thrombosis/embolism of grade 2-4 (2.3% vs. 1.2%) and more cases of endometrial cancer (9 vs. 4 cases). At 4 years, early discontinuation of oral endocrine therapy was greater for exemestane than for tamoxifen (25% vs. 19%).

“After longer follow-up, with a median of 9 years, the combined analysis results confirm a statistically significant improvement in disease outcomes with exemestane plus ovarian suppression. As is critical given the long natural history of estrogen receptor–positive breast cancer, follow-up in these trials is currently continuing,” Dr. Francis summarized.

“To optimally translate the observed absolute trial improvements into clinical practice, oncologists need to discuss and weigh the potential benefits and toxicities in each individual patient who is premenopausal with hormone receptor–positive breast cancer,” she recommended.

Session attendee Hope S. Rugo, MD, of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, noted that exemestane had superior benefit despite the 25% rate of early discontinuation. “I wonder if one of the interpretations of that, given the toxicity of this therapy for very young women, is that we need some but maybe not so much. Maybe they don’t need 5 years altogether,” she said.

“The fact that they stopped their assigned endocrine therapy doesn’t mean that they didn’t continue any therapy. They may have switched over to tamoxifen or they may have decided they wanted to have a baby or there may have been many other things,” Dr. Francis replied, noting that analyses sorting out the reasons for early discontinuation are planned.

Session attendee Mark E. Sherman, MD, of the Mayo Clinic, Jacksonville, Fla., asked, “Do you have any ability to test for tamoxifen metabolites? It’s possible that a third to a half of patients got reduced benefit from that drug.”

Banked samples are available and a substudy is planned, according to Dr. Francis. “We haven’t got data on that yet, but yes, we are analyzing that.”
 

SOFT update

Initial results of the SOFT trial, reported after a median follow-up of 5.6 years, showed that adding OFS to tamoxifen did not significantly improve disease-free survival over tamoxifen alone in the entire trial population (N Engl J Med. 2015;372:436-46). However, there was benefit for women who received chemotherapy and remained premenopausal.

The updated SOFT analysis, now with a median follow-up of 8 years, focused mainly on the 1,018 women given tamoxifen alone and the 1,015 women given tamoxifen plus OFS. (Another 1,014 women were given exemestane plus OFS.)

“SOFT is now positive for its primary endpoint,” reported first author Gini Fleming, MD, director of the Medical Oncology Breast Program and medical oncology director of Gynecologic Oncology at University of Chicago Medicine. The 8-year disease-free survival rate was 83.2% with tamoxifen plus OFS, compared with 78.9% with tamoxifen alone (HR, 0.76; P = .009), corresponding to a 4.2% gain in this outcome. The relative benefit was identical whether patients had received chemotherapy or not, but absolute benefit was greater for those who had (5.3%), as well as for patients younger than 35 years (8.7%).

In addition, exemestane plus OFS was superior to tamoxifen alone (85.9% vs. 78.9%; HR, 0.65), with an absolute benefit of 7.0%. Again, absolute benefit was more pronounced among women who had received prior chemotherapy (9.0%) or were younger than 35 years (13.1%).

The relative disease-free survival benefit of tamoxifen plus OFS over tamoxifen alone was similar across most subgroups stratified by disease characteristics, but patients with HER2-positive disease derived greater relative benefit from the combination as compared with their HER2-negative counterparts (P = .04 for interaction). “When we look at the combination of exemestane plus OFS versus tamoxifen, this heterogeneity is no longer seen,” Dr. Fleming noted.

In the entire trial population, there was no significant benefit of tamoxifen plus OFS over tamoxifen alone for distant recurrence-free interval and a small, significant absolute 1.9% gain in overall survival.

“The cohort who had elected to receive no prior chemotherapy did exceedingly well regardless of therapy,” she said, with little difference in overall survival across the three arms. “There were only 24 deaths total in this cohort, and 12 of those deaths were in the setting of no distant recurrence.”

On the other hand, among the women who received chemotherapy, there were significant absolute overall survival benefits of 4.3% with tamoxifen plus OFS and 2.1% with exemestane plus OFS, over tamoxifen alone. “This late emergence of an overall survival benefit is consistent with the time course of events in estrogen receptor–positive breast cancer,” Dr. Fleming commented.

The proportion of patients who stopped their oral endocrine therapy early was 22.5% with tamoxifen alone and 18.5% with tamoxifen plus OFS. (It was 27.8% with exemestane plus OFS.) “Almost a quarter of the patients on either tamoxifen arm were using extended oral endocrine therapy at 6 years or later prior to any disease progression. Only about 12% of patients in the exemestane group were doing so,” she noted.

There were more cases of endometrial cancer with tamoxifen alone than with tamoxifen plus OFS (7 vs. 4 cases). Thrombosis/embolism of grade 2-4 occurred in 2.2% of each group (and 0.9% of the exemestane plus OFS group). Musculoskeletal symptoms of grade 3 or 4 occurred in 6.7% of patients with tamoxifen alone and 5.9% with tamoxifen plus OFS, but 12.0% with exemestane plus OFS. Respective rates of osteoporosis grade 2-4 were 3.9%, 6.1%, and 11.9%.

“The addition of OFS to tamoxifen significantly improves disease-free survival at 8 years’ median follow-up, and disease-free survival benefits are further improved by the use of exemestane plus OFS,” Dr. Fleming summarized. “Follow-up, which is critically important given the long natural history of ER-positive disease, continues.”

Session attendee Matthew P. Goetz, MD, of the Mayo Clinic, Rochester, Minn., commented, “For the primary endpoint, I was looking at the tail for tamoxifen. It seemed that there was a relatively rapid drop-off between year 5 and this 8-year follow-up. Have you looked carefully to see whether there is a difference between those who stayed on their therapy versus those who went off it per protocol? That is, extended versus not extended? The question is whether there is a carry-over effect, if you will, that is different in those with OFS versus those not.”

“The percent who went on to extended therapy between the tamoxifen and the tamoxifen plus OFS was fairly similar,” Dr. Fleming replied. “But the answer is no, we have not yet done any sort of per protocol analysis.”

Session attendee Steven Vogl, MD, of Montefiore Medical Center, New York, commented, “I worry about your control group. I’m worried, first, how many of your tamoxifen patients lost their menses and became postmenopausal in those 5 years? And of those, why didn’t they switch to an aromatase inhibitor? Only 25% of the patients continued after the 5 years according to your slide, and all of those patients should either have stayed on tamoxifen or switched to an aromatase inhibitor, now probably for 2 years at least.”

“We have not yet looked at data for who became amenorrheic during treatment, although we have it. However, it’s certainly possible to become amenorrheic on tamoxifen and not be postmenopausal, and we didn’t regularly collect estradiol levels on any but the very small subset of women in the SOFT-S trial. So I don’t know that we have exactly the data that you’re looking for,” Dr. Fleming said. “Many of these women are obviously at very, very low risk and have done well with 5 years of tamoxifen alone, and I don’t know, even given current guidelines, that extended tamoxifen would add a lot to that.”

Finally, session attendee Richard Gray, professor of medical statistics at the University of Oxford (England), wondered, “What is the certainty that follow-up will happen? Because obviously, prolonged follow-up is expensive and there are controversies about that. But this would be the one study you would really want to have 15- and 20-year data on.”

“We are working very, very hard on that,” Dr. Fleming replied. “NCI granted additional funds to institutions for prolonging follow-up, and IBCSG has been ceaselessly working to look for funding to continue it. So I think it’s relatively certain that it will happen.”

Dr. Francis disclosed that she has received fees for non-CME services from AstraZeneca and has given an overseas lecture for Pfizer. Dr. Fleming disclosed that she had no relevant financial relationships with commercial interests. The trials received financial support from Pfizer and Ipsen.

SOURCES: Francis et al. SABCS Abstract GS4-02; Fleming et al. SABCS Abstract GS4-03
 

SAN ANTONIO – A new prognostic tool that uses four clinical and pathological variables may help to guide decisions about extending adjuvant endocrine therapy for postmenopausal women with estrogen receptor–positive (ER+) breast cancer, according to a study reported at the San Antonio Breast Cancer Symposium.

ER+ breast cancer is well known for recurring long after endocrine therapy stops, but the risk varies widely, ranging from 10% to 40% (N Engl J Med. 2017;377:1836-46), noted lead investigator Ivana Sestak, MS, PhD, a lecturer in medical statistics at the Queen Mary University of London. “A few trials have shown that extended endocrine therapy can reduce the risk of recurrence, but careful assessment of potential side effects and actual risk of developing a late distant recurrence is essential,” she said.

Courtesy of Dr. Sestak

Study details

The investigators developed and trained the new tool using data from 4,735 women from the ATAC trial. They then validated the tool using data from 6,711 women from the BIG 1-98 trial.

The final CTS5 model contained four clinical variables, Dr. Sestak reported: number of involved nodes, size of the tumor, grade of the tumor, and age of the patient.

In the ATAC population, the CTS5 model did a better job than the original CTS0 model of predicting late distant recurrence. CTS5 improved the prediction of late distant recurrence by a factor of 2.47, whereas CTS0 improved the predictive value by a factor of 2.04. The CTS5 model performed similarly well regardless of whether patients had received chemotherapy.

In the BIG 1-98 population, the findings were much the same: The CTS5 model improved prediction of late distant recurrence by 2.07, while the CTS0 model improved prediction of late distant recurrence by 1.84. Performance of the CTS5 model was again similarly good regardless of whether patients had received chemotherapy.

Observed rates of distant recurrence between years 5 and 10 were similar in the ATAC and BIG 1-98 populations for the CTS5-defined low-risk group (2.5% and 3.0%, respectively), intermediate-risk group (7.7% and 6.9%), and the high-risk group (20.3% and 17.3%).

When the two trials’ populations were combined, the observed rate was 3.0% in the CTS5-defined low-risk group, 7.3% in the intermediate-risk group, and 18.9% in the high-risk group.

In addition, the main results held up among all node-negative women combined and among all women who had between one and three positive nodes combined. “For women with four or more positive lymph nodes, the CTS5 was not informative and categorized virtually all women into the high-risk group,” Dr. Sestak noted.

The investigators did not look at whether local or regional recurrences modulated the risk of late distant recurrence, she said. However, women who had experienced isolated local recurrence during the first 5 years would have been included in analysis.

“A strength of our study is that we used clinicopathological parameters that are measured in all breast cancer patients, and there is no need for further testing,” noted Dr. Sestak, who disclosed that she has received fees for advisory boards and lectures from Myriad Genetics.

On the other hand, it is unclear how the CTS5 would perform among premenopausal women and among women with HER2-positive disease given that two trials took place before routine HER2 testing and HER2-directed therapy were used.

SOURCE: Sestak I et al. SABCS 2017 Abstract GS6-01.

SAN ANTONIO – A new prognostic tool that uses four clinical and pathological variables may help to guide decisions about extending adjuvant endocrine therapy for postmenopausal women with estrogen receptor–positive (ER+) breast cancer, according to a study reported at the San Antonio Breast Cancer Symposium.

ER+ breast cancer is well known for recurring long after endocrine therapy stops, but the risk varies widely, ranging from 10% to 40% (N Engl J Med. 2017;377:1836-46), noted lead investigator Ivana Sestak, MS, PhD, a lecturer in medical statistics at the Queen Mary University of London. “A few trials have shown that extended endocrine therapy can reduce the risk of recurrence, but careful assessment of potential side effects and actual risk of developing a late distant recurrence is essential,” she said.

Courtesy of Dr. Sestak

Study details

The investigators developed and trained the new tool using data from 4,735 women from the ATAC trial. They then validated the tool using data from 6,711 women from the BIG 1-98 trial.

The final CTS5 model contained four clinical variables, Dr. Sestak reported: number of involved nodes, size of the tumor, grade of the tumor, and age of the patient.

In the ATAC population, the CTS5 model did a better job than the original CTS0 model of predicting late distant recurrence. CTS5 improved the prediction of late distant recurrence by a factor of 2.47, whereas CTS0 improved the predictive value by a factor of 2.04. The CTS5 model performed similarly well regardless of whether patients had received chemotherapy.

In the BIG 1-98 population, the findings were much the same: The CTS5 model improved prediction of late distant recurrence by 2.07, while the CTS0 model improved prediction of late distant recurrence by 1.84. Performance of the CTS5 model was again similarly good regardless of whether patients had received chemotherapy.

Observed rates of distant recurrence between years 5 and 10 were similar in the ATAC and BIG 1-98 populations for the CTS5-defined low-risk group (2.5% and 3.0%, respectively), intermediate-risk group (7.7% and 6.9%), and the high-risk group (20.3% and 17.3%).

When the two trials’ populations were combined, the observed rate was 3.0% in the CTS5-defined low-risk group, 7.3% in the intermediate-risk group, and 18.9% in the high-risk group.

In addition, the main results held up among all node-negative women combined and among all women who had between one and three positive nodes combined. “For women with four or more positive lymph nodes, the CTS5 was not informative and categorized virtually all women into the high-risk group,” Dr. Sestak noted.

The investigators did not look at whether local or regional recurrences modulated the risk of late distant recurrence, she said. However, women who had experienced isolated local recurrence during the first 5 years would have been included in analysis.

“A strength of our study is that we used clinicopathological parameters that are measured in all breast cancer patients, and there is no need for further testing,” noted Dr. Sestak, who disclosed that she has received fees for advisory boards and lectures from Myriad Genetics.

On the other hand, it is unclear how the CTS5 would perform among premenopausal women and among women with HER2-positive disease given that two trials took place before routine HER2 testing and HER2-directed therapy were used.

SOURCE: Sestak I et al. SABCS 2017 Abstract GS6-01.

SAN ANTONIO – A new prognostic tool that uses four clinical and pathological variables may help to guide decisions about extending adjuvant endocrine therapy for postmenopausal women with estrogen receptor–positive (ER+) breast cancer, according to a study reported at the San Antonio Breast Cancer Symposium.

ER+ breast cancer is well known for recurring long after endocrine therapy stops, but the risk varies widely, ranging from 10% to 40% (N Engl J Med. 2017;377:1836-46), noted lead investigator Ivana Sestak, MS, PhD, a lecturer in medical statistics at the Queen Mary University of London. “A few trials have shown that extended endocrine therapy can reduce the risk of recurrence, but careful assessment of potential side effects and actual risk of developing a late distant recurrence is essential,” she said.

Courtesy of Dr. Sestak

Study details

The investigators developed and trained the new tool using data from 4,735 women from the ATAC trial. They then validated the tool using data from 6,711 women from the BIG 1-98 trial.

The final CTS5 model contained four clinical variables, Dr. Sestak reported: number of involved nodes, size of the tumor, grade of the tumor, and age of the patient.

In the ATAC population, the CTS5 model did a better job than the original CTS0 model of predicting late distant recurrence. CTS5 improved the prediction of late distant recurrence by a factor of 2.47, whereas CTS0 improved the predictive value by a factor of 2.04. The CTS5 model performed similarly well regardless of whether patients had received chemotherapy.

In the BIG 1-98 population, the findings were much the same: The CTS5 model improved prediction of late distant recurrence by 2.07, while the CTS0 model improved prediction of late distant recurrence by 1.84. Performance of the CTS5 model was again similarly good regardless of whether patients had received chemotherapy.

Observed rates of distant recurrence between years 5 and 10 were similar in the ATAC and BIG 1-98 populations for the CTS5-defined low-risk group (2.5% and 3.0%, respectively), intermediate-risk group (7.7% and 6.9%), and the high-risk group (20.3% and 17.3%).

When the two trials’ populations were combined, the observed rate was 3.0% in the CTS5-defined low-risk group, 7.3% in the intermediate-risk group, and 18.9% in the high-risk group.

In addition, the main results held up among all node-negative women combined and among all women who had between one and three positive nodes combined. “For women with four or more positive lymph nodes, the CTS5 was not informative and categorized virtually all women into the high-risk group,” Dr. Sestak noted.

The investigators did not look at whether local or regional recurrences modulated the risk of late distant recurrence, she said. However, women who had experienced isolated local recurrence during the first 5 years would have been included in analysis.

“A strength of our study is that we used clinicopathological parameters that are measured in all breast cancer patients, and there is no need for further testing,” noted Dr. Sestak, who disclosed that she has received fees for advisory boards and lectures from Myriad Genetics.

On the other hand, it is unclear how the CTS5 would perform among premenopausal women and among women with HER2-positive disease given that two trials took place before routine HER2 testing and HER2-directed therapy were used.

SOURCE: Sestak I et al. SABCS 2017 Abstract GS6-01.